Technology, Computing, and Simulation

Section Editor: Jeffrey M. Feldman

Cardiac Output Measurement in Patients Undergoing

Liver Transplantation: Pulmonary Artery Catheter Versus
Uncalibrated Arterial Pressure Waveform Analysis
Biais Matthieu, MD
Nouette-Gaulain Karine, MD, PhD
Cottenceau Vincent, MD
Vallet Alain, MD
Cochard Jean Francois, MD
Revel Philippe, MD
Sztark Francois, MD, PhD

BACKGROUND: Cardiac output (CO) and invasive hemodynamic measurements are

useful during liver transplantation. The pulmonary artery catheter (PAC) is commonly
used for these patients, despite the potential complications. Recently, a less invasive
device (Vigileo/FloTrac) became available, which estimates CO using arterial
pressure waveform analysis without external calibration. In this study, we compared
CO obtained with a PAC using automatic thermodilution, instantaneous CO stat-mode
(ICOSM), and CO obtained with the new device, arterial pressure waveform analysis
(APCO) in patients undergoing liver transplantation.
METHODS: Twenty sets of simultaneous measurements of APCO and ICOSM were
determined in sedated and mechanically ventilated patients undergoing liver
transplantation. Time points were as follows: after PAC insertion (T13), after
portal clamping (T4 6), during anhepathy (T79), after graft reperfusion (T10 15),
and in the postoperative period in the intensive care unit (T1520).
RESULTS: We enrolled 20 patients and 400 measurements were obtained. No data were
rejected. Bias between ICOSM and APCO was 0.8 L/min, 95% limits of agreement were
1.8 to 3.5 L/min. The percentage error was 43%. Bias between ICOSM and APCO was
correlated with systemic vascular resistance [r2 0.55, P 0.0001, y 15.8 2.2 ln(x)]
and subgroup analysis revealed an increase in the bias and in the percentage error in
patients with low systemic vascular resistance (Child-Pugh grade B and C patients).
There was no difference between the different surgical periods.
CONCLUSIONS: Our results suggest that Vigileo/FloTrac CO monitoring data do not
agree well with those of automatic thermodilution in patients undergoing liver
transplantation, especially in Child-Pugh grade B and C patients with low systemic
vascular resistance.
(Anesth Analg 2008;106:1480 6)

ardiac output (CO) and invasive hemodynamic

measurements are useful during liver transplantation,
especially when hemodynamic instability occurs and
massive transfusion of blood products is anticipated.1,2 The standard clinical method for intraoperative measurements of CO is intermittent pulmonary
artery thermodilution (ICOTD). STAT-Mode (ICOSM)
is an alternative to ICOTD and is obtained using automatic thermodilution.3 Good correlation, high levels of
accuracy and precision are found between ICOTD and
ICOSM.35 However, pulmonary artery catheterization
may cause rare but serious complications and misinterpretations.6 9 For several years, less invasive methods to monitor CO continuously have been developed,
From the Service dAnesthesie Reanimation I, Hopital Pellegrin,
Centre Hospitalo-Universitaire de Bordeaux, Place Amelie RabaLeon, Bordeaux Cedex, France.
Accepted for publication December 28, 2007.
Address correspondence and reprint requests to Francois Sztark,
MD, PhD, Service dAnesthesie Reanimation I, Hopital Pellegrin,
Place Amelie Raba-Leon, 33076 Bordeaux Cedex, France. Address
e-mail to francois.sztark@chu-bordeaux.fr.
Copyright 2008 International Anesthesia Research Society
DOI: 10.1213/ane.0b013e318168b309

1480

including monitors using arterial pressure waveform

analysis. Recently, a new device for monitoring CO
continuously that does not require external calibration
or a pulmonary artery catheter (PAC) has been introduced (Vigileo/FloTrac; Edwards Lifesciences, Irvine, CA). It calculates CO by using arterial pressure
waveform analysis (APCO) in conjunction with patient demographic data (height, weight, age, and
gender) to estimate arterial compliance.10 Previous
studies evaluated the agreement between APCO and
ICOTD and between APCO and transpulmonary thermodilution CO (COTPT) with contradictory results.1114 To
our knowledge, the Vigileo/FloTrac system has not
been evaluated in a specific population of liver transplant patients.
In this clinical study, we evaluated the agreement
between APCO and ICOSM during steady-state periods
in patients undergoing orthotopic liver transplantation.

METHODS
Patients
After obtaining approval from the ethics committee
and informed consent, 20 consecutive patients scheduled to undergo liver transplantation for acute or
Vol. 106, No. 5, May 2008

chronic liver failure were enrolled. Child-Pugh grade

was defined for each patient.15,16
Exclusion criteria were the following: patients
younger than 18 yr, arrhythmias, body mass index
40 kg/m2 or 15 kg/m2, valvular heart disease, in
particular tricuspid regurgitation and intracardiac
shunt. No change was required from established protocols for monitoring and critical care management
used at our institution. Vasopressive drugs and fluid
administration was guided by patients hemodynamic
data.

Perioperative Management
Patients were anesthetized with sufentanil and propofol. Cisatracurium was used for muscle relaxation.
Sufentanil and isoflurane were used for maintenance of
anesthesia. After the induction of anesthesia, the patients trachea was intubated and mechanical ventilation
was instituted using volume-controlled ventilation. All
patients lungs were ventilated with an oxygen-air mixture to maintain an arterial oxygen partial pressure
above 13.3 kPa, and ventilation parameters were adjusted to ensure an arterial carbon dioxide partial pressure between 4.7 and 5.4 kPa.
Liver transplantation was accomplished without
venovenous bypass using the three-phase piggyback.17 First, the attachments of the diseased liver
were resected, and the vascular structures were prepared for resection. The second or anhepatic phase
extends from the time when the host liver was removed until the donor liver was revascularized. Finally, the graft was reperfused.
After liver transplantation, patients were admitted
to the intensive care unit (ICU). Patients were sedated
with propofol and sufentanil, and mechanical volumecontrolled ventilation was continued for a minimum
4 h period.

Cardiopulmonary Monitoring
After the induction of anesthesia and just before the
beginning of surgery, a PAC (CCOmbo, 744HF75, 7.5
Fr, Edwards Lifesciences) was inserted via the left
subclavian vein through an introducer (M3L9FHSI, 9
Fr, Edwards Lifesciences) and was connected to the
Vigilance monitor (Edwards Lifesciences) for CO
monitoring. The position of the catheter was confirmed by pressure curves, -pulmonary artery occlusion pressure/-pulmonary artery pressure (PAP) ratio
as previously described18 and postoperatively by
chest radiograph. Intracardiac pressure and PAP were
monitored continuously. A safe level of heat was
transferred to the blood by a computer-controlled
thermal filament mounted on the PAC.3 To eliminate
the natural temperature variations in the pulmonary
artery, which could constitute background thermal
noise, heat was transferred to the blood in a pseudorandom on off fashion.3,19 The observed changes in
pulmonary artery temperature were recorded by the
distal rapid-response thermistor in the pulmonary
Vol. 106, No. 5, May 2008

artery. There was no need for user calibration because

the Vigilance monitor automatically computed a
cross-correlation between the filament input sequence,
the power, and the distal thermistor response to blood
warming.19 From this cross-correlation, CO was calculated using a modified Stewart-Hamilton equation.19,20 STAT-Mode displayed the actual CO values
determined within the past 60 s (ICOSM) and continuous cardiac output (CCO), which was an average of
the previous 3 6 min ICOSM. Heart rate, central
venous pressure, and PAP were displayed on a bedside monitor, and pressures were recorded at the end
of the expiration with the zero level set at midthorax.

APCO Monitoring
A 3 Fr, 8-cm-long arterial catheter (115.09, Vygon,
Ecouen, France) was inserted in the left radial artery.
A dedicated transducer was connected to the radial
arterial line for APCO evaluation (Vigileo System,
FloTrac, Edwards Lifesciences). This system needs
no external calibration and provides CCO measurements from the arterial pressure wave. The Vigileo
(Software version 1.07) records hemodynamic variables at 20-s intervals, performing its calculations on
the most recent 20 s data. The system calculates the
stroke volume (SV) using arterial pulsatility (standard
deviation of the pulse pressure over a 20-s interval),
resistance, and compliance (Eq. 1). The CO is calculated as follows: CO heart rate SV.

Stroke volume K Pulsatility

(1)

where K is a constant quantifying arterial compliance

and vascular resistance, derived from a multivariate
regression model including (i) Langewouters aortic
compliance,21 (ii) mean arterial blood pressure (MAP),
(iii) variance, (iv) skewness, and (v) kurtosis of the
pressure curve. The rate of adjustment of K was 1 min
(Software 1.07). Pulsatility is proportional to the standard deviation of the arterial pressure wave over a
20-s interval.

Study Protocol
Fifteen sets of measurements were performed in the
operating room after the induction of anesthesia: 5, 15,
and 25 min after PAC insertion (T13); 5, 15, and 25
min after portal clamping (T4 6); 15, 25, and 35 min
after the hepatectomy (T79); and 10, 20, 30, 40, 50,
and 60 min after reperfusion (T10 15). Five sets of
measurements were made in the ICU: 60, 90, 120, 150,
and 180 min after the admission (T16 20). Each set of
measurements was made with the patient in the
supine position and during a steady-state period, i.e.,
at least 5 min after a change in infusion rate of
catecholamine or sedative drugs, or ventilatory settings. At each time point, three consecutive measurements of ICOSM were performed and the plausibility
of every temperature curve was judged visually on the
Vigilance monitor. If ICOSM changed by more than
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Table 1. Hemodynamic Data in Patients Classified as Child-Pugh Grade A, B, and C

Measurements (n)
MAP (mm Hg)
NE (g/kg/min)
SVR (dyne/s/cm5)
ICOSM (L/min)
APCO (L/min)
Temperature (C)

Child-Pugh A

Child-Pugh B

Child-Pugh C

60
89 (20)
0.33 (0.28)
1414 (454)
4.5 (1.1)
4.4 (1.0)
36.1

200
77 (16)*
0.28 (0.27)
1059 (339)*
5.5 (1.8)*
5.8 (1.7)
36.2

140
72 (16)*
0.49 (0.54)*
634 (235)*
8.3 (2.1)*
8.5 (2.0)*
36.1

Data are expressed as mean (SD).

MAP mean arterial blood pressure; NE norepinephrine; SVR systemic vascular resistance; ICOSM instantaneous cardiac output stat-mode; APCO Vigileo/FloTrac Cardiac Output.
* P 0.0001 versus Child-Pugh A.
P 0.001 versus Child-Pugh B.
P 0.01 versus Child-Pugh A.

15% during the steady-state period, five measurements were performed and the highest and lowest
were rejected. For each measurement of ICOSM, a
corresponding simultaneous APCO was recorded.
The average of the consecutive measurements of
ICOSM and APCO was used for statistical analysis.
CCO was not used for statistical analysis.
Hemodynamic data were grouped into five phases:
after PAC insertion (3 measurements), after portal
clamping (3 measurements), after hepatectomy (3
measurements), after reperfusion (6 measurements),
and in the ICU (5 measurements).
ICOSM and APCO measurements were obtained by
two operators who were blinded to the corresponding
CO measurement of the other method.

Statistical Analysis
All results were expressed as mean standard
deviation (sd) unless indicated otherwise. APCO and
ICOSM were compared using the Bland and Altman
method.22 Bias (mean difference between APCO and
ICOSM) represents the systematic error between both
methods. Precision (sd of the bias) is representative of
the random error or variability between the different
techniques. The limits of agreement were calculated as
bias 2sd, and defined the range in which 95% of the
differences between the methods were expected to lie.
The percentage error was calculated as the ratio of
2sd of the bias to mean CO and was considered
clinically acceptable if it was below 30%, as proposed
by Critchley and Critchley.23
Bias, limits of agreements, and percentage error
between ICOSM and APCO were calculated for all
data, separately for the five phases (PAC insertion,
after portal clamping, after hepatectomy, after reperfusion, and after arrival in ICU) and separately for
different Child-Pugh grades (A, B, and C). The relation
between systemic vascular resistance (SVR) and the
bias between ICOSM and APCO were tested using a
logarithmic regression. Changes in CO (-CO) were
calculated as the differences between consecutive
measurements. The ability to detect -CO was tested
using the BlandAltman method. Child-Pugh grade
A, B, and C patient data were compared using a
Students t-test. All statistical analysis was computed
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with StatView (Version 5.0; SAS Institute Inc.). A P

value 0.05 was considered significant.

RESULTS
Twenty patients (6 women, 14 men) were enrolled.
Their average age was 51 9 yr, average weight was
63 12 kg, and average height was 170 9 cm. The
average body surface area was 1.80 0.16 m2. Surgical
indications were hepatitis C virus cirrhosis (n 6),
hepatitis B virus cirrhosis (n 1), alcoholic cirrhosis
(n 11), and others (n 2). The Child-Pugh classification was A, B, and C, respectively, for 3, 10, and 7
patients. The average Model for End-Stage Liver Disease score was 16 5, and the average packed red blood
cell transfusion was 6 4 U. Mean anesthesia time was
7.5 2 h. Four-hundred comparative measurements
performed between ICOSM and APCO were obtained.
No data were rejected. ICOSM values ranged from 2.5 to
12.3 L/min (mean 6.4 2.3 L/min) whereas the values
for APCO ranged from 2.1 to 9.5 L/min (mean 5.5 1.3
L/min). All patients received norepinephrine (0.36
0.40 g kg1 min1). Hemodynamic data are shown in
Table 1. No adverse effect related to PAC was observed.

Global Analysis
The bias between ICOSM and APCO was 0.8 L/min,
and 95% limits of agreement were 1.8 to 3.5 L/min
(Fig. 1). The percentage error between all ICOSM and
APCO measurements was 43%. Bias between ICOSM
and APCO was correlated with SVR [r2 0.55; P
0.0001; y 15.8 2.2 ln(x)] (Fig. 2). Delta-CO was
calculated separately for each method and data comparison revealed a bias of 0.1 L/min; 95% limits of
agreement were 2.4 to 2.7 L/min.

Subgroup Analysis
Bias, limits of agreements, and percentage error of
the five phases are shown in Table 2. Bias between
Delta-ICOSM and Delta-APCO were not different in
the five phases.
Bias, limits of agreements, and percentage error in
different Child-Pugh grades are shown in Table 3. ChildPugh A patients presented a percentage error 30% and
a bias between ICOSM and APCO significantly lower
than Child-Pugh B and C patients (Fig. 3).
ANESTHESIA & ANALGESIA

Bias between Delta-ICOSM and Delta-APCO in

Child-Pugh A, B, and C patients was, respectively,
0.11, 0.5, and 0.1 L/min, and 95% limits of agreement were, respectively 1.09 to 0.86, 2.2 to 3.1, and
2.9 to 2.6 L/min.

DISCUSSION

Figure 1. BlandAltman plot between ICOSM-APCO. The

unbroken lines show the mean difference and the dotted

lines show the 2sd limits of agreement. ICOSM Instantaneous
Cardiac Output Stat-Mode; APCO Vigileo/FloTrac Cardiac
Output.

Figure 2. Regression analysis between systemic vascular

resistance (SVR) and ICOSM-APCO. ICOSM Instantaneous

Cardiac Output Stat-Mode; APCO Vigileo/FloTrac
Cardiac Output.

In the present study, APCO values differed significantly from ICOSM values in patients undergoing liver
transplantation. We found a bias of 0.8 L/min, 95%
limits of agreement of 1.8 to 3.5 L/min. The percentage
error was 43%, exceeding a 30% limit of acceptability.
Recently published studies investigating the
Vigileo/FloTrac showed discordant results (Table 4).
Studies performed in patients undergoing cardiac
surgery, liver transplantation, or in patients with
septic shock found clinically unacceptable bias and
limits of agreement between APCO and ICOTD, and
between APCO and COTPT.1214,24,25 However, three
other cardiosurgical studies found clinically acceptable bias and limits of agreement between APCO and
ICOTD or between APCO and COTPT.11,26,27 De Waal et
al. reported a mean bias of 0.00 L/min (sd 0.87)
between APCO and COTPT in 22 patients studied after
cardiac surgery.27 Button et al. showed that performance of the Vigileo/FloTrac, the PiCCOplus and
the Vigilance CCO monitor for CO measurement were
comparable when tested against ICOTD in 31 patients
undergoing cardiac surgery.26 Manecke et al. studied
50 postoperative cardiac surgery patients and found
that APCO algorithm provided CO assessments that
agreed satisfactorily for clinical purposes with intermittent thermodilution.11 The bias and the precision
were, respectively, 0.55 and 0.98 L/min between
APCO and ICOTD. The authors did not calculate the
percentage error as proposed by Critchley and Critchley and were unable to conclude whether the results
were clinically acceptable.

Table 2. Bias, 95% Limits of Agreement, and Percentage Error Between ICOSM and APCO Measurements at Different Phases of
Liver Transplantation

Bias (sd) (L/min)

95% limits of agreement (L/min)
Percentage error (%)

After PAC
insertion

Portal clamping

Anhepathy

Graft reperfusion

Intensive
care unit

0.7 (1.4)
3.6 to 2.1
54

0.9 (1.5)
2.0 to 3.7
52

0.7 (1.1)
1.5 to 2.9
40

1.2 (1.4)
1.7 to 3.9
43

0.6 (1.3)
1.9 to 3.1
39

Data are expressed as mean (SD).

PAC pulmonary arterial catheter; ICOSM instantaneous cardiac output stat-mode; APCO Vigileo/FloTrac Cardiac Output.

Table 3. Bias, 95% Limits of Agreement, and Percentage Error Between ICOSM and APCO Measurements in Patients with
Child-Pugh Grade A, B, and C
Bias (sd) (L/min)
95% limits of agreement (L/min)
Percentage error (%)

Child-Pugh A

Child-Pugh B

Child-Pugh C

0.025 (0.34)
0.64 to 0.69
15

0.43 (1.1)*
1.7 to 2.6
40

1.8 (1.46)*
1.1 to 4.7
40

Data are expressed as mean (SD).

ICOSM instantaneous cardiac output stat-mode; APCO Vigileo/FloTrac Cardiac Output.
* P 0.01 versus Child-Pugh A; P 0.001 versus Child-Pugh B.

Vol. 106, No. 5, May 2008

2008 International Anesthesia Research Society

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Figure 3. BlandAltman plot between ICOSM and APCO

obtained in patients classified as Child-Pugh A (A), B (B), and
C (C). The unbroken lines show the mean difference and the
dotted lines show the 2sd limits of agreement. ICOSM Instantaneous Cardiac Output Stat-Mode; APCO Vigileo/FloTrac
Cardiac Output.
The Vigileo/FloTrac calculates CO using arterial
waveform characteristics and patients demographic
data. The relation between pressure pulse and SV
depends on the characteristics of the arterial vascular
tree (compliance and resistance). Mechanical arterial
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Cardiac Output Monitoring

properties differ from patient to patient and can differ

in the same patient, particularly during liver transplantation, with a large decrease in SVR after graft
reperfusion. The extent of vasodilation has an impact
on the arterial pressure waveform.28 The lack of
external calibration could explain the value of the bias
and the percentage error between APCO and ICOSM.
Indeed, other techniques using the arterial wave
(PulseCO system, LiDCO Group, London, UK; PiCCO
system, Pulsion SG, Munich, Germany; Finapres Modelflow system, Finapres Medical System, Amsterdam,
Netherlands) require calibration with another method
of CO assessment (Lithium, transpulmonary thermodilution).29,30 The initial invasive calibration decreases the bias due to interindividual differences, and
other calibrations are required in case of marked
changes in SVR with the PiCCO system, for example.31
Our study was performed in patients with mainly a
moderate or severe Child-Pugh grade (B and C). The
patients data revealed a high bias between APCO and
ICOSM and a percentage error higher than 30%,
whereas Child-Pugh grade A patient data showed a
percentage error of 15%. Several reasons might explain
these results. The cardiovascular system in cirrhotic
patients is characterized by increased CO, decreased
peripheral vascular resistance, and decreased MAP.
Child-Pugh grade is directly related to central and
nonsplanchnic hemodynamic alterations.32 In the
present study, SVR and MAP were significantly lower
and CO was significantly higher in patients classified
as Child-Pugh B and C. We hypothesized that in these
groups, vasodilation induced by cirrhosis could interfere with the arterial pressure waveform and with its
analysis. This interpretation is supported by the result
of the logarithmic regression between bias between
ICOSM-APCO and SVR. Costa et al. demonstrated that
during liver transplantation, the bias and the 95%
limits of agreement between ICOTD-APCO increased
significantly in hyperdynamic conditions (CO 8
L/min).24 Moreover, vasoactive treatments induce
changes in vascular impedance and compliance with
an impact on arterial pressure waveform. These may
affect the accuracy of APCO to a greater extent than
the accuracy of ICOSM. In the present study, all of the
patients received norepinephrine (0.36 0.40 g
kg1 min1), which may have impacted the level of
bias between APCO and ICOSM. Furthermore, the
Vigileo/FloTrac uses radial artery pressure waveforms. Systolic radial artery pressure is higher than
systolic aortic pressure, whereas diastolic and mean
pressures were found to be equal in both sites.33,34 In
all pulse contour methods, the aortic pressure waveform should ideally be used as the input for the pulse
contour method. Femoral artery pressure waveforms
as well as the brachial artery waveform are probably
more similar to the aortic pressure waveform than the
radial artery waveform.
Our study had some limitations. APCO was compared with ICOSM and we did not use ICOTD. ICOTD
ANESTHESIA & ANALGESIA

Table 4. Studies Comparing Data Obtained with Vigileo/FloTrac to Those Obtained with PAC or Transpulmonary Thermodilution
Authors Patients Measurements
Costa
et al.24
Opdam
et al.13
Mayer
et al.12

16

Sakka
et al.25
de Waal
et al.27
Manecke
et al.11

24

6
40

22
50

Model

Bias

Correlation Limits of agreement

PE

1.63 to 3.37 L/min

1.2 to 1.19 L/min/m2

Cardiac
output (BTD)
Cardiac
index (BTD
and CCI)
Cardiac
index (BTD)

Liver
0.87 L/min
transplantation
Cardiac surgery 0.0057 L/min/m2
Cardiac surgery

0.46 L/min/m2

Cardiac
output (TPT)
Cardiac
output (TPT)
Cardiac
output (BTD)

Septic shock

0.5 L/min

Cardiac surgery

0.00 L/min

r 0.75

Precision 0.87 L/min

33%

Cardiac surgery

0.55 L/min

Precision 0.98 L/min

r2 0.27
r 0.53

0.73 to 1.64 L/min/m2 46%

(P 0.0001)
r2 0.26
Precision 2.3 L/min

PAC pulmonary arterial catheter; BTD bolus thermodilution; CCI continuous cardiac index; TPT transpulmonary thermodilution; PE percentage error.

is often referred to as the clinical standard, but it has

well-known pitfalls related to operator variation, patient pathologies, and the indicator used.35 Although
ICOSM has its own inherent limitations and is not a
gold standard method, previous studies have
shown acceptable limits of agreement.4,36 42 However,
because of a time delay of the CO calculation, the
STAT-Mode may miss rapid and transient hemodynamic changes.38,43,44 In the case of liver transplantation, accuracy between ICOTD and ICOSM may decrease
when rapid changes in CO occur, when the thermal
noise increases, when caval clamping is required, or
when peripheral IV fluid infusion rates are high.36,37
To avoid these pitfalls, liver transplantation was done
without caval clamping by using the piggy-back technique,17 and measurements were made during stable
hemodynamic and thermal conditions defined in the
protocol as the lack of change in infusion rate of
catecholamine, of sedative drugs or ventilatory setting
for 5 min. Despite these precautions, minimal CO
variations may have occurred during these steadystate periods and influenced our results. This could
explain the lower bias and percentage error in the
ICU, with minimal hemodynamic variations. Finally,
one of the hemodynamic specificities of liver transplant patients is low SVR and high CO. Many sources
of error have been identified regarding the thermodilution method, including high CO levels, and these
may contribute to low accuracy between ICOSM and
APCO.35,45
In conclusion, CO values obtained with uncalibrated arterial pressure waveform analysis (Software
1.07) in patients undergoing liver transplantation do
not agree with thermodilution data (percentage error
of 43%), particularly in patients with low SVR as
attested by Child-Pugh grade B and C. The extent of
vasodilation observed in our patients may account for
the poor correlation between both methods.
ACKNOWLEDGMENTS
The authors thank Francoise Masson for statistical support and Ray Cooke for revising the English.
Vol. 106, No. 5, May 2008

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