I
n
t
e
r
n
a
t
i
o
n
a
l
J
o
u
r
n
a
l
of
P
u
b
l
i
c
H
e
a
l
t
h
S
c
i
e
n
c
e
(
I
J
P
H
S
)
V
o
l
.
10
,
N
o
.
1
,
M
a
r
c
h
2
0
2
1
,
pp.
8
8
~
9
6
I
S
S
N
:
2
2
5
2
-
8
8
0
6
,
D
O
I
:
1
0
.
1
1
5
9
1
/
i
j
p
h
s
.
v
1
0
i
1
.
2
0
5
7
0
88
J
o
u
r
n
a
l
h
o
m
e
p
a
g
e
:
h
t
t
p
:
/
/
i
j
p
h
s
.
i
a
e
s
c
o
r
e
.
c
o
m
N
i
c
o
ti
n
e
l
e
v
e
l
a
s
s
o
c
i
a
te
d
w
i
th
d
e
c
r
e
a
s
i
n
g
T
r
e
g
n
u
m
b
e
r
in
s
m
o
k
e
r
h
e
a
l
th
y
v
o
l
u
n
te
e
r
s
A
k
r
o
m
1
,
T
r
i
J
u
l
i
a
P
u
r
n
a
m
a
s
a
r
i
2
,
Z
a
k
y
N
u
r
f
a
i
z
3
,
A
d
n
a
n
4
,
E
n
d
a
n
g
D
a
r
m
a
w
a
n
5
,
M
u
h
a
m
m
a
d
Mu
h
l
i
s
6
1,4,5,6
D
e
p
a
rt
m
e
nt
P
ha
rm
a
c
ol
og
y
a
nd
Cl
i
ni
c
a
l
P
ha
rm
a
c
y
,
P
ha
rm
a
c
y
F
a
c
ul
t
y
,
U
ni
ve
rs
i
t
as
A
hm
a
d
D
a
hl
a
n,
Indone
s
i
a
1
A
hm
a
d
D
a
hl
a
n
D
rug
Inform
a
t
i
on
a
nd
Cri
s
i
s
Ce
nt
e
r,
Indone
s
i
a
2,3
M
a
g
i
s
t
e
r
Cl
i
ni
c
a
l
P
ha
rm
a
c
y
P
rog
ra
m
,
P
ha
rm
a
c
y
F
a
c
ul
t
y
,
U
ni
ve
rs
i
t
a
s
A
hm
a
d
D
a
hl
a
n
, Indone
s
i
a
A
r
t
i
c
l
e
I
n
f
o
A
B
S
T
R
A
C
T
A
r
t
i
c
l
e
h
i
s
t
o
r
y
:
R
e
c
e
i
v
e
d
Ju
l
7
,
2020
R
e
v
i
s
e
d
D
e
c
9
,
2020
A
c
c
e
p
t
e
d
J
a
n
2
,
20
21
T
he
i
nt
e
ns
i
t
y
of
c
i
g
a
re
t
t
e
e
x
p
os
ure
is
a
s
s
oc
i
a
t
e
d
w
i
t
h
t
he
s
e
ve
ri
t
y
of
t
he
i
nfl
a
m
m
a
t
ory
re
a
c
t
i
on.
T
re
g
cell
p
l
a
y
s
a
rol
e
in
s
up
p
re
s
s
i
ng
t
he
i
nfl
a
m
m
a
t
ory
re
s
p
ons
e
.
T
he
re
ha
s
be
e
n
no
clear
e
vi
de
nc
e
on
t
he
re
l
a
t
i
ons
hi
p
be
t
w
e
e
n
s
m
oke
r
be
ha
vi
or
w
i
t
h
t
he
ni
c
ot
i
ne
l
e
ve
l
a
nd
T
re
g
num
be
r.
We
w
i
l
l
i
nve
s
t
i
g
a
t
e
t
he
re
l
a
t
i
ons
hi
p
be
t
w
e
e
n
s
m
oki
ng
be
ha
vi
or
w
i
t
h
t
he
ni
c
ot
i
ne
l
e
ve
l
a
nd
T
re
g
num
be
r.
We
c
onduc
t
e
d
a
c
ros
s
-
s
e
c
t
i
ona
l
s
t
udy
of
106
he
a
l
t
hy
vol
unt
e
e
rs
in
Y
og
y
a
ka
rt
a
.
We
i
nt
e
rvi
e
w
e
d
t
he
s
ubj
e
c
t
s
a
nd
t
ook
t
he
i
r
bl
ood
s
a
m
p
l
e
s
for
he
m
og
ra
m
,
T
re
g
num
be
r,
ni
c
ot
i
ne
l
e
ve
l
,
a
nd
bl
ood
c
he
m
i
s
t
ry
e
x
a
m
i
na
t
i
on.
T
he
i
nc
l
us
i
on
c
ri
t
e
ri
a
w
e
re
fi
t
,
male
or
fe
m
a
l
e
,
a
g
e
d
18
y
e
a
rs
or
ol
de
r,
a
nd
w
i
l
l
i
ng
to
vol
unt
e
e
r
p
rove
n
by
c
om
p
l
e
t
i
ng
a
nd
s
i
g
ni
ng
t
he
i
nform
ed
c
ons
e
nt
.
We
c
ol
l
e
c
t
e
d
t
he
da
t
a
on
s
m
oki
ng
ha
bi
t
s
t
hroug
h
i
nt
e
rvi
e
w
s
g
ui
de
d
by
a
que
s
t
i
onna
i
re
.
We
e
x
a
m
i
ne
d
he
m
og
ra
m
a
nd
bl
ood
c
he
m
i
s
t
ry
us
i
ng
a
s
p
e
c
t
rop
hot
om
e
t
e
r,
w
hi
l
e
t
he
l
e
ve
l
s
of
ni
c
ot
i
ne
w
e
re
m
e
a
s
ure
d
us
i
ng
T
he
e
nz
y
m
e
-
l
i
nke
d
i
m
m
unos
orbe
nt
a
s
s
a
y
(
EL
IS
A
)
.
We
de
s
c
ri
be
d
t
he
c
ha
ra
c
t
e
ri
s
t
i
c
s
of
t
he
s
ubj
e
c
t
s
by
uni
va
ri
a
t
e
a
na
l
y
s
i
s
.
T
he
bi
va
ri
a
t
e
a
na
l
y
s
i
s
w
a
s
to
de
t
e
rm
i
ne
t
he
re
l
a
t
i
ons
hi
p
be
t
w
e
e
n
c
i
g
a
re
t
t
e
s
m
oki
ng
l
e
ng
t
h
w
i
t
h
ni
c
ot
i
ne
l
e
ve
l
a
nd
T
re
g
num
be
r.
T
he
re
s
ul
t
s
s
how
a
c
onne
c
t
i
on
be
t
w
e
e
n
t
he
ra
ng
e
of
t
oba
c
c
o
a
nd
c
i
g
a
re
t
t
e
num
be
r
w
i
t
h
ni
c
ot
i
ne
l
e
ve
l
s
in
t
he
bl
ood
w
i
t
h
a
va
l
ue
of
r
=
0.63
in
t
he
P
e
a
rs
on
c
orre
l
a
t
i
on
t
e
s
t
p
<
0.00
.
It
can
be
c
onc
l
ude
d
t
ha
t
t
he
re
is
a
re
l
a
t
i
ons
hi
p
be
t
w
e
e
n
be
ha
vi
or
s
m
oki
ng
w
i
t
h
ni
c
ot
i
ne
l
e
ve
l
s
a
nd
T
re
g
c
ount
s
.
K
e
y
w
o
r
d
s
:
C
r
o
s
s
-
s
e
c
t
i
o
n
a
l
s
t
u
d
y
D
u
r
a
t
i
o
n
of
s
m
o
k
i
n
g
S
m
o
k
i
n
g
b
e
h
a
v
i
o
r
T
r
e
g
n
u
m
b
e
r
n
i
c
o
t
i
n
e
l
e
v
e
l
T
hi
s
is
an
ope
n
ac
c
e
s
s
ar
t
i
c
l
e
unde
r
t
he
CC
BY
-
SA
l
i
c
e
ns
e
.
C
o
r
r
e
s
p
o
n
d
i
n
g
A
u
t
h
o
r
:
A
k
r
o
m
D
e
p
a
r
t
m
e
n
t
P
h
a
r
m
a
c
o
l
o
g
y
a
n
d
C
l
i
n
i
c
a
l
P
h
a
r
m
a
c
y
P
h
a
r
m
a
c
y
F
a
c
u
l
t
y
,
U
n
i
v
e
r
s
i
t
a
s
A
h
m
a
d
D
a
h
l
a
n
,
I
n
d
o
n
e
s
i
a
E
m
a
i
l
:
a
k
r
o
m
@p
h
a
r
m
.
u
a
d
.
a
c
.
i
d
1.
I
N
T
R
O
D
U
C
T
I
O
N
S
m
o
k
i
n
g
is
a
s
i
g
n
i
f
i
c
a
n
t
p
u
b
l
i
c
h
e
a
l
t
h
p
r
o
b
l
e
m
in
S
o
u
t
h
e
a
s
t
A
s
i
a
a
n
d
I
n
d
o
n
e
s
i
a
.
I
n
d
o
n
e
s
i
a
is
t
h
e
f
o
u
r
t
h
-
l
a
r
g
e
s
t
c
i
g
a
r
e
t
t
e
c
o
n
s
u
m
i
n
g
c
o
u
n
t
r
y
in
t
h
e
w
o
r
l
d
[
1
]
.
T
h
e
p
r
e
v
a
l
e
n
c
e
of
s
m
o
k
i
n
g
is
75%
(
5
7
.
6
m
i
l
l
i
o
n
)
a
m
o
n
g
m
e
n
a
n
d
2
.
9
%
(
2
.
3
m
i
l
l
i
o
n
)
in
w
o
m
e
n
.
A
m
o
n
g
t
h
e
a
d
u
l
t
p
o
p
u
l
a
t
i
o
n
,
62%
of
a
d
u
l
t
m
e
n
(
5
7
.
6
m
i
l
l
i
o
n
)
,
1
.
7
%
of
a
d
u
l
t
w
o
m
e
n
(
1
.
6
m
i
l
l
i
o
n
)
,
a
n
d
3
1
.
9
%
o
v
e
r
a
l
l
(
5
0
.
3
m
i
l
l
i
o
n
)
a
r
e
d
a
i
l
y
s
m
o
k
e
r
s
[
2
]
.
T
h
e
N
a
t
i
o
n
a
l
B
a
s
i
c
H
e
a
l
t
h
R
e
s
e
a
r
c
h
in
2016
s
h
o
w
e
d
t
h
a
t
t
h
e
a
v
e
r
a
g
e
c
o
n
s
u
m
p
t
i
o
n
of
c
i
g
a
r
e
t
t
e
s
p
e
r
p
e
r
s
o
n
(
a
g
e
d
15
y
e
a
r
s
or
a
b
o
v
e
)
w
a
s
12
s
t
i
c
k
s
/
d
a
y
[
3
]
.
T
o
b
a
c
c
o
s
m
o
k
e
h
a
s
b
e
e
n
a
s
s
o
c
i
a
t
e
d
w
i
t
h
m
a
n
y
d
e
g
e
n
e
r
a
t
i
v
e
a
n
d
i
n
f
e
c
t
i
o
u
s
d
i
s
e
a
s
e
s
,
i
.
e
.,
c
a
n
c
e
r
,
h
y
p
e
r
t
e
n
s
i
o
n
a
n
d
c
a
r
d
i
o
v
a
s
c
u
l
a
r
d
i
s
e
a
s
e
,
c
h
r
o
n
i
c
o
b
s
t
r
u
c
t
i
v
e
p
u
l
m
o
n
a
r
y
d
i
s
e
a
s
e
(
C
O
P
D
)
,
a
s
t
h
m
a
,
d
i
a
b
e
t
e
s
m
e
l
l
i
t
u
s
,
a
n
d
e
n
d
-
s
t
a
g
e
r
e
n
a
l
d
i
s
e
a
s
e
(
E
S
R
D
)
[
4
,
5
]
.
T
h
e
c
i
g
a
r
e
t
t
e
c
o
n
t
a
i
n
s
m
a
n
y
t
o
x
i
c
a
n
d
i
m
m
u
n
o
s
u
p
p
r
e
s
s
a
n
t
a
g
e
n
t
s
,
s
u
c
h
as
d
i
m
e
t
h
y
l
b
e
n
z
a
n
t
h
r
a
c
e
n
e
(
D
M
B
A
)
,
b
e
n
z
o
p
y
r
e
n
e
,
c
a
r
b
o
n
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t
.
J
.
P
u
b
l
i
c
H
e
a
l
t
h
S
c
i
.
I
S
S
N
:
2252
-
8
8
0
6
N
i
c
o
t
i
n
e
l
e
v
e
l
a
s
s
o
c
i
a
t
e
d
w
i
t
h
d
e
c
r
e
a
s
i
n
g
T
r
e
g
n
u
m
b
e
r
i
n
s
m
o
k
e
r
h
e
a
l
t
h
y
v
o
l
u
n
t
e
e
r
s
(
A
k
r
o
m
)
89
m
o
n
o
x
i
d
e
,
a
n
d
n
i
c
o
t
i
n
e
[
6
,
7
]
.
E
x
c
e
s
s
i
v
e
n
i
c
o
t
i
n
e
i
n
t
a
k
e
c
a
u
s
e
s
m
a
n
y
o
r
g
a
n
s
a
n
d
t
i
s
s
u
e
d
i
s
o
r
d
e
r
s
[
8
,
9
]
.
H
e
a
l
t
h
p
r
o
m
o
t
i
o
n
to
a
w
a
k
e
n
s
m
o
k
i
n
g
d
a
n
g
e
r
s
b
a
s
e
d
on
s
c
i
e
n
t
i
f
i
c
e
v
i
d
e
n
c
e
is
u
r
g
e
n
t
l
y
c
o
n
d
u
c
t
e
d
[
1
0
,
1
1
]
.
N
i
c
o
t
i
n
e
is
a
c
i
g
a
r
e
t
t
e
t
o
x
i
c
a
n
t
t
h
a
t
c
a
u
s
e
s
c
e
l
l
d
a
m
a
g
e
.
E
x
p
o
s
u
r
e
to
s
m
o
k
e
c
a
u
s
e
s
c
e
l
l
i
n
j
u
r
y
[
1
2
]
.
C
e
l
l
u
l
a
r
d
a
m
a
g
e
s
t
i
m
u
l
a
t
e
s
p
r
o
i
n
f
l
a
m
m
a
t
o
r
y
c
y
t
o
k
i
n
e
p
r
o
d
u
c
t
i
o
n
.
P
r
o
i
n
f
l
a
m
m
a
t
i
o
n
c
y
t
o
k
i
n
e
s
a
n
d
r
e
a
c
t
i
v
e
p
r
o
t
e
i
n
c
a
u
s
e
an
i
n
c
r
e
a
s
e
in
bone
m
a
r
r
o
w
a
c
t
i
v
i
t
y
[
1
3
]
.
T
h
e
d
i
s
t
r
i
b
u
t
i
o
n
a
n
d
a
b
s
o
r
p
t
i
o
n
of
n
i
c
o
t
i
n
e
i
n
t
o
t
h
e
p
u
l
m
o
n
a
r
y
c
i
r
c
u
l
a
t
i
o
n
a
r
e
s
w
i
f
t
[
1
4
]
.
N
i
c
o
t
i
n
e
can
p
e
n
e
t
r
a
t
e
t
h
e
b
l
o
o
d
-
b
r
a
i
n
b
a
r
r
i
e
r
a
n
d
a
f
f
e
c
t
t
h
e
c
e
n
t
r
a
l
n
e
r
v
o
u
s
s
y
s
t
e
m
w
i
t
h
i
n
20
s
e
c
o
n
d
s
of
i
n
h
a
l
e
d
c
i
g
a
r
e
t
t
e
s
.
In
t
h
e
a
c
u
t
e
p
h
a
s
e
of
n
i
c
o
t
i
n
e
,
s
t
i
m
u
l
a
t
i
o
n
cau
s
e
s
t
h
e
s
y
m
p
a
t
h
e
t
i
c
n
e
r
v
e
s
'
a
c
t
i
v
a
t
i
o
n
a
n
d
m
a
k
e
s
t
h
e
c
o
n
d
i
t
i
o
n
v
i
b
r
a
n
t
a
n
d
r
e
f
r
e
s
h
e
d
.
In
a
s
h
o
r
t
t
i
m
e
(
1
0
m
i
n
u
t
e
s
of
s
m
o
k
i
n
g
)
,
p
l
a
s
m
a
n
i
c
o
t
i
n
e
p
e
a
k
i
s
at
15
to
30
n
g
/
m
L
[
1
5
]
.
R
a
p
i
d
p
h
a
r
m
a
c
o
l
o
g
i
c
a
l
r
e
s
p
o
n
s
e
f
r
o
m
n
i
c
o
t
i
n
e
is
a
s
s
u
m
e
d
to
be
a
c
r
i
t
i
c
a
l
f
a
c
t
o
r
i
n
n
i
c
o
t
i
n
e
d
e
p
e
n
d
e
n
c
e
.
In
t
h
e
a
d
v
a
n
c
e
d
p
h
a
s
e
,
h
i
g
h
l
e
v
e
l
s
of
n
i
c
o
t
i
n
e
a
n
d
r
e
a
c
t
i
v
e
r
a
d
i
c
a
l
s
a
n
d
c
a
r
c
i
n
o
g
e
n
s
h
a
v
e
t
h
e
o
p
p
o
s
i
t
e
e
f
f
e
c
t
.
In
t
h
e
r
o
u
t
i
n
e
s
m
o
k
e
r
,
w
h
o
s
m
o
k
e
s
f
r
e
q
u
e
n
t
l
y
a
n
d
c
o
n
t
i
n
u
o
u
s
l
y
,
t
h
e
c
a
r
b
o
x
y
h
e
m
o
g
l
o
b
i
n
(
Hb
)
l
e
v
e
l
s
i
n
c
r
e
a
s
e
a
n
d
p
r
o
d
u
c
e
p
r
o
g
r
e
s
s
i
v
e
h
y
p
o
x
e
m
i
a
,
a
n
d
as
t
h
e
c
a
r
b
o
n
m
o
n
o
x
i
d
e
(
CO
)
b
i
n
d
s
w
i
t
h
H
b
,
f
u
n
c
t
i
o
n
a
l
a
n
e
m
i
a
is
p
r
o
d
u
c
e
d
.
H
y
p
o
x
e
m
i
a
c
o
n
d
i
t
i
o
n
c
a
u
s
e
s
t
h
e
i
m
p
a
i
r
e
d
o
x
y
g
e
n
a
t
i
o
n
of
t
i
s
s
u
e
s
a
n
d
c
h
a
n
g
e
s
in
b
i
o
l
o
g
i
c
a
l
p
a
r
a
m
e
t
e
r
s
[
1
6
]
.
N
i
c
o
t
i
n
e
,
t
h
r
o
u
g
h
n
i
c
o
t
i
n
i
c
r
e
c
e
p
t
o
r
s
a
n
d
k
i
n
i
n
-
b
e
t
a
r
e
c
e
p
t
o
r
s
,
i
n
c
r
e
a
s
e
s
p
r
o
i
n
f
l
a
m
m
a
t
o
r
y
a
c
t
i
v
i
t
y
.
T
h
e
l
e
v
e
l
of
n
i
c
o
t
i
n
e
a
s
s
o
c
i
a
t
e
w
i
t
h
t
h
e
d
e
p
e
n
d
e
n
c
y
a
n
d
t
h
e
i
m
p
a
i
r
e
d
b
o
d
i
l
y
f
u
n
c
t
i
o
n
s
l
e
v
e
l
[
1
7
]
.
B
u
t
it
t
u
r
n
s
out
n
i
c
o
t
i
n
e
m
e
t
a
b
o
l
i
s
m
in
t
h
e
body
is
i
n
f
l
u
e
n
c
e
d
by
e
t
h
n
i
c
i
t
y
,
so
t
h
e
p
l
a
s
m
a
n
i
c
o
t
i
n
e
l
e
v
e
l
s
in
s
m
o
k
e
r
s
v
a
r
y
d
e
p
e
n
d
i
n
g
on
r
a
c
e
[
8
]
.
H
o
w
e
v
e
r
,
t
h
e
r
e
a
r
e
m
a
n
y
s
t
u
d
i
e
s
on
s
m
o
k
i
n
g
b
e
h
a
v
i
o
r
in
I
n
d
o
n
e
s
i
a
u
n
t
i
l
n
o
w
,
a
n
d
t
h
e
r
e
h
a
s
not
b
e
e
n
m
u
c
h
r
e
s
e
a
r
c
h
on
s
m
o
k
i
n
g
b
e
h
a
v
i
o
r
r
e
l
a
t
e
d
to
p
l
a
s
m
a
n
i
c
o
t
i
n
e
l
e
v
e
l
s
.
In
p
r
e
v
i
o
u
s
s
t
u
d
i
e
s
,
t
o
b
a
c
c
o
s
m
o
k
e
a
n
d
d
i
m
e
t
h
y
l
b
e
n
z
a
n
t
h
r
a
c
e
n
e
a
r
e
c
h
r
o
n
i
c
d
i
s
e
a
s
e
r
i
s
k
f
a
c
t
o
r
s
a
n
d
i
n
c
r
e
a
s
e
c
h
r
o
n
i
c
d
i
s
e
a
s
e
p
r
e
v
a
l
e
n
c
e
in
t
h
e
p
o
p
u
l
a
t
i
o
n
[
1
8
,
1
9
]
.
T
h
e
c
h
r
o
n
i
c
d
i
s
e
a
s
e
p
r
o
v
i
d
e
s
p
h
y
s
i
c
a
l
l
y
,
e
c
o
n
o
m
i
c
a
l
l
y
,
s
o
c
i
a
l
l
y
s
e
v
e
r
e
i
m
p
a
c
t
s
f
o
r
t
h
e
p
a
t
i
e
n
t
,
t
h
e
i
r
f
a
m
i
l
y
,
a
n
d
t
h
e
g
o
v
e
r
n
m
e
n
t
.
U
n
f
o
r
t
u
n
a
t
e
l
y
,
m
o
s
t
c
h
r
o
n
i
c
d
i
s
e
a
s
e
s
(
c
h
r
o
n
i
c
k
i
d
n
e
y
d
i
s
e
a
s
e
(
C
K
D
)
,
c
a
n
c
e
r
,
d
i
a
b
e
t
e
s
m
e
l
l
i
t
u
s
)
p
a
t
i
e
n
t
s
in
I
n
d
o
n
e
s
i
a
w
e
r
e
d
e
t
e
c
t
e
d
l
a
t
e
[
2
0
]
.
C
h
r
o
n
i
c
i
n
f
l
a
m
m
a
t
i
o
n
due
to
c
i
g
a
r
e
t
t
e
e
x
p
o
s
u
r
e
c
a
u
s
e
s
g
l
o
m
e
r
u
l
o
s
c
l
e
r
o
s
i
s
[
2
1
]
.
G
l
o
m
e
r
u
l
o
s
c
l
e
r
o
s
i
s
c
a
u
s
e
s
an
i
s
c
h
e
m
i
c
c
o
n
d
i
t
i
o
n
in
t
h
e
n
e
p
h
r
o
n
.
T
h
e
u
n
c
o
n
t
r
o
l
l
e
d
-
a
c
u
t
e
i
s
c
h
e
m
i
c
i
n
j
u
r
y
w
i
l
l
c
o
n
t
i
n
u
e
to
b
e
c
o
m
e
g
l
o
m
e
r
u
l
o
p
a
t
h
y
a
n
d
t
u
b
u
l
o
p
a
t
h
y
[
2
2
,
2
3
]
.
I
n
c
r
e
a
s
e
d
u
r
e
a
a
n
d
c
r
e
a
t
i
n
i
n
e
l
e
v
e
l
s
w
e
r
e
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
of
i
m
p
a
i
r
e
d
k
i
d
n
e
y
f
u
n
c
t
i
o
n
due
to
d
e
c
r
e
a
s
e
d
g
l
o
m
e
r
u
l
a
r
f
i
l
t
r
a
t
i
o
n
r
a
t
e
[
2
4
,
25]
.
A
l
a
b
o
r
a
t
o
r
y
s
t
u
d
y
h
a
s
s
h
o
w
n
to
c
o
n
t
r
o
l
t
h
e
i
n
f
l
a
m
m
a
t
o
r
y
r
e
s
p
o
n
s
e
to
a
c
u
t
e
i
s
c
h
e
m
i
c
k
i
d
n
e
y
d
a
m
a
g
e
in
v
i
v
o
.
T
r
e
g
is
one
of
t
h
e
i
m
m
u
n
e
s
y
s
t
e
m
c
e
l
l
s
r
e
s
p
o
n
s
i
b
l
e
f
o
r
m
a
i
n
t
a
i
n
i
n
g
k
i
d
n
e
y
d
a
m
a
g
e
'
s
i
n
f
l
a
m
m
a
t
o
r
y
r
e
a
c
t
i
o
n
due
to
c
i
g
a
r
e
t
t
e
e
x
p
o
s
u
r
e
[
2
6
,
2
7
]
.
We
s
u
s
p
e
c
t
e
d
t
h
a
t
t
h
e
n
u
m
b
e
r
of
T
r
e
g
c
e
l
l
s
h
a
s
d
e
c
r
e
a
s
e
d
in
c
h
r
o
n
i
c
s
m
o
k
e
r
s
,
a
n
d
c
r
e
a
t
i
n
i
n
e
l
e
v
e
l
s
h
a
v
e
i
n
c
r
e
a
s
e
d
due
to
d
e
c
r
e
a
s
e
d
g
l
o
m
e
r
u
l
a
r
f
u
n
c
t
i
o
n
[
2
8
,
2
9
]
.
B
a
s
e
d
on
t
h
i
s
b
a
c
k
g
r
o
u
n
d
,
t
h
i
s
s
t
u
d
y
a
i
m
e
d
to
d
e
t
e
r
m
i
n
e
t
h
e
r
e
l
a
t
i
o
n
s
h
i
p
b
e
t
w
e
e
n
s
m
o
k
i
n
g
b
e
h
a
v
i
o
r
w
i
t
h
n
i
c
o
t
i
n
e
l
e
v
e
l
s
a
n
d
t
h
e
a
m
o
u
n
t
of
T
r
e
g
.
2.
R
E
S
E
A
R
C
H
M
E
T
H
O
D
2
.
1
.
R
e
s
e
a
r
c
h
d
e
s
i
g
n
a
n
d
v
a
r
i
a
b
l
e
s
T
h
i
s
r
e
s
e
a
r
c
h
w
a
s
an
a
n
a
l
y
t
i
c
o
b
s
e
r
v
a
t
i
o
n
a
l
s
t
u
d
y
w
i
t
h
a
c
r
o
s
s
-
s
e
c
t
i
o
n
a
l
d
e
s
i
g
n
.
T
h
e
e
x
p
e
r
i
m
e
n
t
w
a
s
c
o
n
d
u
c
t
e
d
in
S
p
e
c
i
a
l
R
e
g
i
o
n
o
f
Y
o
g
y
a
k
a
r
t
a
o
r
D
a
e
r
a
h
I
s
t
i
m
e
w
a
Y
o
g
y
a
k
a
r
t
a
(
D
I
Y
)
,
I
n
d
o
n
e
s
i
a
,
by
t
a
k
i
n
g
a
r
a
n
d
o
m
p
r
o
p
o
r
t
i
o
n
a
l
s
a
m
p
l
e
in
f
i
v
e
d
i
s
t
r
i
c
t
s
:
Y
o
g
y
a
k
a
r
t
a
,
S
l
e
m
a
n
,
B
a
n
t
u
l
,
K
u
l
o
n
P
r
o
g
o
,
a
n
d
G
u
n
u
n
g
k
i
d
u
l
.
T
h
e
i
n
d
e
p
e
n
d
e
n
t
v
a
r
i
a
b
l
e
s
c
o
n
s
i
s
t
e
d
of
d
e
m
o
g
r
a
p
h
i
c
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
,
w
e
i
g
h
t
,
h
e
i
g
h
t
,
a
n
d
s
m
o
k
i
n
g
b
e
h
a
v
i
o
r
.
T
h
e
d
e
p
e
n
d
e
n
t
v
a
r
i
a
b
l
e
w
a
s
n
i
c
o
t
i
n
e
l
e
v
e
l
,
T
r
e
g
n
u
m
b
e
r
,
h
e
m
o
g
r
a
m
p
r
o
f
i
l
e
,
a
n
d
b
l
o
o
d
c
h
e
m
i
s
t
r
y
.
We
d
e
f
i
n
e
d
a
c
t
i
v
e
s
m
o
k
i
n
g
b
e
h
a
v
i
o
r
as
i
n
h
a
l
i
n
g
b
u
r
n
i
n
g
t
o
b
a
c
c
o
s
m
o
k
e
a
n
d
c
h
e
w
i
n
g
t
o
b
a
c
c
o
a
n
d
o
t
h
e
r
t
o
b
a
c
c
o
p
r
o
d
u
c
t
s
f
o
r
t
h
e
l
a
s
t
f
i
v
e
y
e
a
r
s
.
T
h
e
s
m
o
k
e
r
b
e
h
a
v
i
o
r
w
a
s
c
a
t
e
g
o
r
i
z
e
d
as
an
a
c
t
i
v
e
s
m
o
k
e
r
or
“
Y
E
S
”
if
t
h
e
r
e
s
p
o
n
d
e
n
t
s
h
a
v
e
s
m
o
k
e
d
m
o
r
e
t
h
a
n
100
c
i
g
a
r
e
t
t
e
s
in
t
h
e
i
r
l
i
f
e
t
i
m
e
;
NO
if
t
h
e
r
e
s
p
o
n
d
e
n
t
s
d
i
d
not
m
e
e
t
t
h
e
c
r
i
t
e
r
i
a
.
T
h
e
r
e
s
p
o
n
d
e
n
t
s
w
e
r
e
c
a
t
e
g
o
r
i
z
e
d
as
f
o
r
m
e
r
s
m
o
k
e
r
s
(
Y
E
S
)
if
t
h
e
y
h
a
d
s
m
o
k
e
d
m
o
r
e
t
h
a
n
100
c
i
g
a
r
e
t
t
e
s
in
t
h
e
i
r
l
i
f
e
t
i
m
e
but
h
a
d
s
t
o
p
p
e
d
b
e
f
o
r
e
t
h
e
l
a
s
t
f
i
v
e
y
e
a
r
s
.
N
o
n
s
m
o
k
e
r
s
w
e
r
e
t
h
e
r
e
s
p
o
n
d
e
n
t
s
w
h
o
d
i
d
not
s
m
o
k
e
or
h
a
d
s
m
o
k
e
d
but
l
e
s
s
t
h
a
n
100
c
i
g
a
r
e
t
t
e
s
in
t
h
e
i
r
l
i
f
e
t
i
m
e
.
We
c
o
l
l
e
c
t
e
d
s
m
o
k
i
n
g
b
e
h
a
v
i
o
r
d
a
t
a
t
h
r
o
u
g
h
i
n
t
e
r
v
i
e
w
s
s
u
p
p
o
r
t
e
d
by
a
q
u
e
s
t
i
o
n
n
a
i
r
e
.
We
c
o
n
f
i
r
m
e
d
t
h
e
d
a
t
a
by
t
h
e
m
e
a
s
u
r
e
m
e
n
t
of
b
l
o
o
d
n
i
c
o
t
i
n
e
l
e
v
e
l
s
u
s
i
n
g
E
L
I
S
A
.
T
r
e
g
l
e
v
e
l
w
a
s
t
h
e
p
e
r
c
e
n
t
a
g
e
of
T
r
e
g
(
C
D
4
+
C
D
2
5
+
T
l
y
m
p
h
o
c
y
t
e
s
)
a
g
a
i
n
s
t
t
o
t
a
l
l
y
m
p
h
o
c
y
t
e
s
d
e
f
i
n
e
d
by
f
l
o
w
c
y
t
o
m
e
t
r
y
.
2
.
2
.
S
u
b
j
e
c
t
T
h
e
i
n
c
l
u
s
i
o
n
c
r
i
t
e
r
i
a
w
e
r
e
I
n
d
o
n
e
s
i
a
n
(
J
a
v
a
n
e
s
e
,
S
u
n
d
a
n
e
s
e
,
a
n
d
M
a
l
a
y
),
a
g
e
d
18
–
65
y
e
a
r
s
,
h
e
a
l
t
h
y
m
a
l
e
/
f
e
m
a
l
e
,
a
n
d
w
i
l
l
i
n
g
to
p
a
r
t
i
c
i
p
a
t
e
in
t
h
e
s
t
u
d
y
by
c
o
m
p
l
e
t
i
n
g
a
n
d
s
i
g
n
i
n
g
i
n
f
o
r
m
e
d
c
o
n
s
e
n
t
a
n
d
b
e
i
n
g
c
o
o
p
e
r
a
t
i
v
e
.
T
h
e
s
u
b
j
e
c
t
s
w
e
r
e
p
a
t
i
e
n
t
s
w
i
t
h
c
o
n
g
e
n
i
t
a
l
k
i
d
n
e
y
d
i
s
e
a
s
e
,
h
i
s
t
o
r
y
of
k
i
d
n
e
y
t
r
a
n
s
p
l
a
n
t
a
t
i
o
n
,
m
e
n
t
a
l
i
l
l
n
e
s
s
,
a
n
d
g
r
o
w
t
h
d
i
s
o
r
d
e
r
(
d
w
a
r
f
i
s
m
/
g
i
g
a
n
t
i
s
m
)
.
P
r
e
v
i
o
u
s
r
e
s
e
a
r
c
h
h
a
s
s
h
o
w
n
t
h
a
t
t
h
e
p
e
r
c
e
n
t
a
g
e
of
s
m
o
k
e
r
s
in
t
h
e
c
o
m
m
u
n
i
t
y
h
a
d
r
e
a
c
h
e
d
32%
[
5
,
3
0
]
.
We
r
e
c
r
u
i
t
e
d
106
s
u
b
j
e
c
t
s
,
w
h
i
l
e
t
h
e
m
i
n
i
m
u
m
n
u
m
b
e
r
of
r
e
s
e
a
r
c
h
s
u
b
j
e
c
t
s
w
a
s
102.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
S
N
:
2252
-
8806
I
n
t
.
J
.
P
u
b
l
i
c
H
e
a
l
t
h
S
c
i
.
V
o
l
.
1
0
,
N
o
.
1
,
M
a
r
c
h
20
21
:
8
8
–
9
6
90
2
.
3
.
M
a
t
e
r
i
a
l
s
a
n
d
r
e
s
e
a
r
c
h
i
n
s
t
r
u
m
e
n
t
s
We
c
o
l
l
e
c
t
e
d
p
r
i
m
a
r
y
d
a
t
a
u
s
e
d
q
u
e
s
t
i
o
n
n
a
i
r
e
s
,
a
n
d
s
e
c
o
n
d
a
r
y
d
a
t
a
u
s
e
d
d
a
t
a
c
o
l
l
e
c
t
i
o
n
f
o
r
m
s
.
We
d
e
t
e
r
m
i
n
e
d
t
h
e
n
i
c
o
t
i
n
e
l
e
v
e
l
by
t
h
e
E
L
I
S
A
m
e
t
h
o
d
.
We
m
e
a
s
u
r
e
d
T
r
e
g
l
e
v
e
l
s
w
i
t
h
f
l
o
w
c
y
t
o
m
e
t
r
y
.
We
c
a
r
r
i
e
d
out
a
T
r
e
g
e
x
a
m
i
n
a
t
i
o
n
at
t
h
e
c
l
i
n
i
c
a
l
p
a
t
h
o
l
o
g
y
l
a
b
o
r
a
t
o
r
y
of
M
e
d
i
c
a
l
F
a
c
u
l
t
y
,
U
n
i
v
e
r
s
i
t
a
s
G
a
d
j
a
h
M
a
d
a
(
U
G
M
)
.
We
u
s
e
d
t
h
e
q
u
e
s
t
i
o
n
n
a
i
r
e
to
o
b
t
a
i
n
p
r
i
m
a
r
y
d
a
t
a
f
r
o
m
r
e
s
p
o
n
d
e
n
t
s
,
a
n
d
d
a
t
a
c
o
l
l
e
c
t
i
o
n
f
o
r
m
to
c
o
l
l
e
c
t
s
e
c
o
n
d
a
r
y
d
a
t
a
,
i
n
c
l
u
d
i
n
g
n
a
m
e
,
a
g
e
,
a
n
d
g
e
n
d
e
r
e
x
t
r
a
c
t
e
d
f
r
o
m
m
e
d
i
c
a
l
r
e
c
o
r
d
s
.
2
.
4
.
R
e
s
e
a
r
c
h
p
r
o
c
e
d
u
r
e
s
2
.
4
.
1
.
S
u
b
j
e
c
t
r
e
c
r
u
i
t
m
e
n
t
p
r
o
c
e
d
u
r
e
P
a
t
i
e
n
t
s
w
e
r
e
s
e
l
e
c
t
e
d
b
a
s
e
d
on
t
h
e
i
n
c
l
u
s
i
o
n
a
n
d
e
x
c
l
u
s
i
o
n
c
r
i
t
e
r
i
a
.
We
c
o
l
l
e
c
t
e
d
106
h
e
a
l
t
h
y
v
o
l
u
n
t
e
e
r
s
w
i
t
h
a
h
i
g
h
r
i
s
k
of
c
h
r
o
n
i
c
k
i
d
n
e
y
d
i
s
e
a
s
e
f
r
o
m
f
i
v
e
r
e
g
e
n
c
i
e
s
in
D
I
Y
.
T
h
e
r
e
c
r
u
i
t
m
e
n
t
w
a
s
a
d
j
u
s
t
e
d
to
t
h
e
n
u
m
b
e
r
/
p
r
o
p
o
r
t
i
o
n
of
c
h
r
o
n
i
c
k
i
d
n
e
y
d
i
s
e
a
s
e
p
a
t
i
e
n
t
s
u
n
d
e
r
g
o
i
n
g
h
e
m
o
d
i
a
l
y
s
i
s
in
B
a
n
t
u
l
G
e
n
e
r
a
l
H
o
s
p
i
t
a
l
,
Y
o
g
y
a
k
a
r
t
a
M
u
h
a
m
m
a
d
i
y
a
h
H
o
s
p
i
t
a
l
s
,
a
n
d
R
e
d
C
r
o
s
s
I
n
d
o
n
e
s
i
a
C
l
i
n
i
c
s
in
Y
o
g
y
a
k
a
r
t
a
.
2
.
4
.
2
.
D
a
t
a
c
o
l
l
e
c
t
i
o
n
m
e
t
h
o
d
We
c
o
l
l
e
c
t
e
d
t
h
e
d
a
t
a
t
h
r
o
u
g
h
i
n
t
e
r
v
i
e
w
s
a
n
d
d
i
r
e
c
t
o
b
s
e
r
v
a
t
i
o
n
or
m
e
a
s
u
r
e
m
e
n
t
s
.
T
a
b
l
e
1
s
u
m
m
a
r
i
z
e
d
t
h
e
d
a
t
a
t
y
p
e
s
a
n
d
t
h
e
i
r
c
o
l
l
e
c
t
i
o
n
m
e
t
h
o
d
s
.
P
r
i
m
a
r
y
d
a
t
a
w
e
r
e
c
o
l
l
e
c
t
e
d
b
o
t
h
i
n
t
h
e
f
i
e
l
d
a
n
d
i
n
t
h
e
c
l
i
n
i
c
.
W
e
o
b
t
a
i
n
e
d
t
h
e
r
e
s
p
o
n
d
e
n
t
'
s
d
a
t
a
h
a
b
i
t
s
a
n
d
l
i
f
e
s
t
y
l
e
s
u
s
i
n
g
i
n
t
e
r
v
i
e
w
s
g
u
i
d
e
d
b
y
q
u
e
s
t
i
o
n
n
a
i
r
e
s
a
n
d
d
a
t
a
c
o
l
l
e
c
t
i
o
n
f
o
r
m
s
.
W
e
c
o
l
l
e
c
t
e
d
s
m
o
k
i
n
g
h
i
s
t
o
r
y
d
a
t
a
t
h
r
o
u
g
h
a
s
t
r
u
c
t
u
r
e
d
i
n
t
e
r
v
i
e
w
g
u
i
d
e
d
-
q
u
e
s
t
i
o
n
n
a
i
r
e
.
D
a
t
a
c
o
l
l
e
c
t
e
d
t
h
r
o
u
g
h
t
h
e
d
i
s
c
u
s
s
i
o
n
s
i
n
c
l
u
d
e
r
e
s
p
o
n
d
e
n
t
s
'
i
d
e
n
t
i
t
y
,
s
o
c
i
o
e
c
o
n
o
m
i
c
s
t
a
t
u
s
,
m
a
r
i
t
a
l
s
t
a
t
u
s
,
e
d
u
c
a
t
i
o
n
h
i
s
t
o
r
y
,
o
c
c
u
p
a
t
i
o
n
,
a
n
d
s
m
o
k
i
n
g
b
e
h
a
v
i
o
r
d
a
t
a
.
W
e
c
l
a
s
s
i
f
i
e
d
s
m
o
k
i
n
g
b
e
h
a
v
i
o
r
a
s
n
o
s
m
o
k
i
n
g
,
s
m
o
k
i
n
g
,
a
n
d
f
o
r
m
e
r
s
m
o
k
i
n
g
.
P
r
i
m
a
r
y
d
a
t
a
c
o
n
c
e
r
n
i
n
g
t
h
e
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
a
n
d
c
l
i
n
i
c
a
l
m
a
n
i
f
e
s
t
a
t
i
o
n
s
,
a
s
w
e
l
l
a
s
T
r
e
g
l
e
v
e
l
s
,
w
e
r
e
o
b
t
a
i
n
e
d
t
h
r
o
u
g
h
d
i
r
e
c
t
m
e
a
s
u
r
e
m
e
n
t
s
.
W
e
c
a
p
t
u
r
e
d
c
l
i
n
i
c
a
l
d
a
t
a
w
i
t
h
a
l
a
b
o
r
a
t
o
r
y
o
b
s
e
r
v
a
t
i
o
n
m
e
t
h
o
d
.
C
l
i
n
i
c
a
l
d
a
t
a
c
o
l
l
e
c
t
e
d
b
y
p
h
y
s
i
c
a
l
a
n
d
l
a
b
o
r
a
t
o
r
y
e
x
a
m
i
n
a
t
i
o
n
i
n
c
l
u
d
e
b
o
d
y
m
a
s
s
i
n
d
e
x
(
B
M
I
)
,
p
e
r
i
p
h
e
r
a
l
b
l
o
o
d
h
e
m
o
g
r
a
m
,
b
l
o
o
d
c
h
e
m
i
s
t
r
y
,
a
n
d
n
i
c
o
t
i
n
e
a
n
d
T
r
e
g
l
e
v
e
l
s
.
T
h
e
b
r
i
e
f
p
r
o
c
e
d
u
r
e
w
a
s
a
s
f
o
l
l
o
w
s
:
i
)
t
h
e
w
e
i
g
h
t
a
n
d
h
e
i
g
h
t
o
f
p
r
o
s
p
e
c
t
i
v
e
s
u
b
j
e
c
t
s
w
h
o
h
a
v
e
b
e
e
n
f
a
s
t
i
n
g
f
o
r
8
–
1
2
h
o
u
r
s
w
e
r
e
m
e
a
s
u
r
e
d
t
o
d
e
t
e
r
m
i
n
e
B
M
I
.
T
h
e
p
o
t
e
n
t
i
a
l
S
u
b
j
e
c
t
s
h
a
d
r
e
c
e
i
v
e
d
a
n
e
x
p
l
a
n
a
t
i
o
n
a
b
o
u
t
t
h
e
p
u
r
p
o
s
e
o
f
t
h
e
s
t
u
d
y
.
T
h
e
y
w
e
r
e
a
s
k
e
d
t
o
s
i
g
n
i
n
f
o
r
m
e
d
c
o
n
s
e
n
t
a
s
e
v
i
d
e
n
c
e
o
f
t
h
e
i
r
a
g
r
e
e
m
e
n
t
t
o
p
a
r
t
i
c
i
p
a
t
e
i
n
t
h
e
s
t
u
d
y
.
T
h
e
5
m
l
o
f
b
l
o
o
d
w
a
s
d
r
a
w
n
f
r
o
m
t
h
e
v
o
l
u
n
t
e
e
r
'
s
m
e
d
i
a
n
c
u
b
i
t
a
l
v
e
i
n
.
A
t
o
t
a
l
o
f
3
m
l
o
f
b
l
o
o
d
w
a
s
c
e
n
t
r
i
f
u
g
e
d
a
t
3
0
0
0
g
f
o
r
1
5
m
i
n
u
t
e
s
.
T
h
e
b
l
o
o
d
w
a
s
u
s
e
d
t
o
m
e
a
s
u
r
e
b
l
o
o
d
s
u
g
a
r
,
t
r
i
g
l
y
c
e
r
i
d
e
s
,
c
r
e
a
t
i
n
i
n
e
,
u
r
e
a
,
n
i
c
o
t
i
n
e
,
a
n
d
T
r
e
g
.
i
i
)
T
h
e
l
e
v
e
l
s
o
f
c
r
e
a
t
i
n
i
n
e
a
n
d
u
r
e
a
w
e
r
e
m
e
a
s
u
r
e
d
u
s
i
n
g
a
s
p
e
c
t
r
o
p
h
o
t
o
m
e
t
e
r
.
E
L
I
S
A
m
e
a
s
u
r
e
d
n
i
c
o
t
i
n
e
l
e
v
e
l
s
.
T
a
b
l
e
1.
R
e
s
e
a
r
c
h
d
a
t
a
t
y
p
e
s
a
n
d
c
o
l
l
e
c
t
i
o
n
m
e
t
h
o
d
s
in
h
e
a
l
t
h
y
r
e
s
p
o
n
d
e
n
t
s
in
DI
Y
D
a
t
a
t
y
p
e
s
D
e
t
a
i
l
s
D
a
t
a
c
o
l
l
e
c
t
i
o
n
m
e
t
h
o
d
D
e
m
o
g
r
a
p
h
i
c
s
G
e
n
d
e
r
,
a
g
e
,
a
d
d
r
e
s
s
,
p
l
a
c
e
of
b
i
r
t
h
,
d
a
t
e
of
b
i
r
t
h
,
e
m
p
l
o
y
m
e
n
t
h
i
s
t
o
r
y
,
e
d
u
c
a
t
i
o
n
h
i
s
t
o
r
y
D
a
t
a
c
o
l
l
e
c
t
i
o
n
f
o
r
m
a
n
d
i
n
t
e
r
v
i
e
w
s
g
u
i
d
e
d
by
q
u
e
s
t
i
o
n
n
a
i
r
e
s
.
C
h
a
r
a
c
t
e
r
i
s
t
i
c
s
of
t
h
e
S
u
b
j
e
c
t
,
l
i
f
e
s
t
y
l
e
,
a
nd
c
l
i
n
i
c
a
l
m
a
n
i
f
e
s
t
a
t
i
o
n
s
W
e
i
g
h
t
,
h
e
i
g
h
t
,
h
e
m
o
g
l
o
b
i
n
,
l
e
u
c
o
c
y
t
e
s
c
o
u
n
t
s
,
e
r
y
t
h
r
o
c
y
t
e
s
c
o
u
n
t
s
,
u
r
e
a
a
n
d
c
r
e
a
t
i
n
i
n
e
,
r
a
n
d
o
m
b
l
o
o
d
g
l
u
c
o
s
e
l
e
v
e
l
s
,
a
n
d
d
u
r
a
t
i
o
n
o
f
s
m
o
k
i
n
g
,
w
e
e
k
l
y
a
m
o
u
n
t
o
f
t
o
b
a
c
c
o
p
a
c
k
s
;
w
o
r
k
p
l
a
c
e
a
n
d
e
n
v
i
r
o
n
m
e
n
t
(
d
u
r
a
t
i
o
n
a
n
d
i
n
t
e
n
s
i
t
y
)
;
hi
s
t
o
r
y
o
f
s
m
o
k
i
n
g
c
e
s
s
a
t
i
o
n
(
f
i
r
s
t
s
m
o
k
i
n
g
c
e
s
s
a
t
i
o
n
,
l
e
n
g
t
h
o
f
s
m
o
k
i
n
g
c
e
s
s
a
t
i
o
n
)
D
i
r
e
c
t
e
x
a
m
i
n
a
t
i
o
n
of
b
l
o
o
d
c
h
e
m
i
s
t
r
y
w
a
s
m
e
a
s
u
r
e
d
w
i
t
h
s
p
e
c
t
r
o
p
h
o
t
o
m
e
t
r
y
.
S
t
r
u
c
t
u
r
e
d
i
n
t
e
r
v
i
e
w
g
u
i
d
e
d
b
y
a
q
u
e
s
t
i
o
n
n
a
i
r
e
.
S
m
o
k
i
n
g
h
i
s
t
o
r
y
a
n
d
n
i
c
o
t
i
n
e
l
e
v
e
l
s
B
l
o
o
d
n
i
c
o
t
i
n
e
l
e
v
e
l
s
A
d
i
r
e
c
t
e
x
a
m
i
n
a
t
i
o
n
of
b
l
o
o
d
n
i
c
o
t
i
n
e
l
e
v
e
l
s
u
s
i
n
g
t
h
e
E
L
I
S
A
m
e
t
h
o
d
[
3
1
]
2
.
5
.
D
a
t
a
a
n
a
l
y
s
i
s
T
h
e
d
a
t
a
w
e
r
e
p
r
o
c
e
s
s
e
d
a
n
d
t
h
e
n
p
r
e
s
e
n
t
e
d
d
e
s
c
r
i
p
t
i
v
e
l
y
,
f
o
l
l
o
w
e
d
by
b
i
v
a
r
i
a
t
e
a
n
a
l
y
s
i
s
.
O
n
e
-
w
a
y
A
N
O
V
A
c
o
m
p
a
r
e
d
t
h
e
n
u
m
b
e
r
of
c
e
l
l
s
in
H
e
m
o
g
r
a
m
a
n
d
T
r
e
g
or
l
e
v
e
l
s
in
b
l
o
o
d
c
h
e
m
i
s
t
r
y
a
n
d
n
i
c
o
t
i
n
e
l
e
v
e
l
s
a
m
o
n
g
r
e
s
p
o
n
d
e
n
t
s
m
o
k
e
r
s
a
n
d
n
o
n
s
m
o
k
e
r
s
w
i
t
h
a
95%
s
i
g
n
i
f
i
c
a
n
c
e
l
e
v
e
l
.
T
h
e
c
o
r
r
e
l
a
t
i
o
n
b
e
t
w
e
e
n
s
m
o
k
i
n
g
h
a
b
i
t
(
c
l
a
s
s
i
f
i
c
a
t
i
o
n
of
t
h
e
d
u
r
a
t
i
o
n
of
s
m
o
k
i
n
g
a
n
d
n
u
m
b
e
r
of
p
a
c
k
s
/
w
e
e
k
c
i
g
a
r
e
t
t
e
c
o
n
s
u
m
e
)
a
n
d
n
i
c
o
t
i
n
e
l
e
v
e
l
a
n
d
T
r
e
g
c
o
u
n
t
w
a
s
a
n
a
l
y
z
e
d
u
s
i
n
g
P
e
a
r
s
o
n
c
o
r
r
e
l
a
t
i
o
n
.
2
.
6
.
R
e
s
e
a
r
c
h
e
t
h
i
c
s
A
f
t
e
r
b
e
i
n
g
a
p
p
r
o
v
e
d
by
t
h
e
l
o
c
a
l
I
n
s
t
i
t
u
t
i
o
n
a
l
R
e
v
i
e
w
B
o
a
r
d
,
t
h
e
s
t
u
d
y
w
a
s
c
o
n
d
u
c
t
e
d
by
f
o
l
l
o
w
i
n
g
G
o
o
d
C
l
i
n
i
c
a
l
P
r
a
c
t
i
c
e
:
e
x
p
l
a
i
n
i
n
g
to
a
l
l
p
o
t
e
n
t
i
a
l
s
u
b
j
e
c
t
s
a
b
o
u
t
t
h
e
g
o
a
l
a
n
d
o
b
j
e
c
t
i
v
e
of
t
h
e
r
e
s
e
a
r
c
h
,
t
h
e
e
x
p
e
c
t
e
d
b
e
n
e
f
i
t
s
a
n
d
u
s
e
s
,
t
h
e
c
o
n
s
e
q
u
e
n
c
e
s
f
o
r
t
h
e
s
u
b
j
e
c
t
s
,
a
n
d
t
h
e
r
i
g
h
t
s
a
n
d
o
b
l
i
g
a
t
i
o
n
s
of
t
h
e
s
u
b
j
e
c
t
s
.
T
h
e
w
r
i
t
t
e
n
i
n
f
o
r
m
e
d
c
o
n
s
e
n
t
f
o
r
m
w
a
s
o
b
t
a
i
n
e
d
f
r
o
m
each
s
u
b
j
e
c
t
.
T
h
e
s
t
u
d
y
p
r
o
t
o
c
o
l
a
n
d
i
n
t
e
r
v
i
e
w
g
u
i
d
e
l
i
n
e
s
h
a
v
e
b
e
e
n
r
e
v
i
e
w
e
d
a
n
d
a
p
p
r
o
v
e
d
by
t
h
e
h
e
a
l
t
h
r
e
s
e
a
r
c
h
e
t
h
i
c
s
c
o
m
m
i
t
t
e
e
,
M
e
d
i
c
a
l
F
a
c
u
l
t
y
of
U
G
M
(
r
e
f
N
o
:
K
E
/
F
K
/
8
4
7
/
E
C
)
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t
.
J
.
P
u
b
l
i
c
H
e
a
l
t
h
S
c
i
.
I
S
S
N
:
2252
-
8
8
0
6
N
i
c
o
t
i
n
e
l
e
v
e
l
a
s
s
o
c
i
a
t
e
d
w
i
t
h
d
e
c
r
e
a
s
i
n
g
T
r
e
g
n
u
m
b
e
r
i
n
s
m
o
k
e
r
h
e
a
l
t
h
y
v
o
l
u
n
t
e
e
r
s
(
A
k
r
o
m
)
91
3.
R
E
S
U
L
T
S
DAN
D
I
S
C
U
S
S
I
O
N
3
.
1
.
S
u
b
j
e
c
t
s’
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
S
u
b
j
e
c
t
s
h
a
v
e
l
i
v
e
d
in
f
i
v
e
d
i
s
t
r
i
c
t
s
in
D
I
Y
:
Y
o
g
y
a
k
a
r
t
a
,
S
l
e
m
a
n
,
B
a
n
t
u
l
,
K
u
l
o
n
P
r
o
g
o
,
a
n
d
G
u
n
u
n
g
k
i
d
u
l
.
T
a
b
l
e
s
2
a
n
d
3
s
h
o
w
t
h
e
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
of
t
h
e
s
u
b
j
e
c
t
.
T
a
b
l
e
2
s
h
o
w
s
t
h
a
t
t
h
e
n
u
m
b
e
r
of
m
a
l
e
s
u
b
j
e
c
t
s
w
a
s
t
w
i
c
e
t
h
e
h
i
g
h
e
r
of
f
e
m
a
l
e
s
,
i
.
e
.
,
6
6
.
3
%
c
o
m
p
a
r
e
d
to
3
3
.
7
%
.
M
o
s
t
s
u
b
j
e
c
t
s
a
g
e
d
b
e
t
w
e
e
n
46
–
60
y
e
a
r
s
(
5
0
.
3
%
)
,
f
o
l
l
o
w
e
d
by
31
–
45
y
e
a
r
s
(
2
7
%
),
>
6
0
y
e
a
r
s
(
1
8
.
2
%
)
,
a
n
d
16
–
30
y
e
a
r
s
(
7
.
4
%
)
.
M
o
s
t
s
u
b
j
e
c
t
s
w
e
r
e
s
e
n
i
o
r
h
i
g
h
s
c
h
o
o
l
g
r
a
d
u
a
t
e
s
a
n
d
w
o
r
k
i
n
g
in
t
h
e
p
r
i
v
a
t
e
s
e
c
t
o
r
.
I
n
t
h
i
s
c
r
o
s
s
-
s
e
c
t
i
o
n
a
l
s
t
u
d
y
,
t
h
e
n
u
m
b
e
r
o
f
s
m
o
k
e
r
s
>
3
0
%
o
f
r
e
s
p
o
n
d
e
n
t
s
,
m
o
r
e
t
h
a
n
2
0
%
o
f
r
e
s
p
o
n
d
e
n
t
s
s
m
o
k
e
d
2
0
o
r
m
o
r
e
2
0
y
e
a
r
s
,
a
n
d
1
6
%
o
f
r
e
s
p
o
n
d
e
n
t
s
s
m
o
k
e
d
1
5
p
a
c
k
s
/
w
e
e
k
o
r
m
o
r
e
.
T
h
i
s
d
e
s
c
r
i
p
t
i
o
n
i
s
f
o
l
l
o
w
i
n
g
t
h
e
c
o
n
d
i
t
i
o
n
o
f
s
m
o
k
e
r
s
i
n
I
n
d
o
n
e
s
i
a
[
3
2
,
3
3
]
.
T
a
b
l
e
3
p
r
e
s
e
n
t
s
a
n
o
v
e
r
v
i
e
w
o
f
c
l
i
n
i
c
a
l
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
a
n
d
t
h
e
r
e
s
u
l
t
o
f
r
e
s
p
o
n
d
e
n
t
s
'
l
a
b
o
r
a
t
o
r
y
e
x
a
m
i
n
a
t
i
o
n
s
.
B
l
o
o
d
p
r
e
s
s
u
r
e
,
B
M
I
,
h
e
m
o
g
l
o
b
i
n
l
e
v
e
l
s
,
e
r
y
t
h
r
o
c
y
t
e
,
l
e
u
k
o
c
y
t
e
,
r
a
n
d
o
m
b
l
o
o
d
g
l
u
c
o
s
e
l
e
v
e
l
,
u
r
e
a
l
e
v
e
l
,
a
n
d
c
r
e
a
t
i
n
i
n
e
a
r
e
n
o
r
m
a
l
.
T
h
e
m
e
a
n
o
f
t
h
e
n
i
c
o
t
i
n
e
l
e
v
e
l
w
a
s
1
9
.
3
4
n
g
/
m
l
.
T
a
b
l
e
2.
D
e
m
o
g
r
a
p
h
i
c
c
h
a
r
a
c
t
e
r
i
s
t
i
c
s
a
n
d
s
m
o
k
i
n
g
b
e
h
a
v
i
o
r
of
h
e
a
l
t
h
y
v
o
l
u
n
t
e
e
r
s
in
D
I
Y
No
C
h
a
r
a
c
t
e
r
i
s
t
i
c
s
o
f
r
e
s
p
o
n
d
e
n
t
s
N
u
m
b
e
r
(
p
e
r
c
e
n
t
a
g
e
)
1
G
e
n
d
e
r
M
e
n
7
0
(
6
6
.
3
%
)
W
o
m
e
n
3
6
(
3
3
.
7
0
%
)
2
A
g
e
g
r
o
u
p
16
–
3
0
y
e
a
r
s
1
1
(
1
0
.
3
8
%
)
31
–
4
5
y
e
a
r
s
2
9
(
2
7
.
3
6
%
)
46
–
6
0
y
e
a
r
s
5
0
(
4
7
.
1
7
%
)
>
6
0
y
e
a
r
s
1
6
(
1
5
.
0
9
%
)
3
E
d
u
c
a
t
i
o
n
N
o
s
c
h
o
o
l
1
1
(
1
0
.
3
8
%
)
E
l
e
m
e
n
t
a
r
y
s
c
h
o
o
l
g
r
a
d
u
a
t
e
s
3
6
(
3
3
.
9
6
%
)
j
u
n
i
o
r
h
i
g
h
s
c
h
o
o
l
g
r
a
d
u
a
t
e
s
1
8
(
1
6
.
9
8
%
)
s
e
n
i
o
r
h
i
g
h
s
c
h
o
o
l
g
r
a
d
u
a
t
e
s
2
6
(
2
4
.
5
8
%
)
U
n
i
v
e
r
s
i
t
y
1
5
(
1
4
.
1
5
%
)
4
O
c
c
u
p
a
t
i
o
n
C
i
v
i
l
s
e
r
v
a
n
t
s
,
m
i
l
i
t
a
r
y
,
s
t
a
t
e
-
o
w
n
e
d
e
n
t
e
r
p
r
i
s
e
s
,
n
a
t
i
o
n
a
l
p
o
l
i
c
e
1
2
(
1
1
.
3
2
%
)
P
r
i
v
a
t
e
a
n
d
s
e
l
f
-
e
m
p
l
o
y
e
d
1
6
(
1
5
.
1
0
%
)
F
a
r
m
e
r
s
,
l
a
b
o
r
s
,
a
n
d
h
a
n
d
y
m
e
n
4
8
(
4
5
.
2
8
%
)
U
n
e
m
p
l
o
y
e
d
3
0
(
2
8
.
3
0
%
)
5
M
a
r
i
t
a
l
s
t
a
t
u
s
M
a
r
r
i
e
d
1
0
3
(
9
7
.
1
7
%
)
N
o
t
m
a
r
r
i
e
d
3
(
2
.
8
3
%
)
6
S
m
o
k
i
n
g
h
a
b
i
t
S
m
o
k
i
n
g
3
1
(
3
3
.
9
6
%
)
N
o
t
s
m
o
k
i
n
g
7
5
(
7
0
.
7
5
%
)
7
N
o
p
a
c
k
c
i
g
a
r
e
t
t
e
/w
eek
≥
1
5
p
a
c
k
s
/
w
e
e
k
s
1
7
(
1
6
.
0
5
%
)
<
1
5
p
a
c
k
s
/
w
e
e
k
s
1
4
(
1
3
.
2
0
%
)
N
o
s
m
o
k
i
n
g
7
5
(
7
0
.
7
5
%
)
8
D
u
r
a
t
i
o
n
o
f
s
m
o
k
i
n
g
≥
2
0
y
e
a
r
2
3
(
2
1
.
7
0
%
)
<
2
0
y
e
a
r
8
(
7
.
5
5
%
)
N
o
s
m
o
k
i
n
g
7
5
(
7
0
.
7
5
%
)
T
a
b
l
e
3.
L
a
b
o
r
a
t
o
r
y
e
x
a
m
i
n
a
t
i
o
n
of
h
e
a
l
t
h
y
v
o
l
u
n
t
e
e
r
s
in
Y
o
g
y
a
k
a
r
t
a
No
Ch
a
r
a
c
t
e
r
i
s
t
i
c
s
of
r
e
s
p
o
n
d
e
n
t
s
M
e
a
n
±
SD
1
A
g
e
(
y
e
a
r
)
50.
76
±
32
2
W
e
i
g
h
t
(
K
g
)
5
7
.
6
2
±
9
.
0
1
3
H
e
i
g
h
t
(
c
m
)
1
6
0
.
5
5
±
4
.
6
3
4
B
o
d
y
m
a
s
s
i
n
d
e
x
(
B
M
I
)
(
K
g
/
c
m
2
)
2
2
.
3
3
±
3
.
2
7
5
S
y
s
t
o
l
i
c
b
l
o
o
d
p
r
e
s
s
u
r
e
(
m
m
H
g
)
1
2
2
.
4
1
±
2
1
.
4
9
6
D
i
a
s
t
o
l
i
c
b
l
o
o
d
p
r
e
s
s
u
r
e
(
m
m
H
g
)
8
0
.
1
1
±
1
1
.
8
9
7
H
e
m
o
g
l
o
b
i
n
l
e
v
e
l
s
(
%
)
1
1
.
9
1
±
1
.
8
9
8
E
r
y
t
h
r
o
c
y
t
e
c
o
u
n
t
s
(
1
0
6
)
(
c
e
l
l
/
d
l
)
4
.
5
7
±
0
.
6
2
9
L
e
u
k
o
c
y
t
e
c
o
u
n
t
s
(
1
0
3
)
(
c
e
l
l
/
d
l
)
9
.
5
8
±
4
.
7
5
10
P
l
a
t
e
l
e
t
c
o
u
n
t
s
(
1
0
3
)
(
c
e
l
l
/
d
l
)
2
5
5
.
4
2
±
1
0
5
.
7
3
11
H
e
m
a
t
o
c
r
i
t
l
e
v
e
l
s
3
4
.
8
9
±
5
.
7
6
12
B
l
o
o
d
s
u
g
a
r
l
e
v
e
l
s
(
m
g
/
m
l
)
1
1
6
.
8
6
±
3
8
.
2
6
13
T
r
i
g
l
y
c
e
r
i
d
e
l
e
v
e
l
s
(
m
g
/
d
l
)
1
2
2
.
1
0
±
7
0
.
6
1
14
U
r
e
a
l
e
v
e
l
s
(
m
g
/
d
l
)
7
7
.
5
3
±
7
4
.
0
3
15
C
r
e
a
t
i
n
i
n
e
l
e
v
e
l
s
(
m
g
/
d
l
)
1
.
1
6
±
0
.
1
1
16
N
i
c
o
t
i
n
e
l
e
v
e
l
s
(
n
g
/
m
l
)
19
.
3
4
±
1
8
.
7
5
17
T
r
e
g
c
o
u
n
t
(
%
)
2
4
.
9
6
±
7
.
3
7
F
r
o
m
t
h
e
s
t
u
d
y
,
h
e
m
o
g
l
o
b
i
n
a
n
d
h
e
m
a
t
o
c
r
i
t
l
e
v
e
l
s
d
e
c
r
e
a
s
e
d
w
h
i
le
c
r
e
a
t
i
n
i
n
e
l
e
v
e
l
s
i
n
c
r
e
a
s
e
d
.
T
h
e
h
e
m
o
g
l
o
b
i
n
(
H
b
)
l
e
v
e
l
s
in
t
h
i
s
s
t
u
d
y
w
e
r
e
s
u
b
n
o
r
m
a
l
.
T
h
e
a
v
e
r
a
g
e
v
a
l
u
e
s
of
Hb
a
r
e
m
o
r
e
t
h
a
n
12
g
/
d
l
in
w
o
m
e
n
a
n
d
m
o
r
e
t
h
a
n
13
g
/
d
l
in
m
e
n
[
3
4
,
3
5
]
.
L
o
w
h
e
m
o
g
l
o
b
i
n
a
n
d
h
e
m
a
t
o
c
r
i
t
l
e
v
e
l
s
a
r
e
a
s
s
o
c
i
a
t
e
d
w
i
t
h
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
S
N
:
2252
-
8806
I
n
t
.
J
.
P
u
b
l
i
c
H
e
a
l
t
h
S
c
i
.
V
o
l
.
1
0
,
N
o
.
1
,
M
a
r
c
h
20
21
:
8
8
–
9
6
92
m
a
l
n
u
t
r
i
t
i
o
n
an
d
s
o
m
e
c
h
r
o
n
i
c
d
i
s
e
a
s
e
s
[
3
6
]
.
P
r
e
v
i
o
u
s
s
t
u
d
i
e
s
f
o
u
n
d
t
h
a
t
t
h
e
Hb
f
o
r
s
m
o
k
e
r
r
e
s
p
o
n
d
e
n
t
s
w
a
s
h
i
g
h
e
r
t
h
a
n
t
h
e
Hb
l
e
v
e
l
f
o
r
n
o
n
s
m
o
k
e
r
[
1
2
]
.
T
h
e
r
e
s
u
l
t
s
s
h
o
w
e
d
t
h
a
t
t
h
e
M
e
a
n
n
i
c
o
t
i
n
e
p
l
a
s
m
a
l
e
v
e
l
s
in
r
e
s
p
o
n
d
e
n
t
s
w
e
r
e
q
u
i
t
e
h
i
g
h
at
1
9
.
3
4
±
1
8
.
7
5
n
g
/
m
l
.
T
h
e
r
e
s
u
l
ts
of
t
h
e
s
t
u
d
y
a
r
e
t
h
e
f
o
l
l
o
w
i
n
g
p
r
e
v
i
o
u
s
s
t
u
d
i
e
s
[
3
7
]
.
It
w
a
s
r
e
p
o
r
t
e
d
t
h
a
t
a
v
e
r
a
g
e
p
l
a
s
m
a
n
i
c
o
t
i
n
e
l
e
v
e
l
s
in
n
o
n
s
m
o
k
e
r
s
w
h
o
w
e
r
e
not
e
x
p
o
s
e
d
to
c
i
g
a
r
e
t
t
e
s
m
o
k
e
w
e
r
e
0
.
0
9
-
0
.
7
n
g
/
m
L
,
p
a
s
s
i
v
e
s
m
o
k
e
r
s
2
–
10
n
g
/
m
l
,
a
n
d
a
c
t
i
v
e
s
m
o
k
e
r
s
>
1
0
n
g
/
m
l
.
R
e
s
e
a
r
c
h
e
r
s
in
t
h
e
U
S
A
r
e
p
o
r
t
e
d
t
h
a
t
p
l
a
s
m
a
n
i
c
o
t
i
n
e
l
e
v
e
l
s
in
s
m
o
k
e
r
s
in
t
h
e
U
S
A
r
a
n
g
e
d
110
–
494
n
g
/
m
L
[
8
,
3
8
]
.
M
a
n
y
f
a
c
t
o
r
s
can
a
f
f
e
c
t
t
h
e
l
e
v
e
l
of
n
i
c
o
t
i
n
e
in
t
h
e
b
l
o
o
d
a
p
a
r
t
f
r
o
m
t
h
e
n
u
m
b
e
r
,
d
u
r
a
t
i
o
n
,
a
n
d
s
m
o
k
i
n
g
m
e
t
h
o
d
.
F
o
o
d
f
a
c
t
o
r
s
,
d
r
u
g
s
c
o
n
s
u
m
e
d
,
a
n
d
b
i
o
l
o
g
i
c
a
l
co
n
d
i
t
i
o
n
s
a
n
d
i
n
d
i
v
i
d
u
a
l
h
a
b
i
t
s
h
a
v
e
b
e
e
n
p
r
o
v
e
n
to
i
n
f
l
u
e
n
c
e
n
i
c
o
t
i
n
e
l
e
v
e
l
s
in
t
h
e
b
l
o
o
d
,
i
n
c
l
u
d
i
n
g
k
i
d
n
e
y
f
u
n
c
t
i
o
n
d
i
s
o
r
d
e
r
s
.
D
a
t
a
f
r
o
m
r
e
s
e
a
r
c
h
in
I
n
d
o
n
e
s
i
a
s
h
o
w
s
t
h
a
t
t
h
e
a
v
e
r
a
g
e
b
l
o
o
d
c
o
t
i
n
i
n
e
l
e
v
e
l
of
r
e
s
p
o
n
d
e
n
t
s
w
i
t
h
e
n
d
s
t
a
g
e
r
e
n
a
l
d
i
s
e
a
s
e
(
E
S
R
D
)
is
h
i
g
h
e
r
t
h
a
n
non
-
E
S
R
D
,
6
3
.
7
±
3
5
.
1
v
s.
2
3
.
8
±
8
.
3
4
n
g
/
m
l
p
<
0
.
0
5
[
3
9
]
.
3
.
2
.
N
i
c
o
t
i
n
e
l
e
v
e
l
,
h
e
m
o
g
r
a
m
,
a
n
d
T
r
e
g
n
u
m
b
e
r
b
a
s
e
d
on
s
m
o
k
i
n
g
s
t
a
t
u
s
T
a
b
l
e
4
s
h
o
w
s
d
i
f
f
e
r
e
n
c
e
s
in
s
e
v
e
r
a
l
h
e
m
o
g
r
a
m
s
a
n
d
b
l
o
o
d
c
h
e
m
i
s
t
r
y
p
a
r
a
m
e
t
e
r
s
b
e
t
w
e
e
n
s
m
o
k
e
r
s
,
f
o
r
m
e
r
s
m
o
k
e
r
s
,
a
n
d
n
o
n
s
m
o
k
e
r
s
u
b
j
e
c
t
s
.
N
i
c
o
t
i
n
e
l
e
v
e
l
s
,
n
u
m
b
e
r
of
l
e
u
k
o
c
y
t
e
s
,
T
r
e
g
n
u
m
b
e
r
,
a
n
d
c
r
e
a
t
i
n
i
n
e
l
e
v
e
l
w
e
r
e
t
h
e
d
i
f
f
e
r
e
n
c
e
b
e
t
w
e
e
n
g
r
o
u
p
s
p
<
0
.
0
5
.
T
h
e
s
m
o
k
e
r
g
r
o
u
p
'
s
n
i
c
o
t
i
n
e
a
n
d
c
r
e
a
t
i
n
i
n
e
l
e
v
e
l
s
a
n
d
l
e
u
k
o
c
y
t
e
n
u
m
b
e
r
s
w
e
r
e
h
i
g
h
e
r
t
h
a
n
t
h
o
s
e
of
t
h
e
n
o
n
s
m
o
k
e
r
s
’
p
<
0
.
0
5
.
E
r
y
t
h
r
o
c
y
t
e
,
l
e
u
k
o
c
y
t
e
,
p
l
a
t
e
l
e
t
s
,
a
n
d
u
r
e
a
w
e
r
e
r
e
l
a
t
i
v
e
l
y
s
i
m
i
l
a
r
b
e
t
w
e
e
n
s
m
o
k
e
r
s
a
n
d
n
o
n
s
m
o
k
e
r
s
’
p
<
0
.
0
5
.
T
a
b
l
e
4
.
H
e
m
o
g
r
a
m
a
n
d
b
l
o
o
d
c
h
e
m
i
s
t
r
y
b
a
s
e
d
o
n
t
h
e
s
m
o
k
i
n
g
s
t
a
t
u
s
o
f
h
e
a
l
t
h
y
v
o
l
u
n
t
e
e
r
s
i
n
Y
o
g
y
a
k
a
r
t
a
C
h
a
r
a
c
t
e
r
i
s
t
i
c
N
o
s
m
o
k
i
n
g
(
n
=
8
1
)
F
o
r
m
e
r
s
m
o
k
e
r
(
n
=
7)
S
m
o
k
e
r
(
n
=
1
8
)
T
o
t
a
l
p
N
i
c
o
t
i
n
e
l
e
v
e
l
(
n
m
o
l
/
d
l
)
9
.
7
6
±
4
.
6
1
3
5
.
8
5
7
1
±
4
.
2
9
5
6
.
0
5
±
9
.
6
9
1
9
.
3
4
±
1
8
.
7
7
0
.
0
0
0
1
*
Hb
1
2
.
7
7
±
1
.
1
8
1
3
.
3
1
±
1
.
8
2
1
3
.
1
5
±
1
.
7
2
1
2
.
8
7
±
1
.
9
0
0
.
6
E
r
i
t
r
o
c
y
t
e
s
4
.
5
3
±
.
0
.
6
3
4
.
6
7
±
.
0
.
4
2
4
.
6
8
±
.
0
.
5
4
4
.
5
6
±
0
.
6
1
0
.
5
L
e
u
k
o
c
y
t
e
s
9
.
8
3
±
4
.
1
6
7
.
5
8
±
3
.
7
0
1
2
.
3
3
±
6
.
4
1
1
0
.
1
1
±
4
.
6
9
0
.
0
4
*
P
l
a
t
e
l
e
t
s
(
x
1
0
3
c
e
l
l
/
d
l
)
2
5
8
.
8
8
±
1
1
1
.
8
5
2
6
6
.
4
3
±
3
6
.
9
9
2
5
2
.
6
1
±
1
0
3
.
0
3
2
5
8
.
3
1
±
1
0
6
.
4
8
0
.
9
5
H
m
t
3
8
.
4
1
±
5
.
8
5
4
0
.
3
1
±
4
.
5
9
4
0
.
0
2
2
2
±
5
.
6
0
3
8
.
8
1
7
0
±
5
.
7
3
0
.
4
4
B
l
o
o
d
G
l
u
c
o
s
e
l
e
v
e
l
(
m
g
/
d
l
)
1
0
7
.
9
0
±
3
7
.
4
8
1
5
9
.
6
0
±
1
6
1
.
7
1
1
1
0
7
.
1
6
±
4
5
.
6
9
1
1
1
.
1
9
±
5
5
.
4
0
0
.
0
5
6
C
D
4
C
D
2
5
T
r
e
g
2
6
.
3
1
±
7
.
4
3
2
2
.
3
1
±
8
.
2
4
2
0
.
4
5
±
3
.
2
4
2
5
.
0
8
±
7
.
2
7
0
.
0
1
*
T
r
i
g
l
y
c
e
r
i
d
e
1
2
1
.
5
9
±
7
2
.
0
8
1
3
3
.
9
9
±
8
2
.
8
3
1
1
8
.
7
3
±
5
8
.
0
9
1
2
1
.
9
2
±
7
0
.
0
6
0
.
8
6
U
r
e
u
m
(
m
g
/
d
l
)
3
7
.
0
9
±
3
9
.
7
3
7
4
.
6
8
±
9
0
.
4
9
3
8
.
2
6
±
3
6
.
0
4
3
9
.
7
7
8
9
±
4
4
.
3
6
0
.
0
9
6
C
r
e
a
t
i
n
i
n
e
(
m
g
/
d
l
)
0
.
8
3
±
0
.
0
1
1
.
0
1
±
1
.
2
1
0
.
8
9
±
0
.
8
9
1.
09
±
1
.
2
1
0
.
0
2
*
G
F
R
9
4
.
7
6
±
2
1
.
5
6
8
6
.
1
4
±
3
4
.
3
5
1
0
0
.
0
4
±
2
2
.
2
1
9
5
.
1
8
±
2
2
.
2
3
0
.
4
3
H
e
m
o
g
r
a
m
p
r
o
f
i
l
e
,
u
r
e
a
l
e
v
e
l
,
a
n
d
c
r
e
a
t
i
n
i
n
e
l
e
v
e
l
in
t
h
e
s
t
u
d
y
w
e
r
e
in
t
h
e
n
o
r
m
a
l
r
a
n
g
e
.
T
h
e
n
u
m
b
e
r
of
e
r
y
t
h
r
o
c
y
t
e
s
a
n
d
p
l
a
t
e
l
e
t
s
in
t
h
e
s
m
o
k
e
r
s
a
n
d
n
o
n
s
m
o
k
e
r
s
in
t
h
i
s
s
t
u
d
y
d
i
d
n
ot
d
i
f
f
e
r
.
S
t
i
l
l
,
t
h
e
n
u
m
b
e
r
of
l
e
u
k
o
c
y
t
e
s
in
s
m
o
k
e
r
s
w
a
s
h
i
g
h
e
r
t
h
a
n
n
o
n
s
m
o
k
e
r
s
a
n
d
s
t
a
t
i
s
t
i
c
a
l
l
y
s
i
g
n
i
f
i
c
a
n
t
p
<
0
.
0
5
.
P
r
e
v
i
o
u
s
s
t
u
d
i
e
s
w
h
e
r
e
s
m
o
k
e
r
s
h
a
d
h
i
g
h
e
r
l
e
u
k
o
c
y
t
e
s
,
h
e
m
o
g
l
o
b
i
n
,
a
n
d
p
l
a
t
e
l
e
t
s
t
h
a
n
n
o
n
s
m
o
k
e
r
s
f
o
u
n
d
d
i
f
f
e
r
e
n
t
r
e
s
u
l
t
s
.
In
a
c
r
o
s
s
-
s
e
c
t
i
o
n
a
l
s
t
u
d
y
in
J
a
p
a
n
,
e
l
e
v
a
t
e
d
w
h
i
t
e
b
l
o
o
d
c
e
l
l
(
W
B
C
)
c
o
u
n
t
s
a
r
e
s
i
g
n
i
f
i
c
a
n
t
l
y
a
s
s
o
c
i
a
t
e
d
w
i
t
h
a
c
t
i
v
e
s
m
o
k
e
r
s
,
but
not
w
i
t
h
f
o
r
m
e
r
s
m
o
k
e
r
s
[
4
0
]
.
T
h
e
s
u
b
j
e
c
t
s
in
t
h
i
s
s
t
u
d
y
w
e
r
e
h
e
a
l
t
h
y
s
u
b
j
e
c
t
s
at
h
i
g
h
r
i
s
k
of
C
K
D
,
a
n
d
t
h
e
y
w
e
r
e
d
i
f
f
e
r
e
n
t
f
r
o
m
t
h
e
S
u
b
j
e
c
t
s
i
n
v
o
l
v
e
d
in
t
h
e
p
r
e
v
i
o
u
s
s
t
u
d
i
e
s
[
1
2
,
3
4
]
.
C
r
e
a
t
i
n
i
n
e
a
n
d
u
r
e
a
l
e
v
e
l
s
in
s
m
o
k
e
r
s
a
n
d
n
o
n
s
m
o
k
e
r
s
w
e
r
e
w
i
t
h
i
n
n
o
r
m
a
l
l
i
m
i
t
s
.
T
h
e
s
t
u
d
y
f
o
u
n
d
t
h
a
t
s
m
o
k
e
r
s
h
a
d
h
i
g
h
e
r
c
r
e
a
t
i
n
i
n
e
l
e
v
e
l
s
t
h
a
n
non
-
s
m
o
k
i
n
g
(
0
.
8
9
±
0
.
6
7
v
s
.
0
.
8
3
±
0
.
0
1
m
g
/
d
l
,
p
<
0
.
0
5
.
T
h
e
p
r
e
v
i
o
u
s
s
t
u
d
y
s
h
o
w
s
t
h
a
t
t
he
s
a
m
e
r
e
s
u
l
t
s
a
l
s
o
f
o
u
n
d
t
h
a
t
s
m
o
k
i
n
g
i
n
t
e
n
s
i
t
y
w
a
s
a
s
s
o
c
i
a
t
e
d
w
i
t
h
i
n
c
r
e
a
s
e
d
c
r
e
a
t
i
n
i
n
e
l
e
v
e
l
s
[
4
1
,
4
2
]
.
N
i
c
o
t
i
n
e
l
e
v
e
l
s
in
t
h
e
s
m
o
k
e
r
s
w
e
r
e
t
h
e
h
i
g
h
e
s
t
(
5
6
.
0
5
±
9
.
6
9
n
g
/
m
l
)
,
f
o
l
l
o
w
e
d
by
f
o
r
m
e
r
s
m
o
k
e
r
s
(
3
5
.
8
5
7
1
±
4
.
2
9
n
g
/
m
l
)
.
T
h
e
l
o
w
e
s
t
w
a
s
in
n
o
n
s
m
o
k
e
r
s
(
9
.
7
6
±
4
.
6
1
n
g
/
m
l
)
;
s
i
m
i
l
a
r
to
t
h
e
r
e
s
u
l
t
s
,
t
h
e
p
r
e
v
i
o
u
s
s
t
u
d
i
e
s
a
l
s
o
f
o
u
n
d
t
h
a
t
t
h
e
s
m
o
k
e
r
'
s
g
r
o
u
p
h
a
d
h
i
g
h
e
r
n
i
c
o
t
i
n
e
l
e
v
e
l
s
t
h
a
n
t
h
e
non
-
s
m
o
k
i
n
g
(
1
5
.
7
4
±
4
.
2
4
v
.
5
3
.
7
8
±
1
9
.
9
1
m
g
/
d
l
)
p
<
0
.
0
5
.
S
m
o
k
e
r
s
w
i
t
h
m
o
r
e
t
h
a
n
15
p
a
c
k
s
/
w
e
e
k
or
s
m
o
k
i
n
g
f
o
r
m
o
r
e
t
h
a
n
20
y
e
a
r
s
h
a
d
t
h
e
h
i
g
h
e
s
t
b
l
o
o
d
n
i
c
o
t
i
n
e
l
e
v
e
l
s
[
1
1
,
4
3
]
.
T
o
b
a
c
c
o
c
i
g
a
r
e
t
t
e
s
a
n
d
i
t
s
n
i
c
o
t
i
n
e
c
o
n
t
e
n
t
h
a
v
e
s
h
o
w
n
an
i
n
f
l
u
e
n
c
e
on
t
h
e
i
m
m
u
n
e
s
y
s
t
e
m
[
4
4
]
.
C
h
r
o
n
i
c
a
l
l
y
s
m
o
k
e
e
x
p
o
s
u
r
e
i
n
c
r
e
a
s
e
s
t
h
e
i
n
c
i
d
e
n
c
e
of
h
y
p
e
r
u
r
i
c
e
m
i
a
a
n
d
a
l
b
u
m
i
n
u
r
i
a
[
4
5
]
.
On
t
h
e
o
t
h
e
r
h
a
n
d
,
it
d
e
c
r
e
a
s
e
s
t
h
e
n
u
m
b
e
r
a
n
d
a
c
t
i
v
i
t
y
of
C
D
4
T
h
a
n
d
C
D
8
l
y
m
p
h
o
c
y
t
e
s
[
4
6
]
.
In
t
h
e
l
a
b
o
r
a
t
o
r
y
,
it
h
a
s
b
e
e
n
s
h
o
w
n
t
h
a
t
c
i
g
a
r
e
t
t
e
s
m
o
k
e
s
u
p
p
r
e
s
s
e
s
t
h
e
e
x
p
r
e
s
s
i
o
n
of
F
o
x
p
3
in
T
r
e
g
c
e
l
l
s
,
t
h
u
s
d
e
c
r
e
a
s
i
n
g
i
t
s
n
u
m
b
e
r
/
p
e
r
c
e
n
t
a
g
e
.
T
r
e
g
p
l
a
y
s
a
s
i
g
n
i
f
i
c
a
n
t
r
o
l
e
in
t
h
e
r
e
g
u
l
a
t
i
o
n
of
i
n
f
l
a
m
m
a
t
o
r
y
r
e
s
p
o
n
s
e
s
a
n
d
t
i
s
s
u
e
r
e
p
a
i
r
a
f
t
e
r
t
r
a
u
m
a
.
T
r
e
g
f
u
n
c
t
i
o
n
s
a
r
e
as
p
r
o
t
e
c
t
o
r
s
of
i
s
c
h
e
m
i
c
r
e
n
a
l
i
n
j
u
r
y
I
R
I
k
i
d
n
e
y
s
[
4
7
]
.
B
a
s
e
d
on
t
h
e
s
e
r
e
s
u
l
t
s
,
we
s
u
g
g
e
s
t
t
h
a
t
s
m
o
k
e
r
s
'
r
i
s
k
of
k
i
d
n
e
y
d
a
m
a
g
e
is
m
o
r
e
s
i
g
n
i
f
i
c
a
n
t
t
h
a
n
nons
m
o
k
e
r
s
'
due
to
a
d
e
c
r
e
a
s
e
in
T
r
e
g
l
e
v
e
l
.
T
r
e
g
i
n
h
i
b
i
t
s
i
n
f
l
a
m
m
a
t
i
o
n
r
e
s
p
o
n
s
e
in
t
h
e
n
a
t
u
r
a
l
i
m
m
u
n
e
s
y
s
t
e
m
.
In
l
y
m
p
h
o
c
y
t
e
-
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t
.
J
.
P
u
b
l
i
c
H
e
a
l
t
h
S
c
i
.
I
S
S
N
:
2252
-
8
8
0
6
N
i
c
o
t
i
n
e
l
e
v
e
l
a
s
s
o
c
i
a
t
e
d
w
i
t
h
d
e
c
r
e
a
s
i
n
g
T
r
e
g
n
u
m
b
e
r
i
n
s
m
o
k
e
r
h
e
a
l
t
h
y
v
o
l
u
n
t
e
e
r
s
(
A
k
r
o
m
)
93
d
e
f
i
c
i
e
n
t
m
i
c
e
w
i
t
h
I
R
I
,
a
d
o
p
t
i
v
e
T
r
e
g
a
d
m
i
n
i
s
t
r
a
t
i
o
n
can
p
r
o
t
e
c
t
t
e
s
t
a
n
i
m
a
l
s
f
r
o
m
k
i
d
n
e
y
d
a
m
a
g
e
due
to
t
h
e
e
x
c
e
s
s
i
v
e
n
a
t
u
r
a
l
i
m
m
u
n
e
r
e
s
p
o
n
s
e
.
In
n
o
r
m
a
l
c
i
r
c
u
m
s
t
a
n
c
e
s
,
T
r
e
g
e
x
p
r
e
s
s
e
s
C
D
2
5
.
T
h
e
a
d
m
i
n
i
s
t
r
a
t
i
o
n
of
C
D
2
5
a
n
t
i
b
o
d
y
in
t
e
s
t
a
n
i
m
a
l
s
w
i
t
h
I
R
I
h
a
s
b
e
e
n
p
r
o
v
e
n
to
r
e
d
u
c
e
t
h
e
n
u
m
b
e
r
of
C
D
4
F
o
x
p
3
T
r
e
g
in
t
h
e
k
i
d
n
e
y
,
s
p
l
e
e
n
,
a
n
d
b
l
o
o
d
.
T
h
e
t
e
s
t
a
n
i
m
a
l
s
a
r
e
m
o
r
e
s
u
s
c
e
p
t
i
b
l
e
to
d
a
m
a
g
e
t
h
a
n
t
h
e
t
e
s
t
a
n
i
m
a
l
s
w
i
t
h
a
s
u
f
f
i
c
i
e
n
t
a
m
o
u
n
t
of
T
r
e
g
.
T
h
e
p
r
e
v
e
n
t
i
o
n
of
k
i
d
n
e
y
d
a
m
a
g
e
due
to
I
R
I
is
m
o
r
e
e
v
i
d
e
n
t
in
t
h
e
t
e
s
t
a
n
i
m
a
l
s
w
i
t
h
c
o
m
p
l
e
t
e
T
r
e
g
d
e
f
i
c
i
e
n
c
y
a
d
m
i
n
i
s
t
e
r
e
d
w
i
t
h
I
R
I
.
T
h
e
a
b
s
e
n
c
e
of
F
O
X
P
3
as
a
T
r
e
g
t
r
a
n
s
c
r
i
p
t
i
o
n
f
a
c
t
o
r
l
e
a
d
s
to
t
h
e
t
e
s
t
a
n
i
m
a
l
s
e
x
p
e
r
i
e
n
c
i
n
g
a
u
t
o
i
m
m
u
n
e
d
i
s
e
a
s
e
a
n
d
d
e
a
t
h
on
t
h
e
t
h
i
r
d
o
r
f
o
u
r
t
h
w
e
e
k
[
4
8
]
.
3
.
3
.
T
h
e
r
e
l
a
t
i
o
n
s
h
i
p
b
e
t
w
e
e
n
b
e
h
a
v
i
o
r
s
m
o
k
i
n
g
w
i
t
h
n
i
c
o
t
i
n
e
l
e
v
e
l
s
a
n
d
T
r
e
g
c
o
u
n
t
s
a
n
d
a
s
s
o
c
i
a
t
i
o
n
n
i
c
o
t
i
n
e
l
e
v
e
l
w
i
t
h
T
r
e
g
n
u
m
b
e
r
We
c
o
n
d
u
c
t
e
d
a
c
o
r
r
e
l
a
t
i
o
n
a
n
a
l
y
s
i
s
w
i
t
h
t
h
e
P
e
a
r
s
o
n
c
o
r
r
e
l
a
t
i
o
n
to
d
e
t
e
r
m
i
n
e
t
h
e
c
o
r
r
e
l
a
t
i
o
n
b
e
t
w
e
e
n
t
h
e
n
u
m
b
e
r
of
c
i
g
a
r
e
t
t
e
c
o
n
s
u
m
p
t
i
o
n
a
n
d
s
m
o
k
i
n
g
d
u
r
a
t
i
o
n
.
T
a
b
l
e
5
a
p
r
e
s
e
n
t
s
t
h
e
c
o
r
r
e
l
a
t
i
o
n
t
e
s
t
r
e
s
u
l
t
s
b
e
t
w
e
e
n
c
i
g
a
r
e
t
t
e
c
o
n
s
u
m
p
t
i
o
n
a
n
d
s
m
o
k
i
n
g
d
u
r
a
t
i
o
n
w
i
t
h
n
i
c
o
t
i
n
e
l
e
v
e
l
a
n
d
T
r
e
g
n
u
m
b
e
r
)
.
B
a
s
e
d
on
T
a
b
l
e
5
b
,
n
i
c
o
t
i
n
e
l
e
v
e
l
s
a
r
e
a
s
s
o
c
i
a
t
e
d
w
i
t
h
s
m
o
k
i
n
g
d
u
r
a
t
i
o
n
a
n
d
i
n
t
e
n
s
i
t
y
(
s
e
v
e
r
a
l
p
a
c
k
s
/
w
e
e
k
)
.
T
a
b
l
e
5
a
.
T
h
e
r
e
l
a
t
i
o
n
s
h
i
p
b
e
t
w
e
e
n
m
a
n
y
c
i
g
a
r
e
t
t
e
c
o
n
s
u
m
p
t
i
o
n
s
a
n
d
t
h
e
s
m
o
k
i
n
g
d
u
r
a
t
i
o
n
w
i
t
h
n
i
c
o
t
i
n
e
l
e
v
e
l
a
n
d
T
r
e
g
n
u
m
b
e
r
a
n
d
t
h
e
a
s
s
o
c
i
a
t
i
o
n
b
e
t
w
e
e
n
n
i
c
o
t
i
n
e
l
e
v
e
l
w
i
t
h
T
r
e
g
n
u
m
b
e
r
i
n
h
e
a
l
t
h
y
v
o
l
u
n
t
e
e
r
i
n
D
I
Y
:
(
a
)
c
o
r
r
e
l
a
t
i
o
n
a
n
a
l
y
s
i
s
(
P
e
a
r
s
o
n
c
o
r
r
e
l
a
t
i
o
n
t
e
s
t
)
of
t
h
e
n
u
m
b
e
r
of
c
i
g
a
r
e
t
t
e
c
o
n
s
u
m
p
t
i
o
n
a
n
d
d
u
r
a
t
i
o
n
of
s
m
o
k
i
n
g
w
i
t
h
n
i
c
o
t
i
n
e
l
e
v
e
l
a
n
d
T
r
e
g
n
u
m
b
e
r
C
h
a
r
a
c
t
e
r
i
s
t
i
c
s
P
a
r
a
m
e
t
e
r
s
N
i
c
o
t
i
n
e
l
e
v
e
l
s
T
r
e
g
l
e
v
e
l
s
T
o
t
a
l
c
o
n
s
u
m
p
t
i
o
n
o
f
c
i
g
a
r
e
t
t
e
s
p
e
r
w
e
e
k
(
p
a
c
k
s
/
w
e
e
k
s
)
P
e
a
r
s
o
n
C
o
r
r
e
l
a
t
i
o
n
0
.
6
3
1
**
-
0
.
2
3
8
**
S
i
g
.
(2
-
t
a
i
l
e
d
)
0
.
0
0
0
0
.
0
0
2
S
m
o
k
i
n
g
d
u
r
a
t
i
o
n
(
y
e
a
r
s
)
P
e
a
r
s
o
n
C
o
r
r
e
l
a
t
i
o
n
0
.
6
2
3
**
-
0
.
2
1
9
**
S
i
g
.
(2
-
t
a
i
l
e
d
)
0
.
0
0
0
0
.
0
0
5
**
C
o
r
r
e
l
a
t
i
o
n
i
s
s
i
g
n
i
f
i
c
a
n
t
a
t
t
h
e
0
.
0
1
l
e
v
e
l
(
2
-
t
a
i
l
e
d
)
T
a
b
l
e
5
b
.
T
h
e
r
e
l
a
t
i
o
n
s
h
i
p
b
e
t
w
e
e
n
m
a
n
y
c
i
g
a
r
e
t
t
e
c
o
n
s
u
m
p
t
i
o
n
s
a
n
d
t
h
e
s
m
o
k
i
n
g
d
u
r
a
t
i
o
n
w
i
t
h
n
i
c
o
t
i
n
e
l
e
v
e
l
a
n
d
T
r
e
g
n
u
m
b
e
r
a
n
d
t
h
e
a
s
s
o
c
i
a
t
i
o
n
b
e
t
w
e
e
n
n
i
c
o
t
i
n
e
l
e
v
e
l
w
i
t
h
T
r
e
g
n
u
m
b
e
r
i
n
h
e
a
l
t
h
y
v
o
l
u
n
t
e
e
r
i
n
D
I
Y
:
(
b
)
r
e
g
r
e
s
s
i
o
n
a
n
a
l
y
s
i
s
o
f
n
i
c
o
t
i
n
e
l
e
v
e
l
t
o
T
r
e
g
n
u
m
b
e
r
t
e
s
t
P
a
r
a
m
e
t
e
r
s
A
s
s
o
c
i
a
t
i
o
n
n
i
c
o
t
i
n
e
l
e
v
e
l
–
T
r
e
g
n
u
m
b
e
r
B
e
t
a
-
0
.
2
6
8
p
0
.
0
0
2
*
*
*
*
*
*
C
o
r
r
e
l
a
t
i
o
n
i
s
s
i
g
n
i
f
i
c
a
n
t
a
t
t
h
e
0
.
0
1
l
e
v
e
l
(
2
-
t
a
i
l
e
d
)
C
o
r
r
e
l
a
t
i
o
n
t
e
s
t
r
e
s
u
l
t
s
s
h
o
w
t
h
a
t
t
h
e
c
i
g
a
r
e
t
t
e
c
o
n
s
u
m
p
t
i
o
n
a
n
d
s
m
o
k
i
n
g
d
u
r
a
t
i
o
n
w
a
s
r
e
l
a
t
e
d
to
n
i
c
o
t
i
n
e
l
e
v
e
l
s
(
r
=
0
.
6
3
a
n
d
r
=
0
.
6
2
,
p
=
0
.
0
0
0
,
p
o
s
i
t
i
v
e
)
a
n
d
T
r
e
g
l
e
v
e
l
s
(
r
=
0
.
2
4
a
n
d
r
=
0
.
2
2
,
p
=
0
.
0
0
2
a
n
d
p=
0
.
0
0
5
,
n
e
g
a
t
i
v
e
)
.
In
t
e
r
m
s
n
i
c
o
t
i
n
e
l
e
v
e
l
s
,
t
h
e
p
o
s
i
t
i
v
e
c
o
r
r
e
l
a
t
i
o
n
(
)
i
n
d
i
c
a
t
e
s
t
h
a
t
t
h
e
r
e
l
a
t
i
o
n
s
h
i
p
b
e
t
w
e
e
n
t
h
e
c
i
g
a
r
e
t
t
e
c
o
n
s
u
m
p
t
i
o
n
a
n
d
s
m
o
k
i
n
g
d
u
r
a
t
i
o
n
a
n
d
s
e
r
u
m
l
e
v
e
l
s
of
n
i
c
o
t
i
n
e
is
s
o
l
i
d
,
u
n
i
d
i
r
e
c
t
i
o
n
a
l
a
n
d
s
t
a
t
i
s
t
i
c
a
l
l
y
s
i
g
n
i
f
i
c
a
n
t
p<
0
.
0
0
.
M
o
r
e
o
v
e
r
,
s
m
o
k
i
n
g
c
i
g
a
r
e
t
t
e
s
or
l
o
n
g
e
r
s
m
o
k
i
n
g
h
a
b
i
t
l
e
a
d
s
to
h
i
g
h
e
r
n
i
c
o
t
i
n
e
l
e
v
e
l
s
in
t
h
e
b
l
o
o
d
.
T
h
e
n
e
g
a
t
i
v
e
c
o
r
r
e
l
a
t
i
o
n
b
e
t
w
e
e
n
T
r
e
g
c
o
u
n
t
a
n
d
t
h
e
c
i
g
a
r
e
t
t
e
c
o
n
s
u
m
p
t
i
o
n
a
n
d
s
m
o
k
i
n
g
d
u
r
a
t
i
o
n
(
r
=
0
.
2
4
a
n
d
r
=
0
.
2
2
)
s
h
o
w
s
t
h
a
t
t
h
e
r
e
l
a
t
i
o
n
s
h
i
p
is
f
a
i
r
l
y
s
t
r
o
n
g
but
o
p
p
o
s
i
t
e
a
n
d
s
t
a
t
i
s
t
i
c
a
l
l
y
s
i
g
n
i
f
i
c
a
n
t
(
p
<
0
.
0
5
)
.
T
h
e
r
e
s
u
l
t
s
i
n
d
i
c
a
t
e
a
p
o
s
i
t
i
v
e
c
o
r
r
e
l
a
t
i
o
n
b
e
t
w
e
e
n
s
m
o
k
i
n
g
i
n
t
e
n
s
i
t
y
a
n
d
d
u
r
a
t
i
o
n
a
n
d
n
i
c
o
t
i
n
e
l
e
v
e
l
s
(
p
<
0
.
0
5
)
.
In
o
t
h
e
r
w
o
r
d
s
,
b
l
o
o
d
n
i
c
o
t
i
n
e
l
e
v
e
l
s
can
be
u
s
e
d
as
an
i
n
d
i
c
a
t
o
r
of
s
m
o
k
i
n
g
i
n
t
e
n
s
i
t
y
a
n
d
d
u
r
a
t
i
o
n
.
I
n
t
e
r
e
s
t
i
n
g
l
y
,
t
h
e
n
o
n
s
m
o
k
e
r
s
w
e
r
e
f
o
u
n
d
to
h
a
v
e
a
r
e
a
s
o
n
a
b
l
y
h
i
g
h
n
i
c
o
t
i
n
e
l
e
v
e
l
at
9
n
m
o
l
/
d
l
.
T
h
i
s
r
e
s
u
l
t
s
h
o
w
s
t
h
a
t
e
x
p
o
s
u
r
e
to
c
i
g
a
r
e
t
t
e
s
m
o
k
e
in
non
-
s
m
o
k
i
n
g
r
e
s
p
o
n
d
e
n
t
s
is
h
i
g
h
[
4
9
,
5
0
]
.
T
r
e
g
n
u
m
b
e
r
s
in
t
h
e
p
o
p
u
l
a
t
i
o
n
can
v
a
r
y
,
as
b
i
o
l
o
g
i
c
a
l
a
n
d
e
n
v
i
r
o
n
m
e
n
t
a
l
f
a
c
t
o
r
s
i
n
f
l
u
e
n
c
e
t
h
e
m
.
P
r
e
v
i
o
u
s
s
t
u
d
i
e
s
f
o
u
n
d
t
h
a
t
s
m
o
k
e
r
s
h
a
d
a
l
o
w
e
r
n
u
m
b
e
r
of
T
r
e
g
.
In
t
h
i
s
s
t
u
d
y
,
C
D
4
C
D
2
5
T
c
e
l
l
s
in
t
h
e
s
m
o
k
e
r
s
'
g
r
o
u
p
w
e
r
e
l
o
w
e
r
t
h
a
n
t
h
e
non
-
h
e
a
l
t
h
y
h
e
a
l
t
h
y
s
u
b
j
e
c
t
s
,
s
t
a
t
i
s
t
i
c
a
l
l
y
s
i
g
n
i
f
i
c
a
n
t
(
p
<
0
.
0
5
)
.
T
h
e
r
e
s
u
l
t
s
of
t
h
i
s
s
t
u
d
y
a
r
e
c
o
n
s
i
s
t
e
n
t
w
i
t
h
t
h
e
r
e
s
u
l
t
s
of
in
v
i
v
o
e
x
p
e
r
i
m
e
n
t
a
l
l
a
b
o
r
a
t
o
r
i
e
s
,
s
a
f
e
in
t
e
s
t
a
n
i
m
a
l
s
e
x
p
o
s
e
d
to
d
i
m
e
t
h
y
l
b
e
n
z
a
n
t
r
a
c
e
n
e
(
D
M
B
A
)
,
one
of
t
h
e
c
a
r
c
i
n
o
g
e
n
s
in
c
i
g
a
r
e
t
t
e
s
,
h
a
v
i
n
g
l
o
w
e
r
T
r
e
g
c
o
u
n
t
s
t
h
a
n
in
t
e
s
t
a
n
i
m
a
l
s
w
i
t
h
o
u
t
D
M
B
A
e
x
p
o
s
u
r
e
.
T
h
e
D
M
B
A
is
a
c
a
r
c
i
n
o
g
e
n
a
n
d
i
m
m
u
n
o
t
o
x
i
c
a
g
e
n
t
[
5
1
,
5
2
]
.
T
r
e
g
c
e
l
l
s
in
p
e
r
i
p
h
e
r
a
l
b
l
o
o
d
f
r
o
m
a
l
l
e
r
g
i
c
or
a
u
t
o
i
m
m
u
n
e
d
i
s
e
a
s
e
p
a
t
i
e
n
t
s
m
a
y
be
l
o
w
e
r
t
h
a
n
p
e
r
i
p
h
e
r
a
l
b
l
o
o
d
n
u
m
b
e
r
s
in
p
e
r
i
p
h
e
r
a
l
b
l
o
o
d
f
r
o
m
h
e
a
l
t
h
y
s
u
b
j
e
c
t
s
[
2
7
,
5
3
]
.
T
r
e
g
e
x
p
r
e
s
s
i
o
n
is
a
p
h
e
n
o
t
y
p
i
c
s
i
g
n
a
l
to
t
h
e
p
r
o
t
e
c
t
i
o
n
of
t
e
s
t
a
n
i
m
a
l
s
t
r
e
a
t
e
d
w
i
t
h
I
R
I
.
At
t
he
s
t
a
g
e
of
p
o
s
t
-
i
s
c
h
e
m
i
c
r
e
p
e
r
f
u
s
i
o
n
,
t
h
e
r
e
h
a
s
b
e
e
n
an
i
n
c
r
e
a
s
e
d
e
x
p
r
e
s
s
i
o
n
of
T
G
F
-
β.
A
p
a
r
t
f
r
o
m
b
e
i
n
g
p
r
o
d
u
c
e
d
by
T
r
e
g
,
T
G
F
-
β
a
n
d
IL
-
10
a
r
e
a
l
s
o
p
r
o
v
i
d
e
d
by
r
e
n
a
l
t
u
b
u
l
a
r
c
e
l
l
s
d
a
m
a
g
e
d
by
I
R
I
a
n
d
m
a
c
r
o
p
h
a
g
e
s
.
T
r
e
g
a
d
o
p
t
i
v
e
a
d
m
i
n
i
s
t
r
a
t
i
o
n
in
t
e
s
t
a
n
i
m
a
l
s
w
i
t
h
I
R
I
h
a
s
b
e
e
n
s
h
o
w
n
to
i
m
p
r
o
v
e
i
n
f
l
a
m
m
a
t
o
r
y
r
e
a
c
t
i
o
n
s
a
n
d
p
r
e
v
e
n
t
k
i
d
n
e
y
d
a
m
a
g
e
.
In
m
i
c
e
w
i
t
h
c
o
m
p
l
e
t
e
T
r
e
g
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
S
N
:
2252
-
8806
I
n
t
.
J
.
P
u
b
l
i
c
H
e
a
l
t
h
S
c
i
.
V
o
l
.
1
0
,
N
o
.
1
,
M
a
r
c
h
20
21
:
8
8
–
9
6
94
d
e
f
i
c
i
e
n
c
y
,
t
h
e
r
e
is
an
a
c
c
u
m
u
l
a
t
i
o
n
of
n
e
u
t
r
o
p
h
i
l
s
a
n
d
m
a
c
r
o
p
h
a
g
e
s
in
t
h
e
k
i
d
n
e
y
a
f
t
e
r
an
I
R
I
.
N
e
u
t
r
o
p
h
i
l
s
a
c
c
u
m
u
l
a
t
i
n
g
in
t
h
e
k
i
d
n
e
y
a
r
e
s
h
o
w
n
to
a
c
t
i
v
e
l
y
s
e
c
r
e
t
e
I
F
N
-
γ
r
e
s
u
l
t
i
n
g
in
e
x
c
e
s
s
i
v
e
a
n
d
d
e
s
t
r
u
c
t
i
v
e
i
n
f
l
a
m
m
a
t
o
r
y
r
e
a
c
t
i
o
n
s
t
h
a
t
e
n
d
a
n
g
e
r
t
e
s
t
a
n
i
m
a
l
s
[
5
4
,
5
5
]
.
T
h
e
a
d
m
i
n
i
s
t
r
a
t
i
o
n
of
a
d
o
p
t
i
v
e
T
r
e
g
h
a
s
b
e
e
n
p
r
o
v
e
n
to
i
n
h
i
b
i
t
t
h
e
n
a
t
u
r
a
l
i
m
m
u
n
e
r
e
s
p
o
n
s
e
by
d
e
c
r
e
a
s
i
n
g
t
h
e
n
u
m
b
e
r
of
n
e
u
t
r
o
p
h
i
l
s
in
t
h
e
k
i
d
n
e
y
in
t
e
s
t
a
n
i
m
a
l
s
t
r
e
a
t
e
d
w
i
t
h
I
R
I
.
O
t
h
e
r
s
t
u
d
i
e
s
h
a
v
e
s
h
o
w
n
t
h
a
t
a
d
m
i
n
i
s
t
e
r
i
n
g
a
d
o
p
t
i
v
e
T
r
e
g
to
b
u
r
n
t
r
a
u
m
a
t
i
c
can
s
u
p
p
r
e
s
s
e
x
c
e
s
s
i
v
e
n
a
t
u
r
a
l
i
m
m
u
n
e
r
e
s
p
o
n
s
e
s
to
p
r
e
v
e
n
t
t
h
e
d
e
a
t
h
of
t
e
s
t
a
n
i
m
a
l
s
but
m
a
i
n
t
a
i
n
t
h
e
i
r
a
b
i
l
i
t
y
to
i
n
h
i
b
i
t
d
e
a
t
h
s
due
to
i
n
f
e
c
t
i
o
n
[
5
6
]
.
4.
C
O
N
C
L
U
S
I
O
N
We
c
o
n
c
l
u
d
e
t
h
a
t
s
m
o
k
i
n
g
b
e
h
a
v
i
o
r
is
a
s
s
o
c
i
a
t
e
d
w
i
t
h
n
i
c
o
t
i
n
e
l
e
v
e
l
,
l
e
u
k
o
c
y
t
e
s
n
u
m
b
e
r
,
a
n
d
T
r
e
g
a
n
d
t
h
a
t
s
m
o
k
i
n
g
h
a
b
i
t
s
can
i
n
c
r
e
a
s
e
c
r
e
a
t
i
n
i
n
e
l
e
v
e
l
s
.
T
h
e
s
m
o
k
i
n
g
n
u
m
b
e
r
(
p
a
c
k
s
/
w
e
e
k
)
a
n
d
d
u
r
a
t
i
o
n
a
r
e
r
e
l
a
t
e
d
to
n
i
c
o
t
i
n
e
l
e
v
e
l
s
in
t
h
e
b
l
o
o
d
.
F
u
r
t
h
e
r
m
o
r
e
,
t
h
e
l
e
v
e
l
of
n
i
c
o
t
i
n
e
in
t
h
e
b
l
o
o
d
is
r
e
l
a
t
e
d
to
t
h
e
T
r
e
g
c
o
u
n
t
.
A
C
K
N
O
WL
E
D
G
E
M
E
N
T
S
T
h
e
a
u
t
h
o
r
s
e
x
p
r
e
s
s
t
h
e
i
r
g
r
a
t
i
t
u
d
e
to
a
l
l
r
e
s
p
o
n
d
e
n
t
s
w
h
o
h
a
v
e
b
e
e
n
w
i
l
l
i
n
g
to
v
o
l
u
n
t
e
e
r
in
t
h
i
s
r
e
s
e
a
r
c
h
.
R
E
F
E
R
E
N
C
E
S
[1]
A.
A
hs
a
n
,
Int
e
r
e
s
t
of
T
obac
c
o
F
ac
t
s
a
nd
P
r
obl
e
m
s
i
n
Indone
s
i
a
2014/
B
unga
R
am
pai
F
ak
t
a
T
e
m
bak
au
dan
P
e
r
m
as
al
ahanny
a
di
Indone
s
i
a
2014
.
T
oba
c
c
o
Cont
rol
S
up
p
ort
Ce
nt
e
r
–
IA
K
M
I,
2014.
[2]
J.
P.
N
a
ra
i
n
,
R.
G
a
rg
,
a
nd
A.
F
ri
c
,
“
N
on
-
c
om
m
uni
c
a
bl
e
di
s
e
a
s
e
s
in
t
he
S
out
h
-
E
a
s
t
A
s
i
a
Re
g
i
on:
Burde
n,
s
t
ra
t
e
g
i
e
s
a
nd
op
p
ort
uni
t
i
e
s
,
”
T
he
Nat
i
onal
Me
di
c
al
J
our
nal
of
Indi
a
vol
.
24,
no.
5,
pp.
280
-
287,
2011.
[3]
L.
M
i
ha
rdj
a
,
et
a
l
.,
“
P
re
va
l
e
nc
e
of
ki
dne
y
dy
s
func
t
i
on
in
di
a
be
t
e
s
m
e
l
l
i
t
us
a
nd
a
s
s
oc
i
a
t
e
d
ri
s
k
fa
c
t
ors
a
m
ong
p
roduc
t
i
ve
a
g
e
Indone
s
i
a
n,
”
J
our
nal
D
i
abe
t
e
s
Me
t
ab
ol
i
c
D
i
s
or
d
er
.
,
vol
.
17,
no.
1,
pp.
53
-
61,
2018.
[4]
T.
H
i
da
y
a
t
i
,
A.
A
krom
,
a
nd
L.
A
p
ri
a
ni
,
“
T
he
e
ffe
c
t
of
p
hy
s
i
c
a
l
a
c
t
i
vi
t
y
on
l
y
m
p
hoc
y
t
e
c
ount
in
s
m
oke
rs
w
ho
c
ons
um
e
bl
a
c
k
c
um
i
n
s
e
e
d
(
Ni
ge
l
l
a
s
at
i
v
a
L.
)
oi
l
,
”
Int
e
r
nat
i
onal
J
our
nal
of
P
ubl
i
c
H
e
al
t
h
Sc
i
e
nc
e
.
,
vol
.
9,
no.
1,
pp.
8
-
14,
2020.
[5]
M.
B.
Re
i
t
s
m
a
,
et
a
l
.,
“
S
m
oki
ng
p
re
va
l
e
nc
e
a
nd
a
t
t
ri
but
a
bl
e
di
s
e
a
s
e
burde
n
in
195
c
ount
ri
e
s
a
nd
t
e
rri
t
ori
e
s
,
1990
-
2015:
A
s
y
s
t
e
m
a
t
i
c
a
na
l
y
s
i
s
from
t
he
g
l
oba
l
burde
n
of
di
s
e
a
s
e
s
t
udy
2015,
”
L
anc
e
t
,
vol
.
389,
no.
10082,
pp.
1885
-
1906,
2017.
[6]
T.
H
i
da
y
a
t
i
,
A.
A
di
ni
ng
ra
t
,
a
nd
A.
A
krom
,
“
Cl
i
ni
c
a
l
c
ondi
t
i
ons
a
nd
hi
s
t
ory
of
i
l
l
ne
s
s
a
m
ong
t
e
rm
i
na
l
c
hroni
c
ki
dne
y
di
s
e
a
s
e
p
a
t
i
e
nt
s
,
”
Int
e
r
nat
i
onal
J
our
nal
of
P
ubl
i
c
H
e
al
t
h
Sc
i
e
nc
e
,
vol
.
8,
no.
4,
pp.
385
-
390,
2019.
[7]
C.
H.
H
ong
,
et
a
l
.,
“
Be
nz
op
y
re
ne
,
a
m
a
j
or
p
ol
y
a
rom
a
t
i
c
hy
droc
a
rbon
in
s
m
oke
fum
e
,
m
obi
l
i
z
e
s
L
a
ng
e
rha
ns
cells
a
nd
p
ol
a
ri
z
e
s
T
h2/
17
re
s
p
ons
e
s
in
e
p
i
c
ut
a
ne
ous
p
rot
e
i
n
s
e
ns
i
t
i
z
a
t
i
on
t
hroug
h
t
he
a
ry
l
hy
droc
a
rbon
re
c
e
p
t
or,
”
Int
e
r
nat
i
onal
Im
m
unophar
m
ac
ol
ogy
,
vol
.
36,
pp.
111
-
117,
2016.
[8]
R.
B.
G
onç
a
l
ve
s
,
et
a
l
.,
“
Im
p
a
c
t
of
s
m
oki
ng
on
i
nfl
a
m
m
a
t
i
on:
O
ve
rvi
e
w
of
m
ol
e
c
ul
a
r
m
e
c
ha
ni
s
m
s
,
”
Inf
l
am
m
at
i
on
Res
e
ar
c
h
,
vol
.
60,
no.
5,
pp.
409
-
424,
2011.
[9]
M.
H
ua
a
nd
P.
T
a
l
bot
,
“
P
ot
e
nt
i
a
l
he
a
l
t
h
e
ffe
c
t
s
of
e
l
e
c
t
roni
c
c
i
g
a
re
t
t
e
s
:
A
s
y
s
t
e
m
a
t
i
c
re
vi
e
w
of
c
a
s
e
re
p
ort
s
,
”
P
r
e
v
.
Me
d.
R
e
por
t
s
,
vol
.
4,
pp.
169
–
178,
2016.
[10]
G.
E.
Be
ke
l
a
nd
G.
T
hup
a
y
a
g
a
l
e
-
T
s
hw
e
ne
a
g
a
e
,
“
P
re
va
l
e
nc
e
a
nd
a
s
s
oc
i
a
t
e
d
fa
c
t
ors
of
m
e
t
a
bol
i
c
s
y
ndrom
e
a
nd
i
t
s
i
ndi
vi
dua
l
c
om
p
one
nt
s
a
m
ong
a
dol
e
s
c
e
nt
s
,
”
Int
e
r
nat
i
onal
J
our
nal
of
P
ubl
i
c
H
e
al
t
h
Sc
i
e
nc
e
,
vol
.
9,
no.
1,
p.
46
-
56,
2020.
[11]
S.
K
a
l
khora
n
,
N.
L.
Be
now
i
t
z
,
a
nd
N.
A.
Ri
g
ot
t
i
,
“
P
re
ve
nt
i
on
a
nd
T
re
a
t
m
e
nt
of
T
oba
c
c
o
U
s
e
:
J
A
CC
H
e
a
l
t
h
P
rom
ot
i
on
S
e
ri
e
s
,
”
J
our
nal
Am
e
r
i
c
an
Col
l
e
ge
Car
di
ol
ogy
.
,
vol
.
72,
no.
9,
pp.
1030
-
1045,
2018.
[12]
A.
Q.
A
l
khe
da
i
de
,
“
T
oba
c
c
o
s
m
ok
i
ng
c
a
us
e
s
s
e
c
onda
ry
p
ol
y
c
y
t
he
m
i
a
a
nd
a
mild
l
e
ukoc
y
t
os
i
s
a
m
ong
he
a
vy
s
m
oke
rs
in
T
a
i
f
Ci
t
y
in
S
a
udi
A
ra
bi
a
,
”
Saudi
J
our
nal
B
i
ol
ogi
c
al
Sc
i
e
nc
e
s
,
vol
.
27,
no.
1,
pp.
407
-
411,
2019.
[13]
T.
H
i
da
y
a
t
i
,
et
a
l
.,
“
E
va
l
ua
t
i
on
of
bl
a
c
k
c
um
i
n
s
e
e
ds
he
x
a
ne
e
x
t
ra
c
t
as
re
a
c
t
i
ve
ox
y
g
e
n
i
nt
e
rm
e
di
a
t
e
s
(RO
I)
a
nd
p
ha
g
oc
y
t
i
c
a
c
t
i
vi
t
y
m
odul
a
t
or
in
D
M
BA
i
nduc
e
dra
t
s
,
”
B
i
om
e
d
i
c
al
Res
e
ar
c
h
.
,
vol
.
28,
no.
4,
pp.
1755
-
1760,
2017.
[14]
F.
K
oukoul
i
a
nd
J.
P.
Cha
ng
e
ux
,
“
Do
N
i
c
ot
i
ni
c
Re
c
e
p
t
ors
M
odul
a
t
e
H
i
g
h
-
O
rde
r
Cog
ni
t
i
ve
P
roc
e
s
s
i
ng
?
,
”
T
r
e
nds
Ne
u
r
os
c
i
e
nc
e
s
,
vol
.
43,
no.
8,
pp.
550
-
564,
2020.
[15]
N.
L.
Be
now
i
t
z
,
J.
H
ukka
ne
n,
a
nd
P.
J
a
c
ob,
“
N
i
c
ot
i
ne
c
he
m
i
s
t
ry
,
m
e
t
a
bol
i
s
m
,
ki
ne
t
i
c
s
a
nd
bi
om
a
rke
rs
,
”
H
andbook
of
E
x
pe
r
i
m
e
nt
al
P
har
m
ac
ol
ogy
,
vol
.
192.
pp.
29
-
60,
2009.
[16]
F.
S.
A
l
Q
a
ht
a
ny
,
et
a
l
.,
“
A
s
s
oc
i
a
t
i
on
be
t
w
e
e
n
c
i
g
a
re
t
t
e
&
s
hi
s
ha
s
m
oki
ng
a
nd
t
he
s
e
ve
ri
t
y
of
p
ol
y
c
y
t
he
m
i
a
:
A
c
ros
s
s
e
c
t
i
ona
l
s
t
udy
,
”
Saudi
J
our
nal
B
i
ol
ogi
c
al
Sc
i
e
nc
e
s
,
vol
.
27,
no.
1,
pp.
460
-
464,
2019.
[17]
Z.
V
e
rde
,
et
a
l
.,
“
A
s
s
oc
i
a
t
i
on
of
H
T
R2A
-
1438G
/
A
G
e
ne
t
i
c
P
ol
y
m
orp
hi
s
m
w
i
t
h
S
m
oki
ng
a
nd
Chroni
c
O
bs
t
ruc
t
i
ve
P
ul
m
ona
ry
D
i
s
e
a
s
e
,
”
A
r
c
h
i
v
os
B
r
onc
one
um
ol
ogi
a
.
,
vol
.
55,
no.
3,
pp.
128
-
133,
2019.
[18]
P.
F
orm
a
ne
k
,
E.
S
a
l
i
s
bury
-
A
fs
ha
r,
a
nd
M.
A
fs
ha
r,
“
H
e
l
p
i
ng
P
a
t
i
e
nt
s
W
i
t
h
E
S
RD
a
nd
E
a
rl
i
e
r
S
t
a
g
e
s
of
CK
D
to
Q
ui
t
S
m
oki
ng
,
”
A
m
e
r
i
c
an
J
our
nal
of
Ki
dne
y
D
i
s
e
as
e
s
,
vo
l.
72,
no.
2,
pp.
255
-
266,
2018.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
n
t
.
J
.
P
u
b
l
i
c
H
e
a
l
t
h
S
c
i
.
I
S
S
N
:
2252
-
8
8
0
6
N
i
c
o
t
i
n
e
l
e
v
e
l
a
s
s
o
c
i
a
t
e
d
w
i
t
h
d
e
c
r
e
a
s
i
n
g
T
r
e
g
n
u
m
b
e
r
i
n
s
m
o
k
e
r
h
e
a
l
t
h
y
v
o
l
u
n
t
e
e
r
s
(
A
k
r
o
m
)
95
[19]
T.
H
i
da
y
a
t
i
,
et
a
l
.,
“
Che
m
op
re
ve
nt
i
ve
e
ffe
c
t
of
bl
a
c
k
c
um
i
n
s
e
e
d
oi
l
(BCS
O
)
by
i
nc
re
a
s
i
ng
p
53
e
x
p
re
s
s
i
on
in
di
m
e
t
hy
l
be
nz
a
nt
hra
c
e
ne
(D
M
BA
)
-
i
nduc
e
d
S
p
ra
g
ue
D
a
w
l
e
y
ra
t
s
,
”
Res
e
ar
c
h
J
our
nal
Che
m
i
s
t
r
y
E
nv
i
r
on
m
e
nt
,
vol
.
23,
no.
8,
pp.
24
-
32,
2019.
[20]
P.
P.
T
ri
hono
,
L.
Rhodi
a
,
a
nd
M.
R.
K
a
ry
a
nt
i
,
“
K
i
dne
y
D
i
s
e
a
s
e
P
rofi
l
e
s
A
m
ong
A
dol
e
s
c
e
nt
s
in
Indone
s
i
a
,
”
Acta
Me
di
c
a
Indone
s
i
ana
,
vol
.
50,
no.
4,
pp.
283
-
290,
2018.
[21]
S.
J.
E
l
l
i
ot
,
et
a
l
.,
“
S
m
oki
ng
i
nduc
e
s
g
l
om
e
rul
os
c
l
e
ros
i
s
in
a
g
i
ng
e
s
t
rog
e
n
-
de
fi
c
i
e
nt
mice
t
hroug
h
c
ros
s
-
t
a
l
k
be
t
w
e
e
n
T
G
F
-
β1
a
nd
IG
F
-
I
s
i
g
na
l
i
ng
p
a
t
hw
a
y
s
,
”
J
our
nal
Am
e
r
i
c
an
Soc
iety
Ne
phr
ol
ogy
,
vol
.
17,
no.
12,
pp.
3315
-
3324,
2006.
[22]
B.
Bi
kbov
,
et
a
l
.,
“
G
l
oba
l
,
re
g
i
ona
l
,
a
nd
na
t
i
ona
l
burde
n
of
c
hroni
c
ki
dne
y
di
s
e
a
s
e
,
1990
-
2017:
a
s
y
s
t
e
m
a
t
i
c
a
na
l
y
s
i
s
for
t
he
G
l
oba
l
Burde
n
of
D
i
s
e
a
s
e
S
t
udy
2017,
”
L
anc
e
t
,
vol
.
395,
no.
10225,
pp.
709
-
733,
2020.
[23]
A.
B.
F
og
o
,
“
M
e
c
ha
ni
s
m
s
of
p
rog
re
s
s
i
on
of
c
hroni
c
ki
dne
y
di
s
e
a
s
e
,
”
P
e
di
at
r
i
c
Ne
phr
ol
ogy
,
vol
.
22,
no.
12.
pp.
2011
-
2022,
2007.
[24]
T.
H
i
da
y
a
t
i
,
et
a
l
.,
“
T
he
Ins
ul
i
n
L
i
ke
G
row
t
h
F
a
c
t
or
-
1(IG
F
-
1
)
a
nd
Ins
ul
i
n
Bi
ndi
ng
P
rot
e
i
n
-
3
(IG
F
BP
-
3)
L
e
ve
l
As
P
re
di
c
t
or
Bi
om
a
rke
r
of
Chroni
c
K
i
dne
y
D
i
s
e
a
s
e
(CK
D
)
P
a
t
i
e
nt
s
in
Indone
s
i
a
,
”
J
our
nal
Me
d
i
c
al
B
i
oe
ng
i
ne
e
r
i
ng
.
,
vol
.
4,
no.
3,
pp.
254
-
258,
2015.
[25]
M.
E
va
ns
,
et
a
l
.,
“
Ri
s
k
F
a
c
t
ors
for
P
rog
nos
i
s
in
P
a
t
i
e
nt
s
w
i
t
h
S
e
ve
re
l
y
D
e
c
re
a
s
e
d
G
F
R,
”
Ki
dne
y
Int
e
r
nat
i
onal
R
e
por
t
s
,
vol
.
3,
no.
3,
pp.
625
-
637,
M
a
y
2018.
[26]
J.
Z
ha
ng
,
et
a
l
.,
“
Re
g
ul
a
t
ory
T
c
e
l
l
s
/
T
-
he
l
p
e
r
cell
17
func
t
i
ona
l
i
m
ba
l
a
nc
e
in
ura
e
m
i
c
p
a
t
i
e
nt
s
on
m
a
i
nt
e
na
nc
e
ha
e
m
odi
a
l
y
s
i
s
:
A
p
i
vot
a
l
l
i
nk
be
t
w
e
e
n
m
i
c
roi
nfl
a
m
m
a
t
i
on
a
nd
a
dve
rs
e
c
a
rdi
ova
s
c
ul
a
r
e
ve
nt
s
:
O
ri
g
i
na
l
A
rt
i
c
l
e
,
”
Ne
phr
ol
ogy
,
vol
.
15,
no.
1,
pp.
33
-
41,
2010.
[27]
L.
L
i
u,
et
a
l
.,
“
A
bs
ol
ut
e
of
CD
4
+
CD
25
+
F
O
X
P
3
+
re
g
ul
a
t
ory
T
-
cell
c
ount
ra
t
he
r
t
ha
n
i
t
s
ra
t
i
o
in
p
e
ri
p
he
ra
l
bl
ood
is
re
l
a
t
e
d
to
l
ong
-
t
e
rm
s
urvi
va
l
of
re
na
l
a
l
l
og
ra
ft
s
,
”
in
T
r
ans
pl
ant
at
i
on
P
r
oc
e
e
di
ngs
,
2012,
vol
.
44,
no.
1,
pp.
284
-
286.
[28]
T.
H
i
da
y
a
t
i
,
et
a
l
.,
“
Bl
a
c
k
c
um
i
n
s
e
e
d
oi
l
i
nc
re
a
s
e
l
e
uc
oc
y
t
e
a
nd
CD
4
T
he
l
p
e
r
num
be
r
in
s
p
ra
g
ue
-
da
w
l
e
y
ra
t
s
i
nduc
e
d
w
i
t
h
di
m
e
t
hy
l
be
nz
a
nt
hra
c
e
ne
,
”
Int
e
r
nat
i
onal
J
our
nal
of
P
ubl
i
c
H
e
al
t
h
Sc
i
e
nc
e
,
vol
.
8,
no.
2,
pp.
238
-
245,
2019.
[29]
W.
P
rodj
os
udj
a
di
,
et
a
l
.,
“
D
e
t
e
c
t
i
on
a
nd
p
re
ve
nt
i
on
of
c
hroni
c
ki
dne
y
di
s
e
a
s
e
in
Indone
s
i
a
:
Ini
t
i
a
l
c
om
m
uni
t
y
s
c
re
e
ni
ng
,
”
Ne
phr
ol
ogy
,
vol
.
14,
no.
7,
pp.
669
-
674,
2009.
[30]
T
.
H
i
da
y
a
t
i
,
S.
H.
K
us
ha
di
w
i
j
a
y
a,
“
Re
l
a
t
i
ons
hi
p
be
t
w
e
e
n
H
y
p
e
rt
e
ns
i
on,
S
m
oki
ng
A
nd
S
up
p
l
e
m
e
nt
E
ne
rg
y
D
ri
nk
a
nd
t
he
P
re
va
l
e
nc
e
of
Chroni
c
K
i
dne
y
D
i
s
e
a
s
e
s
/
H
ubungan
ant
ar
a
hi
pe
r
t
e
ns
i
,
m
e
r
ok
ok
dan
m
i
num
an
s
upl
e
m
e
n
e
ne
r
gi
dan
k
e
j
adi
an
pe
ny
ak
i
t
gi
nj
al
k
r
oni
k
,
”
Ber
ita
Ke
dok
t
e
r
an
Mas
y
ar
ak
at
,
vol
.
24,
no.
2,
pp.
90
-
102,
2008.
[31]
M.
Che
ł
c
how
s
ka
,
et
a
l
.,
“
Infl
ue
nc
e
of
a
c
t
i
ve
e
x
p
os
ure
to
T
oba
c
c
o
s
m
oke
on
ni
t
ri
c
ox
i
de
s
t
a
t
us
of
p
re
g
na
nt
w
om
e
n,
”
Int
e
r
nat
i
onal
J
our
nal
E
nv
i
r
on
m
e
nt
al
Res
e
ar
c
h
P
ubl
i
c
H
e
al
t
h
,
vol
.
15,
no.
12,
2018.
[32]
P.
H
a
ri
m
urt
i
,
J.
P
ra
w
i
ra
,
a
nd
K.
H
ort
,
“
T
he
Re
p
ubl
i
c
of
Indone
s
i
a
H
e
a
l
t
h
S
y
s
t
e
m
Re
vi
e
w
,
”
A
s
i
a
P
ac
i
f
i
c
O
bs
e
r
v
at
or
y
on
H
e
al
t
h
Sy
s
t
e
m
s
and
P
ol
i
c
i
e
s
,
vol
.
7,
no.
1,
2017.
[33]
R.
D.
S
e
m
ba
,
et
a
l
.,
“
P
a
t
e
rna
l
s
m
oki
ng
is
a
s
s
oc
i
a
t
e
d
w
i
t
h
i
nc
re
a
s
e
d
ri
s
k
of
c
hi
l
d
m
a
l
nut
ri
t
i
on
a
m
ong
p
oor
urba
n
fa
m
i
l
i
e
s
in
Indone
s
i
a
,
”
P
ubl
i
c
H
e
al
t
h
N
ut
r
i
t
i
on
.
,
vol
.
10,
no.
1,
pp.
7
-
15,
2007.
[34]
K.
M.
P
e
de
rs
e
n
,
et
a
l
.,
“
S
m
oki
ng
a
nd
Inc
re
a
s
e
d
W
hi
t
e
a
nd
Re
d
Bl
ood
Ce
l
l
s
:
A
M
e
nde
l
i
a
n
Ra
ndom
i
z
a
t
i
on
A
p
p
roa
c
h
in
t
he
Cop
e
nha
g
e
n
G
e
ne
ra
l
P
op
ul
a
t
i
on
S
t
udy
,
”
A
r
t
e
r
i
os
c
l
e
r
os
i
s
, T
hr
om
bos
i
s
, and V
as
c
ul
ar
B
i
ol
ogy
,
vol
.
39
,
no.
5,
pp.
965
-
977,
2019.
[35]
A.
R.
Is
ka
nda
r
,
et
a
l
.,
“
A
s
y
s
t
e
m
s
t
ox
i
c
ol
og
y
a
p
p
roa
c
h
for
c
om
p
a
ra
t
i
ve
a
s
s
e
s
s
m
e
nt
:
Bi
ol
og
i
c
a
l
i
m
p
a
c
t
of
an
a
e
ros
ol
from
a
c
a
ndi
da
t
e
m
odi
fi
e
d
-
ri
s
k
t
oba
c
c
o
p
roduc
t
a
nd
c
i
g
a
re
t
t
e
s
m
oke
on
hum
a
n
org
a
not
y
p
i
c
bronc
hi
a
l
e
p
i
t
he
l
i
a
l
c
ul
t
ure
s
,
”
T
ox
i
c
ol
ogy
i
n V
i
t
r
o
,
vol
.
39,
no.
2017,
pp.
29
-
51,
2017.
[36]
S.
G
up
t
a
,
P.
P
i
ng
a
l
i
,
a
nd
P.
P
i
ns
t
rup
-
A
nde
rs
e
n,
“
W
om
e
n’s
e
m
p
ow
e
rm
e
nt
a
nd
nut
ri
t
i
on
s
t
a
t
us
:
T
he
c
a
s
e
of
i
ron
de
fi
c
i
e
nc
y
in
Indi
a
,
”
F
ood
P
ol
i
c
y
,
vol
.
88,
no.
A
ug
us
t
,
p.
101763,
2019.
[37]
A.
Che
n
,
et
a
l
.,
“
S
e
x
/
G
e
nde
r
D
i
ffe
re
nc
e
s
in
Cot
i
ni
ne
L
e
ve
l
s
a
m
ong
D
a
i
l
y
S
m
oke
rs
in
t
he
P
e
nns
y
l
va
ni
a
A
dul
t
S
m
oki
ng
S
t
udy
,
”
J
our
nal
of
Wom
e
n'
s
H
e
al
t
h
.
,
vol
.
26,
no.
11,
pp.
1222
-
1230,
2017.
[38]
C.
Cl
a
i
r
,
et
a
l
.,
“
Re
l
a
t
i
ons
hi
p
s
of
c
ot
i
ni
ne
a
nd
s
e
l
f
-
re
p
ort
e
d
c
i
g
a
re
t
t
e
s
m
oki
n
g
w
i
t
h
he
m
og
l
obi
n
A
1c
i
n
t
he
U
.S
.:
Re
s
ul
t
s
from
t
he
N
a
t
i
ona
l
H
e
a
l
t
h
a
nd
N
ut
ri
t
i
on
E
x
a
m
i
na
t
i
on
S
urve
y
,
1999
-
2008,
”
D
i
abe
t
e
s
Car
e
,
vol
.
34,
no.
10,
pp.
2250
-
2255,
2011.
[39]
T.
H
i
da
y
a
t
i
,
et
a
l
.,
“
T
he
Ins
ul
i
n
L
i
ke
G
row
t
h
F
a
c
t
or
-
1(IG
F
-
1)
a
nd
Ins
ul
i
n
Bi
ndi
ng
P
rot
e
i
n
-
3
(IG
F
BP
-
3)
L
e
ve
l
As
P
re
di
c
t
or
Bi
om
a
rke
r
of
Chroni
c
K
i
dne
y
D
i
s
e
a
s
e
(CK
D
)
P
a
t
i
e
nt
s
in
Indone
s
i
a
,
”
J
our
nal
Me
d
i
c
al
B
i
oe
ng
i
ne
e
r
i
ng
.
,
vol
.
4,
no.
3,
pp.
254
-
258,
2015.
[40]
T.
H
i
g
uc
hi
,
et
a
l
.,
“
Curre
nt
c
i
g
a
re
t
t
e
s
m
oki
ng
is
a
re
ve
rs
i
bl
e
c
a
us
e
of
e
l
e
va
t
e
d
w
hi
t
e
bl
oo
d
cell
c
ount
:
Cros
s
-
s
e
c
t
i
ona
l
a
nd
l
ong
i
t
udi
na
l
s
t
udi
e
s
,
”
P
r
e
v
e
nt
i
v
e
Me
d
i
c
i
ne
R
e
por
t
s
,
vol
.
4,
pp.
417
-
422,
2016.
[41]
T.
H
i
da
y
a
t
i
,
H.
P
urnom
o
,
“
Re
l
a
t
i
ons
hi
p
be
t
w
e
e
n
hy
p
e
rt
e
ns
i
on,
s
m
oki
ng
a
nd
s
up
p
l
e
m
e
nt
a
l
dri
nks
w
i
t
h
t
he
i
nc
i
de
nc
e
of
E
S
RD
in
PKU
M
uha
m
m
a
di
y
a
h
G
e
n
e
ra
l
H
os
p
i
t
a
l
Y
og
y
a
ka
rt
a
/
H
ubungan
hi
pe
r
t
e
ns
i
m
i
num
an
s
upl
e
m
e
n
e
ne
r
gi
dan
m
e
r
ok
ok
de
ngan
k
e
j
adi
an
pe
ny
ak
i
t
gi
nj
al
k
r
oni
k
y
ang
m
e
nj
al
ani
H
e
m
odi
al
i
s
i
s
di
R
SU
P
KU
Muham
m
adi
y
ah
Y
ogy
ak
ar
t
),
”
T
he
s
i
s
,
M
a
s
t
e
r
P
rog
ra
m
in
P
ubl
i
c
H
e
a
l
t
h
S
c
i
e
nc
e
s
,
G
a
dj
a
h
M
a
da
U
ni
ve
rs
i
t
y,
Y
og
y
a
ka
rt
a
,
Indone
s
i
a
,
2007.
[42]
O.
I.
A
m
e
h
,
U.
E.
E
kri
kp
o,
a
nd
A.
P.
K
e
ng
ne
,
“
P
re
ve
nt
i
ng
CK
D
in
L
ow
-
a
nd
M
i
ddl
e
-
Inc
om
e
Count
ri
e
s
:
A
Ca
l
l
for
U
rg
e
nt
A
c
t
i
on,
”
Ki
dne
y
Int
e
r
nat
i
onal
R
e
por
t
s
,
vol
.
5,
no.
3,
pp.
255
-
262,
2020.
[43]
H.
R.
M
i
ddl
e
ka
uff
,
J.
P
a
rk,
a
nd
R.
S.
M
ohe
i
m
a
ni
,
“
A
dve
rs
e
e
ffe
c
t
s
of
c
i
g
a
re
t
t
e
a
nd
nonc
i
g
a
re
t
t
e
s
m
oke
e
x
p
os
ure
on
t
he
a
ut
onom
i
c
ne
rvous
s
y
s
t
e
m
:
M
e
c
ha
ni
s
m
s
a
nd
i
m
p
l
i
c
a
t
i
ons
for
c
a
rdi
ova
s
c
ul
a
r
ri
s
k,
”
J
our
nal
Am
e
r
i
c
an
Col
l
e
ge
Car
di
ol
ogy
,
vol
.
64,
no.
16,
pp.
1740
-
1750,
2014.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
S
N
:
2252
-
8806
I
n
t
.
J
.
P
u
b
l
i
c
H
e
a
l
t
h
S
c
i
.
V
o
l
.
1
0
,
N
o
.
1
,
M
a
r
c
h
20
21
:
8
8
–
9
6
96
[44]
M.
S
op
ori
,
“
E
ffe
c
t
s
of
c
i
g
a
re
t
t
e
s
m
oke
on
t
he
i
m
m
une
s
y
s
t
e
m
,
”
Nat
ur
e
R
e
v
i
e
ws
Im
m
unol
ogy
.
,
vol
.
2,
no.
5,
pp.
372
-
377,
2002.
[45]
D.
D
unkl
e
r
,
et
a
l
.,
“
P
op
ul
a
t
i
on
-
A
t
t
ri
but
a
bl
e
F
ra
c
t
i
ons
of
M
odi
fi
a
bl
e
L
i
fe
s
t
y
l
e
F
a
c
t
ors
for
CK
D
a
nd
M
ort
a
l
i
t
y
in
Indi
vi
dua
l
s
w
i
t
h
T
y
p
e
2
D
i
a
be
t
e
s
:
A
Co
hort
S
t
udy
,
”
A
m
e
r
i
c
an J
our
nal
of
Ki
dne
y
D
i
s
e
as
e
s
.
,
vol
.
68,
no.
1,
pp.
29
-
40,
2016.
[46]
A.
T
a
m
i
m
i
,
D.
S
e
rda
re
vi
c
,
a
nd
N.
A.
H
a
na
ni
a
,
“
T
he
e
ffe
c
t
s
of
c
i
g
a
re
t
t
e
s
m
oke
on
a
i
rw
a
y
i
nfl
a
m
m
a
t
i
on
in
a
s
t
hm
a
a
nd
CO
P
D
:
T
he
ra
p
e
ut
i
c
i
m
p
l
i
c
a
t
i
ons
,
”
R
e
s
pi
r
at
or
y
Me
d
i
c
i
ne
.
,
vo
l.
106,
no.
3,
pp.
319
-
328,
2012.
[47]
G.
R.
K
i
ns
e
y
,
et
a
l
.,
“
Re
g
ul
a
t
ory
T
cells
s
up
p
re
s
s
i
nna
t
e
i
m
m
uni
t
y
in
ki
dne
y
i
s
c
he
m
i
a
-
re
p
e
rfus
i
on
i
nj
ury
,
”
J
our
nal
Am
e
r
i
c
an
Soc
iety
Ne
phr
ol
ogy
.
,
vol
.
20,
no.
8,
pp.
1744
-
1753,
2009.
[48]
N.
H.
R.
L
i
t
j
e
ns
,
et
a
l
.,
“
N
a
t
ura
l
re
g
ul
a
t
ory
T
cells
from
p
a
t
i
e
nt
s
w
i
t
h
e
nd
-
s
t
a
g
e
re
na
l
di
s
e
a
s
e
can
be
us
e
d
for
l
a
rg
e
-
s
c
a
l
e
g
e
ne
ra
t
i
on
of
hi
g
hl
y
s
up
p
re
s
s
i
ve
a
l
l
oa
nt
i
g
e
n
-
s
p
e
c
i
fi
c
T
re
g
s
,
”
Ki
dne
y
Int
e
r
nat
i
onal
,
vol
.
91,
no.
5,
pp.
1203
-
1213,
2017.
[49]
J.
X
i
a
,
et
a
l
.,
“
Ci
g
a
re
t
t
e
s
m
oki
ng
a
nd
c
hroni
c
ki
d
ne
y
di
s
e
a
s
e
in
t
he
g
e
ne
ra
l
p
op
ul
a
t
i
on:
A
s
y
s
t
e
m
a
t
i
c
re
vi
e
w
a
nd
m
e
t
a
-
a
na
l
y
s
i
s
of
p
ros
p
e
c
t
i
ve
c
ohort
s
t
udi
e
s
,
”
Ne
phr
ol
ogy
D
i
al
y
s
i
s
T
r
ans
pl
ant
at
i
on
.
,
vol
.
32,
no.
3,
pp.
47
5
-
487,
2017.
[50]
X.
Lan
,
et
a
l
.,
“
N
i
c
ot
i
ne
i
nduc
e
s
p
odoc
y
t
e
a
p
op
t
os
i
s
t
hroug
h
i
nc
re
a
s
i
ng
ox
i
da
t
i
ve
s
t
re
s
s
,
”
P
L
oS
O
ne
,
vol
.
11,
no.
12,
pp.
1
-
17,
2016.
[51]
J
.
P
a
rm
a
r,
P
.
S
ha
rm
a
,
P
.
V
e
rm
a
,
P
.
S
ha
rm
a
,
P
.K
.G
oy
a
l
,
a
nd
I.
J
.
C.
B.
P
.
Re
s
.,
“
M
odul
a
t
i
on
of
D
M
BA
-
i
nduc
e
d
bi
oc
he
m
i
c
a
l
a
nd
hi
s
t
op
a
t
hol
og
i
c
a
l
c
ha
ng
e
s
by
S
y
z
y
g
i
um
c
um
i
ni
s
e
e
d
e
x
t
ra
c
t
duri
ng
s
ki
n
c
a
rc
i
nog
e
ne
s
i
s
,”
Int
e
r
nat
i
onal
J
our
nal
of
Cur
r
e
nt
B
i
om
e
di
c
al
and
P
har
m
ac
e
ut
i
c
al
R
e
s
e
ar
c
h
(IJ
CB
P
R
)
vol
.
1,
no.
2,
p
p
.
24
-
30,
2011.
[52]
J.
G
a
o
,
et
a
l
.,
“
p
53
a
nd
A
T
M
/
A
T
R
re
g
ul
a
t
e
7.
12
-
di
m
e
t
hy
l
be
nz
[a
]a
nt
hra
c
e
ne
-
i
nduc
e
d
i
m
m
unos
up
p
re
s
s
i
on,
”
Mol
e
c
ul
ar
P
har
m
ac
ol
ogy
,
v
ol
.
73,
no.
1,
pp.
137
-
46,
2008.
[53]
U.
K.
L
i
y
a
na
g
e
,
et
a
l
.,
“
P
re
va
l
e
nc
e
of
Re
g
ul
a
t
ory
T
Ce
l
l
s
is
Inc
re
a
s
e
d
in
P
e
ri
p
he
ra
l
Bl
ood
a
nd
T
um
or
M
i
c
roe
nvi
ronm
e
nt
of
P
a
t
i
e
nt
s
w
i
t
h
P
a
nc
re
a
s
or
Bre
a
s
t
A
de
noc
a
rc
i
nom
a
,
”
J
our
nal
of
Im
m
unol
ogy
,
vol
.
169,
no.
5,
pp.
2756
-
276
1,
2002.
[54]
G.
Che
ng
,
A.
Y
u,
a
nd
T.
R.
M
a
l
e
k,
“
T
-
cell
t
ol
e
ra
nc
e
a
nd
t
he
m
ul
t
i
-
func
t
i
ona
l
rol
e
of
IL
-
2R
s
i
g
na
l
i
ng
in
T
-
re
g
ul
a
t
ory
c
e
l
l
s
,
”
Im
m
unol
ogy
Rev
i
e
ws
,
vol
.
241,
no.
1,
pp.
63
-
76,
2011.
[55]
M.
K
a
s
s
a
n
,
et
a
l
.,
“
Int
e
rl
e
uki
n
-
10
re
l
e
a
s
e
d
by
CD
4
+
CD
25
+
N
a
t
ura
l
re
g
ul
a
t
ory
T
cells
i
m
p
rove
s
m
i
c
rova
s
c
ul
a
r
e
ndot
he
l
i
a
l
func
t
i
on
t
hroug
h
i
nhi
bi
t
i
on
of
NADPH
ox
i
da
s
e
a
c
t
i
vi
t
y
in
hy
p
e
rt
e
ns
i
ve
mice,
”
A
r
t
e
r
i
os
c
l
e
r
os
i
s
,
T
hr
om
bos
i
s
, and V
as
c
ul
ar
B
i
ol
ogy
B
i
ol
.
,
vol
.
31,
no.
11,
pp.
2534
-
2542,
2011.
[56]
D.
Q.
T
ra
n
,
“
T
G
F
-
β:
T
he
s
w
ord,
t
he
w
a
nd,
a
nd
t
he
s
hi
e
l
d
of
FOXP3
+
re
g
ul
a
t
ory
T
c
e
l
l
s
,
”
J
our
nal
of
Mol
e
c
ul
ar
Ce
l
l
B
i
ol
ogy
,
vol
.
4,
no.
1.
pp.
29
-
37
,
2012.
Evaluation Warning : The document was created with Spire.PDF for Python.