- Journal of New Remedies & Clinics Vol. 59 No.
7 2010 -
Assessment of the Analytical Performance of MEDISAFE FIT, a
Simplified System for Self-monitoring of Blood Glucose (SMBG)
Using a New double-wavelength Colorimetric Method
- Assessment of the Analytical Performance According to ISO15197 and
the Japanese Approval Standard for SMBG Devices
Introduction
SMBG systems developed in early 1970s
successfully changed the blood glucose
monitoring site from medical institutions to the
homes of patients. As reported by Sonksen et
al.1) and Ikeda et al.,2) the clinical application
of SMBG systems developed in late 1970s
played important roles in the early days. In
Japan, a symposium titled Self-monitoring of
Blood Glucose and Diabetes Management
was held in 1981, while in the U.S., the
American Diabetes Association (ADA) started
to sponsor SMBG Symposium in 1986. In the
same year, health insurance started to cover
home SMBG in patients undergoing insulin
therapy in Japan. During the period, SMBG
system made steady advancements to the
models operable by anyone using a smaller
amount of blood for a broader range of blood
glucose level. The time necessary for the
1
Tokyo Saiseikai Central Hospital
Shu Meguro Masuomi Tomita
Chisato Murata Sonoko Anazawa
Kiyoe Kato Kenpei Matsuoka
Yoshihito Atsumi Yuko Takeda
Nahoko Sato Kunio Koka
measurement decreased substantially.
In May 2003, ISO15197 was enacted for
the assessment of performance of
blood-glucose monitoring systems for
self-testing in managing diabetes mellitus. In
March 2007, the Approval Standard for
SMBG Devices was issued in Japan as a
MHLW notification (PFSB Notification No.
0302006), which obligate the applicants to
obtain data for [1] the assessment of
repeatability (within-run repeatability and
between-run repeatability) and [2] the
assessment of precision (comparison with the
standard measurement method).
The authors had a chance to assess the
performance of a newly developed SMBG
system based on the double-wavelength
colorimetric method, MEDISAFE FIT
(Terumo Corporation) according to the
Japanese Approval Standard for SMBG
Devices.
 - Journal of New Remedies & Clinics Vol. 59 No. 7 2010 -
I. Subjects and methods
1. Subjects
The study was performed using the blood
samples from 116 outpatients who were
undergoing diabetes treatment in Department
of Internal Medicine, Tokyo Saiseikai Central
Hospital, fulfilled the pre-defined inclusion
criteria, and consented in writing to participate
in the study.
2. Collection of samples and treatment
method
Venous blood collected into the vacuum
blood collection tube containing heparin
sodium was refrigerated promptly in
consideration of the risk of glycolysis. In
principle, to perform the measurement by the
end of the day of collection, samples were
subdivided into two tubes, ice-cooled until
immediately before the measurement, and
measured using MEDISAFE FIT. The
temperature of the samples was returned to the
room temperature immediately before the
measurement. The other sample was
centrifuged (3000 rpm, 10 minutes) and the
supernatant was measured using LABOSPECT
008 (Hitachi High-Technologies Corporation)
and L Type Wako Glu2 (Wako Pure Chemical
Industries, Ltd.).
3. Overview of the SMBG device and
measurement principles
MEDISAFE FIT, a SMBG system with
which the chromogen whose color is produced
by the glucose oxidase method is determined
by the double-wavelength measurement
system using the test paper, was used. Photo 1
shows the appearance of the main unit of the
SMBG device and Fig. 1 shows the reagent
reaction and the measurement principles. The
measurement sensitivity was improved by the
enhancement of color production of the test
strip by the use of the reagent
(N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dim
ethyl aniline sodium and the reagent newly
synthesized by Terumo Corporation,
1-(4-sulphonyl)-2,
3-dimethyl-4-amino-5-pyrazolone). In the
main body of the SMBG device, two light
sources, LED1 with the central wavelength
located at 630 nm for reading the optical
absorption of the color production reagent and
LED2 with the central wavelength located at
520 nm for detecting the blood color and
determining the hematocrit (Ht) level, are
2
installed, which enables the correction of
measurement data with Ht level and efficient
colorimetric analysis of blood glucose.
The measurement using MEDISAFE FIT
needs 0.8 L of whole blood samples. The
measurement time is as short as 9 seconds and
the Ht level needs to be between 20 and 60%
and the ambient temperature needs to be
between 5 and 40C. Measurement using
MEDISAFE FIT is verified unaffected by the
substances specified in MHLW notifications
regarding safety measures (maltose (PFAB/SD
Notification No. 0207007) and pralidoxime
methyl iodide (PFAB/SD Notification No.
0907001)).
4. Control comparison method
As the control method, the automatic analysis
system, LABOSPECT 008 and L Type Wako
Glu2, which is the test method routinely used
in the hospital, and the measurement reagent
based on the principle of hexonase/glucose-6-
phosphate dehydrogenase method
(HK-G6PDH method), which is the glucose
measurement method recommended by the
Japan Society of Clinical Chemistry were used.
As for the assessment of precision of the
measurement data obtained using
LABOSPECT 008 and L Type Wako Glu2,
the equipment were calibrated using the
regular standard substance of
nitrogen-contained glucose of Reference
Material Institute for Clinical Chemistry
Standards (JCCRM 521) as specified in
MHLW Notification No. 120 as the standard
substance for the verification of performance
for the application for the in vitro diagnostics.
JCCRM 521 is the primary standard substance
determined using the isotope dilution mass
spectrometry to assure the precision of the
glucose concentration. The certified glucose
concentration is determined by the method
recommended by JCCRM.
II. Study methods
1. Within-run repeatability
Blood samples were prepared at 7 glucose
levels ([1] 24 mg/dL, [2] 41 mg/dL, [3]
109 mg/dL, [4] 141 mg/dL, [5] 185 mg/dL, [6]
272 mg/dL, [7] 561 mg/dL) as specified in
ISO15197 and the Approval Standard for
SMBG Devices using the venous blood
obtained from patients and collected into the
vacuum blood collection tube containing
 - Journal of New Remedies & Clinics Vol. 59 No. 7 2010 -

heparin sodium. Blood samples containing glucose by 7 concentrations were measured

Main unit Appearance of test

tip
Test strip (Color
production area)

Test tip (Aspiration nozzle)

Photo 1: Appearance of the SMBG device using the double-wavelength colorimetric method, MEDISAFE FIT

Reaction principle of the reagent

Glucose oxidase

-D-glucose+O2 + H2O D-glucono--lactone + H2O2

1-(4-sulphonyl)-2,3-dimethyl-4-amin
o-5-pyrazolone

Perodixase

N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethyl
aniline sodium
Light blue production
Framed compound: Active ingredient of the test paper

Measurement principle of the main unit: Cross section image diagram

LED1: Light-emitting diode with the wavelength
located at 630 nm (for the assessment using the color
production reagent)
LED2: Light-emitting diode with the wavelength
located at 520 nm (for the determination of blood/Ht
concentrations)

Fig. 1 Reaction principle of the reagent and measurement principle of the main body

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 - Journal of New Remedies & Clinics Vol. 59 No. 7 2010 -
Table 1 Range of glucose concentration specified in ISO15197 and Japanese Approval Standard for SMBG
Devices
[1] Acceptance criteria for within-run repeatability
Sample Range of glucose concentration (mg/dL)
1 20-29
2 30-50
3 51-110
4 111-150
5 151-250
6 251-400
7 401-600
[2] Acceptance criteria for between-run repeatability
Sample Range of glucose concentration (mg/dL)
1 20-29
2 30-50
3 96-144
4 280-420
5 421-600
using ten MEDISAFE FIT each by 10
repetitions and the mean, standard deviation
(SD), and coefficient of variation (CV) were
calculate to obtain within-run repeatability.
Table 1-(1) shows the range of glucose
concentrations (Samples [1] to [7]) and the
acceptance criteria for within-run repeatability.
2. Between-run repeatability.
Between-run repeatability was assessed
also using the blood samples at 5 glucose
levels ([1] 24 mg/dL, [2] 40 mg/dL, [3]
127 mg/dL, [4] 315 mg/dL, [5] 545 mg/dL) as
specified in the Approval Standard for SMBG
Devices. Using ten MEDISAFE FIT, the
control solutions at 5 glucose concentrations
were measured for 10 days and the mean,
standard deviation (SD), and coefficient of
variation (CV) were calculated to obtain
between-run repeatability. Table 1-(2) shows
the range of glucose concentrations (Samples
[1] to [5]) and the acceptance criteria for
between-run repeatability.
3. Precision assessment (Control
comparison method and correlation
with MEDISAFE FIT)
Dual measurements of 116 samples of
venous blood obtained from patients and
collected into the vacuum blood collection
tube containing heparin sodium were
performed using two of randomly selected
4
Acceptance criteria
SD, not more than 5 mg/dL
SD, not more than 5 mg/dL
CV, not more than 5%
CV, not more than 5%
CV, not more than 5%
CV, not more than 5%
CV, not more than 5%
Acceptance criteria
Total SD, not more than 7.5 mg/dL
Total SD, not more than 7.5 mg/dL
Total CV, not more than 7.5%
Total CV, not more than 7.5%
Total CV, not more than 7.5%
MEDISAFE FIT. The stability of the samples
associated with glycolysis was assessed before
and after the measurement in comparison with
the previously determined acceptable glucose
variation range and the data obtained from the
samples assessed deviating from the
acceptable range were excluded. The
acceptable variation between the first
measurement data and the last measurement
data was designated as less than 4% for the
samples of which glucose concentration is
higher than 100 mg/dL and less than 4 mg/dL
for the samples of which glucose concentration
is not higher than 100 mg/dL. As a result, 14
of the 116 samples were assessed deviating
from the acceptable variation and excluded
from the correlation analysis and dual
measurement data obtained from 102 samples
(from 204 measurements) were subject to the
analysis.
Meanwhile, the same samples were
centrifuged and the correlation between the
data obtained by the recommended glucose
measurement method (HK-G6PDH method)
using LABOSPECT 008 and L Type Wako
Glu2 (control method) and the measurement
data obtained using MEDISAFE FIT was
assessed.
 - Journal of New Remedies & Clinics Vol. 59 No. 7 2010 -
III. Results
1. Within-run repeatability
Table 2 shows the result of assessment of
within-run repeatability. The standard
deviation of the samples containing glucose at
the concentration of not more than 50 mg/dL
(Samples [1] and [2]) was 1.8 and 1.4 mg/dL,
respectively, which was not higher than the
acceptance criteria of 5 mg/dL, and the result
suggests that the data from the samples were
adequately acceptable in terms of within-run
repeatability. As for the samples containing
glucose at the concentration of 51 mg/dL or
over (Samples [3] to [7]), the total CV was as
satisfactory as between 2.5 and 3.3% and less
than the acceptance criterion of not more than
5%.
2. Between-run repeatability
Table 3 shows the result of assessment of
between-run repeatability. The total SD of
Control Solutions [1] and [2] was 0.96 and 1.3
mg/dL, respectively, which was within the
acceptable criterion of 7.5 mg/dL or lower.
Also as for Control Solutions [3] to [5], the
total CV was as satisfactory as between 2.6
and 4.8% and less than the acceptable criterion
of not more than 7.5%.
3. Precision assessment
Fig. 2 shows the correlation with the
control comparison method (x) and the plots of
differences. The linear regression formula of y
= 1.00x 4.11 and the correlation coefficient
(R) of 0.995 substantiate the satisfactory
correlation. Plots of differences between all
measurement data obtained from 204 samples
and the measurement data obtained by the
control comparison method were within the
acceptable range of error (within 15 mg/dL
for the samples containing glucose by less than
75 mg/dL, within 20% for the samples
containing glucose by not less than 75 mg/dL)
and fulfilled the requirements of ISO15197
and the Japanese Approval Standard for
SMBG Devices.
IV. Discussions
The authors assessed a SMBG systems
newly developed by Terumo Corporation and
based on the double-wavelength colorimetric
method, MEDISAFE FIT, in terms of the
within-run repeatability, between-run
repeatability, and precision in accordance with
the criteria for the assessment of analytical
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performance in ISO15197 and the Japanese
Approval Standard for SMBG Devices.
As a result, at the low glucose range at
which within-run repeatability data tend to be
relatively more dispersed, the standard
deviation was between 1.4 and 1.8 mg/dL,
showing that the data were acceptable in terms
of within-run repeatability. Also at the range
of clinical concentration of not less than 100
mg/dL, the total CV was as small as 2.5 to
3.3%, showing that the data were adequately
acceptable in terms of the precision. The result
of assessment of between-run repeatability
fulfills the acceptance criteria, suggesting that
measurement using the device is expected to
produce stable data. Furthermore, in the
assessment of precision, a favorable
correlation was seen between the measurement
data obtained using the device and the data
obtained by the glucose measurement method
(HK method) recommended by the Japanese
Committee for Clinical Laboratory Standards
(JCCLS) using LABOSPECT 008 and L Type
Wako Glu2, and the device is considered to
have basic performance and be usable
according to the global blood glucose
management standards. These days, various
SMBG devices have many advantages, such as
which are simple and easy to operate and can
be handled easily by anyone, so that they are
used widely in medical institutions and at
homes of patients and contribute to the routine
blood glucose control in diabetic patients.
MEDISAFE FIT is also usable widely for
blood glucose control not only in medical
institutions but in elderly care facilities and at
homes of diabetic patients and is considered
highly useful.
Meanwhile, as stricter blood glucose
control is demanded, the devices are expected
to be more accurate and precise. Also along
with the diversification of therapeutic means in
clinical sites, clinicians are required to more
carefully select and use the SMBG devices,
especially in consideration of the influences of
the substances specified in MHLW
notifications regarding safety measures
(maltose (PFAB/SD Notification No.
02507007) and pralidoxime methyl iodide
(PFAB/SD Notification No. 0907001)).
Measurement using MEDISAFE FIT is
verified unaffected by maltose or pralidoxime
methyl iodide and MEDISAFE FIT is
considered usable in various healthcare
 - Journal of New Remedies & Clinics Vol. 59 No. 7 2010 -

environments. various restrictions and conditions in mind as

Furthermore, clinicians need to always bear

Table 2 Result of assessment of within-run repeatability

Glucose concentration in Sample [1]: 24 mg/dL
Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 28 27 27 26 27 26 26 28 26 27
SD (mg/dL) 1.1 2.3 1.8 1.5 1.5 1.5 1.4 2.2 2.1 1.5
95% confidence interval (Mean) 0.79 1.7 1.3 1.1 1.1 1.1 1.0 1.5 1.5 1.1
CV (%) 3.9 8.8 6.9 5.7 5.7 5.9 5.6 7.8 8.0 5.6

Total mean (mg/dL) 27

Total variation 274
Total SD (mg/dL) 1.8
95% confidence interval (Total mean) 0.37
Total CV (%) 6.9

Glucose concentration in Sample [2]: 41 mg/dL

Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 43 43 42 41 42 42 40 43 42 44
SD (mg/dL) 1.2 1.1 1.2 1.7 0.88 0.95 0.95 1.0 1.1 0.85
95% confidence interval (Mean) 0.83 0.77 0.89 1.2 0.63 0.68 0.68 0.71 0.79 0.61
CV (%) 2.7 2.5 3.0 4.1 2.1 2.3 2.4 2.3 2.6 2.0

Total mean (mg/dL) 42

Total variation 112
Total SD (mg/dL) 1.4
95% confidence interval (Total mean) 0.27
Total CV (%) 3.2

Glucose concentration in Sample [3]: 109 mg/dL

Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 94 93 91 90 93 92 90 96 92 93
SD (mg/dL) 1.7 1.6 2.3 1.6 1.6 2.1 1.4 1.2 1.4 1.0
95% confidence interval (Mean) 1.2 1.1 1.6 1.1 1.2 1.5 1.0 0.86 1.0 0.74
CV (%) 1.8 1.7 2.5 1.7 1.8 2.3 1.6 1.2 1.5 1.1

Total mean (mg/dL) 92

Total variation 241
Total SD (mg/dL) 2.3
95% confidence interval (Total mean) 0.46
Total CV (%) 2.5

(Tables continued to the following page)

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 - Journal of New Remedies & Clinics Vol. 59 No. 7 2010 -

(Tables continued from the previous page)

Glucose concentration in Sample [4]: 141 mg/dL

Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 128 123 119 121 124 124 120 125 120 120
SD (mg/dL) 2.5 3.0 1.4 2.6 2.8 3.3 2.7 3.3 1.8 2.0
95% confidence interval (Mean) 1.8 2.1 1.0 1.8 2.0 2.4 1.9 2.3 1.3 1.4
CV (%) 2.0 2.4 1.2 2.1 2.3 2.7 2.3 2.6 1.5 1.7

Total mean (mg/dL) 122

Total variation 610
Total SD (mg/dL) 3.6
95% confidence interval (Total mean) 0.71
Total CV (%) 2.9

Glucose concentration in Sample [5]: 185 mg/dL

Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 171 171 166 163 168 164 165 167 168 168
SD (mg/dL) 3.4 5.0 3.0 4.5 4.5 3.7 4.2 4.7 5.4 4.3
95% confidence interval (Mean) 2.4 3.6 2.2 3.2 3.2 2.7 3.0 3.3 3.9 3.1
CV (%) 2.0 2.9 1.8 2.8 2.7 2.3 2.5 2.8 3.2 2.6

Total mean (mg/dL) 167

Total variation 1688
Total SD (mg/dL) 4.8
95% confidence interval (Total mean) 0.96
Total CV (%) 2.9

Glucose concentration in Sample [6]: 272 mg/dL

Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 245 252 244 242 244 246 242 253 245 240
SD (mg/dL) 9.5 7.4 3.9 6.1 5.5 8.3 4.7 5.0 4.4 5.8
95% confidence interval (Mean) 6.8 5.3 2.8 4.4 4.0 5.9 3.3 3.6 3.2 4.2
CV (%) 3.9 2.9 1.6 2.5 2.3 3.4 1.9 2.0 1.8 2.4

Total mean (mg/dL) 245

Total variation 3590
Total SD (mg/dL) 7.2
95% confidence interval (Total mean) 1.4
Total CV (%) 2.9

(Tables continued to the following page)

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(Table 2 Result of assessment of within-run repeatability continued from the previous page)

Glucose concentration in Sample [7]: 561 mg/dL

Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 578 572 559 541 555 571 551 583 565 558
SD (mg/dL) 14.7 21.6 13.0 14.3 16.5 16.3 14.1 11.2 10.2 12.2
95% confidence interval (Mean) 10.5 15.5 9.3 10.2 11.8 11.6 10.1 8.0 7.3 8.7
CV (%) 2.5 3.8 2.3 2.6 3.0 2.8 2.6 1.9 1.8 2.2

Total mean (mg/dL) 563

Total variation 19533
Total SD (mg/dL) 18.7
95% confidence interval (Total mean) 3.7
Total CV (%) 3.3

Table 3 Result of assessment of between-run repeatability

Glucose concentration in Sample [1]: 24 mg/dL
Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 28 27 28 27 27 27 28 28 27 28
SD (mg/dL) 0.94 0.82 0.52 0.52 1.1 1.1 0.97 1.1 1.1 0.88
95% confidence interval (Mean) 0.67 0.59 0.37 0.37 0.76 0.76 0.69 0.76 0.75 0.63
CV (%) 3.4 3.0 1.9 1.9 3.9 3.9 3.5 3.7 3.9 3.1

Total mean (mg/dL) 28

Total variation 75
Total SD (mg/dL) 0.96
95% confidence interval (Total mean) 0.19
Total CV (%) 3.5

Glucose concentration in Sample [2]: 40 mg/dL

Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 46 45 46 46 46 46 45 46 45 46
SD (mg/dL) 1.3 2.0 0.99 0.67 1.3 0.97 1.1 1.2 0.85 1.2
95% confidence interval (Mean) 0.89 1.5 0.71 0.48 0.90 0.69 0.77 0.88 0.61 0.83
CV (%) 2.7 4.5 2.2 1.5 2.8 2.1 2.4 2.7 1.9 2.5

Total mean (mg/dL) 46

Total variation 130
Total SD (mg/dL) 1.3
95% confidence interval (Total mean) 0.26
Total CV (%) 2.8

(Tables continued to the following page)

(Tables continued from the previous page)

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 - Journal of New Remedies & Clinics Vol. 59 No. 7 2010 -

Glucose concentration in Sample [3]: 127 mg/dL

Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 128 128 126 125 127 126 125 128 125 129
SD (mg/dL) 2.2 3.0 2.5 3.5 2.9 2.2 2.7 4.2 4.1 2.8
95% confidence interval (Mean) 1.6 2.2 1.8 2.5 2.1 1.6 1.9 3.0 2.9 2.0
CV (%) 1.7 2.4 2.0 2.8 2.3 1.8 2.2 3.3 3.2 2.2

Total mean (mg/dL) 127

Total variation 854
Total SD (mg/dL) 3.3
95% confidence interval (Total mean) 0.65
Total CV (%) 2.6

Glucose concentration in Sample [4]: 315 mg/dL

Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 311 310 305 304 301 300 304 307 300 303
SD (mg/dL) 12.7 13.1 7.1 9.1 13.0 14.3 13.7 11.5 11.4 9.1
95% confidence interval (Mean) 9.1 9.3 5.1 6.5 9.3 10.2 9.8 8.2 8.2 6.5
CV (%) 4.1 4.2 2.3 3.0 4.3 4.8 4.5 3.7 3.8 3.0

Total mean (mg/dL) 305

Total variation 12334
Total SD (mg/dL) 11.8
95% confidence interval (Total mean) 2.3
Total CV (%) 3.9

Glucose concentration in Sample [5]: 545 mg/dL

Device No. 1 2 3 4 5 6 7 8 9 10
Mean data (mg/dL) 547 564 547 535 539 524 532 545 545 543
SD (mg/dL) 25.8 26.3 26.3 23.1 20.2 26.2 27.6 23.2 32.0 17.2
95% confidence interval (Mean) 18.5 18.8 18.8 16.5 14.5 18.7 19.7 16.6 22.9 12.3
CV (%) 4.7 4.7 4.8 4.3 3.8 5.0 5.2 4.3 5.9 3.2

Total mean (mg/dL) 542

Total variation 56731
Total SD (mg/dL) 26.0
95% confidence interval (Total mean) 5.2
Total CV (%) 4.8

(Tables continued to the following page)

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[Correlation]

Measurement data obtained using

MEDISAFE FIT

Measurement data obtained using LABOSPECT 008 and L Type Wako Glu2

[Plot of differences from the control method]

Difference from the control method

Measurement data obtained using LABOSPECT 008 and L Type Wako Glu2

Fig. 2 Result of precision assessment

exemplified by the fact that most of the users of MEDISAFE FIT broadens the usability in
SMBG systems are old and have concomitant blood glucose control and team medicine as a
diseases. Simple and easy operating and SMBG system which has undergone
handling procedures are important points to remodeling with adequate consideration and is
bear in mind when selecting the device model. useful for the blood glucose management of
MEDISAFE FIT has superior properties which patients under home care.
existing products do not have as exemplified by
the main body which elderly patients can easily Summary
carry, the considerations for the appearance of
the test tip, dot LED display of operating The authors assessed a SMBG system based
procedures and other information, on the double-wavelength colorimetric method,
easy-to-understand precautions and error MEDISAFE FIT, and has reached the
messages. The main body of MEDISAFE FIT conclusion that the system has the analytical
can save up to 500 test results and the data are performance fulfilling the criteria of ISO15197
uploaded to PC or other devices by Near Field and the Japanese Approval Standard for SMBG
Communication System (FeliCa System), a Devices and is useful for the blood glucose
function introduced for the first time in the management in diabetic patients in future.
world.

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