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A utilidade da HRV como fator de prognóstico em crianças com TCE

Abstract

Objetivo A variabilidade da frequência cardíaca em crianças que sofreram traumatismo craniano ainda não se encontra muito estudada. Assim, este trabalho teve como objetivo avaliar as repercussões cardiovasculares do sistema nervoso autónomo, através da avaliação da variabilidade da frequência cardíaca (VFC), em indivíduos em idade pediátrica com traumatismo craniano. Métodos Bases de dados (Pubmed, World of Science e Scopus) - foram pesquisados estudos desde 1996 até 2017, tendo em conta a variabilidade da frequência cardíaca em idade pediátrica, (0 aos 18 anos), que tinham por base as guidelines Task Force (1996). Foram analisados dez (10) estudos que iam de encontro aos nossos critérios de inclusão. Resultados A potência total normalizada de 0,04 a 0,15 Hz foi utilizada para quantificar a VFC de baixa frequência (LF) e de 0,15 a 0,40 Hz para quantificar a VFC de alta frequência (HF). A proporção LF / HF foi utilizada como medida de modulação simpática da frequência cardíaca. Os doentes que após traumatismo craniano evoluíram para morte cerebral apresentaram uma relação LF / HF marcadamente menor (p<0,001), com uma diminuição significativa após as primeiras horas de internamento. Doentes com prognóstico mais favorável apresentaram ratios LF / HF significativamente mais elevados. Conclusões A disfunção no Sistema Nervoso Autónomo (SNA) em crianças que sofreram um traumatismo craniano conduz a oscilações na variabilidade da frequência cardíaca. Após revisão da literatura concluiu-se que a VFC pode ser útil para a determinação da gravidade dos danos neurológicos, sendo, também, um fator de prognóstico na avaliação da sua recuperação. A relação LF / HF poderá revelar-se útil não apenas nos doentes que evoluirão para a morte cerebral, após traumatismo craniano, como também na previsão de quais terão um melhor prognóstico.

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A utilidade da HRV como fator de prognóstico em crianças com TCE

Author: Natália de Sousa Antunes
Year: 2018
DOI: 10.34626/sydt-3x91
Source: https://repositorio-aberto.up.pt/bitstream/10216/114360/2/278752.pdf
2017/2018
Na ália de Sousa An unes
A u ilidade da a iabilidade da
equência ca díaca como a o de
p ognós ico em c ianças com
auma ismo c aniano
The u ili y o hea a e a iabili y as a
p ognos ic ac o in child en wi h
auma ic b ain inju y
ma ço, 2018
Mes ado In eg ado em Medicina
Á ea: Pedia ia
Tipologia: Monog a ia
T abalho e e uado sob a O ien ação de:
Dou o Ma a João Rod igues da Sil a
T abalho o ganizado de aco do com as no mas da e is a:
Childs Ne Sys
Na ália de Sousa An unes
A u ilidade da a iabilidade da
equência ca díaca como a o de
p ognós ico em c ianças com
auma ismo c aniano
The u ili y o hea a e a iabili y as a
p ognos ic ac o in child en wi h
auma ic b ain inju y
ma ço, 2018
5
Pu pose
Hea a e a iabili y in child en su e ing om head auma is no ye well s udied. This s udy aimed o assess
he ca dio ascula epe cussions o he au onomic ne ous sys em, h ough he e alua ion o hea a e a iabili y (HRV),
as a p ognos ic ac o in child en wi h auma ic b ain inju y (TBI).
Me hods
Da abases (Pubmed, Wo ld o Science and Scopus) - s udies we e conduc ed om 1996 o 2017, conside ing hea
a e a iabili y o pedia ic pa ien s (1 mon h o 18 yea s), based on Task Fo ce guidelines (1996). We analyzed eigh (8)
s udies ha included ou inclusion c i e ia.
Resul s
The no malized o al powe o 0.04 o 0.15 Hz was used o quan i y he hea a e low equency (LF) and om
0.15 o 0.40 Hz o quan i y hea a e high equency (HF). An LF / HF a io was used as a measu e o sympa he ic hea
a e modula ion.
Pa ien s wi h b ain inju y ha became b ain dead had a ma kedly lowe LF/HF a io (p <0.001), wi h a signi ican
dec ease a e he i s ew hou s o hospi aliza ion. Pa ien s wi h a mo e a o able p ognosis had signi ican ly highe LF/
HF a ios.
Conclusions
Au onomic Ne ous Sys em (ANS) dys unc ion in child en su e ing om b ain inju y leads o oscilla ions in
hea a e a iabili y.
A e e iewing he li e a u e, we concluded ha HRV can be use ul o he de e mina ion o he se e i y o neu ological
damage and a p ognos ic ac o in he e alua ion o i s eco e y.
LF/HF a io may be use ul o p edic which pa ien s will become b ain dead and which ones will ha e a be e
p ognosis.
KEYWORDS
Hea a e a iabili y; Child en; Head auma; Pedia ic pa ien s; Dysau onomia;

6
INTRODUCTION
Hea Ra e Va iabili y (HRV) is de ined as he a ia ion o e ime o he in e al be ween consecu i e hea bea s.
I e lec s he hea ´s abili y o adap and espond o changing ci cums ances by de ec ing and esponding o unp edic able
s imuli. I se es as an indica o o au onomous ac i i y in he egula ion o ci cula ion. I is also conside ed as he me hod
o analysis o au onomic ne ous sys em ac i i y. Changes in HRV ha e been associa ed wi h se e al pa hological
condi ions.
HRV measu emen s can be g ouped in ime domain, equency domain and non-linea measu emen s.
HRV de i es om he di e ence in du a ion o in e als be ween wo consecu i e bea s, called R-R in e als, and
is measu ed in milliseconds. These in e als a e ob ained on he ECG: he QRS complexes co espond o hea bea s and
R-R1 and R-R2 a e in e als be ween bea s.
Se e al equency bands ha e been de ined in humans, namely, high equency band (HF): be ween 0.15 and 0.4
Hz - modula ed by he pa asympa he ic ne ous sys em and gene a ed by espi a o y, low equency band (LF): be ween
0.04 and 0.15 Hz - de i es om he ac i i y o he sympa he ic sys em and is hough o e lec he delay in he ba o ecep o
e lex sys em. This delay is a ibu ed o he ac ha he sympa he ic sys em uses a second messenge sys em known as
cyclic AMP (cyclic adenosine monophospha e) and e y low equency band (VLF): be ween 0.01 and 0.04 Hz. I is o
unce ain o igin bu has been a ibu ed o a ma ke o sympa he ic ac i i y [1].
As he hea a e (HR) is a nons a iona y signal, i s a iabili y (especially a educ ion) may indica e he exis ence
o eminence o cu en disease: he educ ion o he HRV is associa ed o inc eased mo ali y. HRV is widely used o
e icien ly moni o he human body, mo e p ecisely in he e alua ion o ANS, h ough i s sympa he ic and pa asympa he ic
componen s. The e o e, i has become a ele an non-in asi e clinical ool [2].
C anioencephalic auma (TBI), which is associa ed wi h au onomic dys unc ion and co esponds o 40% o dea hs
in Ame ican child en unde 1 yea o age [3], is he main cause o auma ic dea h [4].
Despi e he as expe ience and esea ch in his ield, he de e minan s o i s occu ence in child en is s ill no well
de ined.
TBI may esul in dysau onomia, which is a condi ion cha ac e ized by ma ked, pa oxysmal changes in blood
p essu e, hea a e, espi a o y a e, empe a u e and/o swea ing. and is associa ed o dys unc ion o he au onomic ne ous
sys em [5].
Dysau onomy a ec s a small sub-g oup o su i o s who ha e su e ed se e e TBI. They a e mo e likely o su e
om se e e physical o cogni i e impai men , a p olonged pe iod o hospi aliza ion, as well as a long- e m dependence on
heal h ca e [6].
The e o e, he pu pose o his e iew was o examine he ele ance o HRV as a p ognos ic ac o in child en who
su e ed head auma, in he belie ha a dec ease in HRV may lead o a lowe p obabili y o su i al and a highe a e o
mo ali y and mo bidi y.
METHODS
A sys ema ic esea ch o he li e a u e was made in Janua y 2018, based on h ee da abases (Pubmed, Wo ld o
Science and Scopus) wi h he keywo ds: (hea a e a iabili y) and (child en) and (head auma) and (pedia ic pa ien s)
and (dysau onomia). Two hund ed and wen y one a icles om Pubmed, 102 om he Web o Science and 2 om he
Scopus da abase we e ound.
7
The abs ac s we e analyzed acco ding o he ollowing c i e ia: a icles om 1996 o 2017, human s udies in
pedia ic age (1 mon h o 18 yea s), wi hou congeni al diseases o como bidi ies, o empi ical in es iga ions (excluding
me a-analyzes, e iew a icles and epo s o single cases), using ime and equency domain me hods as VFC e alua ion
acco ding o he Task Fo ce guidelines [1] and a ailable in ull ex in Po uguese o English.
Eigh (8) a icles we e included acco ding o he inclusion c i e ia and in o ma ion included in he abs ac s.
In eg al ex s o a icles wi h ma ching p ede ined c i e ia we e sc eened.
Da a ex ac ion eco ds we e pe o med o each o he en selec ed a icles.
The aim, s udy o ma , au ho and yea , cha ac e is ics o pa icipan s, pa ame e s used o measu e HRV ( ime
domain and equency), expe imen al condi ions and key ideas we e ex ac ed.
RESULTS
Acco ding o he Task Fo ce o he Eu opean Socie y o Ca diology and he No h Ame ican Socie y o Rhy hm
and Elec ophysiology [1] and se e al s udies [6-15] we used he ime and equency domains o de e mine he u ili y o
HRV as a p ognos ic ac o in child en wi h TBI. The esul s a e summa ized in Tables 1 and 2.
The da a ex ac ed om he selec ed a icles we e summa ized in able 3.
We e i ied ha he e was a a ia ion (p = 0.027/ p = 0.59), be ween he low equency (LF) and high equency
(HF) alues, espec i ely, in he analyzed s udies when compa ed wi h hose sugges ed by he Task Fo ce (Table 2).
The HF band s a s a he alue a which he LF band ends: 0.15Hz (Table 3).
Six s udies excluded he e y low equency band (VLF), s a ing he LF band be ween 0.01 and 0.04Hz and
hose ha included he VLF band, used he alue 0.01Hz o s a i (Table 3).
Baguley I e al (2006) in es iga ed dysau onomia and HRV ollowing se e e auma ic b ain inju y h ough he
analysis o HRV. Da a was collec ed on age-ma ched subjec s wi h and wi hou dysau onomia and non-inju ed con ols.
The TBI g oup e ealed signi ican di e ences in HRV pa ame e s bo h compa ed o con ols and be ween dysau onomic
and non-dysau onomic subjec s.
VLF powe was ela i ely p ese ed be ween g oups. Only LF was signi ican ly lowe in he TBI g oup (p =
0.009). The mean LF/HF a io was in he no mal ange o con ols and ele a ed in he TBI g oup (1.8 and 3.7, espec i ely,
p < 0.05). The con ol g oup mean SDNN in TBI g oup was signi ican ly lowe han con ols (p = 0.018). HRV da a
demons a ed ha subjec s wi h dysau onomia had signi ican ly lowe LF powe (p < 0.05). The e was no s a is ical
di e ence be ween mean LF/HF a io o he dysau onomic s non-dysau onomic g oups (p = 0.164).
In he cu en s udy, he dysau onomia g oup had signi ican ly educed LF powe and g ea e LF/HF a io
a iabili y ( anging om 0.3 – 12.3) compa ed o he non-dysau onomic g oup [6].
Acco ding o Bismas A e al (2000) pa ien s who p og essed o b ain dea h had a e y low LF / HF a io (p <0.001),
wi h a signi ican dec ease in he i s 4 hou s o hospi aliza ion. Pa ien s wi h be e p ognosis had highe LF / HF a ios
[7].
Golds ein B e al (1998) ound signi ican co ela ions be ween su i al and mean hea a e (p = 0.004) and LF
(p = 0.009). In o he wo ds, he se e i y o he neu ological inju y, p ognosis and su i al we e in e sely ela ed o he
deg ee o ca dio ascula a iabili y. B ain dea h occu ed a e y low alues o HRV (nea ze o). In addi ion, he
ca dio ascula and au onomic sys ems we e p opo ionally decoupled a a ious le els du ing acu e b ain inju y. Thus,
moni o ing he deg ee o decoupling in hese sys ems allows a be e unde s anding o neu oau onomic and ca dio ascula
in e ac ions du ing acu e b ain inju y [8].
8
Golds ein B e al (1998) ound a nega i e co ela ion be ween he minimum alue o LF (p < 0.001), HF (p <
0.001) and LF/HF (p = 0.007), eco ded du ing hospi aliza ion. A discha ge om In ensi e Ca e Uni (ICU), he p ognos ic
showed a nega i e co ela ion be ween he minimum alue o LF (p < 0.001), HF (p < 0.001) and LF/HF (p = 0.008), in
o he wo ds, low alues o HRV demons a ed a g ea e se e i y o he illness and a wo se p ognos ic [9].
Acco ding o Golds ein B e al. (1996), maximal alues o LF (p <0.001), and minimum alues o HF (p < 0.001)
demons a ed a highe p obabili y o su i al, sugges ing ha HRV may p o e o be a sensi i e and speci ic me hod use ul
in de e mining he se e i y o he neu ological inju y in child en who su e ed b ain inju y [10].
Almeida R e al (2013), concluded ha he g oup o pa ien s wi h b ain dea h p esen ed educed HRV in all
equency bands (p <10-16) [11].
Su e al. (2005) p o ed ha a pe cen age inc ease in he LF band and in he LF / HF wi h he dec ease in HF
indica ed a g ea e powe on he pa o he sympa he ic ne ous sys em and a enua ed pa asympa he ic. These changes
we e ela ed o he se e i y o damage o he b ains em.
I was also obse ed ha in b ain dea h, LF and HF p esen ed e y low alues, concluding ha HRV may be a
use ul ool in he e alua ion o ANS unc ions in pa ien s wi h a ious le els o b ain inju y [12].
Kim S e al (2017) ound ha a signi ican inc ease in LF (p = 0.0119) in pa ien s wi h acu e b ain inju y indica ed
a high sympa he ic exci a o y ac i i y since LF had a sympa he ic p edominance. Howe e , HF had a pa asympa he ic
modula ion. The signi ican ly dec eased alues obse ed in he g oup o pa ien s wi h acu e b ain inju y (ABI) sugges ed
a dec eased pa asympa he ic ac i i y. The signi ican inc ease in he LF / HF a io o he g oup o pa ien s wi h acqui ed
b ain inju y in e s a g ea e powe on he pa o hei sympa he ic ne ous sys em (p = 0.0018). In he ime domain, SDNN,
which e lec s e e y cyclic aspec ha was ela ed o he a iabili y du ing he eco ding pe iod, was dec eased in ABI
g oup (p = 0.0134); mSSD, which ep esen s he pa asympa he ic egula ion o he hea , was signi ican ly di e en
be ween he wo g oups (p = 0.0240). In summa y, acco ding o his s udy, he g oup wi h acu e b ain inju y had a
sympa he ic p edominance when compa ed o he con ol g oup [13].
Discussion
The main esul o his s udy is ha HRV can be use ul when de e mining he se e i y o neu ological damage and
a p ognos ic ac o in he e alua ion o i s eco e y. I was ound ha he mo e se e e he neu ological inju y, he wo se
he p ognosis and he lowe he HRV. This sugges s ha as HRV is commonly used o e icien ly moni o he human body
in he e alua ion o ANS, h ough i s sympa he ic and pa asympa he ic componen s, i is a ele an non-in asi e clinical
ool [2].
Sho - e m a ia ions in hea a e a e obse ed a all ages and a e an impo an sign o no mal homeos a ic
mechanisms o he ca dio ascula sys em. The deg ee o hea a e a iabili y p o ides in o ma ion abou how he ne ous
sys em in e e es wi h hea a e and hea esponsi eness. In addi ion, diso de s o he cen al and pe iphe al ne ous
sys em ha e e ec s on HRV. Fu he mo e, all no mal cyclic changes in hea a e a e a enua ed in he p esence o se e e
b ain damage [14].
Ou in e es in he p esen s udy was o explo e HRV changes and o in es iga e hei ela ionship in he p ognosis
o child en wi h TBI. E en hough no much has been published abou his ma e , in he analyzed s udies, HRV was
ma kedly dep essed in child en who p og essed o b ain dea h a e TBI and in pa ien s wi h dysau onomia. In addi ion,
LF / HF a io was signi ican ly educed in b ain-dead child en. The low LF / HF a io was e iden in all b ain-dead and
non-su i ing pa ien s, while in he con ol g oup he e was a p og essi e inc ease in all measu ed a iables. Howe e , i
9
is hypo hesized ha hese conclusions a e biased in ela ion o he impo ance o each a iable, due o he small sample
size o each s udy. Fo his eason, we hink ha a simila s udy wi h a la ge and mo e homogenous g oup could ha e a
signi ican alue in HRV as a p edic i e elemen , a he han simply associa ed, wi h mo ali y.
The mos ele an limi a ion o his e iew was he lack o s anda diza ion o he Task Fo ce guidelines o he
pedia ic popula ion. The s anda d alues desc ibed may no apply o child en wi h he esul ha di e en au ho s used
di e en equency bands. Fu he mo e, he implemen a ion o a s anda d me hod o collec and analyze HRV would
con ibu e o mo e eliable indings. This and he ac ha mos s udies included mos ly adul s and only a small numbe o
child en made i di icul o es ablish a compa ison abou he impo ance o HRV and i s ole in he p ognosis o child en
wi h TBI. Hence, he impo ance o se ing app op ia e guidelines o he pedia ic age as well as a cu -o o de ine he
p ognosis o child en wi h TBI on admission. On he o he hand, he ac ha each s udy uses small samples only, limi ed
he esul s o he s udies. None heless, is seems well es ablished ha LF/HF a io may be help ul no only in iden i ying
hose pa ien s who will p og ess o b ain dea h bu also in p edic ing which pa ien s will ha e a o able ou comes.
Conclusions
In summa y, acco ding o he eligible s udies he analysis o HRV in child en wi h se e e b ain lesions caused by
TBI and he p ognosis o hei eco e y is in e sely associa ed wi h HRV, wi h ce eb al dea h le els o almos ze o
a iabili y.
The equency domain is used mo e equen ly and he LF e lec ed he ac i i y o he sympa he ic componen .
The e idence indica ed ha du ing se e e b ain inju y, he ca dio ascula and au onomic sys ems a e
p opo ionally decoupled a a ious le els in ela ion o he deg ee o neu ological inju y, and hei moni o ing may lead
o a be e unde s anding o neu oau onomic in e ac ions.
Pa ien s who a e b ain inju y e ol ed o b ain dea h had a ma kedly lowe LF / HF a io (p <0.001) wi h a
signi ican dec ease a e he i s hou s o hospi aliza ion. Pa ien s wi h a mo e a o able p ognosis had signi ican ly highe
LF / HF a ios. Thus, he LF / HF a io may be use ul in iden i ying pa ien s who will p og ess o b ain dea h, as well as in
he p ognosis o hose who will eco e a o ably.
16
To ind e idence o au onomic
imbalance and p esen e he
HRV pa ame e s ha e lec
he se e i y o pa oxysmal
sympa he ic hype ac i i y in
child en wi h acqui ed b ain
inju y.
Kim S e al
(2017) [13]
13 child en (8 males/5 emales) wi h acu e
b ain inju y who we e admi ed om
Oc obe 2013 o Janua y 2016.
4 child en had TBI
SA-6000 de ice (Medico e
Co.,Seoul, Ko ea).
Du a ion o eco ding: 5
minu es.
TD: SDNN and mSSD.
FD: LF (0.04 o 0.15), HF
(0.15 o 0.40 Hz) and LF/HF
a io.
13 age-and sex-ma ched pa ien s
wi h ce eb al palsy we e selec ed
as he con ol g oup.
Tes we e conduc ed in a noise-
ee en i onmen a e 30 minu es
o es , in a elaxed supine
posi ion.
In o de o a oid he in luence3 o
ci cadian changes in he HRV
esul s, da a was collec ed be ween
1:00 PM and 3:00 PM in e e y
pa ien .
The oom empe a u e du ing da a
collec ion was 24-26ºC.
Exclusion c i e ia
His o y o ca diac disease,
diabe es o o he pe iphe al
neu ological impai men , pa ien s
aking ca dio ascula medica ions
and sépsis o suspicion o
signi ican in ec ion.
The e was a s a is ically
signi ican inc ease in he
mean hea a e o he acu e
b ain inju y g oup compa ed o
he con ol g oup (p = 0.0119).
Acco ding o he ime domain
analysis, he mSSD was
signi ican ly di e en be ween
he wo g oups (p = 0.0240).
All indices o he equency
domain analysis demons a ed
a s a is ically signi ican
di e ence be ween he wo
g oups.
The LF and HF dec eased in
he acu e b ain inju y g oup
compa ed o he con ol g oup.
Only he LF / HF a io
inc eased in he acu e b ain
inju y g oup compa ed o he
con ol (p=0.0018 and
p=0.0018 espec i ely).
LF – low equency; VLF – e y low equency; MLF – mid-low equency; HF – high equency; Secs - seconds; FD – equency domain; TD – ime domain;

17
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[12] Su C, Kuo T, Kuo J e al (2005) Sympa he ic and pa asympa he ic ac i i ies e alua ed by hea - a e a iabili y
in head inju y o a ious se e i ies. Clinical Neu ophysiology 116:1273-1279.
[13] Kim S, Jeon H, Kim J e al (2017) Hea a e a iabili y among child en wi h acqui ed b ain inju y. Ann
Rehabil Med 41(6):951-960.
[14] Lowensohn I, Weiss M, Hon H (1977) Hea - a e a iabili y in b ain-damaged adul s. Lance 1:626-628.
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A achmen s
 Re iew a icles and in i ed pape s
Re iew pape s may be na a i e o sys ema ic and a e subjec o he pee e iew p ocess. They should o e
exhaus i e in o ma ion on a gi en subjec . The Edi o will in i e expe s in he a ious ields o he neu osciences
o publish In i ed pape s, al hough unsolici ed e iews may also be conside ed. The Abs ac mus no be
s uc u ed and he ex may be a anged eely. The con ibu ion should no be signed by mo e han 7 au ho s,
while he ex should no exceed 4000 wo ds. Up o 15 igu es o ables and 70 e e ences a e allowed. Excep ions
a he disc e ion o he Edi o in Chie .
Abs ac
Please p o ide a s uc u ed abs ac o 150 o 250 wo ds which should be di ided in o he ollowing sec ions:
 Pu pose (s a ing he main pu poses and esea ch ques ion)
 Me hods
 Resul s
 Conclusions
Keywo ds
Please p o ide 4 o 6 keywo ds which can be used o indexing pu poses.
Tex Fo ma ing
Manusc ip s should be submi ed in Wo d.
 Use a no mal, plain on (e.g., 10-poin Times Roman) o ex .
 Use i alics o emphasis.
 Use he au oma ic page numbe ing unc ion o numbe he pages.
 Do no use ield unc ions.
 Use ab s ops o o he commands o inden s, no he space ba .
 Use he able unc ion, no sp eadshee s, o make ables.
 Use he equa ion edi o o Ma hType o equa ions.
 Sa e you ile in docx o ma (Wo d 2007 o highe ) o doc o ma (olde Wo d e sions).
Headings
Please use no mo e han h ee le els o displayed headings.
Abb e ia ions
Abb e ia ions should be de ined a i s men ion and used consis en ly he ea e .
Foo no es
Foo no es can be used o gi e addi ional in o ma ion, which may include he ci a ion o a e e ence included in
he e e ence lis . They should no consis solely o a e e ence ci a ion, and hey should ne e include he
bibliog aphic de ails o a e e ence. They should also no con ain any igu es o ables.
19
Foo no es o he ex a e numbe ed consecu i ely; hose o ables should be indica ed by supe sc ip lowe -case
le e s (o as e isks o signi icance alues and o he s a is ical da a). Foo no es o he i le o he au ho s o he
a icle a e no gi en e e ence symbols.
Always use oo no es ins ead o endno es.
Acknowledgmen s
Acknowledgmen s o people, g an s, unds, e c. should be placed in a sepa a e sec ion on he i le page. The names
o unding o ganiza ions should be w i en in ull.
Ci a ion
Re e ence ci a ions in he ex should be iden i ied by numbe s in squa e b acke s. Some examples:
1. Nego ia ion esea ch spans many disciplines [3].
2. This esul was la e con adic ed by Becke and Seligman [5].
3. This e ec has been widely s udied [1-3, 7].
Re e ence lis
The lis o e e ences should only include wo ks ha a e ci ed in he ex and ha ha e been published o accep ed
o publica ion. Pe sonal communica ions and unpublished wo ks should only be men ioned in he ex . Do no
use oo no es o endno es as a subs i u e o a e e ence lis .
Re e ence lis en ies should be alphabe ized by he las names o he i s au ho o each wo k and numbe ed
consecu i ely.
Tables
 All ables a e o be numbe ed using A abic nume als.
 Tables should always be ci ed in ex in consecu i e nume ical o de .
 Fo each able, please supply a able cap ion ( i le) explaining he componen s o he able.
 Iden i y any p e iously published ma e ial by gi ing he o iginal sou ce in he o m o a e e ence a
he end o he able cap ion.
 Foo no es o ables should be indica ed by supe sc ip lowe -case le e s (o as e isks o signi icance
alues and o he s a is ical da a) and included benea h he able body.