• No results found

Diagnosing pulmonary embolism: establishing and consolidating the role of spiral CT

N/A
N/A
Protected

Academic year: 2021

Share "Diagnosing pulmonary embolism: establishing and consolidating the role of spiral CT"

Copied!
21
0
0

Bezig met laden.... (Bekijk nu de volledige tekst)

Hele tekst

(1)

role of spiral CT

Strijen, M. van

Citation

Strijen, M. van. (2007, March 22). Diagnosing pulmonary embolism: establishing and

consolidating the role of spiral CT. Department of Radiology, Leiden University Medical

Center (LUMC), Faculty of Medicine, Leiden University. Retrieved from

https://hdl.handle.net/1887/11452

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the

Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/11452

Note: To cite this publication please use the final published version (if applicable).

(2)



$FFXUDF\RIVLQJOHGHWHFWRU

VSLUDO&7LQWKHGLDJQRVLV

RISXOPRQDU\HPEROLVPD

SURVSHFWLYHPXOWLFHQWHUFRKRUW

VWXG\RIFRQVHFXWLYHSDWLHQWV

ZLWKDEQRUPDOSHUIXVLRQ

VFLQWLJUDSK\

0-/YDQ6WULMHQ

:GH0RQ\p

*-.LHIW

3073DWW\QDPD

0+3ULQV

09+XLVPDQ

$FFXUDF\RIVLQJOHGHWHFWRUVSLUDO&7LQWKHGLDJQRVLVRISXOPRQDU\HPEROLVP

DSURVSHFWLYHPXOWLFHQWHUFRKRUWVWXG\RIFRQVHFXWLYHSDWLHQWVZLWKDEQRUPDO

SHUIXVLRQVFLQWLJUDSK\

0-/YDQ6WULMHQ:GH0RQ\p*-.LHIW3073DWW\QDPD0+3ULQV-/

%ORHP09+XLVPDQ

-7KURPE+DHPRVW

(3)





$EVWUDFW

%DFNJURXQG 6SLUDO&7KDVHPHUJHGDVDSRWHQWLDOO\

FRQFOXVLYHGLDJQRVWLFWHVWWRH[FOXGH3(LQSDWLHQWVZLWK

QRQKLJKSUREDELOLW\VFLQWLJUDSK\DQGLVDOUHDG\ZLGHO\

XVHGVRPHWLPHVDVWKHVROHSULPDU\GLDJQRVWLFWHVWLQ

WKHGLDJQRVLVRIVXVSHFWHGSXOPRQDU\HPEROLVP,WVWUXH

VHQVLWLYLW\DQGVSHFL¿FLW\KDVKRZHYHUQRWEHHQHYDOXDWHG

SUHYLRXVO\LQDODUJHFRKRUWRIFRQVHFXWLYHSDWLHQWV

0HWKRGV ,QDPXOWLFHQWHUSURVSHFWLYHVWXG\

FRQVHFXWLYHSDWLHQWVZLWKFOLQLFDOO\VXVSHFWHG3(ZHUH

VWXGLHG3DWLHQWVZLWKQRUPDOSHUIXVLRQVFLQWLJUDSK\ZHUH

H[FOXGHGIURPIXUWKHUDQDO\VLV6LQJOHGHWHFWRUVSLUDO&7

VFDQQLQJDQGYHQWLODWLRQVFLQWLJUDSK\ZHUHWKHQSHUIRUPHG

LQDOOSDWLHQWVWRGLDJQRVH3(ZKLOHSXOPRQDU\DQJLRJUDSK\

ZDVSHUIRUPHGDVWKHJROGVWDQGDUG7KHRQO\H[FHSWLRQ

ZHUHWKRVHSDWLHQWVZKRKDGERWKDKLJKSUREDELOLW\94

VFDQDQGD&7VFDQSRVLWLYHIRU3(WKHVHSDWLHQWVZHUH

FRQVLGHUHGWRKDYH3(DQGGLGQRWXQGHUJRDGGLWLRQDO

SXOPRQDU\DQJLRJUDSK\$OOLPDJLQJWHVWVZHUHUHDGE\

LQGHSHQGHQWH[SHUWSDQHOV

5HVXOWVSDWLHQWVZHUHDYDLODEOHIRUFRPSOHWHDQDO\VLV

7KHSUHYDOHQFHRI3(ZDV6SLUDO&7FRUUHFWO\

LGHQWL¿HGRISDWLHQWVZLWK3(DQGRISDWLHQWV

ZLWKRXW3(IRUDVHQVLWLYLW\DQGVSHFL¿FLW\RI 

&, DQG &, UHVSHFWLYHO\

7KHVHQVLWLYLW\RIVSLUDO&7ZDV &, IRU

VHJPHQWDORUODUJHU3(DQG &, LQWKH

JURXSRISDWLHQWVZLWKVXEVHJPHQWDO3(

&RQFOXVLRQ7KHRYHUDOOVHQVLWLYLW\RIVSLUDO&7IRU3(

LVWRRORZWRHQGRUVHLWVXVHDVWKHVROHWHVWWRH[FOXGH

3(7KLVKROGVWUXHHYHQLIRQHOLPLWVWKHGLVFXVVLRQWR

SDWLHQWVZLWKODUJHU3(LQVHJPHQWDORUODUJHUSXOPRQDU\

DUWHU\EUDQFKHV:HFRQFOXGHWKDWLQSDWLHQWVZLWKFOLQLFDOO\

VXVSHFWHG3(DQGDQDEQRUPDOSHUIXVLRQVFLQWLJUDSK\

VLQJOHVOLFHGHWHFWRUVSLUDO&7LVQRWVHQVLWLYHHQRXJKWREH

XVHGDVWKHVROHWHVWWRH[FOXGH3(

(4)





,QWURGXFWLRQ

2EMHFWLYHDQGUDSLGGLDJQRVLVRISXOPRQDU\HPEROLVP 3( LVPDQGDWRU\EHFDXVHLW

LVDSRWHQWLDOO\OHWKDOGLVHDVH:KLOHDQWLFRDJXODQWWUHDWPHQWLVKLJKO\HIIHFWLYHLQWKH

SUHYHQWLRQRIUHFXUUHQWSXOPRQDU\HPEROLVPLWVKRXOGQRWEHXVHGXQQHFHVVDULO\

VLQFHWKLVWUHDWPHQWFDUULHVDFRQVLGHUDEOHULVNRIKHPRUUKDJH

7KHFOLQLFDOGLDJQRVLVRISXOPRQDU\HPEROLVPLVQRWVSHFL¿FEHFDXVHLWKDVEHHQ

VKRZQWKDWRQO\WRRISDWLHQWVSUHVHQWLQJZLWKVLJQVDQGV\PSWRPVVXJJHVWLYH

RISXOPRQDU\HPEROLVPKDYHWKHGLVHDVHFRQ¿UPHGE\REMHFWLYHGLDJQRVWLFWHVWV 7KHFXUUHQWO\DYDLODEOHGLDJQRVWLFWHVWVHLWKHUVKDUHWKLVQRQVSHFL¿FLW\RUKDYH

SUDFWLFDOSUREOHPV$QRUPDOSHUIXVLRQOXQJVFLQWLJUDSK\YLUWXDOO\UXOHVRXW3(DQG

DVHJPHQWDORUODUJHUYHQWLODWLRQSHUIXVLRQPLVPDWFKKDVDKLJKSUREDELOLW\RI

IRU3(+RZHYHUXSWRRISDWLHQWVKDYHQRQGLDJQRVWLFOXQJVFDQV,Q

DGGLWLRQYHQWLODWLRQVFLQWLJUDSK\XVLQJWKHKLJKO\XQVWDEOHUDGLRDFWLYHP.U\SWRQ

LVRIWHQQRWDYDLODEOHRQDGDLO\EDVLV3XOPRQDU\DQJLRJUDSK\LVJHQHUDOO\FRQVL

GHUHGWKHJROGVWDQGDUGGLDJQRVWLFWHVWEXWLWLVRIWHQQRWXVHGZKHQLQGLFDWHG

SUREDEO\EHFDXVHLWLVRIWHQSHUFHLYHGDVDGDQJHURXVDQGFXPEHUVRPHSURFHGXUH

,WPD\EHDVVRFLDWHGZLWKFDUGLDFDQGSXOPRQDU\PRUELGLW\LQRISDWLHQWV 6RPH\HDUVDJRVLQJOHGHWHFWRUKHOLFDOFRPSXWHGWRPRJUDSK\ &7 RUVSLUDO&7KDV

EHHQSURPRWHGDVDQHZDQGHIIHFWLYHWHVWLQWKHGLDJQRVWLFZRUNXSRISDWLHQWVZLWK

VXVSHFWHG3(%\XVLQJVSLUDO&7DYROXPHWULFWZRGLPHQVLRQDOLPDJHRIDSDWLHQW

LVPDGHXVLQJDURWDWLQJGHWHFWRU3XOPRQDU\HPEROLDUHYLVLEOHDV¿OOLQJGHIHFWV

ZKLFKFDQEHORFDWHGFHQWUDOO\PXUDORUHFFHQWULFDQGPD\WRWDOO\RUSDUWLDOO\RFFOXGH

DSXOPRQDU\DUWHU\7KHUHSRUWHGVHQVLWLYLW\RIVLQJOHGHWHFWRUVSLUDO&7IRUWKH

GLDJQRVLVRISXOPRQDU\HPEROLVPKDVUDQJHGIURPWRZLWKVSHFL¿FLWLHV

YDU\LQJIURPWR,QWZRUHFHQWDUWLFOHVKRZHYHUWKHDYDLODEOHOLWHUDWXUH

KDVEHHQFULWLFDOO\UHYLHZHGDQGLWZDVFRQFOXGHGWKDWWKHUHFXUUHQWO\LVQRODUJH

VWXG\DYDLODEOHWKDWKDVPHWDOOFULWHULDIRUDGHTXDWHO\DVVHVVLQJWKHVHQVLWLYLW\

DQGVSHFL¿FLW\ZLWKLQWKLVVHWWLQJ&RQVHTXHQWO\WKHWUXHDFFXUDF\RIVSLUDO&7

UHPDLQVXQFOHDU7RDGGUHVVWKLVLVVXHZHSHUIRUPHGDSURVSHFWLYHFRKRUWVWXG\LQ

ZKLFKWKHDFFXUDF\RIVLQJOHGHWHFWRUVSLUDO&7ZDVHYDOXDWHGDVDSDUWRID¿[HG

GLDJQRVWLFDOJRULWKPLQFRQVHFXWLYHSDWLHQWVZLWKFOLQLFDOO\VXVSHFWHG3(6SHFLDO

HPSKDVLVZDVSODFHGXSRQGHWHUPLQLQJWKHVHQVLWLYLW\DQGVSHFL¿FLW\RIVSLUDO&7LQ

DOOSDWLHQWVZLWKDEQRUPDOSHUIXVLRQVFDQVDVZHOODVWKHVHQVLWLYLW\DQGVSHFL¿FLW\

RIVSLUDO&7VHSDUDWHO\IRU3(LQVHJPHQWDORUJUHDWHUDUWHULHVDVRSSRVHGWR3(LQ

VXEVHJPHQWDODUWHULHV



(5)





0DWHULDOVDQGPHWKRGV

3DWLHQWV

$OOFRQVHFXWLYHLQDQGRXWSDWLHQWVZKRZHUHVHHQEHFDXVHRIFOLQLFDOO\VXVSHFWHG

SXOPRQDU\HPEROLVPLQWKHVL[SDUWLFLSDWLQJKRVSLWDOV IRXUDFDGHPLFDQGWZR

JHQHUDOFRPPXQLW\WHDFKLQJKRVSLWDOV RYHUDRQH\HDUSHULRGZHUHHOLJLEOH

7KHKRVSLWDOVL]HYDULHVIURPWREHGV PHDQEHGV HVWLPDWHG

HPHUJHQF\GHSDUWPHQWYLVLWVRQDYHUDJHSDWLHQWVSHU\HDUSHUKRVSLWDO

DQGDQHVWLPDWHGPD[LPXPRIDGPLVVLRQVSHU\HDUSHUKRVSLWDO,QFOXVLRQ

FULWHULDZHUHFOLQLFDOVXVSLFLRQRISXOPRQDU\HPEROLVPDVMXGJHGE\WKHUHIHUULQJ

SK\VLFLDQEDVHGRQKLVWRU\DQGSK\VLFDOH[DPLQDWLRQDVZHOODVZULWWHQLQIRUPHG

FRQVHQW([FOXVLRQFULWHULDZHUHDQWLFRDJXODQWWUHDWPHQWIRUPRUHWKDQKRXUV

GLDJQRVWLFWHVWVIRUSXOPRQDU\HPEROLDOUHDG\SHUIRUPHG\RXQJHUWKDQ\HDUV

RIDJHDQGSRVVLEOHSUHJQDQF\5HQDOIDLOXUHDQGDOOHUJ\WRFRQWUDVWDJHQWVZHUH

QRWDEVROXWHFRQWUDLQGLFDWLRQVIRUSDUWLFLSDWLRQLQWKHVWXG\7KHVHSDWLHQWVDUH

SDUWRIDQRUPDOSRSXODWLRQRISDWLHQWVVXVSHFWHGRI3(,QSDWLHQWVZLWKUHQDO

LPSDLUPHQWXVHRIFRQWUDVWDJHQWVZDVSRVVLEOHZLWKDSSURSULDWHSUHFDXWLRQV,Q

UDUHFDVHVRISRVVLEOHDOOHUJLFUHDFWLRQVLQWKHSDVWDQDQDSK\OD[LVSUHSDUDWLRQ

SURWRFROZDVXVHGSULRUWR&7VFDQQLQJ7KHLQLWLDOWHVWVKDGWREHSHUIRUPHG

ZLWKLQKRXUVRISUHVHQWDWLRQRI3(DQGDOOGLDJQRVWLFWHVWVKDGWREHFRPSOHWHG

ZLWKLQKRXUV7KHSURWRFROZDVDSSURYHGE\WKHVL[ORFDOHWKLFDOUHYLHZERDUGV

'XULQJWKHVWXG\SHULRGWKHFKDUDFWHULVWLFVRIDVDPSOHRIFRQVHFXWLYHSDWLHQWV

ZKRUHIXVHGRUZHUHLQHOLJLEOHIRUVWXG\HQWU\GXULQJDWZRPRQWKSHULRGZHUH

HYDOXDWHGIRUFRPSDULVRQZLWKVWXG\SDWLHQWV

6WXG\GHVLJQ

3HUIXVLRQVFLQWLJUDSK\ZDVSHUIRUPHGDVWKH¿UVWWHVWLQDOOSDWLHQWV3DWLHQWV

ZLWKDQRUPDOSHUIXVLRQVFLQWLJUDPZHUHFRQVLGHUHGQRWWRKDYH3(DQGZHUH

H[FOXGHGIURPIXUWKHUDQDO\VLV9HQWLODWLRQVFLQWLJUDSK\ZDVREWDLQHGLQSDWLHQWV

ZLWKVHJPHQWDORUODUJHUSHUIXVLRQGHIHFWV VHHLPDJHDQDO\VLVXVLQJ5HYLVHG

3,23('FULWHULDLQFRQMXQFWLRQZLWKFKHVWUDGLRJUDSKV $OORWKHUSDWLHQWVGLG

QRWXQGHUJRYHQWLODWLRQVFLQWLJUDSK\DVWKHUHZDVQRSRVVLELOLW\RIWKHVHVFDQV

EHFRPLQJDKLJKSUREDELOLW\UHVXOW6XEVHTXHQWO\DOOSDWLHQWVZLWKSHUIXVLRQ

GHIHFWVXQGHUZHQWVSLUDO&7VFDQQLQJ,IDSDWLHQWKDGDKLJKSUREDELOLW\OXQJ

VFDQGHIHFWDQGVSLUDO&7VFDQVKRZHGSXOPRQDU\HPEROLVPWKHSDWLHQWZDV

FRQVLGHUHGWRKDYH3(DQGSXOPRQDU\DQJLRJUDSK\ 3$ ZDVQRWLQGLFDWHG,Q

WKHFDVHRIDKLJKSUREDELOLW\OXQJVFDQZKHUHWKHVSLUDO&7VFDQGLGQRWVKRZ

3(DGGLWLRQDOSXOPRQDU\DQJLRJUDSK\KDGWREHSHUIRUPHG,IWKHUHVXOWRID

VSLUDO&7VFDQDIWHUDQRQKLJKSUREDELOLW\OXQJVFDQKDGQRWEHHQYHUL¿HGE\

(6)





SXOPRQDU\DQJLRJUDSK\WKHSDWLHQWZDVH[FOXGHGIURPDQDO\VLV6LQFHWKLVVWXG\

ZDVSHUIRUPHGLQDFOLQLFDOVHWWLQJWKHUHVXOWRIWKHORFDOUHDGLQJRIWKHSHUIXVLRQ

VFLQWLJUDSK\RUWKHFRPELQHGUHVXOWRISHUIXVLRQYHQWLODWLRQVFLQWLJUDSK\ 94

VFDQ GHWHUPLQHGKRZSDWLHQWVSURFHHGHGWRVXEVHTXHQWOHYHOVLQWKHDOJRULWKP

DVLQGLFDWHGLQ¿JXUHEXWWKHODWHUSHUIRUPHGFHQWUDOUHDGLQJZDVXVHGIRU

DQDO\VLV

$IWHUZDUGVWKHVFLQWLJUDSKLFOXQJVFDQVWKHVSLUDO&7VFDQVDQGWKHSXOPRQDU\

DQJLRJUDPVZHUHUHYLHZHGE\LQGHSHQGHQWH[SHUWSDQHOVFRQVLVWLQJRI

QXFOHDUPHGLFLQHVSHFLDOLVWV OXQJVFDQV DQGUDGLRORJLVWV &7DQGSXOPRQDU\

DQJLRJUDPV EOLQGHGWRWKHUHVXOWVRIGLIIHUHQWWHVWVDQGWKHVWDUWHGWUHDWPHQW7KH

VFLQWLJUDSKLFVFDQVZHUHUHDGE\WZRUHDGHUVLQFRQVHQVXV7KH&7VFDQVDQG

SXOPRQDU\DQJLRJUDPVZHUHUHDGE\WZRLQGHSHQGHQWUDGLRORJLVWV'LVFUHSDQW

UHDGLQJVZHUHUHVROYHGE\DWKLUGLQGHSHQGHQWUHDGHUZKHQHYHUQHFHVVDU\7KH

)LJXUH'LDJQRVWLFDOJRULWKP

(7)





UHDGHUVZHUHXQDZDUHRIWKHUHVXOWVRIRWKHUGLDJQRVWLFWHVWVRUWKHSDWLHQWV

FOLQLFDOV\PSWRPV7KHUHIHUHQFHFULWHULDIRUWKHSUHVHQFHRISXOPRQDU\HPEROLVP

DFFRUGLQJWRFHQWUDOUHDGLQJZHUHDSRVLWLYHSXOPRQDU\DQJLRJUDPRUDKLJK

SUREDELOLW\YHQWLODWLRQSHUIXVLRQVFDQ7KHUHIHUHQFHFULWHULDIRUWKHDEVHQFHRI

SXOPRQDU\HPEROLVPZDVDQHJDWLYHSXOPRQDU\DQJLRJUDP7REHLQFOXGHGLQ

WKHDVVHVVPHQWRIDFFXUDF\RIVSLUDO&7SDWLHQWVKDGWRKDYHD94VFDQWKDW

ZDVLQWHUSUHWHGDVQRQKLJKSUREDELOLW\LQERWKWKHORFDODQGFHQWUDOUHDGLQJDQG

DSXOPRQDU\DQJLRJUDSK\RUDKLJKSUREDELOLW\94VFDQUHVXOWDQGDSRVLWLYH&7

VFDQUHVXOW

,PDJLQJVWXGLHV

&KHVWUDGLRJUDSKVZHUHPDGHHUHFWDQGLQWZRGLUHFWLRQV SRVWHULRUDQWHULRUDQG

OHIWODWHUDO ,IWKLVZDVQRWSRVVLEOHDQDQWHULRUSRVWHULRUUDGLRJUDSKLQEHGZDV

PDGH

3HUIXVLRQVFLQWLJUDSK\ZDVSHUIRUPHGDIWHULQWUDYHQRXVDGPLQLVWUDWLRQRI

P&LNJ7FPODEHOHGPDFURDJJUHJDWHGVHUXPDOEXPLQ 0DOOLQFNURGW3HWWHQ

7KH1HWKHUODQGV 3HUIXVLRQLPDJHVZHUHDFTXLUHGZLWKDPLQLPXPRI

FRXQWVSHUYLHZLQDWOHDVWIRXUYLHZVDQWHULRUSRVWHULRUOHIWDQWHULRUREOLTXHDQG

ULJKWDQWHULRUREOLTXHYLHZV9HQWLODWLRQVWXGLHVZHUHSHUIRUPHGXVLQJ.U\SWRQP

0DOOLQFNURGW3HWWHQ7KH1HWKHUODQGV YLD5E.UJHQHUDWRU &\JQH$PHUVKDP  GXULQJDVLQJOHEUHDWK$PLQLPXPRIFRXQWVZDVUHTXLUHGIRUYLHZV

LQWKHVDPHIRXUGLUHFWLRQVDVWKHSHUIXVLRQVFLQWLJUDSKLHV*DPPDFDPHUD

DQGFROOLPDWRUGHSHQGHGRQORFDODYDLODELOLW\ 6LHPHQV2UELWHU'LJLWUDF

6LHPHQV0HGLFDO6\VWHPV,VHOLQ1-86$$'$&9HUWH[DQG$UJXV$'$&

/DERUDWRULHV(XURSH%90DDUVHQ7KH1HWKHUODQGV7RVKLED*&$DQG

*&$D7RVKLED0HGLFDO6\VWHPV'LYLVLRQ7RN\R-DSDQ9DULFDP(OVFLQW

,QF+DFNHQVDFN1-86$FROOLPDWRUVXVHGZHUHPHGLXPHQHUJ\DOOSXUSRVH

0($3 ORZHQHUJ\KLJKUHVROXWLRQ /(+5 PHGLXPHQHUJ\KLJKUHVROXWLRQ

0(+5 DQGORZHQHUJ\JHQHUDOSXUSRVH /(*3 

7KHVSLUDO&7VFDQQHUVXVHGLQWKLVVWXG\ZHUHDOORIWKH¿UVWJHQHUDWLRQZLWK

DVLQJOHGHWHFWRUDQGFDSDEOHRIVFDQQLQJDWOHDVWFHQWLPHWHUV 6LHPHQV

6RPDWRPSOXVDQG6RPDWRPSOXV66LHPHQV0HGLFDO6\VWHPV(UODQJHQ

*HUPDQ\(OVFLQW (OVFLQW+DLID,VUDHO 3KLOLSV65DQG653KLOLSV

0HGLFDO6\VWHPV%HVW7KH1HWKHUODQGV 6FDQQLQJZDVSHUIRUPHGXVLQJDPP

WDEOHVSHHGDQGVOLFHWKLFNQHVV)LUVWWKHOHYHORIWKHDRUWLFDUFKZDVGHWHUPLQHG

RQWKHVFRXWYLHZ8VLQJWKLVDVDUHIHUHQFHSRLQWWKHVWDUWLQJSRLQWZDVLGHQWL¿HG

VL[WHHQFHQWLPHWHUVFDXGDOO\7KHVFDQQLQJSURFHVVZDVWKHQVWDUWHGIURPWKLV

SRVLWLRQLQDFDXGRFHSKDODGGLUHFWLRQVHFRQGVDIWHULQWUDYHQRXVLQMHFWLRQRI

(8)





PJVRILRGLQHIRUVHFRQGVHLWKHUE\LQMHFWLRQRIP/RIQRQLRQLF

FRQWUDVWDJHQWZLWKPJ,POLRGLQHFRQWHQW ,RPHURQ%UDFFR%\N*XOGHQ

.RQVWDQ]*HUPDQ\ DWDQLQMHFWLRQUDWHRIP/VHFRUE\LQMHFWLRQRIP/

RIQRQLRQLFFRQWUDVWDJHQWPJ,P/ 8OWUDYLVW6FKHULQJ%HUOLQ*HUPDQ\  DWDQLQMHFWLRQUDWHRIP/VHF7KHVFDQZDVSHUIRUPHGGXULQJDVLQJOH

EUHDWKKROGDOWKRXJKVKDOORZEUHDWKLQJZDVDOORZHGLQYHU\G\VSQRHLFSDWLHQWV

2YHUODSSLQJLPDJHVZHUHUHFRQVWUXFWHGDWPPLQWHUYDOV

3XOPRQDU\DQJLRJUDSK\ZDVSHUIRUPHGE\XVLQJD)*UROOPDQQFDWKHWHU &RRN

(LQGKRYHQ7KH1HWKHUODQGV YLDDIHPRUDOYHLQXQGHUORFDODQHVWKHVLD7KH

OHIWDQGULJKWPDLQSXOPRQDU\DUWHU\ZHUHVHOHFWLYHO\FDWKHWHUL]HGLQWXUQDQG

DQJLRJUDSKLFLPDJHVZHUHREWDLQHGLQDQWHURSRVWHULRUDQGOHIWDQWHULRUREOLTXH

YLHZV'HSHQGLQJRQWKHSDWLHQWDQGWKHH[SHFWHGFDUGLDFRXWSXWDFRQWUDVW

LQMHFWLRQSURWRFRORIHLWKHUPOVHF WRWDOPO RUPOVHF POWRWDO ZDV

XVHG,IFRQVLGHUHGQHFHVVDU\DGGLWLRQDOLPDJHVZHUHREWDLQHGLQDUHDVRI

VSHFLDOLQWHUHVWDFFRUGLQJWRWKHSHUIXVLRQLPDJHV

,PDJHDQDO\VLV

94VFLQWLJUDPVZHUHLQWHUSUHWHGLQFRQMXQFWLRQZLWKWKHFKHVWUDGLRJUDSKVXVLQJ

WKHUHYLVHG3,23('FULWHULD  7KHSHUIXVLRQYHQWLODWLRQVFLQWLJUDSKLHVZHUH

FODVVL¿HGDVQRUPDOQRQGLDJQRVWLF QRQKLJK RUKLJKSUREDELOLW\

)RULQWHUSUHWDWLRQRIWKH&7VFDQVLQWKHFHQWUDOUHDGLQJDZRUNVWDWLRQDOORZLQJ

FLQHPRGHYLHZLQJZLWKYDULRXVZLQGRZDQGOHYHOVHWWLQJVZDVDOZD\VXVHG

6WDQGDUGVHWWLQJVZHUHZLQGRZZLGWK+8ZLQGRZOHYHO+8IRUPHGLDVWLQDO

VWUXFWXUHVDQGSXOPRQDU\YDVFXODWXUHDQGZLQGRZZLGWK+8ZLQGRZOHYHO

±+8IRUFRPSDULVRQRIRSDFL¿HGOXQJYDVFXODWXUHDQGDQDWRPLFDOUHODWLRQWR

EURQFKLDQGOXQJSDUHQFK\PD

7RGHWHFW3(RQWKH&7VFDQWKHFULWHULDDVSUHYLRXVO\GHVFULEHG ZHUHXVHG

3(ZDVFRQVLGHUHGWREHSUHVHQWLILQFDVHRIDZHOORSDFL¿HGVFDQWKHUHZDVDQ

LQWUDOXPLQDO¿OOLQJGHIHFWRQPRUHWKDQRQHVOLFHDQGQRDUWHIDFWVZHUHSUHVHQW

$¿OOLQJGHIHFWFRXOGEHVHHQDVDFRPSOHWHRFFOXVLRQRIWKHYHVVHODQHFFHQWULF

SDUWLDO¿OOLQJGHIHFWRUDSDUWLDOFHQWUDO¿OOLQJGHIHFWVXUURXQGHGE\WKHFRQWUDVW

DJHQW$&7VFDQZDVFRQVLGHUHGQRUPDOLILQFDVHRIDJRRGTXDOLW\VFDQQR

¿OOLQJGHIHFWVFRXOGEHVHHQ$VFDQZDVFRQVLGHUHGWREHLQFRQFOXVLYHLIWKHUH

ZDVLQVXI¿FLHQWRSDFL¿FDWLRQRIWKHYHVVHOVRULQFDVHRILPDJLQJDUWHIDFWVWKDW

FRXOGOHDGWRIDOVHSRVLWLYHUHVXOWV

,QWHUSUHWDWLRQRIWKHIXOODQJLRJUDSKLFUXQVZDVGRQHRQDYLHZLQJVWDWLRQ7KH

FULWHULDXVHGIRUGHWHUPLQDWLRQRIWKHSUHVHQFHRI3(DVGHVFULEHGE\6DJHODQG

*UHHQVSDQZHUHXVHGWRGLDJQRVH3(

(9)





2IDOOSDWLHQWVZLWKWKH¿QDOGLDJQRVLVRISXOPRQDU\HPEROLVPWKHODUJHVWLQYROYHG

EUDQFKRIWKHSXOPRQDU\YDVFXODWXUHZDVQRWHGDQGFDWHJRUL]HGLQFDWHJRULHV

PDLQSXOPRQDU\VWHPOHIWRUULJKWPDLQSXOPRQDU\DUWHU\OREDUDUWHU\VHJPHQWDO

DUWHU\RUVXEVHJPHQWDODUWHU\7KHVHFDWHJRULHVZHUHXVHGWRPDNHDGLVWLQFWLRQ

EHWZHHQ3(LQVHJPHQWDORUODUJHUDUWHULHVDQG3(LQVXEVHJPHQWDODUWHULHV

7KLVUHDGLQJRQO\DOORZHGIRUDVVHVVPHQWRIWKHPRVWSUR[LPDOO\LQYROYHGEUDQFK

QRVSHFL¿FDWLRQZDVPDGHWRGHWHUPLQHZKHWKHUSDWLHQWVKDGLVRODWHGRUPXOWLSOH

VXEVHJPHQWDOHPEROL

6WDWLVWLFDODQDO\VLV

'DWDPDQDJHPHQWDQGVWDWLVWLFDODQDO\VLVZDVGRQHE\DQLQGHSHQGHQWJURXS

RIELRVWDWLVWLFLDQVDQGHSLGHPLRORJLVWV6HQVLWLYLW\DQGVSHFL¿FLW\ LQFOXGLQJ

WKHLUFRQ¿GHQFHLQWHUYDOV IRUVSLUDO&7ZHUHFDOFXODWHG,QDGGLWLRQWKH

VHQVLWLYLW\IRUVSLUDO&7ZDVFDOFXODWHGVHSDUDWHO\IRUERWKWKHVXEVHJPHQWDODQG

VHJPHQWDORUODUJHUSXOPRQDU\HPEROLVPV6WDWLVWLFDODQDO\VHVZHUHSHUIRUPHG

XVLQJVWDWLVWLFDOVRIWZDUH 6WDWLVWLFDO3URGXFWDQG6HUYLFH6ROXWLRQV 6366 ,QF

&KLFDJR,OOLQRLV 

5HVXOWV

'XULQJWKHLQFOXVLRQSHULRGRIWKHVWXG\RISDWLHQWVWKDWSUHVHQWHGDWWKH

SDUWLFLSDWLQJFHQWHUVZLWKFOLQLFDOO\VXVSHFWHG3(  GLGQ¶WPHHWWKH

LQFOXVLRQFULWHULD6L[WHHQSDWLHQWVZHUHEHORZWKHDJHRIZHUHSUHJQDQW

QHHGHGLPPHGLDWHWUHDWPHQWZLWKWKURPERO\WLFWKHUDS\DWWKHWLPHRIVFUHHQLQJ

DQGSDWLHQWVKDGKDGGLDJQRVWLFWHVWVSHUIRUPHGSULRUWRVWDUWRIWKHVWXG\

SURWRFRO$QRWKHUSDWLHQWVFRXOGQRWEHLQFOXGHGLQWKHVWXG\EHFDXVHWKH

GLDJQRVWLFZRUNXSFRXOGQRWEHVWDUWHGZLWKLQKRXUVDIWHUSUHVHQWDWLRQGXH

WRORJLVWLFRUWHFKQLFDOUHDVRQV HJZHHNHQGVDQGDSSDUDWXVIDLOXUH  ,QIRUPHG

FRQVHQWZDVREWDLQHGIURPRIWKHUHPDLQLQJHOLJLEOHSDWLHQWV  7KH

PDMRULW\RISDWLHQWVUHIXVHGLQIRUPHGFRQVHQWEHFDXVHWKH\GLGQRWZDQW

WRSDUWLFLSDWHLQDVWXG\RUZHUHQRWDEOHWRJLYHLQIRUPHGFRQVHQWZLWKLQWKH

KRXUVUHTXLUHGWRSHUIRUPWKHLQLWLDOLPDJLQJVWXGLHV7KHFKDUDFWHULVWLFVRIWKH

VDPSOHRIFRQVHFXWLYHSDWLHQWVZKRUHIXVHGRUZHUHLQHOLJLEOHIRUVWXG\HQWU\

ZHUHQRWGLIIHUHQWIURPWKHFKDUDFWHULVWLFVRIVWXG\SDWLHQWV

$WRWDORISDWLHQWVKDGWREHH[FOXGHGIRUDQDO\VLV WDEOH $JURXSRI

SDWLHQWVKDGDGLVSDULW\EHWZHHQORFDOO\DVVHVVHG94VFDQUHVXOW ZLWK

QRUPDOZLWKKLJKSUREDELOLW\VFDQ DQGFRQVHQVXV94VFDQUHVXOW DOOQRQ

GLDJQRVWLF94VFDQ ,QDQRWKHUSDWLHQWVHLWKHUYHQWLODWLRQVFLQWLJUDSK\VSLUDO

&7RUSXOPRQDU\DQJLRJUDSK\ZDVQRWSHUIRUPHGGXHWRDORJLVWLFSUREOHPVRU

(10)





KDUGZDUHGRZQWLPH SDWLHQWV EZLWKGUDZDOE\WKHWUHDWLQJSK\VLFLDQGXHWR

DQDSSDUHQWDOWHUQDWLYHGLDJQRVLV SDWLHQWV FYDULRXVPHGLFDOUHDVRQV 

SDWLHQWV RUGZLWKGUDZDORILQIRUPHGFRQVHQW SDWLHQWV 

,QFOXGHGDQGDQDO\]HGSDWLHQWV ¿JXUH

8OWLPDWHO\SDWLHQWVZLWKDPHDQDJHRI\HDUVZHUHDQDO\]HG)LIW\HLJKW

SHUFHQWZHUHPDOHIHPDOHZHUHLQSDWLHQWVDQGZHUHRXWSDWLHQWV

6HYHQW\WKUHHSDWLHQWV  KDGKDGDSUHYLRXVYHQRXVWKURPERHPEROLFHYHQW

7KHPHGLDQGXUDWLRQRIV\PSWRPVRI3(ZDVWKUHHGD\V)XUWKHUGHPRJUDSKLF

FKDUDFWHULVWLFVDQGULVNIDFWRUVIRU3(DUHVKRZQLQWDEOHDQGFRPSDUHGWRWKH

JURXSRIHOLJLEOHSDWLHQWVDQGWKHH[FOXGHGSDWLHQWV

2IWKHSDWLHQWV  KDGDQRUPDOSHUIXVLRQVFLQWLJUDSK\1R3(ZDV

FRQVLGHUHGWREHSUHVHQWDQGDFFRUGLQJWRWKHSURWRFROQRVSLUDO&7VFDQRU

SXOPRQDU\DQJLRJUDSK\ZDVSHUIRUPHG

,QSDWLHQWV  WKHSHUIXVLRQVFDQVKRZHGDEQRUPDOLWLHVRIZKLFK

ZHUHVHJPHQWDO,QDOORIWKHVHSDWLHQWVDGGLWLRQDOYHQWLODWLRQVFLQWLJUDSK\ZDV

SHUIRUPHG

7DEOH3DWLHQWVVFUHHQHGIRUWKHVWXG\

3DWLHQWVVFUHHQHG 

([FOXGHG

$JH\HDUV 

3UHJQDQF\ 

,QGLFDWLRQIRULPPHGLDWHWKURPERO\WLFWKHUDS\ 

2EMHFWLYHGLDJQRVWLFZRUNXSDOUHDG\VWDUWHG

HOVHZKHUH 

/RJLVWLFUHDVRQV ZHHNHQGKROLGD\V 

(OLJLEOHSDWLHQWV 

,QIRUPHGFRQVHQW 

6WXG\SURWRFRO YLRODWRUV

'LVFUHSDQF\EHWZHHQORFDODQGFRQVHQVXV94VFDQ

UHVXOW 

7HFKQLFDOUHDVRQV WLPHFRQVWUDLQWVPDFKLQH

EUHDNGRZQ 

$OWHUQDWLYHGLDJQRVLVDQGLQFRPSOHWHSURWRFRO 

0HGLFDOUHDVRQV HJFDUGLDFDUUK\WKPLD 

:LWKGUDZDORILQIRUPHGFRQVHQW 

)LQDOGLDJQRVLV 

(11)





+LJKSUREDELOLW\UHVXOWRI94VFLQWLJUDSK\

7KHSHUIXVLRQGHIHFWVZHUHQRWPDWFKHGE\YHQWLODWLRQGHIHFWVLQSDWLHQWV

DQGWKXVFDOOHGKLJKSUREDELOLW\ ,Q SDWLHQWVZLWKWKHVHKLJKSUREDELOLW\

VFLQWLJUDSK\UHVXOWVDVSLUDO&7VFDQZDVSHUIRUPHG6SLUDO&7ZDVQRWSHUIRUPHG

LQSDWLHQWVEHFDXVHRIUHIXVDOE\SDWLHQWRUWUHDWLQJSK\VLFLDQLQ¿YHSDWLHQWV

EHFDXVHWKHPD[LPXPDPRXQWRIFRQWUDVWDJHQWKDGEHHQXVHGGXULQJ3$LQIRXU

SDWLHQWVEHFDXVHRIGHWHULRUDWLRQRIWKHFOLQLFDOVLWXDWLRQLQWZRSDWLHQWVEHFDXVH

DVSLUDO&7VFDQZDVQRWSRVVLEOH KDORWUDFWLRQFODXVWURSKRELD LQIRXUSDWLHQWV

DQGEHFDXVHRIDQXQNQRZQUHDVRQLQDQRWKHU¿YHSDWLHQWV,QHLJKWSDWLHQWVRI

WKHSDWLHQWVQRFHQWUDOUHDGLQJRIWKHVSLUDO&7VFDQZDVDYDLODEOHZKLOHLQ

IRXUSDWLHQWVQRFRQVHQVXVDPRQJREVHUYHUVFRXOGEHREWDLQHG7KHUHIRUH

SDWLHQWVZLWK&7VFDQUHVXOWVZHUHDYDLODEOHIRUDQDO\VLV ¿JXUH 

1RQKLJKSUREDELOLW\UHVXOWRI94VFLQWLJUDSK\

,QRISDWLHQWVZLWKVHJPHQWDOSHUIXVLRQGHIHFWVWKHUHZHUHDOVRYHQWLODWLRQ

GHIHFWVDQGWKXVWKHUHVXOWRIWKHFRPELQHGYHQWLODWLRQSHUIXVLRQVFLQWLJUDSK\ZDV

QRQKLJKSUREDELOLW\RUQRQGLDJQRVWLF,QRIWKHSDWLHQWVZLWKDEQRUPDO

SHUIXVLRQVFDQWKHGHIHFWZDVVXEVHJPHQWDO,QHLJKWSDWLHQWVQRFHQWUDOUHDGLQJ

)LJXUH1XPEHURISDWLHQWVDQGWHVWVSHUIRUPHG

(12)





RIWKHYHQWLODWLRQSHUIXVLRQVFLQWLJUDSK\ZDVDYDLODEOHEXWLQWKHORFDOUHDGLQJWKH

VFDQVZHUHDOOZLWKVXEVHJPHQWDOSHUIXVLRQGHIHFWV QRQKLJKSUREDELOLW\ DQG

LWZDVGHFLGHGWKDWIXUWKHUWHVWLQJZDVLQGLFDWHGLQWKHVHSDWLHQWV7KHUHIRUHLQ

WRWDOWKHUHZHUHSDWLHQWVZLWKDQRQGLDJQRVWLFUHVXOWRIYHQWLODWLRQSHUIXVLRQ

VFLQWLJUDSK\,QDOOEXWRIWKHVHSDWLHQWVDVSLUDO&7VFDQZDVDYDLODEOHZLWKD

FHQWUDOUHDGLQJDQGDOORIWKHVHSDWLHQWVKDGSXOPRQDU\DQJLRJUDSK\SHUIRUPHG

,QDOORIWKHVHSDWLHQWVD¿QDOFRQFOXVLRQFRXOGEHPDGHEDVHGRQSXOPRQDU\

DQJLRJUDSK\DVWKHVWURQJHVWVRXUFHRIHYLGHQFH ¿JXUH 

6HQVLWLYLW\DQGVSHFL¿FLW\LQWKHRYHUDOOSRSXODWLRQ

2IWKHSDWLHQWVDYDLODEOHIRUDQDO\VLVORFDOLQWHUSUHWHGQRUPDOSHUIXVLRQ

VFDQZHUHWKHUHIRUHH[FOXGHGIRUWKHFRPSDULVRQDQGSDWLHQWVKDGDEQRUPDO

SHUIXVLRQVFLQWLJUDPV,QRIWKHVHSDWLHQWVDVSLUDO&7VFDQZDV

SHUIRUPHGLQSDWLHQWVZLWKDKLJKSUREDELOLW\VFDQLQSDWLHQWVZLWKD

QRQKLJKSUREDELOLW\VFDQDQGLQ94ZLWKRXWDFHQWUDOUHDGLQJ$OOWKHVH

VFDQVZHUHDYDLODEOHIRUFHQWUDOUHDGLQJDQGUHFHLYHGDGLDJQRVLVDFFRUGLQJWR

WKHVWXG\SURWRFRO6SLUDO&7VFDQVLGHQWL¿HGFRUUHFWO\RISDWLHQWVZLWK

SURYHQ3( SRVLWLYHSXOPRQDU\DQJLRJUDSK\LQSDWLHQWVDQGKLJKSUREDELOLW\

YHQWLODWLRQSHUIXVLRQVFLQWLJUDSK\LQSDWLHQWV IRUDFDOFXODWHGVHQVLWLYLW\RI

7DEOH&RPSDULVRQRIFOLQLFDODQGGHPRJUDSKLFFKDUDFWHULVWLFVRIHOLJLEOHSDWLHQWV

H[FOXGHGSDWLHQWVDQGDQDO\]HGVWXG\SDWLHQWV

$OOSDWLHQWVZLWK

VXVSHFWHG3( ([FOXGHGSDWLHQWV $QDO\]HGVWXG\

SDWLHQWV

1XPEHU   

$JH 6' LQ\HDUV      

)HPDOHPDOHLQ   

,QSDWLHQWVRXWSDWLHQWV   

3UHYLRXVKLVWRU\RI97(      

)DPLOL\KLVWRU\RI97(      

5LVNSHULRGIRU97(      

$FWLYHPDOLJQDQF\      

(VWURJHQXVH      

&23'      

&RQJHVWLYHKHDUWIDLOXUH      

97(YHQRXVWKURPERHPEROLVP

&23'FKURQLFREVWUXFWLYHSXOPRQDU\GLVHDVH

(13)





 FL 6SLUDO&7VFDQVVKRZHGQRVLJQVRI3(LQRI

SDWLHQWVZLWKQRUPDODQJLRJUDPVIRUDFDOFXODWHGVSHFL¿FLW\RI FL

  WDEOH &DOFXODWHGVHQVLWLYLW\DQGVSHFL¿FLW\ZHUHWKHUHIRUH 

FL DQG FL UHVSHFWLYHO\7KHSUHYDOHQFHRI3(LQ

WKHWRWDOJURXSRISDWLHQWVZDV

6XEJURXSDQDO\VLVRIUHVXOWVODUJHU3(YHUVXVLVRODWHGVXEVHJPHQWDO3(

,QSDWLHQWVRISDWLHQWVZLWKD¿QDOGLDJQRVLVRI3(DVHJPHQWDODQDO\VLV

RIWKHODUJHVWLQYROYHGEUDQFKRIWKHSXOPRQDU\YDVFXODWXUHZDVDOVRSHUIRUPHG

,QWZRSDWLHQWVWKHUHDGHUVZHUHXQFHUWDLQDQGLQSDWLHQWVWKLVDQDO\VLVZDV

PLVVLQJLQWKHFDVHUHFRUGIRUP7KLVDQDO\VLVZDVPDGHRQWKHUHVXOWRIWKH

SXOPRQDU\DQJLRJUDPLIDYDLODEOH,QDOORWKHUSDWLHQWVZLWK3(WKLVZDVEDVHG

RQWKHUHVXOWRIWKHVSLUDO&7VFDQ7KHODUJHVWLQYROYHGEUDQFKZDVWKHPDLQ

SXOPRQDU\VWHPLQSDWLHQWV  WKHOHIWRUULJKWSXOPRQDU\EUDQFKLQ

SDWLHQWV  DOREDUDUWHU\LQSDWLHQWV  DVHJPHQWDODUWHU\LQ

SDWLHQWV  DQGDVXEVHJPHQWDODUWHU\LQSDWLHQWV  ,QWKHJURXS

RISDWLHQWVZLWKVHJPHQWDORUODUJHU3(WKHVSLUDO&7VFDQGLGQRWLGHQWLI\3(LQ

RISDWLHQWV  ,QFRQWUDVWVSLUDO&7PLVVHGRXWRISDWLHQWVZLWK

3(  LQWKHVXEVHJPHQWDOJURXS7KHUHIRUHVHQVLWLYLW\ZDV &,

 LQWKHVHJPHQWDORUODUJHU3(JURXSDQG &, LQWKH

JURXSZLWKVXEVHJPHQWDO3(

'LVFXVVLRQ

,QWKLVSURVSHFWLYHVWXG\ZHKDYHHYDOXDWHGWKHDFFXUDF\RIVLQJOHVOLFHGHWHFWRU

VSLUDO&7LQSDWLHQWVZLWKFOLQLFDOVXVSHFWHG3(DQGDQDEQRUPDOSHUIXVLRQ

VFLQWLJUDSK\UHVXOW7KHRYHUDOOVHQVLWLYLW\RIVSLUDO&7ZDVDQGWKHVSHFL¿FLW\

ZDV

:KHQORRNLQJRQO\DW 3(LQVHJPHQWDODQGODUJHUDUWHULHVWKHVHQVLWLYLW\DQG

VSHFL¿FLW\ZHUHDQGUHVSHFWLYHO\7KLVLVWRRORZWRZLWKKROGDQWLFRDJXODQW

WUHDWPHQWRQWKHEDVLVRIDQRUPDOVSLUDO&7UHVXOWDORQH)XUWKHUPRUHWKH  VHQVLWLYLW\IRUVXEVHJPHQWDOWKURPELZDVDPHUH

(DUOLHUVWXGLHVSHUIRUPHGLQDYDU\LQJQXPEHURISDWLHQWVUHSRUWHGGLIIHUHQW

RYHUDOORXWFRPHVZLWKVHQVLWLYLWLHVUDQJLQJIURPDQGVSHFL¿FLWLHV

UDQJLQJIURP7KHUHSRUWHGUHVXOWVIRUVHJPHQWDO3(YDU\EHWZHHQ

DQGDQGIRUVXEVHJPHQWDOHPEROLEHWZHHQDQG2XU

RYHUDOOUHVXOWVDVZHOODVWKHUHVXOWVRIVHJPHQWDODQGVXEVHJPHQWDOHPEROLIDOO

ZHOOZLWKLQWKHVHUDQJHVDQGDUHVLPLODUWRWKHUHVXOWVRIDUHFHQWVWXG\E\3HUULHU

HWDO

(14)





7KHKLJKSHUFHQWDJHRIQRUPDOOXQJVFDQVKDVEHHQUHSRUWHGEHIRUH 7KLVLV

QRWFDXVHGE\OLEHUDOL]DWLRQRIWKHFULWHULDIRUQRUPDOVFDQVEXWLVSUREDEO\D

UHÀHFWLRQRIDUHSUHVHQWDWLYHSRSXODWLRQVXVSHFWHGIRU3(LQWKHSDUWLFLSDWLQJ

KRVSLWDOV

&RPSDUHGWRWKHSUHYLRXVVWXGLHVWKHRYHUDOOVHQVLWLYLW\DQGVSHFL¿FLW\RIVSLUDO

&7VFDQLQWKHSUHVHQWVWXG\ZHUHUHODWLYHO\LQWKHORZHUUDQJH7KUHHLPSRUWDQW

UHDVRQVPD\DFFRXQWIRUWKLVWKHSURVSHFWLYHLQFOXVLRQRIDOOSDWLHQWVVXVSHFWHG

RIKDYLQJ3(LQVWHDGRILQFOXGLQJVHOHFWLYHSDWLHQWVWKHLQGHSHQGHQWUHDGLQJRIDOO

GLDJQRVWLFWHVWVDQGWKHGHFLVLRQWRWDNHSXOPRQDU\DQJLRJUDSK\DVWKHUHIHUHQFH

JROGVWDQGDUGWHVW,QGHHGWKHREVHUYHGSUHYDOHQFHRI3(LQWKHSDWLHQWVRIWKH

SUHVHQWVWXG\  ZDVIXOO\FRPSDUDEOHWRWKHSUHYDOHQFHIRXQGLQWKHODUJH

SURVSHFWLYH3,23('VWXG\  

(YDOXDWLRQRISXOPRQDU\DQJLRJUDSK\LQSDWLHQWVZLWKDFOLQLFDOVXVSLFLRQRI3(KDV

VKRZQDFRQVLGHUDEOHLQWHUREVHUYHUYDULDELOLW\LQEOLQGHGUHDGLQJVXSWR$Q

DQLPDOVWXG\KDVVKRZQWKDWSXOPRQDU\DQJLRJUDSK\DQG&7DQJLRJUDSK\PLJKW

LQIDFWKDYHFRPSDUDEOHUHVXOWVIRUVHQVLWLYLW\DQGVSHFL¿FLW\7DNLQJSXOPRQDU\

DQJLRJUDSK\DVDJROGVWDQGDUGUHIHUHQFHZRXOGWKHUHIRUHDXWRPDWLFDOO\UHVXOW

LQDORZHUVHQVLWLYLW\DQGVSHFL¿FLW\IRU&7DQJLRJUDSK\LQFDVHRIGLIIHUHQWWHVW

UHVXOWVIRUERWKWHVWV

6RPHPHWKRGRORJLFLVVXHVVKRXOGEHIXUWKHUGLVFXVVHG)LUVWVSLUDO&7VFDQQLQJ

ZDVQRWSHUIRUPHGLQFDVHRIDQRUPDOSHUIXVLRQVFLQWLJUDSK\EHFDXVHWKHUHLV

VROLGHYLGHQFHWRVDIHO\H[FOXGH3(DQGZLWKKROGWUHDWPHQWZLWKDQWLFRDJXODQWV

LQFDVHRIDQRUPDOSHUIXVLRQVFLQWLJUDP,QRXUVWXG\LWLVWKHUHIRUHLPSRVVLEOH

7DEOH3DWLHQWVZLWKFRQFOXVLRQDFFRUGLQJWRSURWRFROVSLUDO&7LQGLFDWHGDQGVFDQDYDLODEOHIRU

FHQWUDOUHDGLQJ

'LDJQRVWLFUHVXOW

6SLUDO&7VFDQ

UHVXOW

3( 1R3( 7RWDO

3(   

1R3(   

7RWDO   

6HQVLWLYLW\VSHFL¿FLW\

'LDJQRVWLFUHVXOWRISXOPRQDU\DQJLRJUDSK\RUDSRVLWLYH&7VFDQUHVXOWLQFDVHRIDKLJKSUREDELOLW\

YHQWLODWLRQSHUIXVLRQVFLQWLJUDSK\

(15)





WRDVVHVVWKHVHQVLWLYLW\DQGVSHFL¿FLW\RIVSLUDO&7LQWKHJURXSRISDWLHQWVZLWK

DQRUPDOSHUIXVLRQVFDQ6HFRQGLWZDVGHFLGHGQRWWRSHUIRUPSXOPRQDU\

DQJLRJUDSK\ZKHQSDWLHQWVKDGFRQFRUGDQWUHVXOWVRQERWK94VFDQVDQGVSLUDO

&7VFDQVLQFDVHRIGRXEOHHYLGHQFHRI3(EDVHGRQDKLJKSUREDELOLW\OXQJVFDQ

LQFRQMXQFWLRQZLWK3(VHHQZLWKVSLUDO&7GXHWRPHGLFRHWKLFDOUHDVRQV

)LQDOO\WZRUHFHQWUHYLHZVSRLQWHGRXWWKHHVVHQWLDOUHTXLUHPHQWVIRUSURVSHFWLYH

VWXGLHVWRGH¿QLWLYHO\HYDOXDWHWKHVHQVLWLYLW\DQGVSHFL¿FLW\RIVSLUDO&7LQWKH

GLDJQRVLVRIVXVSHFWHG3(1HDUO\DOORIWKHPDMRUFULWHULDPHQWLRQHGLQWKLV

UHYLHZZHUHIXO¿OOHGE\WKHGHVLJQRIWKHSUHVHQWVWXG\'XULQJWKHVWXG\SHULRG

DOOFRQVHFXWLYHSDWLHQWVVXVSHFWHGRI3(LUUHVSHFWLYHRIWKHVHYHULW\RIV\PSWRPV

RUFRPRUELGFRQGLWLRQVZHUHLQFOXGHGDFFRUGLQJWRSUHVHWLQFOXVLRQFULWHULD$OO

SDWLHQWVKDGDVSLUDO&7VFDQDQGSXOPRQDU\DQJLRJUDSK\SHUIRUPHGLQFDVHRI

SHUIXVLRQGHIHFWV7KH&7WHFKQLTXHXVHGZDVDJHQHUDOO\DFFHSWHGWHFKQLTXH

IRUHYDOXDWLQJ3(DQGZDVIXOO\FRPSDUDEOHWRWKHWHFKQLTXHVGHVFULEHGLQHDUOLHU

VWXGLHV5HFHQWO\QHZHUDFTXLVLWLRQSURWRFROVKDYHEHHQDGYRFDWHGXVLQJPP

FROOLPDWLRQPPWDEOHIHHGUHVXOWLQJLQDSLWFKRIDQGWKHUHFHQWO\LQWURGXFHG

PXOWLGHWHFWRU&7VFDQQHUVSHUPLWVKRUWHULPDJLQJWLPHWKLQQHULPDJLQJVHFWLRQV

DQGPRUHH[WHQVLYHFRYHUDJHRIWKHWKRUD[0RVWVWXG\FHQWHUVKRZHYHUVWLOO

XVHVLQJOHGHWHFWRU&7HTXLSPHQWFDSDEOHRIVFDQQLQJZLWKWKHSDUDPHWHUV

GHVFULEHGLQWKLVVWXG\7KHVWXG\SURWRFROZDVIROORZHGDVULJLGO\DVSRVVLEOH

DQGWKHUHZDVDWKRURXJKUHJLVWUDWLRQRIDOOH[FOXGHGSDWLHQWVDQGWKHUHDVRQV

IRUQRWFRPSOHWLQJWKHVWXG\SURWRFRO3RVVLEOHELDVGXHWRGLDJQRVWLFVXVSLFLRQ

ZDVDYRLGHGE\DFFHSWLQJRQO\DEOLQGHGLQWHUSUHWDWLRQRIDOODYDLODEOH93VFDQV

VSLUDO&7VFDQVDQGSXOPRQDU\DQJLRJUDPV)LQDOO\LQWKLVVWXG\ERWKVSLUDO

&7VFDQVDQGSXOPRQDU\DQJLRJUDPVZHUHERWKHYDOXDWHGIRUVHJPHQWDODQG

VXEVHJPHQWDOOHYHOVRIWKHSXOPRQDU\YDVFXODWXUH

7KHUHVXOWVRIWKLVVWXG\FKDOOHQJHWKHFOLQLFDOSUDFWLFHRIZLWKKROGLQJDQWLFRDJXODQW

WKHUDS\EDVHGRQO\RQDQRUPDOVSLUDO&75HFHQWVWXGLHVVXSSRUWWKDWSDWLHQWV

ZLWKDQRUPDO&7KDYHDORZOLNHOLKRRGRIVXEVHTXHQW3(DQGFDQEHIROORZHG

VDIHO\ZLWKRXWDQWLFRDJXODWLRQ7KHUHDUHWKRXJKOLPLWDWLRQVLQPHWKRGVDQG

IROORZXSRIWKHVHVWXGLHV3DUWLFXODUO\LQWKH¿UVWVWXG\DFRQVLGHUDEOHQXPEHURI

SDWLHQWVGLGQRWFRPSOHWHIROORZXS

,QSDWLHQWVZLWKLQDGHTXDWHFDUGLRUHVSLUDWRU\UHVHUYHDKHOLFDO&7DORQHPD\EH

LQVXI¿FLHQWWRUXOHRXW3(VLQFHHYHQVXEVHJPHQWDOHPEROLPD\EHLPSRUWDQW

+RZHYHULQWKLVVWXG\RQO\VWDEOHSDWLHQWV DEOHWRJLYHZULWWHQLQIRUPHGFRQVHQW  ZHUHLQFOXGHG7KH¿QDOFOLQLFDORXWFRPHZDVQRWDSDUWRIRXUVWXG\EXWVKRXOG

EHLQYHVWLJDWHGDORQJZLWKWKHUHVXOWRISRVVLEOHIXUWKHULQYHVWLJDWLRQVLQSDWLHQWV

ZLWKDQRUPDOVSLUDO&7VFDQUHVXOW)RUWKLVWKHUHDUHVHYHUDORSWLRQV7KH¿UVW

(16)





SRVVLELOLW\LVWRLQYROYHDFOLQLFDOSUHGLFWLRQUXOHLQFRPELQDWLRQZLWK'GLPHU

WHVWLQJ$VHFRQGRSWLRQLVWKHXVHRIVHULDOFRPSUHVVLRQXOWUDVRQRJUDSK\

RULPSHGDQFHSOHWK\VPRJUDSK\WRGHWHFWSRVVLEOHGHHSYHLQWKURPERVLVDVD

VRXUFHRISXOPRQDU\HPEROL ,QGHHGDIWHUWKLVVWXG\ZDVFRPSOHWHGWKUHH

VWXGLHVLQFOXGLQJRQHRIRXUJURXSZLWKDGLIIHUHQWSDWLHQWSRSXODWLRQKDYH

EHHQSXEOLVKHGWKDWKDYHHYDOXDWHGDOJRULWKPVLQZKLFKQRUPDOKHOLFDO&7ZDV

FRPELQHGZLWKFRPSUHVVLRQXOWUDVRQRJUDSK\,QWKH¿UVWVWXG\E\0XVVHWHWDO

ORZWRLQWHUPHGLDWHSUREDELOLW\SDWLHQWVZLWKQHJDWLYH¿QGLQJVRQ&7DQG86ZHUH

OHIWXQWUHDWHGZLWKUHFXUUHQWWKURPERHPEROLVPLQ &,   7KHUHVXOWVRIWKHPRUHUHFHQWVWXGLHVE\3HUULHUDQGYDQ6WULMHQIRXQGUHFXUUHQW

WKURPERHPEROLVPLQFDVHRIQHJDWLYH¿QGLQJVLQ &,  DQG &O UHVSHFWLYHO\%RWK0XVVHWDQG3HUULHUVWUHVV

WKHLPSRUWDQFHRIDGGLWLRQDOXOWUDVRQRJUDSK\RIWKHOHJVLQFDVHRIQHJDWLYH&7

¿QGLQJVWRVDIHO\ZLWKKROGDQWLFRDJXODQWWUHDWPHQW$VRPHZKDWOLPLWHGYDOXH

RIDGGLWLRQDOXOWUDVRQRJUDSK\ZDVIRXQGLQRXURZQVWXG\$PRUHUHFHQWVWXG\

IRXQGFRQVLGHUDEO\PRUH'97LQVXVSHFWHGSDWLHQWVZLWKDFRPSOHWHORZHUOLPE

86ZKHQFRPSDUHGWRWKHPRUHFRPPRQO\SHUIRUPHGOLPLWHGWZRSRLQWHYDOXDWLRQ

WHVW

:HFRQFOXGHWKDWEDVHGRQWKHUHVXOWVRIWKLVVWXG\LQSDWLHQWVZLWKFOLQLFDOO\

VXVSHFWHG3(DQGDQDEQRUPDOSHUIXVLRQVFLQWLJUDSK\VLQJOHGHWHFWRUVSLUDO&7

DORQHLVQRWVHQVLWLYHHQRXJKWREHXVHGDVWKHVROHWHVWWRH[FOXGH3(

(17)





5HIHUHQFHV

*LQVEHUJ-60DQDJHPHQWRIYHQRXVWKURPERHPEROLVP  1HZ(QJODQG-RXUQDORI0HGLFLQH  

%DUULWW':-RUGDQ6& 

$QWLFRDJXODQWGUXJVLQWKHWUHDWPHQWRISXOPRQDU\HPEROLVP$FRQWUROOHGWULDO

/DQFHW

.HDURQ&*HQW0+LUVK-:HLW]-.RYDFV0-$QGHUVRQ'57XUSLH$**UHHQ'*LQVEHUJ

-6:HOOV30DF.LQQRQ%-XOLDQ-$

$FRPSDULVRQRIWKUHHPRQWKVRIDQWLFRDJXODWLRQZLWKH[WHQGHGDQWLFRDJXODWLRQIRUD¿UVW

HSLVRGHRILGLRSDWKLFYHQRXVWKURPERHPEROLVP

1(QJO-0HG  

*ROGKDEHU6=3XOPRQDU\(PEROLVP  1(QJO-0HG

+\HUV70 

6WDWHRIWKH$UW9HQRXV7KURPERHPEROLVP

$P-5HVS&ULW&DUH0HG

+XOO5'+LUVK-&DUWHU&-5DVNRE*(*LOO*--D\50/HFOHUF-5'DYLG0&RDWHV*  'LDJQRVWLF9DOXHRI9HQWLODWLRQSHUIXVLRQOXQJVFDQQLQJLQSDWLHQWVZLWKVXVSHFWHGSXOPRQDU\

HPEROLVP

&KHVW

+XOO5'5DVNRE*(*LQVEHUJ-63DQMX$$%ULOO(GZDUGV3&RDWHV*3LQHR*) 

$QRQLQYDVLYHVWUDWHJ\IRUWKHWUHDWPHQWRISDWLHQWVZLWKVXVSHFWHGSXOPRQDU\HPEROLVP

$UFK,QW0HG  

:HOOV36*LQVEHUJ-6$QGHUVRQ'5.HDURQ&*HQW07XUSLH$*%RUPDQLV-:HLW]-

&KDPEHUODLQ0%RZLH'%DUQHV'+LUVK-

8VHRIDFOLQLFDOPRGHOIRUVDIHPDQDJHPHQWRISDWLHQWVZLWKVXVSHFWHGSXOPRQDU\HPEROLVP

$QQ,QWHUQ0HG

3,23('LQYHVWLJDWRUV 

9DOXHRIWKHYHQWLODWLRQSHUIXVLRQVFDQLQDFXWHSXOPRQDU\HPEROLVP5HVXOWVRIWKH

SURVSHFWLYHLQYHVWLJDWLRQRISXOPRQDU\HPEROLVPGLDJQRVLV 3,23(' 

-$0$

1RYHOOLQH5$%DOWDURZLFK2+$WKDQDVRXOLV&$:DOWPDQ$&*UHHQ¿HOG$-0F.XVLFN.$  7KHFOLQLFDOFRXUVHRISDWLHQWVZLWKVXVSHFWHGSXOPRQDU\HPEROLVPDQGDQHJDWLYHSXOPRQDU\

DUWHULRJUDP

5DGLRORJ\

'DOHQ-(%URRNV+/-RKQVRQ/:0HLVWHU6*6]XFV00-U'H[WHU/ 

3XOPRQDU\DQJLRJUDSK\LQDFXWHSXOPRQDU\HPEROLVPLQGLFDWLRQVWHFKQLTXHVDQGUHVXOWVLQ

SDWLHQWV

$P+HDUW-

+XOO5'+LUVK-&DUWHU&--D\50'RGG3(2FNHOIRUG3$&RDWHV**LOO*-7XUSLH$*

'R\OH'-%XOOHU+55DVNRE*(

3XOPRQDU\DQJLRJUDSK\YHQWLODWLRQOXQJVFDQQLQJDQGYHQRJUDSK\IRUFOLQLFDOO\VXVSHFWHG

SXOPRQDU\HPEROLVPZLWKDEQRUPDOSHUIXVLRQOXQJVFDQ

$QQ,QWHUQ0HG

6WHLQ3'$WKDQDVRXOLV&$ODYL$*UHHQVSDQ5++DOHV&$6DOW]PDQ+$9UHLP&(7HUULQ

0/:HJ-*

&RPSOLFDWLRQVDQGYDOLGLW\RISXOPRQDU\DQJLRJUDSK\LQDFXWHSXOPRQDU\HPEROLVP

&LUFXODWLRQ

YDQ%HHN(-5HHNHUV-$%DWFKHORU'$%UDQGMHV'3%XOOHU+5 

)HDVLELOLW\VDIHW\DQGFOLQLFDOXWLOLW\RIDQJLRJUDSK\LQSDWLHQWVZLWKVXVSHFWHGSXOPRQDU\

HPEROLVP

(XU5DGLRO

(18)





+XGVRQ(56PLWK730F'HUPRWW9*1HZPDQ*(6XKRFNL393D\QH&66WDFNKRXVH'-

3XOPRQDU\DQJLRJUDSK\SHUIRUPHGZLWKLRSDPLGROFRPSOLFDWLRQVLQSDWLHQWV

5DGLRORJ\

5HP\-DUGLQ05HP\-:DWWLQQH/*LUDXG) 

&HQWUDOSXOPRQDU\WKURPERHPEROLVPGLDJQRVLVZLWKVSLUDOYROXPHWULF&7ZLWKWKHVLQJOH

EUHDWKKROGWHFKQLTXHFRPSDULVRQZLWKSXOPRQDU\DQJLRJUDSK\

5DGLRORJ\

5HP\-DUGLQ05HP\-'HVFKLOGUH)$UWDXG'%HUHJL-3+RVVHLQ)RXFKHU&0DUFKDQGLVH

;'XKDPHO$'LDJQRVLVRISXOPRQDU\HPEROLVPZLWKVSLUDO&7FRPSDULVRQZLWKSXOPRQDU\

DQJLRJUDSK\DQGVFLQWLJUDSK\

5DGLRORJ\

YDQ5RVVXP$%3DWW\QDPD307RQ(57UHXUQLHW)($UQGW-:YDQ(FN%.LHIW*-

3XOPRQDU\HPEROLVPYDOLGDWLRQRIVSLUDO&7DQJLRJUDSK\LQSDWLHQWV

5DGLRORJ\

0D\R-55HP\-DUGLQ00XOOHU1/5HP\-:RUVOH\')+RVVHLQ)RXFKHU&.ZRQJ-6

%URZQ0-

3XOPRQDU\(PEROLVP3URVSHFWLYH&RPSDULVRQRI6SLUDO&7ZLWK9HQWLODWLRQ3HUIXVLRQ

6FLQWLJUDSK\

5DGLRORJ\

5DWKEXQ6:5DVNRE*(:KLWVHWW7/ 

6HQVLWLYLW\DQG6SHFL¿FLW\RI+HOLFDO&RPSXWHG7RPRJUDSK\LQWKH'LDJQRVLVRI3XOPRQDU\

(PEROLVP$6\VWHPDWLF5HYLHZ

$QQ,QWHUQ0HG

0XOOLQV0'%HFNHU'0+DJVSLHO.'3KLOEULFN-7 

7KHUROHRIVSLUDOYROXPHWULFFRPSXWHGWRPRJUDSK\LQWKHGLDJQRVLVRISXOPRQDU\HPEROLVP

$UFK,QWHUQ0HG

:RUVOH\')$ODYL$

&RPSUHKHQVLYH$QDO\VLVRIWKH5HVXOWVRI7KH3,23('6WXG\

-1XFO0HG

6DJHO66*UHHQVSDQ5+ 

1RQXQLIRUPSXOPRQDU\DUWHULDOSHUIXVLRQSXOPRQDU\HPEROLVP

5DGLRORJ\

GH0RQ\H:YDQ6WULMHQ0-+XLVPDQ09.LHIW*-3DWW\QDPD30 

6XVSHFWHGSXOPRQDU\HPEROLVPSUHYDOHQFHDQGDQDWRPLFGLVWULEXWLRQLQFRQVHFXWLYH

SDWLHQWV

5DGLRORJ\

*RRGPDQ/5&XUWLQ--0HZLVVHQ0:)ROH\:'/LSFKLN5-&UDLQ056DJDU.%&ROOLHU

%'

'HWHFWLRQRISXOPRQDU\HPEROLVPLQSDWLHQWVZLWKXQUHVROYHGFOLQLFDODQGVFLQWLJUDSKLF

GLDJQRVLVKHOLFDO&7YHUVXVDQJLRJUDSK\

$-5

3HUULHU$+RZDUWK1'LGLHU'/RXEH\UH38QJHU3)GH0RHUORRVH36ORVPDQ'-XQRG$

%RXQDPHDX[+

3HUIRUPDQFHVRIKHOLFDOFRPSXWHGWRPRJUDSK\LQXQVHOHFWHGRXWSDWLHQWVZLWKVXVSHFWHG

SXOPRQDU\HPEROLVP

$QQ,QWHUQ0HG±

%DLOH(0.LQJ**0XOOHU1/'¶<DFKNRYD<&RFKH((3DUH3'0D\R-5 

6SLUDOFRPSXWHGWRPRJUDSK\LVFRPSDUDEOHWRDQJLRJUDSK\IRUWKHGLDJQRVLVRISXOPRQDU\

HPEROLVP

$P-5HVSLU&ULW&DUH0HG

(19)





+XOO5'5DVNRE*(&RDWHV*3DQMX$$ 

&OLQLFDOYDOLGLW\RIDQRUPDOSHUIXVLRQOXQJVFDQLQSDWLHQWVZLWKVXVSHFWHGSXOPRQDU\

HPEROLVP

&KHVW

*RRGPDQ/5/LSFKLN5-.X]R56/LX<0F$XOLIIH7/2¶%ULHQ'- 

6XEVHTXHQWSXOPRQDU\HPEROLVPULVNDIWHUDQHJDWLYHKHOLFDO&7SXOPRQDU\DQJLRJUDP

SURVSHFWLYHFRPSDULVRQZLWKVFLQWLJUDSK\

5DGLRORJ\

/RPLV11<RRQ+&0RUDQ$*0LOOHU)- /RPLV11<RRQ+&0RUDQ$*HWDO

&OLQLFDORXWFRPHVRISDWLHQWVDIWHUDQHJDWLYHVSLUDO&7SXOPRQDU\DUWHULRJUDPLQWKHHYDOXDWLRQ

RIDFXWHSXOPRQDU\HPEROLVP

-9DVF,QWHUY5DGLRO-XQ  

*RWWVDWHU$%HUJ$&HQWHUJDUG-)UHQQE\%1LUKRY11\PDQ8 

&OLQLFDOO\VXVSHFWHGSXOPRQDU\HPEROLVPLVLWVDIHWRZLWKKROGDQWLFRDJXODWLRQDIWHUDQHJDWLYH

VSLUDO&7"

(XU5DGLRO

:HOOV36$QGHUVRQ'55RGJHU06WLHOO,'UH\HU-)%DUQHV')RUJLH0.RYDFV*:DUG-

.RYDFV0-

([FOXGLQJSXOPRQDU\HPEROLVPDWWKHEHGVLGHZLWKRXWGLDJQRVWLFLPDJLQJPDQDJHPHQWRI

SDWLHQWVZLWKVXVSHFWHGSXOPRQDU\HPEROLVPSUHVHQWLQJWRWKHHPHUJHQF\GHSDUWPHQWE\

XVLQJDVLPSOHFOLQLFDOPRGHODQGD'GLPHU

$QQ,QWHU0HG

0XVVHW'3DUHQW)0H\HU*0DLWUH6*LUDUG3/HUR\HU&5HYHO03&DUHWWH0)/DXUHQW0

&KDUERQQLHU%/DXUHQW)0DO+1RQHQW0/DQFDU5*UHQLHU36LPRQQHDX*

'LDJQRVWLFVWUDWHJ\IRUSDWLHQWVZLWKVXVSHFWHGSXOPRQDU\HPEROLVPDSURVSHFWLYHPXOWLFHQWUH

RXWFRPHVWXG\

/DQFHW  

9DQ6WULMHQ0-'H0RQ\p:6FKLHUHFN-.LHIW*-3ULQV0++XLVPDQ093DWW\QDPD307

6LQJOHGHWHFWRU&7DVWKHSULPDU\GLDJQRVWLFWHVWLQVXVSHFWHGSXOPRQDU\HPEROLVPD

PXOWLFHQWUHFOLQLFDOPDQDJHPHQWVWXG\LQSDWLHQWV

$QQDOVRI,QWHUQDO0HGLFLQH

3HUULHU$5R\30$XMHVN\'&KDJQRQ,+RZDUG1*RXUGLHU$//HIWKHULRWKLV*%DUJKRXWK

*&RUQX]-+D\R]'%RXQDPHDX[+'LDJQRVLVSXOPRQDU\HPEROLVPLQRXWSDWLHQWV

ZLWKFOLQLFDODVVHVVPHQW'GLPHUPHDVXUHPHQWYHQRXVXOWUDVRXQGDQGKHOLFDOFRPSXWHG

WRPRJUDSK\DPXOWLFHQWHUPDQDJHPHQWVWXG\

$P-PHG

(OLDV$&RORPELHU'9LFWRU*(OLDV0$UQDXG&-XFKHW+'XFDVVH-/'LGLHU$&ROLQ&

5RXVVHDX+1JX\HQ)-RIIUH)

'LDJQRVWLFSHUIRUPDQFHRIFRPSOHWHORZHUOLPEYHQRXVXOWUDVRXQGLQSDWLHQWVZLWKFOLQLFDOO\

VXVSHFWHGDFXWHSXOPRQDU\HPEROLVP

7KURPE+DHPRVW  



(20)







([DPSOHVRISXOPRQDU\HPEROLVPRQVSLUDO&7

/DUJH3(LQPDLQSXOPRQDU\DUWHULHV 3(DWWKHOHYHORIWKHOREDUDUWHULHV

0RVDLFSHUIXVLRQLQDSDWLHQWZLWK3(

,VRODWHGVHJPHQWDO3(RQWKHULJKW

(21)





Referenties

GERELATEERDE DOCUMENTEN

Peripheral blood cells were stained with HLA-A2.1 tetramers containing the tyrosinase368–376 peptide followed by staining with a panel of lineage antibodies, as described in

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden.. Downloaded

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden.. Downloaded

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden. Downloaded

a large cohort of consecutive patients. Part of phase 1 of the Antelope study was a study that determined the sensitivity and specifi city of helical CT. Patients

Het arts examen werd cum laude behaald in 1996, waarna vrijwel direct gestart werd als arts-assistent Radiologie in het Leyenburg Ziekenhuis te Den Haag.. De

Het gebruik van spiraal CT bij patiënten met een klinische verdenking op longembolie verlaagt de kosten aangezien niet alleen bij ongeveer 25% van de patiënten daadwerkelijk

Blades and blade fragments seem to have been especially used for longitudinal motions, mainly on plant material (7/12). Flake and flake fragments are used in different motions on