• Aucun résultat trouvé

Dupuytren's disease: personal factors and occupational exposure.

N/A
N/A
Protected

Academic year: 2021

Partager "Dupuytren's disease: personal factors and occupational exposure."

Copied!
22
0
0

Texte intégral

(1)Dupuytren’s disease: personal factors and occupational exposure. Gérard Lucas, Anne Brichet, Yves Roquelaure, Annette Leclerc, Alexis Descatha. To cite this version: Gérard Lucas, Anne Brichet, Yves Roquelaure, Annette Leclerc, Alexis Descatha. Dupuytren’s disease: personal factors and occupational exposure.. American Journal of Industrial Medicine, Wiley, 2008, 51 (1), pp.9-15. �10.1002/ajim.20542�. �inserm-00225779�. HAL Id: inserm-00225779 https://www.hal.inserm.fr/inserm-00225779 Submitted on 29 Mar 2013. 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 American Journal of Industrial Medicine 2008;51(1):9-15.  

(3) 

(4) 

(5) 

(6)  ! "#$%&' %($$&

(7) )*

(8). +-, .&/ .&021435/7698:;&<=?>>A@CBD.FEG5H@JI48:K;&<L?M @76NPO'QR3@ST/U3.&@?8WVX;4=?>>@JIYIZ@C1[@5 SG@ .&5?8W\Z;#<=2S@] EY6^_@6&5/JIXH/ HAL author manuscript. 8W\#` a#;b :'^-N?cd9egfh<Rf4/Jig6&jZ0@jk1[O'El. @?@UIBm. @nIZ/ o>A@<e.&/ >A5@p V1[/Uq!O!.&/JIXO.Wi_O!rgd[s'E0@utvETO'STOoi <d.#oAO!>AO!twEG569/ >A0yx-575U3 s /UIXETO>/Szw@/uS{I#HA<!=->o @ .6&<e*jW| }~~~<. inserm-00225779, version 1. e.&/>A5@p \4Y€(Rd9NC‚ƒ<A„_ '†ˆ‡<g / ET>RIZjk‚ƒ/U3 .&ET5@<e*j#}|| ~<e.&/%>57@_p7„>EM@%.6&E‰IZ,Cfh/ .&EY64Š2 <!WeN? }<‹-EKSTSG@#Œ#3gEGr#<e*j }|g†ˆ~‡<e.&/ >A5@2pR„_>EM@%.6&E‰IZ,m‹@ .6&/EGSSG@6&j /ET>RIhP3@%>RIXET><e*/5U3S‰IZ,?0@C‚ƒ,0@5ET> @Cf4/%.FEY6 jW&ST@j#0@j e.&/>A5@j#xm3@R6WIZ<e.&/%>5@p a4=mfhjkz-f4< x-55U3 s /IXETO!>A/SgH@/S‰IZHw0@ s /%.WIXtw@>RIZ<f*OEK>A5/ .,CIZ@/5%HEK>ˆoŽHAO6Zs'E‰IZ/ST< +-/ .&5 HA@A6 <Aej#}‘ ’'†ˆ~< e.&/>A5@p “   

(9) 

(10) $

(11) ?(

(12) * Gg& b7=2SG@ ] EY6^_@R65/UIXHA/<A„>E‰IZ,?0@ms /UIXHAO!SO!o ET@ms.&OrX@66&ETO'>>A@SSG@< z_”!sE‰IZ/SNP/ i twO'>A0fhOET>5/ . ,<!=mfhjkz-fh<'}‘ ’'†ˆ~w+-/ .&5 HA@R6&<e.&/%>5@ c9@uSk•R–*’’y8 ;| ‡ ~—‡‡Ž˜7|gpRe/U]*•R–*’’w8 ;4| ‡ ~—‡‡w '†pA@tv/uETSZ• /SG@ ] Ek6nb{0@A6 5/UIXHA/R™š.Zs 5b{/ s'Hˆsb‰rY. ›œwžK#G

(13) Ÿ NDE6# vr#/5UIZO.6hO!rg^-3 s3'i7IX.&@ > ¡¢690Ek6 @/R6@ £¤ %¥$g •R‘ ’‘g˜?¦O.&0'6h8#/Uqg6XIX.&/5UIk<.&@ rX@ . @u>A5@?SEY6WIh/ >A0IZ/Jq S@769@ ] 5Sl30@0;Jb.

(14) ‘  

(15) 

(16) 

(17) 

(18)  ! "#$%&' %($$&

(19) )*

(20)  › _“ 

(21)  _  BP/5  o.&O3 >0gbhc HA@¥@UIXEO'STOo!i OrC^-3 s3 iRIX. @ > ¡ 60E6@/R6 @¥EY6 3 >ˆ '>AOA¦_></ >A0 IXHA@ .&OST@(O!rPO'55U3 s /UIXETO> /RS HAL author manuscript. @U]As O6X3 .&@ Ek6 6XIXETSSD0@ q/UIZ@0gb9xP3 .Oq%Œ&@5UIZElM @¥¦w/762IZO 6WIY30Ri IXH@ /66&O 5uEG/UIXEO!>šq@UIY¦_@@ > O'55U3 s /UIXETO> /RS @U]As O6X3 .&@R6&<s @ .6 O!>A/S.FEY6Z ŽrX/5UIZO.69/%>02^23 s3 i7IX.&@ >A¡ 690EY6&@/R6 @b ‚ @JIXHO 0'6Jb2Z> IXHEk6 5 .&Og66 jF6&@5UIXETO> /uS(6W3 .#M @ i!<Ž>EK> @ O 55U3 s /UIXEO!> /SŽs Hig6&EG5EG/>g6 s @ .&rXO!.&tw@0¤5uSGET>'EG57/RS @U]!/utvET> /UI#EO!>g6 <rXO 5U36&@0 O>y^-3 s3 iRIX. @u> ¡ 6 0!EY6@/R6 @<O'r9‘ <| ~ ye.&@ >5H tv/SG@y5ElMES46&@ .#M!/u>7I&6ž@tws'SO!i @0. inserm-00225779, version 1. /UIvIXH@ƒd QR3gE s'tv@>RI ‚ ET>EY6WIX.#i ET>. }}'† />0 ET>RIZ@ .XM EY@U¦_@0 IXH@t / q O3I(tw@0!EG57/SŽHEY6WIZO.WiA<wS@EY6W3 .@. tv/>R3/S@ ]s Og6W3 .&@-/>0vO'55J3 s /UIXETO>/Sgq ETO'tv@5H/>EG5/S*@U]s Og6W3 .&@mIXOyM ElqA.&/UIZETO!> 6[/u>A0Žtv/u>73/S'¦wO.# b= 5U3t23S/JI#ElM @?O 55U3 s /JIXETO!>A/Sg@ ]s Og6W3 . @26&5O.&@ ¦_/R690@rXET> @0<A¦E‰IXH2IXHˆ.&@@?ST@ M @SY69O'r*@U]As O6X3 .&@b NP@R6W3S‰I&6nb^-3 s3'i7IX.&@> ¡ 6-0EY6@/R6@y¦_/R6-0E/o >Og6&@0 ET> ‘ ‘ tw@> 8F† bl†  ;Jb*c4H@ O 55U3 s /UIXETO>/S[@ ]s Og6W3 .&@ 6&5O!.&@ ¦w/76 6&Elo >Er#EG5/>RIZSli HETo'H @%. EK> IXHEk6 o.&OA3 s O!rv5/R6 @R6ŽIXHA/u> EK> I#HA@ .&@6WIyO!r2IXHA@ 6&/tws'SG@ 8#’‡‡ 8^‘g†ˆ~; M!@ .6W369‘‘ ’v8^—‘g˜ˆ~;&< .&@R6#s @5nIXElM @STigp s

(22) *~gb‰~ ~~ ;Jbx-55U3 s /IXETO> /Sg@ ]s Og6W3 . @P¦_/R6[/66&O 5ET/UIZ@0 ¦wE‰IXHw^23 s3 i7IX.&@ > ¡¢6ž0Ek6 @/6&@—8Z/0UŒX36XIZ@0 x200'69NP/UIXETO

(23) ‘b¢‘ ~ b{’}j#’ b¢|g˜ rXO!.4IXH@-EK>7IZ@ .&tw@0EG/UIZ@—/ >A0 ’gb ~  b{}}jW|b†7|4rXO.IXH@2HElo H @ ]As O6X3 .&@ o. OA3 sg6Z;#<!¦E‰IXH /0UŒ#36XI#tw@>7I9rXO!.[/ o @<gST@EY6W3 .&@?s Hig6&EG57/uS/5UIZEM E{I#EG@R6 < /ST5OHO'S[5O>g6W3twsIXETO!> 8h˜ 6&@ .WM ET>o6-s @ .—0/ iˆ;&<HEY6WIZO.#i Or?0EG/q!@UIZ@R6 <@ s EKSG@ s6#iA<H/>0 IX.&/U3tw/</>0 rZ/utvESTEG/SgHEY6WIZO.WiwOrg^23 s3 i7IX.&@ > ¡¢690!EY6 @/R6@b žO!>A5S‰36&EO'>gbR‚ƒ/>R3/Sg¦wO.#  @J]s Og6W3 .&@m¦w/76ž/R6J6 O'5ET/UIZ@0_¦wE‰IXHw^23 s3 i7IX.&@ > ¡¢60EY6@/R6@-/rIZ@ ./0UŒ#36WIZtw@>RI rXO.4s @ .6&O>/S.&EY6# vrX/5UIZO.6Jb 1[O>o E‰IY30ET> /Sg6WIY30ET@69/ .&@m> @@0@02IXOw5O>rXEK.&t IXHA@A6 @m.&@R6X3gS‰I&6nb. (

(24) U

(25) _  bu^-3 s3'i7IX.&@%>¡ 6C O>RIX. /5UIY3. @<RN?E6Z —e4/5UIZO.6&<x-55U3 s /JIXETO!>A/S!^wEY6 @/6&@b.

(26) ’. .  › w “  . HAL author manuscript. ^-3 s3'i7IX.&@ > ¡ 6P0!EY6 @/6&@ŽEY6?5HA/ .&/5UIZ@%.F E 7@0 qi 5H.&O>EG5Ž5O>RIX.&/5nIY3A.&@wO!r IXHA@ŽrXOA3 .YIXH / >0 rXEKrIZH rXET>og@ .6?O'r IXH@mH />A0IZO¦_/ .&0 IXHA@ms /uSTtv<36X3/uSGSKiv/55O't—s/>EG@0_qiv.&ET0o EK>ovO'rgIXHA@msg/STtv/ .C6Z 'ET>v8 ž/SEGr4/>0(AIZ/%H'S . ‘ ~~‡;Jb[c HEY6 /Uq >O.&tw/SE‰IXi HA/6yq@@> .&@ s O.kIZ@0 El> IXH @štw@0E5/uS-STE‰IZ@ .&/JIY3 .&@ƒ6&ET>5@ IXH@ @/ .&Sli ~~g6 8k^_@t_q!@ }} ;Jb!BP/ .&O>(+m3 EKSGSG/U3gtv@2^-3 s3'i7IX.&@><ET>(HEW6žs.&@76&@>RIZ/UIXEO!>(Or ^_@5@t—q@ .?˜ˆ< †ˆ’ <*/nI4IXHA@. inserm-00225779, version 1. z_ORIZ@ STjk^wEG@U3(ET>—fh/ .&EY6&<g5ST@/%.FSTivE0@>7I#ETr#EG@0—IXH@-0!E6 O!. 0@ .&¡ 6[ST@6&ETO>Ž/6[5O>RIX.&/5nIY3 .&@DO!rIXH@?s /SKtv/ .[rX/A6 5E/< ¦HE5HwH@-/R66@ .WIZ@0w5O3 ST0_q!@26W3 .#o EG5/SSTi—IX.&@/UIZ@0qi_@ ]5Ek6&EO!>wO rIXHA@ms /Stv/ .9/ s O>@U3 . O6&EY6Jb7=-S‰I#HAOA3 o H O>@ŽOr IXHA@Ž@/ .&SGE@76WIž.&@rX@ . @u>A5@6CIkO IXH@w.&@ST/UIZETO>¥q @UIY¦_@@ > IXHEY6-0Ek6 @/6&@v/u>A0 O 55U3 s /UIXETO> /S9/5UIZElM E‰I#EG@6 0/UIZ@R6 q /5   IZO IXH/JI 5O>rZ@ .&@ > 5@< E‰I&6 @UIXEO'STOo!i .&@tv/uET>g6 3>  >O¦> IZO'0/Ji />0 IXHA@ .&O'ST@ O'r O 55U3 s /IXETO!> /S[@ ]s Og6W3 .&@ E6—6XI#ETSS[0@ q /UIZ@0 8Zc4OA¦>SG@i @UIP/ S b‘ ~~ ;Jb#> twOg6WI-6WIY30E@R6&<9@ ]s Og6W3 .&@y¦_/R6 /R66&@66 @0 /R6 tv/>R3/Sš¦_O!.Z  M!@ .6W36 >O> tv/>R3/ST< q/R6&@0 O!> Œ&O!q IZE‰IZST@ 8Ydž/ .&Sli. } ‘p žH/>R3I . } ’'p

(27) H/> @UI /SYbž‘ ~~|p =mIIZ/ STEw@UI /SYb }'†ˆ‡p¢BP@>>@UIYI }'†7‘gp +m30!t23>0'6J6 O!> @UI /uS bC‘ ~~~gp¢z23@R6WIZO> } '†p¢1EY6J6[/>0(AIZO 5   }} 'pl+-/STEtv/ .&0v@UI9/SYb‘ ~~ ;nbc¦wO¥6YIY30ET@76 ¦wE‰IXHv/2t_O!.&@?s.&@5EY6@-/R6J6&@R6J6&tv@>RI Or9@U]s Og6W3 .&@0!ET0 >OIIZ/   @2ET>RIZO(/55%O3 >RI9s @ .6ZO>/Sr#/5IkO!.6#<6X35 H /R6 /S5O!HAO'S5O>'6X3gtwsIZETO!>A<0!ET/ q!@UIZ@R6 tv@SSE{IY36&<4@ s ESG@ sg6#i O!.P/ >RIZET5O>M3SY6/>RID0.W3 o EK>7IZ/   @<HA/u>A0 IX.&/U3tw/<4rX/tŽEGSKi HEY6WIZO.Wi O'r9^23 s3 i7IX.&@> ¡ 6 0E6@/R6 @Ž8k‚ ET   @SY6&@> }‡'† p 0@ySG/ ž/rXr#ET>'EG@ .&@v@UI /uS b }g†ˆ’;Jbgx?>Sli IY¦wO 6XIY30EG@R6mHA/0 5O>'6&EG0@ . @0¥q OIXH . O 55U3 s /IXETO!> /S />0—s @ .6&O> /uS.&EY6# vr#/5UIZO!.6&<R¦E‰IXHw/ms.&@5EX6&@?/R6J6 @R6J6&tv@u>7I*Or@ ]As O6X3 .&@?O!rM Elq.&/UIZETO>g6q3I ¦wE‰IXHAOA3I IZ/  ET>ovET>RIZOŽ/55O3 >uIORIXH@ .hO'55J3 s /UIXETO>/S'rZ/5UIZO.6h8kBPOAM!@ > 7E }}|p žO 55Ow@UI*/ S b }'†ˆ‡;Jb . xm3 .(OAq%Œ@5UIZE‰M@š¦w/76 IZO 6WIY30Ri IXHA@ /766&O 5EG/UIXETO> q @JIY¦w@@%> O 55U3 s /JI#ETO>/Sw@J]s Og6W3 .&@<-s @ .6&O>/S-.&Ek6&  rZ/5UIZO.6-/ >A0 ^-3 s3 iRIX. @ >¡¢6-0!EY6 @/6&@ EK> / 5 .&Og66&j&6&@5UIZETO> /S6W3 .#M @ i OrCe. @u>A5H tv@> ET>¥IXH@Ž.&@%o'ETO>g6-O'r fh/ i'6 0@ SG/C1[O'El. @?/ >02BD.&E‰IYIZ/ >ib.

(28) |. D. y. . . 9g  HAL author manuscript. #> }}'†ˆ< >ET>A@ O'rmIXH@ IY¦w@ SlM!@ O'55U3 s /UIXETO>/Sžs'Hi6&EG5uE / >g6w/JImIXH@ ‚ EK>EY6XIX. i OrmdžQR3Els tv@u>7I—ET> IXH@R6@ .&@ o ETO>'6?ET> 5Sl30@0 /SS9O r IXH@Žtv/SG@Ž5ElM ESž6&@ .#M />7I&6CIXHA@Uiš6/J¦ IXHA/UIi!@/ .?ET> IXHEY6—6XIY30Ai ET> IXHA@EK.ž36W3/7S ¦_O!.# b #> e. /u>A5@< O'55U3 s /nIXEO!> /S s Hig6&EG5E/>g6 /%.&@ . @R6#s O>'6&Elq SG@ rXO. twO>E‰IZO.FET>ˆo O 55U3 s /JIXETO!>A/RS @U]As O6X3 .&@R6D/>0¥s @%.FrXO.&twEK>o />>R3/S4H @/S‰IZH(@ ] /tŽET> /UIXETO >'6&<g¦wHEG5H / . @ytv/>0/UIZO.Wi(rXO.m/STS¦_O!.#  @%.6Jb. inserm-00225779, version 1. . O!.#  @%.6?5OA3 ST0(.&@rk36 @_IXH@¥6XIZ/UIXE6XI#ET5/uS9/>A/uSTig6@R6PO'r IXHA@EK.Ds @ .6 O!>A/uS90/JIZ/Ž/ >A0 IXH@ye. /u>A5@7¡ 6?>A/UIZETO!>A/RS. 5OtwtŽE‰IYIZ@@ rXO!. 0/JIZ/ s.#ORIZ@5nIXETO> ¦_/R6 ET> rXO!.&tw@0 O r IXHA@ 6WIY30Ri 8

(29) 

(30)  . &('")* +,"-"%%./ 021%3)45 ;Jb. !"$#%. ž)  %

(31). f*Hig6&EG5EG/u>g6 5O>0R35JIZ@0 / 6WIX.W35UIY3 . @0 EK>7IZ@ .WM EG@U¦ IZO OqIZ/%EK> 6X3'q%Œ@75UI&66 / o @ /u>A0 q ETO tŽ@75H/>EG57/RS. . @U]As O6X3 .&@?/ >0wtv@0!EG5/S HEY6WIZO.Wib O!.# (IZ/R6# g6P0@ rXEK> @0 /6?@>RIZ/ETSET>o q ETO't_@R5HA/u>EG5/S9@ ] s Og6W3 .&@—¦w@ . @ •8WEl;C36&ET>ˆo /_IZOOS¦wE{I#H(H />0S@< 8#ETEl;23*6&EK>o /¥M Elq./UIXET>ˆoƒIkOO!ST<ž8#ETEET;wtv/u>73/SmH/>A0!SGEK>o <D/ >0 8#ElM ;—.&@%s /uE .FET>o tv@R5HA/u>EG5/SD@QR3ETs'tv@>RIb 3q%Œ@5UI&6 ¦_@ .&@/R6#  @0 6&@%s / .&/UIZ@Sli(/ q O3I4¦H@UIXHA@ . IXH@Ji s @ .&rXO.Ft_@0 @/75HyIZ/R6Z  <rXO.HAOA¦ t_/u>i i!@/ .J6. IXH@ ivH /0v0O!>A@y6&O <g/ >A0ŽrXO!.[@/5HvO'rIXHAO6 @ i @/ .6&<gEGrIXH@ iŽ¦_@ .&@-@ ]s Og6&@0ŽrXO.ST@669IXH/>vO!>A@2twO'>7IXH / i @/ .&<'rY.&Ot O>@CIXO 6#El]vtwO>RIXHg6&< O.6#El]vtwO'>7IXH'69O.4twO.#@ˆb = 6&5O.&@ rXO. @/5%H @]As O6X3 .&@ ¦_/R6 5O!> 6WIX.W35UIZ@0 IXO @R6XIXEKtv/UIZ@ IXH@ IZORIZ/ S 0R3 .&/UIXEO!> O'r SGETr#@UIZETt @ O 55U3 s /IXETO!> /S*@ ]s Og6W3 .&@<@J]s.&@66 @0¥ET>(twO'>RIXH 6Jb c4H @_>73gt—q@ . O'r i!@/ .J6 ¦_O.#  @0y¦_/R6žt—3gS‰IZETs'SGEG@0 q i / >w@6XI#ETtv/UIZ@?Or/ M!@ .&/ o @?/>>R3/SgrX.&@QR3@>A5i!<'/76J6&@R6J6 @0Ž/R6 ~gb˜rXO!.9@J]s Og6W3 .&@?ST@66IXHA/>wO!>A@ t_O'>RIXH—s @. i @/ .&<9’ rXO.-O!>A@yIXO S@A66mIXH/> 6&El] twO>RIXHg6 < /%>0ƒ† rXO!.—6&El] IZO¥IY¦_@ SlM @ twO'>7IXH'6Jb*c HA@yIZORIZ/ S9@ ]s Og6W3 .&@ 6&5O!.&@2¦_/R6 IXHA@Ž6W3t Or4IXH@yrXO3 .žSTErZ@UI#ETtv@Ž6&5O.&@R6 <O!>A@_rXO.D@/5 H(0@rXET> @0 IZ/76# b!eO!.ET>g6XIZ/ >5@</yt_/R> ¦HO ¦_O.#  @0 0/EKSTi rXO!.?‘ ~ i @/ .6 ¦_E‰IXH M Elq. /UI#ET>ˆo IXOOS68#@UM@%. i 0/i 4†'ph5O>RIX.&Elq3IZETO!>(IZO IXHA@¥6&5O.&@ .

(32) ˜ †]‘ ~ . ~;&<4tw/>R3/S9H/>0SET>o 8#EG0@t—;?/>A0 36 @0 /—IZOO!S¦wE‰IZH H/>0SG@Ž8#ET0@tw;?H/0 / 65O.&@wO!r[|g†ˆ~gb. c4HEk6ž6 5O!. @m.&/ >o @0ŽrY.&O't ~_IkO ’||v8#tw@/>w‘ ’‡<'tv@0E/> '†ˆ<6WIZ/ >A0/ .&0w0@ M E/JI#ETO>v8^—;4‘g˜ˆ‡;p‘g ˜  Or IXH@y¦_O!.Z  @ .6DH/0 / 65O!.&@vO!r[|‘ O!.?t_O!.&@<4’’ . / 6 5O.&@ŽOrž’‘ O!rDtwO.&@Ž/>0 ’’ . ¦v@ . @Ž>OI. HAL author manuscript. @U]As O6 @0w8F6&5O.&@ *~;Jb c4H.&@@ O'55J3 s /UIXETO>/Sž@ ]s Og6W3 .&@ 5/UIZ@ o O.#E@A6-¦w@%.&@ 0@rWET> @0•9@ ]s Og6W3 .&@ 6 5O.&@R6O!r-~ ¦_@ .&@(STOA¦_j#ST@ M @7S @U]As O6X3 .&@Rp 6&5O.&@R69rY.&Ot ~gbl˜ IkO—| ~~_ET>7IZ@ .#tv@0E/JIZ@Rp/%>0Ž/26 5O.&@DOAM!@ .4| ~~—HElo'Hb. inserm-00225779, version 1. =-> /S‰IZ@ .&>/JI#ElM @?IXO(/2oSTOq /S465O!. @ ¦w/76ž5O>'6&ET0@%.FET>o 6@ s /%.&/UIZ@ Sli(rXO3 .m6W3q!jn6 5O.&@R6%•36&ET>o(/ IZOOS'¦wE‰IZH H/>A0!SG@<¥3*6&EK>ˆo / M Elq .&/UIZET>o IZOOST< tv/>R3/S H /u>A0!STEG>o < />0 .&@ s /ET.&ET>o tv@75H/>EG5/Sš@QR3gETs tŽ@>7Ib f*.&@STEKtvET> / .#i /> /Si6@6wEK> 0EG5/UIZ@0 IXHA/UImIXHA@ ST@ M@uSDOr—@J]s Og6W3 .&@ IkO @/5 H O rmIXH@6&@¥.&EY6#  rZ/5UIZO.62¦_/R6 6&Elo >Er#EG5/>7I#Sli HETo H @ . /twO!>ˆo 5/R6&@6 Or ^23 s3 i7IX.&@ > ¡¢6 0!EG6@/R6&@ˆb_z_OA¦_@UM!@ .&<(/ oSTOAq/S 65O.&@ ¦_/R6 s.&@ rZ@ .#. @02q @5/J36 @CIXH@?ST@ M @SY69O'r*@U]s Og6W3 . @CIXO2IXH@mrXO3 .4.#E6Z ŽrX/75UIZO.6¦_@ .&@mHE o'HSTiw5O.#.&@ST/JIZ@0gb c4H@msHig6EG5E/>wET> QR3gE .&@0w/ q O3I4/%>0w/R66 @66&@0ySG@Ek6X3 .&@-/5UIXElM E‰IZE@76 ET>M!O'SlMgET>o—IXH@26 /utv@mq ETO'tv@5H/>EG5/7S @U]As O6X3 .&@R69ET>2IXH@26 /utv@C¦_/ igb c4H@-5uSGET>'EG5/S@ ]/twEK> /JI#ETO>Žq @%o /u>—¦wE{I#Hv/—tv@0!EG5/SHEY6#IXO.WiA<gEK>A5S30ET>o HEY6WIZO.WivO'rh0!EG/ q @UIZ@76tv@SSE{IY36< @ s ETS@%s6#i 8#O. /%>RIZET5O>M3Sk6 />RI(0.X3 o EK>7IZ/   @ ; />0 H/>A0 IX.&/U3tw/</A6 ¦_@SSv/R6 rZ/tŽEGSEG/SyHEY6XIZO!.Wi Or ^-3 s3'i7IX.&@ > ¡ 6 0EY6&@7/R6 @b_f*Hi6EG5EG/u> 6 /SY6&O /76#  @0 / q O3I / ST5OHO'S(5O!> 6W3tysIZETO> />0 >OIZ@0 IXHAO6 @ 6W3q%Œ@75UI&690. / > vtwO!. @ IXH/%>Ž˜w6&@ .WM ET>o690/ETSKib c4H@ s.&@R6&@>A5@¥O r?/ s @ .6&O>/S.&EY6#  rZ/5UIZO.-8#/ >i O!>A@ O!r?HEY6XIZO.Wi O'rP0!EG/ q @UIZ@76—tv@SKSGE‰IY3*6&<@ s ETSG@ s6#i O!. / >7I#ET5O!>Mˆ3gSY6/>RI[0.W3 o ET>7IZ/   @<O!.[H/ >A0 IX.&/J3 tw/<rZ/tŽEGSKi(HEY6WIZO.Wi O'r^-3 s3'i7IX.&@> ¡ 6D0!EY6 @/6&@<O.ž/ST5OHO'S 5O>'6X3gtwsIXETO>wOr ˜w6 @ .#M EK>og6X0/ ivO.4twO.&@<5Ot—s / .&@0¦_E‰IXH—>O> @ ;¦_/R69/S6 OŽ5O>'6&ET0 @ .&@0gb œG.

(33) c4H@ysHi6EG5/S9@ ] /tvEK> /JI#ETO> STO O  @0¥rXO.?5 STET>EG5R/S6&ETo >g6?Or IXHET5   @>ET>o Or IXH@ws /Stv/ .?rX/R6 5uEG/v/u>A0 XO. r#SG@ ] ETO'>w5O!>7IX.&/5IY3 .&@CET>—s H/SG/>]w‘ <'’<|O!.9˜ b HAL author manuscript. . &&GF&G$glG. ^_/UIZ/y¦w@%.&@ / >O>itvE @0< @ >7IZ@ .&@0<9/ >A0 />A/uSTi 7@0 ¦_EKIXH =w 6&O'rIY¦_/ .&@ 8=w Mg† b¢‘ <ž!=w #> 6WIZE‰IY3IZ@. #>A5<ž/ .#iA<!€ ž <!„ '=?;JbRBPElM/ .&ET/UIZ@-/u>A/SKig6@76 3*6&@0¥IY30@ >RI*I9/ >A0Ž5HEGjF6&QR3/%.&@ IZ@R6XI&6&<g/ >A0Žt—3gS‰IZElM / .&EG/UIZ@ / >A/uSTig6EY623*6&@0 STOo'EY6WIZEG5 twO'0@SY6&< ¦wH @%.&@¥.&EY6#  r#/5JIZO!.6?¦_@ .&@ @>7IZ@ .&@0 ET>RIZO IXH@ twO 0@S?/STSIZO!o @UIXHA@ .Jb. inserm-00225779, version 1. #>7IZ@ .&/5UIXEO!> 6q @UIY¦_@@ >vs @ .6&O> /S/>0 O 55U3 s /UIXEO!> /Sr#/75UIkO!.6 ¦_@ .&@mIZ@R6YIZ@0 8kf.ZO'5?1[O!oE6XI#E5 3g>A0@ .?=v 6&OrIY¦_/ .&@ ;Jb7=—66 O'5ET/JI#ETO>'6*¦w@ . @?5O!> 6&EG0@ .&@0Ž6&ETo'>ETr#EG57/>IETrgIXH@ms jWM /Sl3@C¦w/76 SG@R6J6*IXH/ >w~gb{~'˜ b.

(34) ‡ › . . D . . c4H@26WIY30iwET> 5Sl30@0—‘ <| ~ wtw/SG@?5uElMES6&@ .#M!/u>7I&66&@@u>wET> }}'†8 S@A66IXH/>wrXEM@ms@ .&5@u>7I*.&@ r36@02IXO—q @ HAL author manuscript. ET> 5S30@0 IXH@ 6WIY30i;nb . E‰IZH¥‘ ‘ tw@> 6W3r#r#@%.FET>ˆo rY. O!t ^-3 s3'i7IX.&@%> ¡ 6P0!EY6&@/A6 @<IXH@ws O!ET>7Ižs.&@UM!/uS@u> 57@. ¦_/R6?† bl†Žs @ . 5@ >RIb ž/R6 @ 6X3'q%Œ@5JI&6&<'IXH/UI[E6 <IXHOg6&@w0ET/%o'>AO6 @0 ¦_E‰IXHŽ^23 s3 i7IX.&@ > ¡¢6D0!EY6&@/A6 @<¦_@ .&@O!ST0@. O> /UM@ .&/ o @¥IXHA/u>šIXHAO6 @ >AOAIv6&O 0E/ o'>AO6 @0 8F˜ˆ~gb{‡ƒi @/%.6v8^ ˜ b¢|;—M @ .6X36w||bl†ši!@/ .6 8^ ‡gb{ ;&< 0@ o.&@@ O!rvrY.@@0O't 8k^-e; ‘| ~| < M!/uSl3@ O'r—I  b{~'˜ˆ< s

(35) *~gb{~~~ ;bmc9/Uq ST@  .&@ s O.kI&6wIXH@šq ElM/ .&ET/UIZ@. inserm-00225779, version 1. /R66&O 5uE/UI#EO!>g6U• /STSwO'rwIXH@ 6W36Zsg@5JIZ@0 s @ .6&O>/S—/>A0 O'55J3 s /nIXETO> /S—rZ/5UIZO.6 ¦w@ . @ /R66&O 5 ET/UIZ@0 ¦wE‰IZH 0E6@/R6 @ s.&@ M /SG@> 5@bžc4H@ O'55J3 s /UIXETO>/S-@ ]s Og6W3 .&@ 65O!. @ ¦_/R6¥6&E o'>EGrWEG57/>RIZSi HElo'H @%. /twO>o 57/R6@ 6W3q%Œ@75UI&698Z’‡‡—8^ ‘g†ˆ~7;M @ .6X364‘‘ ’w8^ ‘g˜ˆ~7;&<R^2e(‘| ~| <M /S‰3@?OrgI9† b | ‡ˆ<!s

(36) *~ b‰~~~ ;nb ^wE6@/R6&@¥s. @UM/S@>A5@¥/5R5O!.&0ET>ˆo IZOšO 55U3 s /IXETO> /Sž@ ] s O6X3 .&@¥5/UIZ@ oO.Xi ¦_/R6v6WIY30EG@0ƒ6 @ s / .&/JIZ@uSli rXO!. 6W3qAo.&O3 sg6mq /6&@0 O>¥IXHA@Žs.&@R6&@>A5@ O!.-/Jqg6&@>A5R@ Oržsg@%.6&O>/S9r#/5JIZO!.6 8Wc9/Uq ST@Ž#Z;JbZ> /SKSž6&E‰IY3/UIZETO>'6 < s.&@UM!/S@>A5@ ET> 5 . @/6&@0 ¦wE‰IXH SG@ M @S(O'r O 55U3 s /UIXETO>/S @ ]s Og6W3 .&@bwc4H@ 5%.W30@ x200'6 N?/JIXETO 8#xmND; /R66&O 5uE/UIZ@0 ¦wE{I#H O'55U3 s /UIXETO>/S[@]As O6X3 .&@yHA/0 QR3gE{IZ@¥6&EKtvESG/ .?tv/ o >E‰IY30@ /twO>o IXHOg6&@v@]As O6 @0 O. >OIIkO¥s @ .6ZO>/SrZ/5UIZO.6D/ >0(/SKSIXH@wEK>7IZ@ .&/5JIXETO!>ŽIZ@76WI&6q @JIY¦w@@%>ŽIXH@R6 @yrZ/5UIZO.6¦w@J.&@—>ORID6#E o'>EGrWEG57/>RI 8#c9/Uq ST@m#Z#;Jb7c4HE69Etws'STEG@6IXH/JIgIXH@?@ rXrZ@5UI&695/>2q!@?5O>g6&ET0'@%.&@0w/R69t23S‰I#ETs STE57/UIXElM@b BPORIXH¥s @%.6&O>/S9/>0 O 55U3 s /JI#ETO>/S4.&EY6#  rZ/5UIZO.6C¦_@ .&@v/R66 O'5ET/JIZ@0 ¦wE‰IXH(^23 s3 i7IX.&@ > ¡ 6P0Ek6@/R6&@ ET>¥IXH@ t—3gS{I#ElM/ .&ET/UIZ@ / > /Slig6EY6v8Wq O.&0@ .#STET> @š6&EKo >ErZE5/u>A5@ rXO.wHEY6WIZO.Wi Or—0EG/ q @UIZ@R6vtw@SSGE‰IY36#; < ¦wE‰IXH / 0Og6&@ @rWrZ@5UI rXO!.PO'55J3 s /nIXETO>/S9@ ]s Og6W3 . @Ž8#/0JŒW36XIZ@0 xmN¤O!rž‘b¢‘ ~¥rXO.mET>RIZ@ .&tw@0!EG/UIZ@ŽST@ M!@uS9/>A0 O!r ’gb ~ rXO. HETo'H_@]As O6X3 .&@mST@ M@S'ET>2IXHA@?0@UIZ/ETS@0ytwO 0@ST<'c9/Uq SG@m&‹2;nb.

(37) †  “ .  . .  .  %

(38) T& HAL author manuscript. c4HEk6PEk6 O!>A@ŽO'r IXHA@Žr#ET.6WIP6WIY30EG@R6PO'r ^-3 s3'i7IX.&@> ¡ 6-0Ek6@/R6&@ŽET>¥IXHA@y¦wO.# sSG/5@—IZO IZ/   @ŽO 55U3 s /IXETO>/7S / >A0ytwO6XI*OrIXHA@25SG@/ .&Sli @R6WIZ/Jq SEY6&H@0ws @ .6 O!>A/uS .&EY6# ŽrZ/75UIXO.64ET>7IZOŽ/55OA3 >Ih8#+-/ STEtv/ .&0w@UIh/SYb7‘ ~~ ;JbRYI EY6D/Sk6 O O>@wO!r4IXH@wr#El.J6WI4IkO¥ET>5Sl30@w/_s. @5Ek6@wQR3/>RIZE‰IZ/UIXElM!@y/66&@66&tv@>RI O!r[O 55U3 s /UIXETO>/Sh@]As O6X3 .&@< @R6Zs @5E/SGSKiwrXO. t_/u>73/S!¦_O!.Z Ž8Y19Ek669/>0 IXO 5   }} R;Jb. inserm-00225779, version 1. D (K& ¥&& %

(39) œ ¥"* 

(40) m&& . . . c4H@ rXET.6WI_SKEGtwE‰IZ/UIZETO!> ET>ƒIXHEY6 6XIY30Ai EY6—IXH@ 5 . O66&jF6 @5 IXETO!>A/S?0@R6&ETo > /u>A0 @ ]As O6X3 .&@ /R66 @A66&tv@u>7I2q i QR3@R6XIXETO!>> /El. @b O!.#  @%.6¦wE‰IXH-^23 s3 i7IX.&@> ¡ 6 0!EY6&@7/R6 @ tv/ iwq @?twO.&@ SGET  @uSTi—IZOŽ0@76&5 .#Elq!@CIXH@ET.¦wO.# v/R6 . 6WIX. @ >R3O36Jbc4O /UM!O!ET0 6W35uH(.&@5/uSGS q EG/R6 <4@ ]s Og6W3 .&@—¦v/R6P/R6J6&@R6J6 @0¥qi¥IXHA@ O'55U3 s /UIXETO>/S4s Hig6&EG5E/>g6 < ¦HO  >@U¦ IXH@ ¦wO.#  @ .6 / >A0ƒIXH@ET.?Œ&O!q6Jb#> /00!E‰IZEGO!>A< IXHA@ .&@SG/UIXElM@ s.&@5uEY6&ETO > O'r-IXH@šQR3@6XIXETO!>6 6#HAOA3ST0wH/ M @?STEtŽE{IZ@0—.&@5/SSq EG/6Jb c4H@ms Os3gST/JI#ETO>2¦_/R695O t—s O6 @0wO'rtv/SG@?5EMETS6&@%. M!/>I&64ET>2IXH@m‚ ET>Ek6XIX.#iwO'rgd QR3gE s'tv@>RIh/R66&EKo > @02IXO BD.&E‰IYIZ/ >i />0ŽIXH@ fh/ ig6D0 @—S/21[O'E .&@b‚ @>Ž¦_@ .&@w5HOg6&@ > q @5/U36 @ IXH@w0EY6&@7/R6&@wtv/uET> SKi /urXrZ@R5JI&6žtŽ@>A< / >A0ŽtwO6XI¦wO.# sST/57@26XIY30!ET@69H / M @?rXO'5J36 @0wO!>vtŽ/SG@m¦wO.#  @ .6 8k‚ El   @SY6&@> }‡'†'p +m30!t—3>0'66 O!>v@UI /SYbš‘ ~~~'p 0@ SG/ C/r#rZEK>EG@ . @ @UI /SYb }'†ˆ’'p žH/>R3I . . } ’'p¢B?OM @> R E }}|p c4HO'tw/6¤/>0 CSG/ .#  @ . }}‘gp

(41) H/>¤@UI /SYb—‘ ~~|;Jbc HEG6šs Os3gS/UI#EO!> ¦w/76 6@ST@5JIZ@0 s.&@5EY6&@STi q!@R5/U36&@ IXH@ O 55U3 s /JIXETO'> sHig6&EG5EG/>g6ET>—IXHEk64e. @u>A5HŽ0@%s / .WIZtw@>RI*H /0wOAq6@ .WM!@0Žtv/u>iy5/6&@69O'rg^-3 s3'i7IX.&@> ¡ 6[0!EY6&@7/R6 @2ET>—IXH@E. ¦_O!.# ET>ˆoŽs Os3 ST/UIZETO!>g6[/ >A0Ž0@5EG0@0—IZOys / .YIXET5ETs /UIZ@2ET>—IXH@—6WIY30RiwqivEK> 5Sl30EK>o E{I9EK>—IXHA@uE .0/ESTi—¦_O!.#  rXO./ iA@/%.Jbc4H.&@@-ST/5   @0—IXH@mIXETtŽ@mIZOŽs /J.kIXET5ETs /UIZ@bAc HˆEk6[EY6>OIh@U]s @5UIZ@02IXOŽST@/0_IZOv/Pq ET/6 <6&ET>57@2/SGS IXH@ O 55U3 s /IXETO>/Sžs'Hi6EG5EG/u>g6v/%.&@ EK> 5HA/ .#o @ O!rw6&EtvESG/ . 6&/tws S@76vO!r?¦wO.#  @ .6JbmET>5@ IXHA@ / >>R3/7S tv@0E5/uS*@ ] /tvEK> /JI#ETO>ŽqiŽIXHA@—O 55U3 s /UIXETO>/Ss Hig6&EG5E/> 6žEk6D5O!t—s3SY6&O.#i<'IXHA@y6WIY30i ET> 5Sl30@R6ž/SSgIXH @ 5ElM ESw6&@ .WM/>7I&6¥6X3 .WM @ i @70 qi IXH@šO 55U3 s /JI#ETO>/S?s Hi6&EG5uEG/>'6 0R3 .&ET>o IXH@ i!@R/%.&<?@U] 57@ sIIXHOg6&@ ¦HO.

(42) } .&@ r3*6&@0IZO2q!@ ET> 5S‰30 @02IXH@26WIY30Ri_8#SG@R6J6IXH/>wrXEM@ms @%.5@ >RIX;Jbˆ+?STOAq!/SSKi!<AIXHA@26&/tws'SG@?ET>2IXHEY6C6XIY30Riw57/> q @ 5O>'6&EG0@ . @0 /6—.&@ s. @R6&@>RIZ/JIXEM!@ O'rmIXHA@ IZ/ .#o @UI-sAO!s73gS/UI#EO!>bhf*.&@JM /SG@u> 5@ ET>šIXHA@ SGE‰IZ@ .&/JIY3 .&@ M /%.FEG@6 rY.&O't. IXO ‘ ~Žs @ .&5@ >7IX<0@ s @ >A0!ET>ˆo(O!>wIXH@2s Os3 SG/UIXETO> <¦HET5H tv/ i .&/>o @—rY.&O t IXHOg6&@ ¦HOg6&@?¦wO.# . HAL author manuscript. ET>M O'SlM@R6ž>AOyq ETO'tv@5H/>EG5/S@ ]s Og6W3 . @PIZOvO!ST0@%./>0ŽHETo HSKi @ ]s Og6&@0ws O!s3ST/UIZETO>'6[8#+-/SEtv/ . 0Ž@UI /uS b ‘ ~~ ;Jbwc4H@ s.&@JM /SG@u> 5@ O!r ^-3 s3'i7IX.&@> ¡ 6 0Ek6 @/6&@ ET> IXHEY6 6XIY30Ai ¦_/R6 6&EtvESG/ .šIkO¤IXHA/UI ET> IXH@ NP@ i %Œ/ M El (5%.&O66&jF6 @5UIXETO> /S6W3 .#M!@iA<@R6XI#ETtv/UIZ@0v/UI ~ b‰˜—s @ . 5@ >RI /twO!>ˆo tv@u>vET>yIXH@?|g˜ˆjF˜ˆ}jWi @/ ./%og@ o.&O3 s 8Z+P30t23>0'6J6 O!> @UID/SYbg‘ ~~~;P/ >0 IXO IXHA/UIET> IXH@v5 .&Og66&j&6&@5UIZETO>/S6WIY30i(qi¥‚ ET   @SY6@u> 8#}gb{’. inserm-00225779, version 1. s @ .&5@ >RIX;98k‚ El   @SY6@u> }‡'†7;Jb xm3 . 6XIY30Ri(0EG0¥>OIž5O!> 6&ET0@ .IZOAq!/55O 5O!> 6W3t—sIZETO!>bgc4H@—.&OSG@yOrm6&twO  EK>o H/ q E‰I&6DEK>(^23 s3 i7IX.&@ > ¡‰6 0E6@/R6 @ ¦_/R6w>AOAI5 SG@/%.FSli 6&HAOA¦> 3>RIZETSm/rIZ@ .-IXHEk6v6WIY30i ¦w/6w0@6&Elo > @0gbž'ET>A5@ IXH @>< IY¦O 6WIY30ET@6 H/ M!@—5O>5Sl30@0yIXH/UI*IXOq /55O¥5%O>'6W3twsI#EO!> E6 /2.&EY6# (rX/R5JIXO.%•/—5 .ZO66m6&@5UIXETO>/S46WIY30i ET> }}‡ />0 /ms.&Og6#s @5JIXEM!@26WIY30iwET>w‘ ~~| <!q OIXHwOr¦_HE5Hw/SY6&Ov/0JŒ 36XIZ@0yrXO.9ORIXH@%.4s @ .6&O>/S.&EY6# vr#/5JIZO!.6 8kBž3 .#o @ @UI / SYb }}‡'pl+-O 0RIXrY.&@0'6&@>(@UI / SYb ‘ ~~|;Jb!zO¦_@UM @ . <>@E‰IZH@%. 6XIY30AivIXOO ¥sˆ.&@5E6 @uSTi O'55U3 s /UIXETO>/S.&EY6#  rZ/5UIZO.6šET>7IXO /55O3 >RI 8#+-/ STEtv/ .&0¤@UI / SYb—‘ ~~ ;U•Bž3 .#o @ @UI /%S 0E0 >AOAI .&@5%O!. 0@0 O 55U3 s /IXETO>/7S @U]As O6X3 .&@Rpž+-O 0RIXrY.&@0'6&@> @UI/SžO!>STi 6WIY30ET@0 IXHA@¥s.&Os O!.YIXETO> Or?s'Hi6EG5/SD/75UIXElM E‰I#EG@6w/JI?¦wO.#  8W>AORI 6&Elo >Er#EG5/>7I#Sli /R6J6 O'5ET/UIZ@0 ¦wE{IXHš^23 s3 i7IX.&@ > ¡ 6v0EY6&@/6 @u; <m/ >A0 STO¦ @0R35/UIXEO!> SG@M!@S?8#5O>'6&EG0@ . @0 q i /U3IXHAO!.6v/76v/ s.ZO]i O'r—tv/>R3/Sž¦wO.#  / >0 6&ETo'>ETr#EG57/ >RIZSli /R6J6&O 5ET/UIZ@0š¦wE‰IXHš^-3 s3 iRIX. @u> ¡ 6v0EY6@/R6&@; 8kBž3 .#o @?@Ih/ SYb }}‡'pl+-O 0RIXrY.&@0'6&@>w@JI4/%SYbR‘ ~~|;nb $&G

(43)  _

(44) 

(45) (

(46)  %! "Z$ &  —! & %

(47) T[G

(48) J

(49). c4HEk6 6XIY30Ai 0@twO'>'6XIX.&/UIZ@R6 IXH@ /R6J6 O'5ET/UIZETO> q @UIY¦_@@ > s @ .6 O!>A/S¥.&EY6#  rX/75UIZO.6ƒ/ >0 ^23 s3 i7IX.&@ > ¡‰6 0E6@/R6 @b‚ Og6WIw6WIY30E@R6—.&@%s O!.WIPsOg6&E‰IZEM!@ /R6J6 O'5ET/UIZETO>'6—q!@UIY¦w@@ > ^-3 s3'i7IX.&@> ¡¢6w0Ek6 @/6&@ />A0 /uSG5OHOgS ET>RIZ/   @ 8[@ .&/#ŒEG5 />0 e*ET>g6&@> ‘ ~~|pl=mIYIZ/ STE-@UI /SYb }'†ˆ‡'p BD.&/0!STO¦ />A0 ‚ƒOA¦_/UI }'†ˆ 'p¢Bž3 .#o @ @UI / S b }}‡'p €ŽOq SG@w@UIž/SYb }}‘gp +2O 0RIXrY.&@0'6 @u>(@JIž/SYb ‘ ~~|;&</ o @w8#+P30t23>0'6J6 O!>(@UI / SYb ‘ ~~~'pT+-O'0IXrY.&@0'6@> @UI / SYb ‘ ~~|;&<0ET/ q!@UIZ@R6DtŽ@STSE{IY36D8#+m30t23g>A066&O>(@UI / SYb'‘ ~~~gp +2O 0RIXrY.&@0'6 @>(@UIž/SYb ‘ ~~|gp +2@OoH@%og/>.

(50) ~ @UID/%SYbg‘ ~~|;&<rX/tŽEGSEG/S HEY6WIZO.Wi Or ^-3 s3'i7IX.&@> ¡ 6?0EY6@/6&@v8#c O¦>ST@ i @UIC/uS bg‘ ~~ ;&<4/ >0(H /u>A0 IX.&/U3 tv/ 8W=mIYIZ/ STEž@JI/uS b }'†ˆ‡'p¢‚ ET   @SY6@u> }‡'†p‰1[ElM EK>o6WIZO>@ / >0 e*EG@S0 }}}gp¢z23@76WIZO> } '†7;Jb4c4H@(.#OST@ O'r @ s ETS@%s6#iƒ/u>A0 />RIZET5O>M3Sk6 />RI0.W3 o ET>RIZ/   @<HAOA¦_@UM @.&<.&@%tw/EK>g6v5O!>7IX.#OM @ .6&ET/Sm8Z+2@OoH@%og/> @JI/uS b HAL author manuscript. ‘ ~~|gp c H73 .J6WIXO>(‘ ~~’;&<4/ S‰IXHAOA3 oH 6WIY30ET@6?H/ M!@ŽrXOA3 > 0 /wHETo'H(s.&@UM/SG@>5@vO!r ^-3 s3 iRIX. @u> ¡¢6?0EY6&@/6@ ET>—s/UIXEG@u>7I&6¦E‰IXHw@ s ESG@ sg6#iv8#=?.&/rX/?@UIh/ S b }}‘gp  .&E‰IZ5%HSY@ iw@JI4/%SYb }‡ ;nb $&G

(51)  _

(52) 

(53) ($$&G "Z$ & % ' & %

(54) T[G

(55) 

(56). inserm-00225779, version 1. @ rXOA3>0 IXHA/UI tw/>R3/SŽ¦_O!.#  ¦w/R6 6&ETo'>EGr#EG5/>RIZSli /R66 O'5ET/JIZ@0 ¦wE‰IXH ^23 s3 i7IX.&@ > ¡ 6 0Ek6 @7/R6&@ /u> 0 . Oqg6&@%.WM @0w/?5SG@/ .90Og6&@jX.&@R6#s O>'6 @m.&@ST/UIZETO><¦wE‰IXHw/>w/xmN O!r b{‡'˜-rXO!.4tw/>73/uSHOqq E@76&< O!r‘b¢‘wrXO!.9/> ET>RIZ@ .&tv@0EG/UIZ@ t_/u>73/S O 55U3 s /UIXEO!>A/uS @ ]s Og6W3 .&@ 5/UIZ@ o O.WiA<¥/ >A0 O'r ’gb rXO!. IXH@ HETo H @ ]s Og6W3 .&@ 5/UIZ@%oO.Wib'‚ />R3/S9S/ q!O!.&<ET> 5S‰30ET>o H />A0 M ElqA.&/UIZETO!> @U]s Og6W3 .&@v/>0 tv/u>73/S HA/u>A0!SGET>o¥¦w/76?O> @ŽO'r IXH@ rWET.6XIw5/U36&@6vO'rO'55U3 s /UIXETO>/S-0Ek6 @/6&@ 0Ek65J36J6&@70 ET>šIXH @ tv@0EG5/S?SE‰IZ@ . /UIY3 .&@ 8k^_@ut—q!@ }} ;nb z_OA¦_@UM @%.&< IXH@ .&OST@ Or2tv/>R3/SžO 55U3 s /JI#ETO>/Sž@ ]As O6#3 .&@(/R6_/ .&EY6#  rZ/5UIZO.2rXO.?IXHE6w0EY6&@/6&@ EY6Ž6XI#ETSGS 0@Uq!/UIZ@0w8#c4O¦—>ST@ iv@JI4/%SYbR‘ ~~ ;nb #>¤/ 6WIY30i¤/ q O3I H/ >A0j#/ .&t M EqA./UIXETO> 6#i> 0.&O tw@ ET> ¦wO.#  ET>o WIZ/STEG/> tv@u>A<yBPOAM!@u> 7E(@UI /uS b. Oqg6&@%.WM @0 / 6&ETo >Er#EG5/>RI /R66&O 5ET/UIZETO!> q @UIY¦_@@> M Elq .&/ IXETO> />0 ^23 s3 i7IX.&@ > ¡ 6(0EY6@/R6&@ 8Z/xPN . ‘b‰ . b¢‘| jF˜Ab | }

(57) X<g/0JŒW36XIZ@0ŽrXO!.[/ o @</uS5O!HAO'S/>0—IZOAq!/55O 5O!> 6W3tysIXEO!> 8kBPOAM!@u> 7E }}|;#;J

(58) b žO 55O @I9/ S b . rXO3g>A0 IXH/JI(/ HEY6WIZO.Wi O r M Elq. /UI#EO!> @]As O6X3 .&@š¦w/R6 t_O!.&@ rY.&@QR3@>RI /ut_O'>o 5/6&@ 6X3'q%Œ@5UI&6 IXHA/R> 5O>RIX.ZO!SG68 CO 55O @JI9/SYb }'†ˆ‡;Jb'ETtŽEGS/%.FSli!<gc HO tw/R6ž@JI9/SYbrXOA3>0 /—6&ETo'>EGr#EG5/>RI /R6J6&O 5ET/UIZETO!>wq @UIY¦_@@> H/>A0j#/ .&t M ElqA.&/UIZETO!> 6#i> 0.&Otw@ />0 ^-3 s3 iRIX. @u> ¡ 6P0!EX6&@/76&@y¦wE‰IXH /Ž0Og6&@jW. @R6#s O>'6 @y.&@SG/UIZETO!>A<q3Iž>AO .&@ST/UIZETO>2IZO2IXH@26@ M @%.FE{IWivOrIXHA@ HA/>0j#/ .&t M Elq .&/JI#ETO> 6#i> 0.&O tw@?8#c4HO'tw/6[/ >A0 C SG/ .Z  @ }}‘;Jbˆc4H@R6@ 6WIY30E@A6wSG@0š1[Ek6J6v@JI/uS bhIZO 5O>5S‰30@¥IXH/JI?IXH@ .&@ EY6w/ o OO 0 6W3 ss O.kI-rXO.w/ > /76J6&O 5uE/UI#EO!>šq@UIY¦_@@> M Elq .&/UIXETO>w@ ]s Og6W3 . @?/ >02^-3 s3'i7IX.&@ > ¡¢690Ek6 @/6&@?8k1[EY669/>A0 IkO'5   }} 7;Jb  O!t_@ 6XIY30!E@R6w.&@ s O.kI>O 6#Elo >Er#EG5/>7Iw/R66&O 5ET/UIZETO!>šq@JIY¦w@@%>šIXHE6v0!EY6@/76@ /%>0 @uE{I#HA@ .ŽHA/u>A0!SGET>o O. o.&Elss EK>ˆo ¦wE{I#H rXO.&5@bž#> ‘ ~~| <-/ 6XIY30Ai 3*6&EK>ˆo 0/UIZ/ rY.&O't IXHA@ € /UIXETO> /S ‚ƒO!.Xq E0E‰IXi 3 .WM @ i E>.

(59)  d[>o S/>A0 />A0 . /uSG@6-rXOA3 >A0¥IXH /UIDtŽ/>73/uS[O 55U3 s /UIXETO>/Sm6 O'5ET/S[5S/76J6m¦w/6->OIP/R66 O'5%ET/UIZ@0¥¦wE‰IXH /R>. ET> 5 .&@/6 @0ƒET> 5EG0@>5@ Or ^-3 s3'i7IX.&@%> ¡ 6w0EY6&@7/R6 @ 8 —HA/u> @UI/SYb4‘ ~~|;Jb9ch¦_O ORIXH@%.Ž6WIY30EG@R6.&@ s O.WIZ@0

(60). s.&@UM!/S@>A5@ ¦_/6¥6&EGtyEGSG/ . ET> o.&O3 sg6 O!rwtw/>R3/S-/>0 >AO!>Aj t_/u>73/Sm¦wO.#  @ .6 8kd / .#Sli } ‘p žH/>R3I . HAL author manuscript. } ’;Jb=-STS IXH. @@ 6WIY30EG@R6 <HO¦w@UM!@ .&<STEtvE‰IZ@0š@ ]As O6#3 .&@(/R66&@66&tv@>RIDIXO /Ži @R6X>O QR3@R6XIXETO!>b O'tw@ 6#s @5uETr#EG5v@]As O6X3 .&@w/R6J6&O 5ET/UIZ@0Ž¦wE‰IXH(tv/>R3/uS4HA/>0SET>'o EK>ŽIXHEY6Ds O!s3ST/UIZETO>¥tvETo'H7IžET>5 .&@/A6 @2IXH@—.&Ek6&  OrC^-3 s3'i7IX.&@> ¡ 6w0EY6&@7/R6&@ twO.&@ŽIXH/> OAIXHA@ .@]As O6X3 .&@R6EK> tv/>R3/S ¦_O!.#  @%.6/u>A0 IXH736w@ ]s SG/uET> OA3 . .&@R6X3gS{I&6Jb!eO!.D@U]!/uts'SG@<46&O'tw@wOr IXHA@R6@2¦wO.#  @ .6D@U] 5/ M!/UIZ@2IY.&@ >A5H@6¦wE‰IXH s EG5   / ] @6DO!.D5 S@/ .Cqˆ36&H@6. inserm-00225779, version 1. rY.&O't 6#s.&ET>o¥IXH. OA3 oH /U3IY3 tw><¦wE{IXH /yq ETSSTHAO'O ¥q @r&O.&@2IXH@ }'†ˆ~'6?/%>0 ¦wE{IXH /yqA.W36&H 5J3IYIZ@ .D/ rIZ@ .Jb ‚ El  @Sk6 @> @UIw/SYb[0!EY6XI#ET>o3EY6&H @0 0!ETr#rZ@ .&@>RI_ST@ M @SY6vO'rwO 55U3 s /IXETO!> /SP@]As O6X3 .&@ / >0 rXOA3>0 / 5uSG@7/ . 0Og6&@jW. @R6#s O>'6 @Ž.&@ST/UIZETO!> q!@UIY¦w@@u> tv/>R3/S4¦wO.#  / >0 ^23 s3 i7IX.&@ > ¡ 6-0EY6@/6&@<¦wE‰IXH /Žs.&@ M /SG@>5@ E> IXH@ HETo'H @ ]s Og6W3 . @ o.&O3 s 6&ETtvESG/ .?IZOšO3.-.&@R6W3S‰I&68 ˜ s @ .&5@ >7I-ET> IXH @El.v6WIY30i />0 s @ .&5@>7I-E> O3 .6#;b BP@ >>A@UIYIw@I_/ SYbrXO3 >0 / STO¦w@%.ys. @UM /SG@> 5@¥IXH/>š¦w@ 0EG0 ET> q OIXHšIXH@ STOA¦ 8Ws.&@UM!/uS@u>A57@ s @ .&5@ >RIX;-/ >A0 HETo Hš8Z‡ s @%.&5@>RIX;-@U]As O6X3 .&@Žo.&O3 sg6-8B?@>>A@UII }'†7‘;Jbg^w@ ST/ D/urXr#ET> E@%.&@ @UIP/SrXOA3 > 0 . H/%.&0Žtv/u>73/SSG/ q O.9OM @ .t_/u>ivi @/%.64¦w/6[5O.#.&@ ST/JIZ@0_¦wE{IXH_^-3 s3 iRIX. @ > ¡ 6[0Ek6 @/6&@<@R6#s @5EG/SSTi ET>yIXH @ iAOA3>o @%.m/%o @_o. OA3 s(8#0@—ST/ ž/rWrZEK> EG@ .&@w@UI / SYb }'†ˆ’;Jb'X>ŽIXH@2NP@ i %Œ/ M ET  6WIY30i<*+P30t23>0'66&O>(@UIž/S . rXO3g>A0š/ s.&@ M /SG@u> 5@¥O'rž^23 s3 i7IX.&@> ¡ 6—0EY6@/6&@(/twO'>o tw/SG@ tŽ/>73/uS9¦wO.#  @ .68#ET>5Sl30!ET>o tv/>R3/7S SG/ q O.&@ .6 < 6&@/ut_@u> />0¥rX/%.Ftv@ .6#;D/>0¥ET> IX.&/0@R6&tw@>(8&5/ .Zs @ >RIZ@ .6&<q SG/5% 6&twE‰IZHg6&<*/ >0¥tv/6&O>'6Z;DO'r ˜ s @ .&5@ >RI 5Ot—s / .&@0 ¦_E‰I#H s @%.&5@>RI EK> ORIXH@ . O 55U3 s /IXETO>g6 8k¦wE‰IXH 3g>ElM@ .6&E{IWi 0@%o.&@@6#; 8#+m30!t-3g>A0'6J6&O> @JI(/SYbm‘ ~~~;Jbž‚ / >73/S2¦_O!.Z  @ .6 / >0 IX.&/0@R6&tv@> HA/0 /> x N rXO. ^-3 s3'i7IX.&@%> ¡ 6 0E6@/R6 @26&EKo >ErZE5/u>7I#SliwHETo H@ .IXHA/>w/SKSORIXH@%. tw@>wET>2IXH@26XIY30Aib “ $% #>(5O>5Sl36&ETO'>A<O3 .?6kIY30Ri(rXO3>0ŽIXH/UI /rIZ@ .D5 O>'6&EG0@ ./UIXETO>(O'r9s @ .6 O!>A/uS*.&Ek6Z  rX/75UIXO.6 <tw/>R3/S¦wO.#  @U]As O6X3 .&@w/ ss @/ .6IZO q @w/R6J6&O 5ET/UIZ@0Ž¦wE‰IXHŽ^-3 s3 iRIX. @u> ¡ 6P0!EY6 @/6&@b1[O!>ˆo'E‰IY30ET> /S 6WIY30ET@6D/ .&@w>@@0@R0.

(61) ‘ IXOv5 O>rXEl.&t IXHA@A6 @m.&@R6X3gS‰I&6*¦wE‰IZH—s.&@5EY6@?0@UIZ/ETSk6 /q!OA3IIYH@m  ET> 0'69O'rs Hig6&EG57/uS@ ]s Og6W3 .&@?ET>M O'SlM!@0w/u> 0 IZ/  ET>o—IkOAq!/55OwEK>7IZ/   @?EK>7IZOw/55O3 >RI b HAL author manuscript. _“ . . _£ .

(62) ž .  . . c4H@¥6WIY30i(¦w/R66W3 ss O.kIZ@0¥qi(IXH@Ž=?Nžd d x / >A0¥IXH@. . @R6WIPx-55U3 s /UIXETO>/S4zw@/uS{I#H  O 5ET@UIXi rXO!.žIXH@. 0/UIZ/?5%O!STSG@5UIZETO>w/>0wtw/>/ o @tv@>RIb. . @ / .&@ o. /UIZ@ r3SŽIZO IXH@ OAIXHA@ . O 55U3 s /IXETO>/S s'Hi6&EG5EG/>'6 ET>M O SM@0 ET> IXH @ @ ] /tŽET> /UIZETO>•2^—.J6. inserm-00225779, version 1. ž/ 7@>/ M!@ €(b{< žH/UIZ@STEG@ .e9b{<e*EG5uHAOA3 =wb{<1435/76C‚ b‰<gfh/ .&@ >7IZO!ET>@ b{<fh@R6&ST@%. q!@R6že9b{<NPO'@76&5 HŽBb{</>0 . . .  /Uq /%.FSTiw=wb @y/%.&@w/uSY6 O¥o.&/UIZ@ r3SIkO / STSIXHA@w5O!>7IX.#Elq3IZO.6 IkO IXHA@Ž6WIY30Ri•!^w@%.#.&E@>>EG52e9b{<  /U3 .&@Sg‚ bb‰<gIXH@2„-d N Or =?>ˆog@ .6&<'B?ET0. O!>wfb{<'‚ OSTSG/UI4e9b{<'N?/JM /SG@UI[+yb <Bž3 .#o .&@ ^ b{<!IXH@-=mNCd9d x2<!IXHA@. z_@/S‰IXH  O'5ET@JIWi_/ >02IXHA@Ce.&@>5H2‚ ET> Ek6XIX.#iwOr. . . . @R6XI[x255U3 s /UIXETO>/7S. O!.Z b. @?/uSY6 O_IXH/%> J@/>—e.&/%> O'E6 žH/R6XIZ/>oŽrXO.4HE695O!>7IX.FElqˆ3IXETO!>-IZO IXH@26XIZ/nIXEY6WIXE5R/S />/STig6@R6nb .

(63) ’ ›  ž› . . . . “ . . HAL author manuscript inserm-00225779, version 1. =?.&/rZ/C‚ <7€ŽOq ST@ J<NPOAiASG@—'+-< c .&/%EKS&=-<=2SGSG@u> b }}‘bu^-3 s3i7IX.&@ > ¡ 69/>0w@ s ETS@sg6#iw. @UM EY6E‰IZ@0gb  z_/ >0 3 .#o KBD.  ‡•¢‘‘ jW‘‘|gb =mIYIZ/ STEfh<!Z> vx2<fh@ STSG@UI#E@ .9+2<‹@ .#>EG@ . ž< n@/ >2e<A‚ƒOA3S‰IZO>21[<Rd4IXET@>>@ &fb }'†ˆ‡gb^23 s3i7IX.&@ > ¡ 6 5O>RIX.&/5nIY3 .&@%< / ST5OHO'S 5O!> 6W3tysIZETO>< / >0w5H. O!>ET5?SElM@.90E6@/76@bR=?. 5 H—&>RIZ@ .Z>2‚ @0 | ‡• ~ '˜ˆj ~ ‡gb BP@>>@UIGIBb }'†7‘b ^-3 s3i7IX.&@ > ¡ 6 5O!>7IX.&/5IY3 .&@CET>wtv/>R3/uS¦_O.#  @ .6nbuBD. [#>02‚ @0y’}•{}'†ˆj ~~'b BPOAM!@> 7E!‚ b }}|bz_/ >0j#/%.#t M ElqA.&/UIZETO!>v6#i> 0.&O't_@?/u>A0w0O6 @jW.&@R6Zs O!> 6&@m.&@ST/JI#ETO>wrXO!.M ElqA.&/UIZETO!> ET> 0R35@02¦wHE‰IZ@?rXEK>o @%.9/ut_O!>ˆoŽQR3/%.#.#iw0.&ETSSG@ .6 /u>A0Ž6WIZO>@5R/%.WM @ .6Jb7WIZ/ STEG/u> AIY30Ri_+?.&OA3 s_O!>2f*Hi6&E5/uS z_/ 7/ .&0'69ET>2IXHA@—AIkO!>A@m#>0R36XIX.Wibx-55U3 s—d[>M El.&O>2‚ @70Ž˜ •‰ ~’jZ  b BD.&/0STO¦ =-<‚ O¦w/I*=-+yb }'†ˆ gb ^23 s3i7IX.&@%> ¡ 6 5O!>7IX.&/5UIY3 . @m/ >A0y/ST5O!HAO'SYb7=2>>2NPH@U3t ^wEY64|g˜•‰’~| j ’~‡gb Bž3 .#o @Cfh<RzwOi_+2<NP@ o / >2fh<‚ EKST> @CNb }}‡gb!t_O!  ET>o <'/ S5O!HAO'S />02IXH@m.ZEk6Z vO!rg^-3 s3'i7IX.&@ > ¡¢6 5O>RIX.&/5nIY3 .&@7b  BDO>@ JOET>RI[3 .#o2BD.9‡}• ‘ ~ ˆjW‘ ~gb ž/SKEGrgdž<IZ/ HSbR‘ ~~‡gb ^-3 s3i7IX.&@ > ¡ 6 žO!>7IX.&/5UIY3 . @Rb%€ d>ˆo'S  ‚ƒ@0w’'˜ˆ •‰@  b H />R3I  ?b } ’'

(64) b K^-3 s3i7IX.&@ > ¡ 6 0!E6@/R6&@b b7=?.&5H2‚ƒ/uS f.ZOr‘|*•{ ‘ j# ‘g˜ b žO'55O2f1[<e.&/J3—fh<RN?/%s /uSTSTO—‚  < ž/R6W3SG/C^ b }'†ˆ‡g

(65) b Yx?55U3 s /JIXETO!> /S @ ]s Og6W3 . @CIXO2M Elq.&/UIZETO>w/ >A0 ^-3 s3'i7IX.&@ > ¡ 690EY6&@/6 @•/?5/R6 @j#5O>RIX. O!STSG@0Ž6WIY30Ri b‚ @0—1[/UMv‡'†•{’'†ˆ j#’}‘b .&E‰IZ5 HSG@ i—d ‚ƒ<!‹/   ETSA^_<zw/ i7¦v/ .&02z < xm¦w@ >‹2‚ b }‡ gb ^23 s3 i7IX.&@ >A¡ 690EY6&@/R6@?ET>w@ s ETS@sg6#i• .&@R6X3gS{I4Ors.#OSTO>o @0w/0tŽET> EY6WIX.&/UIXEO!>wOr*/>RIXET5O>M3SY6/>RI&6Jb 4€v@U3 .ZO!S7€v@U3 .&Og6W3 .#o—f96Wi!5HE/JIX.Wiw’}•¢| }'†ˆj ˜ˆ~’gb 0@?ST/ ž/urXr#ET> E@%.&@ L< / o >@ .NP<d4I&6&5 HA@E 0 n<A‚ƒ@UI o @ .e9b }'†ˆ’'b K‚ƒ/ >R3/S S/ q!O!.9/ >A02^23 s3 i7IX.&@ > 0E6@/R6 @bc4H@m. @R6W3S‰I&69Or*/?5O!ts3IZ@ .&E 7@0Ž6W3 .#M!@ivET>2IXH @mrXEG@uSG0wOrEl.&O>wtv@UIZ/SKSl3 .#oi b7=2>> žHET.‚ /ET> ‘*•‰  jZ‡‘b ^_@ut—q!@ =wb }} gbx-55U3 s /IXETO>w/>02^wEY6&@/A6 @•uz_OA¦ O5ET/S!eh/5JIZO.64=-rWrZ@5UIgIXHA@ žO!>A5@ sIZETO!>_O!r O!.#  jYN?@ST/JIZ@02^wE6&O.&0@ .6Jb7L—/ S@< žcD•RL/uS@C„w>ElM@ .6&E‰IXi2f*.&@66Jb d / .#Sli—fe9b } ‘buf*Os3 ST/UIZETO>Ž6WIY30ET@R69ET>2^-3 s3'i7IX.&@> ¡¢695O>RIX.&/5IY3 .&@7b 9BDO!>A@ JOET>RI[3 .#o—||B_•‰ ~‘ j ‘b +-/uSTEGtŽ/%.&0?€Ž< 5 H>E‰I 7SG@ .9=-<A^_@R6 5/UIXH/m=-< =2tv@ETSSG@ b7‘ ~~ gbu^-3 s3i7IX.&@ > ¡ 690EY6&@/6&@?/>A0ytw/>R3/S ¦_O!.# A<'5/ >2IXH@ i-q @m.&@SG/UIZ@0NP@M EG@U¦ O!r*SE‰IZ@%.&/UIY3 .&@b=?. 5 H2‚ /Sf*.&O!r*  •l˜ˆ~'˜ˆj ‘b +-@O!oHA@ o />F‚ƒ<AeO!.Wq!@R6 n< žS/%.# —^—&<gtwE‰IZH ž<Az-3qq /%.&02N—b7‘ ~~|b^23 s3i7IX.&@ >A¡ 690EY6&@/6 @m.FEG6#  rZ/5UIZO.6Jb  z_/ >A0 3 .#o KBD. ‘ }• |‘ ’ˆjW|‘ gb +-O'0IXrY.&@0'6&@>?€( <A1435%HRIzw<f.&@76&5ORIGIgd[<AO.&@ >'6 @>wc  <+ .ZO!>7q /7@  —‚ b7‘ ~~|b7= s.ZOg6#s @5IXElM@26WIY30Ri SET>  @02q!OAIXHw/ST5O!HAO'S />02IXOq /55O2IXO2^23 s3 i7IX.&@ >A¡ 690EY6@/R6&@ˆb  žSTEK>—d[s'E0@utvETO'Sg˜ˆ‡•l†˜†ˆjF†ˆ ’gb +m30!t23>0'6J6 O!>

(66) w+-<!=?.Z>o.&Et 6J6&O>2NP<!E o'rY36J6&O>?€v<RB4Œ&O.#>'6J6 O!>=-< nO!> 6J6&O>wcCb7‘ ~~~'b d[sET0'@twETO'SO!oivOr^-3 s3 iRIX. @u> ¡ 690EY6&@/6 @•5STEK> EG57/uS<6 @ .O!STOo ET5/SG<'/ >A0Ž6&O 5uE/uS/R6J6 @A66&tv@u>7Ibc4H@ NP@ i %Œ/ M El (IY30igb  žSKET>2d[s E0@tvETO'Sg˜ˆ’• ‘ } jX‘ } gb . . .

(67) | z-3@R6WIZO>J cžb } '† b ^-3 s3iRIX. @ > ¡ 695O>RIX.&/5JIY3.&@?/ >A0Ž6#s @5ETr#EG5 ET>JŒ#3 .#ibu‚ƒ@0C=m36XI • ~'†7| j ~'†˜ b H/>w=2=-<N?ET0@%.9x n< n/i!/0@ M  „w<z_@ .&/R6 jkfh/uSOA3 ž<+2ET@SG@Czw< +-O!ST0/5 .&@C‚ b7‘ ~~|bˆc HA@m.#OST@?Or tv/>R3/SgO 55U3 s /JIXETO!>wET>2IXHA@?/@UIZETO!SO!oiwO r^-3 s3 iRIX. @ > ¡ 60EY6 @/6&@?EK>wtv@>wEK>-d>ˆo'SG/>0w/>0 /SG@R6Jb  z_/ >0 3 .#o KBD. ‘ }• ‘ j |gb 1[Ek669+m‚ <AIkO'5% ¥N-b }} 'b ž/ >2^-3 s3'i7IX.&@%> ¡ 6 5O!>7IX.&/5UIY3 . @ q @C¦_O.# jW. @ ST/UIZ@0 ˆ•R.&@UM EG@U¦ O!rgIXH@ @UM EG0@>57@b7=2t #>A02‚ @0—‘ }•˜7‘ j&˜ˆ’‘b 1[EM ET>o6WIZO>@ =-<Ae*EG@S 0  b }}}gb7=2S o O'0i 6WIX.&OsHiw/%>0yE{I&69/R6J6&O 5ET/UIZETO>2¦wE‰IXH2^-3 s3 iRIX. @u> ¡ 690EY6&@/6 @b  z_/ >0 3 .#o KBD. ‘|*• }}jW‘ ~‘gb ‚ El  @Sk6 @>wx2=wb }‡'† bu^-3 s3i7IX.&@ > ¡ 690Ek6 @/6&@jZjkIXH@?ET>rWST3@ >57@?OrO 55U3 s /JIXETO!>_/ >0—s.&@ M ETO364H />0 ET> Œ#3 .&ET@6Jbz_/ >0 ~• j&† b €vOAq ST@ n<!=?. /urZ/C‚ <NPOAiASG@—'+-<‚ 5+-@O.#o @?+2<

(68) .&/%> (b }}‘b7c HA@?/R66 O'5ET/UIZETO>—q @UIY¦_@@ >w/SG5OHO'S< H@%s /UI#E5ms /UIXHO'SO!oiw/%>02^23 s3 i7IX.&@> ¡ 690!EY6 @/6&@b  z_/ >0(A3 .Zo KBD.  ‡•{‡ j#‡|b c4HOtŽ/76fN?< CS/ .#  @C^ b }}‘b7‹2ElqA.&/UIXETO>2¦wHE‰IZ@?rXEK>o @.9/ >A02^23 s3 i7IX.&@ > ¡ 695O>RIX.&/5UIY3.&@A•/ .&@ IXH@ i .&@ST/UIZ@0 mx-55U3 s—‚ @0w8k1[O>0;4|‘*• ˜˜ˆj ˜† b c4HR3 .6XIZO!>—= bR‘ ~~’gb^-3 s3iRIX. @ >¡¢690!EY6 @/R6@b  BPO!>A@ JOET>RI[3 .#o—BD.†˜• | }ˆjW| ‡‡gb c9OA¦>ST@ i =-<BP/   @ .NP<HA@ ss / .&0?€v<'+?.#Oqq!@S// .4=-xyb7‘ ~~ gb^23 s3i7IX.&@ > ¡ 695O!>7IX.&/5UIY3 .&@ 3 >rXO'SG0@0gbBž‚ ž’’‘*•{’}‡jW| ~~gb [@ .&/#Œ&EG5C^w<e*ET>g6&@>—‹vbR‘ ~~|b^23 s3i7IX.&@%> ¡ 6 0!EY6&@7/R6 @ ET>—BPO6Z>EG/?/u>A02zw@ . 7@ o OM EK>A/b=-> @ s ET0@tŽETO STO!o EG5/S6XIY30AibBž ‚ š‚š365U3STOg6#  @SG@UI^wE6&O.&0Ž˜• ~gb

(69). . HAL author manuscript inserm-00225779, version 1. . .

(70) ˜. HAL author manuscript. > >@?BA $ '  [9" \  ' ]  5  $  5.  

(71)  

(72)         CEDFEG CHC NPOQO R S Nqqr NR s NPQSr Nq N rrO s N ƒN$R S„ƒ NPS„ƒN NPr„q NPrOS Nqƒ RƒO Q„q. !"$#%  & I JKI TUWV VEVU-t z$U-T V €U- TU- VEŠU-‹ tUWŠ VEVUWŠ. ')(+*-,.0/2134. 7  89-5:6 ;  = <. inserm-00225779, version 1. LBM N XOY OOOZN ^@_a`-#bcedgff! CEu H uwvx=yu h -` djiik#l!"m no$p .* .N 4 XOY OO{N LBM ^@_a`-#bc `-|d"`}#Eb~dgff!=mno$p H uj‚ H uwyx=Cuwy * LBM N 4 XOY OOOZN †‡k#ˆE! i#lE!"`}#Eb‰m no$p CEu}C H uwGx=yuwF * LBM N4 ŒegŽ`-`-#b XOY OR  n $ o p $   %  i #  " ` $ % E!. H } u D. H " u  H  x  H u  * ,4 ‘Eˆ`   $#d{m Q„sq qq U-€ N XOY OOOZN —~fk˜~™šf_ˆ0a ’ZME“•” o–o ” ƒQ„ƒ Q„q z$U-T XOY OOOZN ¢E¢ bafEˆ›_ œožEŸ} ¡ ” o–o ” £ Ÿ ¤¥ ” o–o ” rS„q NPOr V¦U-T LBM NP««„ƒ rr TU- N XOY OOOZN A 9   $ec\§k¨;9-©9-ª9-  NENQQ NPSr V €U- CEu H uwvx=yuwD no$p .* LBM «ZN$sr NPr„s z$U=z N 4 XOY OOOZN ­®  `"!"`j! ¬›  \¨ i`-_dgf"¯f"°

(73) ª   ««O SS €ŠUWŠ no$p ±~ˆšˆ$¯d"a#³² _ yEu}F CEu"Hx=Duwy * 4 l`-_a _ LBM «0qRS Nƒs tU- N XOY OOOZN ´c`-_dgf}¯cf}° l`"|0dg$_ R« NS €0¦U-‹ DEu}F CEu"Hx[‚u no$p * .4  $!"!"`wdgˆ0_ LBM «0qƒO «EOr tU"¦ N XOY OOOZN ´c`-_dgf}¯cf}° Nr r ¶z$U-T Gu-D CuwyExH‚ uj‚ gŽ`}!"g@_}¯®µEµµ no$p * LBM «EOOQ NPrS tU-€ N 4 XOY OR ´c`-_dgf}¯cf}° qƒƒ S„s V €UWŠ i#l no$p H u H u"Hx=CuwC .* 4 djˆ  dj`-_  · !"%fkif! LBM «EOS„q NPSr z$U-€ N XOY OOOZN qr„q rr V tU-€ no$p CEu CEu"Hx=DuwF %fk#_aˆ  ›dj`"fk# ,* 4 ¸¹ la`-#˜E_Kº»l¯ · #¯›_afk#! LBM Ns«« NP«O ¦U"¦ N XOY OOOZN RsS ƒ« V TU-t °E%$dgf_ no$p CEuj‚ CEuwFx=yu .4 ž gG

(74)  9&

(75)   % Ž ¼ "Z$ & "Z' ž—' & %

(76)  

(77) 

(78) 0½ K¾ %&

(79) ?l

(80) 7Ÿ * ¿ÀÁ[Â}Ã0ÄÅÇÆKÈÈɶÊeÂ-ÆgËË0Å$ÃEÌÉ"ÍΧÀ§Á=Â}Ã0ÄÅeÏ0 Ð0Ñ[ÅPÆKÂ-ÃÄÒÆgÈÈÉKÎÓ~Å$ÃkÀ„Å ÉËÅÄÌEÉ}Â-ÄÄÅ$ÃEÌ~Ñ[ÍԄŠÂ}Ñ=Â}Ã0Ä~ÓÒÍ$Õ$Ë0Å$ÃÂ"Õ$Å ÉZÍ$ÖkÀÂ}Ô0Ó~ÍÃEÆ{Å$Ñ[Í ÌÍP×;Â"ÄÍÌØÐ0Ñ[ÈÅ ÌÉwÙ)Ë0ÍÑ[ÍÎ ÆgÈÇÓ~Í$Å$ÃÇÅ$ÆÉ"Í$ÅÁ=ÆÈÃ0Õ$ͳÌkÀÑ;Â-Ã0ÄeÆjË0͎ÙÍÅÑ ¿¿ŽÚ oۄžoۄÜgÝ Ú o$p Ú ¿¿¿ MÞß Û Ú Ÿ}Ü M ÛE–  ” p ß Û Ú ž Þ  ¤Ÿ-Û Ú ß à o á@âäã M žžkp Þß Ú Ÿ M påçæ{è ã Ü M Û=éŸ"žoۄÜ$oŸ-Û Ú o Þ – ß” åÛEp ãÇêë Š$UWŠT .

(81) A . HAL author manuscript. . >. >š?BA ' \§k¨8 9j .  e. inserm-00225779, version 1.  ¬›  \¨ ­  `"!j`"!0i`-_dgfkj¯fj°  e

(82) ª   m ±~Pˆ šˆ$¯d"a#³² _šl`-_$_   ´ `}_dgf}¯cf}°l`"|dj_  e   $!"!j` dgˆ0_ ´ `}_dgf}¯cf}°Òik#l  e d"ˆ   · !j% fi¶f! e  % f#_aˆ  @dj`"f# ¸0¹  lka`-#˜E_ºl¯ · #¯›$_afk#!  e °%dgf_  ž gG

(83)  [

(84) ¾ !G

(85) $

(86). .  ]   $e[k   5 )mEm ¬š u 6 ')( *},E.0/2134 0Q sS D/ u}C NPS N Cuj‚ Nƒ N ‚u}D «0R N yu s N HCu". ‚ qk« N Du}C N N ‚ugH «0R N yuj‚ s N ‚u}v qkO N D q N ‚uj‚ Ns NR. . [ Ÿ . Cu. u, ,  .. $ %

(87). \0[ $ §9K ;]    Ò9 k8~ ]   e ;   5  [    5 ¬š $u ¬š $u 6 ')( 6 ')( *},E.0/2134 *-,.0/ 134 ƒQ„ƒ Er S„q H/ GEu ‚/ u «Q O [ N Y OES =qEY skQ 0« R HyEu}.G u-.C «Y

(88) }u v CEu xHH$u-y .HFEu}F Sr N Y

(89) S -OY  s «0Y S  ¶s N H ‚kuj‚ . Cu"‚ * H ,uwGEx;DEuwG 4 Rq ƒkO H ugH GuWH Hu}v H u"Hx=Cu u-F * y"u H xª‚kuwv 4 «O N Y  R }* OY r =q0Y Q,E4 NPr yDE. u}F y. u * Hwu DEx uwC 4 HvEu}C r„ƒ ƒkQ H uj‚ Du-y.* Cwu vEx;GE, u 4 ‚u-C Hu}v H uwCx=Cu}‚ S Q -O* Y R gS0sEY s 4  ƒ y . ugH s0Y S} O* Y ƒ WQ„RE.Y S4  CGEuj‚ SY

(90) RQ sk« H , u}y Du"‚ yuwEF xª‚ku ‚u-C Cu}F H uwyx=yuwy Nr N YK N }* OY R W«Y Q 4 «ES CCE. u}C yu-D * HuwED x;vEuwF.4 vu RS Gu-.D H u}G HuwFEyx=Cu ‚ rE« HyEuj‚ yu-v * CuwED x;GEuwF 4 N$ƒ «Y  O * }OY r WQYj. N  4 SES CyEu}F yu}G * H u"Hx HCu-C 4 HDEu}y * 4 N qr uWH H u}v HuwFECx=yu}CEy rEr HyEu u-y yu"H x uwF N qQ N Y  R * }OY s W«Y s  4 SEO CGEu}F. y. u-y * HuwvEx;GE, uwD 4 H. yEu}G 4 Žš›—&G  w› "# $$ Ž"Z$ &  * 3. #$ ( 

(91)     %

(92) $ & _K G

(93) )  %

(94)  J %

(95) $ &_ K  wT 

(96) $  

(97) 7 %. "Z$ & Ÿ.    )& + '"    $+ )"! !' %#

(98) !#%#"! ) " +/% $/-"#+&" ' "& )-)(   +*.%,-&$-"% & $## $ - 1 %3)

(99) 2'.3"% 0/ 213+4657 + 1 $- 1%3)

(100) 28' 3 "%3  $%( )"-9#,  :1;/2'"<$& %3+ % % )$3$# .

(101) . HAL author manuscript inserm-00225779, version 1.  

(102)  . .  !"$#%&(')*+,-').-/

(103) 021-#32 D " 32E:&F') *G ,H').-/

(104) 021-#3I. 4%5 687:9;6

(105) 5=<)>8?-454@6A 4%5 6J4K9;6

(106) 5=<)B8?-45 6

(107) L)A. 625 B8C 625=L)B.  !"$#%&(')*+,-').-/

(108) 021 M#)/2#N

(109) E'%OO8"P. D " 32E:&F') *G ,H').-/

(110) 021S #)I/2#TNTEI')OTO"U.. 6 5 Q6 ;9 6

(111) 5 R8<?-45 >

(112) C)A 2 625 BQ 9;

(113) 6 5 R68?-454T4-A. 6 5 BJ4 2 625 68L.  !"$#%&(')*+,-').-/

(114) 021 V#%W";N$"$#)N

(115) EI"P.X')$YW'$V[ZM/@\/Y$0^] .!"P.0%#). D " 32E:&F') *G ,H').-/

(116) 021 V#%W"$N;"$#TNE";. U'`UY 'UVaZM/-/0Y$0] .!)"P.0%#).. 625=L)> 9;6

(117) 5=7I4?_R

(118) 5 7`QA 625 Q87:9;6

(119) 5 R8C?_R

(120) 54@6A. 625 QQ 625=C)>. R25 >T>W9P6

(121) 5 R

(122) C?_R8LT5 CT7)A. 625 BR. 4%5 <TCM9P6

(123) 5 Re4?-4LT5 7T7)A. 625=C)>. 625=C)B 9;6

(124) 5 R68?-45 B

(125) L)A. 625 R87. 625 QJ4K9;6

(126) 5 RQ8?-45 LTL)A. 625=C)6. 4%5 R87:9;6

(127) 5=7)R8?_B

(128) 5 QTQA. 625 Q>. 625=<C:9;6

(129) 5 R>8?i7T5 C`6A. 625=<)B. 625=L7:9;6

(130) 5=7C?-45 <TC)A. 625 >Q. 625 >87ak6

(131) 5 RQ8?-45 BTQA. 625 R8<.  !"$#%&(')*+,-').-/

(132) 021 EI"P. '`;Y';V !)"$#)OU.HW%N;N$"=/

(133) . D " 32E:&F') *G ,H').-/

(134) 021 E";. ');Y'UV:!)"$#)O

(135) -.Sb%N;N$"c/d.  !"$#%&(')*+,-').-/

(136) 021 EI"P. '`;Y';V:EI#)![$0#T/ # D " 32E:&F') *G ,H').-/

(137) 021 E";. ');Y'UVbEI#`I![$0#T/

(138) M#  !"$#%&(')*+,-').-/

(139) 021-#TN;f%')EI'TNf%')2.-/

(140) H$"$')Wg2 +!`";*).h !T#XY D " 32E:&F') *G ,H').-/

(141) 021-#TN;f%')EI'TN

(142) f')2.-/

(143) SU"$')g

(144) G!`"P2*.Ih !)#Y  !"$#%&(')*+,-').-/

(145) 021P .0')#)NjV2#)fU'`. D " 32E:&F') *G ,H').-/

(146) 021P .0'`I#NV#)f') .. lMmenoip q)qrq)seq)tup

(147) vmHwTuxiyet{zu@|~}SnpTu€p

(148) p8t‚€ƒyevT„ p

(149) †J‡~yHz%|v

(150) pmet}{p

(151) mew

(152) ˆ{yu-ˆp

(153) vM‰-mewuySvWz%p

(154) ‡mHvTmu@pdo$\s ŠŒ‹HŽŒ_\‘ŽT’%“H”d‘_i•—–:˜‘™H_š`‘_•’j›œ•XžŽjŸMi iŽjŸ+ši›œ•’¡“H\‘_j”

(155) •H¢

(156) £e _šr“e\‘¥¤e’)£

(157) ¦œ\‘“e§2ŽT¨©¤H£eŽª‘_•«šr¬­“H j  H£¬ƒ®ŽT’M•X”T“eš)Žš¯_±°+²e³´¨H”

(158) •e£e ¤µH•H‘H®Ž š‘£¤HiŽT¤H¶ ·+¸ƒ°¹•¤e¤eš+’%“\‘i•šº¶¼»(½I°¡”

(159) •˜e_¤HŽTH”

(160) Ž\‘_ŽT’º¢T“H .

(161) . 576 ?. C ;DE0FGHB HAL author manuscript. i  HB 

(162) 2j2k2k2 G m hG@ 

(163) n G. IKJL M4NPOQR STQ;U*VWOXQ eV fFg l opWSTVqXVWqgVYrsO J RXt Juwvx yzx tBOYR QNK{ r|U*V rsQWr Q eVYrsO J RXt Ju UVYW}*Q;OQ;r~STQqYqXVYO x r eVYrsO J RXt Ju Q y VXqYQ y rXt.Š eVYrsO J RXt Ju gPWNPU‹O RsW x STW Œ q J g J q J N*r x S y O V J N$Ž‚‹URVYNrz‘bUW4t. inserm-00225779, version 1. Œ Nt y QR r J NWq u WO J R r   s •;–G.  

(164) 

(165)  "$#&%('*)+-,. / 021 ) % '/ >@? ??? 9 8 89:8 8;98<=48;98 >@? ??? ? % ' )8 / ]@9^_^^` 8 <9Y< ? % 8;9 '*Z ' =[Z9 \ / ]@^_^^^` Z9:8 ) % 8;9 ) =[\9 A*\ / >@? ? 89c % 8;9 <? =[<9 \*? \ / >@? ??9 ? 8 8 ƒZ € 9 2<†;l[=‡c€(9 *‡Z ˆ 9 €: h‰ 8 \€ 9Ya2‚„ ) ? % ) / >@? ? 9 A) 8;% 9 aZ*= 8 9XcA?/ >@? 9 ?) 8 89 A % 8;9 ?a*Z=[<9 ?*Z )/ >@? 9 ?) 89Y\\ 8;9 8=[<9 9 =. = =. =. 4. =. =. 65 Q8L:9;6

(166) 5=7)R

(167) ?045=<I4-A. IKJL’L|J R4TQ“ y”J r x R QBŠ y Q;R4r J NWq u WO J R r L J R TQs“ y~J r x R Q@Š y Q R r J NW*q u WO J R r M4NPOQR STQ;U*VWOXQ | eV fFg LpJ R4TQ “ y~J r x RQ@Š y QR r J  N Wq u *W ;O J R r.      !

(168)  *"#&%3')+-,.4/ 021 )% / B > ? ??? 9 8 898 8;9:8<*= 8;9:8A >B? ??? 8/ ?% ]@9 ^_d^` 8 <*9 'a % 8;9Y\Z*=b\9c?8 / ]B^h_d^^^` Z*9 8 % <9Y<\*=ba9YA / >@? ? 89XcA 8;9Y<A*=b<9Y\Pc 9 8 = = = = = = = = = = ?)% ' / >@? ? \*9 8;9 \*=bA9Y\Z 9 8. =. =. 65 QJ4K9;6

(169) 5=7)6

(170) ?045 >8<)A. lMmenoip q ™ szš  y up

(171) tuxjmovxiz)„¼‰0mewTuyHvTza‰0yH• v › |~‡|SHuv

(172) p8tœzM}~xjz%p

(173) mezrpxitŸž |oux  \mevTxjmupmetmo^z%xjz+nmez%p

(174) } yet oiz y ¡exjzuxjw–ž e y }pTo˜z%s. ¢ £z¤–¥4¦§¨ ©.ª¬«~­z¤®”¯s°­z¤©±!¦®b¤­²ª²«~­z¤®³P´‹¦µ”¶®·|­z¤­²±*¸”¤¹@º²«z§s»²¤¼¾½”«¿¨ ·”§;¤¹zª²±µF·|±®”£z«@ÀzÀ”¦[¤@¨T±µz­²¤±2¶*£  ½”¤*§¨Á«Kµ¾±®~¥±¶©«@§Â2¢£z¤Ã¨Á¤¶«zµz­²ª²«~­z¤®”¯4°P¦:µ2©¤*§;±¶©s¦«zµ²ªÄ«~­z¤*®X³´‹¦µ¾¶!®·|­”¤­²±*¸”¤¹@º²«@§»Å¤¼z½”«p¨4·”§;¤¹ ªÄ±µF·|±®p£z«@ÀzÀ”¦b¤F¨;¹”±*µ@Ʋ½”¤§¨;«zµz±®p¥±¶©«@§¨Á¹~±µz­Ç¦µF©¤*§;±P¶© ¦b«Kµ”¨.©¤*§sªÅ¨ÀK¤©º²¤P¤*µ²±µ@Æú¬«z§s»Ä¤¼z½”«p¨4·”§;¤–±µz­ ±*µ@Ʋ½”¤§¨;«zµz±®p¥ ±2¶©È«K§¨h “\·+¸ƒ°. “e¤ É£š`‘_ŽT¤•¤e¤eš+’r“\‘_i•šr¨‚»±½°. Š J RÊWNPO V J NË x qYrWNOUR x f VYNOWhQ. ”

(175) •˜e_¤HŽTH”8Ž_\‘_Ž’)¢T“H . 625 QTB. € ‚* € —*˜.

(176) . HAL author manuscript. Unité 687 Santé publique et épidémiologie des déterminants professionnels et sociaux de la santé Hôpital National de Saint-Maurice 14 rue du Val d’Osne 94415 SAINT MAURICE CEDEX  01 45 18 38 74/50. . 01 45 18 38 89. . 

(177) . ¶©«@À”¤*§;¹. . inserm-00225779, version 1.  ¦X§;¹   !"#$&%('*)+,-(,-.)+(#/#0

(178) #12)435.3 )6 2%(7%("98:6;<=;>$?@"ABCDFE2GDHA-I2DHA2JK<=A-@"DL-BMI-NO+I2P ?HL$@D*I-BMEL2PP.;=<I?HGL-BI0N AQ$<=L$D;@.A28HR%#4S5412S2TU %%(VW#X)Y3$12S$7!".%W#F7 Z\[6]"^ _7`.a$b\c5d0e$^b-afd7g

(179) hib2j5e0kml^+_na$f"op] j_7`_7b]R0q S2)r)+.3#)%+s tu 32)+,-#1vi7w&%('#1x'%(' 70%W.)H!y%W#z%Wi%W{S$.%(|6."z3.)i#X5W!y%W#)m{"z#-!! 1235.%(#5.}$3#$i1-)+ 2#&5#X%

(180) 7T*3-)+#-,-~%('*35.3$.) s 6#|6,-.)mR!"#(2.)H7xz%(' )+,-.|€.)F!"#Xv$y)+ %(#vRq|6zx-,-&5#|(%'5~)+-1 %r*#0

(181) %'5&72%(.)r!y%W(#X‚n/.5#%'5y)6%(.S$(zƒ%W#„i%(w !"") s .  ¦µz¶¤*§Á¤!®ÆÇƾ«¾·”§¨ † ‡Wˆ0‰ŠH‹Œˆ$‹ Ž-0W‘M$’v“. Œ 5. -” 5. ‘ Œ 5. •–— — ˜ ™iš-–.›$œ-˜›$ ˜ž ›œ4— ˜ š-—Ÿ ›0 W™ ¡¢Y£7¤ ¥"¦7§=¨ ¤ §©+ªH«¬ª ­®  ¦ «¯  ¤±°ªH«¬-²"£7².³¦ ¤q°"´W².µ¤ §H§¦7² . ¤+£7£ ¤ ­¶K·.°¦ «ª £-¸Mª ¹º

(182) ² X » ²¦  ©+ª´H¯¢ »2¼ ¶ » ­½ ¼7¾¿À-Á"Â\à ª´©H¬-¤ §H­ ½´ª  © ¤ Ĥ£¡mÅ ÀÀ Æ+ÇÈ2ÉÊ6Ç ÊÊ

(183) Ë.É-Ì ½0ª ¥-¡ Å ÀÀ ÆÇ+È2ÉÊ6Ç ÊÊ Í-ÁÌ ¤º

(184) ª ¦ £(¡ Î=Ï Ð2ÑMÒ Ó$Ô7Õ=ÐÓÖÎ2×.Ø5Î=ÙÚÛ5Ö2Ô7Î=ÛØ=ÛÔ ÜÚ Ý7Ÿ Þ Ý7Ÿ Ÿ Þ Ý7Ÿ Ÿ Ÿ Þ Ý7Ÿ òÞ Ý7òÞ. Ÿ7™á*ž ›2â$™H —Ÿ7š  ž.™=›$–. 5ã-˜ ˜›6™âã0ဟ  ( ˜ œ\›$–—MŸ ™=â2›$œ-˜ —Y –.›$™rŸ(œ-˜ — ž  Ÿ –›4ä(–—šâ5ãXå Ÿ7"žy (Ÿ7–"›6ã0æ

Références

Documents relatifs

Monsieur le Maire rappelle la délibération du conseil municipal du 06 décembre 2020 qui sollicitait le cabinet LARBRE INGENIERIE afin qu’il présente un devis pour la

« Mon enfant, si vous cherchez Dieu dans ses œuvres, c'est à dire dans la nature, plus jamais, aucun doute, n'éclora dans votre âme, pensez quelque fois à ma pa- rabole des

Maurice with deveIopments at La Gabelle, Shawinigan Falls and Grand'Mère, ntilizing 285 feet of head on 1(; miles of river, has an installed eapacity of 8fi2,nOO horsepower, of

Qu'on trouve ou non chez Massis qui a la foi cette sym- pathie naturelle, cette philanthropie, il est bien sûr, il est bien évident, pour 1e dernier des théologiens, à plus forte

- la croix tréflée de saint Maurice - les initiales SM pour saint Maurice - l’étoile du berger à cinq branches - un épi de blé (qui représente l’agriculture) - deux clochettes

Cette pensée fameuse et bien vraie nous est revenue à la mémoire l'autre jour en relisant un écrivain montrant le peuple chrétien terrorisé à la pensée que le monde allait finir

Methods In this cross-sectional survey, nine occupational physicians performed clinical examinations, focused on Dupuytren’s disease, of 2,406 French male civil servants employed at

Résignez-vous à ignorer si vous ferez jamais usage dans un article ou dans un discours de ce que vous aurez copié. N'ayez pas des vues trop immédiatement