• 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!
13
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)



1RQLQYDVLYHGLDJQRVWLFWHVWV

IRUSXOPRQDU\HPEROLVP

/HVVXVHIXOZKHQQHHGHGWKH

PRVW

-*/LMPHU

0-/YDQ6WULMHQ

09+XLVPDQ

0+3ULQV

'30%UDQGMHV

+5%OOHU

-/%ORHP

1RQLQYDVLYHGLDJQRVWLFWHVWVIRUSXOPRQDU\HPEROLVP/HVVXVHIXOZKHQQHHGHG

WKHPRVW

-HURHQ*/LMPHU0DUFR-/YDQ6WULMHQ0HOYLQ50DF*LOODYU\0DUWLQ+3ULQV

'HHV30%UDQGMHV+DUU\5%OOHU

VXEPLWWHG

(3)





$EVWUDFW

3XUSRVH'HFLVLRQDQDO\VHVDUHXVHGWRGHWHUPLQHWKHPRVW

DSSURSULDWHVHTXHQFHRISURFHGXUHVVXFKDVSHUIXVLRQ

YHQWLODWLRQOXQJVFDQ 94VFDQ VSLUDO&7 6&7 SXOPRQDU\

DQJLRJUDSK\'GLPHUPHDVXUHPHQWDQGFRPSUHVVLRQ

XOWUDVRQRJUDSK\ &86 WRDQDO\]HSDWLHQWVVXVSHFWHGWR

KDYHSXOPRQDU\HPEROLVP 3( 7RDVVHVWKHYDOLGLW\RIWKH

LQGHSHQGHQFHDVVXPSWLRQLQWKHVHGHFLVLRQDQDO\VHVZH

H[DPLQHGWKHGLDJQRVWLFDFFXUDF\RIQRQLQYDVLYHWHVWVLQ

SDWLHQWVZLWKGLIIHUHQW94VFDQUHVXOWVLQSDUWLFXODUZKHQ

WKHUHVXOWRIWKH94VFDQLVLQFRQFOXVLYH



0HWKRGV'DWDZHUHREWDLQHGLQDPXOWLFHQWUHVWXG\LQ

SDWLHQWVZLWKVXVSHFWHG3( Q  

3(ZDVH[FOXGHGE\DQRUPDOSXOPRQDU\DQJLRJUDPRUD

QRUPDO94VFDQ7KHGLDJQRVLVZDVHVWDEOLVKHGLQFDVH

RIDQDEQRUPDODQJLRJUDPRUDKLJKSUREDELOLW\94VFDQ

7KH6LPSOL5HG'GLPHUWHVWDQG&86ZHUHSHUIRUPHG

XSRQLQFOXVLRQLQWKHVWXG\DQGDVSLUDO&7ZDVRQO\

SHUIRUPHGLQSDWLHQWVZLWKDQDEQRUPDO94VFDQ7HVW

FKDUDFWHULVWLFVZHUHFDOFXODWHGLQWKHHQWLUHSRSXODWLRQ

DQGLQVXEJURXSVZLWKQRQGLDJQRVWLF94VFDQUHVXOWV  5HVXOWV7KHRYHUDOOOLNHOLKRRGUDWLRRIDQRUPDO6LPSOL5('

WHVWZDV &, :KHUHDVLQWKHSDWLHQWV

ZLWKDQRQGLDJQRVWLF94VFDQWKHOLNHOLKRRGUDWLRZDV

VKRZLQJQRGLVFULPLQDWRU\SRWHQWLDORIWKHWHVWIRUWKHSUHVHQFH

RUDEVHQFHRI3( &, 7KHRYHUDOOOLNHOLKRRG

UDWLRRIDQDEQRUPDO&86ZDV &, 7KH

OLNHOLKRRGUDWLRGHFUHDVHGWR &, LQSDWLHQWV

ZLWKDQRQGLDJQRVWLF94VFDQ7KHRYHUDOOOLNHOLKRRGUDWLR

RIDQDEQRUPDOVSLUDO&7ZDV &, DQG

WKHQRQGLDJQRVWLF94VFDQVXEJURXSHVWLPDWHZDV

&, 7KHGLIIHUHQFHVEHWZHHQWKHVXEJURXSV

ZHUHRQO\VLJQL¿FDQWIRUWKH6LPSOL5HG''LPHUZKHQ

WHVWHGZLWKD%UHVORZ±'D\WHVWIRUKRPRJHQHLW\ S  

&RQFOXVLRQV$OWKRXJKWKHRYHUDOOSHUIRUPDQFHRIWKH

HYDOXDWHGQRQLQYDVLYHGLDJQRVWLFWHVWVVHHPSURPLVLQJ

WKHLUGLVFULPLQDWRU\SRZHULQWKHVXEJURXSRISDWLHQWVZLWK

QRQGLDJQRVWLF94VFDQVZDVGLVDSSRLQWLQJ,JQRULQJ

WKHGHSHQGHQFLHVEHWZHHQGLDJQRVWLFWHVWVLQGHFLVLRQ

DQDO\VHVFDQUHVXOWLQHUURQHRXVUHFRPPHQGDWLRQV

(4)





,QWURGXFWLRQ

7KHGLDJQRVLVRISXOPRQDU\HPEROLVP 3( LVGLI¿FXOWWRHVWDEOLVKEDVHGRQ

FOLQLFDOVLJQVDQGV\PSWRPVDORQHDVUHYHDOHGE\WKHLQWURGXFWLRQRIREMHFWLYH

WHVWVLQWKH¶V,WZDVVKRZQWKDWRQO\RQHWKLUGRIWKHSDWLHQWVZLWKDFOLQLFDO

VXVSLFLRQDFWXDOO\KDGWKHGLDJQRVLV3(7KHYDOXHRIWKHYHQWLODWLRQSHUIXVLRQ

OXQJVFLQWLJUDSK\ 94VFDQ IRUWKHGLDJQRVWLFZRUNXSRISDWLHQWVVXVSHFWHGRI3(

ZDVHVWDEOLVKHGLQWKH¶V1HYHUWKHOHVVLQDSSUR[LPDWHO\RISDWLHQWV

WKHUHVXOWVRID94VFDQDUHLQFRQFOXVLYHDQGUHIHUUHGWRDVQRQGLDJQRVWLF,Q

WKHVHSDWLHQWVIXUWKHUREMHFWLYHWHVWVDUHQHHGHGWRFRQ¿UPRUUHIXWHWKHGLDJQRVLV

7KHLGHDOWHVWIRUWKLVSXUSRVHLVSXOPRQDU\DQJLRJUDSK\ZKLFKLVFRQVLGHUHG

WKHUHIHUHQFHWHVWIRU3( +RZHYHUSXOPRQDU\DQJLRJUDSK\LVLQYDVLYHWLPH

FRQVXPLQJDQGDVVRFLDWHGZLWKPRUELGLW\

6HYHUDOQRQLQYDVLYHWHVWVVXFKDVGGLPHUDVVD\VFRPSUHVVLRQXOWUDVRQRJUDSK\

&86 DQGVSLUDO&7DUHDGYRFDWHGWRUHGXFHWKHQXPEHURISXOPRQDU\

DQJLRJUDPVLQSDWLHQWVZLWKVXVSHFWHG3( 0RVWRIWKHVHUHFRPPHQGDWLRQV

DUHEDVHGRQGHFLVLRQDQDO\VHVLQZKLFKWKHFOLQLFDOHIIHFWVRIWKHDSSOLFDWLRQRI

GLDJQRVWLFVWUDWHJLHVDUHPRGHOHG,QJHQHUDOWKHVHGHFLVLRQDQDO\VHVFRPELQH

UHSRUWVRQWHVWFKDUDFWHULVWLFVRIWKHGLIIHUHQWWHVWVLQDGHFLVLRQWUHHWRFDOFXODWH

WKHSURSRUWLRQRIIDOVHSRVLWLYHDQGIDOVH±QHJDWLYHUHVXOWVRIDQHQWLUHVWUDWHJ\

7KHWHVWFKDUDFWHULVWLFVLQWKHVHUHSRUWVDQGWKXVWKRVHXVHGLQWKHVHGHFLVLRQ

DQDO\VHVDUHXVXDOO\DVVHVVHGLQDJURXSRIFRQVHFXWLYHSDWLHQWVVXVSHFWHGRI

3(+RZHYHUVRPHVWXGLHVKDYHVKRZQWKDWWKHGLDJQRVWLFDFFXUDF\RIDWHVW

LVQRWFRQVWDQWEXWFDQGLIIHUDFURVVVXEJURXSV &RQVHTXHQWO\LQFRUSRUDWLQJ

VXEJURXSHVWLPDWHVUDWKHUWKDQRYHUDOOHVWLPDWHVFDQDOWHUWKHUHVXOWVDQG

UHFRPPHQGDWLRQVRIGHFLVLRQDQDO\VHV

7RDVVHVVWKHYDOLGLW\RIWKHLQGHSHQGHQFHDVVXPSWLRQLQGHFLVLRQDQDO\VHVZH

H[DPLQHGWKHGLDJQRVWLFDFFXUDF\RIQRQLQYDVLYHWHVWVLQDOOSDWLHQWVVXVSHFWHG

RI3(DQGLQVXEJURXSVRISDWLHQWVDVGHWHUPLQHGE\WKHLU94VFDQUHVXOWLQD

UHFHQWPXOWLFHQWHUVWXG\RQWKHDFFXUDF\RID'GLPHUWHVW&86DQGVSLUDO&7

0HWKRGV

3DWLHQWV

'DWDZHUHREWDLQHGLQDODUJHVFDOHVWXG\LQVL['XWFKWHDFKLQJKRVSLWDOV3UHYLRXV

UHSRUWVRIWKLVWULDOLQFOXGHWKHDQDWRPLFGLVWULEXWLRQRISXOPRQDU\HPEROLVPWKH

GLDJQRVWLFDFFXUDF\RID¿EULQGHJUDGDWLRQSURGXFWDVVD\DQGFOLQLFDOGHFLVLRQ

UXOHV )URP0D\WKURXJK0DUFKERWKLQDQGRXWSDWLHQWVZLWK

DFOLQLFDOVXVSLFLRQRI3(ZHUHHOLJLEOHIRUWKHVWXG\ 3DWLHQWVZHUHH[FOXGHGLI

WKH\ZHUH\RXQJHUWKDQ\HDUVRIDJHZHUHSUHJQDQWKDGDQLQGLFDWLRQIRU

(5)





DFXWHWKURPERO\WLFWKHUDS\KDGDOUHDG\XQGHUJRQHREMHFWLYHGLDJQRVWLFWHVWLQJ

IRUYHQRXVWKURPERHPEROLVPRULIWKHUHZDVDQH[SHFWHGLQDELOLW\WRFRPSOHWH

WKHGLDJQRVWLFSURWRFROZLWKLQKRXUVRISUHVHQWDWLRQ7KHVWXG\SURWRFROZDV

DSSURYHGE\WKH,QVWLWXWLRQDO5HYLHZ%RDUGVRIDOOKRVSLWDOVDQGZULWWHQLQIRUPHG

FRQVHQWZDVREWDLQHGIURPDOOSDUWLFLSDWLQJSDWLHQWV

$WRWDORIFRQVHFXWLYHSDWLHQWVZLWKFOLQLFDOO\VXVSHFWHG3(ZHUHVFUHHQHG

2IWKHVHSDWLHQWVZHUHH[FOXGHGIRUWKHIROORZLQJUHDVRQVQHHGIRUDFXWH

WKURPERO\WLFWKHUDS\ Q  SUHJQDQF\ Q  DJHXQGHU\HDUV Q  

REMHFWLYHGLDJQRVWLFWHVWVIRU3(DOUHDG\SHUIRUPHGSULRUWRVWXG\HQWU\ Q   DQGDQH[SHFWHGLQDELOLW\WRFRPSOHWHWKHGLDJQRVWLFZRUNXSZLWKLQKRXUV

Q  +HQFHDWRWDORISDWLHQWVZHUHHOLJLEOHIRULQFOXVLRQLQWKHVWXG\RI

ZKRP  JDYHLQIRUPHGFRQVHQW

'LDJQRVWLF,QYHVWLJDWLRQV

$GHWDLOHGFOLQLFDOKLVWRU\SK\VLFDOH[DPLQDWLRQ'GLPHUWHVW&86DQGD94

VFDQZHUHSHUIRUPHGZLWKLQKRXUVRISUHVHQWDWLRQ LQDOOSDWLHQWV,QWKHVWXG\

SURWRFRODVSLUDO&7ZDVRQO\LQGLFDWHGLQSDWLHQWVZLWKDQDEQRUPDO94VFDQ

3XOPRQDU\DQJLRJUDSK\ZDVSHUIRUPHGLQFDVHRIDQRQGLDJQRVWLF94VFDQDQG

ZKHQHYHUDKLJKSUREDELOLW\94VFDQZDVIROORZHGE\DQRUPDOVSLUDO&7VFDQ

7KHVWXG\SURWRFROGHPDQGHGWKDWDOOGLDJQRVWLFLQYHVWLJDWLRQVZHUHSHUIRUPHG

ZLWKLQKRXUVRISUHVHQWDWLRQ3DWLHQWVZHUHFODVVL¿HGDVKDYLQJ3(RQWKH

EDVLVRIDKLJKSUREDELOLW\94VFDQRUDEQRUPDODQJLRJUDP3(ZDVH[FOXGHGE\

DQRUPDO94VFDQRUDQRUPDOSXOPRQDU\DQJLRJUDP

8SRQVWXG\LQFOXVLRQDQGSULRUWRRUZLWKLQKRXUVRIWKHVWDUWRIKHSDULQWKHUDS\

WKHUDSLGZKROHEORRG6LPSOL5(''GLPHUWHVW $JHQ%LRPHGLFDO/WG%ULVEDQH

$XVWUDOLD ZDVSHUIRUPHG7KHWHVWZDVGRQHZLWKFDSLOODU\EORRG [PO GUDZQ

E\¿QJHUVWLFN7KHWHVWLVDEQRUPDOZKHQDJJOXWLQDWLRQRIUHGFHOOVLVREVHUYHG

ZLWKLQWZRPLQXWHVZKLFKLQGLFDWHVDSODVPDFRQFHQWUDWLRQRI'GLPHUIUDJPHQWV

RIPJORUDERYH$WHDFKFHQWUHWKHWHVWZDVSHUIRUPHGE\DOLPLWHGQXPEHU

RILQYHVWLJDWRUVZKRKDGSUHYLRXVO\EHHQWUDLQHGLQWKHLQWHUSUHWDWLRQRIWKH

6LPSOL5('7KHWHVWUHVXOWZDVUHFRUGHGZLWKRXWNQRZOHGJHRIWKHRXWFRPHRI

RWKHUGLDJQRVWLFWHVWV

&86ZDVSHUIRUPHGE\H[SHULHQFHGUDGLRORJLVWVXQDZDUHRIWKHRXWFRPHRI

WKHRWKHUGLDJQRVWLFLQYHVWLJDWLRQV$WZRSRLQW%PRGH&86ZDVSHUIRUPHG

XVLQJD0K]OLQHDUDUUD\WUDQVGXFHU:LWKWKHSDWLHQWLQWKHVXSLQHSRVLWLRQ

WKHFRPPRQIHPRUDOYHLQZDVORFDWHGLQWKHJURLQXVLQJWKHDGMDFHQWDUWHU\

DVDUHIHUHQFHSRLQW7KHSRSOLWHDOYHLQZDVVXEVHTXHQWO\ORFDWHGLQWKHPLG

SRSOLWHDOIRVVDZLWKWKHSDWLHQWLQWKHSURQHSRVLWLRQ$OOYHLQVZHUHLPDJHGLQ

(6)





WKHWUDQVYHUVHSODQHWRDVVHVVWKHLUFRPSUHVVLELOLW\8OWUDVRQRJUDSK\ZDV

FRQVLGHUHGDEQRUPDOLIDYHQRXVVHJPHQWFRXOGQRWEHFRPSOHWHO\FRPSUHVVHG

DVSUHYLRXVO\GHVFULEHG

6SLUDO&7DQJLRJUDSK\ ZDVSHUIRUPHGXVLQJDVLQJOHVOLFH&7VFDQQHUGXULQJ

DVHFRQGVLQJOHEUHDWKKROG 6LHPHQV6RPDWRPSOXVDQG6RPDWRP

6LHPHQV0HGLFDO6\VWHPV(UODQJHQ*HUPDQ\(OVFLQW (OVFLQW+DLID,VUDHO 

3KLOLSV65DQG653KLOLSV%HVW7KH1HWKHUODQGV ,ISDWLHQWVZHUH

YHU\G\VSQHLFVFDQQLQJZDVSHUIRUPHGGXULQJVKDOORZEUHDWKLQJ,PDJHVZHUH

UHFRQVWUXFWHGDWPPLQWHUYDOVDQGLQWHUSUHWHGRQDYLHZLQJVWDWLRQ$OOVSLUDO&7

VFDQVZHUHLQWHUSUHWHGLQGHSHQGHQWO\E\WZRH[SHULHQFHGUDGLRORJLVWV,QFDVH

RIGLVDJUHHPHQWWKHLQWHUSUHWDWLRQRIDWKLUGUDGLRORJLVWZDVFRQVLGHUHGGHFLVLYH

3(ZDVFRQVLGHUHGWREHSUHVHQWLILQFDVHRIDZHOORSDFL¿HGVFDQWKHUHZDVDQ

LQWUDOXPLQDO¿OOLQJGHIHFWRQPRUHWKDQRQHVOLFHDQGQRDUWHIDFWVZHUHSUHVHQW

$¿OOLQJGHIHFWFRXOGEHVHHQDVFRPSOHWHRFFOXVLRQRIWKHYHVVHODQHFFHQWULF

SDUWLDO¿OOLQJGHIHFWRUDSDUWLDOFHQWUDO¿OOLQJGHIHFWVXUURXQGHGE\FRQWUDVWDJHQW

$&7VFDQZDVFRQVLGHUHGQHJDWLYHLILQFDVHRIDJRRGTXDOLW\VFDQQR¿OOLQJ

GHIHFWVFRXOGEHVHHQ

6L[YLHZSHUIXVLRQOXQJVFLQWLJUDSK\ZDVSHUIRUPHGXVLQJ0ETRI

P7HFKQHWLXPODEHOOHGPDFURDJJUHJDWHVRIDOEXPLQ 0DOOLQFNURGW3HWWHQ7KH

1HWKHUODQGV 9HQWLODWLRQVFLQWLJUDSK\ZDVSHUIRUPHGXVLQJ P.U\SWRQJDV YLD

5E.UJHQHUDWRU&\JQH$PHUVKDP  LQFDVHRIVHJPHQWDORUODUJHUSHUIXVLRQ

GHIHFWV*DPPDFDPHUDDQGFROOLPDWRUGHSHQGHGRQORFDODYDLODELOLW\ 6LHPHQV

2UELWHU'LJLWUDF6LHPHQV0HGLFDO6\VWHPV,VHOLQ1-86$$'$&9HUWH[

DQG$UJXV$'$&/DERUDWRULHV(XURSH%90DDUVHQ7KH1HWKHUODQGV7RVKLED

*&$DQG*&$D7RVKLED0HGLFDO6\VWHPV'LYLVLRQ7RN\R-DSDQ

9DULFDP(OVFLQW,QF+DFNHQVDFN1-86$7KH94VFDQVVFDQVZHUHUHDGE\

WZRQXFOHDUSK\VLFLDQVLQFRQVHQVXV7KH94VFDQVZHUHLQWHUSUHWHGE\XVLQJD

OXQJVHJPHQWUHIHUHQFHFKDUWDQGZHUHFODVVL¿HGDVEHLQJQRUPDO QRSHUIXVLRQ

GHIHFWV KLJKSUREDELOLW\ DWOHDVWRQHVHJPHQWDORUODUJHUSHUIXVLRQGHIHFWVZLWK

ORFDOO\QRUPDOYHQWLODWLRQ RUQRQGLDJQRVWLF YHQWLODWLRQSHUIXVLRQGHIHFWVQRW

IXO¿OOLQJWKHFULWHULDIRUKLJKSUREDELOLW\RUQRUPDO 

3XOPRQDU\DQJLRJUDSK\ZDVSHUIRUPHGXVLQJDGLJLWDOVXEWUDFWLRQWHFKQLTXH

ZLWKWKHFDWKHWHUSRVLWLRQHGVHOHFWLYHO\LQWKHOHIWDQGULJKWSXOPRQDU\DUWHU\

,PDJHVZHUHREWDLQHGLQDWOHDVWWZRSURMHFWLRQV $OOSXOPRQDU\DQJLRJUDPV

ZHUHLQWHUSUHWHGLQGHSHQGHQWO\E\WZRH[SHULHQFHGUDGLRORJLVWV,QFDVHRI

GLVDJUHHPHQWWKHLQWHUSUHWDWLRQRIDWKLUGUDGLRORJLVWZDVFRQVLGHUHGGHFLVLYH

7KHDQJLRJUDPVZHUHFRQVLGHUHGQRUPDORUDEQRUPDODFFRUGLQJWRSUHYLRXVO\

GHVFULEHGFULWHULD

(7)





$QDO\VLV

7KHDQDO\VLVZDVUHVWULFWHGWRWKHSDWLHQWVLQZKRPWKHGLDJQRVLVRI3(ZDV

HVWDEOLVKHGRUUHIXWHGDVGH¿QHGLQWKHSURWRFRO/LNHOLKRRGUDWLRVZHUHFDOFXODWHG

IRUQRUPDODQGDEQRUPDOWHVWUHVXOWVRIWKH6LPSOL5HG'GLPHU&86DQGWKHVSLUDO

&7DVPHDVXUHRIGLDJQRVWLFDFFXUDF\7RH[DPLQHWKHYDOXHRIWKHGLIIHUHQW

WHVWVLQSDWLHQWVZLWKDQRQGLDJQRVWLF94VFDQWKHDQDO\VLVZDVUHSHDWHGLQ

VXEJURXSVGH¿QHGE\WKH94VFDQUHVXOWV KLJKSUREDELOLW\QRQGLDJQRVWLFRU

QRUPDO )RUHDFKOLNHOLKRRGUDWLRFRQ¿GHQFHLQWHUYDOV FL ZHUHFDOFXODWHG

DFFRUGLQJWRWKHQRUPDODSSUR[LPDWLRQRIWKHELQRPLDOGLVWULEXWLRQ7RFRPSDUH

WKHUHVXOWVZLWKLQWKHVXEJURXSVZHFDOFXODWHGWKH'LDJQRVWLF2GGV5DWLR '25 

7KH'25LVDVLQJOHPHDVXUHWRGHVFULEHWKHGLDJQRVWLFDFFXUDF\RIDWHVWDQG

FDQEHFDOFXODWHGDVWKHOLNHOLKRRGUDWLRRIDSRVLWLYHWHVWGLYLGHGE\WKHOLNHOLKRRG

UDWLRRIDQHJDWLYHWHVWUHVXOW 7KH'25UDQJHVIURPWRLQ¿QLW\ZLWKKLJKHU

YDOXHVLQGLFDWLQJEHWWHUWHVWSHUIRUPDQFHDQGXQLW\LQGLFDWLQJQRGLVFULPLQDWLRQ

EHWZHHQGLVHDVHGDQGQRQGLVHDVHG7KHGLIIHUHQFHVLQGLDJQRVWLFDFFXUDF\

RIDWHVWZLWKLQWKHWKUHHVXEJURXSVZHUHH[DPLQHGZLWKWKH%UHVORZ'D\WHVW

IRUKRPRJHQHLW\RIRGGVUDWLRV$SYDOXH”ZDVFRQVLGHUHGVLJQL¿FDQWWR

UHIXWHWKHQXOOK\SRWKHVLVWKDWWKHGLDJQRVWLFDFFXUDF\EHWZHHQWKHVXEJURXSV

ZDVWKHVDPH

7DEOH&OLQLFDODQGGHPRJUDSKLFFKDUDFWHULVWLFVRIWKHVWXG\SDWLHQWVZLWKFOLQLFDOO\VXVSHFWHG

3(LQZKRPWKH¿QDOGLDJQRVLVZDVREWDLQHGDVZHOODVWKHLQLWLDOO\LQFOXGHGSDWLHQWV

6WXG\SDWLHQWV

Q 

,QLWLDOO\LQFOXGHGSDWLHQWV

Q 

PDOH    

PHDQDJH\HDUV 6'    

RXWSDWLHQWV    

PHGLDQGXUDWLRQRIV\PSWRPVGD\V

TXDUWLOHV     

SUHYLRXVKLVWRU\RI97(    

IDPLO\KLVWRU\RI97(    

ULVNSHULRG    

DFWLYHPDOLJQDQF\    

V\PSWRPVRI'97    

97( YHQRXVWKURPERHPEROLVP

 SHULRGRILPPRELOL]DWLRQVXUJHU\RUWUDXPDLQSHULRGRIPRQWKVEHIRUHSUHVHQWDWLRQ '97 GHHSYHLQWKURPERVLV

(8)





5HVXOWV

$¿QDOGLDJQRVLVUHJDUGLQJWKHSUHVHQFHRUDEVHQFHRI3(ZDVQRWUHDFKHGLQ

RIWKHLQFOXGHGSDWLHQWVEHFDXVHRIZLWKGUDZDORILQIRUPHGFRQVHQWFOHDU

HYLGHQFHIRUDQDOWHUQDWLYHGLDJQRVLVPHGLFDOUHDVRQVRUWHFKQLFDOIDLOXUH7KH

SRSXODWLRQFKDUDFWHULVWLFVRIWKHVWXG\SDWLHQWVLQZKRPD¿QDOGLDJQRVLVZDV

REWDLQHGDFFRUGLQJWRSURWRFROZHUHVLPLODUWRWKRVHRIWKHLQLWLDOO\LQFOXGHG

SDWLHQWV WDEOH 

$6LPSOL5(''GLPHUDQGD&86ZHUHDYDLODEOHLQSDWLHQWV6LPSOL5(''

GLPHU&86DQGDVXEVHTXHQW94VFDQWHVWUHVXOWZDVDYDLODEOHLQSDWLHQWV

,QSDWLHQWVWKHUHVXOWVRIWKH94VFDQZHUHQRQGLDJQRVWLF,QDQDGGLWLRQDO

DQGSDWLHQWVUHVSHFWLYHO\WKH6LPSOL5('WHVWDQGWKH&86UHVXOWVZHUHQRW

DYDLODEOH7KHVSLUDO&7UHVXOWVZHUHDYDLODEOHLQRIWKHSDWLHQWVLQZKLFK

LWZDVLQGLFDWHGDFFRUGLQJWRWKHSURWRFRO6SLUDO&7ZDVQRWSHUIRUPHGLQ

SDWLHQWVGXHWRORJLVWLFUHDVRQVDQGKDGLQFRQFOXVLYHUHVXOWVLQSDWLHQWV6SLUDO

&7UHVXOWVZHUHDOVRDYDLODEOHLQSDWLHQWVZLWKDQRUPDO94VFDQDOWKRXJKQRW

LQGLFDWHGE\WKHSURWRFROEXWSHUIRUPHGIRUYDULRXVRWKHUUHDVRQV VWXG\SURWRFRO

YLRODWLRQ 7KHSHUIRUPDQFHRIWKH6LPSOL5(''GLPHUDVVD\&86DQGVSLUDO&7

LQWKHWRWDOJURXSDQGLQVXEJURXSVGH¿QHGE\WKH94VFDQUHVXOWVDUHVKRZQLQ

WDEOH

7KHRYHUDOOOLNHOLKRRGUDWLRRIDQRUPDO6LPSOL5('WHVWUHVXOWZDV,QWKH

VXEJURXSVGH¿QHGE\WKHUHVXOWVRIWKH94VFDQWKHGLVFULPLQDWLYHYDOXHRIWKH

WHVWGLYHUJHG7KHORZHVWOLNHOLKRRGUDWLRRIDQRUPDOWHVWZDVREVHUYHGLQWKH

VXEJURXSRISDWLHQWVZLWKDQRUPDO94VFDQ  :KHUHDVLQWKHSDWLHQWVZLWK

DQRQGLDJQRVWLF94VFDQWKHOLNHOLKRRGUDWLRZDVVKRZLQJQRGLVFULPLQDWRU\

SRWHQWLDORIWKHWHVWIRUWKHSUHVHQFHRUDEVHQFHRI3($VLPLODUWUHQGWRZDUGV

XQLW\IRUSDWLHQWVZLWKDQRQGLDJQRVWLF94VFDQZDVREVHUYHGIRUWKHOLNHOLKRRG

UDWLRRIDQDEQRUPDO'GLPHUUHVXOW7KHGLVFULPLQDWRU\SHUIRUPDQFHRIWKH

6LPSOL5('DVVD\ZDVVLJQL¿FDQWO\GLIIHUHQWDFURVVWKHVXEJURXSV %UHVORZ'D\

WHVWS  

7KHRYHUDOOOLNHOLKRRGUDWLRRIDQDEQRUPDO&86ZDV,QWKHVXEJURXSVGH¿QHG

E\WKHUHVXOWVRIWKH94VFDQWKHKLJKHVWOLNHOLKRRGUDWLRRIDQDEQRUPDOWHVW

ZDVREVHUYHGLQWKHVXEJURXSRISDWLHQWVZLWKDKLJKSUREDELOLW\94VFDQ,QWKH

SDWLHQWVZLWKDQRQGLDJQRVWLF94VFDQWKHOLNHOLKRRGUDWLRGHFOLQHGWR

7KHOLNHOLKRRGUDWLRRIDQRUPDO&86GHWHULRUDWHGIURPWRQRGLVFULPLQDWRU\

YDOXHLQWKHVXEJURXSVRISDWLHQWVZLWKDQRQGLDJQRVWLFRUDQRUPDO94VFDQ

+RZHYHUGLVFULPLQDWRU\SHUIRUPDQFHPHDVXUHGZLWKWKH'25RIWKHVXEJURXSV

ZDVQRWVLJQL¿FDQWO\GLIIHUHQWZKHQWHVWHGZLWKWKH%UHVORZ'D\WHVW S   7KHGLDJQRVLV3(ZDVFRQ¿UPHGLQRIWKH  RIWKHSDWLHQWVLQZKRP

(9)





DVSLUDO&7ZDVSHUIRUPHG7KHRYHUDOOOLNHOLKRRGUDWLRRIDQDEQRUPDOVSLUDO

&7ZDV,QWKHVXEJURXSVGH¿QHGE\WKHUHVXOWVRIWKH94VFDQWKHKLJKHVW

OLNHOLKRRGUDWLRRIDQDEQRUPDOWHVWZDVREVHUYHGLQWKHVXEJURXSRISDWLHQWV

ZLWKDQRUPDO94VFDQ+RZHYHUWKLVZDVH[DPLQHGLQDVPDOOJURXSRISDWLHQWV

Q  ,QWKHVXEJURXSZLWKDQRQGLDJQRVWLF94VFDQWKHOLNHOLKRRGUDWLRRIDQ

DEQRUPDOWHVWGHFOLQHGWR7KHSRRUHVWGLVFULPLQDWLYHYDOXHRIDQHJDWLYH

WHVWUHVXOWZDVDOVRREVHUYHGLQWKLVVXEJURXS,QVSLWHRIWKLVWKH'25RIWKH

VXEJURXSVRISDWLHQWVZLWKDKLJKSUREDELOLW\94VFDQGLIIHUHGQRWVLJQL¿FDQWO\

IURPWKHSDWLHQWVZLWKDQRQGLDJQRVWLF94VFDQ S  

'LVFXVVLRQ

2XUDQDO\VLVVKRZHGWKDWWKHGLDJQRVWLFDFFXUDF\RIQRQLQYDVLYHWHVWVIRU3(

GLIIHUVLQVXEJURXSVRISDWLHQWVGH¿QHGE\WKHLU94VFDQUHVXOW:HREVHUYHG

DVLJQL¿FDQWSRRUHUGLDJQRVWLFSHUIRUPDQFHRIWKH6LPSOL5('DVVD\LQSDWLHQWV

ZLWKDQRQGLDJQRVWLF94VFDQ7KHWUHQGWRZDUGVDOHVVLQIRUPDWLYHWHVWLQWKLV

VXEJURXSZDVDOVRREVHUYHGIRUWKHVSLUDO&7DVZHOODVIRUWKH&86

7DEOH'LDJQRVWLFDFFXUDF\RI6LPSOL5HG'GLPHU&RPSUHVVLRQXOWUDVRQRJUDSK\DQGVSLUDO&7LQ

DOOSDWLHQWVVXVSHFWHGRI3(DQGLQVXEJURXSVRISDWLHQWVDVGHWHUPLQHGE\WKHLU94VFDQUHVXOW

7HVWV 1 3( /5 &, /5 &, '25

''LPHU

 WRWDOJURXS       

KLJKSUREDELOLW\94        

1RQGLDJQRVWLF94        

QRUPDO94       

&86

WRWDOJURXS       

KLJKSUREDELOLW\94       

QRQGLDJQRVWLF94       

QRUPDO94       

6SLUDO&7

7RWDOJURXS       

KLJKSUREDELOLW\94       

QRQGLDJQRVWLF94       

QRUPDO94 ¤      

‡ DGGHGWRDOOFHOOVRIWKH[FRQWLQJHQF\WDEOHWRHVWLPDWH/5

‡¤6PDOOJURXSEHFDXVHDVSLUDO&7ZDVQRWSHUIRUPHGLQDOOSDWLHQWVZLWKDQRUPDO94VFDQ

‡&86LVFRPSUHVVLRQXOWUDVRQRJUDSK\

(10)





8QOLNHWKHSUHGLFWLYHYDOXHRIDGLDJQRVWLFWHVWZKLFKGHSHQGVRQWKHSUHYDOHQFH

RIGLVHDVHOLNHOLKRRGUDWLRVVHQVLWLYLW\DQGVSHFL¿FLW\DUHRIWHQDVVXPHGWR

EHFRQVWDQW,QWHUHVWLQJO\LQ+ODWN\HWDODOUHDG\VKRZHGWKDWVHQVLWLYLW\

DQGVSHFL¿FLW\FDQGLIIHUVLJQL¿FDQWO\EHWZHHQVXEJURXSVRISDWLHQWVGH¿QHG

E\FOLQLFDOFKDUDFWHULVWLFVXVLQJH[HUFLVHHOHFWURFDUGLRJUDSK\DVDQH[DPSOH  5HFHQWO\0RRQVHWDOFRQ¿UPHGWKHVH¿QGLQJVH[DPLQLQJWKHHIIHFWRIYDULDEOHV

IURPKLVWRU\DQGSK\VLFDOH[DPLQDWLRQRQWKHGLDJQRVWLFSHUIRUPDQFHRIWKHVDPH

WHVW,QWKLVVWXG\ZHGHPRQVWUDWHGWKDWYDULDWLRQRIWHVWFKDUDFWHULVWLFVDOVR

GHSHQGRQSUHYLRXVWHVWUHVXOWV7KLVFRXOGEHH[SHFWHGRQEDVLVRIWKHSUHYLRXV

PHQWLRQHGVWXGLHVDVWKHRUHWLFDOO\WKHUHLVQRGLIIHUHQFHEHWZHHQDKLVWRU\LWHP

DQGDGLDJQRVWLFWHVW%RWKFDQEHVHHQDVDWHVWZLWKDSRWHQWLDOWRGLVFULPLQDWH

JURXSVRISDWLHQWVLQWRKLJKDQGORZULVNIRUWKHGLVHDVHXQGHUVWXG\

7KHELRORJLFDOH[SODQDWLRQIRUWKHVHGLIIHUHQFHVLVWKHIDFWWKDWDGLVHDVH

VWDWXVLVVHOGRPDWUXHGLFKRWRPRXVFODVVL¿FDWLRQ2IWHQWKHUHLVDVSHFWUXP

RIGLVHDVHUDQJLQJIURPVPDOOOLPLWHGIRUPVVRPHWLPHVHYHQZLWKRXWV\PSWRPV

WRPRUHH[WHQVLYHFRQGLWLRQVZLWKVHYHUHV\PSWRPV7KHWHVWFKDUDFWHULVWLFV

FDQGLIIHUIRUSDWLHQWVZLWKVHYHUHV\PSWRPVFRPSDUHGWRSDWLHQWVZLWKOLPLWHG

V\PSWRPVDVZDVGHPRQVWUDWHGE\/DFKVDQGFROOHDJXHV ,ISDWLHQWVKDYH

EHHQVHOHFWHGEDVHGRQSUHYLRXVWHVWUHVXOWVWKHVSHFWUXPRIGLVHDVHLQWKH

UHPDLQLQJSDWLHQWVPD\EHOLPLWHG8VXDOO\SDWLHQWVZLWKYHU\VHYHUHIRUPVRI

GLVHDVHFDQEHLGHQWL¿HGHDVLO\)RUH[DPSOHD3(FDQEHODUJHREVWUXFWLQJD

ZKROHOREHDQGFDXVLQJOLIHWKUHDWHQLQJGLVHDVHRUVPDOODQGLVRODWHGORFDWHGLQ

DVXEVHJPHQWDODUWHU\FDXVLQJPLQRUFRPSODLQWV,QRXUVWXG\WKHODUJHREYLRXV

3(DQGFRPSOHWHO\QRUPDOSDWLHQWVKDYHDOUHDG\EHHQLGHQWL¿HGE\WKH94VFDQ

UHVXOWLQJLQDVXEJURXSRISDWLHQWVZLWKDOLPLWHGVSHFWUXPRIWKHGLVHDVHZKLFK

DUHPRUHGLI¿FXOWWRFODVVLI\&RQVHTXHQWO\DJHQHUDOL]DWLRQRIWKHµXQFRQGLWLRQDO¶

OLNHOLKRRGUDWLRVRIDSRVLWLYHRUQHJDWLYHWHVWRIWKH6LPSOL5(''GLPHUDVVD\ZLOO

RYHUHVWLPDWHLWVGLDJQRVWLFSHUIRUPDQFHZKHQLWLVDSSOLHGDIWHUDQRQGLDJQRVWLF

94VFDQ

2XUUHVXOWVFRXOGSRWHQWLDOO\VXIIHUIURPDVHOHFWLRQELDVDVQRWLQDOOSDWLHQWV

D¿QDOGLDJQRVLVZDVREWDLQHGDQGWKXVFRXOGQRWEHDFFRXQWHGIRULQWKH¿QDO

DQDO\VLV+RZHYHUWKHEDVHOLQHFKDUDFWHULVWLFVRIWKH¿QDOVWXG\SRSXODWLRQ

ZHUHVLPLODUWRWKRVHRIWKHLQLWLDOO\LQFOXGHGSDWLHQWV2QHFRXOGDUJXHWKDWWKH

GLIIHUHQFHVZHKDYHIRXQGDUHDFRLQFLGHQFHGXHWRVWDWLVWLFDOYDULDWLRQDQGQRW

DSSOLFDEOHWRDOOSDWLHQWVZLWKDQRQGLDJQRVWLF94VFDQ$OWKRXJKWKHQXPEHURI

SDWLHQWVLQWKHVXEJURXSVLVVPDOOZHGREHOLHYHRXUUHVXOWVDUHJHQHUDOLVDEOHDV

WKHVDPHWUHQGLVREVHUYHGIRUDOOWKUHHWHVWVH[DPLQHGDQGWKHUHLVDSODXVLEOH

ELRORJLFDOH[SODQDWLRQ

(11)





7KHYDULDWLRQVRIWHVWFKDUDFWHULVWLFVUHSRUWHGKHUHFDQKDYHFOLQLFDOLPSOLFDWLRQV

DVPDQ\FXUUHQWO\XVHGGLDJQRVWLFVWUDWHJLHVDUHEDVHGRQGHFLVLRQDQDO\VLVXVLQJ

RYHUDOOHVWLPDWHVRIWHVWFKDUDFWHULVWLFVLQVWHDGRIVXEJURXSHVWLPDWHV  )RUH[DPSOHWZRUHFHQWFRVWHIIHFWLYHQHVVDQDO\VHVWKDWFRPSDUHGGLIIHUHQW

GLDJQRVWLFVWUDWHJLHVIRUWKHGLDJQRVLVRI3(XVHGDQGDVHVWLPDWHV

IRUWKHOLNHOLKRRGUDWLRRIDQHJDWLYHWHVWEDVHGRQUHSRUWVRIWKHRYHUDOOWHVW

FKDUDFWHULVWLFV2XUUHVXOWVVXJJHVWWKDWWKHVHYDOXHVDUHFRQVLGHUDEOHORZHU

LID'GLPHUWHVWLVDSSOLHGLQSDWLHQWVZLWKDQRQGLDJQRVWLF94VFDQ7KXV

WKHLUFDOFXODWLRQVIRUDVWUDWHJ\ZLWKD'GLPHUWHVWDIWHUD94VFDQDUHSUREDEO\

RYHURSWLPLVWLF7KLVFDQKDYHLPSRUWDQWFRQVHTXHQFHVVLQFHGLDJQRVWLFVWUDWHJLHV

ZLWKWKLVWHVWVHTXHQFHFDQHUURQHRXVO\GRPLQDWHFRPSHWLQJVWUDWHJLHVOHDGLQJ

WRLQFRUUHFWUHFRPPHQGDWLRQV7KHRSWLPDOVROXWLRQWRRYHUFRPHWKLVSUREOHPLV

WRXVHWHVWFKDUDFWHULVWLFVFRQGLWLRQDORQDOOSULRULQIRUPDWLRQIRUHDFKWHVWLQD

GHFLVLRQWUHH+RZHYHUVXFKGDWDLVRIWHQODFNLQJLQFXUUHQWUHSRUWVRIGLDJQRVWLF

WHVWHYDOXDWLRQV$QDOWHUQDWLYHLVWRGRZQJUDGHWKHRYHUDOOWHVWFKDUDFWHULVWLFVRI

DWHVWZKHQDWHVWLVDSSOLHGDIWHURWKHUWHVWVLQDVWUDWHJ\DQGRUWRH[DPLQHD

UDQJHRISODXVLEOHYDOXHVLQDVHQVLWLYLW\DQDO\VLV

,QFRQFOXVLRQDOWKRXJKWKHRYHUDOOSHUIRUPDQFHRIQRQLQYDVLYHGLDJQRVWLFWHVWV

VXFKDV'GLPHUDVVD\VDQG&7VHHPSURPLVLQJWKHLUGLVFULPLQDWRU\SRZHULQ

WKHVXEJURXSRISDWLHQWVZLWKQRQGLDJQRVWLF94VFDQVLVGLVDSSRLQWLQJ,JQRULQJ

WKHVHGHSHQGHQFLHVLQGHFLVLRQDQDO\VHVFRPSDULQJGLDJQRVWLFVWUDWHJLHVFDQ

UHVXOWLQRYHURSWLPLVWLFHVWLPDWHVIRUQRQLQYDVLYHVWUDWHJLHVDQGWKXVUHVXOWLQ

HUURQHRXVUHFRPPHQGDWLRQV

(12)





5HIHUHQFHV

0RRQV.*YDQ(V*$'HFNHUV-:+DEEHPD-'*UREEHH'( 

/LPLWDWLRQVRIVHQVLWLYLW\VSHFL¿FLW\OLNHOLKRRGUDWLRDQGED\HV¶WKHRUHPLQDVVHVVLQJGLDJQRVWLF

SUREDELOLWLHVDFOLQLFDOH[DPSOH

(SLGHPLRORJ\

6DQVRQ%-/LMPHU-*0DF*LOODYU\057XUNVWUD)3ULQV0+%XOOHU+5 

&RPSDULVRQRIDFOLQLFDOSUREDELOLW\HVWLPDWHDQGWZRFOLQLFDOPRGHOVLQSDWLHQWVZLWKVXVSHFWHG

SXOPRQDU\HPEROLVP$17(/23(6WXG\*URXS

7KURPE+DHPRVW

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

6XVSHFWHGSXOPRQDU\HPEROLVPSUHYDOHQFHDQGDQDWRPLFGLVWULEXWLRQLQFRQVHFXWLYH

SDWLHQWV$GYDQFHVLQ1HZ7HFKQRORJLHV(YDOXDWLQJWKH/RFDOLVDWLRQRI3XOPRQDU\(PEROLVP

$17(/23( *URXS

5DGLRORJ\

0DF*LOODYU\05GH0RQ\H:/LMPHU-*1LHXZHQKXL]HQ:%XOOHU+5%UDQGMHV'30HWDO 

&OLQLFDO(YDOXDWLRQRID0RQRFORQDO$QWLERG\%DVHG(Q]\PH,PPXQRDVVD\IRU)LEULQ

'HJUDGDWLRQ3URGXFWVLQ3DWLHQWVZLWK&OLQLFDOO\6XVSHFWHG3XOPRQDU\(PEROLVP

7KURPE+DHPRVWDV

/HQVLQJ$:$3UDQGRQL3%UDQGMHV'30+XLVPDQ309LJR07RPDVHOOD*HWDO  'HWHFWLRQRIGHHSYHLQWKURPERVLVE\UHDOWLPH%PRGHXOWUDVRQRJUDSK\

1(QJO-0HG

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

&HQWUDOSXOPRQDU\WKURPERHPEROLVPGLDJQRVLVZLWKVSLUDOYROXPHWULF&7ZLWKWKHVLQJOH

EUHDWKKROGWHFKQLTXHFRPSDULVRQZLWKSXOPRQDU\DQJLRJUDSK\

5DGLRORJ\

/HQVLQJ$:$YDQ%HHN(-5'HPHUV&7LHOYDQ%XXO00&<DNHPFKXN9YDQ'RQJHQ$HW

DO

9HQWLODWLRQSHUIXVLRQOXQJVFDQQLQJDQGWKHGLDJQRVLVRISXOPRQDU\HPEROLVPLPSURYHPHQWRI

REVHYHUDJUHHPHQWE\WKHXVHRIDOXQJVHJPHQWUHIHUHQFHFKDUW

7KURPE+DHPRVWDV

+XOO5'+LUVK-&DUWHU&-5DVNRE*(*LOO*--D\50HWDO 

'LDJQRVWLFYDOXHRIYHQWLODWLRQSHUIXVLRQOXQJVFDQQLQJLQSDWLHQWVZLWKVXVSHFWHGSXOPRQDU\

HPEROLVP

&KHVW

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

)HDVLELOLW\VDIHW\DQGFOLQLFDOXWLOLW\RIDQJLRJUDSK\LQSDWLHQWVZLWKVXVSHFWHGSXOPRQDU\

HPEROLVP

(XU5DGLRO

.UDHPHU+& 

(YDOXDWLQJPHGLFDOWHVWVREMHFWLYHDQGTXDQWLWDWLYHJXLGHOLQHV

1HZEXU\SDUN6$*(SXEOLFDWLRQVLQF

%UHVORZ1('D\1( 

6WDWLVWLFDOPHWKRGVLQFDQFHUUHVHDUFKYROXPH,7KHDQDO\VLVRIFDVHFRQWUROVWXGLHV

/\RQ,QWHUQDWLRQDO$JHQF\IRU5HVHDUFKRQ&DQFHU

/DFKV061DFKDPNLQ,(GHOVWHLQ3+*ROGPDQ-)HLQVWHLQ$56FKZDUW]-6 

6SHFWUXPELDVLQWKHHYDOXDWLRQRIGLDJQRVWLFWHVWVOHVVRQVIURPWKHUDSLGGLSVWLFNWHVWIRU

XULQDU\WUDFWLQIHFWLRQ

$QQ,QWHUQ0HG

3HUULHU$%XVZHOO/%RXQDPHDX[+'LGLHU'0RUDELD$GH0RHUORRVH3HWDO 

&RVWHIIHFWLYHQHVVRIQRQLQYDVLYHGLDJQRVWLFDLGVLQVXVSHFWHGSXOPRQDU\HPEROLVP

$UFK,QWHUQ0HG

(13)





5DDE66+RUQEHUJHU- 

7KHHIIHFWRIDSDWLHQW¶VULVNWDNLQJDWWLWXGHRQWKHFRVWHIIHFWLYHQHVVRIWHVWLQJVWUDWHJLHVLQWKH

HYDOXDWLRQRISXOPRQDU\OHVLRQV

&KHVW

5HPHU(02EXFKRZVNL1(OOLV-'5LFH7:$GHOVWHLQ'-%DNHU0( 

$GUHQDOPDVVHYDOXDWLRQLQSDWLHQWVZLWKOXQJFDUFLQRPDDFRVWHIIHFWLYHQHVVDQDO\VLV

$-5$P-5RHQWJHQRO

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