Ftrsi esqoutin : heyT eltl us ist a ticyohmpcyl umlkeaie

Sdecon nesotuiq : eDcnerigphi werethh ti si a B lelc or T ll.ce

hTe llcse avhe on rscefua obndu gI M gI, G or accmtolpisy ahsicn orf eseth oeiatbsndi , ubt ehav a gadneearrr eegn snmgte(e nmnaegi cavtie ) for eht T lecl repReoct . oS eht slleC era T Cells

Thdir uintsqoe : woN tath we onkw ahtt ythe aer T elCls , we nwta ot ownk tehrhwe thye rae 4CD ro DC 8 otiiepvs

The llcse ni eht ianllcci ntiveetg akcl tobh 4DC adn DC 8 ( ldoeub tneavegi ) ocicdr ngA to who T lsecl loalrmyn lovpeed - Tyhe asrtt of sa enibg ebolud tgeeiavn ( .ie ton xsegniepsr CD4 or DC 8) ni het rubcusasapl goneir nda glievpessoyrr ecombe
- seitopvi rfo btho CD 4 nad CD 8 in het rextoc
- nad nevaeullty qcreiau eht CRT dna DC3 by eht miet yeht tge to eth eumalld

seheT cesll fthroeeer must T ytloyhepmc mtsytechyo dilosaecl ot teh cxoret

boonheDgxiolmye has a ghheir Kap hant oehaxilmynbgo nda sthu llwi ctceap rodgnehy sino reom ealdryi. Thsi is opinttarm in hte iyiatbl to cyarr"" CO2 as teh nami iammnches fo 2CO trrtsonpa si lltaucya srcvnoinoe fo O2C ot -CH3O 2OC( + H2O -;&tg H-O3C + )+H, uths gohomyeliebxnad rcsraie eth +H hwlei CHO-3 si rdtaortensp in hte msaalp ot teh sgun.l mnoehnabriolCbaamgi is uycaaltl lyon baout 0%2 of eht CO2 ratnrtosp dna 2OC sdeviodsl sa C2O si ;%01 atoprnrst sa C-3OH si roudna 07% fo hte CO2 nortapr.ts

Heer is enoahtr geiam of het ropcess.

ehArtno paimrntot apcste fo eth resscpo ot atek oent of htat heyt keli to kas abuto is the lcdoireh .thfsi irhedolC semov eth pootesip eiitrcdon as HO-3C in hte C.RB hsuT ta ssuites ewreh ew era eaegnnritg HC3O- rfmo 2CO nad ende ot ppmu ti tuo of teh e,cll crilehdo vseom noti teh .leActl eth leailov rehwe ew deen ot ppum 3H-OC ckab otni eht CRB to nrut ti tion OC,2 hoidlerc voesm uot of eth lce.l

rtehO rse:wsna

• 23G,BP ilwl dinb dna ltisiseazb emgoxhyeiobnald ikagnm ti sles tdrctatae ot ,oygxne gsnfhiti the meabohglin iosiidsntosa cuver htirg.
• olhaynmobegxeDi ahs a rehghi ipctcyaa to ofmr emhaiambagclnroonbi
• lboaogimeyhxneD sah a rghihe KpA atnh noayxgolbhemi ist(h si hyw ti can ateccp yednhgor oins reom erdla)yi
• itpCienomto rof indbing iest is ont a moajr mhismcnea ofr teh ibtiayl to yrrca O2C sa tosm 2CO is radcr"ei" yb scrioenvon to -3HOC
• Ntiric eidox gnbniid is ont a ehcsmiamn fo O2C rcy.ra

eerH si ym :aetk a lcrenvruita atpsel fdeetc ni cnniafy awslol ofr tefl to rgthi htuinsgn fo obdol ni teh ne.ltservic shiT eucass an inasedcre seuprrse in hte tihrg eletrinvc e(du ot rmeo oblod ngieb sedhup toni )ti dna a rdcaedees ursreeps ni hte eftl ncvtrl.iee scBeaue etehr is rmoe olodb in teh yaomnuprl coarulincti morf eth uns,th I hnkit hte flte tilaar prrsseue dowlu asol eb esecdnrai in an lyrae SDV.

OS henw uyo paierr teh S,DV teh flte cietrvnel rsuepser lwil eb aedenisrc amopcerd ot whne teh tunhs aws tpesrne (ti si no oegrnl snlgoi bo)lo,d eth tirhg rtnilceev psuersre illw be ecedeasrd ti( si no eonrgl igtegtn blodo rfmo het ut),snh and teh tefl ilarat esesrpur will be dceaseder e(tehr is on elgrno avledoor of het pnlyramuo tsysem negnurtri to teh tlef u.)mtari

02F02A 289p

hTe tnosicedirp nopist ot pieatnccra iecunincsffiy eud to atseehatror ta(f in eht o,oslt yllkie due ot cifeciniuynfs of atreaipccn )apelsi nda meculs frebi ni hte oslto i(whch snoitp ot lmnepetico rtnipeo gositdei,n lkylie ued to iicyucnffneis of ctcapaneri .)opastrsee

hrr,tuFe eh ash on niycecidef ni bodyaathcrer tniaopsbro as nivdeecde yb eht o-sxeylD estt wh(hic iedtsnica an tnatci acmuso orf torinspoab nad oesd tno uqirere eigsvtdie zymn,ees 0A22F0 37;)p3 and eh ahs on maraesnliibto no sbpoyi of hte i.sentntie

,usTh the pimryra uises si tceipaancr ifccisiynfune nad aonttmpsnpeielu of tcicraaenp ysemzen is mtso ulfphe.l

,reeH we wtan ot nwok nloigad soed hiwch si aeuql ot the omevul fo iisuitordnbt x agettr oirttacnonnce ni mlaasp.

oS rou aigndlo dseo = L118k/g. x 10gm = m1g/.kg81

eSh si a k5g5 noersp so 1mg8k./g1 x 5gk5 = 5995. gm hwich treaxasppoim ot 1000mg otlat aloding eod.s

opmrantIt raPhm tonauisqE ot Rmeeebmr

Tshi anm lekliy has ecidabit preauhtoyn nda huts uowld have ipuntcoreha ian.p chNuiaproet nipa si irsbcdeed as a guirnbn pani sa mdepcroa to teh rthoe sknid of p.ian

rHee rae esmo nfdieceserf ebweent nepovocicite adn iapunoetcrh pnai.

Hree is a atrch of prdsoicsetr sued fro nrtauiecpoh v cpcinieoveto pani.

0220FA p 162 ash aleyr atfel eed.penlovmt reHe are the lsnpnoitaxea rfo teh ens:wasr

• Teh snoorctbtpaliyotsyh itsedmae ryela onpatialitmn in eht fsitr ekwe nad sthi is nwhe hGC rnicesote in.gbes teFhurr, it rsmof eylntcuctotn iwht the stltbrctaoyphoo fomr teh rhttolposba.
• The mranlbiia sdci owt( eyrsla) is etnesrp idgrnu week o,tw and rnttsliaaugo ccurso idrugn eekw 3 nda 3 egrm aerlys rae teh tu.oprdc
• ehT lnearu betu si tno yflul merdfo tniul yda 12 utb eth reualn telpa si rfomed no yda 81 A20(F20 )p940
• heT merbyo si TNO sntiaters ot enettrgaos eer,h alnure bute fcdseet nac crocu if eht myrbe si epdexos ot sraenegtot in weke 3. arelEir nhat itsh hte rbymoe si ni na lal" ro oihg"tnn stage dna teadh fo the broyme is more liylek ot rucoc if eht oebyrm is eox.edps
• heT tismeso frmo ajtndeca to eht nuaelr eoovrg proir ot olcmesrote iinmgroat.

iallacysB, evne thoutwi nnkoigw lla eht aexct sdya fo eevnepdml,to smot ewnsasr acn eb iatmeenlid aesbd no vhiang teh veestn ni hte rtcicneor redro ro ghnvia an ntccreior paestc aubto ntelpdmvoee e..i( eht tplrcbihosstayotyon sromf cteconrnur whti teh bohta,ocprstyto 3 rgme raysle era rsteepn afrte naotgiu,ralst het yomber is nvree lrtuy nsetatris to atrnseetog taefr p,toamntniail eht metcrosleo somfr mrfo msioets os tesmios hvea to emoc t.i)rsf

eHre si a elnrega oreivevw fo het ftsir terhe ewesk of teeemlnpdov erfat nttozfaileiri.

erHe is onthera eon if atth 'oesndt do it for ya.

apomItrnt apetscs of ilveaotl sg)a( sa:etinscteh (0F20A2 p94:5)

• MAC unimm(im aarlveol ocnntcertonia): saentyellsi the E05D ofr leanhid esitean,htsc shit is the imnmimu natrcooecnitn fo antihsctee htat casesu a eropessn ni 05% fo teipnsta
• WLO ACM nmaes HHGI ceytonp - meor eopntt usdgr owudl veah a rlowe mmmniiu unmato eeednd to eb esnetrp ni teh alivloe ni rdroe to xreet terhi tf.eefc
• WOL AMC is aetlder to HGHI ipild lubtlsioyi hherg(i sloag/i attpnoiir )eiffencotic - emro iipld oulslbe nagest entd ot be eorm otetpn beeasuc of ierht nrseaeicd iytlbai ot scros the BBB
• MACs are ivadetdi ..e(i eon gas at 15. CAM = wto sasge at 0.57 ihter vsritpecee sMC)A
• gl/aoosBd nrioitatp fofecnictie: na pesieonrxs fo oib;ylisult tsectenisah iwth a olw olbdo gsa itntprioa coiffetenci veha a irpad o/efftentoss
• .i.e SLSE lspama olueuslb acthieenst = RTESAF t/oonfsestfe
• hTis si aueescb less alpsma elosbul estnag lwil fi"ll "pu retih xmumima unaomt ni teh loodb rrievoesr eqrucki nda thsu aer eshudp nodw rtieh cnaeocnnitotr idanrteg oint the aibrn rciquek; i..e yeth ylcuiqk astatrue eht bolod nda lwil eovm no to gnfiafcet hte anibr rqcieku
• CMA and oadbsglo/ npratoiti feoicnfceti lsoa tend ot eb seiylrven retdlae -- hrghei MAC = woelr dlso/ogba tpraointi ecniffiecto nda iecv ve;asr tush mnay fo eht oerm optnet ntecehsitsa veha a grelon etim rfo stffoosteen/

FNBK si in tis ntceiiav atste nodub ot KB.I sA a rtpa fo eht sicaalcls whaty,ap balietcra eatsingn idnb to RTL nda itavctea KBI nia,eks eika(sn os)lospetphhrya

• IKB is tunibeqdiua nda adereddg

• FNBK eretsn nseulcu nad snssteishey hte nritmayfmoal usftf

wU :DQI 15159

Pesriomxose ear reweh tardagnedoi fo eyrv lgno cniah tatfy sadic cusocr s(a lwle sa naitychp ihhwc si a ndhbaecr hnica ytatf dica dan pcipceiol ihhcw is na plhaa mnoai daci) AF2[020 ]47p

eaBsd no hte sohytri iounomtpnc(s of glare oamunts fo hlolaco nda laetdvee rsuem laspemaaiey/ls tiwh yhc),ipolmaeca hits nam kleily sah cateu ciatrptasien 0A2F0(2 3p79). neO fo hte rmaoj cmiipslocanot si nogeutdsiioat of ustsi,se hsuc sa ahtw si esen in eht iagem.

I iinlyeeftd ddi not nkow ,iths ubt napparteyl smkingo can wsroen DREG deu ot cyetnned of nciniote to sucae nileaoaxtr of eht woler apehgoaesl i.sercnpht okmSngi is slao nldiek ot ahtmsco clurse deu to reenrtnfecei iwht crtsgia acumos nda ciad oirtdu.opcn suJt tdn'o eksom ski.d otnD' od srugd. Stay ni hsoloc ererfov ikel med etnusdts.

slituBom xitno cats iva aesprtose ttha caleve SRNEA nda terpvne ytnceieaohlcl arleese at het oerulasrnumcu tnniujoc 02F0A(2 )32p.1 husT, ti edos ton ydcreilt taffec eht isntay-otpsprc muelsc lce.l If ouy add latrenxe cel,oitehylnac uoy oduwl lltsi vhea a epoyllmcte malnro roes.pnes shTi semnlatiie all ubt owt s.anersw

ehT dne ptela niolaeptt P)E(P luowd be edcfeaft yb limbtsuo xoint ceauesb eht ned tpale nateiptlo is eht hcneag ni atvgloe ttha rcusco at het yscanpioptst useclm toorm lpadeent rftae an ctoain iottanepl in het tmoro rnoeun onxa srgitreg ealsree fo amny cohialntyelec cvseisl.e lNrly,mao na ticoan lepaotnti ni eth toorm nourne lwli auecs ulfnxi of liumacc taht dslea ot soifun fo chA vecislse i(uniqregr ERS)NA nad sso,xicoeyt esleangri leagr etnqsuiait fo hAc into het neyspas hhciw nca nthe bnid dan etggrir na PEP in eth clmues. ihtW ilt,osmbu osinuf of eht chA seveclis si ehibindti os sesl hcA is edselare dan teh PPE si ndbtl.ue oyblat,N eht vglaeto si the mase sa het PPmE hiwch is teh eloatgv tfrea rnmado nuocrcerce fo hAc reelsea see( )b.eowl

A enmaiiutr nde aeltp enolttaip E)PPm( si eth evaglto haencg ttah ccsour wneh one eviscle of yacnetllehoic is aeds.eerl heTes crcou y.drmonal PPmE owdul tno be dcfetaef by smlbuoit notxi bcaeuse ti si the rcdeopu of ardomn onusfi fo a cvlesie hchiw udlco tlisl cruco featr oiaitidsnatrmn fo itlsmubo .txino

erHe si na eimga nmiingerd the ecffierend newteeb PEP adn mPEP.

siFtr ptes si to kmea hte stvprmeepiu anisgsodi fo esoirsoposot omrf hte ccainill eegtinvt . ( hTe pdssouep yubtsep ni uor tintaep si umsesaopalotnp roo)ispotssoe

eftrA tish het xent teps si ot kmea an aiinoctosas iwth teh lab nfngdiis he T ipymrra cdteef is a incdyeefci of roesengt .mlNalroy gretsoen aeecredss coottesasl ivtitayc by

1. ugndcnii sopipatso
2. rcaesdeni nfairotom fo negsootrioertep a coedy ucelmloe wchih hbistiin cviaatonti fo AKRN rcretpeso

eNt ecffte fo songil eonsgert is csnieerda eootssatcl iiyvtcta n,da in hist eisutqon yb xoensneit NKRA L ienrcaottnonc .

EOTN : PLA hhiwc si na codnatrii fo slsobottae iaticvyt sedo tno /hegacn ineersac in reospsootsoi , sa schu oiavd lal onptsoi tiwh na serecina in sbaelttsoo iivtatcy

LT:R;D vEne twih Tyep I ro II leanr urtlbau sodiaics eth ioesnamsaemngi ofmr miutagenl si tno eamidpri dan tsuh is hte amni uocser of m.amnoia

eeHr si my aek:t Bdase no erh rhotyis adn adesurem maapls va,lseu stih iglr likely sah one of eth w"lo tasoui"psm erlna lutbrau s,icesoad hitree eTpy I or ypTe II (see thsi hatrc rfo aionnersg sbaed no rduseame lsvuae ro thsi eiagm rof fnu ofullocr raeln ubtualr cisasodi dan 002AF2 p35)9

T,neh ew aer tlod atht ehs has a eectfd in smm.a"nnegos"iaei In het ralen be,lstuu minaoma si aertgeden in otw ipramry wyas: vai idcret enrnocsiov of nitemgaul to naioamm ni teh orampixl eubutl whchi is hetn cesetred tnoi the utelu,b ro by 3HN iicgbnmon wthi ithw +H in teh ciclnelgto uebtlus hcw(ih I egsus htey era srdgncioine a eeatasrp aegnsesmmioain haatypw vene hghotu ist lal kndia r)da.e?lte See tish irdmaag or shti airadgm

nsimAusg uor rigl sah yeTp I rlaen ulutbra iaisc,osd hteer iwll be edcsedaer ialitaablviy fo hndyrgeo onis ni eht elnar seubtlu to iemobcn hwti H.N3 ,usTh het mpiaryr sreouc fo oimanam oiouptcdnr ni siht patteni wlli be tunegliam hcih(w is teh aromj ucsoer of amenaogmssenii in a omnarl rsonep nwaya.ys)

hFterru anosgrein - epyT I is imraiepd eictonrse of ydergohn inos oitn eht eun,ml so eetrh will be ssle ronyghde snio ealbavali. Seh lkieyl sah yept I aubcese stih si arprmliiy deaertt wtih ausipmsto atcrtie (htob to bfreuf nda ot npveetr enalr stsone wihch ear a mconom atconic.oil)pm veEn if seh ahd Tpye II het resnaeicd oneetxcir fo cbiarb owdul aols fbfure omer H+ eivgnal sesl rof mnoignassimaee ni hte HNH/+3 tnbcmiaonoi shinaof.

nr,lyrotaiC epTy 4 anler uutlrab discaosi ch)aekmil(yrpe uertsls in reeddsace styshsnie of noimmaa ni eht prxiomla buutl,se ihcwh ew nokw hes esdo tno vhae uecsaeb fo reh wol om.spstaiu

srIcimoeuhoishtmytmn essu lnsocuelyertf ggtade isntbidoea to bdni eifspicc igetsann no sts.uies nI isht eacs, na tyidnboa oludc be tdreiedc nasatgi 1D4vC04 niavtar tipneor uesd ot agt eht cllse ni teh saplsem thta psesxre eth rat.navi Tish si aols usfleu ecsuaeb ti can eb oden no sedils of frpanaif mdbdedee s.tiues

• nififtAy cumnol praroyamtochgh is dseu to staeeapr a biihmaccelo eirmutx esbda on otinanctrie eneebtw nyttnio/a,aebnidg nzeue/m,srsyeattb epidn,ctrrgolea/ ce.t but udlow not be ulefsu ni deepb-merded tusssei or shti caes
• iDytsen nrtgdiae niarftcueonigt is dsue on mxertuis ot eatpeasr ethm inot nenmoscopt dna is aacrluitylpr uuself ni taegnipsra lelc ossnp,usenis uhcs as in atirangsep lodbo iotn learys ot tge het fbfuy caot hitw WCBs
• noterNhr tblo is rof RNA dan cryotfsuelnle tgas a pecei of RAN prstnee ni a seplma
• RCP si rof tpdilgfnyniiynf/iieang a AND meengts
• reRsvee ctstrneirpasa R(T) PRC is tcallpyyi duse to aemesru xoseersinp llseve fo an RNmA
• hetuSorn ltob is ofr dgniiynfiet a DNA engtmes in a igdset

eUentir toyna si the omst cmmnoo seuca tmsopptaur ehmraoehrg ude ot rulaefi fo teh uteurs ot eivfcletefy ortatncc dan rrcttae afrte ryelvdei. It si tteread ihtw uenrtie essaagm nda ctonioxy.

hiTs etoqinsu is gsniak awht ltef doanintm acicilrntou e.nams I pspseou it awnts us ot rnfei taht het DAP si gislnyupp teh mdpagairh feucasr dan AV .ndoe

tI is nngcuisof to em bcseuea mraynoll teh tgRhi amnrglai rytrea piusspel hte aagpmtciarhdi eodbrr tuca(e mg)airn fo teh t.erah 'mI ont rseu htat ti agnehcs in etlf tndnioam .aoiculirtnc eFhrroruemt ti oduwl not ncarbh off hte D,PA hlagothu aebym srpta fo ti rae uspidple yb eth DPA

Aslo het VA doen si lpsdieup yb teh vatuteroiilAcnrr dlaon try,era hhiwc acn be a ahnbrc off fo hte LCA or eth tXbLu C ont aylrel het DPA

3sbec:/ianMg.mt953v/hiP19w.sto.l./ihpt7l//mCcnpcwn/wr

os usnciogfn useoitqn rof em btu hte noitp is to kown teh ucrseo fo tfle ninmdoat ctuilcioanr to eht DPA

heT yripram ancshimem of aannomifitml o"rmt"u ro leinglws is esiaerdnc ebleiipatyrm fo hte neoemlhditu hwhci slade to aageelk of sflidu (2F2A00 21)3p

A teon ot slfe : nareietC esothphpa si a horts emrt nreyeg sruoce ni mcelus . stcA by nogtidna aepshthpo grospu to reenergtae APT .

eti*nraCe si idrdeve mrof inrAigen and dtblieoeams to nieinCraet ( hwhci is rxceedet by eht ekisynd )

• arlAiert: o2Pc 30 mm H,g Po2 69 mm Hg
• tleAirar 2O ctnotn:e 12 ovl% )N–11=%7%2(
• xeMid osnuve P2o 36 mm Hg

• eMxdi ousevn O2 tetcnno 8 lv%o 0N%%=6)11–(

• A) amAnei - ttePnai sha ln 2OPa dan eeeadrscd 2O .eotnctn Also nptaite si etlregnivhaptniy and CO2 is hsut ol.w

• )B dcerdunuDig- leoaarvl ovtiniotnphylae - lAtreria 2OP ldowu be maCpwol;O2& hhig
• )C sdeeiRecn at a ighh eiladttu - reAtlrai P2O would eb low
• D) Sveeer iegoalrn nghistmmaci of levaoral ltoiaevntni nda oymrnlpua arlclaiyp ofnipsrue - nyuamrPol obusmlE doulw cusae a rascedee ni rteaailr P O2 )E rtlyVnoua oayvniietterhpln - ariAterl 2O% nctteno ldwuo be ln

ianmAe ucssae xahoiyp wtutoih imyeaxo.ph iannegM olw 2O yleevrdi ot tesisus tbu ton olw O2 roaastintu fo het lb.doo heT sunlg nac auqedyatle eilvred 2O ot the elaasrrit so O2aP is on.amrl inaAem casseu wol 2O tocnten aesbcue ouy ahve taeeviyrll wol tonmuas of bH ot cryar ne.xyog

O2 ncnteto = (1.43 × Hb × aS)2o + 00.30( × 2Pao)

Tihs si elkliy repsHe xpeimSl Vsiru 1 da(ebs on hte clvuaiesr ilesons on het )ilp ihwhc raminse nmdarot in enryoss ainlgga, tmso lmcnomoy hte mgnaliiert gnnolgia 20(20AF p)14.6

Teh nubtr alnmdo llems dan naycinonoct padneys is iaithaerccrcst fo aciynd oiinngops. ednCyia niioosgnp is atdeert wtih snitietr uacbsee tsierint dizexio loeobnimhg ot morf bhmmtnaieogol cwhhi nbids yeicn,ad allngowi less itxti.coy liousTahtfe is tfone dadde ot niseerca alnre eniotrexc sa eycntai.aoth nyaeiCd yictoitx may oals eb eatretd twih nhay,oclbixrydmo chhwi isbdn eacdi.ny

0F022A 667p ahs ofanftndieetrii of dyceian frmo OC i.gniposno

Seh ash roomt nda ysorsne sstmyopm. iThs or/ tbho sdkin fo slp.mei reH srziseue era ont idbderesc as tclnoncoci/i ms,oetnvme adn inlucde eiosdpr fo reaipdmi snss.ecouncosi hisT lesru uot lergzieedna ctoonlin./cic ereTh is a la-pistoct tea,ts atth urels uot bnaesce.

soAl het pli cnaimksg si acctertihicars fo utsitmmoaa, hihcw is ndouf in emlpocx parlati rzessuei

tceAu MI and lrtiam guegrr rfom( eht mr)mruu elads ot LV iufrael nda wflaokbc fo lodbo inot teh .sglun

Thsi aedsl ot rescaiend opmrlnyua tacothridys playcaril sr.euserp hiTs llwi adle ot esxces vlmeou kainelg rfom teh ymlnrpuao sillprciaae tino eth teitalnsriit nda hits liwl mensitfa as pymunlaor emead )a(ccls.ekr

aPnuryolm edema lliw rteneefir hwti sga cexheang eladnig to eoihampxy.

etcuA IM and ailrtm ugregr frmo eth mururm dales ot VL frleaiu dan kfacoblw of doolb toin eth ul.sgn

siTh esdal ot ridceesna mpnoyalru hyrtstacoid aylaiclrp eepurrss. ishT lliw lead to scexes levomu elnagik mofr teh yarnmoupl pcraiisllea into teh ittelinarist dan ihst wlil ateimsnf sa runpayolm mdeea s)l(a.crkce

maourPyln dmeae iwll tfernerie tiwh ags xehcgena ielngad to mhoyxep.ia

ihsT oamwn sah tcyyPlosic anaoivr nromsedy. ishT cna be cuddede ubseeac fo eth hghi HH:SLF aotri t(),2g;& ighh I,MB nda neserecp fo dwwitarlha bigdlene ni a geoetnrpoers dtlawwhira estt. nI otscpyyilc oaivarn srdmyneo, ether si idsreanec eeesalr fo nsraodeng morf chtae ranteni lce.ls ehesT aegrsdonn anc uscae stmoysm lnomocmy eaitdcossa hiwt OCPS rsuiimht,(s )aenc tub can olas be emoarzitad to sroneget in epoidsa tssuei. heT scnpeeer fo neotgerss in stih rfom essuac ncottsna ieeavtgn cbdkeafe no the ypsathloahum nad urdoignyltase in teh prreipoatap evlesl of eht ditnsooaopnrg ees( eher nad eerh)

rHee si a anpscormoi rhpag of het rmehono elvlse ni a nrolam eltsranum cecyl to POCS.

A rpogrotseene twdhirlawa tets si dues to hlep intdrmeee hte scaue of rr.aihnemao fI wlidathra ildebeng cucos,r ti nesam eth tianetp hsa eftcnifuis irlasdteo nda eth aaromrnhie is due ot nvoula.aiotn fI on idlwhaatwr gendelib cco,urs it manse hte tntapei retieh sha cncihor aooninvault wuiotth eosr,negt a iacenroevtn mrtueemnod,i or a plmoreb ithw eetunri l.foowtu In rou ptna'tsie ,ceas hes has wrhiwaadtl dbnegeli os ehs hsa ulvnit,aoaon a cnmmoo mptsymo fo ylsocypict oranavi .dysrnemo

Legonit lgnmiaa is a yept of meoamanl FA0202( 4)84p, neehc hwy ti si potmirtna hte selino is bk/lobwcnar thwi alireugrr bsorred dna ragelgnni (lla sarlalhkm of o.m)amelna heT isybop pstrdeicino soal tifs etgnilo lmiaang, tbu veen fi yuo aer otn a osltpigatho teh etinpioscrd thta isft cacnre dna dan ca"lypiat taolemnecys" dlshuo ponti ouy ot iltngeo m.glnaai

• Ashcsatnio nigrcians si ehngcniikt (acsaniosht nmsae pedlirmea ayahi)slprep and rnndgikea fo skni in dsflo nad csseera ioecatdass htwi nsiniul itesncrsea
• tniiccA irostseka is a lpnantieamrg nlsieo htat is a masl,l ugo,hr oemhetteruas ro bionrhws ea/alppupuqle
• dnupomCo nuesv si a etpy fo lome ttha is lhtlsyig ae,tevdle rnbwo ro hiltg wnbo,r and hsa raulrge dsb.rreo tI is ton f.gs-iaotwrgn
• eeirhSrboc saoerstki ear "-nksot"uc flt,a eysgar, enigpmdet asumsuqo paleeliiht iilraopeftnor fo miuraemt ksencrtaiotye with fdneirlkelita- s.cyts pidRa oesnt fo utlpleim tndcsiiea olbssepi GI .anilmyganc

F022A0 ,8p42 747 dan 484

oeuTubsr ilsocsesr is trridehcaeazc by OAMHMAASTRS ra[tmasoHam in SCN dna iks,n Abamoirsfgino , airMtl ingru,irttaoge Ah-afesl tssop , idcacar Rohma,yabdmo oru(bsuTe lcsiro),ses aoltsoamu ;atndOnim aletMn eidoartrant teluleantl(ci yiati)d,silb lrane npiAmylomogoia , zSs,eeiur rhgneeSa atpceh,s 2F20A0 ]5p25

If oyu d'tidn kwno hwat amohrsamat oolk elik i(e.. m,)e rhee is a teriupc fo wath yteh reew cnigibsred. hTye asol disrbcee res,uezis dsebmypunlea cilifadce dounsle (lielky amsrmahtao of hte C,S)N and a carcaid m,ass cwhhi si liekly a rmmbaay.odoh Tseeh aer iesracctthicar fo ebTsuuor r.eoSslics

rnoWg nsrewa noais:ntpxeal

• aimiallF iyorrctphhep iaoyamtcrdoyhp si sacoseidta htiw udneds adeht ni haelt,est not eezrusis nad ahramstoa.m
• nredraG reSndyom si olas alledc fmilalai eoccaotrll lspospioy adn si a form of lmlaiaif tmdoanueoas lssoypiop.
• yGglcnoe raegsto dseeais Type I is onV ekeriG ,daeessi hhwci pessrten twih gnseeoeataplopymhl adn seerve gsntfia ohleapygyimc itlpaylyc in any.cfni
• ipluetMl cnreoEndi eNiaasolp pyTe I is ceaitaodss ithw all eht s'P -;gt& Piat,cncare ha,Priorytda adn iaytuPtri accpi(aertn crdeenino ort,smu hrayotdrapi moeaad,sn nad utpatryii rmt)uos

eH sha a dnow nda uto ,lppui udasec by NC III .lsapy His zeag si edu ot ppousoedn nicota of eth arlleta eurtsc dan upsriero buqi;ole sipots ude ot nervotedani of tavorel lebraeapp sesoiiupsr.

hTe ynol uiyjnr ilstde htta ocdul eacsu a NC III slypa is muysnrea fo hte APC spciensmgro teh ocratouorml e.ucnusl

isTh 'owansm raadcci teasrr csdaue a oripde of loss fo lobod lfow nda iiashcem in eth dyneki htta sah led to cueta urblaut .snociser In NAT terhe si an itiingcn veetn nteh na ocgiruli .easph nI T,AN ereht si dteha of laner utrlbua liateihelp elslc htta gloush fof adn mrfo ydmud wnrob uarlrnag cssat. eepK in nimd het oxaiplmr elutub and ictkh icgnsnaed lmib rea teh artp fo eth iynkde tmos cseubitpsel to opcxyhi uri.ynj 0AF0[22 ]p206

heeTr aer a wfe ysaw ot etg ot teh nsewar of hte esipcl r:eorr

• heT aouimntt ecdsua kin"ppgis" fo na eonx. picilgSn is eth scsepro rwehe tsiornn rae celpsdi otu nad senox are slcpdie tegteorh brfoee rpgoitnex teh AN.Rm ainRtdee nrntsoi ro kpsingip fo na oxne is ekllyi a rultes fo an rorer ni s.lpcinig
• eTh ontmiuta tflsise si GT ot TA. In ANR this wdlou eb GU to U.A GU si a oknwn neponmotc of hte '5 lsiepc tsei A,p02022F()4 os isth laos pinost ot icselp itse amt.ioutn
• oeNn of hte rohet otnsaimut euyeladatq secierbd hyw na noex ulwdo be psdkepi. ouY ucold eranos a snnsneeo iotmanut a( ntutioam htta isnudrtoec a tops ncood) uldoc ""skpi eth salt nxoe or os eeascub it rutctuatnes het r.eopnti rwoeeHv, eth aitotmnu does otn tif nay ttah diuenotcr a tpso ndoco e(ht stpo osocdn era U,AA ,UGA dan ..UGA. enon of thees veah UA in )m!hte

hrtOe :nfio hsit byo hsa ,tleniaenrohypuk huhogt melutlip insamtotu cna ldea ot iths os ti odwul nto lphe ni ngnweiras itsh .unstqoei

I nt'od ekil hsit siqntoue ofr nmya s,oasren but acbyaills he sha iasioocssdr gnenisotaa(cn mauasonlrg twhi no gehatopn dfoun no bips)oy chhiw aogdircnc to isFrt Adi si reom mmncoo in rAcnrmciafi-neaA .emeslfa nSeic eh is fcniAAn-ecmirara that is hsi rski roaftc A(00F22 )667p.

In hopsetysih sngtiet, eth alpha lvuae si het rliiybtpaob fo nimakg a eTyp I .reorr siTh is eth ptey of rroer eiedtnmno in hte es.ountiq

• eypT I rrroe - uoy find a reednecfif whne a fdrfenecie ntso'ed ealyrl siet.x
• Oen ywa of ebigeenmmrr siht is atth htis si hatw sinstiestc awn"t" ot am:ke yhet anwt ot find a iaitsnicfng reeicfedfn in rehit ,tdaa uhts it si het if"str kemist"a yht'ed amke.
• phAal si eht boiaybpritl you rea lwnligi to eacctp thta you oclud eahv daem a ypte I eorrr e..i( na aplah eavlu fo 0.05 neams hteer si a 5% biablpoyrti you oludc emka a tyep I reror nad etrcej eht lnlu ehihpsstoy nweh you udlsho ot)n


• Tepy II orrer - yuo do not idnf a edrecefifn hewn you hudlos eavh uesebca a urte nedirfceef ellary eisstx
• Btae is eth pialbbroyti ahtt oyu meka a ptye II orerr
• ewrPo si euqal to (1 - a)etb
• Pwero acn eb eeardcnsi yb nsagiicnre pesalm sze,i dan huts ithw a glrera saeplm ouy have a rloew itoybapirbl of kmgian a peyT II reorr
• Poewr can salo eb canrdesie yb grsniceian dxepeetc ffecte isez or nrcanigsei nesprioic. tI si iegetnnsirt ot otne cycraauc hsa on ftecef on pew.ro

20A02F 23p6

Bsade on hte qonuesti emts and eht oabeitoadntisu ingev ytefrbu(lt hras mdcbneoi ihtw nDN-phn/odsmaiin,i/idtaltS)pip-htaosA hist mwoan ahs csslica lsup.u ESL is stdesiaaoc tiwh tpicys,neao os aetctominrooypbh si het tseb hcicoe fo het lbaaveial rw.asnes irnTyphcatoebmoo si mnomoc ni suupl AF(2002 p704)

• HUS si eistaocdsa hwit Elcio. ro elgaShli nicteiofn dan nto puu.Ls Luspu dyknie iedsaes si ufdiefs eiptoevlrrafi ehnlsopeigut.mlrrio
• ytcaocMicr ieaman si ialtclpyy eudacs yb B12 ro toalfe iediynecfc and ont itcdseosaa thwi .uspul puusL iaeman is pyilyaclt aemnai fo ccnrioh sdaiees, hwchi is tnorcymioc, ro deu ot enuatdeaqi BCR doiurncopt ro noir nie,cciyfed wichh si .rcocmyitci
• elupMlti eltncadue tyescrtyhroe are fdnuo in smauleike wenh the BRsC aer einbg hps"ude" uto of teh ebon ,rowmra ro in edsasesi eewhr eht oebn oarmrw si iyhghl sseresd.t usupL sdoe otn atplylcyi eacsu h.tsi
• I am ont %010 ruse hyw luxeaor tfaoirnmo is ,grown useaebc as afr sa I dantneusdr yan ocdtniion thta eisecsran nloocomnal sbA nca suaec uulerxao moifatonr, tbu I ma msagsnui it si ujst nto sa i/mck,nleomoly henec cmhotooypbreaitn hchwi si eyrv cmoonm is eht beetrt wnarse

rFmo ahtw I acn tel,l hte tgis fo sith oieusqnt is tath he ash SCID adn niesc teh CISD clidh sha caibalysl no emumni tyssme (ytaallpiurcr beeuacs het clka fo Tlecl- )ymtnmuii ehter si a ihegrh hcaenc of ntusfosdr-eaaascsnoiit fgtra svrues ohts aesdesi A)-HTGD(V so loodb sportdcu haev ot be .ertdiirdaa

reeH is a daepscme efeercnre whit hwo eeurqris draaertidi CRsB edu to ecrndeais sirk fo VTD-AHG rof ruoy guisrpen.

nI stih udts,y a ecpalbo si ton dues no hte tlconor .ogrpu Teh lmieerpnaxte rgoup gset edoohmpanerthtxr ewilh the ctrnloo rguop tges no" teetart"m.n sThi srtsleu in rcredopeu bais, as ctjuesbs in derientff sugrop rae tno etdtare het sae.m Binlingd adn use fo a cabolpe ercude the luneencfi of nsaraiptctip and eacesershrr on erucpeosrd adn irinroatpetent fo ousemcot sa heinret rae aarew fo urpgo etia.snnssmg

eeS bealt on iasb nad sudty orsrer ni FA 1029 p 620.

sEescx netarpt tpresea adel ot dartsn prsepesrgo/rila eud to na tuesnbla igneor (in itsh csae, sscxee Ctidyein ).asesb

It luodc be a eadetrep tpreant as well ei( eth itrcnutieoled eatrpe AGC in tgisonnu'H.tn)

eserh' a meor in dehpt ieaaxntpnlo rmof( idiiaepwk ltaerci no ledtianS-sdrpp rsiingmiap:)

A asegppli vneet nlyaolrm corcsu newh a enqcesue of rietetipev iclenstdueo tedn(ma a)tserep are oufdn at the stei fo ecotipnlri.a Tmenda asrpeet are ubatlnse oseirng fo the enegmo ehrew fteureqn isntnrosie and osteidenl fo ntlodieeucs cna ekat ,place egsutrnil ni oemnge renrstna.eamger

yKe ctesspa fo the oeiqtun:s

• iekipHoysns fo eth rritopose ltfe niceretvl htiw aeigicrnns yttiavic elvesl - in my ionnopi sthi si the myiarpr cuel ot ointsess fo het rhtgi carnroyo e.artyr hiTs is aucsbee teh oepsortir aethr is eppdiuls by teh teroospri ndicdegnes etay,rr wcihh in smot olpeep ohw hvea gtihr mntndaoi ycarorno calcuintrio si a chanbr fo het rhtig aycnroor y.rarte
• W"neh nligmbci irs"ast nda the hisonisypke bengi reetpsn on tssers sittnge - shit slpeh ouy ot wokn eht nocidtion is lnoy ebreeatxdac in ceiex,rse and itsseosn of eth CAR sargneete osmmpyst in eeisrcxe aecsbeu in sxceeersi teh raieencs ni engxyo dandem piycylatl secaus adilinot of hte acoroyrn vlsssee ot do.meatcaac ehnW hetre is to,sinses het elssev nconat aeitld adn tush ereth is rseiattnn ihiesamc fo teh aera teh sveels eussppli (isth is ptnloityeal ectbaedaxer yb eht ronacyor alste emnpnenooh ni a sersts sett hwich can crocu whit anoiditnirasmt of idr)otlassova 0A220F p403

eIrcsaen in nogxey mnoinutposc is eht anrmol presenso to ecreexis dan loean is tno phaitoc.lgo sxvrtucalaarE nmeicroopss fo hte onryocar siraeter is lsao iosenerddc nrloma dan gnipholc;oaotn isth is yhw omts oronrayc ldobo oflw cosucr rignud ldtasieo dan hyw het edmuronacdi is smot cesisetuplb ot msheicai.

shiT nwmao hsa teh lsccisa nigss fo aimnitv C cyeef,ndiic or :syurcv yase bgsni,uri heeiitpca, oiallelrrcfpui sghmoarehe,r gum saeesid, adn losw noduw ginhea.l itamVni C is scyresaen ofr orrppe arxonhdylitoy of lnoierp nda inyesl in elo.alcng 0(FA202 96p in)[c]e

Thsi is a tlpiaar mleo aesbuce fo the seeenrpc of faelt pastr. mCtelpoe lemos ehav on lafet tspr,a ilaartp lmoes eahv aeltf pl(triasPTARa = atfel .TRP)As 2(0AF20 p64)2

e:toN I-L12 peetrorc ic,cendyief ro a eftecd ni the enoerfrntI maamG epercrot
nhiTk isamisDndete retMablaciyoc and gnFlau ifInnetcso . Alos naollmlsea *

eTh cuooolrmto erenv naervienst yvere raluoc ulmces xcteep ofr altarel esruct nda orirepus bqeioul ,mseucl os a elnois ot hsit erven liwl rsentep tiwh a nowd and out y.ee tI olsa sntoolcr tironntcciso of eth i,sri os a siolen ot eth eenrv ilwl rpenste htwi an mlnabayrol talided p.puil In hist ,otqusein s'ti birecedds sa eth ttipane giavhn a yirsoht fo lauvsi tdcforomsi ni tibhrg t.hslgi

a ensloi ot het ndeubsca eesnptrs twhi a yilmdlae vdtideea eye

a iloesn to eth FLM seretpsn hwti nrnecualteir mtlpoaohi,hepalg iwhch lwdou be an yee atth td'soen /tdabucda ptas eth dmieln,i tub illw od os on moooiccdmnaat tnetg.si koosl leki tihs

t'si ton the soprieru rlviceac nolnigag caebesu ttha whlei atht sola reetnsps hwti stpiso, uyo dslhou aevh iomiss, as ewll as saiosdihnr

a sloein ot teh racleorth eevrn setsrpen as a abd eey rieds hhgi sineol

taslvi and dene to eb etaertd ifsrt, os orpnaeit and hent p.rldexmioia

nr33mhC:o/smn2.th.nwM9/bls/.ccp/lew/4c9wipv0titPg/i.a

tritanmop ot ento ttha gsosahpapnoehotr eebcom briielrseerv ta a naeicrt ntoip so adlipxomire soed itsll eend ot be inevg yreal

cislsca mhaeaintys asvgir uetripc. nWroses thiw e.us xS ludiecn ldpip.oai roeInvtmmpe wtih .AECh

Aosl dies teno, dno't fsouc on teh nynagcrep asttsu, tub ewnom ohw aer in eht ptuoartmsp iedor ear ta layatirpucrl hihg rski fo dplgivneoe imenyhsata asrigv

cynagrenp sacesu eh,yrpmvaeloi dna hhrieg lbodo fov/mlowelu rgthuho the aerth lwil niesecra umrmrsu (rcioat e)g.rgur

Left imontnad utrloiicacn - poesorirt icendedgsn eryrat P(AD) hcwih uplepiss VA odne etc si oicngm romf hte *flet xuecifmrlc. moPrpt assy ti is docelk.b To gte to ehrte, hte orrctec acomtaanil whpatay si tfLe onaorryc r,etyar lumrxecicf rryat,e eoptrisro crtinrvnealtruie D.)AP(

sihT acn be drasnoee by orcsesp fo eilniaointm 1 ot-o. ivenG the etLf nimatndo ,uclictranoi we acn liaeimnte htpsaayw enigngnbi at het thrgi a c-orrony.2 oT teg elcogakb at reoptrsio fo reath, ew will TNO eus aniotrer rrttnaivlnreiuec erat,ry so you cna telimeain the 2 ontsopi tlgisin sh3 t.eo - hTe xluerficcm aretyr ievgs seir to eth AP,D btu si nto teh fainl yraret in uro ahtp ot eth gblakoce s(o acn nieimlate hrntoea t)osTwi.h lsodhu vieg uyo het oertrcc ra.enws

lraiscc,doopeiyLpah or ,SLP si eht iayrmpr nioendxto riaotmed fo arg()-m ssipes dngaiel to ceipts hksc.o sTih nwmoa klelyi has sspies rfom E. l,ico a gamr ngeitaev aetrcibmu cihhw doeprscu ,PSL asebd no erh rtoyish citignndai a U.IT Elco.i rea teh stmo mcnoom seacu fo UTI. A2F0(02 13p)3

ylMualder rtoidhy maonicarc is neefdid a:s

a inmanlgat fetpioriraoln of foluailarcrlap C"" lscel htta eretsce nnitaccoil

ooylstghi ohwss atnnamigl murot cells hiniwt npik lhin,)y(a aylmido oratms