• No results found

Studies on leptospirosis : clinical aspects and pathophysiology - Chapter 10: Rapid serologic assays for leptospirosis are of limited value in southern Vietnam.

N/A
N/A
Protected

Academic year: 2021

Share "Studies on leptospirosis : clinical aspects and pathophysiology - Chapter 10: Rapid serologic assays for leptospirosis are of limited value in southern Vietnam."

Copied!
13
0
0

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

Hele tekst

(1)

UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl)

UvA-DARE (Digital Academic Repository)

Studies on leptospirosis : clinical aspects and pathophysiology

Wagenaar, J.F.P.

Publication date

2010

Link to publication

Citation for published version (APA):

Wagenaar, J. F. P. (2010). Studies on leptospirosis : clinical aspects and pathophysiology.

General rights

It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons).

Disclaimer/Complaints regulations

If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.

(2)

5DSLGVHURORJLFDODVVD\VIRUOHSWRVSLURVLVDUHRI

OLPLWHGYDOXHLQVRXWKHUQ9LHWQDP

-)3:DJHQDDU7+))DONH191DP74%LQK+/6PLWV)*- &REHOHQVDQG3-GH9ULHV 'LYLVLRQRI,QIHFWLRXV'LVHDVHV7URSLFDO0HGLFLQHDQG$,'6$FDGHPLF0HGLFDO&HQWHU $PVWHUGDPWKH1HWKHUODQGV %LQK7KXDQ3URYLQFLDO0DODULD6WDWLRQ3KDQ7KLHW%LQK7KXDQ3URYLQFH9LHWQDP 7URSLFDO'LVHDVHV&OLQLFDO5HVHDUFK&HQWHU&KR5D\+RVSLWDO+R&KL0LQK&LW\9LHWQDP 5R\DO7URSLFDO,QVWLWXWH .,7 .,7ELRPHGLFDO5HVHDUFK$PVWHUGDPWKH1HWKHUODQGV 7URS0HG 3DUDVLWRORJ\  



&+$37(5

(3)

&KDSWHU



/HSWRVSLURVLV DOWKRXJK XELTXLWRXV DQG SRWHQWLDOO\ OHWKDO LV RIWHQ QRW GLDJQRVHG 7KHVHURSUHYDOHQFHRIDQWL/HSWRVSLUDDQWLERGLHVDQGWKHXWLOLW\RIWZRUDSLGWHVWV IRUWKHVHURGLDJQRVLVRIWKHGLVHDVHZHUHVWXGLHGLQ%LQK7KXDQDQDUHDLQVRXWKHUQ 9LHWQDPZLWKIDYRXUDEOHFRQGLWLRQVIRU/HSWRVSLUD,QDQLQLWLDOVXUYH\EORRGVDPSOHV IURP  SDWLHQWV ZLWK XQGLIIHUHQWLDWHG IHYHU DQG  KHDOWK\ VXEMHFWV ZHUH HDFK H[DPLQHGIRUDQWL/HSWRVSLUDDQWLERGLHVXVLQJWKUHHWHVWVDQ(/,6$DODWH[FDUG DJJOXWLQDWLRQWHVW 'UL'RW‹ DQGDODWHUDOÁRZDVVD\ /HSWR7HN/DWHUDO)ORZ‹ ,Q WKH(/,6$VDPSOHVIURPRIWKHKHDOWK\VXEMHFWVDQGRIWKHIHEULOHSDWLHQWV ZHUHIRXQGWRKDYHWLWUHVRIDQWL/HSWRVSLUD,J0RIDWOHDVW2QO\RQHRIWKH SDWLHQWVFKHFNHGDJDLQLQ(/,6$ZHHNVODWHUVKRZHGWKHPDUNHGLQFUHDVHLQ,J0 WLWUHWKDWLVLQGLFDWLYHRIDFXWHOHSWRVSLURVLV ,QWKHLQLWLDOVXUYH\DOWKRXJKWKHSRVLWLYHUHVXOWVRIWKHODWHUDOÁRZDVVD\DSSOLHG WR ZKROH EORRG DQG VHUXP VKRZHG D JRRG DJUHHPHQW ZLWK WKRVH RI WKH (/,6$ NDSSD   WKH UHVXOWV RI WKH ODWHUDOÁRZ DVVD\ ZHUH RIWHQ LQGHWHUPLQDWH 7KH FDUGDJJOXWLQDWLRQ WHVW ZDV PRUH VSHFLÀF 7KH RYHUDOO DJUHHPHQW EHWZHHQ WKHUHVXOWVRIWKHUDSLGWHVWVDQGWKRVHRIWKH(/,6$ZDVJHQHUDOO\SRRU:KHQWKH VDPSOHV FODVVLÀHG DV ¶LQGHWHUPLQDWH· LQ WKH ODWHUDOÁRZ DVVD\ ZHUH FRQVLGHUHG SRVLWLYHWKHPD[LPXPNDSSDYDOXHIRUWKLVDVVD\DSSOLHGWRZKROHEORRGZDVRQO\  ,Q FRQFOXVLRQ LW DSSHDUV WKDW KLJK VHURSUHYDOHQFHV RI DQWL/HSWRVSLUD ,J0 DQG ORZ LQFLGHQFHV RI DFXWH OHSWRVSLURVLV OLPLW WKH GLDJQRVWLF YDOXH RI WKH UDSLG WHVWVWKDWZHUHLQYHVWLJDWHG7KHODWHUDOÁRZDVVD\LVQRWVSHFLÀFHQRXJK7KHFDUG DJJOXWLQDWLRQWHVWLVSRVVLEO\EHWWHUEXWEHFDXVHRIWKHORZLQFLGHQFHLWVVHQVLWLYLW\ FRXOGQRWEHHYDOXDWHGDGHTXDWHO\LQWKHSUHVHQWVWXG\

(4)

5DSLGVHURORJLFDODVVD\VIRUOHSWRVSLURVLVDUHRIOLPLWHGYDOXHLQVRXWKHUQ9 LHWQDP  $OWKRXJKKXPDQOHSWRVSLURVLVLVXELTXLWRXVDQGSRWHQWLDOO\IDWDOLWVFOLQLFDOGLDJQRVLV PD\EHGLIÀFXOWDQGWKLVRIWHQOHDGVWRXQGHUUHSRUWLQJHYHQLQRXWEUHDNVRIVHYHUH GLVHDVH  7UHDWPHQWZLWKDQWLELRWLFVHVSHFLDOO\LILQLWLDWHGHDUO\LQWKHGLVHDVH PD\EHEHQHÀFLDODOWKRXJKWKHHYLGHQFHIRUWKLVLVVFDQW\  ,QVSHFLDOLVHGZHOO HTXLSSHGODERUDWRULHVDGLDJQRVLVRIOHSWRVSLURVLVFDQEHFRQÀUPHGE\PLFURVFRSLF DJJOXWLQDWLRQWHVWV 0$7 DQGWKHLVRODWLRQRIOHSWRVSLUDH  ,QSULPDU\KHDOWKFDUH VHWWLQJVKRZHYHUHYHQ(/,6$PD\EHLPSRVVLEOHRUWRRODERULRXVDQGVXFKOLPLWDWLRQV KDYHVWLPXODWHGWKHGHYHORSPHQWDQGPDUNHWLQJRIVHYHUDOUDSLGWHVWVIRUGLDJQRVLQJ OHSWRVSLURVLV

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ÁRZDVVD\ WRHYDOXDWHWKHGLDJQRVWLFDFFXUDF\RIWKHUDSLGWHVWV 7KHODWHUDOÁRZWHVWZDVDSSOLHGQRWRQO\WRVHUDEXWDOVRWRVDPSOHVRIZKROHEORRG ZKLFKFDQEHFROOHFWHGHDVLO\IURPÀQJHUSULFNV  6WXG\6LWH 7KHSURYLQFHRI%LQK7KXDQOLHVE\WKH6RXWK&KLQD6HDLQVRXWKHUQ9LHWQDP)RUHVWHG PRXQWDLQVFRYHUKDOIWKHSURYLQFHEXWWKHRWKHUORZODQGDUHDVKDYHODUJHO\EHHQ GHYHORSHGDVULFHSDGGLHVDQGRUFKDUGVLQVPDOOVFDOHIDUPV0RVWRIWKHIDUPHUVDOVR UDLVHVRPHSLJVFDWWOHRUSRXOWU\)RUWKHSUHVHQWVWXG\VHURVXUYH\VZHUHFRQGXFWHG DPRQJDSSDUHQWO\KHDOWK\VXEMHFWVIURPWKHUXUDOFRPPXQHVRI+DP0\DQG7UD7DQ DQGDPRQJIHEULOHSDWLHQWVIURP+DP0\RUWKHPDODULDFOLQLFLQ3KDQ7KLHWWKH SURYLQFLDOFDSLWDO

,1752'8&7,21

68%-(&76$1'0(7+2'6

(5)

&KDSWHU



6XEMHFWV

7R EH FRQVLGHUHG D IHEULOH SDWLHQW DQ LQGLYLGXDO KDG WR SUHVHQW ZLWK D D[LOODU\ WHPSHUDWXUHRI!ƒ&DQGWRKDYHEHHQIHEULOHIRUZHHNV3DWLHQWVIRXQGVPHDU SRVLWLYHIRUPDODULD E\PLFURVFRS\ WKRVHZLWKVHYHUHGLVHDVHUHTXLULQJUHIHUUDO VXFK DVPHQLQJLWLVRUVHSVLV RUVLJQVDQGV\PSWRPVLQGLFDWLQJDVSHFLÀFORFDOLVHGGLVHDVH VXFKDVWRQVLOOLWLVSQHXPRQLDDEVFHVVHVSHULWRQLWLVDUWKULWLVS\HORQHSKULWLV RU FKURQLFXQGHUO\LQJFRQGLWLRQVVXFKDVUHQDORUKHSDWLFGLVHDVHGLDEHWHV PHOOLWXV +,9 LQIHFWLRQ DQG WKRVH WDNLQJ LPPXQRVXSSUHVVLYH PHGLFDWLRQ ZHUH H[FOXGHG 7UHDWPHQW ZLWK DPR[LFLOOLQ ZDV LQLWLDWHG XSRQ FOLQLFDO VXVSLFLRQ RI OHSWRVSLURVLV ,QIRUPHGFRQVHQWZDVREWDLQHGIURPDOOSDUWLFLSDQWVRUWKHLUFDUHJLYHUV 7KHVWXG\SURWRFROZDVDSSURYHGE\WKHVFLHQWLÀFERDUGRI&KR5D\+RVSLWDOLQ+R&KL 0LQK&LW\WKH9LHWQDPHVH0LQLVWU\RI+HDOWKDQGWKH%LQK7KXDQSURYLQFLDOKHDOWK DXWKRULWLHV 6DPSOHV ,QWKHLQLWLDOVXUYH\YHQRXVEORRGZDVGUDZQIURPDOOSDUWLFLSDQWV$VHFRQGEORRG VDPSOHZDVFROOHFWHGIURPVRPHRIWKHIHEULOHSDWLHQWVDIWHUZHHNV6HUXPZDV VHSDUDWHGE\LPPHGLDWHFHQWULIXJDWLRQDWWKHVWXG\VLWHDQGVWRUHGDWƒ& (/,6$

$Q (/,6$ IRU WKH GHWHFWLRQ RI DQWL/HSWRVSLUD ,J0 ZDV SHUIRUPHG XVLQJ DQWLJHQ SUHSDUHG

IURPWKH3DWRF,VWUDLQRI/ELÁH[D  6HUDJLYLQJWLWUHVRIRUKLJKHUZHUH FRQVLGHUHG SRVLWLYH $ WZRIROG RU JUHDWHU LQFUHDVH LQ WLWUHV DIWHU  ZHHNV ZDV FRQVLGHUHGLQGLFDWLYHRI¶DFXWHOHSWRVSLURVLV· /DWHUDO)ORZDVVD\ %RWKVHUDDQGZKROHEORRGVDPSOHVZHUHWHVWHGXVLQJWKH/HSWR7HN/DWHUDO)ORZŠ DVVD\ 2UJDQRQ7HNQLND'XUKDP1& 7KLVRQHVWHSFROORLGDOJROGLPPXQRDVVD\ LVEDVHGRQWKHELQGLQJRIVSHFLÀF,J0DQWLERGLHVWRLPPRELOL]HGDQWLJHQIURPWKH 3DWRF,VWUDLQ  7KHERXQG,J0DQWLERGLHVDUHGHWHFWHGXVLQJDQWL,J0DQWLERGLHV WKDWDUHFRQMXJDWHGWRPRELOHUHGSDUWLFOHVRIFROORLGDOJROG

(6)

5DSLGVHURORJLFDODVVD\VIRUOHSWRVSLURVLVDUHRIOLPLWHGYDOXHLQVRXWKHUQ9

LHWQDP



6HUXP  —O  RU ZKROH EORRG  —O  ZDV GUDZQ LQWR D KHSDULQL]HG FDSLOODU\ DQG WKHQVSRWWHGRQWKHSDGLQWKHURXQGVDPSOHSRUWEHIRUH—ORIUXQQLQJEXIIHU ZHUHDGGHG5HVXOWVZHUHUHDGDIWHUPLQ,QWKHSUHVHQFHRIDSRVLWLYHFRQWURO OLQHVSHFLÀFDQWL/HSWRVSLUD,J0DQWLERGLHVDUHLQGLFDWHGE\WKHDSSHDUDQFHRID GLVWLQFWFRORXUHGOLQHLQWKHWHVW]RQH6DPSOHVJLYLQJKD]\OLQHVZHUHFODVVLÀHGDV LQGHWHUPLQDWH &DUGDJJOXWLQDWLRQWHVW 6HUDZHUHDOVRWHVWHGXVLQJWKH'UL'RWŠFDUGDJJOXWLQDWLRQWHVW 2UJDQRQ7HNQLND  ,QWKLVWHVW/HSWRVSLUDVSHFLÀFDQWLERGLHVDUHGHWHFWHGZKHQWKH\DJJOXWLQDWHEOXH ODWH[SDUWLFOHVWKDWKDYHEHHQFRDWHGZLWKDQWLJHQIURPWKH/HO\VWUDLQ   $GU\VSRWRIWKHVHODWH[SDUWLFOHVDIÀ[HGWRDZKLWHFDUGZDVPL[HGZLWK—O VHUXPVWLUULQJZLWKDVSDWXOD$IWHUJHQWO\VZLUOLQJWKHVXVSHQVLRQVIRUVHDFK WHVWVSRWZDVVFRUHGSRVLWLYHQHJDWLYHRULQGHWHUPLQDWHDFFRUGLQJWRWKHGHJUHHRI DJJOXWLQDWLRQREVHUYHG 'DWD$QDO\VLV 9HUVLRQRIWKH6366VRIWZDUHSDFNDJH 6366,QF&KLFDJR,/ ZDVXVHGIRUDOO WKH GDWD DQDO\VLV 7KH UHVXOWV RI WKH UHVSHFWLYH WHVWV ZHUH FRPSDUHG /HYHOV RI DJUHHPHQW EHWZHHQ WKH WHVWV ZHUH HYDOXDWHG E\ FDOFXODWLQJ &RKHQ·V NDSSD Κ  6HQVLWLYLWLHVVSHFLÀFLWLHVDQGSUHGLFWLYHYDOXHVZHUHQRWFDOFXODWHGEHFDXVH(/,6$LV QRWXQHTXLYRFDOO\WKH¶JROGVWDQGDUG·LQWKHGLDJQRVLVRIOHSWRVSLURVLV )RUW\ÀYHIHEULOHSDWLHQWV³IHPDOHVDQGPDOHVZLWKDPHDQDJH UDQJH RI  ² \HDUV³ZHUHHQUROOHG1LQHWHHQRIWKHSDWLHQWVZHUHIDUPHUVRUIRUHVW ODERXUHUV7HQSDWLHQWVDFNQRZOHGJHGUHFHQWFRQWDFWZLWKIUHVKZDWHU7KHPHDQ GXUDWLRQRILOOQHVVZDVGD\V UDQJH ²GD\V ,QWKHLQLWLDOVXUYH\EORRGVDPSOHV ZHUHREWDLQHGIURPSDWLHQWV7KUHHZHHNVODWHUSDWLHQWVZHUHUHWHVWHGZLWK WKH UDSLG WHVWV DQG  ZLWK WKH (/,6$ 7KH  DSSDUHQWO\ KHDOWK\ VXEMHFWV ZHUH

5(68/76

(7)

&KDSWHU



IDUPHUVRUFKLOGUHQRIIDUPHUV PDOHVDQGIHPDOHVDJHG\HDUV HDFK ZLWKDKLVWRU\RIDWOHDVWRQHHSLVRGHRIXQGLIIHUHQWLDWHGIHYHULQWKHSUHYLRXV\HDU 7KH VHURSUHYDOHQFHV RIDQWL/HSWRVSLUD,J0 DVGHWHFWHG LQ WKH(/,6$ZHUH KLJK DPRQJWKHKHDOWK\VXEMHFWVDQGDPRQJWKHSDWLHQWV7KHWLWUHVVHHQLQWKH LQLWLDOVXUYH\ZHUHKRZHYHUQHYHUKLJKHUWKDQ2QHSDWLHQWDVXVSHFWHGFDVH RIOHSWRVSLURVLVZKRZDVWUHDWHG ZLWKDPR[LFLOOLQZDVFRQÀUPHGDVKDYLQJ DFXWH OHSWRVSLURVLVE\DIRXUIROGLQFUHDVHLQ,J0WLWUHDIWHUZHHNV7KLVSDWLHQWKRZHYHU ZDVVFRUHGQHJDWLYHDQGWKHQ ZHHNVODWHU LQGHWHUPLQDWHLQWKHODWHUDOÁRZDVVD\ ERWK LQ WHVWV RI VHUXP DQG ZKROH EORRG  DQG FRQVLVWHQWO\ QHJDWLYH LQ WKH FDUG DJJOXWLQDWLRQWHVWV 7KHIXOOUHVXOWVRIWKHLQLWLDOVXUYH\DQGWKHUHWHVWLQJRIVRPHRIWKHSDWLHQWVZHHNV ODWHUDUHVXPPDUL]HGLQWKH7DEOH7KH)LJXUHVKRZVKRZWKHUHVXOWVRIWKHUDSLG WHVWVFRPSDUHZLWKWKRVHRIWKH,J0(/,6$7KHVDPSOHVVFRUHG¶LQGHWHUPLQDWH·LQ WKHUDSLGWHVWVZKLFKZHUHPRUHFRPPRQZLWKWKHODWHUDOÁRZDVVD\WKDQWKHFDUG DJJOXWLQDWLRQWHVWUHTXLUHGUHVFRULQJDVSRVLWLYHRUQHJDWLYHIRUWKHGDWDDQDO\VLV (YDOXDWLRQRIWKHOHYHOVRIDJUHHPHQWEHWZHHQDSRVLWLYHUHVXOWLQWKH,J0(/,6$ LH DWLWUHRI• DQGDSRVLWLYHUHVXOWLQDUDSLGWHVWH[SUHVVHGDV.YDOXHVZDV RFFDVLRQDOO\XQIHDVLEOHEHFDXVHWKHUHZHUHWRRIHZSRVLWLYHUHVXOWV7KHKLJKHVWYDOXH RI.REVHUYHGIRUVXFKDFRPSDULVRQZDV VHHQIRUWKHFRPSDULVRQEHWZHHQ WKH(/,6$DQGWKHODWHUDOÁRZDVVD\ZKHQWKHVDPSOHVFODVVLÀHGDV¶LQGHWHUPLQDWH· LQWKHODWHUDOÁRZDVVD\ZHUHFRQVLGHUHGSRVLWLYH )RUWKHODWHUDOÁRZDVVD\WKH UHVXOWVREWDLQHGZKHQZKROHEORRGZDVWHVWHGVKRZHGUHDVRQDEOHDJUHHPHQWZLWK WKRVH VHHQ ZKHQ VHUXP ZDV WHVWHG QRWDEO\ DIWHU UHFODVVLI\LQJ WKH LQGHWHUPLQDWH VDPSOHVDVSRVLWLYH .  

(8)

5DSLGVHURORJLFDODVVD\VIRUOHSWRVSLURVLVDUHRIOLPLWHGYDOXHLQVRXWKHUQ9 LHWQDP  7DEOH/HSWRVSLURVLVDQWLERGLHVLQVHUDRIKHDOWK\VXEMHFWVDQGIHEULOHSDWLHQWV /DWHUDOÁRZDVVD\EDVHGRQ (/,6$ 6HUXP :KROHEORRG &DUG DJJOXWLQDWLRQ WHVW  'D\ 'D\ 'D\ 'D\ 'D\ 'D\ 'D\ 'D\ 1RDQG  RIVDPSOHV IURPKHDOWK\VXEMHFWV 7HVWHG         6FRUHGSRVLWLYH   B   B   B   B 6FRUHGQHJDWLYH   B   B   B   B 6FRUHGLQGHWHUPLQDWH   B   B   B   B 1RDQG  RIVDPSOHV IURPIHEULOHSDWLHQWV 7HVWHG         6FRUHGSRVLWLYH                 6FRUHGQHJDWLYH                 6FRUHGLQGHWHUPLQDWH                 /HSWRVSLUDDQWLERGLHVLQWKHVHUDRIKHDOWK\VXEMHFWVDQGIHEULOHSDWLHQWVDVGHWHFWHGE\(/,6$ GHWHFWLQJ DQWL/HSWRVSLUD ,J0 LQ VHUD  WKH /HSWR7HN /DWHUDO )ORZ DVVD\ GHWHFWLQJ VSHFLÀF ,J0LQEORRGRUVHUXP DQGWKH'UL'RWWHVWFDUGDJJOXWLQDWLRQWHVW GHWHFWLQJDQWL/HSWRVSLUD DJJOXWLQDWLQJDQWLERGLHVLQVHUD 6DPSOHVZHUHFROOHFWHGIURPDOOWKHVXEMHFWVGXULQJDQLQLWLDO VXUYH\ GD\ DQGIURPVRPHRIWKHSDWLHQWVZHHNVODWHU GD\

(9)

&KDSWHU  )LJXUH $FRPSDULVRQRIWKHUHVXOWVRIWKHU DSLGWHVWV $ FRPSDULVRQ RI WKH UHVXOWV RI WKH UDSLG WHVWV  WKH WHVWLQJ RI VHUD ZLWK WKH 'UL 'RW FDUGDJJOXWLQDWLRQ WHVW DQG WKH WHVWLQJ RI VHUD DQG ZKROH EORRGZLWKWKH/HSWR7 HN/DWHUDO)ORZDVVD\²ZLWKWKHWLWUHVREWDLQHGLQWKH,J0(/,6$ 7KH GDWD SRLQWV VKRZ UHVXOWV IRU WKH KHDOWK\ VXEMHFWV Á  DQG IRU WKH SDWLHQWV ZLWK XQGLIIHUHQWLDWHG IHYHU ZKHQ WKH\ ZHUH WHVWHG XSRQ SUHVHQWDWLRQDWDSULPDU\KHDOWKFDUHIDFLOLW\ Ú RUWKUHHZHHNVODWHU Þ               SRVL WLYH       ,QGHWHU P QHJDWLYH QHJDWLYH QHJDWLYH ,QGHWHUP ,QGHWHUP SRV LWLYH SRV LWLYH /DWHU DOIOR Z RQEOR RG /DWHU DOIOR Z RQVH UXP 'UL'RW 5HFLSURFD O( /,6$ WLWU H SRVL WLYH SRVL WLYH       ,QGHWHU P ,QGHWHU P QHJDWLYHQHJDWLYH QHJDWLYHQHJDWLYH QHJDWLYHQHJDWLYH ,QGHWHUP,QGHWHUP ,QGHWHUP,QGHWHUP SRV LWLYH SRV LWLYH SRV LWLYH SRV LWLYH /DWHU DOIOR Z RQEOR RG /DWHU DOIOR Z RQVH UXP 'UL'RW 5HFLSURFD O( /,6$ WLWU H

(10)

5DSLGVHURORJLFDODVVD\VIRUOHSWRVSLURVLVDUHRIOLPLWHGYDOXHLQVRXWKHUQ9 LHWQDP  $OWKRXJKWKHSUHVHQWUHVXOWVLQGLFDWHDKLJKVHURSUHYDOHQFHRIDQWL/HSWRVSLUD,J0 DPRQJDSSDUHQWO\KHDOWK\VXEMHFWVLQ%LQK7KXDQSURYLQFHRQO\RQHRIWKHSDWLHQWV WHVWHGWZLFHZLWKDZHHNLQWHUYDODSSHDUHGWRKDYHDFXWHOHSWRVSLURVLV6LPLODUO\ 9DQHWDO  IRXQGRIWKHLUVXEMHFWVIURPWKH0HNRQJGHOWDWREHVHURSRVLWLYH LQ D /HSWRVSLUDVSHFLÀF 0$7 EXW VDZ QR LQGLFDWLRQV RI DFXWH OHSWRVSLURVLV 7KLV FRPELQDWLRQRIKLJKVHURSUHYDOHQFHVEXWORZLQFLGHQFHVRIDFXWHGLVHDVHKDYHEHHQ VHHQHOVHZKHUHLQ6RXWK²HDVW$VLD  ,WLVDFRPELQDWLRQWKDWQHJDWHVWKHXVH RIVLQJOHVDPSOH,J0(/,6$GHVSLWHWKHFRQÀUPHGGLDJQRVWLFYDOXHRIVXFKWHVWVLQ RWKHUHSLGHPLRORJLFDOVLWXDWLRQV  ,QWKHSUHVHQWVWXG\DUHDUDLVLQJWKHFXWRII WKUHVKROGIRUSRVLWLYLW\LQWKH(/,6$WRFRPSHQVDWHIRUWKHORZVSHFLÀFLW\ZRXOG UHGXFHWKHVHQVLWLYLW\WROHYHOVWKDWDUHXVHOHVV VHH)LJXUH $OWKRXJKWKHGLDJQRVWLF DFFXUDF\RI(/,6$FDQEHLPSURYHGE\WHVWLQJERWK¶DFXWH·DQG¶FRQYDOHVFHQW·VHUD SDLUHGVHUDDUHRIWHQGLIÀFXOWWRFROOHFWDQGGHOD\LQJGLDJQRVLVXQWLODIWHUFROOHFWLRQ RIWKHFRQYDOHVFHQWVDPSOHLVOLNHO\WRKDYHDQHJDWLYHLPSDFWRQWKHSURJQRVLV   ,QHDUOLHULQYHVWLJDWLRQVLQZKLFKWKHUHVXOWVRI0$7ZHUHXVHGDVWKH¶JROGVWDQGDUG· WKHODWHUDOÁRZDVVD\ZDVIRXQGWRKDYHDVHQVLWLYLW\RIDQGDVSHFLÀFLW\RI ZKHUHDVWKHFDUGDJJOXWLQDWLRQWHVWKDGDVHQVLWLYLW\RI²DQGDVSHFLÀFLW\ RI  ,QWKHSUHVHQWVWXG\LWZDVSHUKDSVQRWVXUSULVLQJWKDWWKHKLJK IUHTXHQFLHVRISRVLWLYLW\LQWKHODWHUDOÁRZDVVD\SDUDOOHOHGWKHKLJKVHURSUHYDOHQFHV UHFRUGHGZLWKWKH,J0(/,6$VLQFHERWKDVVD\VDUHEDVHGRQWKHGHWHFWLRQRIVSHFLÀF ,J0DQWLERGLHV DQGWKHUHIRUHKDYHUHODWLYHO\ORZVSHFLÀFLWLHVIRUWKHGLDJQRVLVRI FOLQLFDOOHSWRVSLURVLV $VLVVKRZQLQWKH)LJXUHWKHFDUGDJJOXWLQDWLRQWHVWZKLFK LV EDVHG RQ WKH GHWHFWLRQ RI VSHFLÀF DJJOXWLQDWLQJ DQWLERGLHV ZDV PRUH VSHFLÀF 7KHKLJKVHURSUHYDOHQFHVUHFRUGHGDPRQJWKHKHDOWK\VXEMHFWVRIWKHSUHVHQWVWXG\ LQGLFDWHV UHSHDWHG H[SRVXUH RI WKH SRSXODWLRQ WR OHSWRVSLUDH ZKLFK LV SODXVLEOH FRQVLGHULQJ WKH PDQ\ ULVN IDFWRUV ³ VXFK DV ZHWULFH FXOWLYDWLRQ KLJK DQLPDO GHQVLWLHV DQG WKH PRQVRRQ FOLPDWH ³ LQ %LQK 7KXDQ   /HSWRVSLURVLV DSSHDUV WR EH DVVRFLDWHG ZLWK WKH PRQVRRQ VHDVRQ ZKHQ WKH JHQHUDO VHURSUHYDOHQFH RI /HSWRVSLUDVSHFLÀF,J0DOVRVKRZVDVHDVRQDOSHDN  7KDWWKHSUHVHQWVWXG\ZDV FDUULHG RXW EHIRUH WKH PRQVRRQ PD\ EH RQH UHDVRQ ZK\ WKH LQFLGHQFH RI DFXWH

',6&866,21

(11)

&KDSWHU



OHSWRVSLURVLV REVHUYHG ZDV ORZ 7KH ORZ LQFLGHQFH RI FRQÀUPHG DFXWH GLVHDVH PD\ KRZHYHU DOVR LQGLFDWH LPPXQLW\ SHUKDSV LQGXFHG E\ UHSHDWHG H[SRVXUH WR UHODWLYHO\QRQSDWKRJHQLFVHURJURXSVDQGSUHYHQWLQJFRPSOLFDWHGGLVHDVHDQGPDMRU RXWEUHDNV7KLV VFHQDULR ZKLFK LV FRPSDUDEOH ZLWK WKDW RI KRORHQGHPLF PDODULD RUVHYHUDOSDUDVLWLFLQIHFWLRQVRIFKLOGKRRGFRXOGEHFRQÀUPHGE\GHPRQVWUDWLQJ GHFUHDVLQJLQFLGHQFHRIGLVHDVHDQGLQFUHDVLQJVHURSUHYDOHQFHZLWKLQFUHDVLQJDJH $OWKRXJK DJHGHSHQGHQW FKDQJHV LQ VHURSUHYDOHQFH PD\ EH PRUH DSSDUHQW LQ ,J* DQWLERGLHVWKDQLQ,J0DQWL/HSWRVSLUD,J0PD\UHPDLQGHWHFWDEOHIRUVHYHUDO\HDUV SRVWLQIHFWLRQ  7KHSRVVLELOLW\WKDWWKHDSSDUHQWO\KLJKVHURSUHYDOHQFHVRI DQWL/HSWRVSLUD,J0REVHUYHGLQWKHSUHVHQWVWXG\DQGVHYHUDORWKHULQYHVWLJDWLRQV LVWKHUHVXOWRIFURVVUHDFWLYLW\ZLWKWKHSDWKRJHQVFDXVLQJRWKHUHQGHPLFGLVHDVHV VXFKDVGHQJXHFDQQRWEHH[FOXGHG  

0DQ\ GLIÀFXOWLHV UHPDLQ IRU WKRVH DWWHPSWLQJ WR GLDJQRVH DFXWH OHSWRVSLURVLV SDUWLFXODUO\DWWKHOHYHORISULPDU\KHDOWKFDUHLQKLJKO\HQGHPLFDUHDV  ,Q LQGXVWULDOL]HGFRXQWULHVZKHUHOHSWRVSLUDOLQIHFWLRQLVUDUHDQGXQGHUWKHRSWLPDO FRQGLWLRQV WR EH IRXQG LQ UHIHUUDO ODERUDWRULHV DQG VHUXP EDQNV WKH UDSLG WHVWV KDYHEHHQIRXQGWREHVXIÀFLHQWO\VHQVLWLYHDQGVSHFLÀF  7KHWHVWVKDYH DOVREHHQIRXQGXVHIXOLQVRPHHQGHPLFDUHDV  ,QKLJKO\HQGHPLFDUHDV KRZHYHU OHSWRVSLURVLV VHURORJ\ UHPDLQV IDU IURP RSWLPDO DQG FXWRII OHYHOV KDYH WREHUDLVHGWKHUHE\WKUHDWHQLQJVHQVLWLYLW\  ,QWKHSUHVHQWVWXG\WKHFDUG DJJOXWLQDWLRQWHVWZKLFKGHWHFWVQRWRQO\,J0EXWDOVR,J*ZDVOHVVDIIHFWHGE\WKH KLJKVHURSUHYDOHQFHWKDQWKHODWHUDOÁRZDVVD\:KHWKHUWKHFDUGDJJOXWLQDWLRQWHVW KDVDGHTXDWHVHQVLWLYLW\HVSHFLDOO\ZKHQFXWRIIOHYHOVKDYHWREHLQFUHDVHGQHHGV IXUWKHUVWXG\ ,QFRQFOXVLRQWKHKLJKVHURSUHYDOHQFHRIDQWL/HSWRVSLUD,J0DQWLERGLHVLQVRXWKHUQ 9LHWQDP OLPLWHG WKH DELOLW\ RI D UHFHQWO\ GHYHORSHG ODWHUDOÁRZ DVVD\ WR FRQÀUP DFWLYHOHSWRVSLURVLV$FDUGDJJOXWLQDWLRQWHVWZDVPRUHVSHFLÀFEXWLWVVHQVLWLYLW\ HVSHFLDOO\ZKHQVHURSUHYDOHQFHVDUHKLJKQHHGVIXUWKHUHYDOXDWLRQ

(12)

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ÀF,J0DQG,J* LQKXPDQOHSWRVSLURVLV-*HQ0LFURELRO)HEUXDU\      6PLWV+/(DSHQ&.6XJDWKDQ6.XULDNRVH0*DVHP0+<HUVLQ&HWDO/DWHUDOÁ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

&KRRPNDVLHQ 3 HW DO 5LVN IDFWRUV DVVRFLDWHG ZLWK OHSWRVSLURVLV LQ QRUWKHDVWHUQ 7KDLODQG$P-7URS0HG+\J6HSWHPEHU  

   $VKIRUG'$.DLVHU506SLHJHO5$3HUNLQV%$:H\DQW56%UDJJ6/HWDO$V\PSWRPDWLF LQIHFWLRQ DQG ULVN IDFWRUV IRU OHSWRVSLURVLV LQ 1LFDUDJXD$P -7URS 0HG +\J  1RYHPEHU  

   GD 6LOYD 09 1DNDPXUD 30 &DPDUJR (' %DWLVWD / 9D] $- 5RPHUR (& HW DO ,PPXQRGLDJQRVLVRIKXPDQOHSWRVSLURVLVE\GRW(/,6$IRUWKHGHWHFWLRQRI,J0,J* DQG,J$DQWLERGLHV$P-7URS0HG+\J-XQH  

   )ODQQHU\ % 3HUHLUD 00 9HOORVR /G &DUYDOKR &G 'H &RGHV /* 2UULFR *G HW DO 5HIHUUDOSDWWHUQRIOHSWRVSLURVLVFDVHVGXULQJDODUJHXUEDQHSLGHPLFRIGHQJXH$P- 7URS0HG+\J1RYHPEHU  

   /HYHWW 31 %UDQFK 6/ (GZDUGV &1 'HWHFWLRQ RI GHQJXH LQIHFWLRQ LQ SDWLHQWV LQYHVWLJDWHGIRUOHSWRVSLURVLVLQ%DUEDGRV$P-7URS0HG+\J-DQXDU\      (IÁHU39%RJDUG$.'RPHQ+<.DW]$5+LJD +< 6DVDNL '0(YDOXDWLRQ RIHLJKW

UDSLG VFUHHQLQJ WHVWV IRU DFXWH OHSWRVSLURVLV LQ +DZDLL - &OLQ 0LFURELRO  $SULO  

(13)

&KDSWHU     =RFKRZVNL:-3DOPHU0)&ROHPDQ7-$QHYDOXDWLRQRIWKUHHFRPPHUFLDONLWVIRU XVHDVVFUHHQLQJPHWKRGVIRUWKHGHWHFWLRQRIOHSWRVSLUDODQWLERGLHVLQWKH8.-&OLQ 3DWKRO-DQXDU\      6HKJDO6&9LMD\DFKDUL36KDUPD66XJXQDQ$3/(372'LSVWLFNDUDSLGDQGVLPSOH PHWKRG IRU VHURGLDJQRVLV RI DFXWH OHSWRVSLURVLV 7UDQV 5 6RF 7URS 0HG +\J  0DUFK  

   6PLWV+/$QDQ\LQD<9&KHUHVKVN\$'DQFHO//DL$)5&KHH+'HWDO,QWHUQDWLRQDO PXOWLFHQWHU HYDOXDWLRQ RI WKH FOLQLFDO XWLOLW\ RI D GLSVWLFN DVVD\ IRU GHWHFWLRQ RI /HSWRVSLUDVSHFLÀFLPPXQRJOREXOLQ0DQWLERGLHVLQKXPDQVHUXPVSHFLPHQV-&OLQ 0LFURELRO6HSWHPEHU  

   6PLWV +/ +DUWVNHHUO 5$ 7HUSVWUD :- ,QWHUQDWLRQDO PXOWLFHQWUH HYDOXDWLRQ RI D GLSVWLFNDVVD\IRUKXPDQOHSWRVSLURVLV7URS0HG,QW+HDOWK)HEUXDU\      9LMD\DFKDUL36XJXQDQ$36HKJDO6&(YDOXDWLRQRIPLFURVFRSLFDJJOXWLQDWLRQWHVWDVD

GLDJQRVWLFWRROGXULQJDFXWHVWDJHRIOHSWRVSLURVLVLQKLJK ORZHQGHPLFDUHDV,QGLDQ -0HG5HV6HSWHPEHU

Referenties

GERELATEERDE DOCUMENTEN

Introducing matching learning [157] allows for accurate instance search of generic objects even when the relevant images in the search set show drastically different views of the

Beauvoir and Foucault, then, in spite of major differences between their overall theoretical frameworks, both appear to embrace the idea of ethics as an art of living that is

Several strains produced substantially higher amounts of aroma alcohols and esters compared to the lager yeast strain Weihenstephan 34/70.. Consequently, co-fermentation of this

[r]

The general features in the spectrum of corannuleneH + , that is, an isolated band assigned to a strong CH out-of-plane mode located near 750 cm −1 , the 1200–1450 cm −1

While the deployment and operational execution of streaming networks is handled by the S-N ET runtime system [3], the mapping of boxes to cores as well as the stream communication

Accord- ingly, we investigated the influence of low glucose levels in the extracellular space on the vasorelaxation induced by isoproterenol and salbutamol in rat isolated

Since a galE deletion restored cell division in the zapA ezrA double mutant, we were curious whether such deletion could also restore growth and cell division in the synthetic