%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Peter C. Elwood, Janet E. Pickering, Gareth Morgan, Julieta Galante, Alison L. Weightman, Delyth Morris, Marcus Longley, Malcolm Mason, Richard Adams, Sunil Dolwani, John Chia W. K., Angel Lanas
Systematic review update of observational studies further supports aspirin role in cancer treatment: Time to share evidence and decision-making with patients?
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 12 0 R/Contents 13 0 R/TrimBox[0 0 612 792]>>
endobj
12 0 obj
[14 0 R 15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R]
endobj
14 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref001)>>
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref002)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref003)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref005)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref006)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref007)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref008)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref010)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref011)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref006)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref012)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref014)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref015)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref016)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref017)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
30 0 obj
<>/Border[0 0 0]/A 31 0 R>>
endobj
31 0 obj
<>
endobj
13 0 obj
[32 0 R 33 0 R 34 0 R 35 0 R 36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R]
endobj
32 0 obj
<>stream
q
0.45 0.36 0.35 0.01 k
0 w
575.9997 439.6144 m
199.9998 439.6144 l
199.9998 440.1145 l
575.9997 440.1145 l
f*
0.83 0.64 0.02 0 k
513.978 380.9197 m
518.7402 380.9197 l
h
f*
521.0079 380.9197 m
525.7701 380.9197 l
h
f*
408.4157 367.937 m
413.178 367.937 l
h
f*
418.337 367.937 m
423.0992 367.937 l
h
f*
496.2331 354.8976 m
500.9953 354.8976 l
h
f*
562.0535 328.9323 m
566.8157 328.9323 l
h
f*
302.2866 302.9102 m
307.0488 302.9102 l
h
f*
312.2079 302.9102 m
321.7323 302.9102 l
h
f*
345.4299 263.9055 m
354.9543 263.9055 l
h
f*
480.9827 224.9008 m
485.7449 224.9008 l
h
f*
515.9055 198.9354 m
525.3732 198.9354 l
h
f*
530.589 198.9354 m
540.1134 198.9354 l
h
f*
325.5874 185.8961 m
335.1118 185.8961 l
h
f*
289.1339 146.948 m
298.6583 146.948 l
h
f*
300.926 146.948 m
310.4504 146.948 l
h
f*
364.1386 81.9213 m
373.663 81.9213 l
h
f*
0 g
1 j
1 J
9.5 0 0 9.5 200.0125 707.7543 cm
BT
/F0 1 Tf
1 TL
-0.0042 Tc
0 0 Td
(taking)Tj
2.8525 0 Td
(aspirin.)Tj
3.4016 0 Td
(Ten)Tj
1.9275 0 Td
(of)Tj
1.0443 0 Td
(the)Tj
1.5994 0 Td
(studies)Tj
3.3478 0 Td
(also)Tj
2.029 0 Td
(give)Tj
2.029 0 Td
(evidence)Tj
4.1714 0 Td
(on)Tj
1.3189 0 Td
(the)Tj
1.5933 0 Td
(incidence)Tj
4.3863 0 Td
(of)Tj
1.0503 0 Td
(metastatic)Tj
4.7323 0 Td
(cancer)Tj
-35.4836 -1.474 Td
(spread.)Tj
1.2591 -1.474 Td
(There)Tj
2.8108 0 Td
(are)Tj
1.6471 0 Td
(now)Tj
2.0349 0 Td
(twenty-nine)Tj
5.2695 0 Td
(observational)Tj
6.0929 0 Td
(studies)Tj
3.3539 0 Td
(describing)Tj
4.7144 0 Td
(colorectal)Tj
4.4459 0 Td
(cancer)Tj
3.1868 0 Td
(\(CRC\))Tj
3.0256 0 Td
(and)Tj
-37.8409 -1.474 Td
(post-diagnostic)Tj
6.8628 0 Td
(aspirin.)Tj
3.4015 0 Td
(Pooling)Tj
3.509 0 Td
(the)Tj
1.5934 0 Td
(estimates)Tj
4.4578 0 Td
(of)Tj
1.0503 0 Td
(reduction)Tj
4.2788 0 Td
(by)Tj
1.2652 0 Td
(aspirin)Tj
3.121 0 Td
(which)Tj
2.7452 0 Td
(are)Tj
1.647 0 Td
(reported)Tj
3.9029 0 Td
(as)Tj
-37.8349 -1.474 Td
(hazard)Tj
3.2404 0 Td
(ratios)Tj
2.6377 0 Td
(\(HR\),)Tj
2.584 0 Td
(gives)Tj
2.5243 0 Td
(an)Tj
1.3189 0 Td
(overall)Tj
3.121 0 Td
(HR)Tj
1.6531 0 Td
(for)Tj
1.3785 0 Td
(aspirin)Tj
3.1211 0 Td
(and)Tj
1.8679 0 Td
(CRC)Tj
2.3632 0 Td
(mortality)Tj
3.9625 0 Td
(0.72)Tj
2.1424 0 Td
(\(95%)Tj
2.5303 0 Td
(CI)Tj
1.2114 0 Td
(0.64)Tj
-35.6567 -1.474 Td
(0.80\).)Tj
2.751 0 Td
(Fourteen)Tj
4.1774 0 Td
(observational)Tj
6.093 0 Td
(studies)Tj
3.3538 0 Td
(have)Tj
2.3632 0 Td
(reported)Tj
3.8969 0 Td
(on)Tj
1.3188 0 Td
(aspirin)Tj
3.1211 0 Td
(and)Tj
1.8679 0 Td
(breast)Tj
2.9719 0 Td
(cancer)Tj
3.1867 0 Td
(mortality)Tj
-35.1017 -1.474 Td
(and)Tj
1.8619 0 Td
(pooling)Tj
3.3956 0 Td
(those)Tj
2.6436 0 Td
(that)Tj
1.8679 0 Td
(report)Tj
2.8048 0 Td
(the)Tj
1.5934 0 Td
(association)Tj
5.162 0 Td
(with)Tj
1.9753 0 Td
(aspirin)Tj
3.1211 0 Td
(as)Tj
1.2651 0 Td
(a)Tj
0.7698 0 Td
(hazard)Tj
3.2405 0 Td
(ratio)Tj
2.1424 0 Td
(gives)Tj
2.5243 0 Td
(HR)Tj
1.653 0 Td
(0.69)Tj
-36.0207 -1.474 Td
(\(0.530.90\).)Tj
5.5499 0 Td
(Sixteen)Tj
3.5209 0 Td
(studies)Tj
3.3478 0 Td
(report)Tj
2.8048 0 Td
(on)Tj
1.3189 0 Td
(aspirin)Tj
3.1211 0 Td
(and)Tj
1.8679 0 Td
(prostate)Tj
3.7954 0 Td
(cancer)Tj
3.1867 0 Td
(mortality)Tj
3.9625 0 Td
(and)Tj
1.8619 0 Td
(a)Tj
0.7699 0 Td
(pooled)Tj
-35.1077 -1.474 Td
(estimate)Tj
3.9625 0 Td
(yields)Tj
2.7391 0 Td
(an)Tj
1.3189 0 Td
(HR)Tj
1.653 0 Td
(of)Tj
1.0444 0 Td
(0.87)Tj
2.1423 0 Td
(\(95%)Tj
2.5303 0 Td
(CI)Tj
1.2115 0 Td
(0.731.05\).)Tj
5.2217 0 Td
(Data)Tj
2.3154 0 Td
(from)Tj
2.2021 0 Td
(12)Tj
1.3188 0 Td
(reports)Tj
3.3001 0 Td
(relating)Tj
3.4494 0 Td
(to)Tj
1.0503 0 Td
(other)Tj
-35.4598 -1.474 Td
(cancers)Tj
3.682 0 Td
(are)Tj
1.6471 0 Td
(also)Tj
2.029 0 Td
(listed.)Tj
2.7988 0 Td
(Ten)Tj
1.9335 0 Td
(studies)Tj
3.3479 0 Td
(give)Tj
2.029 0 Td
(evidence)Tj
4.1714 0 Td
(of)Tj
1.0443 0 Td
(a)Tj
0.7698 0 Td
(reduction)Tj
4.2848 0 Td
(in)Tj
0.9847 0 Td
(metastatic)Tj
4.7323 0 Td
(spread;)Tj
3.5209 0 Td
(four)Tj
-36.9755 -1.4741 Td
(give)Tj
2.029 0 Td
(a)Tj
0.7698 0 Td
(pooled)Tj
3.1748 0 Td
(HR)Tj
1.653 0 Td
(0.31)Tj
2.1424 0 Td
(\(95%)Tj
2.5303 0 Td
(CI)Tj
1.2114 0 Td
(0.18,)Tj
2.4229 0 Td
(0.54\))Tj
2.4706 0 Td
(and)Tj
1.8679 0 Td
(five)Tj
1.7604 0 Td
(studies)Tj
3.3479 0 Td
(which)Tj
2.7451 0 Td
(reported)Tj
3.9029 0 Td
(odds)Tj
2.3631 0 Td
(ratio)Tj
2.1365 0 Td
(of)Tj
1.0503 0 Td
(met-)Tj
-37.5783 -1.474 Td
(astatic)Tj
3.0793 0 Td
(spread)Tj
3.2404 0 Td
(give)Tj
2.029 0 Td
(OR)Tj
1.7127 0 Td
(0.79)Tj
2.1424 0 Td
(\(0.66)Tj
2.4766 0 Td
(to)Tj
1.0443 0 Td
(0.95\).)Tj
ET
Q
q
1 j
1 J
0 w
11.4998 0 0 11.4998 200.0125 526.1102 cm
BT
/F2 1 Tf
1 TL
-0.0035 Tc
0 0 Td
(Conclusion)Tj
ET
Q
q
1 j
1 J
0 w
9.5 0 0 9.5 200.0125 509.1023 cm
BT
/F0 1 Tf
1 TL
-0.0042 Tc
0 0 Td
(Being)Tj
2.7451 0 Td
(almost)Tj
3.133 0 Td
(entirely)Tj
3.4016 0 Td
(from)Tj
2.208 0 Td
(observational)Tj
6.087 0 Td
(studies,)Tj
3.6283 0 Td
(the)Tj
1.5994 0 Td
(evidence)Tj
4.1714 0 Td
(of)Tj
1.0443 0 Td
(benefit)Tj
3.1867 0 Td
(from)Tj
2.2021 0 Td
(aspirin)Tj
3.127 0 Td
(is)Tj
0.931 0 Td
(lim-)Tj
-37.4649 -1.474 Td
(ited.)Tj
2.0886 0 Td
(There)Tj
2.8048 0 Td
(is)Tj
0.931 0 Td
(heterogeneity)Tj
6.2063 0 Td
(between)Tj
3.9566 0 Td
(studies)Tj
3.3538 0 Td
(and)Tj
1.8619 0 Td
(the)Tj
1.5994 0 Td
(results)Tj
3.127 0 Td
(are)Tj
1.6471 0 Td
(subject)Tj
3.3538 0 Td
(to)Tj
1.0443 0 Td
(important)Tj
4.3445 0 Td
(biases,)Tj
-36.3191 -1.474 Td
(only)Tj
2.029 0 Td
(some)Tj
2.6436 0 Td
(of)Tj
1.0444 0 Td
(which)Tj
2.7451 0 Td
(can)Tj
1.8142 0 Td
(be)Tj
1.3188 0 Td
(identified.)Tj
4.4399 0 Td
(Nevertheless,)Tj
6.2661 0 Td
(the)Tj
1.5993 0 Td
(evidence)Tj
4.1714 0 Td
(would)Tj
2.7929 0 Td
(seem)Tj
2.6436 0 Td
(to)Tj
1.0503 0 Td
(merit)Tj
2.4169 0 Td
(wide)Tj
-36.9755 -1.474 Td
(discussion)Tj
4.8278 0 Td
(regarding)Tj
4.3862 0 Td
(whether)Tj
3.7417 0 Td
(or)Tj
1.0981 0 Td
(not)Tj
1.5933 0 Td
(it)Tj
0.7102 0 Td
(is)Tj
0.9309 0 Td
(adequate)Tj
4.3385 0 Td
(to)Tj
1.0503 0 Td
(justify)Tj
2.7452 0 Td
(the)Tj
1.5933 0 Td
(recommenda)Tj
5.7827 0 Td
(tion)Tj
1.8082 0 Td
(of)Tj
1.0443 0 Td
(low-)Tj
-35.6507 -1.474 Td
(dose)Tj
2.3631 0 Td
(therapeutic)Tj
5.1084 0 Td
(aspirin,)Tj
3.3956 0 Td
(and)Tj
1.8678 0 Td
(if)Tj
0.7102 0 Td
(it)Tj
0.7161 0 Td
(is,)Tj
1.2055 0 Td
(for)Tj
1.3785 0 Td
(which)Tj
2.7451 0 Td
(cancers?)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 399.0047 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 381.9968 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(role)Tj
1.7688 0 Td
(of)Tj
1.0148 0 Td
(low-dose)Tj
3.8267 0 Td
(aspirin)Tj
2.9877 0 Td
(prophylaxis)Tj
4.8869 0 Td
(is)Tj
0.8504 0 Td
(well)Tj
1.8199 0 Td
(established)Tj
4.5977 0 Td
(in)Tj
1.0318 0 Td
(vascular)Tj
3.4753 0 Td
(disease)Tj
3.016 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(])Tj
2.075 0 Td
(and)Tj
1.7348 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
-35.8977 -1.2982 Td
(reduction)Tj
4.1158 0 Td
(of)Tj
1.0148 0 Td
(colorectal,)Tj
4.3257 0 Td
(and)Tj
1.7291 0 Td
(probably)Tj
3.7644 0 Td
(other)Tj
2.347 0 Td
(cancers)Tj
3.2032 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(],)Tj
2.5965 0 Td
(and)Tj
1.7291 0 Td
(it)Tj
0.788 0 Td
(has)Tj
1.5421 0 Td
(been)Tj
2.1203 0 Td
(predicted)Tj
4.0025 0 Td
(that)Tj
1.7745 0 Td
(that)Tj
-35.053 -1.3039 Td
(`prevention)Tj
4.8018 0 Td
(of)Tj
1.0148 0 Td
(cancer)Tj
2.846 0 Td
(could)Tj
2.4548 0 Td
(become)Tj
3.3221 0 Td
(the)Tj
1.4684 0 Td
(main)Tj
2.2904 0 Td
(justification)Tj
4.9662 0 Td
(for)Tj
1.3833 0 Td
(aspirin)Tj
2.9877 0 Td
(use')Tj
1.7462 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
-28.0855 -1.2983 Td
(The)Tj
1.7858 0 Td
(earliest)Tj
3.0444 0 Td
(reports)Tj
3.067 0 Td
(on)Tj
1.2756 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7291 0 Td
(cancer)Tj
2.846 0 Td
(described)Tj
4.0535 0 Td
(a)Tj
0.652 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0374 0 Td
(metastatic)Tj
4.2747 0 Td
(spread)Tj
2.8573 0 Td
(and)Tj
-34.9226 -1.2983 Td
(focused)Tj
3.2768 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(role)Tj
1.7688 0 Td
(of)Tj
1.0148 0 Td
(platelets,)Tj
3.6964 0 Td
(consistent)Tj
4.2519 0 Td
(with)Tj
2.0012 0 Td
(a)Tj
0.652 0 Td
(treatment,)Tj
4.3597 0 Td
(rather)Tj
2.6475 0 Td
(than)Tj
2.0296 0 Td
(a)Tj
0.652 0 Td
(preventive)Tj
4.405 0 Td
(effect)Tj
2.3641 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
-35.8637 -1.2982 Td
(Later,)Tj
2.5058 0 Td
(evidence)Tj
3.7077 0 Td
(of)Tj
1.0091 0 Td
(effects)Tj
2.7156 0 Td
(of)Tj
1.0091 0 Td
(aspirin)Tj
2.982 0 Td
(on)Tj
1.2699 0 Td
(certain)Tj
2.9821 0 Td
(biological)Tj
4.0875 0 Td
(mechanisms)Tj
5.1987 0 Td
(relevant)Tj
3.4129 0 Td
(to)Tj
1.0205 0 Td
(cancer)Tj
2.8402 0 Td
(growth)Tj
-34.7411 -1.3039 Td
(and)Tj
1.7291 0 Td
(to)Tj
1.0261 0 Td
(metastatic)Tj
4.2746 0 Td
(spread)Tj
2.8573 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(])Tj
2.846 0 Td
(justified)Tj
3.4356 0 Td
(an)Tj
1.2018 0 Td
(expectation)Tj
4.8246 0 Td
(of)Tj
1.0148 0 Td
(benefit)Tj
2.9763 0 Td
(from)Tj
2.2054 0 Td
(aspirin)Tj
2.9877 0 Td
(treatment)Tj
4.1385 0 Td
(of)Tj
-35.5178 -1.2983 Td
(cancer.)Tj
3.067 0 Td
(Some)Tj
2.4491 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(long-term)Tj
4.2519 0 Td
(follow-up)Tj
4.0932 0 Td
(studies)Tj
2.982 0 Td
(of)Tj
1.0148 0 Td
(early)Tj
2.1544 0 Td
(vascular)Tj
3.4695 0 Td
(trials)Tj
2.1997 0 Td
(gave)Tj
1.9956 0 Td
(evidence)Tj
3.7134 0 Td
(of)Tj
1.0147 0 Td
(reduc-)Tj
-34.8885 -1.2983 Td
(tions)Tj
2.1996 0 Td
(attributable)Tj
4.8359 0 Td
(to)Tj
1.0205 0 Td
(aspirin)Tj
2.9877 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(metastatic)Tj
4.2803 0 Td
(spread)Tj
2.8516 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(range)Tj
2.4605 0 Td
(of)Tj
1.0148 0 Td
(cancers)Tj
3.2031 0 Td
(in)Tj
1.0375 0 Td
(subjects)Tj
3.3789 0 Td
(who)Tj
1.9388 0 Td
(had)Tj
-35.3874 -1.3039 Td
(been)Tj
2.1203 0 Td
(free)Tj
1.7234 0 Td
(of)Tj
1.0148 0 Td
(metastases)Tj
4.4334 0 Td
(at)Tj
0.9524 0 Td
(diagnosis)Tj
3.9571 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(])Tj
1.8482 0 Td
(again)Tj
2.3698 0 Td
(suggesting)Tj
4.3993 0 Td
(a)Tj
0.6576 0 Td
(treatment)Tj
4.1329 0 Td
(effect)Tj
2.3641 0 Td
(of)Tj
1.0148 0 Td
(aspirin.)Tj
3.2088 0 Td
(Further-)Tj
-34.1969 -1.2983 Td
(more,)Tj
2.5681 0 Td
(while)Tj
2.3641 0 Td
(there)Tj
2.2677 0 Td
(is)Tj
0.8447 0 Td
(usually)Tj
3.0217 0 Td
(a)Tj
0.652 0 Td
(delay)Tj
2.3074 0 Td
(before)Tj
2.7382 0 Td
(evidence)Tj
3.7134 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(reduction)Tj
4.1158 0 Td
(in)Tj
1.0375 0 Td
(incident)Tj
3.5206 0 Td
(cancer)Tj
2.846 0 Td
(becomes)Tj
-33.664 -1.2982 Td
(apparent,)Tj
3.9911 0 Td
(a)Tj
0.652 0 Td
(reduction)Tj
4.1158 0 Td
(in)Tj
1.0319 0 Td
(mortality)Tj
3.9174 0 Td
(appears)Tj
3.2768 0 Td
(to)Tj
1.0262 0 Td
(commence)Tj
4.6091 0 Td
(without)Tj
3.3335 0 Td
(any)Tj
1.6554 0 Td
(delay)Tj
2.3074 0 Td
(in)Tj
1.0375 0 Td
(patients)Tj
3.3675 0 Td
(who)Tj
-34.3216 -1.3039 Td
(already)Tj
3.1124 0 Td
(have)Tj
2.0579 0 Td
(metastases,)Tj
4.6601 0 Td
(again)Tj
2.3698 0 Td
(suggesting)Tj
4.3993 0 Td
(a)Tj
0.6577 0 Td
(treatment)Tj
4.1329 0 Td
(effect)Tj
2.364 0 Td
(of)Tj
1.0148 0 Td
(aspirin)Tj
2.9877 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
-26.5604 -1.2983 Td
(On)Tj
1.5193 0 Td
(the)Tj
1.4684 0 Td
(other)Tj
2.347 0 Td
(hand,)Tj
2.4832 0 Td
(the)Tj
1.4683 0 Td
(treatment)Tj
4.1386 0 Td
(of)Tj
1.0148 0 Td
(cancer)Tj
2.8459 0 Td
(by)Tj
1.1792 0 Td
(aspirin)Tj
2.9877 0 Td
(has)Tj
1.5421 0 Td
(been)Tj
2.1203 0 Td
(examined)Tj
4.1329 0 Td
(in)Tj
1.0318 0 Td
(only)Tj
1.9785 0 Td
(a)Tj
0.652 0 Td
(very)Tj
1.9275 0 Td
(few)Tj
/F10 1 Tf
-36.0337 -1.2983 Td
[()6()]TJ
1.2018 0 Td
[()6()4()]TJ
/F5 1 Tf
1.5647 0 Td
(randomised)Tj
5.006 0 Td
(controlled)Tj
4.32 0 Td
(trials,)Tj
2.4207 0 Td
(and)Tj
1.7292 0 Td
(these)Tj
2.2563 0 Td
(were)Tj
2.1203 0 Td
(either)Tj
2.5342 0 Td
(unrealistically)Tj
5.7656 0 Td
(small)Tj
2.3301 0 Td
([)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(],)Tj
3.5433 0 Td
(or)Tj
1.0998 0 Td
(ran-)Tj
-35.892 -1.3039 Td
(domisation)Tj
4.7565 0 Td
(was)Tj
1.7007 0 Td
(compromised)Tj
5.76 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(].)Tj
2.0806 0 Td
(The)Tj
1.7802 0 Td
(bulk)Tj
1.9955 0 Td
(of)Tj
1.0148 0 Td
(clinical)Tj
3.0784 0 Td
(evidence)Tj
3.7134 0 Td
(on)Tj
1.2756 0 Td
(aspirin)Tj
2.9877 0 Td
(taken)Tj
2.4208 0 Td
(by)Tj
1.1792 0 Td
(patients)Tj
-33.7434 -1.2982 Td
(with)Tj
1.9955 0 Td
(cancer)Tj
2.846 0 Td
(is)Tj
0.8447 0 Td
(therefore)Tj
3.8551 0 Td
(limited)Tj
3.0727 0 Td
(to)Tj
1.0262 0 Td
(observational)Tj
5.5785 0 Td
(studies.)Tj
-18.0225 -1.2983 Td
(Concurrently,)Tj
5.8336 0 Td
(patients)Tj
3.3676 0 Td
(with)Tj
1.9955 0 Td
(cancer)Tj
2.846 0 Td
(are)Tj
1.4457 0 Td
(being)Tj
2.4321 0 Td
(recruited)Tj
3.8551 0 Td
(into)Tj
1.8425 0 Td
(randomised)Tj
5.0059 0 Td
(trials)Tj
2.1997 0 Td
(of)Tj
1.0148 0 Td
(aspirin)Tj
2.9877 0 Td
(as)Tj
-36.0224 -1.2983 Td
(an)Tj
1.2018 0 Td
(adjunct)Tj
3.2372 0 Td
(treatment)Tj
4.1329 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(].)Tj
3.2541 0 Td
(It)Tj
0.8617 0 Td
(will)Tj
1.6611 0 Td
(however)Tj
3.6114 0 Td
(be)Tj
1.1508 0 Td
(perhaps)Tj
3.3732 0 Td
(1015)Tj
2.6362 0 Td
(years)Tj
2.2677 0 Td
(before)Tj
2.7383 0 Td
(evidence)Tj
3.7133 0 Td
(from)Tj
-33.8397 -1.3039 Td
(these)Tj
2.2506 0 Td
(begins)Tj
2.795 0 Td
(to)Tj
1.0261 0 Td
(become)Tj
3.3222 0 Td
(available,)Tj
3.8948 0 Td
(and)Tj
1.7291 0 Td
(it)Tj
0.7824 0 Td
(is)Tj
0.8504 0 Td
(likely)Tj
2.3527 0 Td
(that)Tj
1.7801 0 Td
(trials)Tj
2.1997 0 Td
(will)Tj
1.6611 0 Td
(focus)Tj
2.3244 0 Td
(on)Tj
1.2756 0 Td
(only)Tj
1.9786 0 Td
(a)Tj
0.6519 0 Td
(very)Tj
1.9276 0 Td
(few)Tj
1.6157 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-35.4328 -1.2983 Td
(most)Tj
2.2053 0 Td
(common)Tj
3.8437 0 Td
(cancers.)Tj
3.4299 0 Td
(In)Tj
1.1112 0 Td
(the)Tj
1.4684 0 Td
(meantime,)Tj
4.4787 0 Td
(evidence)Tj
3.7133 0 Td
(from)Tj
2.2054 0 Td
(observational)Tj
5.5785 0 Td
(studies)Tj
2.9877 0 Td
(is,)Tj
1.0715 0 Td
(by)Tj
1.1849 0 Td
(default,)Tj
3.1918 0 Td
(of)Tj
-36.4703 -1.2982 Td
(considerable)Tj
5.261 0 Td
(and)Tj
1.7291 0 Td
(immediate)Tj
4.5014 0 Td
(importance.)Tj
-10.2953 -1.3039 Td
(In)Tj
1.1111 0 Td
(2016)Tj
2.1203 0 Td
(we)Tj
1.3323 0 Td
(reported)Tj
3.6567 0 Td
(a)Tj
0.6576 0 Td
(systematic)Tj
4.3597 0 Td
(review)Tj
2.8403 0 Td
(and)Tj
1.7348 0 Td
(meta-analysis)Tj
5.6522 0 Td
(of)Tj
1.0148 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4683 0 Td
(reports)Tj
3.0728 0 Td
(then)Tj
2.0182 0 Td
(available)Tj
-33.3805 -1.2983 Td
(on)Tj
1.2755 0 Td
(aspirin)Tj
2.9877 0 Td
(taken)Tj
2.4208 0 Td
(by)Tj
1.1792 0 Td
(patients)Tj
3.3675 0 Td
(with)Tj
1.9956 0 Td
(cancer)Tj
2.846 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.8538 0 Td
(Since)Tj
2.3584 0 Td
(then)Tj
2.0183 0 Td
(new)Tj
1.8765 0 Td
(evidence)Tj
3.7077 0 Td
(has)Tj
1.5421 0 Td
(been)Tj
2.1259 0 Td
(reported)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
32.2798 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(17)Tj
/F8 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(Foundation,)Tj
4.5779 0 Td
(but)Tj
1.4174 0 Td
(nothing)Tj
3.0402 0 Td
(in)Tj
0.8858 0 Td
(recent)Tj
2.5158 0 Td
(years.)Tj
2.4378 0 Td
(MM)Tj
-14.8749 -1.3748 Td
(received)Tj
3.3023 0 Td
(personal)Tj
3.4016 0 Td
(payments)Tj
3.8623 0 Td
(for)Tj
1.2543 0 Td
(advisory)Tj
3.3591 0 Td
(boards:)Tj
-15.1796 -1.3749 Td
(Sanofi,)Tj
2.785 0 Td
(Bayer,)Tj
2.5441 0 Td
(Takeda)Tj
2.8489 0 Td
(Lecture)Tj
2.9976 0 Td
(fees:)Tj
1.963 0 Td
(Bayer,)Tj
2.5371 0 Td
(Janssen,)Tj
-15.6757 -1.3748 Td
(Sanofi.)Tj
2.785 0 Td
(JC:)Tj
1.389 0 Td
(Ownership)Tj
4.2166 0 Td
(of)Tj
0.9425 0 Td
(Stocks)Tj
2.7425 0 Td
(-)Tj
0.5244 0 Td
(QuantumD)Tj
4.0253 0 Td
(x,)Tj
-16.6253 -1.3748 Td
(Biomark,)Tj
3.5433 0 Td
(AstraZe)Tj
2.8205 0 Td
(neca,)Tj
2.1827 0 Td
(Roche)Tj
2.6008 0 Td
(Holdings,)Tj
3.7276 0 Td
(Pfizer,)Tj
-14.8749 -1.3748 Td
(Bristol-Me)Tj
3.848 0 Td
(yerSquibb,)Tj
4.2095 0 Td
(SeattleGeneti)Tj
4.8473 0 Td
(cs,)Tj
1.2827 0 Td
(Natera,)Tj
-14.1875 -1.3748 Td
(Nektar,)Tj
2.8559 0 Td
(Spark)Tj
2.374 0 Td
(Therapeuti)Tj
3.9119 0 Td
(cs,)Tj
1.2897 0 Td
(Biocept,)Tj
3.2032 0 Td
(Nanostring)Tj
-13.6347 -1.3748 Td
(Technologi)Tj
4.0677 0 Td
(es,)Tj
1.2898 0 Td
(Incyte)Tj
2.4661 0 Td
(2.)Tj
0.9213 0 Td
(Consulta)Tj
3.2315 0 Td
(ncy/)Tj
1.7929 0 Td
(Paid)Tj
-13.7693 -1.3748 Td
(employment)Tj
4.8614 0 Td
(-)Tj
0.5244 0 Td
(Tessa)Tj
2.3811 0 Td
(Therapeuti)Tj
3.9119 0 Td
(cs)Tj
1.063 0 Td
(3.)Tj
0.9212 0 Td
(Researc)Tj
2.9977 0 Td
(h)Tj
-16.6607 -1.3748 Td
(grants)Tj
2.5724 0 Td
(-)Tj
0.5244 0 Td
(BMS)Tj
2.0268 0 Td
(\(drug)Tj
2.2536 0 Td
(supply)Tj
2.6787 0 Td
(for)Tj
1.2544 0 Td
(Investigator)Tj
4.5921 0 Td
(Trial\))Tj
2.119 0 Td
(-)Tj
-18.0214 -1.3749 Td
(Bayer)Tj
2.3173 0 Td
(\(drug)Tj
2.2536 0 Td
(supply)Tj
2.6787 0 Td
()Tj
0.6945 0 Td
(Aspirin,)Tj
3.026 0 Td
(for)Tj
1.2614 0 Td
(Investiga)Tj
3.3308 0 Td
(tor)Tj
1.2614 0 Td
(Trial\))Tj
-16.8237 -1.3748 Td
(-)Tj
0.5244 0 Td
(Oncoquest)Tj
4.2236 0 Td
(\(drug)Tj
2.2536 0 Td
(supply)Tj
2.6787 0 Td
()Tj
0.6945 0 Td
(Oregovo)Tj
3.1536 0 Td
(mab,)Tj
2.0977 0 Td
(for)Tj
-15.6261 -1.3748 Td
(Investigator)Tj
4.5921 0 Td
(Trial,)Tj
2.0339 0 Td
(and)Tj
1.5874 0 Td
(study)Tj
2.2677 0 Td
(expenses)Tj
3.4725 0 Td
(\))Tj
0.5244 0 Td
(4.)Tj
0.9213 0 Td
(Travel)Tj
-15.3993 -1.3748 Td
(Grants)Tj
2.6858 0 Td
(-)Tj
0.5315 0 Td
(AstraZe)Tj
2.8205 0 Td
(neca,)Tj
2.1827 0 Td
(Bristol)Tj
2.5866 0 Td
(Meyer)Tj
2.5512 0 Td
(Squibb,)Tj
3.0544 0 Td
(MSD)Tj
-16.4127 -1.3748 Td
(5.)Tj
0.9141 0 Td
(Travel)Tj
2.4591 0 Td
(grants)Tj
2.5725 0 Td
(and)Tj
1.5874 0 Td
(honoraria)Tj
3.7701 0 Td
(for)Tj
1.2543 0 Td
(speaking)Tj
3.515 0 Td
(or)Tj
-16.0725 -1.3748 Td
(participation)Tj
4.7764 0 Td
(at)Tj
0.8929 0 Td
(meetings)Tj
3.6354 0 Td
(-)Tj
0.5245 0 Td
(AstraZeneca)Tj
-9.8292 -1.3748 Td
(\(speakers)Tj
3.6142 0 Td
(hip\).)Tj
1.8921 0 Td
(Membersh)Tj
4.0252 0 Td
(ip)Tj
0.8859 0 Td
(in)Tj
0.8929 0 Td
(a)Tj
0.6378 0 Td
(governmen)Tj
4.2165 0 Td
(t)Tj
0.4819 0 Td
(or)Tj
-16.6465 -1.3749 Td
(other)Tj
2.1543 0 Td
(advisory)Tj
3.352 0 Td
(board)Tj
2.3669 0 Td
(o)Tj
0.6945 0 Td
(Board)Tj
2.4166 0 Td
(member,)Tj
3.5788 0 Td
(Singapore)Tj
-14.5631 -1.3819 Td
(Gynaecolo)Tj
3.8834 0 Td
(gic)Tj
1.3111 0 Td
(Oncology)Tj
3.7347 0 Td
(Group)Tj
2.537 0 Td
(Council)Tj
2.9764 0 Td
(member,)Tj
-14.4426 -1.3748 Td
(College)Tj
2.9197 0 Td
(of)Tj
0.9496 0 Td
(Clinician)Tj
3.3094 0 Td
(Scientist)Tj
3.3804 0 Td
(Singapore)Tj
3.9827 0 Td
(Scientifi)Tj
2.9268 0 Td
(c)Tj
-17.4686 -1.3748 Td
(advisory)Tj
3.3519 0 Td
(board,)Tj
2.5938 0 Td
(Aspirin)Tj
2.8063 0 Td
(Foundation.)Tj
4.578 0 Td
(AL)Tj
1.2189 0 Td
(is)Tj
0.8362 0 Td
(n)Tj
0.6874 0 Td
(advisor)Tj
-16.0725 -1.3748 Td
(to)Tj
0.9496 0 Td
(Bayer)Tj
2.3173 0 Td
(A.G.)Tj
1.7788 0 Td
(There)Tj
2.3173 0 Td
(are)Tj
1.3748 0 Td
(no)Tj
1.1622 0 Td
(patents,)Tj
3.1678 0 Td
(products)Tj
3.522 0 Td
(in)Tj
-16.5898 -1.3748 Td
(developm)Tj
3.6283 0 Td
(ent)Tj
1.3748 0 Td
(or)Tj
0.9993 0 Td
(marketed)Tj
3.6992 0 Td
(products)Tj
3.515 0 Td
(to)Tj
0.9496 0 Td
(declare.)Tj
3.104 0 Td
(This)Tj
-17.2702 -1.3748 Td
(does)Tj
2.0126 0 Td
(not)Tj
1.4173 0 Td
(alter)Tj
1.8213 0 Td
(our)Tj
1.474 0 Td
(adherence)Tj
4.0536 0 Td
(to)Tj
0.9496 0 Td
(all)Tj
1.0276 0 Td
(the)Tj
1.3677 0 Td
(PLOS)Tj
2.3315 0 Td
(ONE)Tj
-16.4552 -1.3748 Td
(policies)Tj
3.0118 0 Td
(on)Tj
1.1622 0 Td
(sharing)Tj
2.9835 0 Td
(data)Tj
1.7929 0 Td
(and)Tj
1.5874 0 Td
(materials,)Tj
3.8339 0 Td
(as)Tj
1.063 0 Td
(detailed)Tj
-15.4347 -1.3749 Td
(online)Tj
2.4449 0 Td
(in)Tj
0.8858 0 Td
(the)Tj
1.3748 0 Td
(guide)Tj
2.2536 0 Td
(for)Tj
ET
endstream
endobj
33 0 obj
<>stream
endstream
endobj
34 0 obj
<>stream
endstream
endobj
35 0 obj
<>stream
endstream
endobj
36 0 obj
<>stream
endstream
endobj
37 0 obj
<>stream
endstream
endobj
38 0 obj
<>stream
endstream
endobj
39 0 obj
<>stream
endstream
endobj
40 0 obj
<>stream
endstream
endobj
41 0 obj
<>stream
endstream
endobj
42 0 obj
<>stream
endstream
endobj
43 0 obj
<>stream
endstream
endobj
44 0 obj
<>stream
endstream
endobj
45 0 obj
<>stream
endstream
endobj
46 0 obj
<>stream
endstream
endobj
47 0 obj
<>stream
endstream
endobj
48 0 obj
<>stream
BT
8.2134 49.7129 Td
(authors.)Tj
ET
Q
endstream
endobj
49 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 50 0 R/Contents 51 0 R/TrimBox[0 0 612 792]>>
endobj
50 0 obj
[52 0 R 53 0 R 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R 61 0 R 62 0 R 63 0 R]
endobj
52 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
53 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref019)>>
endobj
54 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s005)>>
endobj
55 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref020)>>
endobj
56 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s006)>>
endobj
57 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref021)>>
endobj
58 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s007)>>
endobj
59 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
60 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
61 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s006)>>
endobj
62 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.t001)>>
endobj
63 0 obj
<>/Border[0 0 0]/A 64 0 R>>
endobj
64 0 obj
<>
endobj
51 0 obj
[65 0 R 66 0 R 67 0 R 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R 73 0 R 74 0 R 75 0 R]
endobj
65 0 obj
<>stream
q
0.83 0.64 0.02 0 k
317.4803 569.6504 m
327.0047 569.6504 l
327.0047 569.5937 l
317.4803 569.5937 l
f*
494.1921 517.6063 m
503.7165 517.6063 l
h
f*
375.6472 504.6236 m
402.0094 504.6236 l
h
f*
427.9181 361.6441 m
437.4425 361.6441 l
h
f*
460.7433 361.6441 m
487.1055 361.6441 l
h
f*
219.4016 296.6173 m
228.926 296.6173 l
h
f*
306.3685 244.6299 m
332.7307 244.6299 l
h
f*
506.4378 198.9354 m
515.9622 198.9354 l
h
f*
556.8378 185.8961 m
566.3622 185.8961 l
h
f*
481.2661 146.948 m
507.6283 146.948 l
h
f*
485.915 81.9213 m
515.0551 81.9213 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(which)Tj
2.6475 0 Td
(we)Tj
1.3266 0 Td
(believe)Tj
2.9707 0 Td
(justifies)Tj
3.2655 0 Td
(a)Tj
0.6576 0 Td
(re-evaluation)Tj
5.5049 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(topic.)Tj
2.4605 0 Td
(In)Tj
1.1055 0 Td
(what)Tj
2.1656 0 Td
(follows)Tj
3.0614 0 Td
(we)Tj
1.3266 0 Td
(therefore)Tj
3.8551 0 Td
(summarise)Tj
-32.8306 -1.3039 Td
(the)Tj
1.4683 0 Td
(new)Tj
1.8765 0 Td
(evidence)Tj
3.7134 0 Td
(and)Tj
1.7291 0 Td
(we)Tj
1.3266 0 Td
(follow)Tj
2.6986 0 Td
(this)Tj
1.6724 0 Td
(with)Tj
2.0012 0 Td
(meta-analyses)Tj
5.8054 0 Td
(of)Tj
1.0148 0 Td
(all)Tj
1.1508 0 Td
(the)Tj
1.4684 0 Td
(available)Tj
3.6623 0 Td
(relevant)Tj
3.4242 0 Td
(studies.)Tj
3.2088 0 Td
(In)Tj
-36.2208 -1.2982 Td
(particular,)Tj
4.3369 0 Td
(we)Tj
1.3266 0 Td
(summarise)Tj
4.6035 0 Td
(the)Tj
1.4683 0 Td
(evidence)Tj
3.7134 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(three)Tj
2.2677 0 Td
(main)Tj
2.2904 0 Td
(cancers:)Tj
3.4299 0 Td
(colorectal,)Tj
4.3256 0 Td
(breast)Tj
2.6135 0 Td
(and)Tj
1.7292 0 Td
(pros-)Tj
-34.8489 -1.2983 Td
(tate,)Tj
1.8992 0 Td
(and)Tj
1.7291 0 Td
(we)Tj
1.3266 0 Td
(then)Tj
2.0182 0 Td
(list)Tj
1.3947 0 Td
(the)Tj
1.4683 0 Td
(evidence)Tj
3.7134 0 Td
(from)Tj
2.2053 0 Td
(single)Tj
2.5342 0 Td
(studies)Tj
2.982 0 Td
(of)Tj
1.0148 0 Td
(other)Tj
2.3471 0 Td
(cancers.)Tj
3.4355 0 Td
(All)Tj
1.3947 0 Td
(this)Tj
1.6724 0 Td
(leads)Tj
2.211 0 Td
(to)Tj
1.0261 0 Td
(a)Tj
0.6577 0 Td
(pre-)Tj
-35.0303 -1.2983 Td
(sentation)Tj
3.9061 0 Td
(of)Tj
1.0148 0 Td
(what)Tj
2.1656 0 Td
(we)Tj
1.3266 0 Td
(believe)Tj
2.965 0 Td
(is)Tj
0.8448 0 Td
(a)Tj
0.6576 0 Td
(basic)Tj
2.211 0 Td
(issue:)Tj
2.3868 0 Td
(whether)Tj
3.4752 0 Td
(or)Tj
1.0999 0 Td
(not)Tj
1.5703 0 Td
(the)Tj
1.474 0 Td
(present)Tj
3.1635 0 Td
(evidence)Tj
3.7077 0 Td
(is)Tj
0.8504 0 Td
(adequate)Tj
3.7927 0 Td
(to)Tj
-36.612 -1.3039 Td
(justify)Tj
2.6702 0 Td
(the)Tj
1.474 0 Td
(informing)Tj
4.2973 0 Td
(of)Tj
1.0148 0 Td
(patients)Tj
3.3732 0 Td
(with)Tj
1.9956 0 Td
(cancer,)Tj
3.067 0 Td
(and)Tj
1.7348 0 Td
(if)Tj
0.771 0 Td
(it)Tj
0.7881 0 Td
(is)Tj
0.8447 0 Td
(adequate,)Tj
4.0251 0 Td
(then)Tj
2.0183 0 Td
(patients)Tj
3.3675 0 Td
(with)Tj
1.9956 0 Td
(which)Tj
-33.4372 -1.2982 Td
(cancers?)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 600.7181 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Methods)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 583.7102 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(In)Tj
1.1055 0 Td
(2015)Tj
2.1259 0 Td
(we)Tj
1.3266 0 Td
(reported)Tj
3.6567 0 Td
(the)Tj
1.474 0 Td
(results)Tj
2.8063 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(systematic)Tj
4.3597 0 Td
(review)Tj
2.8459 0 Td
(and)Tj
1.7292 0 Td
(meta-analysis)Tj
5.6522 0 Td
(of)Tj
1.0148 0 Td
(all)Tj
1.1452 0 Td
(available)Tj
3.668 0 Td
(reports)Tj
-34.5824 -1.2982 Td
(published)Tj
4.1215 0 Td
(up)Tj
1.2699 0 Td
(to)Tj
1.0205 0 Td
(March)Tj
2.8743 0 Td
(2015)Tj
2.1203 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
2.0749 0 Td
(We)Tj
1.6101 0 Td
(have)Tj
2.0579 0 Td
(now)Tj
1.9616 0 Td
(updated)Tj
3.4753 0 Td
(that)Tj
1.7801 0 Td
(search)Tj
2.7609 0 Td
(to)Tj
1.0262 0 Td
(August)Tj
3.084 0 Td
(2017)Tj
2.1204 0 Td
(and)Tj
1.7291 0 Td
(we)Tj
-35.087 -1.3039 Td
(present)Tj
3.1634 0 Td
(a)Tj
0.652 0 Td
(review)Tj
2.8459 0 Td
(and)Tj
1.7291 0 Td
(meta-analysis)Tj
5.6523 0 Td
(of)Tj
1.0148 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.474 0 Td
(recent)Tj
2.7042 0 Td
(papers)Tj
2.846 0 Td
(identified)Tj
4.0592 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.6519 0 Td
(search)Tj
2.7609 0 Td
(from)Tj
2.2054 0 Td
(April)Tj
-33.9418 -1.2983 Td
(2015)Tj
2.1203 0 Td
(to)Tj
1.0261 0 Td
(August)Tj
3.0841 0 Td
(2017)Tj
2.1203 0 Td
(inclusive.)Tj
3.9684 0 Td
(We)Tj
1.6101 0 Td
(then)Tj
2.0183 0 Td
(present)Tj
3.1634 0 Td
(a)Tj
0.652 0 Td
(summary,)Tj
4.2349 0 Td
(meta-analyses)Tj
5.8053 0 Td
(and)Tj
1.7348 0 Td
(interpretation)Tj
-31.538 -1.2983 Td
(of)Tj
1.0147 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4684 0 Td
(available)Tj
3.668 0 Td
(reports)Tj
3.067 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.474 0 Td
(topic.)Tj
-11.9167 -1.3039 Td
(The)Tj
1.7858 0 Td
(procedures)Tj
4.6714 0 Td
(adopted)Tj
3.4583 0 Td
(throughout)Tj
4.7792 0 Td
(followed)Tj
3.6453 0 Td
(the)Tj
1.474 0 Td
(PRISMA)Tj
3.7927 0 Td
(guidelines)Tj
4.2747 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(])Tj
1.8538 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.652 0 Td
(full)Tj
-33.3125 -1.2982 Td
(description)Tj
4.7338 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(search)Tj
2.7609 0 Td
(strategy)Tj
3.3279 0 Td
(is)Tj
0.8447 0 Td
(given)Tj
2.3811 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0318 0 Td
(S1)Tj
1.1735 0 Td
(File)Tj
0 g
(.)Tj
1.9106 0 Td
(In)Tj
1.1055 0 Td
(brief:)Tj
2.3074 0 Td
(systematic)Tj
4.3596 0 Td
(searches)Tj
3.5433 0 Td
(using)Tj
2.3924 0 Td
(key)Tj
-34.3556 -1.2983 Td
(words)Tj
2.6702 0 Td
(were)Tj
2.1203 0 Td
(conducted)Tj
4.4277 0 Td
(in)Tj
1.0374 0 Td
(Medline)Tj
3.549 0 Td
(and)Tj
1.7291 0 Td
(Embase,)Tj
3.5603 0 Td
(limited)Tj
3.0727 0 Td
(to)Tj
1.0205 0 Td
(human)Tj
3.0784 0 Td
(studies)Tj
2.9877 0 Td
(in)Tj
1.0375 0 Td
(peer-reviewed)Tj
-30.2908 -1.3039 Td
(journals.)Tj
3.6963 0 Td
(Studies)Tj
3.1011 0 Td
(were)Tj
2.1203 0 Td
(selected)Tj
3.3505 0 Td
(by)Tj
1.1792 0 Td
(two)Tj
1.7121 0 Td
(authors)Tj
3.2485 0 Td
(\(PE)Tj
1.6838 0 Td
(and)Tj
1.7348 0 Td
(GM\))Tj
2.1656 0 Td
(if)Tj
0.7767 0 Td
(\(a\))Tj
1.3323 0 Td
(the)Tj
1.4683 0 Td
(studied)Tj
3.1521 0 Td
(population)Tj
4.5921 0 Td
(com-)Tj
-35.3137 -1.2983 Td
(prised)Tj
2.6872 0 Td
(patients)Tj
3.3675 0 Td
(diagnosed)Tj
4.2803 0 Td
(with)Tj
2.0013 0 Td
(cancer;)Tj
3.067 0 Td
(\(b\))Tj
1.406 0 Td
(aspirin)Tj
2.9877 0 Td
(was)Tj
1.7008 0 Td
(taken)Tj
2.4207 0 Td
(regularly)Tj
3.7588 0 Td
(after)Tj
2.0352 0 Td
(cancer)Tj
2.846 0 Td
(diagnosis;)Tj
-32.5585 -1.2983 Td
(\(c\))Tj
1.3209 0 Td
(the)Tj
1.4683 0 Td
(studies)Tj
2.9877 0 Td
(were)Tj
2.126 0 Td
(randomised)Tj
5.0059 0 Td
(trials,)Tj
2.4208 0 Td
(case-control)Tj
5.1137 0 Td
(studies)Tj
2.9877 0 Td
(or)Tj
1.0998 0 Td
(cohort)Tj
2.8517 0 Td
(studies.)Tj
3.2144 0 Td
(Data)Tj
2.1203 0 Td
(on)Tj
1.2756 0 Td
(cancer)Tj
-33.9928 -1.3039 Td
(specific)Tj
3.1917 0 Td
(and)Tj
1.7292 0 Td
(all-cause)Tj
3.668 0 Td
(mortality,)Tj
4.1385 0 Td
(and)Tj
1.7292 0 Td
(data)Tj
1.9162 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.4684 0 Td
(incidence)Tj
4.0762 0 Td
(of)Tj
1.0148 0 Td
(metastatic)Tj
4.2746 0 Td
(spread)Tj
2.8573 0 Td
(and)Tj
1.7291 0 Td
(adverse)Tj
-33.0687 -1.2982 Td
(effects)Tj
2.7269 0 Td
(attributable)Tj
4.8302 0 Td
(to)Tj
1.0261 0 Td
(aspirin)Tj
2.9877 0 Td
(were)Tj
2.1203 0 Td
(extracted.)Tj
4.1102 0 Td
(Reference)Tj
4.1669 0 Td
(lists)Tj
1.7518 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(relevant)Tj
3.4186 0 Td
(studies)Tj
2.9877 0 Td
(identified)Tj
-32.6152 -1.2983 Td
(were)Tj
2.1203 0 Td
(searched)Tj
3.7133 0 Td
(for)Tj
1.3833 0 Td
(relevant)Tj
3.4242 0 Td
(reports.)Tj
3.2939 0 Td
(Many)Tj
2.5511 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(authors)Tj
3.2485 0 Td
(were)Tj
2.1203 0 Td
(written)Tj
3.1124 0 Td
(to)Tj
1.0261 0 Td
(for)Tj
1.3833 0 Td
(additional)Tj
4.2803 0 Td
(details)Tj
-34.1402 -1.2983 Td
(and)Tj
1.7291 0 Td
(authors)Tj
3.2485 0 Td
(of)Tj
1.0148 0 Td
(all)Tj
1.1451 0 Td
(the)Tj
1.4684 0 Td
(studies)Tj
2.9877 0 Td
(were)Tj
2.1203 0 Td
(asked)Tj
2.4661 0 Td
(specifically)Tj
4.5694 0 Td
(about)Tj
2.4945 0 Td
(gastrointestinal)Tj
6.3496 0 Td
(bleeding)Tj
3.6283 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
-34.2593 -1.3039 Td
(patients)Tj
3.3675 0 Td
(included)Tj
3.7134 0 Td
(in)Tj
1.0318 0 Td
(their)Tj
2.1089 0 Td
(study.)Tj
-9.0254 -1.2982 Td
(The)Tj
1.7858 0 Td
(methodological)Tj
6.4176 0 Td
(quality)Tj
2.9537 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(studies)Tj
2.982 0 Td
(was)Tj
1.7008 0 Td
(assessed)Tj
3.4752 0 Td
(and)Tj
1.7291 0 Td
(graded)Tj
2.9707 0 Td
(independently)Tj
5.9754 0 Td
(by)Tj
1.1792 0 Td
(two)Tj
-34.8545 -1.2983 Td
(authors)Tj
3.2484 0 Td
(\(AW)Tj
2.2054 0 Td
(and)Tj
1.7348 0 Td
(PE\))Tj
1.6837 0 Td
(using)Tj
2.3925 0 Td
(the)Tj
1.4683 0 Td
(Newcastle-Ottawa)Tj
7.4948 0 Td
(Scale)Tj
2.2223 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(])Tj
1.8538 0 Td
(\(see)Tj
0.83 0.64 0.02 0 k
1.7689 0 Td
(S2)Tj
1.1678 0 Td
(File)Tj
0 g
(\).)Tj
2.2507 0 Td
(Disagreements)Tj
6.1568 0 Td
(in)Tj
-35.6482 -1.3039 Td
(grade)Tj
2.4377 0 Td
(on)Tj
1.2756 0 Td
(a)Tj
0.6576 0 Td
(nine)Tj
2.007 0 Td
(point)Tj
2.3584 0 Td
(scale,)Tj
2.3357 0 Td
(were)Tj
2.1203 0 Td
(discussed)Tj
3.9968 0 Td
(and)Tj
1.7348 0 Td
(agreed.)Tj
-17.7277 -1.2983 Td
(Meta-analyses)Tj
5.8847 0 Td
(were)Tj
2.1203 0 Td
(conducted,)Tj
4.6544 0 Td
(using)Tj
2.3924 0 Td
(a)Tj
0.652 0 Td
('random)Tj
3.6453 0 Td
(effects')Tj
2.9367 0 Td
(model.)Tj
2.9707 0 Td
(Analyses)Tj
3.7304 0 Td
(were)Tj
2.1259 0 Td
(performed)Tj
-32.309 -1.2983 Td
(first)Tj
1.8028 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(new)Tj
1.8765 0 Td
(papers)Tj
2.846 0 Td
(published)Tj
4.1272 0 Td
(since)Tj
2.245 0 Td
(April)Tj
2.3017 0 Td
(2015,)Tj
2.3471 0 Td
(and)Tj
1.7348 0 Td
(then)Tj
2.0183 0 Td
(on)Tj
1.2755 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4684 0 Td
(available)Tj
3.668 0 Td
(studies)Tj
2.9877 0 Td
(from)Tj
-34.5881 -1.3039 Td
(both)Tj
2.0579 0 Td
(the)Tj
1.4683 0 Td
(earlier)Tj
2.761 0 Td
(search)Tj
2.7609 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(new)Tj
1.8766 0 Td
(search)Tj
2.7609 0 Td
(were)Tj
2.1203 0 Td
(pooled)Tj
2.9537 0 Td
(and)Tj
1.7291 0 Td
(meta-analyses)Tj
5.8053 0 Td
(performed.)Tj
4.6942 0 Td
(Egger's)Tj
-34.1856 -1.2982 Td
(test)Tj
1.5987 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(])Tj
1.8538 0 Td
(was)Tj
1.6951 0 Td
(used)Tj
2.0636 0 Td
(in)Tj
1.0318 0 Td
(looking)Tj
3.2599 0 Td
(for)Tj
1.3889 0 Td
(publication)Tj
4.7622 0 Td
(bias)Tj
1.7858 0 Td
(and)Tj
1.7348 0 Td
(funnel)Tj
2.8006 0 Td
(plots)Tj
2.1487 0 Td
(were)Tj
2.126 0 Td
(created)Tj
3.118 0 Td
(to)Tj
1.0262 0 Td
(highlight)Tj
-32.3941 -1.2983 Td
(outlying)Tj
3.5319 0 Td
(studies.)Tj
3.2145 0 Td
(Results)Tj
3.0557 0 Td
(of)Tj
1.0148 0 Td
(attempts)Tj
3.6737 0 Td
(to)Tj
1.0261 0 Td
(reduce)Tj
2.914 0 Td
(heterogeneity)Tj
5.6522 0 Td
(were)Tj
2.126 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(omission)Tj
3.8608 0 Td
(of)Tj
-35.2854 -1.3039 Td
(studies)Tj
2.9876 0 Td
(which,)Tj
2.8744 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.4684 0 Td
(tree)Tj
1.7348 0 Td
(diagrams)Tj
3.9004 0 Td
(and)Tj
1.7291 0 Td
(sensitivity)Tj
4.2236 0 Td
(analyses)Tj
3.481 0 Td
(identified)Tj
4.0591 0 Td
(studies)Tj
2.9877 0 Td
(which)Tj
2.6476 0 Td
(were)Tj
2.126 0 Td
(out-)Tj
-35.4952 -1.2983 Td
(lying)Tj
2.1996 0 Td
(or)Tj
1.0999 0 Td
(appeared)Tj
3.8664 0 Td
(to)Tj
1.0261 0 Td
(have)Tj
2.058 0 Td
(an)Tj
1.2075 0 Td
(excessive)Tj
3.8211 0 Td
(influence)Tj
3.9174 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4684 0 Td
(pooled)Tj
2.948 0 Td
(hazard)Tj
2.931 0 Td
(ratios.)Tj
2.6815 0 Td
(The)Tj
1.7802 0 Td
(detailed)Tj
-32.2807 -1.2983 Td
(work)Tj
2.279 0 Td
(on)Tj
1.2756 0 Td
(all)Tj
1.1452 0 Td
(this)Tj
1.6724 0 Td
(is)Tj
0.8504 0 Td
(given)Tj
2.3754 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(S3)Tj
1.1735 0 Td
(File)Tj
0 g
(.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 217.0204 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Results)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 200.0125 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(A)Tj
0.9014 0 Td
(literature)Tj
3.8834 0 Td
(search)Tj
2.7609 0 Td
(\(April)Tj
2.6476 0 Td
(2015)Tj
2.1203 0 Td
(to)Tj
1.0261 0 Td
(August)Tj
3.0841 0 Td
(2017\))Tj
2.4604 0 Td
(to)Tj
1.0262 0 Td
(up-date)Tj
3.2995 0 Td
(our)Tj
1.6271 0 Td
(earlier)Tj
2.7552 0 Td
(report)Tj
2.7099 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.8539 0 Td
(identified)Tj
-32.156 -1.3039 Td
(229)Tj
1.644 0 Td
(new)Tj
1.8766 0 Td
(reports)Tj
3.0727 0 Td
(additional)Tj
4.2746 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(640)Tj
1.6497 0 Td
(papers)Tj
2.8403 0 Td
(we)Tj
1.3323 0 Td
(had)Tj
1.7065 0 Td
(already)Tj
3.1124 0 Td
(identified)Tj
4.0592 0 Td
(up)Tj
1.2642 0 Td
(to)Tj
1.0261 0 Td
(March)Tj
2.8687 0 Td
(2015)Tj
2.1203 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
-35.3421 -1.2982 Td
(Thirty-one)Tj
4.5807 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(229)Tj
1.6441 0 Td
(new)Tj
1.8766 0 Td
(reports)Tj
3.0727 0 Td
(were)Tj
2.1203 0 Td
(judged)Tj
2.948 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(of)Tj
1.0148 0 Td
(relevance)Tj
3.9685 0 Td
(and)Tj
1.7291 0 Td
(on)Tj
1.2756 0 Td
(inspection)Tj
4.3823 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(full)Tj
-35.7559 -1.2983 Td
(text)Tj
1.6951 0 Td
(29)Tj
1.1622 0 Td
(fulfilled)Tj
3.2711 0 Td
(the)Tj
1.4627 0 Td
(criteria)Tj
3.0671 0 Td
(for)Tj
1.3776 0 Td
(inclusion.)Tj
4.1329 0 Td
(A)Tj
0.89 0 Td
(summary)Tj
4.0025 0 Td
(of)Tj
1.0035 0 Td
(each)Tj
2.0182 0 Td
(of)Tj
1.0092 0 Td
(these,)Tj
2.4718 0 Td
(together)Tj
3.5262 0 Td
(with)Tj
1.9843 0 Td
(an)Tj
1.1962 0 Td
(estimate)Tj
-34.2706 -1.2983 Td
(of)Tj
1.0147 0 Td
(quality)Tj
2.9537 0 Td
(according)Tj
4.1896 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(Newcastle-Ottawa)Tj
7.4947 0 Td
(assessment)Tj
4.6091 0 Td
(protocol)Tj
3.6 0 Td
(\(see)Tj
0.83 0.64 0.02 0 k
1.7688 0 Td
(S2)Tj
1.1679 0 Td
(File)Tj
0 g
(\).)Tj
-28.0968 -1.3039 Td
(No)Tj
1.4683 0 Td
(new)Tj
1.8709 0 Td
(randomised)Tj
5.0116 0 Td
(trial)Tj
1.8368 0 Td
(was)Tj
1.6951 0 Td
(identified)Tj
4.0592 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(up-dating)Tj
4.1556 0 Td
(search,)Tj
2.9877 0 Td
(but)Tj
1.5534 0 Td
(there)Tj
2.2677 0 Td
(were)Tj
2.1203 0 Td
(13)Tj
1.1735 0 Td
(new)Tj
-33.9021 -1.2982 Td
(reports)Tj
3.067 0 Td
(of)Tj
1.0148 0 Td
(observational)Tj
5.5786 0 Td
(studies)Tj
2.9877 0 Td
(of)Tj
1.0148 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7291 0 Td
(colorectal)Tj
4.0988 0 Td
(cancer,)Tj
3.0728 0 Td
(four)Tj
1.9105 0 Td
(new)Tj
1.8765 0 Td
(reports)Tj
3.0728 0 Td
(in)Tj
1.0375 0 Td
(patients)Tj
-33.4486 -1.2983 Td
(with)Tj
1.9955 0 Td
(breast)Tj
2.6136 0 Td
(cancer,)Tj
3.0727 0 Td
(six)Tj
1.3096 0 Td
(of)Tj
1.0148 0 Td
(patients)Tj
3.3732 0 Td
(with)Tj
1.9956 0 Td
(prostate)Tj
3.4299 0 Td
(cancer)Tj
2.8459 0 Td
(and)Tj
1.7292 0 Td
(six)Tj
1.3152 0 Td
(of)Tj
1.0148 0 Td
(patients)Tj
3.3676 0 Td
(with)Tj
1.9955 0 Td
(other)Tj
2.3471 0 Td
(cancers.)Tj
-33.4202 -1.3039 Td
(Six)Tj
1.4286 0 Td
(reports)Tj
3.0671 0 Td
(gave)Tj
1.9955 0 Td
(evidence)Tj
3.7134 0 Td
(on)Tj
1.2756 0 Td
(metastatic)Tj
4.2803 0 Td
(spread.)Tj
3.0784 0 Td
(Details)Tj
2.9877 0 Td
(of)Tj
1.0148 0 Td
(these,)Tj
2.4774 0 Td
(including)Tj
4.0422 0 Td
(the)Tj
1.4684 0 Td
(published)Tj
4.1272 0 Td
(esti-)Tj
-34.9566 -1.2983 Td
(mates)Tj
2.5568 0 Td
(of)Tj
1.0148 0 Td
(both)Tj
2.0579 0 Td
(the)Tj
1.4684 0 Td
(cause-specific)Tj
5.7146 0 Td
(and)Tj
1.7291 0 Td
(all-cause)Tj
3.668 0 Td
(mortality)Tj
3.9118 0 Td
(are)Tj
1.4513 0 Td
(displayed)Tj
3.9798 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(Table)Tj
2.4378 0 Td
(1)Tj
0 g
(.)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
32.2798 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
66 0 obj
<>stream
endstream
endobj
67 0 obj
<>stream
endstream
endobj
68 0 obj
<>stream
endstream
endobj
69 0 obj
<>stream
endstream
endobj
70 0 obj
<>stream
endstream
endobj
71 0 obj
<>stream
endstream
endobj
72 0 obj
<>stream
endstream
endobj
73 0 obj
<>stream
endstream
endobj
74 0 obj
<>stream
endstream
endobj
75 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
76 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 79 0 R/Contents 80 0 R/TrimBox[0 0 612 792]>>
endobj
79 0 obj
[81 0 R 82 0 R 83 0 R 84 0 R 85 0 R 86 0 R 87 0 R 88 0 R 89 0 R 90 0 R 91 0 R 92 0 R 93 0 R 94 0 R 95 0 R 96 0 R 97 0 R 98 0 R 99 0 R 100 0 R]
endobj
81 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
82 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
83 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.t002)>>
endobj
84 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
85 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s004)>>
endobj
86 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s004)>>
endobj
87 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s006)>>
endobj
88 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref012)>>
endobj
89 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref015)>>
endobj
90 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.t001)>>
endobj
91 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
92 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref025)>>
endobj
93 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref030)>>
endobj
94 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref032)>>
endobj
95 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s007)>>
endobj
96 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref022)>>
endobj
97 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref048)>>
endobj
98 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref049)>>
endobj
99 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref026)>>
endobj
100 0 obj
<>/Border[0 0 0]/A 101 0 R>>
endobj
101 0 obj
<>
endobj
80 0 obj
[102 0 R 103 0 R 104 0 R 105 0 R 106 0 R 107 0 R 108 0 R 109 0 R 110 0 R 111 0 R 112 0 R 113 0 R 114 0 R 115 0 R 116 0 R 117 0 R 118 0 R]
endobj
102 0 obj
<>stream
q
0.83 0.64 0.02 0 k
430.6961 706.337 m
440.2205 706.337 l
h
f*
297.411 589.3228 m
306.9354 589.3228 l
h
f*
210.3307 537.3354 m
239.5843 537.3354 l
h
f*
475.8236 511.3134 m
485.2913 511.3134 l
h
f*
561.9402 498.3307 m
571.4646 498.3307 l
h
f*
200.0126 485.348 m
212.5984 485.348 l
h
f*
511.7669 420.3213 m
538.1291 420.3213 l
h
f*
327.3449 341.915 m
336.8126 341.915 l
h
f*
203.4142 302.9102 m
212.9386 302.9102 l
h
f*
248.2583 276.9449 m
277.5118 276.9449 l
h
f*
381.6567 276.9449 m
391.1244 276.9449 l
h
f*
304.6677 250.9228 m
314.1921 250.9228 l
h
f*
316.4598 250.9228 m
325.9843 250.9228 l
h
f*
328.1953 250.9228 m
337.7197 250.9228 l
h
f*
509.8394 172.9134 m
536.2016 172.9134 l
h
f*
324.5669 159.9307 m
334.0346 159.9307 l
h
f*
476.9575 107.9433 m
486.4819 107.9433 l
h
f*
488.7496 107.9433 m
498.2173 107.9433 l
h
f*
460.1197 94.9039 m
469.6441 94.9039 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 211.9748 707.4141 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(These)Tj
2.5681 0 Td
(results)Tj
2.812 0 Td
(confirm)Tj
3.4412 0 Td
(the)Tj
1.474 0 Td
(earlier)Tj
2.7553 0 Td
(findings)Tj
3.4922 0 Td
(we)Tj
1.3266 0 Td
(reported)Tj
3.6624 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
2.0749 0 Td
(For)Tj
1.6271 0 Td
(colorectal)Tj
4.0989 0 Td
(cancer)Tj
2.8459 0 Td
(our)Tj
1.6271 0 Td
(earlier)Tj
-35.0019 -1.3039 Td
(review)Tj
2.8402 0 Td
(of)Tj
1.0148 0 Td
(16)Tj
1.1736 0 Td
(observational)Tj
5.5785 0 Td
(studies)Tj
2.9877 0 Td
(had)Tj
1.7121 0 Td
(given)Tj
2.3754 0 Td
(a)Tj
0.6577 0 Td
(pooled)Tj
2.948 0 Td
(HR)Tj
1.6044 0 Td
(0.71)Tj
1.8765 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.58,)Tj
2.0976 0 Td
(0.87\))Tj
2.211 0 Td
(and)Tj
1.7291 0 Td
(this)Tj
-34.2989 -1.2982 Td
(more)Tj
2.3413 0 Td
(recent)Tj
2.7099 0 Td
(review)Tj
2.8403 0 Td
(gives)Tj
2.194 0 Td
(HR)Tj
1.6101 0 Td
(=)Tj
0.7994 0 Td
(0.68)Tj
1.8708 0 Td
(\(0.57,)Tj
2.4378 0 Td
(0.81\).)Tj
2.4378 0 Td
(Our)Tj
1.8652 0 Td
(earlier)Tj
2.7552 0 Td
(report)Tj
2.7099 0 Td
(gave)Tj
2.0013 0 Td
(a)Tj
0.6519 0 Td
(pooled)Tj
2.9481 0 Td
(estimate)Tj
-32.173 -1.2983 Td
(based)Tj
2.4717 0 Td
(on)Tj
1.2756 0 Td
(10)Tj
1.1736 0 Td
(studies)Tj
2.982 0 Td
(of)Tj
1.0148 0 Td
(breast)Tj
2.6192 0 Td
(cancer)Tj
2.8403 0 Td
(as)Tj
1.0148 0 Td
(HR)Tj
1.61 0 Td
(=)Tj
0.7994 0 Td
(0.68)Tj
1.8709 0 Td
(\(95%)Tj
2.2733 0 Td
(CI)Tj
1.2189 0 Td
(0.46,)Tj
2.0976 0 Td
(1.02\),)Tj
2.4378 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4683 0 Td
(estimate)Tj
3.5433 0 Td
(based)Tj
-34.4463 -1.2983 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.4684 0 Td
(recent)Tj
2.7099 0 Td
(reports)Tj
3.067 0 Td
(is)Tj
0.8504 0 Td
(HR)Tj
1.6101 0 Td
(0.70)Tj
1.8708 0 Td
(\(0.471.03\).)Tj
4.9493 0 Td
(For)Tj
1.6214 0 Td
(prostate)Tj
3.4356 0 Td
(cancer)Tj
2.8403 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7121 0 Td
(estimates)Tj
3.9061 0 Td
(are)Tj
1.4514 0 Td
(not)Tj
1.5704 0 Td
(as)Tj
-35.807 -1.3039 Td
(close,)Tj
2.4037 0 Td
(the)Tj
1.4683 0 Td
(earlier)Tj
2.761 0 Td
(series)Tj
2.4264 0 Td
(of)Tj
1.0148 0 Td
(ten)Tj
1.491 0 Td
(reports)Tj
3.0671 0 Td
(giving)Tj
2.6872 0 Td
(HR)Tj
1.6101 0 Td
(0.94)Tj
1.8765 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2189 0 Td
(0.76,)Tj
2.0976 0 Td
(1.17\))Tj
2.2167 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4684 0 Td
(six)Tj
1.3152 0 Td
(new)Tj
1.8766 0 Td
(stud-)Tj
-34.9963 -1.2982 Td
(ies,)Tj
1.4966 0 Td
(when)Tj
2.4038 0 Td
(pooled,)Tj
3.1748 0 Td
(yield)Tj
2.1373 0 Td
(an)Tj
1.2019 0 Td
(HR)Tj
1.61 0 Td
(of)Tj
1.0148 0 Td
(0.74)Tj
1.8709 0 Td
(\(0.590.92\).)Tj
-13.7139 -1.2983 Td
(These)Tj
2.5681 0 Td
(pooled)Tj
2.948 0 Td
(results)Tj
2.812 0 Td
(for)Tj
1.3833 0 Td
(the)Tj
1.474 0 Td
(studies)Tj
2.982 0 Td
(published)Tj
4.1272 0 Td
(up)Tj
1.2643 0 Td
(to)Tj
1.0261 0 Td
(March)Tj
2.8687 0 Td
(2015)Tj
2.1203 0 Td
(and)Tj
1.7348 0 Td
(studies)Tj
2.982 0 Td
(published)Tj
-31.487 -1.3039 Td
(since)Tj
2.245 0 Td
(April)Tj
2.3017 0 Td
(2015)Tj
2.126 0 Td
(are)Tj
1.4456 0 Td
(homogeneous)Tj
5.8393 0 Td
(\(P)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
-0.004 Tc
(0.05\))Tj
3.8835 0 Td
(for)Tj
1.3833 0 Td
(each)Tj
2.0296 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(three)Tj
2.2677 0 Td
(cancers.)Tj
-24.8086 -1.2983 Td
(In)Tj
1.1111 0 Td
(our)Tj
1.6271 0 Td
(earlier)Tj
2.7553 0 Td
(report)Tj
2.7099 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.8481 0 Td
(we)Tj
1.3323 0 Td
(summarised)Tj
5.1307 0 Td
(the)Tj
1.4683 0 Td
(findings)Tj
3.4923 0 Td
(on)Tj
1.2756 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.474 0 Td
(incidence)Tj
4.0705 0 Td
(of)Tj
1.0148 0 Td
(meta-)Tj
-35.223 -1.2983 Td
(static)Tj
2.3017 0 Td
(spread)Tj
2.8516 0 Td
(in)Tj
1.0375 0 Td
(four)Tj
1.9162 0 Td
(studies,)Tj
3.2088 0 Td
(which,)Tj
2.8743 0 Td
(when)Tj
2.4037 0 Td
(pooled)Tj
2.9537 0 Td
(gave)Tj
1.9956 0 Td
(a)Tj
0.652 0 Td
(relative)Tj
3.1407 0 Td
(risk)Tj
1.7178 0 Td
(in)Tj
1.0318 0 Td
(patients)Tj
3.3676 0 Td
(on)Tj
1.2755 0 Td
(aspirin)Tj
2.9877 0 Td
(of)Tj
-35.7162 -1.3039 Td
(0.77)Tj
1.8708 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.86,)Tj
2.0976 0 Td
(0.92;)Tj
2.0976 0 Td
(heterogeneity)Tj
5.6522 0 Td
(P)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
-0.004 Tc
(0.0005\).)Tj
4.7169 0 Td
(Six)Tj
1.4286 0 Td
(reports)Tj
3.0728 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(studies)Tj
2.982 0 Td
(published)Tj
4.1272 0 Td
(since)Tj
-34.0438 -1.2982 Td
(March)Tj
2.8629 0 Td
(2015)Tj
2.1203 0 Td
(report)Tj
2.7042 0 Td
(metastatic)Tj
4.2747 0 Td
(spread,)Tj
3.0784 0 Td
(and)Tj
1.7234 0 Td
(the)Tj
1.4684 0 Td
(relationships)Tj
5.3461 0 Td
(with)Tj
1.9955 0 Td
(aspirin)Tj
2.9821 0 Td
(in)Tj
1.0318 0 Td
(these)Tj
2.2507 0 Td
(is)Tj
0.8447 0 Td
(summarised)Tj
-32.6832 -1.2983 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0318 0 Td
(Table)Tj
2.4434 0 Td
(2)Tj
0 g
0.6973 0 Td
(\(HR)Tj
1.9502 0 Td
(0.31)Tj
1.8709 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2245 0 Td
(0.18,)Tj
2.0977 0 Td
(0.51;)Tj
2.0976 0 Td
(Heterogeneity)Tj
5.8904 0 Td
(P)Tj
0.7823 0 Td
(=)Tj
0.7994 0 Td
(0.89\).)Tj
-21.957 -1.3039 Td
(We)Tj
1.61 0 Td
(then)Tj
2.0183 0 Td
(proceeded)Tj
4.3653 0 Td
(to)Tj
1.0261 0 Td
(pool)Tj
1.9956 0 Td
(the)Tj
1.474 0 Td
(results)Tj
2.8063 0 Td
(of)Tj
1.0148 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.474 0 Td
(available)Tj
3.6623 0 Td
(published)Tj
4.1273 0 Td
(reports,)Tj
3.2938 0 Td
(that)Tj
1.7801 0 Td
(is,)Tj
1.0715 0 Td
(both)Tj
2.0636 0 Td
(the)Tj
-36.1244 -1.2983 Td
(42)Tj
1.1679 0 Td
(results)Tj
2.8119 0 Td
(in)Tj
1.0374 0 Td
(papers)Tj
2.8403 0 Td
(identified)Tj
4.0592 0 Td
(in)Tj
1.0375 0 Td
(our)Tj
1.6271 0 Td
(literature)Tj
3.8777 0 Td
(search)Tj
2.761 0 Td
(to)Tj
1.0261 0 Td
(March)Tj
2.8686 0 Td
(2015)Tj
2.126 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.8482 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.474 0 Td
(29)Tj
1.1679 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
-34.4974 -1.2982 Td
(recent)Tj
2.7098 0 Td
(search)Tj
2.761 0 Td
(April)Tj
2.3017 0 Td
(2015)Tj
2.126 0 Td
(to)Tj
1.0261 0 Td
(August)Tj
3.0841 0 Td
(2017)Tj
2.1203 0 Td
(described)Tj
4.0535 0 Td
(above.)Tj
2.7723 0 Td
(A)Tj
0.9014 0 Td
(flow)Tj
1.9445 0 Td
(diagram)Tj
3.5376 0 Td
(is)Tj
0.8504 0 Td
(given)Tj
2.3811 0 Td
(below)Tj
2.5852 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(S1)Tj
-36.1925 -1.2983 Td
(Fig)Tj
0 g
(.)Tj
1.7064 0 Td
(Tests)Tj
2.2734 0 Td
(of)Tj
1.0148 0 Td
(significance)Tj
4.9379 0 Td
(of)Tj
1.0148 0 Td
(differences)Tj
4.5637 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(mean)Tj
2.4435 0 Td
(estimates)Tj
3.9061 0 Td
(given)Tj
2.3811 0 Td
(for)Tj
1.389 0 Td
(the)Tj
1.4683 0 Td
(three)Tj
2.262 0 Td
(main)Tj
2.2904 0 Td
(cancers)Tj
-34.1572 -1.3039 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.4739 0 Td
(two)Tj
1.7065 0 Td
(reviews,)Tj
3.4299 0 Td
(gave)Tj
2.0012 0 Td
(no)Tj
1.2756 0 Td
(evidence)Tj
3.7077 0 Td
(of)Tj
1.0148 0 Td
(heterogeneity)Tj
5.6523 0 Td
(\(for)Tj
1.7291 0 Td
(all)Tj
1.1452 0 Td
(three:)Tj
2.4888 0 Td
(P)Tj
/F11 1 Tf
0 Tc
(>)Tj
/F5 1 Tf
-0.004 Tc
(0.10\).)Tj
3.77 0 Td
(The)Tj
1.7802 0 Td
(review)Tj
2.8459 0 Td
(that)Tj
-35.0529 -1.2983 Td
(follows)Tj
3.0557 0 Td
(is)Tj
0.8504 0 Td
(therefore)Tj
3.855 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(71)Tj
1.1736 0 Td
(published)Tj
4.1215 0 Td
(reports,)Tj
3.2938 0 Td
(which)Tj
2.6533 0 Td
(together)Tj
3.5319 0 Td
(describe)Tj
3.5263 0 Td
(a)Tj
0.6576 0 Td
(total)Tj
2.0013 0 Td
(of)Tj
1.0148 0 Td
(over)Tj
1.9785 0 Td
(120)Tj
-35.4611 -1.2983 Td
(thousand)Tj
3.9514 0 Td
(patients)Tj
3.3675 0 Td
(taking)Tj
2.727 0 Td
(aspirin.)Tj
-8.8497 -1.3039 Td
(Assessment)Tj
4.8642 0 Td
(and)Tj
1.7291 0 Td
(grading)Tj
3.2995 0 Td
(of)Tj
1.0148 0 Td
(each)Tj
2.0296 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(reports,)Tj
3.2939 0 Td
(using)Tj
2.3924 0 Td
(the)Tj
1.4683 0 Td
(Newcastle-Ottawa)Tj
7.4948 0 Td
(grading)Tj
3.2995 0 Td
(scheme)Tj
-34.5654 -1.2982 Td
(and)Tj
1.7291 0 Td
(including)Tj
4.0421 0 Td
(the)Tj
1.4684 0 Td
(papers)Tj
2.8459 0 Td
(which)Tj
2.6476 0 Td
(give)Tj
1.8312 0 Td
(evidence)Tj
3.7133 0 Td
(on)Tj
1.2756 0 Td
(metastatic)Tj
4.2803 0 Td
(spread,)Tj
3.0784 0 Td
(is)Tj
0.8447 0 Td
(given)Tj
2.3811 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(S2)Tj
1.1678 0 Td
(File)Tj
0 g
(.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 386.022 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Colorectal)Tj
4.5449 0 Td
(cancer)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 369.0141 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Only)Tj
2.2166 0 Td
(one)Tj
1.6951 0 Td
(small)Tj
/F10 1 Tf
2.3301 0 Td
[()6()]TJ
1.2019 0 Td
[()6()4()]TJ
/F5 1 Tf
1.5647 0 Td
(randomised)Tj
5.0059 0 Td
(trial)Tj
1.8369 0 Td
(of)Tj
1.0148 0 Td
(aspirin)Tj
2.9877 0 Td
(in)Tj
1.0318 0 Td
(66)Tj
1.1735 0 Td
(patients)Tj
3.3676 0 Td
(with)Tj
1.9955 0 Td
(colorectal)Tj
4.1046 0 Td
(cancer)Tj
2.8403 0 Td
(appears)Tj
-34.367 -1.3039 Td
(to)Tj
1.0261 0 Td
(have)Tj
2.0579 0 Td
(been)Tj
2.1203 0 Td
(reported.)Tj
3.8891 0 Td
(This)Tj
1.9843 0 Td
(showed)Tj
3.2541 0 Td
(an)Tj
1.2019 0 Td
(HR)Tj
1.6101 0 Td
(of)Tj
1.0148 0 Td
(0.65)Tj
1.8708 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.02,)Tj
2.0976 0 Td
(18.06\))Tj
2.6872 0 Td
(for)Tj
1.3833 0 Td
(the)Tj
1.474 0 Td
(mortality)Tj
3.9118 0 Td
(of)Tj
-35.0756 -1.2982 Td
(patients)Tj
3.3675 0 Td
(randomised)Tj
5.0059 0 Td
(to)Tj
1.0262 0 Td
(aspirin.[)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
(])Tj
4.8415 0 Td
(A)Tj
0.9071 0 Td
(semi-randomised)Tj
7.2283 0 Td
(study)Tj
2.3868 0 Td
(of)Tj
1.0148 0 Td
(patients)Tj
3.3675 0 Td
(with)Tj
2.0012 0 Td
(another)Tj
3.3279 0 Td
(gastro-)Tj
-34.4747 -1.2983 Td
(intestinal)Tj
3.9117 0 Td
(cancer,)Tj
3.0671 0 Td
(oesophageal)Tj
5.0683 0 Td
(cancer,)Tj
3.0671 0 Td
(reported)Tj
3.6623 0 Td
(on)Tj
1.2756 0 Td
(445)Tj
1.6498 0 Td
(patients)Tj
3.3675 0 Td
(admitted)Tj
3.8154 0 Td
(to)Tj
1.0261 0 Td
(two)Tj
1.7065 0 Td
(wards,)Tj
2.8233 0 Td
(in)Tj
1.0375 0 Td
(only)Tj
-35.4782 -1.2983 Td
(one)Tj
1.6951 0 Td
(of)Tj
1.0148 0 Td
(which)Tj
2.6532 0 Td
(aspirin)Tj
2.9877 0 Td
(was)Tj
1.6951 0 Td
(prescribed,)Tj
4.6431 0 Td
(showed)Tj
3.2485 0 Td
(an)Tj
1.2019 0 Td
(HR)Tj
1.61 0 Td
(for)Tj
1.3833 0 Td
(aspirin)Tj
2.9877 0 Td
(of)Tj
1.0148 0 Td
(0.83)Tj
1.8709 0 Td
(\(95%)Tj
2.2733 0 Td
(CI)Tj
1.2189 0 Td
(0.68,)Tj
2.0977 0 Td
(1.10\).)Tj
-33.596 -1.3039 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(])Tj
1.1962 -1.2982 Td
(A)Tj
0.907 0 Td
(total)Tj
2.0013 0 Td
(of)Tj
1.0148 0 Td
(29)Tj
1.1735 0 Td
(observational)Tj
5.5786 0 Td
(studies)Tj
2.9877 0 Td
(of)Tj
1.0148 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7291 0 Td
(colorectal)Tj
4.0989 0 Td
(cancer)Tj
2.8459 0 Td
(have)Tj
2.058 0 Td
(been)Tj
2.1259 0 Td
(reported)Tj
3.6567 0 Td
(and)Tj
-35.3761 -1.2983 Td
(are)Tj
1.4456 0 Td
(listed)Tj
2.3471 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0318 0 Td
(Table)Tj
2.4434 0 Td
(1)Tj
0 g
0.6974 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0375 0 Td
(our)Tj
1.627 0 Td
(earlier)Tj
2.7553 0 Td
(report)Tj
2.7099 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
2.0749 0 Td
(Twenty-seven)Tj
5.7997 0 Td
(give)Tj
1.8312 0 Td
(data)Tj
1.9162 0 Td
(on)Tj
1.2755 0 Td
(cause)Tj
2.3868 0 Td
(specific)Tj
-33.1084 -1.3039 Td
(mortality)Tj
3.9174 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0375 0 Td
(24)Tj
1.1679 0 Td
(the)Tj
1.4683 0 Td
(measure)Tj
3.583 0 Td
(of)Tj
1.0148 0 Td
(association)Tj
4.6261 0 Td
(with)Tj
2.0012 0 Td
(aspirin)Tj
2.9821 0 Td
(suggests)Tj
3.4866 0 Td
(benefit,)Tj
3.1974 0 Td
(15)Tj
1.1735 0 Td
(significantly)Tj
5.091 0 Td
(\(at)Tj
-36.4759 -1.2983 Td
(P)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
-0.004 Tc
(0.05\).)Tj
3.7643 0 Td
(In)Tj
1.1112 0 Td
(three)Tj
2.262 0 Td
(studies)Tj
2.9877 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(])Tj
4.2066 0 Td
(the)Tj
1.4684 0 Td
(measure)Tj
3.5829 0 Td
(of)Tj
1.0148 0 Td
(association)Tj
4.6261 0 Td
(exceeded)Tj
3.8608 0 Td
(1.00)Tj
1.8709 0 Td
(but)Tj
1.5533 0 Td
(in)Tj
1.0318 0 Td
(none)Tj
2.2507 0 Td
(of)Tj
-35.5915 -1.2983 Td
(these)Tj
2.2506 0 Td
(three)Tj
2.2677 0 Td
(is)Tj
0.8448 0 Td
(the)Tj
1.474 0 Td
(association)Tj
4.6261 0 Td
(significant)Tj
4.388 0 Td
(\(at)Tj
1.2926 0 Td
(P)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
-0.004 Tc
(0.05\).)Tj
-15.9476 -1.3039 Td
(Further)Tj
3.2711 0 Td
(analyses)Tj
3.4809 0 Td
(are)Tj
1.4514 0 Td
(limited)Tj
3.067 0 Td
(because)Tj
3.3222 0 Td
(the)Tj
1.4684 0 Td
(reports)Tj
3.0727 0 Td
(of)Tj
1.0148 0 Td
(effects)Tj
2.7212 0 Td
(by)Tj
1.1849 0 Td
(different)Tj
3.6567 0 Td
(authors)Tj
3.2428 0 Td
(use)Tj
1.5364 0 Td
(different)Tj
-33.6867 -1.2982 Td
(indices:)Tj
3.2598 0 Td
(hazard)Tj
2.931 0 Td
(ratios,)Tj
2.6815 0 Td
(risk)Tj
1.7178 0 Td
(ratios)Tj
2.4605 0 Td
(and)Tj
1.7291 0 Td
(odds)Tj
2.143 0 Td
(ratios)Tj
2.4604 0 Td
(and)Tj
1.7292 0 Td
(these)Tj
2.2507 0 Td
(cannot)Tj
2.982 0 Td
(be)Tj
1.1508 0 Td
(pooled)Tj
2.9481 0 Td
(together.)Tj
3.7587 0 Td
(How-)Tj
-34.2026 -1.2983 Td
(ever,)Tj
2.1146 0 Td
(twenty-one)Tj
4.7622 0 Td
(authors)Tj
3.2428 0 Td
(report)Tj
2.7099 0 Td
(the)Tj
1.4683 0 Td
(association)Tj
4.6318 0 Td
(with)Tj
1.9956 0 Td
(aspirin)Tj
2.9877 0 Td
(as)Tj
1.0148 0 Td
(hazard)Tj
2.9253 0 Td
(ratios,)Tj
2.6872 0 Td
(and)Tj
1.7292 0 Td
(these)Tj
2.2506 0 Td
(give)Tj
1.8312 0 Td
(a)Tj
-36.3512 -1.3039 Td
(pooled)Tj
2.948 0 Td
(HR)Tj
1.61 0 Td
(0.72)Tj
1.8709 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2245 0 Td
(0.640.81;)Tj
4.269 0 Td
(heterogeneity)Tj
5.6522 0 Td
(0.0005\))Tj
3.1635 0 Td
(Eggers)Tj
2.8743 0 Td
(test)Tj
1.5987 0 Td
(is)Tj
0.8504 0 Td
(significant)Tj
4.388 0 Td
(\(P)Tj
1.1169 0 Td
(=)Tj
0.7993 0 Td
(0.02\))Tj
-34.6334 -1.2983 Td
(suggesting)Tj
4.3993 0 Td
(some)Tj
2.3357 0 Td
(publication)Tj
4.7622 0 Td
(bias.)Tj
2.0126 0 Td
(A)Tj
0.9071 0 Td
(forest)Tj
2.4661 0 Td
(plot)Tj
1.7915 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.652 0 Td
(funnel)Tj
2.8062 0 Td
(plot)Tj
1.7859 0 Td
(are)Tj
1.4513 0 Td
(shown)Tj
2.846 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0374 0 Td
(S3)Tj
1.1679 0 Td
(File)Tj
0 g
(,)Tj
1.9105 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
-35.79 -1.2982 Td
(removal)Tj
3.4752 0 Td
(of)Tj
1.0148 0 Td
(one)Tj
1.7008 0 Td
(outlying)Tj
3.5319 0 Td
(study)Tj
2.3924 0 Td
([)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(])Tj
1.8482 0 Td
(which)Tj
2.6532 0 Td
(appears)Tj
3.2769 0 Td
(to)Tj
1.0261 0 Td
(have)Tj
2.0579 0 Td
(excessive)Tj
3.8211 0 Td
(influence)Tj
3.9175 0 Td
(reduces)Tj
3.2825 0 Td
(the)Tj
1.4683 0 Td
(het-)Tj
-35.4668 -1.2983 Td
(erogeneity)Tj
4.3993 0 Td
(\(P)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
-0.004 Tc
(0.001\))Tj
4.3596 0 Td
(and)Tj
1.7292 0 Td
(gives)Tj
2.194 0 Td
(HR)Tj
1.61 0 Td
(0.75)Tj
1.8709 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.680.83\).)Tj
4.6091 0 Td
(We)Tj
1.6044 0 Td
(were)Tj
2.1259 0 Td
(unable)Tj
2.9084 0 Td
(to)Tj
1.0204 0 Td
(reduce)Tj
2.9197 0 Td
(het-)Tj
-34.8432 -1.3039 Td
(erogeneity)Tj
4.3993 0 Td
(further.)Tj
-3.2031 -1.2983 Td
(Evidence)Tj
3.8607 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(occurrence)Tj
4.6658 0 Td
(of)Tj
1.0148 0 Td
(metastatic)Tj
4.2746 0 Td
(spread)Tj
2.8573 0 Td
(in)Tj
1.0318 0 Td
(colorectal)Tj
4.1045 0 Td
(cancer)Tj
2.8403 0 Td
(associ-)Tj
-34.1345 -1.2983 Td
(ated)Tj
1.9048 0 Td
(with)Tj
1.9956 0 Td
(aspirin)Tj
2.9877 0 Td
(comes)Tj
2.7496 0 Td
(from)Tj
2.211 0 Td
(three)Tj
2.262 0 Td
(studies,)Tj
3.2145 0 Td
(two)Tj
1.7064 0 Td
(of)Tj
1.0148 0 Td
(which)Tj
2.6532 0 Td
(report)Tj
2.7043 0 Td
(ORs)Tj
1.9502 0 Td
([)Tj
0.83 0.64 0.02 0 k
(48)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(49)Tj
0 g
(])Tj
3.0274 0 Td
(and)Tj
1.7291 0 Td
(together)Tj
3.5376 0 Td
(give)Tj
-35.6482 -1.3039 Td
(0.91)Tj
1.8708 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.65,)Tj
2.0976 0 Td
(1.26;)Tj
2.0976 0 Td
(heterogeneity)Tj
5.6523 0 Td
(P)Tj
0.7767 0 Td
(=)Tj
0.7993 0 Td
(0.569\).)Tj
2.914 0 Td
(Another)Tj
3.583 0 Td
(study)Tj
2.3867 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(])Tj
1.8539 0 Td
(reported)Tj
3.6623 0 Td
(a)Tj
0.652 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
-35.9544 -1.2982 Td
(rectal)Tj
2.4151 0 Td
(metastases)Tj
4.4333 0 Td
(in)Tj
1.0375 0 Td
(patients)Tj
3.3675 0 Td
(on)Tj
1.2756 0 Td
(aspirin)Tj
2.9877 0 Td
(as)Tj
1.0148 0 Td
(HR)Tj
1.6101 0 Td
(0.31)Tj
1.8708 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.18,)Tj
2.0976 0 Td
(0.54\).)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
32.2798 0 Td
(4)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
103 0 obj
<>stream
endstream
endobj
104 0 obj
<>stream
endstream
endobj
105 0 obj
<>stream
endstream
endobj
106 0 obj
<>stream
endstream
endobj
107 0 obj
<>stream
endstream
endobj
108 0 obj
<>stream
endstream
endobj
109 0 obj
<>stream
endstream
endobj
110 0 obj
<>stream
endstream
endobj
111 0 obj
<>stream
endstream
endobj
112 0 obj
<>stream
endstream
endobj
113 0 obj
<>stream
endstream
endobj
114 0 obj
<>stream
endstream
endobj
115 0 obj
<>stream
endstream
endobj
116 0 obj
<>stream
endstream
endobj
117 0 obj
<>stream
endstream
endobj
118 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
119 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 120 0 R/Contents 121 0 R/TrimBox[0 0 612 792]>>
endobj
120 0 obj
[122 0 R 123 0 R 124 0 R 125 0 R 126 0 R 127 0 R 128 0 R 129 0 R 130 0 R 131 0 R 132 0 R 133 0 R 134 0 R 135 0 R 136 0 R 137 0 R]
endobj
122 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.t001)>>
endobj
123 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
124 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref022)>>
endobj
125 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref023)>>
endobj
126 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref024)>>
endobj
127 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref025)>>
endobj
128 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref026)>>
endobj
129 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref027)>>
endobj
130 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref028)>>
endobj
131 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref029)>>
endobj
132 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref030)>>
endobj
133 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref031)>>
endobj
134 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref032)>>
endobj
135 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref033)>>
endobj
136 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref034)>>
endobj
137 0 obj
<>/Border[0 0 0]/A 138 0 R>>
endobj
138 0 obj
<>
endobj
121 0 obj
[139 0 R 140 0 R 141 0 R 142 0 R 143 0 R 144 0 R 145 0 R 146 0 R 147 0 R 148 0 R 149 0 R 150 0 R 151 0 R 152 0 R 153 0 R 154 0 R]
endobj
139 0 obj
<>stream
q
0.45 0.36 0.35 0.01 k
0 w
36 703.8893 m
576 703.8893 l
576 703.3893 l
36 703.3893 l
f*
106.2924 703.3893 m
106.2924 671.8893 l
105.7924 671.8893 l
105.7924 703.3893 l
f*
105.7924 671.8893 m
36 671.8893 l
36 672.3893 l
105.7924 672.3893 l
f*
171.2313 703.3893 m
171.2313 671.8893 l
170.7313 671.8893 l
170.7313 703.3893 l
f*
170.7313 671.8893 m
106.2924 671.8893 l
106.2924 672.3893 l
170.7313 672.3893 l
f*
216.8833 703.3893 m
216.8833 671.8893 l
216.3832 671.8893 l
216.3832 703.3893 l
f*
216.3832 671.8893 m
171.2313 671.8893 l
171.2313 672.3893 l
216.3832 672.3893 l
f*
267.1699 703.3893 m
267.1699 671.8893 l
266.6699 671.8893 l
266.6699 703.3893 l
f*
266.6699 671.8893 m
216.8833 671.8893 l
216.8833 672.3893 l
266.6699 672.3893 l
f*
342.6335 703.3893 m
342.6335 671.8893 l
342.1335 671.8893 l
342.1335 703.3893 l
f*
342.1335 671.8893 m
267.1699 671.8893 l
267.1699 672.3893 l
342.1335 672.3893 l
f*
402.8451 703.3893 m
402.8451 671.8893 l
402.3451 671.8893 l
402.3451 703.3893 l
f*
402.3451 671.8893 m
342.6335 671.8893 l
342.6335 672.3893 l
402.3451 672.3893 l
f*
576 671.8893 m
402.8451 671.8893 l
402.8451 672.3893 l
576 672.3893 l
f*
36 671.8893 m
576 671.8893 l
576 669.8891 l
36 669.8891 l
f*
576 657.3892 m
36 657.3892 l
36 657.8892 l
576 657.8892 l
f*
106.2924 657.3892 m
106.2924 613.3893 l
105.7924 613.3893 l
105.7924 657.3892 l
f*
105.7924 613.3893 m
36 613.3893 l
36 613.8893 l
105.7924 613.8893 l
f*
171.2313 657.3892 m
171.2313 613.3893 l
170.7313 613.3893 l
170.7313 657.3892 l
f*
170.7313 613.3893 m
106.2924 613.3893 l
106.2924 613.8893 l
170.7313 613.8893 l
f*
216.8833 657.3892 m
216.8833 613.3893 l
216.3832 613.3893 l
216.3832 657.3892 l
f*
216.3832 613.3893 m
171.2313 613.3893 l
171.2313 613.8893 l
216.3832 613.8893 l
f*
267.1699 657.3892 m
267.1699 613.3893 l
266.6699 613.3893 l
266.6699 657.3892 l
f*
266.6699 613.3893 m
216.8833 613.3893 l
216.8833 613.8893 l
266.6699 613.8893 l
f*
342.6335 657.3892 m
342.6335 635.3892 l
342.1335 635.3892 l
342.1335 657.3892 l
f*
342.1335 635.3892 m
267.1699 635.3892 l
267.1699 635.8893 l
342.1335 635.8893 l
f*
402.8451 657.3892 m
402.8451 635.3892 l
402.3451 635.3892 l
402.3451 657.3892 l
f*
402.3451 635.3892 m
342.6335 635.3892 l
342.6335 635.8893 l
402.3451 635.8893 l
f*
576 613.3893 m
402.8451 613.3893 l
402.8451 613.8893 l
576 613.8893 l
f*
342.6335 635.3892 m
342.6335 613.3893 l
342.1335 613.3893 l
342.1335 635.3892 l
f*
342.1335 613.3893 m
267.1699 613.3893 l
267.1699 613.8893 l
342.1335 613.8893 l
f*
402.8451 635.3892 m
402.8451 613.3893 l
402.3451 613.3893 l
402.3451 635.3892 l
f*
402.3451 613.3893 m
342.6335 613.3893 l
342.6335 613.8893 l
402.3451 613.8893 l
f*
106.2924 613.3893 m
106.2924 569.3893 l
105.7924 569.3893 l
105.7924 613.3893 l
f*
105.7924 569.3893 m
36 569.3893 l
36 569.8894 l
105.7924 569.8894 l
f*
171.2313 613.3893 m
171.2313 569.3893 l
170.7313 569.3893 l
170.7313 613.3893 l
f*
170.7313 569.3893 m
106.2924 569.3893 l
106.2924 569.8894 l
170.7313 569.8894 l
f*
216.8833 613.3893 m
216.8833 569.3893 l
216.3832 569.3893 l
216.3832 613.3893 l
f*
216.3832 569.3893 m
171.2313 569.3893 l
171.2313 569.8894 l
216.3832 569.8894 l
f*
267.1699 613.3893 m
267.1699 569.3893 l
266.6699 569.3893 l
266.6699 613.3893 l
f*
266.6699 569.3893 m
216.8833 569.3893 l
216.8833 569.8894 l
266.6699 569.8894 l
f*
342.6335 613.3893 m
342.6335 591.3893 l
342.1335 591.3893 l
342.1335 613.3893 l
f*
342.1335 591.3893 m
267.1699 591.3893 l
267.1699 591.8893 l
342.1335 591.8893 l
f*
402.8451 613.3893 m
402.8451 591.3893 l
402.3451 591.3893 l
402.3451 613.3893 l
f*
402.3451 591.3893 m
342.6335 591.3893 l
342.6335 591.8893 l
402.3451 591.8893 l
f*
576 569.3893 m
402.8451 569.3893 l
402.8451 569.8894 l
576 569.8894 l
f*
342.6335 591.3893 m
342.6335 569.3893 l
342.1335 569.3893 l
342.1335 591.3893 l
f*
342.1335 569.3893 m
267.1699 569.3893 l
267.1699 569.8894 l
342.1335 569.8894 l
f*
402.8451 591.3893 m
402.8451 569.3893 l
402.3451 569.3893 l
402.3451 591.3893 l
f*
402.3451 569.3893 m
342.6335 569.3893 l
342.6335 569.8894 l
402.3451 569.8894 l
f*
106.2924 569.3893 m
106.2924 525.3894 l
105.7924 525.3894 l
105.7924 569.3893 l
f*
105.7924 525.3894 m
36 525.3894 l
36 525.8894 l
105.7924 525.8894 l
f*
171.2313 569.3893 m
171.2313 525.3894 l
170.7313 525.3894 l
170.7313 569.3893 l
f*
170.7313 525.3894 m
106.2924 525.3894 l
106.2924 525.8894 l
170.7313 525.8894 l
f*
216.8833 569.3893 m
216.8833 525.3894 l
216.3832 525.3894 l
216.3832 569.3893 l
f*
216.3832 525.3894 m
171.2313 525.3894 l
171.2313 525.8894 l
216.3832 525.8894 l
f*
267.1699 569.3893 m
267.1699 525.3894 l
266.6699 525.3894 l
266.6699 569.3893 l
f*
266.6699 525.3894 m
216.8833 525.3894 l
216.8833 525.8894 l
266.6699 525.8894 l
f*
342.6335 569.3893 m
342.6335 547.3894 l
342.1335 547.3894 l
342.1335 569.3893 l
f*
342.1335 547.3894 m
267.1699 547.3894 l
267.1699 547.8894 l
342.1335 547.8894 l
f*
402.8451 569.3893 m
402.8451 547.3894 l
402.3451 547.3894 l
402.3451 569.3893 l
f*
402.3451 547.3894 m
342.6335 547.3894 l
342.6335 547.8894 l
402.3451 547.8894 l
f*
576 525.3894 m
402.8451 525.3894 l
402.8451 525.8894 l
576 525.8894 l
f*
342.6335 547.3894 m
342.6335 525.3894 l
342.1335 525.3894 l
342.1335 547.3894 l
f*
342.1335 525.3894 m
267.1699 525.3894 l
267.1699 525.8894 l
342.1335 525.8894 l
f*
402.8451 547.3894 m
402.8451 525.3894 l
402.3451 525.3894 l
402.3451 547.3894 l
f*
402.3451 525.3894 m
342.6335 525.3894 l
342.6335 525.8894 l
402.3451 525.8894 l
f*
106.2924 525.3894 m
106.2924 481.3894 l
105.7924 481.3894 l
105.7924 525.3894 l
f*
105.7924 481.3894 m
36 481.3894 l
36 481.8895 l
105.7924 481.8895 l
f*
171.2313 525.3894 m
171.2313 481.3894 l
170.7313 481.3894 l
170.7313 525.3894 l
f*
170.7313 481.3894 m
106.2924 481.3894 l
106.2924 481.8895 l
170.7313 481.8895 l
f*
216.8833 525.3894 m
216.8833 481.3894 l
216.3832 481.3894 l
216.3832 525.3894 l
f*
216.3832 481.3894 m
171.2313 481.3894 l
171.2313 481.8895 l
216.3832 481.8895 l
f*
267.1699 525.3894 m
267.1699 481.3894 l
266.6699 481.3894 l
266.6699 525.3894 l
f*
266.6699 481.3894 m
216.8833 481.3894 l
216.8833 481.8895 l
266.6699 481.8895 l
f*
342.6335 525.3894 m
342.6335 503.3894 l
342.1335 503.3894 l
342.1335 525.3894 l
f*
342.1335 503.3894 m
267.1699 503.3894 l
267.1699 503.8894 l
342.1335 503.8894 l
f*
402.8451 525.3894 m
402.8451 503.3894 l
402.3451 503.3894 l
402.3451 525.3894 l
f*
402.3451 503.3894 m
342.6335 503.3894 l
342.6335 503.8894 l
402.3451 503.8894 l
f*
576 481.3894 m
402.8451 481.3894 l
402.8451 481.8895 l
576 481.8895 l
f*
342.6335 503.3894 m
342.6335 481.3894 l
342.1335 481.3894 l
342.1335 503.3894 l
f*
342.1335 481.3894 m
267.1699 481.3894 l
267.1699 481.8895 l
342.1335 481.8895 l
f*
402.8451 503.3894 m
402.8451 481.3894 l
402.3451 481.3894 l
402.3451 503.3894 l
f*
402.3451 481.3894 m
342.6335 481.3894 l
342.6335 481.8895 l
402.3451 481.8895 l
f*
106.2924 481.3894 m
106.2924 437.3895 l
105.7924 437.3895 l
105.7924 481.3894 l
f*
105.7924 437.3895 m
36 437.3895 l
36 437.8895 l
105.7924 437.8895 l
f*
171.2313 481.3894 m
171.2313 437.3895 l
170.7313 437.3895 l
170.7313 481.3894 l
f*
170.7313 437.3895 m
106.2924 437.3895 l
106.2924 437.8895 l
170.7313 437.8895 l
f*
216.8833 481.3894 m
216.8833 437.3895 l
216.3832 437.3895 l
216.3832 481.3894 l
f*
216.3832 437.3895 m
171.2313 437.3895 l
171.2313 437.8895 l
216.3832 437.8895 l
f*
267.1699 481.3894 m
267.1699 437.3895 l
266.6699 437.3895 l
266.6699 481.3894 l
f*
266.6699 437.3895 m
216.8833 437.3895 l
216.8833 437.8895 l
266.6699 437.8895 l
f*
342.6335 481.3894 m
342.6335 459.3895 l
342.1335 459.3895 l
342.1335 481.3894 l
f*
342.1335 459.3895 m
267.1699 459.3895 l
267.1699 459.8895 l
342.1335 459.8895 l
f*
402.8451 481.3894 m
402.8451 459.3895 l
402.3451 459.3895 l
402.3451 481.3894 l
f*
402.3451 459.3895 m
342.6335 459.3895 l
342.6335 459.8895 l
402.3451 459.8895 l
f*
576 437.3895 m
402.8451 437.3895 l
402.8451 437.8895 l
576 437.8895 l
f*
342.6335 459.3895 m
342.6335 437.3895 l
342.1335 437.3895 l
342.1335 459.3895 l
f*
342.1335 437.3895 m
267.1699 437.3895 l
267.1699 437.8895 l
342.1335 437.8895 l
f*
402.8451 459.3895 m
402.8451 437.3895 l
402.3451 437.3895 l
402.3451 459.3895 l
f*
402.3451 437.3895 m
342.6335 437.3895 l
342.6335 437.8895 l
402.3451 437.8895 l
f*
106.2924 437.3895 m
106.2924 393.3896 l
105.7924 393.3896 l
105.7924 437.3895 l
f*
105.7924 393.3896 m
36 393.3896 l
36 393.8896 l
105.7924 393.8896 l
f*
171.2313 437.3895 m
171.2313 393.3896 l
170.7313 393.3896 l
170.7313 437.3895 l
f*
170.7313 393.3896 m
106.2924 393.3896 l
106.2924 393.8896 l
170.7313 393.8896 l
f*
216.8833 437.3895 m
216.8833 393.3896 l
216.3832 393.3896 l
216.3832 437.3895 l
f*
216.3832 393.3896 m
171.2313 393.3896 l
171.2313 393.8896 l
216.3832 393.8896 l
f*
267.1699 437.3895 m
267.1699 393.3896 l
266.6699 393.3896 l
266.6699 437.3895 l
f*
266.6699 393.3896 m
216.8833 393.3896 l
216.8833 393.8896 l
266.6699 393.8896 l
f*
342.6335 437.3895 m
342.6335 415.3895 l
342.1335 415.3895 l
342.1335 437.3895 l
f*
342.1335 415.3895 m
267.1699 415.3895 l
267.1699 415.8896 l
342.1335 415.8896 l
f*
402.8451 437.3895 m
402.8451 415.3895 l
402.3451 415.3895 l
402.3451 437.3895 l
f*
402.3451 415.3895 m
342.6335 415.3895 l
342.6335 415.8896 l
402.3451 415.8896 l
f*
576 393.3896 m
402.8451 393.3896 l
402.8451 393.8896 l
576 393.8896 l
f*
342.6335 415.3895 m
342.6335 393.3896 l
342.1335 393.3896 l
342.1335 415.3895 l
f*
342.1335 393.3896 m
267.1699 393.3896 l
267.1699 393.8896 l
342.1335 393.8896 l
f*
402.8451 415.3895 m
402.8451 393.3896 l
402.3451 393.3896 l
402.3451 415.3895 l
f*
402.3451 393.3896 m
342.6335 393.3896 l
342.6335 393.8896 l
402.3451 393.8896 l
f*
106.2924 393.3896 m
106.2924 349.3896 l
105.7924 349.3896 l
105.7924 393.3896 l
f*
105.7924 349.3896 m
36 349.3896 l
36 349.8897 l
105.7924 349.8897 l
f*
171.2313 393.3896 m
171.2313 349.3896 l
170.7313 349.3896 l
170.7313 393.3896 l
f*
170.7313 349.3896 m
106.2924 349.3896 l
106.2924 349.8897 l
170.7313 349.8897 l
f*
216.8833 393.3896 m
216.8833 349.3896 l
216.3832 349.3896 l
216.3832 393.3896 l
f*
216.3832 349.3896 m
171.2313 349.3896 l
171.2313 349.8897 l
216.3832 349.8897 l
f*
267.1699 393.3896 m
267.1699 349.3896 l
266.6699 349.3896 l
266.6699 393.3896 l
f*
266.6699 349.3896 m
216.8833 349.3896 l
216.8833 349.8897 l
266.6699 349.8897 l
f*
342.6335 393.3896 m
342.6335 371.3896 l
342.1335 371.3896 l
342.1335 393.3896 l
f*
342.1335 371.3896 m
267.1699 371.3896 l
267.1699 371.8896 l
342.1335 371.8896 l
f*
402.8451 393.3896 m
402.8451 371.3896 l
402.3451 371.3896 l
402.3451 393.3896 l
f*
402.3451 371.3896 m
342.6335 371.3896 l
342.6335 371.8896 l
402.3451 371.8896 l
f*
576 349.3896 m
402.8451 349.3896 l
402.8451 349.8897 l
576 349.8897 l
f*
342.6335 371.3896 m
342.6335 349.3896 l
342.1335 349.3896 l
342.1335 371.3896 l
f*
342.1335 349.3896 m
267.1699 349.3896 l
267.1699 349.8897 l
342.1335 349.8897 l
f*
402.8451 371.3896 m
402.8451 349.3896 l
402.3451 349.3896 l
402.3451 371.3896 l
f*
402.3451 349.3896 m
342.6335 349.3896 l
342.6335 349.8897 l
402.3451 349.8897 l
f*
106.2924 349.3896 m
106.2924 305.3897 l
105.7924 305.3897 l
105.7924 349.3896 l
f*
105.7924 305.3897 m
36 305.3897 l
36 305.8897 l
105.7924 305.8897 l
f*
171.2313 349.3896 m
171.2313 305.3897 l
170.7313 305.3897 l
170.7313 349.3896 l
f*
170.7313 305.3897 m
106.2924 305.3897 l
106.2924 305.8897 l
170.7313 305.8897 l
f*
216.8833 349.3896 m
216.8833 305.3897 l
216.3832 305.3897 l
216.3832 349.3896 l
f*
216.3832 305.3897 m
171.2313 305.3897 l
171.2313 305.8897 l
216.3832 305.8897 l
f*
267.1699 349.3896 m
267.1699 305.3897 l
266.6699 305.3897 l
266.6699 349.3896 l
f*
266.6699 305.3897 m
216.8833 305.3897 l
216.8833 305.8897 l
266.6699 305.8897 l
f*
342.6335 349.3896 m
342.6335 327.3897 l
342.1335 327.3897 l
342.1335 349.3896 l
f*
342.1335 327.3897 m
267.1699 327.3897 l
267.1699 327.8897 l
342.1335 327.8897 l
f*
402.8451 349.3896 m
402.8451 327.3897 l
402.3451 327.3897 l
402.3451 349.3896 l
f*
402.3451 327.3897 m
342.6335 327.3897 l
342.6335 327.8897 l
402.3451 327.8897 l
f*
576 305.3897 m
402.8451 305.3897 l
402.8451 305.8897 l
576 305.8897 l
f*
342.6335 327.3897 m
342.6335 305.3897 l
342.1335 305.3897 l
342.1335 327.3897 l
f*
342.1335 305.3897 m
267.1699 305.3897 l
267.1699 305.8897 l
342.1335 305.8897 l
f*
402.8451 327.3897 m
402.8451 305.3897 l
402.3451 305.3897 l
402.3451 327.3897 l
f*
402.3451 305.3897 m
342.6335 305.3897 l
342.6335 305.8897 l
402.3451 305.8897 l
f*
106.2924 305.3897 m
106.2924 283.3897 l
105.7924 283.3897 l
105.7924 305.3897 l
f*
105.7924 283.3897 m
36 283.3897 l
36 283.8898 l
105.7924 283.8898 l
f*
171.2313 305.3897 m
171.2313 283.3897 l
170.7313 283.3897 l
170.7313 305.3897 l
f*
170.7313 283.3897 m
106.2924 283.3897 l
106.2924 283.8898 l
170.7313 283.8898 l
f*
216.8833 305.3897 m
216.8833 283.3897 l
216.3832 283.3897 l
216.3832 305.3897 l
f*
216.3832 283.3897 m
171.2313 283.3897 l
171.2313 283.8898 l
216.3832 283.8898 l
f*
267.1699 305.3897 m
267.1699 283.3897 l
266.6699 283.3897 l
266.6699 305.3897 l
f*
266.6699 283.3897 m
216.8833 283.3897 l
216.8833 283.8898 l
266.6699 283.8898 l
f*
342.6335 305.3897 m
342.6335 283.3897 l
342.1335 283.3897 l
342.1335 305.3897 l
f*
342.1335 283.3897 m
267.1699 283.3897 l
267.1699 283.8898 l
342.1335 283.8898 l
f*
402.8451 305.3897 m
402.8451 283.3897 l
402.3451 283.3897 l
402.3451 305.3897 l
f*
402.3451 283.3897 m
342.6335 283.3897 l
342.6335 283.8898 l
402.3451 283.8898 l
f*
576 283.3897 m
402.8451 283.3897 l
402.8451 283.8898 l
576 283.8898 l
f*
106.2924 283.3897 m
106.2924 239.3898 l
105.7924 239.3898 l
105.7924 283.3897 l
f*
105.7924 239.3898 m
36 239.3898 l
36 239.8898 l
105.7924 239.8898 l
f*
171.2313 283.3897 m
171.2313 239.3898 l
170.7313 239.3898 l
170.7313 283.3897 l
f*
170.7313 239.3898 m
106.2924 239.3898 l
106.2924 239.8898 l
170.7313 239.8898 l
f*
216.8833 283.3897 m
216.8833 239.3898 l
216.3832 239.3898 l
216.3832 283.3897 l
f*
216.3832 239.3898 m
171.2313 239.3898 l
171.2313 239.8898 l
216.3832 239.8898 l
f*
267.1699 283.3897 m
267.1699 239.3898 l
266.6699 239.3898 l
266.6699 283.3897 l
f*
266.6699 239.3898 m
216.8833 239.3898 l
216.8833 239.8898 l
266.6699 239.8898 l
f*
342.6335 283.3897 m
342.6335 261.3898 l
342.1335 261.3898 l
342.1335 283.3897 l
f*
342.1335 261.3898 m
267.1699 261.3898 l
267.1699 261.8898 l
342.1335 261.8898 l
f*
402.8451 283.3897 m
402.8451 261.3898 l
402.3451 261.3898 l
402.3451 283.3897 l
f*
402.3451 261.3898 m
342.6335 261.3898 l
342.6335 261.8898 l
402.3451 261.8898 l
f*
576 239.3898 m
402.8451 239.3898 l
402.8451 239.8898 l
576 239.8898 l
f*
342.6335 261.3898 m
342.6335 239.3898 l
342.1335 239.3898 l
342.1335 261.3898 l
f*
342.1335 239.3898 m
267.1699 239.3898 l
267.1699 239.8898 l
342.1335 239.8898 l
f*
402.8451 261.3898 m
402.8451 239.3898 l
402.3451 239.3898 l
402.3451 261.3898 l
f*
402.3451 239.3898 m
342.6335 239.3898 l
342.6335 239.8898 l
402.3451 239.8898 l
f*
106.2924 239.3898 m
106.2924 185.8898 l
105.7924 185.8898 l
105.7924 239.3898 l
f*
105.7924 185.8898 m
36 185.8898 l
36 186.3899 l
105.7924 186.3899 l
f*
171.2313 239.3898 m
171.2313 207.8898 l
170.7313 207.8898 l
170.7313 239.3898 l
f*
170.7313 207.8898 m
106.2924 207.8898 l
106.2924 208.3898 l
170.7313 208.3898 l
f*
216.8833 239.3898 m
216.8833 207.8898 l
216.3832 207.8898 l
216.3832 239.3898 l
f*
216.3832 207.8898 m
171.2313 207.8898 l
171.2313 208.3898 l
216.3832 208.3898 l
f*
267.1699 239.3898 m
267.1699 185.8898 l
266.6699 185.8898 l
266.6699 239.3898 l
f*
266.6699 185.8898 m
216.8833 185.8898 l
216.8833 186.3899 l
266.6699 186.3899 l
f*
342.6335 239.3898 m
342.6335 207.8898 l
342.1335 207.8898 l
342.1335 239.3898 l
f*
342.1335 207.8898 m
267.1699 207.8898 l
267.1699 208.3898 l
342.1335 208.3898 l
f*
402.8451 239.3898 m
402.8451 207.8898 l
402.3451 207.8898 l
402.3451 239.3898 l
f*
402.3451 207.8898 m
342.6335 207.8898 l
342.6335 208.3898 l
402.3451 208.3898 l
f*
576 185.8898 m
402.8451 185.8898 l
402.8451 186.3899 l
576 186.3899 l
f*
171.2313 207.8898 m
171.2313 185.8898 l
170.7313 185.8898 l
170.7313 207.8898 l
f*
170.7313 185.8898 m
106.2924 185.8898 l
106.2924 186.3899 l
170.7313 186.3899 l
f*
216.8833 207.8898 m
216.8833 185.8898 l
216.3832 185.8898 l
216.3832 207.8898 l
f*
216.3832 185.8898 m
171.2313 185.8898 l
171.2313 186.3899 l
216.3832 186.3899 l
f*
342.6335 207.8898 m
342.6335 185.8898 l
342.1335 185.8898 l
342.1335 207.8898 l
f*
342.1335 185.8898 m
267.1699 185.8898 l
267.1699 186.3899 l
342.1335 186.3899 l
f*
402.8451 207.8898 m
402.8451 185.8898 l
402.3451 185.8898 l
402.3451 207.8898 l
f*
402.3451 185.8898 m
342.6335 185.8898 l
342.6335 186.3899 l
402.3451 186.3899 l
f*
106.2924 185.8898 m
106.2924 141.8899 l
105.7924 141.8899 l
105.7924 185.8898 l
f*
105.7924 141.8899 m
36 141.8899 l
36 142.3899 l
105.7924 142.3899 l
f*
171.2313 185.8898 m
171.2313 141.8899 l
170.7313 141.8899 l
170.7313 185.8898 l
f*
170.7313 141.8899 m
106.2924 141.8899 l
106.2924 142.3899 l
170.7313 142.3899 l
f*
216.8833 185.8898 m
216.8833 141.8899 l
216.3832 141.8899 l
216.3832 185.8898 l
f*
216.3832 141.8899 m
171.2313 141.8899 l
171.2313 142.3899 l
216.3832 142.3899 l
f*
267.1699 185.8898 m
267.1699 141.8899 l
266.6699 141.8899 l
266.6699 185.8898 l
f*
266.6699 141.8899 m
216.8833 141.8899 l
216.8833 142.3899 l
266.6699 142.3899 l
f*
342.6335 185.8898 m
342.6335 163.8899 l
342.1335 163.8899 l
342.1335 185.8898 l
f*
342.1335 163.8899 m
267.1699 163.8899 l
267.1699 164.3899 l
342.1335 164.3899 l
f*
402.8451 185.8898 m
402.8451 163.8899 l
402.3451 163.8899 l
402.3451 185.8898 l
f*
402.3451 163.8899 m
342.6335 163.8899 l
342.6335 164.3899 l
402.3451 164.3899 l
f*
576 141.8899 m
402.8451 141.8899 l
402.8451 142.3899 l
576 142.3899 l
f*
342.6335 163.8899 m
342.6335 141.8899 l
342.1335 141.8899 l
342.1335 163.8899 l
f*
342.1335 141.8899 m
267.1699 141.8899 l
267.1699 142.3899 l
342.1335 142.3899 l
f*
402.8451 163.8899 m
402.8451 141.8899 l
402.3451 141.8899 l
402.3451 163.8899 l
f*
402.3451 141.8899 m
342.6335 141.8899 l
342.6335 142.3899 l
402.3451 142.3899 l
f*
106.2924 141.8899 m
106.2924 119.8899 l
105.7924 119.8899 l
105.7924 141.8899 l
f*
105.7924 119.8899 m
36 119.8899 l
36 120.39 l
105.7924 120.39 l
f*
171.2313 141.8899 m
171.2313 119.8899 l
170.7313 119.8899 l
170.7313 141.8899 l
f*
170.7313 119.8899 m
106.2924 119.8899 l
106.2924 120.39 l
170.7313 120.39 l
f*
216.8833 141.8899 m
216.8833 119.8899 l
216.3832 119.8899 l
216.3832 141.8899 l
f*
216.3832 119.8899 m
171.2313 119.8899 l
171.2313 120.39 l
216.3832 120.39 l
f*
267.1699 141.8899 m
267.1699 119.8899 l
266.6699 119.8899 l
266.6699 141.8899 l
f*
266.6699 119.8899 m
216.8833 119.8899 l
216.8833 120.39 l
266.6699 120.39 l
f*
342.6335 141.8899 m
342.6335 119.8899 l
342.1335 119.8899 l
342.1335 141.8899 l
f*
342.1335 119.8899 m
267.1699 119.8899 l
267.1699 120.39 l
342.1335 120.39 l
f*
402.8451 141.8899 m
402.8451 119.8899 l
402.3451 119.8899 l
402.3451 141.8899 l
f*
402.3451 119.8899 m
342.6335 119.8899 l
342.6335 120.39 l
402.3451 120.39 l
f*
576 119.8899 m
402.8451 119.8899 l
402.8451 120.39 l
576 120.39 l
f*
576 97.89 m
36 97.89 l
36 98.39 l
576 98.39 l
f*
36 97.89 m
576 97.89 l
576 97.3899 l
36 97.3899 l
f*
0.83 0.64 0.02 0 k
521.6882 707.6409 m
529.285 707.6409 l
h
f*
75.0047 646.8094 m
82.6583 646.8094 l
h
f*
77.1024 602.8157 m
84.6992 602.8157 l
h
f*
91.4457 558.822 m
99.0992 558.822 l
h
f*
87.8173 514.8283 m
95.4142 514.8283 l
h
f*
80.9575 470.8346 m
88.611 470.8346 l
h
f*
83.9055 426.7843 m
91.5024 426.7843 l
h
f*
73.2472 382.7906 m
80.9008 382.7906 l
h
f*
71.263 338.7969 m
78.9165 338.7969 l
h
f*
38.7213 285.3354 m
46.3748 285.3354 l
h
f*
83.7921 272.8063 m
91.4457 272.8063 l
h
f*
38.7213 219.2882 m
46.3748 219.2882 l
h
f*
38.7213 165.8268 m
46.3748 165.8268 l
h
f*
84.8126 131.3008 m
92.4661 131.3008 l
h
f*
0 g
1 j
1 J
7.9999 0 0 7.9999 36 708.7181 cm
BT
/F12 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Table)Tj
2.5512 0 Td
(1.)Tj
1.1763 0 Td
(Aspirin)Tj
3.3733 0 Td
(treatment)Tj
4.3512 0 Td
(of)Tj
1.063 0 Td
(cancer)Tj
2.9055 0 Td
(in)Tj
1.063 0 Td
(observationa)Tj
5.3292 0 Td
(l)Tj
0.4961 0 Td
(studies)Tj
3.1252 0 Td
(reported)Tj
3.8268 0 Td
(2015201)Tj
3.9544 0 Td
(7.)Tj
/F5 1 Tf
1.1764 0 Td
(For)Tj
1.6228 0 Td
(details)Tj
2.7567 0 Td
(of)Tj
1.0063 0 Td
(studies)Tj
2.9693 0 Td
(published)Tj
4.1032 0 Td
(before)Tj
2.7213 0 Td
(2015,)Tj
2.3386 0 Td
(see)Tj
1.4173 0 Td
(our)Tj
1.6158 0 Td
(earlier)Tj
2.7425 0 Td
(report)Tj
2.693 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
/F12 1 Tf
0 Tc
-60.3784 -1.8567 Td
(Study)Tj
9.0355 0 Td
(Aspirin/no)Tj
0 -1.1834 Td
(Aspirin)Tj
8.1213 1.1834 Td
(Events)Tj
0 -1.1834 Td
(aspirin/)Tj
0 -1.1906 Td
(none)Tj
5.7047 2.374 Td
(Follow-up)Tj
0 -1.1834 Td
(duration)Tj
8.7804 1.1834 Td
(Outcom)Tj
3.4442 0 Td
(e)Tj
3.4937 0 Td
(HR/RR)Tj
0 -1.1834 Td
(\(95%)Tj
2.3386 0 Td
(CI\))Tj
5.1874 1.1834 Td
(Comment)Tj
-46.1058 -4.1811 Td
(COLOREC)Tj
4.6701 0 Td
(TAL)Tj
2.1331 0 Td
(and)Tj
1.8071 0 Td
(GASTROIN)Tj
5.1094 0 Td
(TESTINAL)Tj
4.9678 0 Td
(CANCER)Tj
/F5 1 Tf
-18.6875 -1.5661 Td
(Bains)Tj
2.4307 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.148 0 Td
([)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(])Tj
4.6276 0 Td
(6,102/17)Tj
3.4229 0 Td
(,06)Tj
1.4173 0 Td
(0)Tj
3.4158 0 Td
(1,158/5,37)Tj
4.1315 0 Td
(5)Tj
2.7922 0 Td
(3)Tj
0.7086 0 Td
(years)Tj
5.7119 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1906 Td
(mortality)Tj
6.9874 1.1906 Td
(HR)Tj
1.6158 0 Td
(0.85)Tj
1.8921 0 Td
(\(0.79,)Tj
-3.5079 -1.1906 Td
(0.92\))Tj
-8.9575 -1.5591 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(0.95)Tj
1.8921 0 Td
(\(0.90,)Tj
-3.5079 -1.1905 Td
(1.01\))Tj
-38.7073 -1.5591 Td
(Frows)Tj
2.6929 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(])Tj
5.719 0 Td
(1,008/8,27)Tj
4.1315 0 Td
(8)Tj
4.0182 0 Td
(5,138)Tj
5.322 0 Td
(Up)Tj
1.4882 0 Td
(to)Tj
1.0418 0 Td
(15)Tj
-1.8142 -1.1906 Td
(years)Tj
6.0662 1.1906 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1906 Td
(mortality)Tj
6.9874 1.1906 Td
(HR)Tj
1.6158 0 Td
(0.44)Tj
1.8921 0 Td
(\(0.33,)Tj
-3.5079 -1.1906 Td
(0.58\))Tj
7.5261 1.1906 Td
(Time)Tj
2.3528 0 Td
(dependent)Tj
4.4929 0 Td
(survival)Tj
3.3662 0 Td
(analyse)Tj
2.9126 0 Td
(s)Tj
-29.6081 -2.7496 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(0.52)Tj
1.8921 0 Td
(\(0.44,)Tj
-3.5079 -1.1906 Td
(0.63\))Tj
-38.7073 -1.5591 Td
(Giamperie)Tj
4.4858 0 Td
(et)Tj
0.9567 0 Td
(al,)Tj
1.1481 0 Td
([)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(])Tj
5.1024 0 Td
(20/46)Tj
7.1504 0 Td
(8/43)Tj
5.4993 0 Td
(6)Tj
0.7086 0 Td
(years)Tj
5.2725 0 Td
(Progression)Tj
4.9961 0 Td
(free)Tj
-3.3095 -1.1905 Td
(survival)Tj
6.6969 1.1905 Td
(HR)Tj
1.6158 0 Td
(0.48)Tj
1.8921 0 Td
(\(0.30,)Tj
-3.5079 -1.1905 Td
(0.79\))Tj
-8.9575 -1.5591 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(0.43)Tj
1.8921 0 Td
(\(0.26,)Tj
-3.5079 -1.1905 Td
(0.72\))Tj
-38.7073 -1.5591 Td
(Shimoike)Tj
4.0323 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(])Tj
5.0882 0 Td
(148/34)Tj
2.7142 0 Td
(3)Tj
/F12 1 Tf
5.5985 0 Td
(?)Tj
/F5 1 Tf
3.6922 0 Td
(Over)Tj
2.2323 0 Td
(5)Tj
0.7086 0 Td
(years)Tj
4.5993 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1906 Td
(mortality)Tj
6.9874 1.1906 Td
(HR)Tj
1.6158 0 Td
(1.38)Tj
1.8921 0 Td
(\(0.84,)Tj
-3.5079 -1.1906 Td
(2.26\))Tj
7.5261 1.1906 Td
(Poster)Tj
2.7638 0 Td
(presentat)Tj
3.6921 0 Td
(ion.)Tj
1.793 0 Td
(Our)Tj
1.8779 0 Td
(estimates)Tj
3.9402 0 Td
(of)Tj
1.0276 0 Td
(HR.)Tj
1.8496 0 Td
(Other)Tj
-16.9442 -1.1906 Td
(antiplatel)Tj
3.7347 0 Td
(et)Tj
0.9567 0 Td
(drugs)Tj
2.4945 0 Td
(used)Tj
-23.6695 -1.559 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(0.61)Tj
1.8921 0 Td
(\(0.28,)Tj
-3.5079 -1.1906 Td
(1.33\))Tj
-38.7073 -1.5591 Td
(Restivo)Tj
3.1819 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(])Tj
6.1725 0 Td
(37/204)Tj
8.0859 0 Td
(?)Tj
4.167 0 Td
(37months)Tj
0.1346 -1.1905 Td
(\(19-57m)Tj
3.4229 0 Td
(\))Tj
2.8063 1.1905 Td
(Prog)Tj
2.1402 0 Td
(free)Tj
1.7504 0 Td
(survival)Tj
4.748 0 Td
(HR)Tj
1.6158 0 Td
(0.20)Tj
1.8921 0 Td
(\(0.07,)Tj
-3.5079 -1.1905 Td
(0.60\))Tj
-8.4614 -1.5591 Td
(Overrall)Tj
3.5362 0 Td
(survival)Tj
4.9252 0 Td
(HR)Tj
1.6158 0 Td
(0.21)Tj
1.8921 0 Td
(\(0.05,)Tj
-3.5079 -1.1906 Td
(0.89\))Tj
-38.7073 -1.5661 Td
(Ventura)Tj
3.5433 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(])Tj
4.2733 0 Td
(9,938/)Tj
2.7 0 Td
(217,070)Tj
5.7544 0 Td
(45/742)Tj
5.9741 0 Td
(6)Tj
0.7086 0 Td
(years)Tj
5.7119 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1835 Td
(mortality)Tj
6.9874 1.1835 Td
(HR)Tj
1.6158 0 Td
(0.71)Tj
1.8921 0 Td
(\(0.52,)Tj
-3.5079 -1.1835 Td
(0.97\))Tj
7.5261 1.1835 Td
(`No)Tj
1.7008 0 Td
(certainty)Tj
3.7701 0 Td
(that)Tj
1.8 0 Td
(aspirin)Tj
3.0118 0 Td
(taking)Tj
2.7568 0 Td
(continue)Tj
3.5575 0 Td
(d)Tj
0.7582 0 Td
(to)Tj
1.0418 0 Td
(death')Tj
-34.8806 -2.7496 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(1.18)Tj
1.8921 0 Td
(\(1.12,)Tj
-3.5079 -1.1835 Td
(1.23\))Tj
-38.7073 -1.5662 Td
(Gray)Tj
2.211 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.148 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(])Tj
6.9024 0 Td
(146/53)Tj
2.7142 0 Td
(4)Tj
4.4363 0 Td
(40/172)Tj
7.1646 0 Td
(?)Tj
5.23 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1834 Td
(mortality)Tj
6.9874 1.1834 Td
(HR)Tj
1.6158 0 Td
(0.69)Tj
1.8921 0 Td
(\(0.47,)Tj
-3.5079 -1.1834 Td
(0.98\))Tj
7.5261 1.1834 Td
(PIK3CA)Tj
3.6354 0 Td
(and)Tj
1.7434 0 Td
(PTGS2)Tj
3.0756 0 Td
(evaluated)Tj
-24.938 -2.7496 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(0.76)Tj
1.8921 0 Td
(\(0.57,)Tj
-3.5079 -1.1835 Td
(1.03\))Tj
-38.7073 -1.5661 Td
(Hua)Tj
1.963 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.148 0 Td
([)Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(])Tj
6.7961 0 Td
(676/1,39)Tj
3.4229 0 Td
(7)Tj
4.3158 0 Td
(17/61)Tj
5.4992 0 Td
(11)Tj
1.1835 0 Td
(years)Tj
5.478 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1835 Td
(mortality)Tj
6.9874 1.1835 Td
(HR)Tj
1.6158 0 Td
(0.44)Tj
1.8921 0 Td
(\(0.25,)Tj
-3.5079 -1.1835 Td
(0.71\))Tj
-8.9575 -1.5662 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(0.75)Tj
1.8921 0 Td
(\(0.59,)Tj
-3.5079 -1.1834 Td
(0.95\))Tj
-38.7073 -1.5662 Td
(Vietonmaki)Tj
5.0031 0 Td
(et)Tj
0.9638 0 Td
(al.)Tj
-5.9669 -1.1835 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(])Tj
10.8638 1.1835 Td
(676/1,39)Tj
3.4229 0 Td
(7)Tj
4.7197 0 Td
(413)Tj
5.0953 0 Td
(15)Tj
1.1835 0 Td
(years)Tj
5.478 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1835 Td
(mortality)Tj
6.9874 1.1835 Td
(HR)Tj
1.6158 0 Td
(1.28)Tj
1.8921 0 Td
(\(0.40,)Tj
-3.5079 -1.1835 Td
(4.12\))Tj
7.5261 1.1835 Td
(Competing)Tj
4.7551 0 Td
(risk)Tj
1.7363 0 Td
(analyses)Tj
-52.7248 -2.7496 Td
(Murphy)Tj
3.5291 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1481 0 Td
([)Tj
0.83 0.64 0.02 0 k
(31)Tj
0 g
(])Tj
5.8181 0 Td
(95/296)Tj
7.3914 0 Td
(8/43)Tj
4.5071 0 Td
(110)Tj
1.6654 0 Td
(months)Tj
5.7473 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1835 Td
(mortality)Tj
6.9874 1.1835 Td
(RR)Tj
1.4741 0 Td
(0.72)Tj
1.8921 0 Td
(\(0.34)Tj
-3.3662 -1.1835 Td
(1.53\))Tj
7.5261 1.1835 Td
(Data)Tj
2.1402 0 Td
(for)Tj
1.4031 0 Td
(mutant)Tj
3.1678 0 Td
(and)Tj
1.7433 0 Td
(wild)Tj
1.963 0 Td
(PIK3CA)Tj
3.6355 0 Td
(combined)Tj
-30.5365 -2.7496 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(RR)Tj
1.4741 0 Td
(2.36)Tj
1.8921 0 Td
(\(1.44)Tj
-3.3662 -1.1906 Td
(3.87\))Tj
-38.7073 -1.5591 Td
(Ratnsingh)Tj
4.089 0 Td
(e)Tj
0.659 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
-5.7047 -1.1905 Td
([)Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(])Tj
10.5095 1.1905 Td
(5,935/3,93)Tj
4.1315 0 Td
(4)Tj
2.6646 0 Td
(44/42)Tj
2.4732 0 Td
(Males)Tj
3.5859 0 Td
(1721)Tj
2.6575 0 Td
(years)Tj
4.2945 0 Td
(M)Tj
1.1268 0 Td
(cause)Tj
2.4095 0 Td
(specific)Tj
-2.1331 -1.1905 Td
(mortality)Tj
6.9874 1.1905 Td
(RR)Tj
1.4741 0 Td
(0.68)Tj
1.8921 0 Td
(\(0.37.)Tj
-3.3662 -1.1905 Td
(1.26\))Tj
-28.1978 -2.7497 Td
(8.903/4,06)Tj
4.1315 0 Td
(2)Tj
3.9615 0 Td
(71/36)Tj
-0.5032 -1.1834 Td
(Females)Tj
12.4017 1.1834 Td
(F)Tj
0.7583 0 Td
(cause)Tj
2.4094 0 Td
(specific)Tj
-1.9488 -1.1834 Td
(mortality)Tj
6.9874 1.1834 Td
(RR)Tj
1.4741 0 Td
(1.61)Tj
1.8921 0 Td
(\(0.91,)Tj
-3.3662 -1.1834 Td
(2.85\))Tj
-38.7073 -1.5662 Td
(Hippisley-Cox)Tj
6.0661 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
-7.0228 -1.1835 Td
([)Tj
0.83 0.64 0.02 0 k
(33)Tj
0 g
(])Tj
10.2685 1.1835 Td
(4,528/39,6)Tj
4.1316 0 Td
(17)Tj
5.1378 0 Td
(?)Tj
4.0677 0 Td
(125)Tj
2.1827 0 Td
(years)Tj
4.9749 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1835 Td
(mortality)Tj
6.9874 1.1835 Td
(HR)Tj
1.6158 0 Td
(0.81)Tj
1.8921 0 Td
(\(0.73,)Tj
-3.5079 -1.1835 Td
(0.90\))Tj
7.5261 1.1835 Td
(Male)Tj
2.2323 0 Td
(and)Tj
1.7433 0 Td
(female)Tj
2.8772 0 Td
(data)Tj
1.9347 0 Td
(combined)Tj
-25.2711 -2.7496 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(0.85)Tj
1.8921 0 Td
(\(0.78,)Tj
-3.5079 -1.1835 Td
(0.93\))Tj
-38.7073 -1.5661 Td
(Hamada)Tj
3.6567 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(34)Tj
0 g
(])Tj
5.4638 0 Td
(269/34)Tj
2.7142 0 Td
(8)Tj
4.6702 0 Td
(37/81)Tj
5.1449 0 Td
(11.5)Tj
1.8921 0 Td
(years)Tj
3.6284 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-2.6504 -1.1835 Td
(mortality)Tj
9.4394 1.1835 Td
(HR)Tj
1.6158 0 Td
(0.65)Tj
1.8921 0 Td
(\(0.40,)Tj
-3.5079 -1.1835 Td
(1.07\))Tj
-30.6285 -1.5662 Td
(Colorectal)Tj
4.3795 0 Td
(cancer)Tj
2.863 0 Td
(deaths:)Tj
/F12 1 Tf
3.0473 0 Td
(Pooled)Tj
3.1323 0 Td
(HR)Tj
1.6654 0 Td
(for)Tj
1.4882 0 Td
(eleven)Tj
2.8488 0 Td
(studies:)Tj
3.4158 0 Td
(0.68)Tj
/F5 1 Tf
1.9701 0 Td
(\(0.57,)Tj
2.4661 0 Td
(0.81\),)Tj
2.4591 0 Td
(heterogeneity)Tj
5.6977 0 Td
(p)Tj
/F11 1 Tf
(<)Tj
/F5 1 Tf
(0.000)Tj
3.4229 0 Td
(5,)Tj
0.9354 0 Td
(Egger's)Tj
3.1181 0 Td
(test)Tj
1.6229 0 Td
(for)Tj
1.4031 0 Td
(bias)Tj
1.8071 0 Td
(p)Tj
0.7512 0 Td
(=)Tj
0.8079 0 Td
(0.09)Tj
-45.5177 -1.1834 Td
(All)Tj
1.4174 0 Td
(cause)Tj
2.4094 0 Td
(deaths:)Tj
/F12 1 Tf
3.0402 0 Td
(Pooled)Tj
3.1394 0 Td
(HR)Tj
1.6654 0 Td
(for)Tj
1.4811 0 Td
(nine)Tj
2.0835 0 Td
(studies:)Tj
3.4158 0 Td
(0.76)Tj
/F5 1 Tf
1.9771 0 Td
(\(0.630.)Tj
3.2245 0 Td
(91\))Tj
1.5307 0 Td
(heterogeneit)Tj
5.0032 0 Td
(y)Tj
0.6874 0 Td
(p)Tj
/F11 1 Tf
(<)Tj
/F5 1 Tf
(0.0005,)Tj
4.3654 0 Td
(Egger's)Tj
3.1181 0 Td
(test)Tj
1.6158 0 Td
(p)Tj
0.7512 0 Td
(=)Tj
0.8149 0 Td
(0.04)Tj
8.9717 -1.8142 Td
(\()Tj
/F10 1 Tf
[()-2()11()22()7( )12()18(\n)4()]TJ
3.9828 0 Td
[()]TJ
/F5 1 Tf
0.6023 0 Td
(\))Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
32.2798 0 Td
(5)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
140 0 obj
<>stream
endstream
endobj
141 0 obj
<>stream
endstream
endobj
142 0 obj
<>stream
endstream
endobj
143 0 obj
<>stream
endstream
endobj
144 0 obj
<>stream
endstream
endobj
145 0 obj
<>stream
endstream
endobj
146 0 obj
<>stream
endstream
endobj
147 0 obj
<>stream
endstream
endobj
148 0 obj
<>stream
endstream
endobj
149 0 obj
<>stream
endstream
endobj
150 0 obj
<>stream
endstream
endobj
151 0 obj
<>stream
endstream
endobj
152 0 obj
<>stream
endstream
endobj
153 0 obj
<>stream
endstream
endobj
154 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
155 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 156 0 R/Contents 157 0 R/TrimBox[0 0 612 792]>>
endobj
156 0 obj
[158 0 R 159 0 R 160 0 R 161 0 R 162 0 R 163 0 R 164 0 R 165 0 R 166 0 R 167 0 R 168 0 R 169 0 R 170 0 R 171 0 R 172 0 R 173 0 R]
endobj
158 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref035)>>
endobj
159 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref036)>>
endobj
160 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref032)>>
endobj
161 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref037)>>
endobj
162 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref038)>>
endobj
163 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref039)>>
endobj
164 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref040)>>
endobj
165 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref041)>>
endobj
166 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref032)>>
endobj
167 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref042)>>
endobj
168 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref043)>>
endobj
169 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref044)>>
endobj
170 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref045)>>
endobj
171 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref030)>>
endobj
172 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref046)>>
endobj
173 0 obj
<>/Border[0 0 0]/A 174 0 R>>
endobj
174 0 obj
<>
endobj
157 0 obj
[175 0 R 176 0 R 177 0 R 178 0 R 179 0 R 180 0 R 181 0 R 182 0 R 183 0 R 184 0 R 185 0 R 186 0 R 187 0 R 188 0 R 189 0 R]
endobj
175 0 obj
<>stream
q
0.45 0.36 0.35 0.01 k
0 w
36 700.9999 m
576 700.9999 l
576 700.4999 l
36 700.4999 l
f*
106.2924 700.4999 m
106.2924 668.9999 l
105.7924 668.9999 l
105.7924 700.4999 l
f*
105.7924 668.9999 m
36 668.9999 l
36 669.4999 l
105.7924 669.4999 l
f*
171.2313 700.4999 m
171.2313 668.9999 l
170.7313 668.9999 l
170.7313 700.4999 l
f*
170.7313 668.9999 m
106.2924 668.9999 l
106.2924 669.4999 l
170.7313 669.4999 l
f*
216.8833 700.4999 m
216.8833 668.9999 l
216.3832 668.9999 l
216.3832 700.4999 l
f*
216.3832 668.9999 m
171.2313 668.9999 l
171.2313 669.4999 l
216.3832 669.4999 l
f*
267.1699 700.4999 m
267.1699 668.9999 l
266.6699 668.9999 l
266.6699 700.4999 l
f*
266.6699 668.9999 m
216.8833 668.9999 l
216.8833 669.4999 l
266.6699 669.4999 l
f*
342.6335 700.4999 m
342.6335 668.9999 l
342.1335 668.9999 l
342.1335 700.4999 l
f*
342.1335 668.9999 m
267.1699 668.9999 l
267.1699 669.4999 l
342.1335 669.4999 l
f*
402.8451 700.4999 m
402.8451 668.9999 l
402.3451 668.9999 l
402.3451 700.4999 l
f*
402.3451 668.9999 m
342.6335 668.9999 l
342.6335 669.4999 l
402.3451 669.4999 l
f*
576 668.9999 m
402.8451 668.9999 l
402.8451 669.4999 l
576 669.4999 l
f*
36 668.9999 m
576 668.9999 l
576 666.9998 l
36 666.9998 l
f*
576 654.4998 m
36 654.4998 l
36 654.9999 l
576 654.9999 l
f*
106.2924 654.4998 m
106.2924 610.4999 l
105.7924 610.4999 l
105.7924 654.4998 l
f*
105.7924 610.4999 m
36 610.4999 l
36 610.9999 l
105.7924 610.9999 l
f*
171.2313 654.4998 m
171.2313 610.4999 l
170.7313 610.4999 l
170.7313 654.4998 l
f*
170.7313 610.4999 m
106.2924 610.4999 l
106.2924 610.9999 l
170.7313 610.9999 l
f*
216.8833 654.4998 m
216.8833 610.4999 l
216.3832 610.4999 l
216.3832 654.4998 l
f*
216.3832 610.4999 m
171.2313 610.4999 l
171.2313 610.9999 l
216.3832 610.9999 l
f*
267.1699 654.4998 m
267.1699 610.4999 l
266.6699 610.4999 l
266.6699 654.4998 l
f*
266.6699 610.4999 m
216.8833 610.4999 l
216.8833 610.9999 l
266.6699 610.9999 l
f*
342.6335 654.4998 m
342.6335 632.4999 l
342.1335 632.4999 l
342.1335 654.4998 l
f*
342.1335 632.4999 m
267.1699 632.4999 l
267.1699 632.9999 l
342.1335 632.9999 l
f*
402.8451 654.4998 m
402.8451 632.4999 l
402.3451 632.4999 l
402.3451 654.4998 l
f*
402.3451 632.4999 m
342.6335 632.4999 l
342.6335 632.9999 l
402.3451 632.9999 l
f*
576 610.4999 m
402.8451 610.4999 l
402.8451 610.9999 l
576 610.9999 l
f*
342.6335 632.4999 m
342.6335 610.4999 l
342.1335 610.4999 l
342.1335 632.4999 l
f*
342.1335 610.4999 m
267.1699 610.4999 l
267.1699 610.9999 l
342.1335 610.9999 l
f*
402.8451 632.4999 m
402.8451 610.4999 l
402.3451 610.4999 l
402.3451 632.4999 l
f*
402.3451 610.4999 m
342.6335 610.4999 l
342.6335 610.9999 l
402.3451 610.9999 l
f*
106.2924 610.4999 m
106.2924 566.5 l
105.7924 566.5 l
105.7924 610.4999 l
f*
105.7924 566.5 m
36 566.5 l
36 567 l
105.7924 567 l
f*
171.2313 610.4999 m
171.2313 566.5 l
170.7313 566.5 l
170.7313 610.4999 l
f*
170.7313 566.5 m
106.2924 566.5 l
106.2924 567 l
170.7313 567 l
f*
216.8833 610.4999 m
216.8833 566.5 l
216.3832 566.5 l
216.3832 610.4999 l
f*
216.3832 566.5 m
171.2313 566.5 l
171.2313 567 l
216.3832 567 l
f*
267.1699 610.4999 m
267.1699 566.5 l
266.6699 566.5 l
266.6699 610.4999 l
f*
266.6699 566.5 m
216.8833 566.5 l
216.8833 567 l
266.6699 567 l
f*
342.6335 610.4999 m
342.6335 588.4999 l
342.1335 588.4999 l
342.1335 610.4999 l
f*
342.1335 588.4999 m
267.1699 588.4999 l
267.1699 589 l
342.1335 589 l
f*
402.8451 610.4999 m
402.8451 588.4999 l
402.3451 588.4999 l
402.3451 610.4999 l
f*
402.3451 588.4999 m
342.6335 588.4999 l
342.6335 589 l
402.3451 589 l
f*
576 566.5 m
402.8451 566.5 l
402.8451 567 l
576 567 l
f*
342.6335 588.4999 m
342.6335 566.5 l
342.1335 566.5 l
342.1335 588.4999 l
f*
342.1335 566.5 m
267.1699 566.5 l
267.1699 567 l
342.1335 567 l
f*
402.8451 588.4999 m
402.8451 566.5 l
402.3451 566.5 l
402.3451 588.4999 l
f*
402.3451 566.5 m
342.6335 566.5 l
342.6335 567 l
402.3451 567 l
f*
106.2924 566.5 m
106.2924 544.5 l
105.7924 544.5 l
105.7924 566.5 l
f*
105.7924 544.5 m
36 544.5 l
36 545 l
105.7924 545 l
f*
171.2313 566.5 m
171.2313 544.5 l
170.7313 544.5 l
170.7313 566.5 l
f*
170.7313 544.5 m
106.2924 544.5 l
106.2924 545 l
170.7313 545 l
f*
216.8833 566.5 m
216.8833 544.5 l
216.3832 544.5 l
216.3832 566.5 l
f*
216.3832 544.5 m
171.2313 544.5 l
171.2313 545 l
216.3832 545 l
f*
267.1699 566.5 m
267.1699 544.5 l
266.6699 544.5 l
266.6699 566.5 l
f*
266.6699 544.5 m
216.8833 544.5 l
216.8833 545 l
266.6699 545 l
f*
342.6335 566.5 m
342.6335 544.5 l
342.1335 544.5 l
342.1335 566.5 l
f*
342.1335 544.5 m
267.1699 544.5 l
267.1699 545 l
342.1335 545 l
f*
402.8451 566.5 m
402.8451 544.5 l
402.3451 544.5 l
402.3451 566.5 l
f*
402.3451 544.5 m
342.6335 544.5 l
342.6335 545 l
402.3451 545 l
f*
576 544.5 m
402.8451 544.5 l
402.8451 545 l
576 545 l
f*
106.2924 544.5 m
106.2924 522.5 l
105.7924 522.5 l
105.7924 544.5 l
f*
105.7924 522.5 m
36 522.5 l
36 523.0001 l
105.7924 523.0001 l
f*
171.2313 544.5 m
171.2313 522.5 l
170.7313 522.5 l
170.7313 544.5 l
f*
170.7313 522.5 m
106.2924 522.5 l
106.2924 523.0001 l
170.7313 523.0001 l
f*
216.8833 544.5 m
216.8833 522.5 l
216.3832 522.5 l
216.3832 544.5 l
f*
216.3832 522.5 m
171.2313 522.5 l
171.2313 523.0001 l
216.3832 523.0001 l
f*
267.1699 544.5 m
267.1699 522.5 l
266.6699 522.5 l
266.6699 544.5 l
f*
266.6699 522.5 m
216.8833 522.5 l
216.8833 523.0001 l
266.6699 523.0001 l
f*
342.6335 544.5 m
342.6335 522.5 l
342.1335 522.5 l
342.1335 544.5 l
f*
342.1335 522.5 m
267.1699 522.5 l
267.1699 523.0001 l
342.1335 523.0001 l
f*
402.8451 544.5 m
402.8451 522.5 l
402.3451 522.5 l
402.3451 544.5 l
f*
402.3451 522.5 m
342.6335 522.5 l
342.6335 523.0001 l
402.3451 523.0001 l
f*
576 522.5 m
402.8451 522.5 l
402.8451 523.0001 l
576 523.0001 l
f*
576 500.5001 m
36 500.5001 l
36 501.0001 l
576 501.0001 l
f*
36 500.5001 m
576 500.5001 l
576 498.4999 l
36 498.4999 l
f*
576 486 m
36 486 l
36 486.5 l
576 486.5 l
f*
106.2924 486 m
106.2924 464 l
105.7924 464 l
105.7924 486 l
f*
105.7924 464 m
36 464 l
36 464.5001 l
105.7924 464.5001 l
f*
171.2313 486 m
171.2313 464 l
170.7313 464 l
170.7313 486 l
f*
170.7313 464 m
106.2924 464 l
106.2924 464.5001 l
170.7313 464.5001 l
f*
216.8833 486 m
216.8833 464 l
216.3832 464 l
216.3832 486 l
f*
216.3832 464 m
171.2313 464 l
171.2313 464.5001 l
216.3832 464.5001 l
f*
267.1699 486 m
267.1699 464 l
266.6699 464 l
266.6699 486 l
f*
266.6699 464 m
216.8833 464 l
216.8833 464.5001 l
266.6699 464.5001 l
f*
342.6335 486 m
342.6335 464 l
342.1335 464 l
342.1335 486 l
f*
342.1335 464 m
267.1699 464 l
267.1699 464.5001 l
342.1335 464.5001 l
f*
402.8451 486 m
402.8451 464 l
402.3451 464 l
402.3451 486 l
f*
402.3451 464 m
342.6335 464 l
342.6335 464.5001 l
402.3451 464.5001 l
f*
576 464 m
402.8451 464 l
402.8451 464.5001 l
576 464.5001 l
f*
106.2924 464 m
106.2924 442.0001 l
105.7924 442.0001 l
105.7924 464 l
f*
105.7924 442.0001 m
36 442.0001 l
36 442.5001 l
105.7924 442.5001 l
f*
171.2313 464 m
171.2313 442.0001 l
170.7313 442.0001 l
170.7313 464 l
f*
170.7313 442.0001 m
106.2924 442.0001 l
106.2924 442.5001 l
170.7313 442.5001 l
f*
216.8833 464 m
216.8833 442.0001 l
216.3832 442.0001 l
216.3832 464 l
f*
216.3832 442.0001 m
171.2313 442.0001 l
171.2313 442.5001 l
216.3832 442.5001 l
f*
267.1699 464 m
267.1699 442.0001 l
266.6699 442.0001 l
266.6699 464 l
f*
266.6699 442.0001 m
216.8833 442.0001 l
216.8833 442.5001 l
266.6699 442.5001 l
f*
342.6335 464 m
342.6335 442.0001 l
342.1335 442.0001 l
342.1335 464 l
f*
342.1335 442.0001 m
267.1699 442.0001 l
267.1699 442.5001 l
342.1335 442.5001 l
f*
402.8451 464 m
402.8451 442.0001 l
402.3451 442.0001 l
402.3451 464 l
f*
402.3451 442.0001 m
342.6335 442.0001 l
342.6335 442.5001 l
402.3451 442.5001 l
f*
576 442.0001 m
402.8451 442.0001 l
402.8451 442.5001 l
576 442.5001 l
f*
106.2924 442.0001 m
106.2924 398.0001 l
105.7924 398.0001 l
105.7924 442.0001 l
f*
105.7924 398.0001 m
36 398.0001 l
36 398.5002 l
105.7924 398.5002 l
f*
171.2313 442.0001 m
171.2313 398.0001 l
170.7313 398.0001 l
170.7313 442.0001 l
f*
170.7313 398.0001 m
106.2924 398.0001 l
106.2924 398.5002 l
170.7313 398.5002 l
f*
216.8833 442.0001 m
216.8833 398.0001 l
216.3832 398.0001 l
216.3832 442.0001 l
f*
216.3832 398.0001 m
171.2313 398.0001 l
171.2313 398.5002 l
216.3832 398.5002 l
f*
267.1699 442.0001 m
267.1699 398.0001 l
266.6699 398.0001 l
266.6699 442.0001 l
f*
266.6699 398.0001 m
216.8833 398.0001 l
216.8833 398.5002 l
266.6699 398.5002 l
f*
342.6335 442.0001 m
342.6335 420.0001 l
342.1335 420.0001 l
342.1335 442.0001 l
f*
342.1335 420.0001 m
267.1699 420.0001 l
267.1699 420.5001 l
342.1335 420.5001 l
f*
402.8451 442.0001 m
402.8451 420.0001 l
402.3451 420.0001 l
402.3451 442.0001 l
f*
402.3451 420.0001 m
342.6335 420.0001 l
342.6335 420.5001 l
402.3451 420.5001 l
f*
576 398.0001 m
402.8451 398.0001 l
402.8451 398.5002 l
576 398.5002 l
f*
342.6335 420.0001 m
342.6335 398.0001 l
342.1335 398.0001 l
342.1335 420.0001 l
f*
342.1335 398.0001 m
267.1699 398.0001 l
267.1699 398.5002 l
342.1335 398.5002 l
f*
402.8451 420.0001 m
402.8451 398.0001 l
402.3451 398.0001 l
402.3451 420.0001 l
f*
402.3451 398.0001 m
342.6335 398.0001 l
342.6335 398.5002 l
402.3451 398.5002 l
f*
106.2924 398.0001 m
106.2924 354.0002 l
105.7924 354.0002 l
105.7924 398.0001 l
f*
105.7924 354.0002 m
36 354.0002 l
36 354.5002 l
105.7924 354.5002 l
f*
171.2313 398.0001 m
171.2313 354.0002 l
170.7313 354.0002 l
170.7313 398.0001 l
f*
170.7313 354.0002 m
106.2924 354.0002 l
106.2924 354.5002 l
170.7313 354.5002 l
f*
216.8833 398.0001 m
216.8833 354.0002 l
216.3832 354.0002 l
216.3832 398.0001 l
f*
216.3832 354.0002 m
171.2313 354.0002 l
171.2313 354.5002 l
216.3832 354.5002 l
f*
267.1699 398.0001 m
267.1699 354.0002 l
266.6699 354.0002 l
266.6699 398.0001 l
f*
266.6699 354.0002 m
216.8833 354.0002 l
216.8833 354.5002 l
266.6699 354.5002 l
f*
342.6335 398.0001 m
342.6335 376.0002 l
342.1335 376.0002 l
342.1335 398.0001 l
f*
342.1335 376.0002 m
267.1699 376.0002 l
267.1699 376.5002 l
342.1335 376.5002 l
f*
402.8451 398.0001 m
402.8451 376.0002 l
402.3451 376.0002 l
402.3451 398.0001 l
f*
402.3451 376.0002 m
342.6335 376.0002 l
342.6335 376.5002 l
402.3451 376.5002 l
f*
576 354.0002 m
402.8451 354.0002 l
402.8451 354.5002 l
576 354.5002 l
f*
342.6335 376.0002 m
342.6335 354.0002 l
342.1335 354.0002 l
342.1335 376.0002 l
f*
342.1335 354.0002 m
267.1699 354.0002 l
267.1699 354.5002 l
342.1335 354.5002 l
f*
402.8451 376.0002 m
402.8451 354.0002 l
402.3451 354.0002 l
402.3451 376.0002 l
f*
402.3451 354.0002 m
342.6335 354.0002 l
342.6335 354.5002 l
402.3451 354.5002 l
f*
106.2924 354.0002 m
106.2924 332.0002 l
105.7924 332.0002 l
105.7924 354.0002 l
f*
105.7924 332.0002 m
36 332.0002 l
36 332.5003 l
105.7924 332.5003 l
f*
171.2313 354.0002 m
171.2313 332.0002 l
170.7313 332.0002 l
170.7313 354.0002 l
f*
170.7313 332.0002 m
106.2924 332.0002 l
106.2924 332.5003 l
170.7313 332.5003 l
f*
216.8833 354.0002 m
216.8833 332.0002 l
216.3832 332.0002 l
216.3832 354.0002 l
f*
216.3832 332.0002 m
171.2313 332.0002 l
171.2313 332.5003 l
216.3832 332.5003 l
f*
267.1699 354.0002 m
267.1699 332.0002 l
266.6699 332.0002 l
266.6699 354.0002 l
f*
266.6699 332.0002 m
216.8833 332.0002 l
216.8833 332.5003 l
266.6699 332.5003 l
f*
342.6335 354.0002 m
342.6335 332.0002 l
342.1335 332.0002 l
342.1335 354.0002 l
f*
342.1335 332.0002 m
267.1699 332.0002 l
267.1699 332.5003 l
342.1335 332.5003 l
f*
402.8451 354.0002 m
402.8451 332.0002 l
402.3451 332.0002 l
402.3451 354.0002 l
f*
402.3451 332.0002 m
342.6335 332.0002 l
342.6335 332.5003 l
402.3451 332.5003 l
f*
576 332.0002 m
402.8451 332.0002 l
402.8451 332.5003 l
576 332.5003 l
f*
106.2924 332.0002 m
106.2924 288.0003 l
105.7924 288.0003 l
105.7924 332.0002 l
f*
105.7924 288.0003 m
36 288.0003 l
36 288.5003 l
105.7924 288.5003 l
f*
171.2313 332.0002 m
171.2313 288.0003 l
170.7313 288.0003 l
170.7313 332.0002 l
f*
170.7313 288.0003 m
106.2924 288.0003 l
106.2924 288.5003 l
170.7313 288.5003 l
f*
216.8833 332.0002 m
216.8833 288.0003 l
216.3832 288.0003 l
216.3832 332.0002 l
f*
216.3832 288.0003 m
171.2313 288.0003 l
171.2313 288.5003 l
216.3832 288.5003 l
f*
267.1699 332.0002 m
267.1699 288.0003 l
266.6699 288.0003 l
266.6699 332.0002 l
f*
266.6699 288.0003 m
216.8833 288.0003 l
216.8833 288.5003 l
266.6699 288.5003 l
f*
342.6335 332.0002 m
342.6335 310.0003 l
342.1335 310.0003 l
342.1335 332.0002 l
f*
342.1335 310.0003 m
267.1699 310.0003 l
267.1699 310.5003 l
342.1335 310.5003 l
f*
402.8451 332.0002 m
402.8451 310.0003 l
402.3451 310.0003 l
402.3451 332.0002 l
f*
402.3451 310.0003 m
342.6335 310.0003 l
342.6335 310.5003 l
402.3451 310.5003 l
f*
576 288.0003 m
402.8451 288.0003 l
402.8451 288.5003 l
576 288.5003 l
f*
342.6335 310.0003 m
342.6335 288.0003 l
342.1335 288.0003 l
342.1335 310.0003 l
f*
342.1335 288.0003 m
267.1699 288.0003 l
267.1699 288.5003 l
342.1335 288.5003 l
f*
402.8451 310.0003 m
402.8451 288.0003 l
402.3451 288.0003 l
402.3451 310.0003 l
f*
402.3451 288.0003 m
342.6335 288.0003 l
342.6335 288.5003 l
402.3451 288.5003 l
f*
36 288.0003 m
576 288.0003 l
576 286.0002 l
36 286.0002 l
f*
576 273.5002 m
36 273.5002 l
36 274.0003 l
576 274.0003 l
f*
106.2924 273.5002 m
106.2924 229.5003 l
105.7924 229.5003 l
105.7924 273.5002 l
f*
105.7924 229.5003 m
36 229.5003 l
36 230.0003 l
105.7924 230.0003 l
f*
171.2313 273.5002 m
171.2313 251.5003 l
170.7313 251.5003 l
170.7313 273.5002 l
f*
170.7313 251.5003 m
106.2924 251.5003 l
106.2924 252.0003 l
170.7313 252.0003 l
f*
216.8833 273.5002 m
216.8833 229.5003 l
216.3832 229.5003 l
216.3832 273.5002 l
f*
216.3832 229.5003 m
171.2313 229.5003 l
171.2313 230.0003 l
216.3832 230.0003 l
f*
267.1699 273.5002 m
267.1699 251.5003 l
266.6699 251.5003 l
266.6699 273.5002 l
f*
266.6699 251.5003 m
216.8833 251.5003 l
216.8833 252.0003 l
266.6699 252.0003 l
f*
342.6335 273.5002 m
342.6335 251.5003 l
342.1335 251.5003 l
342.1335 273.5002 l
f*
342.1335 251.5003 m
267.1699 251.5003 l
267.1699 252.0003 l
342.1335 252.0003 l
f*
402.8451 273.5002 m
402.8451 251.5003 l
402.3451 251.5003 l
402.3451 273.5002 l
f*
402.3451 251.5003 m
342.6335 251.5003 l
342.6335 252.0003 l
402.3451 252.0003 l
f*
576 229.5003 m
402.8451 229.5003 l
402.8451 230.0003 l
576 230.0003 l
f*
171.2313 251.5003 m
171.2313 229.5003 l
170.7313 229.5003 l
170.7313 251.5003 l
f*
170.7313 229.5003 m
106.2924 229.5003 l
106.2924 230.0003 l
170.7313 230.0003 l
f*
267.1699 251.5003 m
267.1699 229.5003 l
266.6699 229.5003 l
266.6699 251.5003 l
f*
266.6699 229.5003 m
216.8833 229.5003 l
216.8833 230.0003 l
266.6699 230.0003 l
f*
342.6335 251.5003 m
342.6335 229.5003 l
342.1335 229.5003 l
342.1335 251.5003 l
f*
342.1335 229.5003 m
267.1699 229.5003 l
267.1699 230.0003 l
342.1335 230.0003 l
f*
402.8451 251.5003 m
402.8451 229.5003 l
402.3451 229.5003 l
402.3451 251.5003 l
f*
402.3451 229.5003 m
342.6335 229.5003 l
342.6335 230.0003 l
402.3451 230.0003 l
f*
106.2924 229.5003 m
106.2924 185.5003 l
105.7924 185.5003 l
105.7924 229.5003 l
f*
105.7924 185.5003 m
36 185.5003 l
36 186.0004 l
105.7924 186.0004 l
f*
171.2313 229.5003 m
171.2313 207.5003 l
170.7313 207.5003 l
170.7313 229.5003 l
f*
170.7313 207.5003 m
106.2924 207.5003 l
106.2924 208.0003 l
170.7313 208.0003 l
f*
216.8833 229.5003 m
216.8833 185.5003 l
216.3832 185.5003 l
216.3832 229.5003 l
f*
216.3832 185.5003 m
171.2313 185.5003 l
171.2313 186.0004 l
216.3832 186.0004 l
f*
267.1699 229.5003 m
267.1699 185.5003 l
266.6699 185.5003 l
266.6699 229.5003 l
f*
266.6699 185.5003 m
216.8833 185.5003 l
216.8833 186.0004 l
266.6699 186.0004 l
f*
342.6335 229.5003 m
342.6335 207.5003 l
342.1335 207.5003 l
342.1335 229.5003 l
f*
342.1335 207.5003 m
267.1699 207.5003 l
267.1699 208.0003 l
342.1335 208.0003 l
f*
402.8451 229.5003 m
402.8451 207.5003 l
402.3451 207.5003 l
402.3451 229.5003 l
f*
402.3451 207.5003 m
342.6335 207.5003 l
342.6335 208.0003 l
402.3451 208.0003 l
f*
576 185.5003 m
402.8451 185.5003 l
402.8451 186.0004 l
576 186.0004 l
f*
171.2313 207.5003 m
171.2313 185.5003 l
170.7313 185.5003 l
170.7313 207.5003 l
f*
170.7313 185.5003 m
106.2924 185.5003 l
106.2924 186.0004 l
170.7313 186.0004 l
f*
342.6335 207.5003 m
342.6335 185.5003 l
342.1335 185.5003 l
342.1335 207.5003 l
f*
342.1335 185.5003 m
267.1699 185.5003 l
267.1699 186.0004 l
342.1335 186.0004 l
f*
402.8451 207.5003 m
402.8451 185.5003 l
402.3451 185.5003 l
402.3451 207.5003 l
f*
402.3451 185.5003 m
342.6335 185.5003 l
342.6335 186.0004 l
402.3451 186.0004 l
f*
106.2924 185.5003 m
106.2924 163.5004 l
105.7924 163.5004 l
105.7924 185.5003 l
f*
105.7924 163.5004 m
36 163.5004 l
36 164.0004 l
105.7924 164.0004 l
f*
171.2313 185.5003 m
171.2313 163.5004 l
170.7313 163.5004 l
170.7313 185.5003 l
f*
170.7313 163.5004 m
106.2924 163.5004 l
106.2924 164.0004 l
170.7313 164.0004 l
f*
216.8833 185.5003 m
216.8833 163.5004 l
216.3832 163.5004 l
216.3832 185.5003 l
f*
216.3832 163.5004 m
171.2313 163.5004 l
171.2313 164.0004 l
216.3832 164.0004 l
f*
267.1699 185.5003 m
267.1699 163.5004 l
266.6699 163.5004 l
266.6699 185.5003 l
f*
266.6699 163.5004 m
216.8833 163.5004 l
216.8833 164.0004 l
266.6699 164.0004 l
f*
342.6335 185.5003 m
342.6335 163.5004 l
342.1335 163.5004 l
342.1335 185.5003 l
f*
342.1335 163.5004 m
267.1699 163.5004 l
267.1699 164.0004 l
342.1335 164.0004 l
f*
402.8451 185.5003 m
402.8451 163.5004 l
402.3451 163.5004 l
402.3451 185.5003 l
f*
402.3451 163.5004 m
342.6335 163.5004 l
342.6335 164.0004 l
402.3451 164.0004 l
f*
576 163.5004 m
402.8451 163.5004 l
402.8451 164.0004 l
576 164.0004 l
f*
106.2924 163.5004 m
106.2924 119.5004 l
105.7924 119.5004 l
105.7924 163.5004 l
f*
105.7924 119.5004 m
36 119.5004 l
36 120.0005 l
105.7924 120.0005 l
f*
171.2313 163.5004 m
171.2313 141.5004 l
170.7313 141.5004 l
170.7313 163.5004 l
f*
170.7313 141.5004 m
106.2924 141.5004 l
106.2924 142.0004 l
170.7313 142.0004 l
f*
216.8833 163.5004 m
216.8833 119.5004 l
216.3832 119.5004 l
216.3832 163.5004 l
f*
216.3832 119.5004 m
171.2313 119.5004 l
171.2313 120.0005 l
216.3832 120.0005 l
f*
267.1699 163.5004 m
267.1699 119.5004 l
266.6699 119.5004 l
266.6699 163.5004 l
f*
266.6699 119.5004 m
216.8833 119.5004 l
216.8833 120.0005 l
266.6699 120.0005 l
f*
342.6335 163.5004 m
342.6335 141.5004 l
342.1335 141.5004 l
342.1335 163.5004 l
f*
342.1335 141.5004 m
267.1699 141.5004 l
267.1699 142.0004 l
342.1335 142.0004 l
f*
402.8451 163.5004 m
402.8451 141.5004 l
402.3451 141.5004 l
402.3451 163.5004 l
f*
402.3451 141.5004 m
342.6335 141.5004 l
342.6335 142.0004 l
402.3451 142.0004 l
f*
576 119.5004 m
402.8451 119.5004 l
402.8451 120.0005 l
576 120.0005 l
f*
171.2313 141.5004 m
171.2313 119.5004 l
170.7313 119.5004 l
170.7313 141.5004 l
f*
170.7313 119.5004 m
106.2924 119.5004 l
106.2924 120.0005 l
170.7313 120.0005 l
f*
342.6335 141.5004 m
342.6335 119.5004 l
342.1335 119.5004 l
342.1335 141.5004 l
f*
342.1335 119.5004 m
267.1699 119.5004 l
267.1699 120.0005 l
342.1335 120.0005 l
f*
402.8451 141.5004 m
402.8451 119.5004 l
402.3451 119.5004 l
402.3451 141.5004 l
f*
402.3451 119.5004 m
342.6335 119.5004 l
342.6335 120.0005 l
402.3451 120.0005 l
f*
106.2924 119.5004 m
106.2924 94.5006 l
105.7924 94.5006 l
105.7924 119.5004 l
f*
105.7924 94.5006 m
36 94.5006 l
36 95.0006 l
105.7924 95.0006 l
f*
171.2313 119.5004 m
171.2313 107.0005 l
170.7313 107.0005 l
170.7313 119.5004 l
f*
170.7313 107.0005 m
106.2924 107.0005 l
106.2924 107.5005 l
170.7313 107.5005 l
f*
216.8833 119.5004 m
216.8833 94.5006 l
216.3832 94.5006 l
216.3832 119.5004 l
f*
216.3832 94.5006 m
171.2313 94.5006 l
171.2313 95.0006 l
216.3832 95.0006 l
f*
267.1699 119.5004 m
267.1699 94.5006 l
266.6699 94.5006 l
266.6699 119.5004 l
f*
266.6699 94.5006 m
216.8833 94.5006 l
216.8833 95.0006 l
266.6699 95.0006 l
f*
342.6335 119.5004 m
342.6335 94.5006 l
342.1335 94.5006 l
342.1335 119.5004 l
f*
342.1335 94.5006 m
267.1699 94.5006 l
267.1699 95.0006 l
342.1335 95.0006 l
f*
402.8451 119.5004 m
402.8451 94.5006 l
402.3451 94.5006 l
402.3451 119.5004 l
f*
402.3451 94.5006 m
342.6335 94.5006 l
342.6335 95.0006 l
402.3451 95.0006 l
f*
576 94.5006 m
402.8451 94.5006 l
402.8451 95.0006 l
576 95.0006 l
f*
171.2313 107.0005 m
171.2313 94.5006 l
170.7313 94.5006 l
170.7313 107.0005 l
f*
170.7313 94.5006 m
106.2924 94.5006 l
106.2924 95.0006 l
170.7313 95.0006 l
f*
36 94.5006 m
576 94.5006 l
576 94.0005 l
36 94.0005 l
f*
0.83 0.64 0.02 0 k
38.7213 634.4504 m
46.3748 634.4504 l
h
f*
75.1748 599.9244 m
82.8283 599.9244 l
h
f*
38.7213 546.4063 m
46.3748 546.4063 l
h
f*
89.5181 533.9339 m
97.1717 533.9339 l
h
f*
84.8126 475.4268 m
92.4661 475.4268 l
h
f*
38.7213 443.9055 m
46.3748 443.9055 l
h
f*
74.7213 431.4331 m
82.3748 431.4331 l
h
f*
86.2866 387.4394 m
93.9402 387.4394 l
h
f*
89.348 343.4457 m
97.0016 343.4457 l
h
f*
83.622 321.4488 m
91.2756 321.4488 l
h
f*
68.5417 262.9417 m
76.1386 262.9417 l
h
f*
81.6378 218.948 m
89.2913 218.948 l
h
f*
63.8929 174.8976 m
71.4898 174.8976 l
h
f*
38.7213 143.4331 m
46.3748 143.4331 l
h
f*
90.0283 108.9071 m
97.6819 108.9071 l
h
f*
0 g
1 j
1 J
7.9999 0 0 7.9999 36 708.4913 cm
BT
/F12 1 Tf
1 TL
0 0 Td
(Table)Tj
2.5866 0 Td
(1.)Tj
/F5 1 Tf
1.2472 0 Td
(\(Continu)Tj
3.7135 0 Td
(ed)Tj
1.0417 0 Td
(\))Tj
/F12 1 Tf
-8.589 -2.1897 Td
(Study)Tj
9.0355 0 Td
(Aspirin/no)Tj
0 -1.1835 Td
(Aspirin)Tj
8.1213 1.1835 Td
(Events)Tj
0 -1.1835 Td
(aspirin/)Tj
0 -1.1906 Td
(none)Tj
5.7047 2.3741 Td
(Follow-up)Tj
0 -1.1835 Td
(duration)Tj
8.7804 1.1835 Td
(Outcom)Tj
3.4442 0 Td
(e)Tj
3.4937 0 Td
(HR/RR)Tj
0 -1.1835 Td
(\(95%)Tj
2.3386 0 Td
(CI\))Tj
5.1874 1.1835 Td
(Comment)Tj
-46.1058 -4.1812 Td
(BREAST)Tj
3.9472 0 Td
(CANCER)Tj
/F5 1 Tf
-3.9472 -1.5661 Td
(McMenam)Tj
4.4433 0 Td
(in)Tj
1.0488 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
-6.4488 -1.1835 Td
([)Tj
0.83 0.64 0.02 0 k
(35)Tj
0 g
(])Tj
10.2685 1.1835 Td
(2,822/12,3)Tj
4.1316 0 Td
(18)Tj
3.7276 0 Td
(261/929)Tj
5.7118 0 Td
(36)Tj
1.7079 0 Td
(years)Tj
5.2158 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1835 Td
(mortality)Tj
6.9874 1.1835 Td
(HR)Tj
1.6158 0 Td
(0.92)Tj
1.8921 0 Td
(\(0.75,)Tj
-3.5079 -1.1835 Td
(1.14\))Tj
-8.9575 -1.5661 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(1.21)Tj
1.8921 0 Td
(\(1.04,)Tj
-3.5079 -1.1906 Td
(1.40\))Tj
-38.7073 -1.5591 Td
(Shiao)Tj
2.4519 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.141 0 Td
([)Tj
0.83 0.64 0.02 0 k
(36)Tj
0 g
(])Tj
6.9024 0 Td
(65/157)Tj
7.1505 0 Td
(11/50)Tj
5.3787 0 Td
(Up)Tj
1.4882 0 Td
(to)Tj
1.0418 0 Td
(10)Tj
-1.8142 -1.1905 Td
(years)Tj
6.0662 1.1905 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1905 Td
(mortality)Tj
6.9874 1.1905 Td
(HR)Tj
1.6158 0 Td
(0.41)Tj
1.8921 0 Td
(\(0.20,)Tj
-3.5079 -1.1905 Td
(0.83\))Tj
7.5261 1.1905 Td
(`aspirin')Tj
3.4583 0 Td
(includes)Tj
3.5717 0 Td
(other)Tj
2.3669 0 Td
(anticoagulant)Tj
5.4638 0 Td
(s)Tj
-31.3443 -2.7496 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(0.67)Tj
1.8921 0 Td
(\(0.35,)Tj
-3.5079 -1.1906 Td
(1.27\))Tj
-38.7073 -1.559 Td
(Ratnasinghe)Tj
5.1803 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
-6.137 -1.1906 Td
([)Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(])Tj
10.5095 1.1906 Td
(8,903/4,06)Tj
4.1315 0 Td
(2)Tj
3.9615 0 Td
(84/47)Tj
4.7622 0 Td
(1721)Tj
2.6575 0 Td
(years)Tj
4.741 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1906 Td
(mortality)Tj
6.9874 1.1906 Td
(RR)Tj
1.4741 0 Td
(0.82)Tj
1.8921 0 Td
(\(0.49,)Tj
-3.3662 -1.1906 Td
(1.36\))Tj
7.5261 1.1906 Td
(Two)Tj
2.0339 0 Td
(cohorts)Tj
3.2386 0 Td
(pooled)Tj
-51.5059 -2.7497 Td
(MsCarthy)Tj
4.252 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(37)Tj
0 g
(])Tj
5.3434 0 Td
(60/52)Tj
7.3134 0 Td
(n.a.)Tj
5.9953 0 Td
(n.a.)Tj
5.9032 0 Td
(Breast)Tj
2.7142 0 Td
(cancer)Tj
-2.2039 -1.1905 Td
(recurrence)Tj
7.2921 1.1905 Td
(HR)Tj
1.6158 0 Td
(0.65)Tj
1.8921 0 Td
(\(0.46,)Tj
-3.5079 -1.1905 Td
(0.91\))Tj
7.5261 1.1905 Td
(Aspirin)Tj
3.2599 0 Td
(and)Tj
1.7433 0 Td
(NSAID)Tj
3.2102 0 Td
(use.)Tj
1.7788 0 Td
(Includes)Tj
3.6496 0 Td
(data)Tj
1.9276 0 Td
(on)Tj
1.2898 0 Td
(PIK3CA)Tj
-51.8107 -2.7496 Td
(Breast)Tj
2.7142 0 Td
(cancer)Tj
2.863 0 Td
(deaths:)Tj
/F12 1 Tf
3.0473 0 Td
(Pooled)Tj
3.1394 0 Td
(HR)Tj
1.6583 0 Td
(for)Tj
1.4882 0 Td
(three)Tj
2.4024 0 Td
(studies:)Tj
3.4157 0 Td
(0.70)Tj
/F5 1 Tf
1.9772 0 Td
(\(0.471.)Tj
3.2245 0 Td
(03\))Tj
1.5307 0 Td
(heterogeneit)Tj
5.0032 0 Td
(y)Tj
0.6874 0 Td
(p)Tj
0.7512 0 Td
(=)Tj
0.8078 0 Td
(0.04,)Tj
2.119 0 Td
(Egger's)Tj
3.1181 0 Td
(test)Tj
1.6228 0 Td
(P)Tj
/F11 1 Tf
(<)Tj
/F5 1 Tf
(0.16)Tj
-41.1593 -1.1905 Td
(All)Tj
1.4102 0 Td
(cause)Tj
2.4095 0 Td
(deaths:)Tj
/F12 1 Tf
3.0472 0 Td
(Pooled)Tj
3.1394 0 Td
(HR)Tj
1.6583 0 Td
(for)Tj
1.4882 0 Td
(two)Tj
1.7788 0 Td
(studies)Tj
3.1677 0 Td
(0.98)Tj
/F5 1 Tf
1.9772 0 Td
(\(0.561.)Tj
3.2244 0 Td
(71\))Tj
1.5307 0 Td
(heterogeneit)Tj
5.0032 0 Td
(y)Tj
0.6874 0 Td
(p)Tj
0.7512 0 Td
(=)Tj
0.8079 0 Td
(0.08,)Tj
2.126 0 Td
(Egger's)Tj
3.1111 0 Td
(test)Tj
1.6228 0 Td
(not)Tj
1.5945 0 Td
(possible)Tj
/F12 1 Tf
-52.2287 -1.8142 Td
(PROSTAT)Tj
4.5142 0 Td
(E)Tj
0.8149 0 Td
(CANCER)Tj
/F5 1 Tf
-5.3291 -1.5591 Td
(Osborrn)Tj
3.6567 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(38)Tj
0 g
(])Tj
5.4638 0 Td
(147/14)Tj
2.7142 0 Td
(2)Tj
5.1521 0 Td
(2/5)Tj
5.2583 0 Td
(6)Tj
0.7086 0 Td
(years)Tj
5.7119 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1906 Td
(mortality)Tj
6.9874 1.1906 Td
(HR)Tj
1.6158 0 Td
(0.20)Tj
1.8921 0 Td
(\(0.04,)Tj
-3.5079 -1.1906 Td
(1.13\))Tj
-38.7073 -1.559 Td
(Veitonmaki)Tj
5.0031 0 Td
(et)Tj
0.9638 0 Td
(al.)Tj
-5.9669 -1.1906 Td
([)Tj
0.83 0.64 0.02 0 k
(39)Tj
0 g
(])Tj
10.8638 1.1906 Td
(332/6,20)Tj
3.4229 0 Td
(5)Tj
4.0819 0 Td
(23/592)Tj
5.6197 0 Td
(7.5)Tj
1.4103 0 Td
(years)Tj
5.3646 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1906 Td
(mortality)Tj
6.9874 1.1906 Td
(HR)Tj
1.6158 0 Td
(0.62)Tj
1.8921 0 Td
(\(0.30,)Tj
-3.5079 -1.1906 Td
(1.32\))Tj
7.5261 1.1906 Td
(Estimates)Tj
4.0819 0 Td
(with)Tj
2.0126 0 Td
(`lag)Tj
1.6158 0 Td
(time')Tj
2.2606 0 Td
(ignored)Tj
-56.2043 -2.7497 Td
(Zhou)Tj
2.4023 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.141 0 Td
([)Tj
0.83 0.64 0.02 0 k
(40)Tj
0 g
(])Tj
7.7741 0 Td
(?/?)Tj
6.0945 0 Td
(103/67)Tj
5.4709 0 Td
(27)Tj
1.7079 0 Td
(years)Tj
5.2158 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1905 Td
(mortality)Tj
6.9874 1.1905 Td
(HR)Tj
1.6158 0 Td
(0.83)Tj
1.8921 0 Td
(\(0.72,)Tj
-3.5079 -1.1905 Td
(0.95\))Tj
7.5261 1.1905 Td
(Results)Tj
3.0827 0 Td
(of)Tj
1.0276 0 Td
(daily)Tj
2.1756 0 Td
(aspirin)Tj
3.0118 0 Td
(in)Tj
1.0488 0 Td
(two)Tj
1.7292 0 Td
(cohorts)Tj
3.2386 0 Td
(pooled)Tj
-31.7979 -2.7496 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(0.75)Tj
1.8921 0 Td
(\(0.66,)Tj
-3.5079 -1.1905 Td
(0.86\))Tj
-38.7073 -1.5591 Td
(Cardwell)Tj
3.8409 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1481 0 Td
([)Tj
0.83 0.64 0.02 0 k
(41)Tj
0 g
(])Tj
4.5638 0 Td
(1,184/3,53)Tj
4.1315 0 Td
(1)Tj
3.4867 0 Td
(616/568)Tj
5.4779 0 Td
(412)Tj
2.1827 0 Td
(years)Tj
4.9749 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1906 Td
(mortality)Tj
6.9874 1.1906 Td
(OR)Tj
1.5945 0 Td
(1.02)Tj
1.8922 0 Td
(\(0.78,)Tj
-3.4867 -1.1906 Td
(1.34\))Tj
-8.9575 -1.559 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(OR)Tj
1.5945 0 Td
(1.22)Tj
-1.5945 -1.1906 Td
(\(1.02,1.45)Tj
3.8906 0 Td
(\))Tj
-42.5979 -1.5591 Td
(Ratnasing)Tj
4.2307 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(])Tj
3.9402 0 Td
(14,943/8,8)Tj
4.1316 0 Td
(06)Tj
3.0189 0 Td
(2,735/3,17)Tj
4.1315 0 Td
(0)Tj
1.8142 0 Td
(1721)Tj
2.6575 0 Td
(years)Tj
4.741 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1905 Td
(mortality)Tj
6.9874 1.1905 Td
(RR)Tj
1.4741 0 Td
(1.11)Tj
1.8921 0 Td
(\(0.60)Tj
-3.3662 -1.1905 Td
(2.05\))Tj
-38.7073 -1.5591 Td
(Downer)Tj
3.5079 0 Td
(et)Tj
0.9637 0 Td
(al.)Tj
1.141 0 Td
([)Tj
0.83 0.64 0.02 0 k
(42)Tj
0 g
(])Tj
6.13 0 Td
(3,277)Tj
6.3851 0 Td
(190/307)Tj
6.874 0 Td
(n.a.)Tj
5.7615 0 Td
(Cause)Tj
2.6504 0 Td
(specific)Tj
-1.6937 -1.1906 Td
(mortality)Tj
6.9874 1.1906 Td
(HR)Tj
1.6158 0 Td
(0.68)Tj
1.8921 0 Td
(\(0.52,)Tj
-3.5079 -1.1906 Td
(0.90\))Tj
7.5261 1.1906 Td
(Long-ter)Tj
3.515 0 Td
(m)Tj
1.0559 0 Td
(follow-up)Tj
4.1244 0 Td
(of)Tj
1.0276 0 Td
(a)Tj
0.6661 0 Td
(previous)Tj
3.4442 0 Td
(ly)Tj
0.9354 0 Td
(randomised)Tj
-14.7686 -1.1906 Td
(trial)Tj
-16.4836 -1.5661 Td
(All-cause)Tj
3.9473 0 Td
(mortality)Tj
5.0102 0 Td
(HR)Tj
1.6158 0 Td
(0.72)Tj
1.8921 0 Td
(\(0.61,)Tj
-3.5079 -1.1835 Td
(0.84\))Tj
/F12 1 Tf
-38.7073 -1.8142 Td
(OTHER)Tj
3.6567 0 Td
(CANCERS)Tj
/F5 1 Tf
-3.6567 -1.559 Td
(Bar)Tj
1.6228 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.141 0 Td
([)Tj
0.83 0.64 0.02 0 k
(43)Tj
0 g
(])Tj
7.9725 0 Td
(31/11)Tj
6.9095 0 Td
(29/34)Tj
5.7402 0 Td
(4)Tj
0.7086 0 Td
(years)Tj
4.2166 0 Td
(Recurrent-free)Tj
0 -1.1906 Td
(survival)Tj
9.4394 1.1906 Td
(HR)Tj
1.6158 0 Td
(0.52)Tj
1.8921 0 Td
(\(0.30,)Tj
-3.5079 -1.1906 Td
(0.90\))Tj
-27.5317 -1.5591 Td
(Ovarian)Tj
11.8631 0 Td
(3173)Tj
2.6575 0 Td
(month)Tj
3.5717 0 Td
(Overall)Tj
3.1748 0 Td
(survival)Tj
6.2646 0 Td
(HR)Tj
1.6158 0 Td
(0.50)Tj
1.8921 0 Td
(\(0.29,)Tj
-3.5079 -1.1905 Td
(0.84\))Tj
-38.7073 -1.5591 Td
(Matsuo)Tj
3.2598 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1481 0 Td
([)Tj
0.83 0.64 0.02 0 k
(44)Tj
0 g
(])Tj
5.4992 0 Td
(158/1,52)Tj
3.4229 0 Td
(9)Tj
4.7197 0 Td
(127)Tj
4.5851 0 Td
(31)Tj
1.1834 0 Td
(months)Tj
4.493 0 Td
(Disease)Tj
3.2528 0 Td
(specific)Tj
6.1866 0 Td
(HR)Tj
1.6158 0 Td
(0.46)Tj
1.8921 0 Td
(\(0.25,)Tj
-3.5079 -1.1906 Td
(0.86\))Tj
-28.8569 -1.559 Td
(Endome)Tj
3.4016 0 Td
(trium.)Tj
16.0159 0 Td
(Overall)Tj
3.1748 0 Td
(survival)Tj
6.2646 0 Td
(HR)Tj
1.6158 0 Td
(0.23)Tj
1.8921 0 Td
(\(0.08,)Tj
-3.5079 -1.1906 Td
(0.64\))Tj
-38.7073 -1.5661 Td
(Li)Tj
1.0417 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(45)Tj
0 g
(])Tj
8.5537 0 Td
(60/60)Tj
0.085 -1.1835 Td
(Liver)Tj
7.7599 1.1835 Td
(?)Tj
4.0536 0 Td
(80)Tj
1.1834 0 Td
(months)Tj
4.493 0 Td
(Total)Tj
2.3386 0 Td
(mortality)Tj
7.1008 0 Td
(HR)Tj
1.6158 0 Td
(0.60)Tj
1.8921 0 Td
(\(0.35,)Tj
-3.5079 -1.1835 Td
(1.03\))Tj
7.5261 1.1835 Td
(Matched)Tj
3.7701 0 Td
(pairs)Tj
-50.0035 -2.7497 Td
(Veitonmaki)Tj
5.0031 0 Td
(et)Tj
0.9638 0 Td
(al.)Tj
-5.9669 -1.1834 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(])Tj
10.2685 1.1834 Td
(7,183/17,5)Tj
4.1316 0 Td
(09)Tj
4.4433 0 Td
(19/6)Tj
0.241 -1.1834 Td
(6/4)Tj
5.0173 1.1834 Td
(15)Tj
1.1835 0 Td
(years)Tj
3.9827 0 Td
(Disease)Tj
3.2528 0 Td
(specific)Tj
6.1866 0 Td
(HR)Tj
1.6158 0 Td
(1.27)Tj
1.8921 0 Td
(\(0.57,)Tj
-3.5079 -1.1834 Td
(2.83\))Tj
-26.9364 -1.5662 Td
(Lung)Tj
-0.7441 -1.1835 Td
(Pancreas)Tj
18.2411 1.1835 Td
(Disease)Tj
3.2528 0 Td
(specific)Tj
6.1866 0 Td
(HR)Tj
1.6158 0 Td
(0.85)Tj
1.8921 0 Td
(\(0.24,)Tj
-3.5079 -1.1835 Td
(3.05\))Tj
-38.7073 -1.5661 Td
(Maddison)Tj
4.3086 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1481 0 Td
([)Tj
0.83 0.64 0.02 0 k
(46)Tj
0 g
(])Tj
5.2796 0 Td
(60/60)Tj
6.3 0 Td
(284)Tj
1.6654 0 Td
(total)Tj
4.4929 0 Td
(?5)Tj
1.0843 0 Td
(years)Tj
4.0323 0 Td
(Disease)Tj
3.2528 0 Td
(specific)Tj
6.1866 0 Td
(HR)Tj
1.6158 0 Td
(1.00)Tj
-1.6158 -1.1835 Td
(\(0.73,1.37)Tj
3.8906 0 Td
(\))Tj
-30.827 -0.3756 Td
(Lung)Tj
50.8043 -1.8142 Td
(\()Tj
/F10 1 Tf
[()-2()11()22()7( )12()18(\n)4()]TJ
3.9828 0 Td
[()]TJ
/F5 1 Tf
0.6023 0 Td
(\))Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
32.2798 0 Td
(6)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
176 0 obj
<>stream
endstream
endobj
177 0 obj
<>stream
endstream
endobj
178 0 obj
<>stream
endstream
endobj
179 0 obj
<>stream
endstream
endobj
180 0 obj
<>stream
endstream
endobj
181 0 obj
<>stream
endstream
endobj
182 0 obj
<>stream
endstream
endobj
183 0 obj
<>stream
endstream
endobj
184 0 obj
<>stream
endstream
endobj
185 0 obj
<>stream
endstream
endobj
186 0 obj
<>stream
endstream
endobj
187 0 obj
<>stream
endstream
endobj
188 0 obj
<>stream
endstream
endobj
189 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
190 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 191 0 R/Contents 192 0 R/TrimBox[0 0 612 792]>>
endobj
191 0 obj
[193 0 R 194 0 R 195 0 R 196 0 R 197 0 R 198 0 R 199 0 R 200 0 R 201 0 R 202 0 R 203 0 R 204 0 R 205 0 R 206 0 R 207 0 R 208 0 R 209 0 R 210 0 R 211 0 R 212 0 R 213 0 R 214 0 R 215 0 R]
endobj
193 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref027)>>
endobj
194 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref031)>>
endobj
195 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref022)>>
endobj
196 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref023)>>
endobj
197 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref027)>>
endobj
198 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.t001)>>
endobj
199 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
200 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref051)>>
endobj
201 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s007)>>
endobj
202 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref052)>>
endobj
203 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref053)>>
endobj
204 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref036)>>
endobj
205 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref047)>>
endobj
206 0 obj
<>/Border[0 0 0]/A 216 0 R>>
endobj
216 0 obj
<>
endobj
207 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.t002)>>
endobj
208 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref026)>>
endobj
209 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref036)>>
endobj
210 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref038)>>
endobj
211 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref048)>>
endobj
212 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref049)>>
endobj
213 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref050)>>
endobj
214 0 obj
<>/Border[0 0 0]/A 217 0 R>>
endobj
217 0 obj
<>
endobj
215 0 obj
<>/Border[0 0 0]/A 218 0 R>>
endobj
218 0 obj
<>
endobj
192 0 obj
[219 0 R 220 0 R 221 0 R 222 0 R 223 0 R 224 0 R 225 0 R 226 0 R 227 0 R 228 0 R 229 0 R 230 0 R 231 0 R 232 0 R 233 0 R 234 0 R 235 0 R 236 0 R 237 0 R 238 0 R]
endobj
219 0 obj
<>stream
q
0.83 0.64 0.02 0 k
261.4677 531.6661 m
270.9354 531.6661 l
h
f*
273.2031 531.6661 m
282.7276 531.6661 l
h
f*
203.4142 479.6787 m
212.9386 479.6787 l
h
f*
215.1496 479.6787 m
224.674 479.6787 l
h
f*
226.9417 479.6787 m
236.4661 479.6787 l
h
f*
329.3858 353.8772 m
358.2992 353.8772 l
h
f*
461.0268 353.8772 m
470.4378 353.8772 l
h
f*
273.4866 288.9071 m
282.9543 288.9071 l
h
f*
217.7008 275.8677 m
244.063 275.8677 l
h
f*
339.7606 249.9024 m
349.285 249.9024 l
h
f*
351.5528 249.9024 m
361.0772 249.9024 l
h
f*
260.6173 236.863 m
270.085 236.863 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 211.9748 558.7653 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Twenty-one)Tj
5.0739 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(studies)Tj
2.9877 0 Td
(of)Tj
1.0148 0 Td
(colorectal)Tj
4.0988 0 Td
(cancer)Tj
2.846 0 Td
(also)Tj
1.7688 0 Td
(report)Tj
2.7042 0 Td
(all-cause)Tj
3.6681 0 Td
(mortality.)Tj
4.1442 0 Td
(In)Tj
1.1055 0 Td
(19)Tj
1.1735 0 Td
(the)Tj
-34.2649 -1.2982 Td
(association)Tj
4.626 0 Td
(with)Tj
1.9956 0 Td
(aspirin)Tj
2.9877 0 Td
(suggest)Tj
3.1238 0 Td
(a)Tj
0.6519 0 Td
(reduction)Tj
4.1159 0 Td
(with)Tj
1.9956 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0375 0 Td
(ten)Tj
1.491 0 Td
(the)Tj
1.4684 0 Td
(reduction)Tj
4.1158 0 Td
(is)Tj
0.8448 0 Td
(significant.)Tj
-33.1708 -1.3039 Td
(In)Tj
1.1055 0 Td
(two)Tj
1.7121 0 Td
(studies)Tj
2.9877 0 Td
([)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(31)Tj
0 g
(])Tj
3.0273 0 Td
(the)Tj
1.4684 0 Td
(association)Tj
4.6261 0 Td
(with)Tj
2.0012 0 Td
(aspirin)Tj
2.9821 0 Td
(is)Tj
0.8504 0 Td
(consistent)Tj
4.2576 0 Td
(with)Tj
1.9955 0 Td
(an)Tj
1.2019 0 Td
(excess)Tj
2.6816 0 Td
(in)Tj
1.0318 0 Td
(all-cause)Tj
-31.9292 -1.2983 Td
(deaths)Tj
2.7892 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0318 0 Td
(both)Tj
2.0636 0 Td
(the)Tj
1.4684 0 Td
(association)Tj
4.6261 0 Td
(is)Tj
0.8447 0 Td
(significant)Tj
4.388 0 Td
(\(at)Tj
1.2926 0 Td
(P)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
-0.004 Tc
(0.05\).)Tj
3.7644 0 Td
(Eighteen)Tj
3.7417 0 Td
(studies)Tj
2.9877 0 Td
(of)Tj
1.0091 0 Td
(colorectal)Tj
4.1046 0 Td
(can-)Tj
-35.841 -1.2983 Td
(cer)Tj
1.4343 0 Td
(report)Tj
2.7099 0 Td
(all-cause)Tj
3.668 0 Td
(mortality)Tj
3.9174 0 Td
(as)Tj
1.0148 0 Td
(hazard)Tj
2.9254 0 Td
(ratios)Tj
2.4604 0 Td
(and)Tj
1.7291 0 Td
(pooling)Tj
3.2769 0 Td
(these)Tj
2.2563 0 Td
(gives)Tj
2.194 0 Td
(HR)Tj
1.6044 0 Td
(0.80)Tj
1.8766 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2245 0 Td
(0.72,)Tj
-34.5597 -1.2982 Td
(0.89;)Tj
2.0976 0 Td
(heterogeneity)Tj
5.6522 0 Td
(P)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
-0.004 Tc
(0.0005;)Tj
4.3767 0 Td
(Eggers)Tj
2.88 0 Td
(test)Tj
1.5987 0 Td
(for)Tj
1.3833 0 Td
(bias)Tj
1.7915 0 Td
(P)Tj
0.7767 0 Td
(=)Tj
0.7993 0 Td
(0.002\).)Tj
2.914 0 Td
(The)Tj
1.7858 0 Td
(omission)Tj
3.8551 0 Td
(of)Tj
1.0148 0 Td
(three)Tj
2.2677 0 Td
(studies)Tj
-33.1934 -1.3039 Td
([)Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(],)Tj
4.4276 0 Td
(selected)Tj
3.3506 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.4684 0 Td
(basis)Tj
2.1486 0 Td
(of)Tj
1.0148 0 Td
(sensitivity)Tj
4.2236 0 Td
(analyses,)Tj
3.7077 0 Td
(reduced)Tj
3.4412 0 Td
(heterogeneity)Tj
5.6523 0 Td
(\(P)Tj
1.1225 0 Td
(=)Tj
0.7994 0 Td
(0.03\))Tj
2.211 0 Td
(and)Tj
-34.8432 -1.2983 Td
(gave)Tj
1.9955 0 Td
(HR)Tj
1.6101 0 Td
(0.78)Tj
1.8708 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.72,)Tj
2.0976 0 Td
(0.85\))Tj
-9.8701 -1.2983 Td
(Overall)Tj
3.1464 0 Td
(therefore,)Tj
4.0762 0 Td
(the)Tj
1.474 0 Td
(evidence)Tj
3.7077 0 Td
(on)Tj
1.2756 0 Td
(colorectal)Tj
4.1045 0 Td
(cancer)Tj
2.8403 0 Td
(is)Tj
0.8504 0 Td
(consistent)Tj
4.2576 0 Td
(that)Tj
1.7745 0 Td
(aspirin)Tj
2.9877 0 Td
(is)Tj
0.8504 0 Td
(associated)Tj
-32.5415 -1.3039 Td
(with)Tj
1.9898 0 Td
(a)Tj
0.6463 0 Td
(reduction)Tj
4.1046 0 Td
(in)Tj
1.0318 0 Td
(colorectal)Tj
4.0932 0 Td
(mortality)Tj
3.9061 0 Td
(and)Tj
1.7235 0 Td
(a)Tj
0.6463 0 Td
(probable)Tj
3.7247 0 Td
(reduction)Tj
4.1102 0 Td
(in)Tj
1.0261 0 Td
(the)Tj
1.4627 0 Td
(incidence)Tj
4.0648 0 Td
(of)Tj
1.0092 0 Td
(metastatic)Tj
-33.5393 -1.2983 Td
(spread.)Tj
3.0783 0 Td
(Egger's)Tj
3.0898 0 Td
(test)Tj
1.6044 0 Td
(however)Tj
3.6113 0 Td
(suggests)Tj
3.4809 0 Td
(that)Tj
1.7802 0 Td
(there)Tj
2.262 0 Td
(may)Tj
1.9276 0 Td
(be)Tj
1.1508 0 Td
(some)Tj
2.3301 0 Td
(publication)Tj
4.7678 0 Td
(bias)Tj
1.7858 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(available)Tj
-33.3748 -1.2982 Td
(data)Tj
1.9105 0 Td
(for)Tj
1.3889 0 Td
(this)Tj
1.6725 0 Td
(cancer.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 384.9448 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Breast)Tj
2.8724 0 Td
(cancer)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 367.9937 cm
BT
/F5 1 Tf
1 TL
-0.01 Tc
0 0 Td
(Our)Tj
1.8481 0 Td
(searches)Tj
3.498 0 Td
(identified)Tj
3.9968 0 Td
(no)Tj
1.2642 0 Td
(study)Tj
2.3584 0 Td
(of)Tj
1.0035 0 Td
(aspirin)Tj
2.9423 0 Td
(randomised)Tj
4.9493 0 Td
(to)Tj
1.0148 0 Td
(patients)Tj
3.3165 0 Td
(with)Tj
1.9786 0 Td
(breast)Tj
2.5738 0 Td
(cancer.)Tj
3.0331 0 Td
(However,)Tj
-33.7774 -1.3039 Td
(14)Tj
1.1565 0 Td
(observational)Tj
5.5048 0 Td
(studies)Tj
2.9424 0 Td
(listed)Tj
2.3074 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0261 0 Td
(Table)Tj
2.4094 0 Td
(1)Tj
0 g
0.6917 0 Td
(and)Tj
1.7121 0 Td
(in)Tj
1.0205 0 Td
(our)Tj
1.61 0 Td
(earlier)Tj
2.7156 0 Td
(report)Tj
2.6702 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.8312 0 Td
(have)Tj
2.0352 0 Td
(been)Tj
2.0977 0 Td
(reported,)Tj
3.8324 0 Td
(and)Tj
-35.5632 -1.2982 Td
(in)Tj
1.0204 0 Td
(eleven)Tj
2.7043 0 Td
(the)Tj
1.4513 0 Td
(association)Tj
4.5637 0 Td
(suggests)Tj
3.4356 0 Td
(benefit,)Tj
3.1521 0 Td
(significant)Tj
4.3256 0 Td
(in)Tj
1.0205 0 Td
(six)Tj
1.2983 0 Td
(studies.)Tj
3.1634 0 Td
(Three)Tj
2.5455 0 Td
(of)Tj
1.0035 0 Td
(the)Tj
1.4513 0 Td
(studies)Tj
2.9423 0 Td
(report)Tj
-34.0778 -1.2983 Td
(associations)Tj
4.9152 0 Td
(of)Tj
1.0035 0 Td
(1.00)Tj
1.8481 0 Td
(or)Tj
1.0885 0 Td
(greater)Tj
2.965 0 Td
(with)Tj
1.9729 0 Td
(aspirin,)Tj
3.1635 0 Td
(but)Tj
1.5364 0 Td
(in)Tj
1.0204 0 Td
(none)Tj
2.2224 0 Td
(of)Tj
1.0034 0 Td
(these)Tj
2.2281 0 Td
(is)Tj
0.8333 0 Td
(the)Tj
1.4514 0 Td
(association)Tj
4.5637 0 Td
(significant.)Tj
-0.004 Tc
-30.6196 -1.3039 Td
(Eight)Tj
2.3527 0 Td
(studies)Tj
2.982 0 Td
(report)Tj
2.7099 0 Td
(the)Tj
1.4684 0 Td
(association)Tj
4.6318 0 Td
(with)Tj
1.9955 0 Td
(aspirin)Tj
2.9877 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(hazard)Tj
2.931 0 Td
(ratio,)Tj
2.3187 0 Td
(and)Tj
1.7348 0 Td
(pooling)Tj
3.2768 0 Td
(these)Tj
2.2507 0 Td
(gives)Tj
-34.503 -1.2983 Td
(HR)Tj
1.61 0 Td
(0.69)Tj
1.8709 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2245 0 Td
(0.53,)Tj
2.0977 0 Td
(0.92;)Tj
2.0976 0 Td
(heterogeneity)Tj
5.6522 0 Td
(0.0005)Tj
2.8233 0 Td
(and)Tj
1.7291 0 Td
(Egger's)Tj
3.0898 0 Td
(test)Tj
1.6044 0 Td
(for)Tj
1.3833 0 Td
(bias)Tj
1.7915 0 Td
(P)Tj
0.7767 0 Td
(=)Tj
0.7993 0 Td
(0.14\).)Tj
2.4378 0 Td
(The)Tj
1.7858 0 Td
(exclu-)Tj
-35.0416 -1.2982 Td
(sion)Tj
1.9048 0 Td
(of)Tj
1.0148 0 Td
(one)Tj
1.6951 0 Td
(study)Tj
2.3924 0 Td
([)Tj
0.83 0.64 0.02 0 k
(51)Tj
0 g
(])Tj
1.8482 0 Td
(reduces)Tj
3.2825 0 Td
(heterogeneity)Tj
5.6523 0 Td
(\(P)Tj
1.1168 0 Td
(=)Tj
0.7994 0 Td
(0.80\))Tj
2.211 0 Td
(and)Tj
1.7291 0 Td
(gives)Tj
2.194 0 Td
(HR)Tj
1.6101 0 Td
(0.80)Tj
1.8708 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.66,)Tj
2.0976 0 Td
(0.97\))Tj
-34.9112 -1.304 Td
(\(see)Tj
0.83 0.64 0.02 0 k
1.7688 0 Td
(S3)Tj
1.1678 0 Td
(File)Tj
0 g
(\).)Tj
-1.7404 -1.2982 Td
(On)Tj
1.5193 0 Td
(the)Tj
1.4684 0 Td
(occurrence)Tj
4.6658 0 Td
(of)Tj
1.0148 0 Td
(metastatic)Tj
4.2746 0 Td
(spread)Tj
2.8573 0 Td
(in)Tj
1.0318 0 Td
(breast)Tj
2.6192 0 Td
(cancer,)Tj
3.067 0 Td
(evidence)Tj
3.7134 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(reduction)Tj
4.1158 0 Td
(with)Tj
1.9956 0 Td
(aspi-)Tj
-35.206 -1.2983 Td
(rin)Tj
1.4059 0 Td
(is)Tj
0.8504 0 Td
(shown)Tj
2.846 0 Td
(in)Tj
1.0375 0 Td
(three)Tj
2.262 0 Td
(studies.)Tj
3.2145 0 Td
(Two)Tj
2.0182 0 Td
([)Tj
0.83 0.64 0.02 0 k
(52)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(53)Tj
0 g
(])Tj
3.0274 0 Td
(give)Tj
1.8312 0 Td
(a)Tj
0.6576 0 Td
(combined)Tj
4.2406 0 Td
(RR)Tj
1.4627 0 Td
(of)Tj
1.0148 0 Td
(0.92)Tj
1.8765 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2189 0 Td
(0.86.)Tj
2.0976 0 Td
(0.99\))Tj
2.2167 0 Td
(and)Tj
-35.5462 -1.3039 Td
(another)Tj
3.3278 0 Td
(study)Tj
2.3924 0 Td
([)Tj
0.83 0.64 0.02 0 k
(36)Tj
0 g
(])Tj
1.8482 0 Td
(gives)Tj
2.194 0 Td
(HR)Tj
1.6101 0 Td
(0.34)Tj
1.8708 0 Td
(\(0.15,)Tj
2.4378 0 Td
(0.81\).)Tj
ET
Q
q
0.45 0.36 0.35 0.01 k
1 j
1 J
0 w
36 700.9999 m
576 700.9999 l
576 700.4999 l
36 700.4999 l
f*
106.2924 700.4999 m
106.2924 668.9999 l
105.7924 668.9999 l
105.7924 700.4999 l
f*
105.7924 668.9999 m
36 668.9999 l
36 669.4999 l
105.7924 669.4999 l
f*
171.2313 700.4999 m
171.2313 668.9999 l
170.7313 668.9999 l
170.7313 700.4999 l
f*
170.7313 668.9999 m
106.2924 668.9999 l
106.2924 669.4999 l
170.7313 669.4999 l
f*
216.8833 700.4999 m
216.8833 668.9999 l
216.3832 668.9999 l
216.3832 700.4999 l
f*
216.3832 668.9999 m
171.2313 668.9999 l
171.2313 669.4999 l
216.3832 669.4999 l
f*
267.1699 700.4999 m
267.1699 668.9999 l
266.6699 668.9999 l
266.6699 700.4999 l
f*
266.6699 668.9999 m
216.8833 668.9999 l
216.8833 669.4999 l
266.6699 669.4999 l
f*
342.6335 700.4999 m
342.6335 668.9999 l
342.1335 668.9999 l
342.1335 700.4999 l
f*
342.1335 668.9999 m
267.1699 668.9999 l
267.1699 669.4999 l
342.1335 669.4999 l
f*
402.8451 700.4999 m
402.8451 668.9999 l
402.3451 668.9999 l
402.3451 700.4999 l
f*
402.3451 668.9999 m
342.6335 668.9999 l
342.6335 669.4999 l
402.3451 669.4999 l
f*
576 668.9999 m
402.8451 668.9999 l
402.8451 669.4999 l
576 669.4999 l
f*
106.2924 668.9999 m
106.2924 625 l
105.7924 625 l
105.7924 668.9999 l
f*
105.7924 625 m
36 625 l
36 625.5 l
105.7924 625.5 l
f*
171.2313 668.9999 m
171.2313 625 l
170.7313 625 l
170.7313 668.9999 l
f*
170.7313 625 m
106.2924 625 l
106.2924 625.5 l
170.7313 625.5 l
f*
216.8833 668.9999 m
216.8833 625 l
216.3832 625 l
216.3832 668.9999 l
f*
216.3832 625 m
171.2313 625 l
171.2313 625.5 l
216.3832 625.5 l
f*
267.1699 668.9999 m
267.1699 625 l
266.6699 625 l
266.6699 668.9999 l
f*
266.6699 625 m
216.8833 625 l
216.8833 625.5 l
266.6699 625.5 l
f*
342.6335 668.9999 m
342.6335 646.9999 l
342.1335 646.9999 l
342.1335 668.9999 l
f*
342.1335 646.9999 m
267.1699 646.9999 l
267.1699 647.5 l
342.1335 647.5 l
f*
402.8451 668.9999 m
402.8451 646.9999 l
402.3451 646.9999 l
402.3451 668.9999 l
f*
402.3451 646.9999 m
342.6335 646.9999 l
342.6335 647.5 l
402.3451 647.5 l
f*
576 625 m
402.8451 625 l
402.8451 625.5 l
576 625.5 l
f*
342.6335 646.9999 m
342.6335 625 l
342.1335 625 l
342.1335 646.9999 l
f*
342.1335 625 m
267.1699 625 l
267.1699 625.5 l
342.1335 625.5 l
f*
402.8451 646.9999 m
402.8451 625 l
402.3451 625 l
402.3451 646.9999 l
f*
402.3451 625 m
342.6335 625 l
342.6335 625.5 l
402.3451 625.5 l
f*
0.83 0.64 0.02 0 k
71.4898 658.4315 m
79.1433 658.4315 l
h
f*
36 611.9433 m
186.7465 611.9433 l
h
f*
0 g
7.9999 0 0 7.9999 36 708.4913 cm
BT
/F12 1 Tf
1 TL
0 0 Td
(Table)Tj
2.5866 0 Td
(1.)Tj
/F5 1 Tf
1.2472 0 Td
(\(Continu)Tj
3.7135 0 Td
(ed)Tj
1.0417 0 Td
(\))Tj
/F12 1 Tf
-8.589 -2.1897 Td
(Study)Tj
9.0355 0 Td
(Aspirin/no)Tj
0 -1.1835 Td
(Aspirin)Tj
8.1213 1.1835 Td
(Events)Tj
0 -1.1835 Td
(aspirin/)Tj
0 -1.1906 Td
(none)Tj
5.7047 2.3741 Td
(Follow-up)Tj
0 -1.1835 Td
(duration)Tj
8.7804 1.1835 Td
(Outcom)Tj
3.4442 0 Td
(e)Tj
3.4937 0 Td
(HR/RR)Tj
0 -1.1835 Td
(\(95%)Tj
2.3386 0 Td
(CI\))Tj
5.1874 1.1835 Td
(Comment)Tj
/F5 1 Tf
-46.1058 -3.9331 Td
(Kim)Tj
1.9984 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(47)Tj
0 g
(])Tj
6.1017 0 Td
(Head)Tj
2.3953 0 Td
(&)Tj
0.9354 0 Td
(neck)Tj
4.5993 0 Td
(81/1311)Tj
6.1441 0 Td
(24192)Tj
-0.085 -1.1906 Td
(months)Tj
5.0811 1.1906 Td
(Disease)Tj
3.2528 0 Td
(specific)Tj
6.1866 0 Td
(HR)Tj
1.6158 0 Td
(1.30)Tj
1.8921 0 Td
(\(0.78,)Tj
-3.5079 -1.1906 Td
(2.18\))Tj
-9.4394 -1.5591 Td
(Overall)Tj
3.1748 0 Td
(survival)Tj
6.2646 0 Td
(HR)Tj
1.6158 0 Td
(1.30)Tj
1.8921 0 Td
(\(0.96,)Tj
-3.5079 -1.1905 Td
(1.92\))Tj
0.83 0.64 0.02 0 k
/F8 1 Tf
-0.025 Tc
-38.7073 -1.8709 Td
(https://do)Tj
3.5575 0 Td
(i.org/10.1371/j)Tj
5.4425 0 Td
(ournal.pone)Tj
4.4079 0 Td
(.0203957.t001)Tj
ET
Q
q
0.45 0.36 0.35 0.01 k
1 j
1 J
0 w
36 209.8579 m
576 209.8579 l
576 209.3579 l
36 209.3579 l
f*
180.2769 209.3579 m
180.2769 187.3579 l
179.7769 187.3579 l
179.7769 209.3579 l
f*
179.7769 187.3579 m
36 187.3579 l
36 187.8579 l
179.7769 187.8579 l
f*
294.4548 209.3579 m
294.4548 187.3579 l
293.9547 187.3579 l
293.9547 209.3579 l
f*
293.9547 187.3579 m
180.2769 187.3579 l
180.2769 187.8579 l
293.9547 187.8579 l
f*
419.7645 209.3579 m
419.7645 187.3579 l
419.2645 187.3579 l
419.2645 209.3579 l
f*
419.2645 187.3579 m
294.4548 187.3579 l
294.4548 187.8579 l
419.2645 187.8579 l
f*
575.9991 187.3579 m
419.7645 187.3579 l
419.7645 187.8579 l
575.9991 187.8579 l
f*
180.2769 187.3579 m
180.2769 174.858 l
179.7769 174.858 l
179.7769 187.3579 l
f*
179.7769 174.858 m
36 174.858 l
36 175.358 l
179.7769 175.358 l
f*
294.4548 187.3579 m
294.4548 174.858 l
293.9547 174.858 l
293.9547 187.3579 l
f*
293.9547 174.858 m
180.2769 174.858 l
180.2769 175.358 l
293.9547 175.358 l
f*
419.7645 187.3579 m
419.7645 174.858 l
419.2645 174.858 l
419.2645 187.3579 l
f*
419.2645 174.858 m
294.4548 174.858 l
294.4548 175.358 l
419.2645 175.358 l
f*
575.9991 174.858 m
419.7645 174.858 l
419.7645 175.358 l
575.9991 175.358 l
f*
180.2769 174.858 m
180.2769 162.358 l
179.7769 162.358 l
179.7769 174.858 l
f*
179.7769 162.358 m
36 162.358 l
36 162.858 l
179.7769 162.858 l
f*
294.4548 174.858 m
294.4548 162.358 l
293.9547 162.358 l
293.9547 174.858 l
f*
293.9547 162.358 m
180.2769 162.358 l
180.2769 162.858 l
293.9547 162.858 l
f*
419.7645 174.858 m
419.7645 162.358 l
419.2645 162.358 l
419.2645 174.858 l
f*
419.2645 162.358 m
294.4548 162.358 l
294.4548 162.858 l
419.2645 162.858 l
f*
575.9991 162.358 m
419.7645 162.358 l
419.7645 162.858 l
575.9991 162.858 l
f*
180.2769 162.358 m
180.2769 149.8581 l
179.7769 149.8581 l
179.7769 162.358 l
f*
179.7769 149.8581 m
36 149.8581 l
36 150.3581 l
179.7769 150.3581 l
f*
294.4548 162.358 m
294.4548 149.8581 l
293.9547 149.8581 l
293.9547 162.358 l
f*
293.9547 149.8581 m
180.2769 149.8581 l
180.2769 150.3581 l
293.9547 150.3581 l
f*
419.7645 162.358 m
419.7645 149.8581 l
419.2645 149.8581 l
419.2645 162.358 l
f*
419.2645 149.8581 m
294.4548 149.8581 l
294.4548 150.3581 l
419.2645 150.3581 l
f*
575.9991 149.8581 m
419.7645 149.8581 l
419.7645 150.3581 l
575.9991 150.3581 l
f*
180.2769 149.8581 m
180.2769 137.3581 l
179.7769 137.3581 l
179.7769 149.8581 l
f*
179.7769 137.3581 m
36 137.3581 l
36 137.8582 l
179.7769 137.8582 l
f*
294.4548 149.8581 m
294.4548 137.3581 l
293.9547 137.3581 l
293.9547 149.8581 l
f*
293.9547 137.3581 m
180.2769 137.3581 l
180.2769 137.8582 l
293.9547 137.8582 l
f*
419.7645 149.8581 m
419.7645 137.3581 l
419.2645 137.3581 l
419.2645 149.8581 l
f*
419.2645 137.3581 m
294.4548 137.3581 l
294.4548 137.8582 l
419.2645 137.8582 l
f*
575.9991 137.3581 m
419.7645 137.3581 l
419.7645 137.8582 l
575.9991 137.8582 l
f*
180.2769 137.3581 m
180.2769 124.8582 l
179.7769 124.8582 l
179.7769 137.3581 l
f*
179.7769 124.8582 m
36 124.8582 l
36 125.3582 l
179.7769 125.3582 l
f*
294.4548 137.3581 m
294.4548 124.8582 l
293.9547 124.8582 l
293.9547 137.3581 l
f*
293.9547 124.8582 m
180.2769 124.8582 l
180.2769 125.3582 l
293.9547 125.3582 l
f*
419.7645 137.3581 m
419.7645 124.8582 l
419.2645 124.8582 l
419.2645 137.3581 l
f*
419.2645 124.8582 m
294.4548 124.8582 l
294.4548 125.3582 l
419.2645 125.3582 l
f*
575.9991 124.8582 m
419.7645 124.8582 l
419.7645 125.3582 l
575.9991 125.3582 l
f*
180.2769 124.8582 m
180.2769 112.3583 l
179.7769 112.3583 l
179.7769 124.8582 l
f*
179.7769 112.3583 m
36 112.3583 l
36 112.8583 l
179.7769 112.8583 l
f*
294.4548 124.8582 m
294.4548 112.3583 l
293.9547 112.3583 l
293.9547 124.8582 l
f*
293.9547 112.3583 m
180.2769 112.3583 l
180.2769 112.8583 l
293.9547 112.8583 l
f*
419.7645 124.8582 m
419.7645 112.3583 l
419.2645 112.3583 l
419.2645 124.8582 l
f*
419.2645 112.3583 m
294.4548 112.3583 l
294.4548 112.8583 l
419.2645 112.8583 l
f*
575.9991 112.3583 m
419.7645 112.3583 l
419.7645 112.8583 l
575.9991 112.8583 l
f*
575.9991 90.3583 m
36 90.3583 l
36 90.8583 l
575.9991 90.8583 l
f*
0.83 0.64 0.02 0 k
80.9575 176.7685 m
88.611 176.7685 l
h
f*
75.1748 164.2961 m
82.8283 164.2961 l
h
f*
81.8079 151.7669 m
89.4614 151.7669 l
h
f*
91.389 139.2945 m
98.9858 139.2945 l
h
f*
84.0756 126.7654 m
91.6724 126.7654 l
h
f*
91.8425 114.2929 m
99.4961 114.2929 l
h
f*
36 77.2724 m
186.7465 77.2724 l
h
f*
0 g
7.9999 0 0 7.9999 36 214.696 cm
BT
/F12 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Table)Tj
2.5512 0 Td
(2.)Tj
1.1763 0 Td
(Association)Tj
5.0599 0 Td
(between)Tj
3.6071 0 Td
(aspirin)Tj
3.1394 0 Td
(taking)Tj
2.8489 0 Td
(and)Tj
1.7787 0 Td
(metastatic)Tj
4.5142 0 Td
(spread.)Tj
0 Tc
-24.6757 -1.8567 Td
(Author)Tj
23.6553 0 Td
(Cancer)Tj
14.5135 0 Td
(Numbe)Tj
3.0897 0 Td
(rs)Tj
-3.9189 -1.1834 Td
(ASA/Contr)Tj
4.7339 0 Td
(ol)Tj
10.9277 1.1834 Td
(Estimates)Tj
4.3016 0 Td
(of)Tj
1.0842 0 Td
(reduction)Tj
-2.5228 -1.1834 Td
(\(95%)Tj
2.3386 0 Td
(CI\))Tj
/F5 1 Tf
-58.2028 -1.5662 Td
(Restivo)Tj
3.1819 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.1409 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(])Tj
18.2978 0 Td
(Rectum)Tj
15.1726 0 Td
(37/204)Tj
14.9954 0 Td
(HR)Tj
1.6228 0 Td
(0.31)Tj
1.8921 0 Td
(\(0.18,)Tj
2.4591 0 Td
(0.54\))Tj
-59.7193 -1.5591 Td
(Shiao)Tj
2.4519 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.141 0 Td
([)Tj
0.83 0.64 0.02 0 k
(36)Tj
0 g
(])Tj
19.3466 0 Td
(Breast)Tj
14.8537 0 Td
(65/157)Tj
14.9954 0 Td
(HR)Tj
1.6228 0 Td
(0.34)Tj
1.8921 0 Td
(\(0.15,)Tj
2.4591 0 Td
(0.81\))Tj
-59.7193 -1.5661 Td
(Osborn)Tj
3.2811 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.148 0 Td
([)Tj
0.83 0.64 0.02 0 k
(38)Tj
0 g
(])Tj
18.1206 0 Td
(Prostate)Tj
15.0025 0 Td
(147/142)Tj
15.2364 0 Td
(HR)Tj
1.6228 0 Td
(0.23)Tj
1.8921 0 Td
(\(0.06,)Tj
2.4591 0 Td
(0.91\))Tj
-59.7193 -1.5591 Td
(Rosenber)Tj
3.7771 0 Td
(g)Tj
0.7016 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.141 0 Td
([)Tj
0.83 0.64 0.02 0 k
(48)Tj
0 g
(])Tj
16.4907 0 Td
(Colorectal)Tj
15.6828 0 Td
(49/191)Tj
15.0095 0 Td
(OR)Tj
1.5945 0 Td
(0.96)Tj
1.8922 0 Td
(\(0.65,)Tj
2.4661 0 Td
(1.40\))Tj
-59.7122 -1.5661 Td
(Sanbury)Tj
3.5645 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.141 0 Td
([)Tj
0.83 0.64 0.02 0 k
(49)Tj
0 g
(])Tj
17.4049 0 Td
(Colorectal)Tj
15.9166 0 Td
(75/34)Tj
14.7757 0 Td
(OR)Tj
1.5945 0 Td
(0.77)Tj
1.8922 0 Td
(\(0.40,)Tj
2.4661 0 Td
(1.48\))Tj
-59.7122 -1.5591 Td
(Leitzman)Tj
3.7559 0 Td
(n)Tj
0.7866 0 Td
(et)Tj
0.9567 0 Td
(al.)Tj
1.141 0 Td
([)Tj
0.83 0.64 0.02 0 k
(50)Tj
0 g
(])Tj
16.8662 0 Td
(Prostate)Tj
14.6482 0 Td
(16/33,076)Tj
15.6615 0 Td
(RR)Tj
1.4811 0 Td
(0.71)Tj
1.8922 0 Td
(\(0.31,)Tj
2.4591 0 Td
(1.62\))Tj
/F12 1 Tf
-38.1263 -1.5661 Td
(Pooled)Tj
3.1394 0 Td
(HR)Tj
1.6653 0 Td
(0.31)Tj
/F5 1 Tf
1.9701 0 Td
(\(95%)Tj
2.289 0 Td
(CI)Tj
1.2402 0 Td
(0.18,)Tj
2.1189 0 Td
(0.51\))Tj
2.2323 0 Td
(Heterogen)Tj
4.2449 0 Td
(eity)Tj
1.6866 0 Td
(P)Tj
0.7867 0 Td
(=)Tj
0.8149 0 Td
(0.89;)Tj
-15.1938 -1.1835 Td
(Egger's)Tj
3.1181 0 Td
(test)Tj
1.6229 0 Td
(for)Tj
1.4032 0 Td
(bias)Tj
1.8071 0 Td
(0.138)Tj
0.83 0.64 0.02 0 k
/F8 1 Tf
-0.025 Tc
-36.468 -1.878 Td
(https://do)Tj
3.5575 0 Td
(i.org/10.1371/j)Tj
5.4425 0 Td
(ournal.pone)Tj
4.4079 0 Td
(.0203957.t002)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
32.2798 0 Td
(7)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
220 0 obj
<>stream
endstream
endobj
221 0 obj
<>stream
endstream
endobj
222 0 obj
<>stream
endstream
endobj
223 0 obj
<>stream
endstream
endobj
224 0 obj
<>stream
endstream
endobj
225 0 obj
<>stream
endstream
endobj
226 0 obj
<>stream
endstream
endobj
227 0 obj
<>stream
endstream
endobj
228 0 obj
<>stream
endstream
endobj
229 0 obj
<>stream
endstream
endobj
230 0 obj
<>stream
endstream
endobj
231 0 obj
<>stream
endstream
endobj
232 0 obj
<>stream
endstream
endobj
233 0 obj
<>stream
endstream
endobj
234 0 obj
<>stream
endstream
endobj
235 0 obj
<>stream
endstream
endobj
236 0 obj
<>stream
endstream
endobj
237 0 obj
<>stream
endstream
endobj
238 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
239 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 240 0 R/Contents 241 0 R/TrimBox[0 0 612 792]>>
endobj
240 0 obj
[242 0 R 243 0 R 244 0 R 245 0 R 246 0 R 247 0 R 248 0 R 249 0 R 250 0 R 251 0 R 252 0 R 253 0 R 254 0 R 255 0 R 256 0 R 257 0 R 258 0 R 259 0 R 260 0 R 261 0 R]
endobj
242 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref036)>>
endobj
243 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref054)>>
endobj
244 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s007)>>
endobj
245 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.t001)>>
endobj
246 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
247 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref053)>>
endobj
248 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s007)>>
endobj
249 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref038)>>
endobj
250 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref041)>>
endobj
251 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref055)>>
endobj
252 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref055)>>
endobj
253 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.s007)>>
endobj
254 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref055)>>
endobj
255 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref042)>>
endobj
256 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.t001)>>
endobj
257 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
258 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.t001)>>
endobj
259 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref056)>>
endobj
260 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref057)>>
endobj
261 0 obj
<>/Border[0 0 0]/A 262 0 R>>
endobj
262 0 obj
<>
endobj
241 0 obj
[263 0 R 264 0 R 265 0 R 266 0 R 267 0 R 268 0 R 269 0 R 270 0 R 271 0 R 272 0 R 273 0 R 274 0 R 275 0 R 276 0 R 277 0 R]
endobj
263 0 obj
<>stream
q
0.83 0.64 0.02 0 k
356.485 680.315 m
366.463 680.315 l
h
f*
368.9575 680.315 m
378.9921 680.315 l
h
f*
323.8299 615.3449 m
351.6094 615.3449 l
h
f*
428.1449 517.6063 m
457.3417 517.6063 l
h
f*
203.4142 504.6236 m
212.9386 504.6236 l
h
f*
331.8803 426.6142 m
341.4047 426.6142 l
h
f*
214.2992 413.6315 m
240.6614 413.6315 l
h
f*
505.6441 387.6094 m
515.1685 387.6094 l
h
f*
493.2283 348.6047 m
502.6961 348.6047 l
h
f*
504.9638 348.6047 m
514.4882 348.6047 l
h
f*
493.2283 309.6 m
502.7528 309.6 l
h
f*
200.0126 283.6346 m
226.3748 283.6346 l
h
f*
430.2425 244.6299 m
439.7669 244.6299 l
h
f*
394.4693 218.6079 m
403.9937 218.6079 l
h
f*
489.7701 133.9087 m
518.9669 133.9087 l
h
f*
260.3339 120.926 m
269.8016 120.926 l
h
f*
463.6346 94.9039 m
492.8315 94.9039 l
h
f*
421.3417 81.9213 m
430.8094 81.9213 l
h
f*
532.2331 81.9213 m
541.7575 81.9213 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 211.9748 707.4141 cm
BT
/F5 1 Tf
1 TL
0.02 Tc
0 0 Td
(Seven)Tj
2.6702 0 Td
(studies)Tj
3.1521 0 Td
(of)Tj
1.0658 0 Td
(breast)Tj
2.7553 0 Td
(cancer)Tj
2.9877 0 Td
(also)Tj
1.8651 0 Td
(reported)Tj
3.8495 0 Td
(all-cause)Tj
3.8834 0 Td
(mortality.)Tj
4.3823 0 Td
(In)Tj
1.1566 0 Td
(five)Tj
1.7518 0 Td
(the)Tj
1.542 0 Td
(association)Tj
-32.258 -1.3039 Td
(with)Tj
2.0862 0 Td
(aspirin)Tj
3.1521 0 Td
(suggested)Tj
4.286 0 Td
(benefit)Tj
3.1351 0 Td
(and)Tj
1.7971 0 Td
(in)Tj
1.0829 0 Td
(three)Tj
2.3811 0 Td
(the)Tj
1.5363 0 Td
(reduction)Tj
4.3257 0 Td
(in)Tj
1.0771 0 Td
(mortality)Tj
4.1272 0 Td
(associated)Tj
4.4958 0 Td
(with)Tj
2.0862 0 Td
(aspi-)Tj
-35.5688 -1.2982 Td
(rin)Tj
1.4796 0 Td
(was)Tj
1.7688 0 Td
(significant.)Tj
4.9039 0 Td
(However,)Tj
4.269 0 Td
(in)Tj
1.0828 0 Td
(two)Tj
1.7802 0 Td
([)Tj
0.83 0.64 0.02 0 k
(36)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(54)Tj
0 g
(])Tj
3.1974 0 Td
(the)Tj
1.542 0 Td
(association)Tj
4.8869 0 Td
(indicated)Tj
4.1556 0 Td
(an)Tj
1.2529 0 Td
(excess)Tj
2.8176 0 Td
(in)Tj
1.0829 0 Td
(all-)Tj
-34.2196 -1.2983 Td
(cause)Tj
2.5057 0 Td
(deaths)Tj
2.9367 0 Td
(in)Tj
1.0829 0 Td
(patients)Tj
3.5602 0 Td
(on)Tj
1.3266 0 Td
(aspirin,)Tj
3.4016 0 Td
(and)Tj
1.8028 0 Td
(in)Tj
1.0829 0 Td
(one)Tj
1.7744 0 Td
(of)Tj
1.0602 0 Td
(these)Tj
2.3754 0 Td
(the)Tj
1.542 0 Td
(excess)Tj
2.8177 0 Td
(was)Tj
1.7744 0 Td
(significant)Tj
4.6488 0 Td
(at)Tj
-33.6923 -1.2983 Td
(P)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
0.02 Tc
(0.05.)Tj
3.5716 0 Td
(Six)Tj
1.4967 0 Td
(studies)Tj
3.1577 0 Td
(of)Tj
1.0602 0 Td
(breast)Tj
2.7609 0 Td
(cancer)Tj
2.9877 0 Td
(give)Tj
1.9275 0 Td
(a)Tj
0.6747 0 Td
(pooled)Tj
3.0954 0 Td
(estimate)Tj
3.736 0 Td
(of)Tj
1.0659 0 Td
(all-cause)Tj
3.8777 0 Td
(mortality)Tj
4.1329 0 Td
(as)Tj
1.0658 0 Td
(HR)Tj
-34.6107 -1.3039 Td
(0.79)Tj
1.9672 0 Td
(\(95%)Tj
2.364 0 Td
(CI)Tj
1.27 0 Td
(0.54,)Tj
2.2166 0 Td
(1.16;)Tj
2.2224 0 Td
(heterogeneity)Tj
5.964 0 Td
(p)Tj
0.7597 0 Td
(=)Tj
0.8221 0 Td
(0.0005)Tj
2.9707 0 Td
(and)Tj
1.7971 0 Td
(Egger's)Tj
3.2598 0 Td
(test)Tj
1.7008 0 Td
(for)Tj
1.457 0 Td
(bias)Tj
1.8822 0 Td
(p)Tj
0.7654 0 Td
(=)Tj
0.822 0 Td
(0.74\).)Tj
2.5795 0 Td
(The)Tj
-34.8205 -1.2982 Td
(omission)Tj
4.0478 0 Td
(of)Tj
1.0658 0 Td
(three)Tj
2.3811 0 Td
(studies)Tj
3.1578 0 Td
(removes)Tj
3.7473 0 Td
(heterogeneity)Tj
5.9641 0 Td
(\(p)Tj
1.1225 0 Td
(=)Tj
0.8277 0 Td
(0.33\))Tj
2.3301 0 Td
(and)Tj
1.8028 0 Td
(gives)Tj
2.3131 0 Td
(HR)Tj
1.6554 0 Td
(for)Tj
1.457 0 Td
(total)Tj
2.126 0 Td
(mortal-)Tj
-33.9985 -1.2983 Td
(ity)Tj
1.3095 0 Td
(0.97\(95%)Tj
4.1159 0 Td
(CI)Tj
1.2699 0 Td
(0.77,)Tj
2.2167 0 Td
(1.21)Tj
1.9672 0 Td
(see)Tj
0.83 0.64 0.02 0 k
1.5024 0 Td
(S3)Tj
1.2189 0 Td
(File)Tj
0 g
(\).)Tj
-0.004 Tc
-12.4043 -1.3039 Td
(Overall)Tj
3.1464 0 Td
(therefore,)Tj
4.0762 0 Td
(there)Tj
2.2677 0 Td
(is)Tj
0.8447 0 Td
(evidence)Tj
3.7134 0 Td
(of)Tj
1.0148 0 Td
(benefit)Tj
2.9763 0 Td
(from)Tj
2.2054 0 Td
(aspirin)Tj
2.9877 0 Td
(taken)Tj
2.4207 0 Td
(by)Tj
1.1792 0 Td
(patients)Tj
3.3676 0 Td
(with)Tj
2.0012 0 Td
(breast)Tj
-33.3975 -1.2983 Td
(cancer)Tj
2.8402 0 Td
(as)Tj
1.0205 0 Td
(an)Tj
1.2019 0 Td
(adjuvant)Tj
3.702 0 Td
(treatment)Tj
4.1329 0 Td
(in)Tj
1.0375 0 Td
(terms)Tj
2.4944 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0318 0 Td
(breast)Tj
2.6192 0 Td
(cancer)Tj
2.8403 0 Td
(deaths)Tj
2.7949 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.6577 0 Td
(signifi-)Tj
-33.8851 -1.2983 Td
(cant)Tj
1.9218 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(incidence)Tj
4.0705 0 Td
(of)Tj
1.0148 0 Td
(metastatic)Tj
4.2803 0 Td
(spread.)Tj
3.0784 0 Td
(Evidence)Tj
3.8608 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6519 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0375 0 Td
(all-cause)Tj
3.6623 0 Td
(mor-)Tj
-35.3307 -1.3039 Td
(tality)Tj
2.2166 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
2.2564 0 Td
(patients)Tj
3.3675 0 Td
(is)Tj
0.8447 0 Td
(suggestive,)Tj
4.4958 0 Td
(but)Tj
1.5533 0 Td
(not)Tj
1.5704 0 Td
(consistent)Tj
4.2576 0 Td
(across)Tj
2.6816 0 Td
(the)Tj
1.4683 0 Td
(studies.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 535.6913 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Prostate)Tj
3.6992 0 Td
(cancer)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 518.6834 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Our)Tj
1.8651 0 Td
(searches)Tj
3.5433 0 Td
(identified)Tj
4.0592 0 Td
(16)Tj
1.1735 0 Td
(observational)Tj
5.5786 0 Td
(studies,)Tj
3.2088 0 Td
(listed)Tj
2.3471 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0374 0 Td
(Table)Tj
2.4378 0 Td
(1)Tj
0 g
0.6973 0 Td
(and)Tj
1.7292 0 Td
(in)Tj
1.0374 0 Td
(our)Tj
1.6271 0 Td
(earlier)Tj
2.7553 0 Td
(report.)Tj
-33.0971 -1.2982 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.8481 0 Td
(Fifteen)Tj
2.9991 0 Td
(focused)Tj
3.2768 0 Td
(on)Tj
1.2756 0 Td
(prostate)Tj
3.4299 0 Td
(cancer)Tj
2.8459 0 Td
(mortality)Tj
3.9175 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0375 0 Td
(ten)Tj
1.491 0 Td
(the)Tj
1.4683 0 Td
(index)Tj
2.4492 0 Td
(of)Tj
1.0148 0 Td
(association)Tj
4.6317 0 Td
(suggested)Tj
-33.4145 -1.2983 Td
(a)Tj
0.6519 0 Td
(reduction)Tj
4.1159 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(aspirin,)Tj
3.2145 0 Td
(significant)Tj
4.388 0 Td
(in)Tj
1.0318 0 Td
(three.)Tj
2.4944 0 Td
(In)Tj
1.1055 0 Td
(five)Tj
1.6555 0 Td
(studies)Tj
2.982 0 Td
(the)Tj
1.474 0 Td
(measure)Tj
3.5773 0 Td
(of)Tj
1.0148 0 Td
(associa-)Tj
-33.9588 -1.3039 Td
(tion)Tj
1.8425 0 Td
(with)Tj
1.9955 0 Td
(aspirin)Tj
2.9877 0 Td
(exceeded)Tj
3.8551 0 Td
(1.00,)Tj
2.0977 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0374 0 Td
(one)Tj
1.7008 0 Td
(the)Tj
1.4684 0 Td
(excess)Tj
2.6759 0 Td
(in)Tj
1.0374 0 Td
(prostate)Tj
3.4299 0 Td
(mortality)Tj
3.9175 0 Td
(with)Tj
1.9956 0 Td
(aspirin)Tj
2.9877 0 Td
(is)Tj
-34.7582 -1.2983 Td
(significant.)Tj
1.1962 -1.2982 Td
(A)Tj
0.907 0 Td
(pooled)Tj
2.9481 0 Td
(HR)Tj
1.61 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(thirteen)Tj
3.3789 0 Td
(studies)Tj
2.9877 0 Td
(that)Tj
1.7802 0 Td
(report)Tj
2.7042 0 Td
(the)Tj
1.474 0 Td
(association)Tj
4.6261 0 Td
(with)Tj
1.9956 0 Td
(aspirin)Tj
2.9877 0 Td
(using)Tj
-33.8114 -1.3039 Td
(this)Tj
1.6724 0 Td
(index)Tj
2.4548 0 Td
(is)Tj
0.8447 0 Td
(0.87)Tj
1.8708 0 Td
(\(95%)Tj
2.2734 0 Td
(CI)Tj
1.2189 0 Td
(0.73,)Tj
2.0976 0 Td
(1.05;)Tj
2.0977 0 Td
(heterogeneity)Tj
5.6522 0 Td
(p)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
-0.004 Tc
(0.0005)Tj
4.1159 0 Td
(and)Tj
1.7291 0 Td
(Egger's)Tj
3.0897 0 Td
(test)Tj
1.6044 0 Td
(P)Tj
0.7767 0 Td
(=)Tj
0.7994 0 Td
(0.13\).)Tj
2.4378 0 Td
(The)Tj
-34.7355 -1.2983 Td
(omission)Tj
3.855 0 Td
(of)Tj
1.0148 0 Td
(one)Tj
1.7008 0 Td
(out-lying)Tj
3.8835 0 Td
(study)Tj
2.3924 0 Td
([)Tj
0.83 0.64 0.02 0 k
(53)Tj
0 g
(])Tj
1.8482 0 Td
(gives)Tj
2.194 0 Td
(HR)Tj
1.61 0 Td
(0.84)Tj
1.8709 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2245 0 Td
(0.77,)Tj
2.0977 0 Td
(0.92;)Tj
2.0976 0 Td
(heterogeneity)Tj
5.6522 0 Td
(p)Tj
0.737 0 Td
(=)Tj
0.7994 0 Td
(0.17;)Tj
-35.2457 -1.2983 Td
(see)Tj
0.83 0.64 0.02 0 k
1.4286 0 Td
(S3)Tj
1.1679 0 Td
(File)Tj
0 g
(\).)Tj
-1.4003 -1.2982 Td
(Evidence)Tj
3.8607 0 Td
(on)Tj
1.2756 0 Td
(metastatic)Tj
4.2746 0 Td
(spread)Tj
2.8573 0 Td
(in)Tj
1.0375 0 Td
(prostate)Tj
3.4299 0 Td
(cancer)Tj
2.846 0 Td
(associated)Tj
4.2519 0 Td
(with)Tj
2.0013 0 Td
(aspirin,)Tj
3.2088 0 Td
(comes)Tj
2.7552 0 Td
(from)Tj
2.2054 0 Td
(four)Tj
-35.2004 -1.304 Td
(studies.)Tj
3.2087 0 Td
(Pooling)Tj
3.3222 0 Td
(three)Tj
2.2621 0 Td
(of)Tj
1.0148 0 Td
(there,)Tj
2.4944 0 Td
(gives)Tj
2.1884 0 Td
(RR)Tj
1.4626 0 Td
(0.52)Tj
1.8709 0 Td
(\(0.390.68\),)Tj
4.9492 0 Td
(and)Tj
1.7292 0 Td
(another)Tj
3.3335 0 Td
(study)Tj
2.3868 0 Td
([)Tj
0.83 0.64 0.02 0 k
(38)Tj
0 g
(])Tj
1.8538 0 Td
(gives)Tj
2.1883 0 Td
(HR)Tj
1.6101 0 Td
(0.23)Tj
-35.875 -1.2982 Td
(\(0.06,)Tj
2.4377 0 Td
(0.91\).)Tj
-1.2415 -1.2983 Td
(Five)Tj
1.8935 0 Td
(studies)Tj
2.9877 0 Td
(on)Tj
1.2756 0 Td
(prostate)Tj
3.4299 0 Td
(cancer)Tj
2.8459 0 Td
(also)Tj
1.7688 0 Td
(reported)Tj
3.6567 0 Td
(all-cause)Tj
3.668 0 Td
(mortality)Tj
3.9175 0 Td
(and)Tj
1.7291 0 Td
(three)Tj
2.2677 0 Td
(show)Tj
2.2961 0 Td
(a)Tj
0.6576 0 Td
(reduction)Tj
-33.5903 -1.3039 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9955 0 Td
(aspirin,)Tj
3.2088 0 Td
(significant)Tj
4.3937 0 Td
(in)Tj
1.0318 0 Td
(two.)Tj
1.9332 0 Td
(However,)Tj
4.0819 0 Td
(in)Tj
1.0318 0 Td
(two)Tj
1.7121 0 Td
(other)Tj
2.3471 0 Td
(studies)Tj
2.9877 0 Td
([)Tj
0.83 0.64 0.02 0 k
(41)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(55)Tj
0 g
(])Tj
3.0274 0 Td
(the)Tj
1.4683 0 Td
(associa-)Tj
-33.4769 -1.2983 Td
(tion)Tj
1.8425 0 Td
(with)Tj
1.9955 0 Td
(aspirin)Tj
2.9877 0 Td
(exceeded)Tj
3.8551 0 Td
(1.00)Tj
1.8709 0 Td
(and)Tj
1.7348 0 Td
(was)Tj
1.6951 0 Td
(significant)Tj
4.388 0 Td
(in)Tj
1.0375 0 Td
(both.)Tj
2.2847 0 Td
(Four)Tj
2.1543 0 Td
(studies)Tj
2.9877 0 Td
(report)Tj
2.7099 0 Td
(the)Tj
1.4683 0 Td
(association)Tj
-33.012 -1.2982 Td
(with)Tj
1.9955 0 Td
(aspirin)Tj
2.9877 0 Td
(as)Tj
1.0148 0 Td
(hazard)Tj
2.9254 0 Td
(ratios)Tj
2.4604 0 Td
(and)Tj
1.7291 0 Td
(together)Tj
3.5377 0 Td
(these)Tj
2.2506 0 Td
(give)Tj
1.8312 0 Td
(HR)Tj
1.6101 0 Td
(0.84)Tj
1.8708 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.54,)Tj
2.0976 0 Td
(1.30;)Tj
2.0977 0 Td
(heterogeneity)Tj
-31.9009 -1.3039 Td
(P)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
-0.004 Tc
(0.0005)Tj
4.1555 0 Td
(and)Tj
1.7291 0 Td
(Egger's)Tj
3.0898 0 Td
(test)Tj
1.5987 0 Td
(for)Tj
1.389 0 Td
(bias)Tj
1.7858 0 Td
(P)Tj
0.7824 0 Td
(=)Tj
0.7993 0 Td
(0.42\).)Tj
2.4378 0 Td
(The)Tj
1.7801 0 Td
(omission)Tj
3.8608 0 Td
(of)Tj
1.0148 0 Td
(one)Tj
1.6951 0 Td
(outlier)Tj
2.863 0 Td
([)Tj
0.83 0.64 0.02 0 k
(55)Tj
0 g
(])Tj
1.8538 0 Td
(removes)Tj
3.5773 0 Td
(hetero-)Tj
-34.4123 -1.2983 Td
(geneity)Tj
3.101 0 Td
(and)Tj
1.7292 0 Td
(gives)Tj
2.194 0 Td
(for)Tj
1.3833 0 Td
(all)Tj
1.1451 0 Td
(cause)Tj
2.3925 0 Td
(mortality)Tj
3.9174 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(prostate)Tj
3.4299 0 Td
(studies,)Tj
3.2088 0 Td
(HR)Tj
1.6101 0 Td
(0.73)Tj
1.8709 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2245 0 Td
(0.66,)Tj
2.0976 0 Td
(0.81;)Tj
2.0977 0 Td
(see)Tj
0.83 0.64 0.02 0 k
-36.1755 -1.2983 Td
(S3)Tj
1.1678 0 Td
(File)Tj
0 g
(\).)Tj
0.0284 -1.3039 Td
(The)Tj
1.7858 0 Td
(evidence)Tj
3.7133 0 Td
(on)Tj
1.2756 0 Td
(prostate)Tj
3.4299 0 Td
(cancer)Tj
2.8403 0 Td
(is)Tj
0.8504 0 Td
(therefore)Tj
3.8551 0 Td
(fairly)Tj
2.279 0 Td
(consistent)Tj
4.2577 0 Td
(for)Tj
1.3889 0 Td
(both)Tj
2.058 0 Td
(prostate)Tj
3.4299 0 Td
(cancer)Tj
2.8459 0 Td
(mor-)Tj
-35.206 -1.2983 Td
(tality,)Tj
2.4434 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4684 0 Td
(hazard)Tj
2.931 0 Td
(ratio)Tj
2.0976 0 Td
(for)Tj
1.3833 0 Td
(all)Tj
1.1452 0 Td
(cause)Tj
2.3924 0 Td
(mortality)Tj
3.9175 0 Td
(also)Tj
1.7688 0 Td
(suggests)Tj
3.4809 0 Td
(benefit.)Tj
3.2031 0 Td
(Correspondence)Tj
6.8371 0 Td
(with)Tj
-34.7978 -1.2982 Td
(the)Tj
1.4683 0 Td
(author)Tj
2.8856 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(one)Tj
1.7007 0 Td
(report)Tj
2.71 0 Td
(that)Tj
1.7744 0 Td
(is)Tj
0.8504 0 Td
(seriously)Tj
3.7417 0 Td
(inconsistent)Tj
5.0683 0 Td
([)Tj
0.83 0.64 0.02 0 k
(55)Tj
0 g
(])Tj
1.8539 0 Td
(led)Tj
1.4173 0 Td
(to)Tj
1.0261 0 Td
(no)Tj
1.2756 0 Td
(clue)Tj
1.8425 0 Td
(as)Tj
1.0148 0 Td
(to)Tj
1.0205 0 Td
(why)Tj
1.8879 0 Td
(it)Tj
0.788 0 Td
(differs)Tj
-34.8092 -1.2983 Td
(markedly)Tj
3.9911 0 Td
(from)Tj
2.2053 0 Td
(the)Tj
1.4741 0 Td
(other)Tj
2.347 0 Td
(studies.)Tj
3.2088 0 Td
(The)Tj
1.7858 0 Td
(reduction)Tj
4.1102 0 Td
(in)Tj
1.0375 0 Td
(metastatic)Tj
4.2803 0 Td
(spread)Tj
2.8516 0 Td
(associated)Tj
4.2577 0 Td
(with)Tj
1.9955 0 Td
(aspirin)Tj
2.9877 0 Td
(is)Tj
-36.5326 -1.3039 Td
(otherwise)Tj
4.0818 0 Td
(marked)Tj
3.2939 0 Td
(and)Tj
1.7291 0 Td
(consistent.)Tj
4.4844 0 Td
(In)Tj
1.1055 0 Td
(one)Tj
1.7007 0 Td
(report)Tj
2.7099 0 Td
([)Tj
0.83 0.64 0.02 0 k
(42)Tj
0 g
(],)Tj
2.075 0 Td
(it)Tj
0.788 0 Td
(is)Tj
0.8447 0 Td
(suggested)Tj
4.0762 0 Td
(that)Tj
1.7745 0 Td
(some)Tj
2.3301 0 Td
(inconsistencies)Tj
-30.9938 -1.2983 Td
(in)Tj
1.0261 0 Td
(studies)Tj
2.9763 0 Td
(of)Tj
1.0092 0 Td
(this)Tj
1.6611 0 Td
(cancer)Tj
2.8403 0 Td
(may)Tj
1.9162 0 Td
(be)Tj
1.1452 0 Td
(introduced)Tj
4.6317 0 Td
(by)Tj
1.1736 0 Td
(a)Tj
0.6463 0 Td
(selective)Tj
3.5319 0 Td
(up-take)Tj
3.2598 0 Td
(of)Tj
1.0035 0 Td
(PSA)Tj
1.9332 0 Td
(\(prostate)Tj
3.7587 0 Td
(specific)Tj
3.1805 0 Td
(anti-)Tj
-35.6936 -1.2982 Td
(gen\))Tj
1.9955 0 Td
(screening,)Tj
4.2803 0 Td
(leading)Tj
3.1294 0 Td
(to)Tj
1.0262 0 Td
(bias)Tj
1.7915 0 Td
(resulting)Tj
3.7247 0 Td
(from)Tj
2.2053 0 Td
(an)Tj
1.2019 0 Td
(early)Tj
2.1543 0 Td
(diagnosis)Tj
3.9571 0 Td
(of)Tj
1.0148 0 Td
(cancer)Tj
2.846 0 Td
(in)Tj
1.0318 0 Td
(subjects)Tj
3.3789 0 Td
(taking)Tj
-33.7377 -1.304 Td
(aspirin.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 151.9937 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Other)Tj
2.7118 0 Td
(cancers)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 134.9858 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Our)Tj
1.8651 0 Td
(searches)Tj
3.5433 0 Td
(identified)Tj
4.0592 0 Td
(15)Tj
1.1735 0 Td
(reports)Tj
3.0671 0 Td
(on)Tj
1.2756 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7291 0 Td
(other)Tj
2.3471 0 Td
(cancers)Tj
3.2088 0 Td
(\(listed)Tj
2.6815 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(Table)Tj
2.4378 0 Td
(1)Tj
0 g
0.6973 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0375 0 Td
(our)Tj
-34.8772 -1.2982 Td
(earlier)Tj
2.7552 0 Td
(report.)Tj
2.9367 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.8482 0 Td
(No)Tj
1.4626 0 Td
(study)Tj
2.3925 0 Td
(showed)Tj
3.2484 0 Td
(significant)Tj
4.388 0 Td
(evidence)Tj
3.7134 0 Td
(of)Tj
1.0148 0 Td
(detriment)Tj
4.2009 0 Td
(from)Tj
2.2054 0 Td
(aspirin)Tj
2.982 0 Td
(specific)Tj
-33.1481 -1.2983 Td
(mortality,)Tj
4.1385 0 Td
(or)Tj
1.0998 0 Td
(all-cause)Tj
3.6681 0 Td
(mortality.)Tj
4.1385 0 Td
(There)Tj
2.5795 0 Td
(is)Tj
0.8504 0 Td
(however)Tj
3.6113 0 Td
(suggestive)Tj
4.2633 0 Td
(evidence)Tj
3.7134 0 Td
(of)Tj
1.0148 0 Td
(benefit)Tj
2.9763 0 Td
(in)Tj
1.0375 0 Td
(10)Tj
1.1679 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-35.2741 -1.3039 Td
(15)Tj
1.1678 0 Td
(studies,)Tj
3.2145 0 Td
(significant)Tj
4.388 0 Td
(in)Tj
1.0375 0 Td
(six.)Tj
1.5363 0 Td
(In)Tj
1.1112 0 Td
(addition)Tj
3.5943 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(reports)Tj
3.0727 0 Td
(included)Tj
3.7077 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(Table)Tj
2.4434 0 Td
(1)Tj
0 g
0.6974 0 Td
(we)Tj
1.3266 0 Td
(earlier)Tj
2.7552 0 Td
(reported)Tj
-33.5846 -1.2983 Td
(evidence)Tj
3.7133 0 Td
(on)Tj
1.2756 0 Td
(ovarian)Tj
3.2315 0 Td
(cancer)Tj
2.8459 0 Td
(\(HR)Tj
1.9503 0 Td
(0.92)Tj
1.8708 0 Td
(95%)Tj
1.9276 0 Td
(CI)Tj
1.2245 0 Td
(0.81,1.06)Tj
3.7531 0 Td
([)Tj
0.83 0.64 0.02 0 k
(56)Tj
0 g
(],)Tj
2.0749 0 Td
(lung)Tj
2.0069 0 Td
(cancer)Tj
2.846 0 Td
(\(HR)Tj
1.9502 0 Td
(0.84\))Tj
2.211 0 Td
([)Tj
0.83 0.64 0.02 0 k
(57)Tj
0 g
(],)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
32.2798 0 Td
(8)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
264 0 obj
<>stream
endstream
endobj
265 0 obj
<>stream
endstream
endobj
266 0 obj
<>stream
endstream
endobj
267 0 obj
<>stream
endstream
endobj
268 0 obj
<>stream
endstream
endobj
269 0 obj
<>stream
endstream
endobj
270 0 obj
<>stream
endstream
endobj
271 0 obj
<>stream
endstream
endobj
272 0 obj
<>stream
endstream
endobj
273 0 obj
<>stream
endstream
endobj
274 0 obj
<>stream
endstream
endobj
275 0 obj
<>stream
endstream
endobj
276 0 obj
<>stream
endstream
endobj
277 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
278 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 279 0 R/Contents 280 0 R/TrimBox[0 0 612 792]>>
endobj
279 0 obj
[281 0 R 282 0 R 283 0 R 284 0 R 285 0 R 286 0 R 287 0 R 288 0 R 289 0 R 290 0 R 291 0 R 292 0 R 293 0 R 294 0 R 295 0 R 296 0 R 297 0 R 298 0 R 299 0 R]
endobj
281 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref058)>>
endobj
282 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref059)>>
endobj
283 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref060)>>
endobj
284 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref047)>>
endobj
285 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref061)>>
endobj
286 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.t002)>>
endobj
287 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref044)>>
endobj
288 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref030)>>
endobj
289 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref032)>>
endobj
290 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref003)>>
endobj
291 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
292 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.t002)>>
endobj
293 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
294 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref027)>>
endobj
295 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref045)>>
endobj
296 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref025)>>
endobj
297 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref062)>>
endobj
298 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref063)>>
endobj
299 0 obj
<>/Border[0 0 0]/A 300 0 R>>
endobj
300 0 obj
<>
endobj
280 0 obj
[301 0 R 302 0 R 303 0 R 304 0 R 305 0 R 306 0 R 307 0 R 308 0 R 309 0 R 310 0 R 311 0 R 312 0 R 313 0 R 314 0 R 315 0 R 316 0 R 317 0 R 318 0 R 319 0 R 320 0 R]
endobj
301 0 obj
<>stream
q
0.83 0.64 0.02 0 k
348.6047 706.337 m
358.1291 706.337 l
h
f*
225.5244 693.2976 m
235.0488 693.2976 l
h
f*
470.948 693.2976 m
480.4724 693.2976 l
h
f*
442.4315 680.315 m
451.9559 680.315 l
h
f*
454.2236 680.315 m
463.6913 680.315 l
h
f*
371.7921 667.3323 m
400.989 667.3323 l
h
f*
457.7386 654.3496 m
467.2063 654.3496 l
h
f*
437.8394 519.874 m
447.3071 519.874 l
h
f*
378.5386 506.8346 m
388.063 506.8346 l
h
f*
358.2992 467.8299 m
363.0614 467.8299 l
h
f*
473.6126 415.8425 m
483.5906 415.8425 l
h
f*
321.9591 389.8772 m
352.3465 389.8772 l
h
f*
291.3449 333.411 m
301.3228 333.411 l
h
f*
534.4441 242.3622 m
544.422 242.3622 l
h
f*
559.1055 216.3969 m
569.0835 216.3969 l
h
f*
394.8094 203.4142 m
404.8441 203.4142 l
h
f*
253.2472 94.9039 m
262.7717 94.9039 l
h
f*
267.9307 94.9039 m
277.4551 94.9039 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(bladder)Tj
3.2541 0 Td
(\(OR)Tj
1.9275 0 Td
(0.75)Tj
1.8766 0 Td
(95%)Tj
1.9275 0 Td
(CI)Tj
1.2246 0 Td
(0.45,)Tj
2.0976 0 Td
(1.24\))Tj
2.211 0 Td
([)Tj
0.83 0.64 0.02 0 k
(58)Tj
0 g
(],)Tj
2.075 0 Td
(a)Tj
0.6576 0 Td
(mix)Tj
1.7688 0 Td
(of)Tj
1.0148 0 Td
(women's)Tj
3.7814 0 Td
(cancers)Tj
3.2031 0 Td
(\(HR)Tj
1.9502 0 Td
(0.82;)Tj
2.0977 0 Td
(95%)Tj
1.9275 0 Td
(CI)Tj
1.2246 0 Td
(0.57,)Tj
-34.2196 -1.3039 Td
(1.18\))Tj
2.211 0 Td
([)Tj
0.83 0.64 0.02 0 k
(59)Tj
0 g
(])Tj
1.8538 0 Td
(and)Tj
1.7291 0 Td
(lymphocytic)Tj
5.1591 0 Td
(leukaemia)Tj
4.2916 0 Td
(\(HR)Tj
1.9502 0 Td
(0.40;)Tj
2.0976 0 Td
(95%)Tj
1.9276 0 Td
(CI)Tj
1.2245 0 Td
(0.21,)Tj
2.0977 0 Td
(0.79\))Tj
2.211 0 Td
([)Tj
0.83 0.64 0.02 0 k
(60)Tj
0 g
(].)Tj
2.0749 0 Td
(There)Tj
2.5795 0 Td
(have)Tj
2.058 0 Td
(also)Tj
1.7688 0 Td
(been)Tj
-35.2344 -1.2982 Td
(two)Tj
1.7064 0 Td
(reports)Tj
3.0727 0 Td
(on)Tj
1.2756 0 Td
(head)Tj
2.1317 0 Td
(and)Tj
1.7291 0 Td
(neck)Tj
2.1146 0 Td
(cancer)Tj
2.8403 0 Td
(which)Tj
2.6532 0 Td
(differ)Tj
2.3868 0 Td
(markedly)Tj
3.9911 0 Td
([)Tj
0.83 0.64 0.02 0 k
(47)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(61)Tj
0 g
(].)Tj
3.2542 0 Td
(Associations)Tj
5.2384 0 Td
(between)Tj
-32.3941 -1.2983 Td
(aspirin)Tj
2.9876 0 Td
(and)Tj
1.7292 0 Td
(metastatic)Tj
4.2746 0 Td
(spread)Tj
2.8573 0 Td
(are)Tj
1.4457 0 Td
(shown)Tj
2.8516 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0318 0 Td
(Table)Tj
2.4434 0 Td
(2)Tj
0 g
(,)Tj
0.9241 0 Td
(and)Tj
1.7292 0 Td
(there)Tj
2.262 0 Td
(is)Tj
0.8504 0 Td
(also)Tj
1.7688 0 Td
(an)Tj
1.2019 0 Td
(earlier)Tj
2.7552 0 Td
(report)Tj
2.7099 0 Td
(on)Tj
1.2756 0 Td
(aspi-)Tj
-35.0983 -1.2983 Td
(rin)Tj
1.4059 0 Td
(and)Tj
1.7291 0 Td
(endometrial)Tj
5.0854 0 Td
(cancer)Tj
2.8459 0 Td
(spread)Tj
2.8573 0 Td
(\(HR)Tj
1.9503 0 Td
(0.23;)Tj
2.0976 0 Td
(05%)Tj
1.9275 0 Td
(CI)Tj
1.2189 0 Td
(0.06,)Tj
2.0977 0 Td
(0.91\))Tj
2.2166 0 Td
([)Tj
0.83 0.64 0.02 0 k
(44)Tj
0 g
(].)Tj
-24.236 -1.3039 Td
(While)Tj
2.6532 0 Td
(these)Tj
2.2563 0 Td
(single)Tj
2.5285 0 Td
(reports)Tj
3.0728 0 Td
(are)Tj
1.4456 0 Td
(a)Tj
0.652 0 Td
(rather)Tj
2.6475 0 Td
(uncertain)Tj
4.0649 0 Td
(basis)Tj
2.1486 0 Td
(for)Tj
1.389 0 Td
(clinical)Tj
3.0727 0 Td
(intervention,)Tj
5.4028 0 Td
(they)Tj
1.9219 0 Td
(very)Tj
-34.452 -1.2982 Td
(strongly)Tj
3.4695 0 Td
(give)Tj
1.8312 0 Td
(encouragement)Tj
6.4346 0 Td
(for)Tj
1.389 0 Td
(the)Tj
1.4683 0 Td
(conduct)Tj
3.4753 0 Td
(of)Tj
1.0148 0 Td
(further)Tj
3.0273 0 Td
(studies,)Tj
3.2145 0 Td
(both)Tj
2.058 0 Td
(observational)Tj
5.5785 0 Td
(and)Tj
-32.961 -1.2983 Td
(randomised.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 589.9464 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(All)Tj
1.4787 0 Td
(cancers)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 572.9385 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Pooling)Tj
3.3165 0 Td
(the)Tj
1.474 0 Td
(association)Tj
4.6261 0 Td
(of)Tj
1.0148 0 Td
(aspirin)Tj
2.9877 0 Td
(with)Tj
1.9956 0 Td
(all)Tj
1.1451 0 Td
(the)Tj
1.4684 0 Td
(cancers)Tj
3.2088 0 Td
(in)Tj
1.0375 0 Td
(our)Tj
1.6214 0 Td
(reports)Tj
3.0727 0 Td
(which)Tj
2.6475 0 Td
(have)Tj
2.0637 0 Td
(been)Tj
2.1203 0 Td
(reported)Tj
-33.8001 -1.2982 Td
(as)Tj
1.0147 0 Td
(hazard)Tj
2.9254 0 Td
(ratios)Tj
2.4604 0 Td
(gives)Tj
2.1884 0 Td
(74)Tj
1.1735 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.66,)Tj
2.0976 0 Td
(0.82\))Tj
2.211 0 Td
(for)Tj
1.389 0 Td
(cancer)Tj
2.8403 0 Td
(mortality)Tj
3.9174 0 Td
(and)Tj
1.7291 0 Td
(0.81)Tj
1.8766 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2245 0 Td
(0.73,)Tj
2.0977 0 Td
(0.89\))Tj
-34.9056 -1.3039 Td
(for)Tj
1.3832 0 Td
(all-cause)Tj
3.6681 0 Td
(mortality.)Tj
4.1442 0 Td
(Several)Tj
3.0444 0 Td
(published)Tj
4.1272 0 Td
(reports)Tj
3.0727 0 Td
(give)Tj
1.8255 0 Td
(similar)Tj
2.9877 0 Td
(estimates)Tj
3.9061 0 Td
(for)Tj
1.389 0 Td
(total)Tj
2.0013 0 Td
(cancer)Tj
2.8459 0 Td
(mortal-)Tj
-34.3953 -1.2983 Td
(ity.)Tj
1.4626 0 Td
(A)Tj
0.9071 0 Td
(study)Tj
2.3868 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2755 0 Td
(11,001)Tj
2.8233 0 Td
(men)Tj
2.0126 0 Td
(taking)Tj
2.7326 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7291 0 Td
(followed)Tj
3.651 0 Td
(for)Tj
1.3833 0 Td
(15)Tj
1.1735 0 Td
(years,)Tj
2.4888 0 Td
(reported)Tj
3.6567 0 Td
(an)Tj
1.2076 0 Td
(overall)Tj
-34.35 -1.2983 Td
(reduction)Tj
4.1158 0 Td
(in)Tj
1.0318 0 Td
(all)Tj
1.1452 0 Td
(cancer)Tj
2.846 0 Td
(deaths)Tj
2.7949 0 Td
(\(HR)Tj
1.9503 0 Td
(0.76;)Tj
2.0976 0 Td
(95%)Tj
1.9275 0 Td
(CI)Tj
1.2189 0 Td
(0.70,)Tj
2.0976 0 Td
(0.82\))Tj
2.2167 0 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(].)Tj
2.075 0 Td
(In)Tj
1.1111 0 Td
(a)Tj
0.652 0 Td
(report)Tj
2.7099 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(US)Tj
-35.206 -1.3039 Td
(studies)Tj
2.9763 0 Td
(NHANES)Tj
4.1783 0 Td
(I)Tj
0.5555 0 Td
(and)Tj
1.7178 0 Td
(II,)Tj
1.1169 0 Td
(Ratnasinghe)Tj
5.142 0 Td
(et)Tj
0.9354 0 Td
(al)Tj
0.8901 0 Td
([)Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(])Tj
1.8425 0 Td
(give)Tj
1.8198 0 Td
(an)Tj
1.1962 0 Td
(RR)Tj
1.4514 0 Td
(of)Tj
1.0091 0 Td
(0.98)Tj
1.8652 0 Td
(\(95%)Tj
2.2563 0 Td
(CI)Tj
1.2133 0 Td
(0.84,)Tj
2.0919 0 Td
(1.14\))Tj
2.2054 0 Td
(for)Tj
1.3776 0 Td
(can-)Tj
-35.841 -1.2982 Td
(cer)Tj
1.4343 0 Td
(mortality)Tj
3.9174 0 Td
(in)Tj
1.0375 0 Td
(14,838)Tj
2.8233 0 Td
(subjects)Tj
3.3789 0 Td
(taking)Tj
2.7269 0 Td
(aspirin.)Tj
3.2144 0 Td
(Elsewhere,)Tj
4.4731 0 Td
(Algra)Tj
2.4208 0 Td
(&)Tj
0.9297 0 Td
(Rothwell)Tj
3.7701 0 Td
(give)Tj
1.8311 0 Td
(pooled)Tj
2.9481 0 Td
(esti-)Tj
-34.9056 -1.2983 Td
(mates)Tj
2.5568 0 Td
(of)Tj
1.0148 0 Td
(reductions)Tj
4.473 0 Td
(in)Tj
1.0375 0 Td
(total)Tj
2.0012 0 Td
(cancers)Tj
3.2088 0 Td
(in)Tj
1.0318 0 Td
(overviews)Tj
4.167 0 Td
(of)Tj
1.0147 0 Td
(three)Tj
2.2677 0 Td
(previously)Tj
4.3484 0 Td
(randomised)Tj
5.0059 0 Td
(vascular)Tj
3.4753 0 Td
(trials)Tj
-35.6029 -1.3039 Td
(of)Tj
1.0147 0 Td
(aspirin)Tj
2.9877 0 Td
(\(OR)Tj
1.9276 0 Td
(0.48;)Tj
2.0976 0 Td
(95%)Tj
1.9276 0 Td
(CI)Tj
1.2245 0 Td
(0.30,)Tj
2.0976 0 Td
(0.75\))Tj
2.2111 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(],)Tj
1.5987 0 Td
(and)Tj
1.7291 0 Td
(these)Tj
2.2564 0 Td
(authors)Tj
3.2485 0 Td
(also)Tj
1.7688 0 Td
(give)Tj
1.8311 0 Td
(an)Tj
1.2019 0 Td
(overall)Tj
2.9027 0 Td
(estimate)Tj
3.5433 0 Td
(for)Tj
-35.5689 -1.2983 Td
(the)Tj
1.4683 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0318 0 Td
(metastatic)Tj
4.2803 0 Td
(spread)Tj
2.8573 0 Td
(in)Tj
1.0318 0 Td
(long-term)Tj
4.2519 0 Td
(studies)Tj
2.9877 0 Td
(in)Tj
1.0318 0 Td
(which)Tj
2.6532 0 Td
(aspirin)Tj
2.9877 0 Td
(had)Tj
1.7065 0 Td
(originally)Tj
4.0308 0 Td
(been)Tj
-34.435 -1.2983 Td
(randomised:)Tj
5.2327 0 Td
(OR)Tj
1.5874 0 Td
(0.69)Tj
1.8708 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.57,)Tj
2.0976 0 Td
(0.83\).)Tj
0.02 Tc
-13.0846 -1.2982 Td
(Pooled)Tj
3.1351 0 Td
(estimates)Tj
4.1215 0 Td
(of)Tj
1.0658 0 Td
(the)Tj
1.5421 0 Td
(reductions)Tj
4.7168 0 Td
(in)Tj
1.0828 0 Td
(metastatic)Tj
4.5184 0 Td
(spread)Tj
2.9934 0 Td
(associated)Tj
4.5014 0 Td
(with)Tj
2.0919 0 Td
(aspirin)Tj
3.1521 0 Td
(in)Tj
1.0829 0 Td
(dif-)Tj
-35.2004 -1.3039 Td
(ferent)Tj
2.7155 0 Td
(cancers)Tj
3.3732 0 Td
(are)Tj
1.5194 0 Td
(also)Tj
1.8652 0 Td
(suggestive)Tj
4.507 0 Td
(of)Tj
1.0659 0 Td
(benefit:)Tj
3.3902 0 Td
(in)Tj
1.0828 0 Td
(our)Tj
1.7008 0 Td
(earlier)Tj
2.9253 0 Td
(report)Tj
2.8516 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.9446 0 Td
(estimates)Tj
4.1215 0 Td
(reported)Tj
-33.063 -1.2983 Td
(in)Tj
1.0828 0 Td
(five)Tj
1.7461 0 Td
(studies)Tj
3.1578 0 Td
(give)Tj
1.9275 0 Td
(a)Tj
0.6747 0 Td
(pooled)Tj
3.0954 0 Td
(RR)Tj
1.508 0 Td
(of)Tj
1.0658 0 Td
(0.77)Tj
1.9673 0 Td
(\(95%)Tj
2.364 0 Td
(CI)Tj
1.27 0 Td
(0.65,)Tj
2.2166 0 Td
(0.92;)Tj
2.2167 0 Td
(heterogeneity)Tj
5.9641 0 Td
(P)Tj
0.805 0 Td
(=)Tj
0.822 0 Td
(0.002\))Tj
2.8347 0 Td
(and)Tj
-34.7185 -1.2983 Td
(three)Tj
2.381 0 Td
(of)Tj
1.0659 0 Td
(the)Tj
1.542 0 Td
(studies)Tj
3.1521 0 Td
(shown)Tj
2.9707 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0828 0 Td
(Table)Tj
2.5625 0 Td
(2)Tj
0 g
0.72 0 Td
(give)Tj
1.9219 0 Td
(a)Tj
0.6803 0 Td
(pooled)Tj
3.0898 0 Td
(HR)Tj
1.661 0 Td
(of)Tj
1.0602 0 Td
(0.31)Tj
1.9672 0 Td
(\(95%)Tj
2.3641 0 Td
(CI)Tj
1.2756 0 Td
(0.20,)Tj
2.2167 0 Td
(0.48;)Tj
2.2166 0 Td
(hetero-)Tj
-33.9304 -1.3039 Td
(geneity)Tj
3.2654 0 Td
(P)Tj
0.8051 0 Td
(=)Tj
0.822 0 Td
(0.89\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 351.4393 cm
BT
/F12 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Reports)Tj
3.496 0 Td
(on)Tj
1.2945 0 Td
(bleeding)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 334.4881 cm
BT
/F5 1 Tf
1 TL
0.02 Tc
0 0 Td
(In)Tj
1.1565 0 Td
(our)Tj
1.6951 0 Td
(earlier)Tj
2.9253 0 Td
(review)Tj
2.9877 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.9502 0 Td
(we)Tj
1.372 0 Td
(stated)Tj
2.7099 0 Td
(that)Tj
1.8709 0 Td
(four)Tj
2.0125 0 Td
(authors)Tj
3.4129 0 Td
(mentioned)Tj
4.8019 0 Td
(in)Tj
1.0828 0 Td
(their)Tj
2.228 0 Td
(reports)Tj
3.2372 0 Td
(that)Tj
1.8765 0 Td
(no)Tj
-35.3194 -1.3039 Td
(patient)Tj
3.1747 0 Td
(had)Tj
1.7802 0 Td
(experienced)Tj
5.3007 0 Td
(a)Tj
0.6747 0 Td
(major)Tj
2.7269 0 Td
(bleeding)Tj
3.8211 0 Td
(event,)Tj
2.7382 0 Td
(and)Tj
1.8028 0 Td
(in)Tj
1.0829 0 Td
(21)Tj
1.2189 0 Td
(answers)Tj
3.5716 0 Td
(to)Tj
1.0771 0 Td
(an)Tj
1.2473 0 Td
(email)Tj
2.5341 0 Td
(sent)Tj
1.9446 0 Td
(to)Tj
1.0715 0 Td
(the)Tj
-35.7673 -1.2982 Td
(corresponding)Tj
6.3722 0 Td
(author)Tj
3.0274 0 Td
(of)Tj
1.0601 0 Td
(each)Tj
2.126 0 Td
(report,)Tj
3.1011 0 Td
(none)Tj
2.3471 0 Td
(reported)Tj
3.8494 0 Td
(a)Tj
0.6803 0 Td
(major)Tj
2.7269 0 Td
(bleeding)Tj
3.8211 0 Td
(event.)Tj
2.7382 0 Td
(Again,)Tj
2.9877 0 Td
(the)Tj
-34.8375 -1.2983 Td
(recent)Tj
2.8516 0 Td
(reports)Tj
3.2371 0 Td
(since)Tj
2.3641 0 Td
(March)Tj
2.9877 0 Td
(2017)Tj
2.2224 0 Td
(were)Tj
2.2166 0 Td
(scanned)Tj
3.651 0 Td
(and)Tj
1.8029 0 Td
(all)Tj
1.2188 0 Td
(the)Tj
1.5421 0 Td
(corresponding)Tj
6.3722 0 Td
(authors)Tj
3.4129 0 Td
(were)Tj
-33.8794 -1.3039 Td
(written)Tj
3.2768 0 Td
(to)Tj
1.0771 0 Td
(and)Tj
1.7972 0 Td
(asked)Tj
2.5852 0 Td
(about)Tj
2.6135 0 Td
(bleeding.)Tj
4.0705 0 Td
(The)Tj
1.8539 0 Td
(author)Tj
3.0274 0 Td
(of)Tj
1.0658 0 Td
(one)Tj
1.7688 0 Td
(report)Tj
2.8516 0 Td
(supplied)Tj
3.8041 0 Td
(data)Tj
2.0069 0 Td
(which)Tj
-31.7988 -1.2983 Td
(showed)Tj
3.3958 0 Td
(that)Tj
1.8709 0 Td
(aspirin)Tj
3.1578 0 Td
(had)Tj
1.7801 0 Td
(not)Tj
1.6441 0 Td
(been)Tj
2.2167 0 Td
(associated)Tj
4.5014 0 Td
(with)Tj
2.0919 0 Td
(any)Tj
1.7291 0 Td
(significant)Tj
4.6488 0 Td
(excess)Tj
2.8233 0 Td
(in)Tj
1.0828 0 Td
(either)Tj
2.6759 0 Td
(serious)Tj
-33.6186 -1.2982 Td
(bleeding)Tj
3.821 0 Td
(\(HR)Tj
2.0183 0 Td
(1.11)Tj
1.9672 0 Td
(95%)Tj
2.0013 0 Td
(CI)Tj
1.2699 0 Td
(0.85,)Tj
2.2223 0 Td
(1.44\))Tj
2.3301 0 Td
(or)Tj
1.1452 0 Td
(in)Tj
1.0828 0 Td
(fatal)Tj
2.0409 0 Td
(bleeding:)Tj
4.0706 0 Td
(3%)Tj
1.5023 0 Td
(of)Tj
1.0602 0 Td
(the)Tj
1.542 0 Td
(bleeds)Tj
2.8516 0 Td
(had)Tj
1.7859 0 Td
(been)Tj
2.2166 0 Td
(fatal)Tj
-34.9282 -1.304 Td
(in)Tj
1.0828 0 Td
(patients)Tj
3.5603 0 Td
(taking)Tj
2.8743 0 Td
(aspirin)Tj
3.1521 0 Td
(and)Tj
1.8028 0 Td
(3.2%)Tj
2.2507 0 Td
(had)Tj
1.7802 0 Td
(been)Tj
2.2166 0 Td
(fatal)Tj
2.041 0 Td
(in)Tj
1.0828 0 Td
(patients)Tj
3.5603 0 Td
(not)Tj
1.6497 0 Td
(taking)Tj
2.8687 0 Td
(aspirin)Tj
3.1578 0 Td
([)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(].)Tj
-33.0801 -1.2982 Td
(Another)Tj
3.7473 0 Td
(author)Tj
3.0274 0 Td
(stated)Tj
2.7099 0 Td
(that)Tj
1.8709 0 Td
(within)Tj
2.9593 0 Td
(their)Tj
2.228 0 Td
(cohort)Tj
2.9991 0 Td
(of)Tj
1.0601 0 Td
(120)Tj
1.7235 0 Td
(patients)Tj
3.5603 0 Td
(with)Tj
2.0919 0 Td
(liver)Tj
2.1033 0 Td
(cancer,)Tj
3.2372 0 Td
(six)Tj
-33.3182 -1.2983 Td
(patients)Tj
3.5602 0 Td
(taking)Tj
2.8744 0 Td
(aspirin)Tj
3.1521 0 Td
(and)Tj
1.8028 0 Td
(seven)Tj
2.5511 0 Td
(not)Tj
1.6441 0 Td
(on)Tj
1.3266 0 Td
(aspirin)Tj
3.1521 0 Td
(had)Tj
1.7802 0 Td
(had)Tj
1.7801 0 Td
(a)Tj
0.6803 0 Td
(fatal)Tj
2.041 0 Td
(gastrointestinal)Tj
6.7351 0 Td
(bleed)Tj
2.4661 0 Td
([)Tj
0.83 0.64 0.02 0 k
(45)Tj
0 g
(].)Tj
-35.5462 -1.2983 Td
(A)Tj
0.924 0 Td
(further)Tj
3.1975 0 Td
(author)Tj
3.0331 0 Td
(of)Tj
1.0601 0 Td
(a)Tj
0.6803 0 Td
(report)Tj
2.8516 0 Td
(with)Tj
2.092 0 Td
(491)Tj
1.7178 0 Td
(patients)Tj
3.5603 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(])Tj
1.9502 0 Td
(stated)Tj
2.7042 0 Td
(that)Tj
1.8766 0 Td
(a)Tj
0.6746 0 Td
(single)Tj
2.6759 0 Td
(bleeding)Tj
3.8211 0 Td
(event)Tj
-32.8193 -1.3039 Td
(occurred)Tj
3.9854 0 Td
(in)Tj
1.0829 0 Td
(a)Tj
0.6803 0 Td
(patient)Tj
3.1748 0 Td
(on)Tj
1.3209 0 Td
(antiplatelet)Tj
4.9436 0 Td
(treatment,)Tj
4.6034 0 Td
(and)Tj
1.8028 0 Td
(three)Tj
2.3811 0 Td
(events)Tj
2.8743 0 Td
(occurred)Tj
3.9912 0 Td
(in)Tj
1.0828 0 Td
(patients)Tj
3.5603 0 Td
(not)Tj
-35.4838 -1.2982 Td
(on)Tj
1.3209 0 Td
(antiplatelet)Tj
4.9436 0 Td
(treatment'.)Tj
4.8415 0 Td
(Three)Tj
2.6986 0 Td
(other)Tj
2.4661 0 Td
(authors)Tj
3.4129 0 Td
(stated)Tj
2.7099 0 Td
(than)Tj
2.1203 0 Td
(no)Tj
1.3266 0 Td
(major)Tj
2.7269 0 Td
(bleeding)Tj
3.8211 0 Td
(had)Tj
-32.3884 -1.2983 Td
(occurred)Tj
3.9854 0 Td
(in)Tj
1.0829 0 Td
(the)Tj
1.542 0 Td
(patients)Tj
3.5603 0 Td
(they)Tj
2.0182 0 Td
(had)Tj
1.7859 0 Td
(followed.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 139.011 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Discussion)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 122.0031 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Ever)Tj
2.0352 0 Td
(since)Tj
2.245 0 Td
(Gasic)Tj
2.4208 0 Td
(and)Tj
1.7291 0 Td
(colleagues)Tj
4.2803 0 Td
(reported)Tj
3.6624 0 Td
(in)Tj
1.0318 0 Td
(196884)Tj
3.5943 0 Td
(a)Tj
0.6519 0 Td
(series)Tj
2.4265 0 Td
(of)Tj
1.0148 0 Td
(pioneering)Tj
4.5581 0 Td
(studies)Tj
2.9877 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.4684 0 Td
(role)Tj
-35.3818 -1.2982 Td
(of)Tj
1.0147 0 Td
(platelets)Tj
3.4696 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.4684 0 Td
(metastatic)Tj
4.2803 0 Td
(spread)Tj
2.8573 0 Td
(of)Tj
1.0148 0 Td
(cancer)Tj
2.8403 0 Td
(and)Tj
1.7348 0 Td
(a)Tj
0.6519 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(incidence)Tj
4.0705 0 Td
(of)Tj
1.0148 0 Td
(metastases)Tj
-32.0709 -1.3039 Td
(with)Tj
1.9955 0 Td
(aspirin)Tj
2.9877 0 Td
([)Tj
0.83 0.64 0.02 0 k
(62)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(63)Tj
0 g
(])Tj
3.3165 0 Td
(there)Tj
2.2677 0 Td
(has)Tj
1.5421 0 Td
(been)Tj
2.1203 0 Td
(an)Tj
1.2019 0 Td
(increasing)Tj
4.3313 0 Td
(interest)Tj
3.2144 0 Td
(in)Tj
1.0318 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7292 0 Td
(cancer.)Tj
3.0727 0 Td
(Now,)Tj
2.3698 0 Td
(there)Tj
2.2677 0 Td
(is)Tj
-36.4363 -1.2983 Td
(extensive)Tj
3.8834 0 Td
(experimental)Tj
5.4595 0 Td
(evidence)Tj
3.7133 0 Td
(on)Tj
1.2756 0 Td
(how)Tj
1.9389 0 Td
(platelets)Tj
3.4639 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4684 0 Td
(coagulation)Tj
4.8755 0 Td
(system)Tj
2.9424 0 Td
(protect)Tj
3.0557 0 Td
(tumour)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
32.2798 0 Td
(9)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
302 0 obj
<>stream
endstream
endobj
303 0 obj
<>stream
endstream
endobj
304 0 obj
<>stream
endstream
endobj
305 0 obj
<>stream
endstream
endobj
306 0 obj
<>stream
endstream
endobj
307 0 obj
<>stream
endstream
endobj
308 0 obj
<>stream
endstream
endobj
309 0 obj
<>stream
endstream
endobj
310 0 obj
<>stream
endstream
endobj
311 0 obj
<>stream
endstream
endobj
312 0 obj
<>stream
endstream
endobj
313 0 obj
<>stream
endstream
endobj
314 0 obj
<>stream
endstream
endobj
315 0 obj
<>stream
endstream
endobj
316 0 obj
<>stream
endstream
endobj
317 0 obj
<>stream
endstream
endobj
318 0 obj
<>stream
endstream
endobj
319 0 obj
<>stream
endstream
endobj
320 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
321 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 322 0 R/Contents 323 0 R/TrimBox[0 0 612 792]>>
endobj
322 0 obj
[324 0 R 325 0 R 326 0 R 327 0 R 328 0 R 329 0 R 330 0 R 331 0 R 332 0 R]
endobj
324 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref064)>>
endobj
325 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref011)>>
endobj
326 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref006)>>
endobj
327 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
328 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref065)>>
endobj
329 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref066)>>
endobj
330 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref068)>>
endobj
331 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref069)>>
endobj
332 0 obj
<>/Border[0 0 0]/A 333 0 R>>
endobj
333 0 obj
<>
endobj
323 0 obj
[334 0 R 335 0 R 336 0 R 337 0 R 338 0 R 339 0 R 340 0 R 341 0 R 342 0 R]
endobj
334 0 obj
<>stream
q
0.83 0.64 0.02 0 k
441.1843 693.2976 m
450.7087 693.2976 l
h
f*
468.1701 654.3496 m
477.6945 654.3496 l
h
f*
373.2661 576.3402 m
378.0283 576.3402 l
h
f*
368.6173 550.3181 m
378.1417 550.3181 l
h
f*
437.0457 225.2976 m
446.5701 225.2976 l
h
f*
312.7181 186.3496 m
322.2425 186.3496 l
h
f*
327.4016 186.3496 m
336.926 186.3496 l
h
f*
344.2961 160.3276 m
353.8205 160.3276 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(cells)Tj
1.9218 0 Td
(within)Tj
2.812 0 Td
(the)Tj
1.4683 0 Td
(circulation)Tj
4.5354 0 Td
(from)Tj
2.2054 0 Td
(immune)Tj
3.6226 0 Td
(elimination,)Tj
5.074 0 Td
(enable)Tj
2.8063 0 Td
(cancer)Tj
2.8403 0 Td
(cells)Tj
1.9219 0 Td
(to)Tj
1.0261 0 Td
(adhere)Tj
2.9253 0 Td
(to)Tj
1.0262 0 Td
(vascular)Tj
-34.1856 -1.3039 Td
(endothelium)Tj
5.3291 0 Td
(and)Tj
1.7234 0 Td
(enhance)Tj
3.5433 0 Td
(the)Tj
1.4627 0 Td
(growth)Tj
3.067 0 Td
(of)Tj
1.0092 0 Td
(the)Tj
1.4626 0 Td
(metastatic)Tj
4.269 0 Td
(cells)Tj
1.9105 0 Td
([)Tj
0.83 0.64 0.02 0 k
(64)Tj
0 g
(].)Tj
2.0693 0 Td
(With)Tj
2.2734 0 Td
(this)Tj
1.6667 0 Td
(knowledge)Tj
4.5354 0 Td
(a)Tj
0.6463 0 Td
(reduc-)Tj
-34.9679 -1.2982 Td
(tion)Tj
1.8425 0 Td
(in)Tj
1.0318 0 Td
(metastatic)Tj
4.2803 0 Td
(spread)Tj
2.8516 0 Td
(by)Tj
1.1849 0 Td
(aspirin)Tj
2.982 0 Td
(is)Tj
0.8504 0 Td
(a)Tj
0.6519 0 Td
(highly)Tj
2.7099 0 Td
(reasonable)Tj
4.4788 0 Td
(expectation.)Tj
-21.6679 -1.2983 Td
(The)Tj
1.7858 0 Td
(first)Tj
1.8028 0 Td
(evidence)Tj
3.7134 0 Td
(of)Tj
1.0148 0 Td
(an)Tj
1.2018 0 Td
(effect)Tj
2.3641 0 Td
(by)Tj
1.1849 0 Td
(aspirin)Tj
2.9877 0 Td
(on)Tj
1.2756 0 Td
(metastatic)Tj
4.2746 0 Td
(spread)Tj
2.8573 0 Td
(in)Tj
1.0318 0 Td
(human)Tj
3.0784 0 Td
(subjects)Tj
3.3789 0 Td
(came)Tj
2.3187 0 Td
(in)Tj
-35.4668 -1.2983 Td
(one)Tj
1.6951 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(long-term)Tj
4.2462 0 Td
(follow-up)Tj
4.0989 0 Td
(studies)Tj
2.982 0 Td
(by)Tj
1.1849 0 Td
(Rothwell)Tj
3.7757 0 Td
(and)Tj
1.7292 0 Td
(colleagues)Tj
4.2746 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(].)Tj
2.0806 0 Td
(Aspirin)Tj
3.2315 0 Td
(was)Tj
1.7007 0 Td
(reported)Tj
-33.4882 -1.3039 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1508 0 Td
(associated)Tj
4.252 0 Td
(with)Tj
2.0012 0 Td
(significant)Tj
4.388 0 Td
(reductions)Tj
4.4731 0 Td
(in)Tj
1.0375 0 Td
(metastases)Tj
4.4333 0 Td
(across)Tj
2.6759 0 Td
(a)Tj
0.6576 0 Td
(range)Tj
2.4605 0 Td
(of)Tj
1.0148 0 Td
(cancers,)Tj
3.4299 0 Td
(both)Tj
2.0636 0 Td
(in)Tj
-35.0643 -1.2982 Td
(subjects)Tj
3.3788 0 Td
(with)Tj
1.9956 0 Td
(metastases)Tj
4.4334 0 Td
(at)Tj
0.9524 0 Td
(initial)Tj
2.5512 0 Td
(diagnosis)Tj
3.9571 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(risk)Tj
1.7178 0 Td
(of)Tj
1.0148 0 Td
(later)Tj
1.9899 0 Td
(metastases)Tj
4.4334 0 Td
(in)Tj
1.0375 0 Td
(patients)Tj
3.3675 0 Td
(who)Tj
-35.0643 -1.2983 Td
(had)Tj
1.7064 0 Td
(been)Tj
2.126 0 Td
(free)Tj
1.7234 0 Td
(of)Tj
1.0148 0 Td
(metastases)Tj
4.4334 0 Td
(at)Tj
0.9524 0 Td
(diagnosis.)Tj
4.1839 0 Td
(In)Tj
1.1112 0 Td
(a)Tj
0.652 0 Td
(later)Tj
1.9955 0 Td
(report)Tj
2.7099 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(long-term)Tj
4.252 0 Td
(follow-up)Tj
4.0932 0 Td
(of)Tj
1.0148 0 Td
(par-)Tj
-35.7163 -1.3039 Td
(ticipants)Tj
3.6339 0 Td
(in)Tj
1.0375 0 Td
(51)Tj
1.1679 0 Td
(vascular)Tj
3.4752 0 Td
(randomised)Tj
5.006 0 Td
(trials,)Tj
2.4208 0 Td
(Rothwell)Tj
3.7757 0 Td
(et)Tj
0.9411 0 Td
(al)Tj
0.9014 0 Td
(commented)Tj
5.0116 0 Td
(on)Tj
1.2756 0 Td
(a)Tj
0.6576 0 Td
(reduction)Tj
4.1102 0 Td
(in)Tj
1.0375 0 Td
(short-)Tj
-34.452 -1.2983 Td
(term)Tj
2.1316 0 Td
(cancer)Tj
2.846 0 Td
(mortality)Tj
3.9174 0 Td
(which)Tj
2.6476 0 Td
(they)Tj
1.9218 0 Td
(judged)Tj
2.9537 0 Td
(was)Tj
1.6951 0 Td
(too)Tj
1.5364 0 Td
(rapid)Tj
2.3357 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1508 0 Td
(attributable)Tj
4.8302 0 Td
(to)Tj
1.0262 0 Td
(`prevention')Tj
5.0172 0 Td
(and)Tj
-35.0359 -1.2983 Td
(much)Tj
2.5171 0 Td
(more)Tj
2.3414 0 Td
(likely)Tj
2.3527 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1508 0 Td
(a)Tj
0.652 0 Td
(`treatment')Tj
4.5808 0 Td
(effect)Tj
2.364 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
-15.7888 -1.3039 Td
(Cochrane)Tj
4.1215 0 Td
(and)Tj
1.7291 0 Td
(others)Tj
2.7099 0 Td
(have)Tj
2.058 0 Td
(stressed)Tj
3.3505 0 Td
(the)Tj
1.4683 0 Td
(importance)Tj
4.8303 0 Td
(of)Tj
1.0147 0 Td
(replication)Tj
4.5241 0 Td
(in)Tj
1.0375 0 Td
(science.)Tj
3.3165 0 Td
(This)Tj
1.9842 0 Td
(paper)Tj
-33.3408 -1.2982 Td
(presents)Tj
3.5206 0 Td
(a)Tj
0.6576 0 Td
(replication)Tj
4.5241 0 Td
(of)Tj
1.0148 0 Td
(an)Tj
1.2018 0 Td
(earlier)Tj
2.7553 0 Td
(review)Tj
2.846 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(])Tj
1.8481 0 Td
(and)Tj
1.7348 0 Td
(then,)Tj
2.2394 0 Td
(because)Tj
3.3222 0 Td
(the)Tj
1.4683 0 Td
(estimates)Tj
3.9061 0 Td
(of)Tj
1.0148 0 Td
(effect)Tj
2.3641 0 Td
(of)Tj
1.0148 0 Td
(aspi-)Tj
-35.4328 -1.2983 Td
(rin)Tj
1.4059 0 Td
(are)Tj
1.4514 0 Td
(comparable)Tj
4.8982 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7121 0 Td
(reviews,)Tj
3.4299 0 Td
(we)Tj
1.3266 0 Td
(have)Tj
2.058 0 Td
(based)Tj
2.4774 0 Td
(overall)Tj
2.9027 0 Td
(conclusions)Tj
4.9379 0 Td
(on)Tj
1.2756 0 Td
(meta-analyses)Tj
5.811 0 Td
(of)Tj
-36.1925 -1.3039 Td
(the)Tj
1.4683 0 Td
(pooled)Tj
2.948 0 Td
(results)Tj
2.812 0 Td
(from)Tj
2.2053 0 Td
(the)Tj
1.4683 0 Td
(two)Tj
1.7065 0 Td
(reviews.)Tj
3.4355 0 Td
(These)Tj
2.5625 0 Td
(results)Tj
2.812 0 Td
(give)Tj
1.8312 0 Td
(extensive)Tj
3.8834 0 Td
(evidence)Tj
3.7134 0 Td
(consistent)Tj
4.2576 0 Td
(with)Tj
-35.104 -1.2983 Td
(reductions)Tj
4.473 0 Td
(of)Tj
1.0148 0 Td
(about)Tj
2.4945 0 Td
(1525%)Tj
3.3958 0 Td
(in)Tj
1.0375 0 Td
(cancer)Tj
2.846 0 Td
(mortality)Tj
3.9174 0 Td
(by)Tj
1.1792 0 Td
(aspirin.)Tj
3.2145 0 Td
(The)Tj
1.7802 0 Td
(evidence)Tj
3.7133 0 Td
(suggests)Tj
3.4809 0 Td
(however)Tj
-32.5471 -1.2982 Td
(that)Tj
1.7744 0 Td
(there)Tj
2.2677 0 Td
(may)Tj
1.9276 0 Td
(be)Tj
1.1508 0 Td
(different)Tj
3.6567 0 Td
(levels)Tj
2.3754 0 Td
(of)Tj
1.0148 0 Td
(benefit)Tj
2.9764 0 Td
(in)Tj
1.0318 0 Td
(different)Tj
3.6567 0 Td
(cancers.)Tj
3.4299 0 Td
(Thus,)Tj
2.4774 0 Td
(there)Tj
2.2621 0 Td
(appears)Tj
3.2768 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
-34.3046 -1.2983 Td
(about)Tj
2.4944 0 Td
(a)Tj
0.652 0 Td
(25%)Tj
1.9275 0 Td
(reduction)Tj
4.1159 0 Td
(with)Tj
1.9956 0 Td
(aspirin)Tj
2.9877 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(mortality)Tj
3.9175 0 Td
(of)Tj
1.0148 0 Td
(colon)Tj
2.4491 0 Td
(cancer)Tj
2.8459 0 Td
(\(HR)Tj
1.9503 0 Td
(0.75;)Tj
2.0976 0 Td
(95%)Tj
1.9275 0 Td
(CI)Tj
1.2246 0 Td
(0.68)Tj
-34.1062 -1.3039 Td
(0.83\),)Tj
2.4377 0 Td
(about)Tj
2.4945 0 Td
(20%)Tj
1.9275 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0318 0 Td
(breast)Tj
2.6192 0 Td
(cancer)Tj
2.8403 0 Td
(mortality)Tj
3.9175 0 Td
(\(HR)Tj
1.9502 0 Td
(0.80;)Tj
2.0976 0 Td
(95%)Tj
1.9276 0 Td
(CI)Tj
1.2245 0 Td
(0.66,)Tj
2.0977 0 Td
(0.97\))Tj
2.211 0 Td
(and)Tj
1.7291 0 Td
(a)Tj
0.6576 0 Td
(prob-)Tj
-35.2797 -1.2983 Td
(able)Tj
1.8311 0 Td
(15%)Tj
1.9276 0 Td
(reduction)Tj
4.1158 0 Td
(in)Tj
1.0319 0 Td
(prostate)Tj
3.4299 0 Td
(cancer)Tj
2.8459 0 Td
(deaths)Tj
2.795 0 Td
(\(HR)Tj
1.9502 0 Td
(0.86)Tj
1.8708 0 Td
(\(95%)Tj
2.2677 0 Td
(CI)Tj
1.2246 0 Td
(0.78,)Tj
2.0976 0 Td
(0.95\).)Tj
2.4378 0 Td
(There)Tj
2.5738 0 Td
(is)Tj
0.8504 0 Td
(also)Tj
1.7688 0 Td
(evi-)Tj
-35.0189 -1.2983 Td
(dence)Tj
2.5681 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(substantial)Tj
4.5014 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(incidence)Tj
4.0705 0 Td
(of)Tj
1.0148 0 Td
(metastatic)Tj
4.2803 0 Td
(spread)Tj
2.8516 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
2.2564 0 Td
(cancers,)Tj
3.4299 0 Td
(together)Tj
-34.2763 -1.3039 Td
(with)Tj
1.9955 0 Td
(a)Tj
0.652 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0374 0 Td
(all-cause)Tj
3.6681 0 Td
(mortality)Tj
3.9174 0 Td
(across)Tj
2.6759 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4683 0 Td
(cancers.)Tj
-19.4795 -1.2982 Td
(Almost)Tj
3.1407 0 Td
(all)Tj
1.1452 0 Td
(the)Tj
1.4684 0 Td
(evidence)Tj
3.7133 0 Td
(we)Tj
1.3266 0 Td
(present)Tj
3.1635 0 Td
(is,)Tj
1.0715 0 Td
(however,)Tj
3.838 0 Td
(from)Tj
2.2054 0 Td
(observational)Tj
5.5842 0 Td
(studies)Tj
2.982 0 Td
(within)Tj
2.812 0 Td
(which)Tj
2.6532 0 Td
(the)Tj
-36.3002 -1.2983 Td
(taking)Tj
2.7269 0 Td
(of)Tj
1.0148 0 Td
(aspirin)Tj
2.9877 0 Td
(is)Tj
0.8503 0 Td
(selective,)Tj
3.7644 0 Td
(leading)Tj
3.1351 0 Td
(to)Tj
1.0205 0 Td
(a)Tj
0.6576 0 Td
(number)Tj
3.4186 0 Td
(of)Tj
1.0148 0 Td
(important)Tj
4.2803 0 Td
(uncertainties.)Tj
5.6352 0 Td
(First,)Tj
2.2734 0 Td
(there)Tj
2.262 0 Td
(is)Tj
-35.0416 -1.3039 Td
(marked)Tj
3.2938 0 Td
(heterogeneity)Tj
5.6522 0 Td
(between)Tj
3.5263 0 Td
(the)Tj
1.4683 0 Td
(studies)Tj
2.9877 0 Td
(and)Tj
1.7292 0 Td
(our)Tj
1.627 0 Td
(limited)Tj
3.0671 0 Td
(success)Tj
3.1011 0 Td
(in)Tj
1.0375 0 Td
(reducing)Tj
3.7757 0 Td
(this)Tj
1.6724 0 Td
(limits)Tj
2.4832 0 Td
(con-)Tj
-35.4215 -1.2983 Td
(fidence)Tj
3.118 0 Td
(in)Tj
1.0375 0 Td
(interpretation.)Tj
6.0208 0 Td
(There)Tj
2.5795 0 Td
(are)Tj
1.4456 0 Td
(many)Tj
2.4775 0 Td
(sources)Tj
3.1975 0 Td
(of)Tj
1.0148 0 Td
(possible)Tj
3.4072 0 Td
(differences)Tj
4.5637 0 Td
(between)Tj
3.532 0 Td
(the)Tj
1.4683 0 Td
(series)Tj
2.4265 0 Td
(of)Tj
-36.2889 -1.2983 Td
(patients)Tj
3.3675 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(various)Tj
3.1408 0 Td
(studiesdifferences)Tj
8.2544 0 Td
(in)Tj
1.0375 0 Td
(age)Tj
1.542 0 Td
(and)Tj
1.7291 0 Td
(social)Tj
2.4605 0 Td
(factors,)Tj
3.1294 0 Td
(differences)Tj
4.5638 0 Td
(in)Tj
1.0374 0 Td
(other)Tj
2.3471 0 Td
(treat-)Tj
-35.1153 -1.2982 Td
(ments)Tj
2.6702 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0375 0 Td
(general)Tj
3.1294 0 Td
(clinical)Tj
3.0784 0 Td
(managementand)Tj
7.8689 0 Td
(heterogeneity)Tj
5.6523 0 Td
(is)Tj
0.8504 0 Td
(probably)Tj
3.7643 0 Td
(inevitable,)Tj
4.3144 0 Td
(but)Tj
1.5533 0 Td
(at)Tj
-35.6482 -1.3039 Td
(the)Tj
1.4683 0 Td
(same)Tj
2.2564 0 Td
(time)Tj
2.0295 0 Td
(it)Tj
0.7881 0 Td
(seems)Tj
2.6078 0 Td
(unlikely)Tj
3.4299 0 Td
(that)Tj
1.7802 0 Td
(such)Tj
2.0579 0 Td
(differences)Tj
4.5638 0 Td
(could)Tj
2.4548 0 Td
(generate)Tj
3.6056 0 Td
(the)Tj
1.4683 0 Td
(overall)Tj
2.9084 0 Td
(benefits)Tj
3.3335 0 Td
(we)Tj
-34.7525 -1.2983 Td
(find)Tj
1.8481 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1508 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(aspirin)Tj
2.9877 0 Td
(taking.)Tj
-12.0698 -1.2983 Td
(There)Tj
2.5795 0 Td
(are)Tj
1.4513 0 Td
(many)Tj
2.4775 0 Td
(sources)Tj
3.1918 0 Td
(of)Tj
1.0148 0 Td
(possible)Tj
3.4128 0 Td
(bias)Tj
1.7859 0 Td
(and)Tj
1.7291 0 Td
(in)Tj
1.0375 0 Td
(reviewing)Tj
4.1272 0 Td
(the)Tj
1.4683 0 Td
(present)Tj
3.1635 0 Td
(reports)Tj
3.067 0 Td
(we)Tj
1.3266 0 Td
(were)Tj
-33.029 -1.3039 Td
(impressed)Tj
4.2802 0 Td
(by)Tj
1.1736 0 Td
(the)Tj
1.457 0 Td
(frequency)Tj
4.1782 0 Td
(with)Tj
1.9899 0 Td
(which)Tj
2.6362 0 Td
(authors)Tj
3.2372 0 Td
(included)Tj
3.702 0 Td
(evidence)Tj
3.702 0 Td
(that)Tj
1.7688 0 Td
(the)Tj
1.4627 0 Td
(patients)Tj
3.3562 0 Td
(taking)Tj
2.7212 0 Td
(aspi-)Tj
-35.6652 -1.2982 Td
(rin)Tj
1.4059 0 Td
(were)Tj
2.1203 0 Td
(older)Tj
2.2961 0 Td
(than)Tj
2.0296 0 Td
(patients)Tj
3.3675 0 Td
(not)Tj
1.5761 0 Td
(taking)Tj
2.7269 0 Td
(aspirin,)Tj
3.2144 0 Td
(and)Tj
1.7292 0 Td
(had)Tj
1.7121 0 Td
(a)Tj
0.6519 0 Td
(higher)Tj
2.8007 0 Td
(prevalence)Tj
4.49 0 Td
(of)Tj
1.0148 0 Td
(co-morbidity,)Tj
-31.1355 -1.2983 Td
(usually)Tj
3.016 0 Td
(because)Tj
3.3222 0 Td
(of)Tj
1.0148 0 Td
(prevalent)Tj
3.9344 0 Td
(cardiovascular)Tj
6.0038 0 Td
(disease.)Tj
3.2428 0 Td
(Both)Tj
2.1316 0 Td
(these)Tj
2.2564 0 Td
(differences)Tj
4.5637 0 Td
(will)Tj
1.6668 0 Td
(operate)Tj
3.1918 0 Td
(against)Tj
-34.3443 -1.3039 Td
(the)Tj
1.4683 0 Td
(detection)Tj
3.9401 0 Td
(of)Tj
1.0148 0 Td
(possible)Tj
3.4072 0 Td
(benefit)Tj
2.9764 0 Td
(being)Tj
2.4321 0 Td
(shown)Tj
2.846 0 Td
(for)Tj
1.3889 0 Td
(aspirin.)Tj
-18.2776 -1.2983 Td
(In)Tj
1.1111 0 Td
(a)Tj
0.652 0 Td
(commentary)Tj
5.3234 0 Td
(that)Tj
1.7745 0 Td
(details)Tj
2.7779 0 Td
(a)Tj
0.6577 0 Td
(number)Tj
3.4185 0 Td
(of)Tj
1.0148 0 Td
(possible)Tj
3.4073 0 Td
(sources)Tj
3.1974 0 Td
(of)Tj
1.0148 0 Td
(bias,)Tj
2.0126 0 Td
(Frouws)Tj
3.1975 0 Td
(and)Tj
1.7291 0 Td
(colleagues)Tj
-32.4848 -1.2983 Td
(comment)Tj
4.0591 0 Td
(that)Tj
1.7802 0 Td
(`oncologists)Tj
4.9322 0 Td
(may)Tj
1.9333 0 Td
(withhold)Tj
3.804 0 Td
(aspirin)Tj
2.9877 0 Td
(treatment)Tj
4.1329 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(most)Tj
2.2054 0 Td
(seriously)Tj
3.7417 0 Td
(ill)Tj
0.9807 0 Td
(patients)Tj
-33.063 -1.3039 Td
(because)Tj
3.3165 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(poor)Tj
2.1203 0 Td
(prognosis,)Tj
4.3483 0 Td
(leading)Tj
3.1351 0 Td
(to)Tj
1.0261 0 Td
(reverse)Tj
3.0501 0 Td
(causality')Tj
3.8778 0 Td
([)Tj
0.83 0.64 0.02 0 k
(65)Tj
0 g
(].)Tj
2.0806 0 Td
(We)Tj
1.6044 0 Td
(see)Tj
1.4286 0 Td
(no)Tj
1.2756 0 Td
(way)Tj
1.7915 0 Td
(to)Tj
1.0261 0 Td
(examine)Tj
-32.5698 -1.2982 Td
(this)Tj
1.6724 0 Td
(particular)Tj
4.1102 0 Td
(bias,)Tj
2.0126 0 Td
(and)Tj
1.7348 0 Td
(yet,)Tj
1.6214 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(other)Tj
2.3471 0 Td
(hand,)Tj
2.4831 0 Td
(if)Tj
0.7767 0 Td
(physicians)Tj
4.3823 0 Td
(had)Tj
1.7065 0 Td
(withdrawn)Tj
4.5637 0 Td
(aspirin)Tj
2.9877 0 Td
(from)Tj
-33.1424 -1.2983 Td
(patients)Tj
3.3675 0 Td
(who)Tj
1.9389 0 Td
(were)Tj
2.1203 0 Td
(seriously)Tj
3.7417 0 Td
(ill)Tj
0.9808 0 Td
(or)Tj
1.0941 0 Td
(showed)Tj
3.2542 0 Td
(marked)Tj
3.2938 0 Td
(deterioration)Tj
5.4595 0 Td
(this)Tj
1.6781 0 Td
(could)Tj
2.4491 0 Td
(have)Tj
2.0636 0 Td
(led)Tj
1.4174 0 Td
(to)Tj
1.0261 0 Td
(a)Tj
-33.8851 -1.2983 Td
(rebound)Tj
3.6339 0 Td
(in)Tj
1.0318 0 Td
(vascular)Tj
3.4753 0 Td
(deaths)Tj
2.7893 0 Td
([)Tj
0.83 0.64 0.02 0 k
(66)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(68)Tj
0 g
(],)Tj
3.5489 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.4683 0 Td
(evidence)Tj
3.7134 0 Td
(presented)Tj
4.1158 0 Td
(for)Tj
1.3833 0 Td
(all-cause)Tj
3.668 0 Td
(mortality)Tj
3.9175 0 Td
(makes)Tj
-34.4747 -1.3039 Td
(it)Tj
0.7823 0 Td
(seem)Tj
2.2507 0 Td
(likely)Tj
2.3527 0 Td
(that)Tj
1.7802 0 Td
(if)Tj
0.771 0 Td
(any)Tj
1.6611 0 Td
(such)Tj
2.0579 0 Td
(a)Tj
0.652 0 Td
(process)Tj
3.1861 0 Td
(did)Tj
1.5421 0 Td
(occur,)Tj
2.6985 0 Td
(it)Tj
0.7881 0 Td
(must)Tj
2.228 0 Td
(have)Tj
2.0579 0 Td
(been)Tj
2.1203 0 Td
(minor.)Tj
-25.7327 -1.2983 Td
(A)Tj
0.907 0 Td
(recent)Tj
2.7043 0 Td
(paper)Tj
2.4831 0 Td
(by)Tj
1.1849 0 Td
(Rothwell)Tj
3.77 0 Td
(et)Tj
0.9411 0 Td
(al)Tj
0.9015 0 Td
([)Tj
0.83 0.64 0.02 0 k
(69)Tj
0 g
(])Tj
1.8481 0 Td
(based)Tj
2.4718 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(long-term)Tj
4.252 0 Td
(follow-up)Tj
4.0932 0 Td
(of)Tj
1.0148 0 Td
(five)Tj
1.6497 0 Td
(primary)Tj
3.4526 0 Td
(trials)Tj
-35.6142 -1.2982 Td
(of)Tj
1.0147 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7292 0 Td
(vascular)Tj
3.4696 0 Td
(disease,)Tj
3.2428 0 Td
(investigated)Tj
4.9889 0 Td
(possible)Tj
3.4129 0 Td
(interactions)Tj
4.9663 0 Td
(between)Tj
3.5262 0 Td
(age/body)Tj
3.8721 0 Td
(weight/)Tj
-33.2104 -1.3039 Td
(dose)Tj
2.0352 0 Td
(of)Tj
1.0148 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.474 0 Td
(20-year)Tj
3.2032 0 Td
(incidence)Tj
4.0705 0 Td
(of)Tj
1.0148 0 Td
(colon)Tj
2.4548 0 Td
(cancer.)Tj
3.067 0 Td
(In)Tj
1.1112 0 Td
(brief,)Tj
2.3017 0 Td
(while)Tj
2.3698 0 Td
(low-dose)Tj
3.8267 0 Td
(aspirin)Tj
2.9877 0 Td
(\(75)Tj
-35.6482 -1.2983 Td
(100)Tj
1.644 0 Td
(mg\))Tj
1.8482 0 Td
(was)Tj
1.6951 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
2.0013 0 Td
(a)Tj
0.6519 0 Td
(significant)Tj
4.388 0 Td
(reduction)Tj
4.1159 0 Td
(in)Tj
1.0318 0 Td
(participants)Tj
4.9606 0 Td
(who)Tj
1.9389 0 Td
(weighed)Tj
3.5376 0 Td
(less)Tj
1.6101 0 Td
(than)Tj
-33.681 -1.2983 Td
(70Kg,)Tj
2.5341 0 Td
(significance)Tj
4.9379 0 Td
(was)Tj
1.7008 0 Td
(lost)Tj
1.6271 0 Td
(in)Tj
1.0375 0 Td
(subjects)Tj
3.3788 0 Td
(weighing)Tj
3.8665 0 Td
(70Kg)Tj
2.313 0 Td
(and)Tj
1.7291 0 Td
(over.)Tj
2.2054 0 Td
(With)Tj
2.279 0 Td
(reference)Tj
3.9118 0 Td
(to)Tj
1.0261 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
-35.5348 -1.3039 Td
(the)Tj
1.4683 0 Td
(treatment)Tj
4.1329 0 Td
(of)Tj
1.0204 0 Td
(cancer,)Tj
3.0671 0 Td
(the)Tj
1.4683 0 Td
(report)Tj
2.7099 0 Td
(suggests)Tj
3.481 0 Td
(`that)Tj
2.0069 0 Td
(low-dose)Tj
3.8267 0 Td
(aspirin)Tj
2.9877 0 Td
(might)Tj
2.5966 0 Td
(accelerate)Tj
4.1215 0 Td
(growth)Tj
3.0727 0 Td
(of)Tj
-35.96 -1.2982 Td
(some)Tj
2.33 0 Td
(existing)Tj
3.3165 0 Td
(cancers)Tj
3.2032 0 Td
(at)Tj
0.9524 0 Td
(lower)Tj
2.4548 0 Td
(body)Tj
2.2167 0 Td
(size,)Tj
1.9105 0 Td
(particularly)Tj
4.8075 0 Td
(at)Tj
0.9525 0 Td
(older)Tj
2.296 0 Td
(ages.')Tj
2.3471 0 Td
(A)Tj
0.9014 0 Td
(number)Tj
3.4186 0 Td
(of)Tj
1.0148 0 Td
(randomised)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
31.7412 0 Td
(10)Tj
1.304 0 Td
(/)Tj
ET
endstream
endobj
335 0 obj
<>stream
endstream
endobj
336 0 obj
<>stream
endstream
endobj
337 0 obj
<>stream
endstream
endobj
338 0 obj
<>stream
endstream
endobj
339 0 obj
<>stream
endstream
endobj
340 0 obj
<>stream
endstream
endobj
341 0 obj
<>stream
endstream
endobj
342 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
343 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 344 0 R/Annots 345 0 R/Contents 346 0 R/TrimBox[0 0 612 792]>>
endobj
345 0 obj
[347 0 R 348 0 R 349 0 R 350 0 R 351 0 R 352 0 R 353 0 R 354 0 R 355 0 R 356 0 R 357 0 R 358 0 R 359 0 R 360 0 R 361 0 R 362 0 R 363 0 R 364 0 R 365 0 R 366 0 R 367 0 R 368 0 R 369 0 R 370 0 R 371 0 R 372 0 R 373 0 R 374 0 R 375 0 R]
endobj
347 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref016)>>
endobj
348 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref070)>>
endobj
349 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref073)>>
endobj
350 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref074)>>
endobj
351 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref075)>>
endobj
352 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref075)>>
endobj
353 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref076)>>
endobj
354 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref077)>>
endobj
355 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref078)>>
endobj
356 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref079)>>
endobj
357 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref080)>>
endobj
358 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref081)>>
endobj
359 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref082)>>
endobj
360 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref083)>>
endobj
361 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref084)>>
endobj
362 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref085)>>
endobj
363 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref086)>>
endobj
364 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref087)>>
endobj
365 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref088)>>
endobj
366 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref089)>>
endobj
367 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref016)>>
endobj
368 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref070)>>
endobj
369 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref073)>>
endobj
370 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref016)>>
endobj
371 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref016)>>
endobj
372 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref016)>>
endobj
373 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref073)>>
endobj
374 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref016)>>
endobj
375 0 obj
<>/Border[0 0 0]/A 376 0 R>>
endobj
376 0 obj
<>
endobj
346 0 obj
[377 0 R 378 0 R 379 0 R 380 0 R 381 0 R 382 0 R 383 0 R 384 0 R 385 0 R 386 0 R 387 0 R 388 0 R 389 0 R 390 0 R 391 0 R 392 0 R 393 0 R 394 0 R 395 0 R 396 0 R 397 0 R]
endobj
377 0 obj
<>stream
q
0.83 0.64 0.02 0 k
460.6866 706.337 m
470.211 706.337 l
h
f*
474.6898 706.337 m
484.1575 706.337 l
h
f*
489.3732 706.337 m
498.8409 706.337 l
h
f*
431.4331 615.3449 m
441.411 615.3449 l
h
f*
425.2535 589.3228 m
435.2315 589.3228 l
h
f*
419.3008 498.3307 m
429.2787 498.3307 l
h
f*
203.6409 472.3087 m
213.6189 472.3087 l
h
f*
366.8598 420.3213 m
376.3843 420.3213 l
h
f*
378.652 420.3213 m
388.1764 420.3213 l
h
f*
388.5732 407.3386 m
398.0976 407.3386 l
h
f*
400.3654 407.3386 m
409.8898 407.3386 l
h
f*
365.5559 381.3165 m
375.5339 381.3165 l
h
f*
378.0283 381.3165 m
388.0063 381.3165 l
h
f*
296.0504 368.3339 m
306.085 368.3339 l
h
f*
316.1764 355.3512 m
326.1543 355.3512 l
h
f*
328.6488 355.3512 m
338.6835 355.3512 l
h
f*
239.2441 329.3291 m
249.222 329.3291 l
h
f*
501.1087 303.3071 m
511.1433 303.3071 l
h
f*
327.2315 238.337 m
337.3228 238.337 l
h
f*
203.6976 173.3102 m
213.7323 173.3102 l
h
f*
489.3732 107.9433 m
498.8976 107.9433 l
h
f*
501.1654 107.9433 m
510.6898 107.9433 l
h
f*
515.8488 107.9433 m
525.3732 107.9433 l
h
f*
221.2724 94.9039 m
230.7969 94.9039 l
h
f*
268.1575 94.9039 m
277.6819 94.9039 l
h
f*
323.2063 94.9039 m
332.7307 94.9039 l
h
f*
334.9417 94.9039 m
344.4661 94.9039 l
h
f*
430.8094 94.9039 m
440.2772 94.9039 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(trials)Tj
2.194 0 Td
(of)Tj
1.0147 0 Td
(aspirin)Tj
2.9877 0 Td
(as)Tj
1.0148 0 Td
(an)Tj
1.2019 0 Td
(adjunct)Tj
3.2372 0 Td
(treatment)Tj
4.1385 0 Td
(of)Tj
1.0148 0 Td
(cancer)Tj
2.8403 0 Td
(are)Tj
1.4514 0 Td
(in)Tj
1.0374 0 Td
(progress)Tj
3.5943 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7405 0 Td
(70)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(73)Tj
0 g
(])Tj
2.9764 0 Td
(and)Tj
1.7291 0 Td
(these)Tj
2.2563 0 Td
(will)Tj
-34.4293 -1.3039 Td
(give)Tj
1.8311 0 Td
(opportunity)Tj
5.0343 0 Td
(to)Tj
1.0262 0 Td
(test)Tj
1.5987 0 Td
(any)Tj
1.6554 0 Td
(interactions)Tj
4.9719 0 Td
(of)Tj
1.0148 0 Td
(benefit)Tj
2.9764 0 Td
(with)Tj
1.9956 0 Td
(age,)Tj
1.7688 0 Td
(body)Tj
2.2167 0 Td
(weight)Tj
2.8856 0 Td
(and)Tj
1.7291 0 Td
(dose)Tj
2.041 0 Td
(of)Tj
1.0148 0 Td
(aspirin.)Tj
-33.7604 -1.2982 Td
(In)Tj
1.1055 0 Td
(the)Tj
1.474 0 Td
(meantime,)Tj
4.4787 0 Td
(observational)Tj
5.5785 0 Td
(evidence)Tj
3.7134 0 Td
(is)Tj
0.8447 0 Td
(the)Tj
1.4683 0 Td
(main)Tj
2.2904 0 Td
(basis)Tj
2.1487 0 Td
(for)Tj
1.3889 0 Td
(decisions)Tj
3.9062 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.4684 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(aspirin)Tj
2.9877 0 Td
(in)Tj
-36.6744 -1.2983 Td
(cancer)Tj
2.8402 0 Td
(treatment.)Tj
0.02 Tc
-1.644 -1.2983 Td
(Iatrogenic)Tj
4.541 0 Td
(bleeding)Tj
3.8211 0 Td
(attributable)Tj
5.1194 0 Td
(to)Tj
1.0714 0 Td
(aspirin)Tj
3.1578 0 Td
(is)Tj
0.8958 0 Td
(clearly)Tj
2.9877 0 Td
(a)Tj
0.6746 0 Td
(most)Tj
2.3017 0 Td
(important)Tj
4.5014 0 Td
(issue.)Tj
2.5285 0 Td
(It)Tj
0.9071 0 Td
(is)Tj
0.8957 0 Td
(impor-)Tj
-34.5994 -1.3039 Td
(tant)Tj
1.8935 0 Td
(however)Tj
3.7814 0 Td
(to)Tj
1.0715 0 Td
(consider)Tj
3.8437 0 Td
(not)Tj
1.6441 0 Td
(only)Tj
2.075 0 Td
(the)Tj
1.5363 0 Td
(frequency)Tj
4.405 0 Td
(but)Tj
1.6271 0 Td
(also)Tj
1.8652 0 Td
(the)Tj
1.542 0 Td
(severity)Tj
3.4639 0 Td
(of)Tj
1.0602 0 Td
(bleeding,)Tj
4.0705 0 Td
(and)Tj
1.8028 0 Td
(to)Tj
-35.6822 -1.2982 Td
(evaluate)Tj
3.651 0 Td
(this)Tj
1.7688 0 Td
(in)Tj
1.0885 0 Td
(comparison)Tj
5.2157 0 Td
(with)Tj
2.0919 0 Td
(the)Tj
1.5421 0 Td
(likely)Tj
2.4944 0 Td
(benefits)Tj
3.532 0 Td
(of)Tj
1.0601 0 Td
(aspirin)Tj
3.1578 0 Td
(taking,)Tj
3.1238 0 Td
(and)Tj
1.7971 0 Td
(in)Tj
1.0885 0 Td
(particular)Tj
4.3483 0 Td
(the)Tj
-35.96 -1.2983 Td
(reduction)Tj
4.3313 0 Td
(in)Tj
1.0828 0 Td
(all-cause)Tj
3.8834 0 Td
(mortality)Tj
4.1329 0 Td
(attributable)Tj
5.1194 0 Td
(to)Tj
1.0714 0 Td
(aspirin)Tj
3.1521 0 Td
([)Tj
0.83 0.64 0.02 0 k
(74)Tj
0 g
(].)Tj
2.1997 0 Td
(The)Tj
1.8539 0 Td
(evidence)Tj
3.9061 0 Td
(on)Tj
1.3209 0 Td
(bleeding)Tj
-32.0539 -1.3039 Td
(summarised)Tj
5.3687 0 Td
(earlier)Tj
2.9254 0 Td
(in)Tj
1.0828 0 Td
(this)Tj
1.7745 0 Td
(report)Tj
2.8516 0 Td
(gives)Tj
2.3131 0 Td
(a)Tj
0.6746 0 Td
(measure)Tj
3.7474 0 Td
(of)Tj
1.0658 0 Td
(reassurance)Tj
5.1647 0 Td
(on)Tj
1.3209 0 Td
(bleeding)Tj
3.8211 0 Td
(and)Tj
1.8028 0 Td
(on)Tj
1.321 0 Td
(fatal)Tj
-35.2344 -1.2983 Td
(bleeding)Tj
3.821 0 Td
(attributable)Tj
5.1194 0 Td
(to)Tj
1.0715 0 Td
(aspirin.)Tj
3.4072 0 Td
(Elsewhere,)Tj
4.7111 0 Td
(however,)Tj
4.0309 0 Td
([)Tj
0.83 0.64 0.02 0 k
(75)Tj
0 g
(])Tj
1.9445 0 Td
(we)Tj
1.3777 0 Td
(have)Tj
2.1543 0 Td
(reported)Tj
3.8551 0 Td
(a)Tj
0.6746 0 Td
(careful)Tj
-32.1673 -1.2983 Td
(examination)Tj
5.4935 0 Td
(of)Tj
1.0658 0 Td
(the)Tj
1.542 0 Td
(published)Tj
4.337 0 Td
(evidence)Tj
3.9061 0 Td
(on)Tj
1.3266 0 Td
(fatal)Tj
2.0353 0 Td
(bleeding)Tj
3.8211 0 Td
(attributable)Tj
5.125 0 Td
(to)Tj
1.0715 0 Td
(aspirin,)Tj
3.4015 0 Td
(showing)Tj
-33.1254 -1.3039 Td
(than)Tj
2.1259 0 Td
(the)Tj
1.5364 0 Td
(proportion)Tj
4.8755 0 Td
(of)Tj
1.0602 0 Td
(fatal)Tj
2.0409 0 Td
(bleeds)Tj
2.8517 0 Td
(which)Tj
2.7722 0 Td
(occurred)Tj
3.9855 0 Td
(in)Tj
1.0828 0 Td
(subjects)Tj
3.5717 0 Td
(randomised)Tj
5.2497 0 Td
(to)Tj
1.0715 0 Td
(aspirin)Tj
3.1521 0 Td
(is)Tj
-35.3761 -1.2982 Td
(lower)Tj
2.5681 0 Td
(that)Tj
1.8765 0 Td
(deaths)Tj
2.9367 0 Td
(due)Tj
1.7688 0 Td
(to)Tj
1.0772 0 Td
(spontaneous)Tj
5.5162 0 Td
(bleeding)Tj
3.8211 0 Td
(in)Tj
1.0828 0 Td
(subjects)Tj
3.5716 0 Td
(not)Tj
1.6441 0 Td
(on)Tj
1.3209 0 Td
(aspirin)Tj
3.1578 0 Td
(\(RR)Tj
1.8765 0 Td
(0.45;)Tj
2.2167 0 Td
(95%)Tj
2.0013 0 Td
(CI)Tj
-36.4363 -1.2983 Td
(0.25,)Tj
2.2166 0 Td
(0.80\),)Tj
2.5795 0 Td
(and)Tj
1.8029 0 Td
(overall,)Tj
3.3221 0 Td
(in)Tj
1.0829 0 Td
(52,583)Tj
2.965 0 Td
(subjects)Tj
3.5716 0 Td
(randomised)Tj
5.2498 0 Td
(to)Tj
1.0714 0 Td
(take)Tj
1.9673 0 Td
(aspirin,)Tj
3.4072 0 Td
(who)Tj
2.0069 0 Td
(together)Tj
3.7304 0 Td
(expe-)Tj
-34.9736 -1.3039 Td
(rienced)Tj
3.3732 0 Td
(261)Tj
1.7177 0 Td
(bleeding)Tj
3.8211 0 Td
(events,)Tj
3.1238 0 Td
(there)Tj
2.3811 0 Td
(was)Tj
1.7744 0 Td
(no)Tj
1.321 0 Td
(significant)Tj
4.6544 0 Td
(increase)Tj
3.6624 0 Td
(in)Tj
1.0828 0 Td
(fatal)Tj
2.0409 0 Td
(bleeds)Tj
2.8517 0 Td
(in)Tj
1.0828 0 Td
(the)Tj
1.542 0 Td
(sub-)Tj
-34.4293 -1.2983 Td
(jects)Tj
2.1032 0 Td
(on)Tj
1.321 0 Td
(aspirin,)Tj
3.4015 0 Td
(compared)Tj
4.4391 0 Td
(to)Tj
1.0715 0 Td
(spontaneous)Tj
5.5161 0 Td
(fatal)Tj
2.041 0 Td
(bleeds)Tj
2.8573 0 Td
(in)Tj
1.0828 0 Td
(subjects)Tj
3.566 0 Td
(randomised)Tj
5.2497 0 Td
(not)Tj
1.6441 0 Td
(to)Tj
-34.2933 -1.2982 Td
(receive)Tj
3.1747 0 Td
(aspirin)Tj
3.1521 0 Td
(\(RR)Tj
1.8766 0 Td
(0.77;)Tj
2.2166 0 Td
(95%)Tj
2.0013 0 Td
(CI)Tj
1.2699 0 Td
(0.41,)Tj
2.2167 0 Td
(1.43)Tj
1.9672 0 Td
(P)Tj
/F11 1 Tf
0 Tc
(<)Tj
/F5 1 Tf
0.02 Tc
(0.91\))Tj
3.6907 0 Td
([)Tj
0.83 0.64 0.02 0 k
(75)Tj
0 g
(].)Tj
2.194 0 Td
(A)Tj
0.9298 0 Td
(recent)Tj
2.8516 0 Td
(report)Tj
2.8516 0 Td
(describes)Tj
-30.3928 -1.2983 Td
(200,000)Tj
3.4639 0 Td
(new)Tj
1.9502 0 Td
(users)Tj
2.3867 0 Td
(of)Tj
1.0602 0 Td
(low-dose)Tj
4.0195 0 Td
(aspirin,)Tj
3.4016 0 Td
(matched)Tj
3.8437 0 Td
(with)Tj
2.092 0 Td
(a)Tj
0.6803 0 Td
(1:1)Tj
1.4683 0 Td
(cohort)Tj
2.999 0 Td
(of)Tj
1.0602 0 Td
(non)Tj
1.8992 0 Td
(aspirin)Tj
3.1521 0 Td
(users)Tj
-33.4769 -1.3039 Td
([)Tj
0.83 0.64 0.02 0 k
(76)Tj
0 g
(].)Tj
2.194 0 Td
(During)Tj
3.2825 0 Td
(a)Tj
0.6746 0 Td
(follow-up)Tj
4.3143 0 Td
(of)Tj
1.0601 0 Td
(5.4)Tj
1.4684 0 Td
(years)Tj
2.3867 0 Td
(there)Tj
2.3811 0 Td
(was)Tj
1.7745 0 Td
(an)Tj
1.2472 0 Td
(excess)Tj
2.8233 0 Td
(in)Tj
1.0829 0 Td
(total)Tj
2.1259 0 Td
(gastrointestinal)Tj
6.7294 0 Td
(bleeds)Tj
-33.5449 -1.2983 Td
(among)Tj
3.1124 0 Td
(the)Tj
1.542 0 Td
(patients)Tj
3.5603 0 Td
(taking)Tj
2.8743 0 Td
(aspirin,)Tj
3.4016 0 Td
(but)Tj
1.627 0 Td
(no)Tj
1.321 0 Td
(excess)Tj
2.8233 0 Td
(in)Tj
1.0828 0 Td
(fatal)Tj
2.0409 0 Td
(bleeds)Tj
2.8517 0 Td
(\(Rodr)Tj
0 Tc
2.4264 0.051 Td
()Tj
0.02 Tc
0.3515 -0.051 Td
(guez)Tj
2.1486 0 Td
(G,)Tj
1.2076 0 Td
(Lanas)Tj
2.6532 0 Td
(A,)Tj
-35.0246 -1.2983 Td
(2018.)Tj
2.4661 0 Td
(Personal)Tj
3.8607 0 Td
(communication.)Tj
7.1773 0 Td
(July,)Tj
2.1203 0 Td
(19\).)Tj
-0.004 Tc
-14.4282 -1.3039 Td
(Furthermore,)Tj
5.6182 0 Td
(proton)Tj
2.9707 0 Td
(pump)Tj
2.6022 0 Td
(inhibitor)Tj
3.7814 0 Td
(drugs)Tj
2.4718 0 Td
(\(PPIs\))Tj
2.7155 0 Td
(provide)Tj
3.2882 0 Td
(a)Tj
0.6576 0 Td
(high)Tj
2.007 0 Td
(level)Tj
2.0125 0 Td
(of)Tj
1.0148 0 Td
(protection)Tj
4.3824 0 Td
(from)Tj
-34.7185 -1.2982 Td
(intestinal)Tj
3.9117 0 Td
(bleeding)Tj
3.6284 0 Td
(whatever)Tj
3.838 0 Td
(its)Tj
1.1452 0 Td
(aetiology)Tj
3.8211 0 Td
([)Tj
0.83 0.64 0.02 0 k
(77)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(78)Tj
0 g
(],)Tj
3.2542 0 Td
(and)Tj
1.7291 0 Td
(formulae)Tj
3.8381 0 Td
(to)Tj
1.0261 0 Td
(assist)Tj
2.3017 0 Td
(in)Tj
1.0375 0 Td
(judging)Tj
3.2768 0 Td
(the)Tj
1.4684 0 Td
(risk)Tj
1.7178 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
-37.0089 -1.2983 Td
(gastrointestinal)Tj
6.3495 0 Td
(bleed)Tj
2.3471 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.6519 0 Td
(subject)Tj
3.0161 0 Td
(are)Tj
1.4513 0 Td
(available)Tj
3.6623 0 Td
([)Tj
0.83 0.64 0.02 0 k
(79)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(80)Tj
0 g
(].)Tj
0.02 Tc
-17.3195 -1.3039 Td
(There)Tj
2.6985 0 Td
(is)Tj
0.8958 0 Td
(also)Tj
1.8652 0 Td
(the)Tj
1.542 0 Td
(issue)Tj
2.279 0 Td
(of)Tj
1.0659 0 Td
(venous)Tj
3.1861 0 Td
(thromboembolism)Tj
8.0673 0 Td
(associated)Tj
4.4957 0 Td
(with)Tj
2.092 0 Td
(cancer,)Tj
3.2371 0 Td
(and)Tj
1.8029 0 Td
(aspirin)Tj
-34.4237 -1.2983 Td
(appears)Tj
3.4469 0 Td
(to)Tj
1.0714 0 Td
(be)Tj
1.1963 0 Td
(an)Tj
1.2529 0 Td
(effective)Tj
3.7247 0 Td
(prophylactic)Tj
5.4991 0 Td
([)Tj
0.83 0.64 0.02 0 k
(81)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(82)Tj
0 g
(].)Tj
3.4413 0 Td
(Patients)Tj
3.6056 0 Td
(with)Tj
2.092 0 Td
(malignancy)Tj
5.1023 0 Td
(appear)Tj
3.0614 0 Td
(to)Tj
1.0715 0 Td
(be)Tj
1.1962 0 Td
(in)Tj
1.0828 0 Td
(a)Tj
-36.8444 -1.2983 Td
(hypercoagulable)Tj
7.0865 0 Td
(state)Tj
2.1543 0 Td
([)Tj
0.83 0.64 0.02 0 k
(83)Tj
0 g
(])Tj
1.9503 0 Td
(with)Tj
2.0919 0 Td
(marked)Tj
3.4356 0 Td
(increases)Tj
4.0478 0 Td
(in)Tj
1.0829 0 Td
(both)Tj
2.1599 0 Td
(incidence)Tj
4.286 0 Td
(and)Tj
1.8028 0 Td
(mortality)Tj
4.1329 0 Td
(of)Tj
-34.2309 -1.2982 Td
(venous)Tj
3.1861 0 Td
(thromboembolism)Tj
8.0673 0 Td
([)Tj
0.83 0.64 0.02 0 k
(84)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(85)Tj
0 g
(])Tj
3.1975 0 Td
(and)Tj
1.8028 0 Td
(The)Tj
1.8539 0 Td
(American)Tj
4.3823 0 Td
(Society)Tj
3.2371 0 Td
(of)Tj
1.0602 0 Td
(Clinical)Tj
3.5093 0 Td
(Oncology)Tj
4.3143 0 Td
(has)Tj
-34.6108 -1.3039 Td
(recommended)Tj
6.2985 0 Td
(that)Tj
1.8765 0 Td
(prophylactic)Tj
5.4935 0 Td
(anticoagulants)Tj
6.3496 0 Td
(be)Tj
1.1962 0 Td
(considered)Tj
4.8415 0 Td
(for)Tj
1.457 0 Td
(all)Tj
1.2189 0 Td
(hospitalized)Tj
5.3008 0 Td
(cancer)Tj
-34.0325 -1.2983 Td
(patients)Tj
3.5602 0 Td
([)Tj
0.83 0.64 0.02 0 k
(86)Tj
0 g
(].)Tj
0.024 Tc
-2.364 -1.2983 Td
(A)Tj
0.9354 0 Td
(plea)Tj
1.9502 0 Td
(for)Tj
1.474 0 Td
(better)Tj
2.7099 0 Td
(and)Tj
1.8142 0 Td
(more)Tj
2.4491 0 Td
(complete)Tj
4.1045 0 Td
(information)Tj
5.3858 0 Td
(on)Tj
1.3323 0 Td
(aspirin)Tj
3.1805 0 Td
(and)Tj
1.8141 0 Td
(cancer)Tj
3.0104 0 Td
(has)Tj
1.6271 0 Td
(been)Tj
2.2337 0 Td
(made)Tj
-35.2174 -1.3039 Td
(by)Tj
1.2302 0 Td
(representatives)Tj
6.616 0 Td
(of)Tj
1.0658 0 Td
(the)Tj
1.5534 0 Td
(general)Tj
3.3222 0 Td
(public)Tj
2.8743 0 Td
(in)Tj
1.0885 0 Td
(a)Tj
0.6803 0 Td
(Citizens')Tj
3.9231 0 Td
(Jury)Tj
2.0126 0 Td
(held)Tj
2.0523 0 Td
(in)Tj
1.0885 0 Td
(2006)Tj
2.2337 0 Td
([)Tj
0.83 0.64 0.02 0 k
(87)Tj
0 g
(])Tj
1.9559 0 Td
(and)Tj
1.8141 0 Td
(the)Tj
1.5477 0 Td
(jurors)Tj
-35.0586 -1.2982 Td
(added)Tj
2.8006 0 Td
(to)Tj
1.0771 0 Td
(their)Tj
2.2507 0 Td
(plea)Tj
1.9502 0 Td
(the)Tj
1.5534 0 Td
(phrase:)Tj
3.2768 0 Td
(`even)Tj
2.4378 0 Td
(before)Tj
2.9084 0 Td
(there)Tj
2.4037 0 Td
(is)Tj
0.9014 0 Td
(agreement)Tj
4.6828 0 Td
(between)Tj
3.7247 0 Td
(doctors'.)Tj
3.9062 0 Td
(A)Tj
0.9354 0 Td
(recent)Tj
-34.8092 -1.2983 Td
(judgement)Tj
4.7621 0 Td
(by)Tj
1.2359 0 Td
(the)Tj
1.5534 0 Td
(UK)Tj
1.6894 0 Td
(Supreme)Tj
3.9742 0 Td
(Court)Tj
2.7269 0 Td
(went)Tj
2.2847 0 Td
(further)Tj
3.2258 0 Td
(and)Tj
1.8142 0 Td
(established)Tj
4.9039 0 Td
(that)Tj
1.8878 0 Td
(if)Tj
0.8334 0 Td
(a)Tj
0.6803 0 Td
(patient)Tj
3.2032 0 Td
(had)Tj
-34.7752 -1.3039 Td
(not)Tj
1.6554 0 Td
(had)Tj
1.7971 0 Td
(opportunity)Tj
5.3405 0 Td
(to)Tj
1.0828 0 Td
(review)Tj
3.0104 0 Td
(all)Tj
1.2302 0 Td
(reasonable)Tj
4.7565 0 Td
(variant)Tj
3.2201 0 Td
(treatments)Tj
4.7792 0 Td
(and)Tj
1.8142 0 Td
(to)Tj
1.0828 0 Td
(express)Tj
3.3392 0 Td
(his/her)Tj
-33.1084 -1.2983 Td
(views)Tj
2.5511 0 Td
(in)Tj
1.0885 0 Td
(a)Tj
0.6803 0 Td
(dialogue)Tj
3.8438 0 Td
(between)Tj
3.7247 0 Td
(doctor)Tj
3.0217 0 Td
(and)Tj
1.8142 0 Td
(patient,)Tj
3.4582 0 Td
(then)Tj
2.1316 0 Td
(the)Tj
1.5534 0 Td
(process)Tj
3.3789 0 Td
(of)Tj
1.0715 0 Td
(`informed)Tj
4.4503 0 Td
(consent')Tj
-32.7682 -1.2983 Td
(could)Tj
2.5908 0 Td
(be)Tj
1.2076 0 Td
(called)Tj
2.6872 0 Td
(into)Tj
1.9559 0 Td
(question.[)Tj
0.83 0.64 0.02 0 k
(88)Tj
0 g
(])Tj
5.879 0 Td
(The)Tj
1.8652 0 Td
(court)Tj
2.4888 0 Td
(added)Tj
2.8006 0 Td
(to)Tj
1.0828 0 Td
(this)Tj
1.7858 0 Td
(judgement)Tj
4.7622 0 Td
(that)Tj
1.8879 0 Td
(if)Tj
0.8334 0 Td
(information)Tj
-31.8272 -1.3039 Td
(is)Tj
0.9014 0 Td
(material,)Tj
3.9911 0 Td
(doctors)Tj
3.4129 0 Td
(should)Tj
3.0841 0 Td
(generally)Tj
4.0875 0 Td
(disclose)Tj
3.5603 0 Td
(it)Tj
0.8391 0 Td
(and)Tj
1.8141 0 Td
(should)Tj
3.0841 0 Td
(not)Tj
1.6611 0 Td
(wait)Tj
2.0126 0 Td
(for)Tj
1.474 0 Td
(the)Tj
1.5534 0 Td
(patient)Tj
3.2031 0 Td
(to)Tj
1.0771 0 Td
(ask.)Tj
-35.7559 -1.2982 Td
(Unfortunately)Tj
6.2645 0 Td
(however,)Tj
4.0592 0 Td
(knowledge)Tj
4.7962 0 Td
(of)Tj
1.0714 0 Td
(the)Tj
1.5534 0 Td
(likely)Tj
2.5228 0 Td
(benefit)Tj
3.1692 0 Td
(from)Tj
2.3187 0 Td
(aspirin)Tj
3.1804 0 Td
(is)Tj
0.9071 0 Td
(limited,)Tj
3.5206 0 Td
(and)Tj
-33.3635 -1.2983 Td
(apprehension)Tj
6.0037 0 Td
(about)Tj
2.6305 0 Td
(the)Tj
1.5534 0 Td
(possible)Tj
3.634 0 Td
(side)Tj
1.9105 0 Td
(effects)Tj
2.9254 0 Td
(and)Tj
1.8141 0 Td
(attitudes)Tj
3.9061 0 Td
(towards)Tj
3.6 0 Td
(aspirin)Tj
3.1805 0 Td
(amongst)Tj
3.8494 0 Td
(pri-)Tj
-35.0076 -1.2983 Td
(mary)Tj
2.4094 0 Td
(care)Tj
1.9842 0 Td
(physicians)Tj
4.6602 0 Td
(is)Tj
0.907 0 Td
(likely)Tj
2.5229 0 Td
(to)Tj
1.0771 0 Td
(impede)Tj
3.3675 0 Td
(acceptance)Tj
4.8529 0 Td
(of)Tj
1.0715 0 Td
(the)Tj
1.5534 0 Td
(growing)Tj
3.7247 0 Td
(evidence)Tj
3.9345 0 Td
(of)Tj
1.0714 0 Td
(benefit.)Tj
-33.1367 -1.3039 Td
([)Tj
0.83 0.64 0.02 0 k
(89)Tj
0 g
(])Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 139.011 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Implications)Tj
6.0189 0 Td
(for)Tj
1.5402 0 Td
(clinical)Tj
3.5858 0 Td
(practice)Tj
4.0158 0 Td
(and)Tj
1.989 0 Td
(for)Tj
1.5402 0 Td
(research)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 122.0031 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(A)Tj
0.9014 0 Td
(number)Tj
3.4185 0 Td
(of)Tj
1.0148 0 Td
(randomised)Tj
5.006 0 Td
(trials)Tj
2.1996 0 Td
(are)Tj
1.4514 0 Td
(in)Tj
1.0318 0 Td
(progress.)Tj
3.8267 0 Td
(It)Tj
0.8561 0 Td
(will)Tj
1.6667 0 Td
(however)Tj
3.6114 0 Td
(be)Tj
1.1508 0 Td
(some)Tj
2.3301 0 Td
(years)Tj
2.262 0 Td
(before)Tj
2.7383 0 Td
(these)Tj
-33.4656 -1.2982 Td
(report)Tj
2.7099 0 Td
(and)Tj
1.7291 0 Td
(evidence)Tj
3.7133 0 Td
(will)Tj
1.6611 0 Td
(be)Tj
1.1509 0 Td
(limited)Tj
3.0671 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(more)Tj
2.3414 0 Td
(common)Tj
3.8495 0 Td
(cancers:)Tj
3.4299 0 Td
(colon)Tj
2.4491 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(70)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(73)Tj
0 g
(],)Tj
4.7225 0 Td
(oesopha-)Tj
-33.3182 -1.3039 Td
(geal)Tj
1.7858 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(],)Tj
2.0749 0 Td
(breast)Tj
2.6135 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(],)Tj
2.075 0 Td
(prostate)Tj
3.4299 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(73)Tj
0 g
(])Tj
3.0274 0 Td
(and)Tj
1.7291 0 Td
(lung.)Tj
2.228 0 Td
(One)Tj
1.9389 0 Td
(trial)Tj
1.8368 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(])Tj
1.8482 0 Td
(will)Tj
1.6611 0 Td
(also)Tj
1.7688 0 Td
(give)Tj
1.8255 0 Td
(evidence)Tj
3.7134 0 Td
(on)Tj
1.2699 0 Td
(aspirin)Tj
-34.8262 -1.2983 Td
(dose.)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
31.7412 0 Td
(11)Tj
1.304 0 Td
(/)Tj
ET
endstream
endobj
378 0 obj
<>stream
endstream
endobj
379 0 obj
<>stream
endstream
endobj
380 0 obj
<>stream
endstream
endobj
381 0 obj
<>stream
endstream
endobj
382 0 obj
<>stream
endstream
endobj
383 0 obj
<>stream
endstream
endobj
384 0 obj
<>stream
endstream
endobj
385 0 obj
<>stream
endstream
endobj
386 0 obj
<>stream
endstream
endobj
387 0 obj
<>stream
endstream
endobj
388 0 obj
<>stream
endstream
endobj
389 0 obj
<>stream
endstream
endobj
390 0 obj
<>stream
endstream
endobj
391 0 obj
<>stream
endstream
endobj
392 0 obj
<>stream
endstream
endobj
393 0 obj
<>stream
endstream
endobj
394 0 obj
<>stream
endstream
endobj
395 0 obj
<>stream
endstream
endobj
396 0 obj
<>stream
endstream
endobj
397 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
398 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 344 0 R/Annots 399 0 R/Contents 400 0 R/TrimBox[0 0 612 792]>>
endobj
399 0 obj
[401 0 R 402 0 R 403 0 R 404 0 R 405 0 R 406 0 R 407 0 R 408 0 R 409 0 R 410 0 R]
endobj
401 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref090)>>
endobj
402 0 obj
<>/Border[0 0 0]/A 411 0 R>>
endobj
411 0 obj
<>
endobj
403 0 obj
<>/Border[0 0 0]/A 412 0 R>>
endobj
412 0 obj
<>
endobj
404 0 obj
<>/Border[0 0 0]/Dest(Rpone.0203957.ref018)>>
endobj
405 0 obj
<>/Border[0 0 0]/A 413 0 R>>
endobj
413 0 obj
<>
endobj
406 0 obj
<>/Border[0 0 0]/A 414 0 R>>
endobj
414 0 obj
<>
endobj
407 0 obj
<>/Border[0 0 0]/A 415 0 R>>
endobj
415 0 obj
<>
endobj
408 0 obj
<>/Border[0 0 0]/A 416 0 R>>
endobj
416 0 obj
<>
endobj
409 0 obj
<>/Border[0 0 0]/A 417 0 R>>
endobj
417 0 obj
<>
endobj
410 0 obj
<>/Border[0 0 0]/A 418 0 R>>
endobj
418 0 obj
<>
endobj
400 0 obj
[419 0 R 420 0 R 421 0 R 422 0 R 423 0 R 424 0 R 425 0 R 426 0 R 427 0 R 428 0 R 429 0 R]
endobj
419 0 obj
<>stream
q
0.83 0.64 0.02 0 k
370.5449 641.3102 m
380.0693 641.3102 l
h
f*
448.4976 447.6472 m
458.022 447.6472 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 211.9748 707.4141 cm
BT
/F5 1 Tf
1 TL
-0.004 Tc
0 0 Td
(In)Tj
1.1055 0 Td
(the)Tj
1.4683 0 Td
(meantime,)Tj
4.473 0 Td
(observational)Tj
5.5786 0 Td
(evidence)Tj
3.7077 0 Td
(is)Tj
0.8447 0 Td
(the)Tj
1.4627 0 Td
(main)Tj
2.2847 0 Td
(basis)Tj
2.1486 0 Td
(for)Tj
1.3776 0 Td
(decisions)Tj
3.9062 0 Td
(on)Tj
1.2699 0 Td
(the)Tj
1.4683 0 Td
(use)Tj
1.525 0 Td
(of)Tj
1.0092 0 Td
(aspirin)Tj
-34.8262 -1.3039 Td
(as)Tj
1.0148 0 Td
(an)Tj
1.2018 0 Td
(additional)Tj
4.2746 0 Td
(treatment)Tj
4.1386 0 Td
(of)Tj
1.0148 0 Td
(cancer.)Tj
3.0671 0 Td
(There)Tj
2.5795 0 Td
(is)Tj
0.8504 0 Td
(much)Tj
2.5171 0 Td
(favourable)Tj
4.4107 0 Td
(evidence)Tj
3.7133 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4684 0 Td
(three)Tj
2.2677 0 Td
(main)Tj
-33.7944 -1.2982 Td
(cancers,)Tj
3.4298 0 Td
(but)Tj
1.5534 0 Td
(very)Tj
1.9219 0 Td
(little)Tj
2.0012 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4684 0 Td
(less)Tj
1.6157 0 Td
(common)Tj
3.8438 0 Td
(cancers,)Tj
3.4299 0 Td
(though)Tj
3.0727 0 Td
(what)Tj
2.1656 0 Td
(is)Tj
0.8448 0 Td
(available)Tj
3.668 0 Td
(is,)Tj
1.0715 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.474 0 Td
(whole,)Tj
-34.1118 -1.2983 Td
(encouraging.)Tj
5.4254 0 Td
(Because)Tj
3.3959 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(various)Tj
3.1408 0 Td
(uncertainties,)Tj
5.6409 0 Td
(the)Tj
1.4683 0 Td
(adequate)Tj
3.7928 0 Td
(informing)Tj
4.3029 0 Td
(of)Tj
1.0148 0 Td
(patients)Tj
3.3676 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-35.0473 -1.2983 Td
(benefits)Tj
3.3335 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4683 0 Td
(harm)Tj
2.3697 0 Td
(is)Tj
0.8504 0 Td
(difficult,)Tj
3.5773 0 Td
(but)Tj
1.5534 0 Td
(it)Tj
0.788 0 Td
(is)Tj
0.8447 0 Td
(important)Tj
4.2803 0 Td
(that)Tj
1.7802 0 Td
(shared)Tj
2.8686 0 Td
(decision)Tj
3.5433 0 Td
(making)Tj
3.2485 0 Td
(is)Tj
0.8504 0 Td
(not)Tj
1.576 0 Td
(com-)Tj
-34.6674 -1.3039 Td
(promised)Tj
4.0138 0 Td
(by)Tj
1.1792 0 Td
(`intrusive)Tj
3.9685 0 Td
(external)Tj
3.4299 0 Td
(decisions')Tj
4.1215 0 Td
([)Tj
0.83 0.64 0.02 0 k
(90)Tj
0 g
(].)Tj
-15.5167 -1.2982 Td
(Every)Tj
2.4944 0 Td
(possible)Tj
3.4129 0 Td
(effort)Tj
2.3924 0 Td
(should)Tj
2.9197 0 Td
(be)Tj
1.1509 0 Td
(made)Tj
2.4264 0 Td
(to)Tj
1.0205 0 Td
(encourage)Tj
4.3483 0 Td
(observational)Tj
5.5785 0 Td
(studies.)Tj
3.2088 0 Td
(More)Tj
2.4151 0 Td
(information)Tj
-32.5641 -1.2983 Td
(is)Tj
0.8448 0 Td
(required)Tj
3.6395 0 Td
(on)Tj
1.2756 0 Td
(markers)Tj
3.4979 0 Td
(of)Tj
1.0148 0 Td
(likely)Tj
2.3528 0 Td
(benefit)Tj
2.9763 0 Td
(from)Tj
2.2054 0 Td
(aspirin)Tj
2.9877 0 Td
(such)Tj
2.0636 0 Td
(as)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(PIK3CA)Tj
3.617 0 Td
(mutation,)Tj
4.1442 0 Td
(and)Tj
1.7291 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
-36.1074 -1.3039 Td
(optimal)Tj
3.2994 0 Td
(dose)Tj
2.0296 0 Td
(of)Tj
1.0035 0 Td
(aspirin)Tj
2.9764 0 Td
(for)Tj
1.3776 0 Td
(treatment,)Tj
4.354 0 Td
(taking)Tj
2.7155 0 Td
(account)Tj
3.3733 0 Td
(of)Tj
1.0091 0 Td
(age,)Tj
1.7574 0 Td
(body)Tj
2.2054 0 Td
(weight)Tj
2.8743 0 Td
(smoking)Tj
3.6793 0 Td
(and)Tj
1.7178 0 Td
(possibly)Tj
-34.3726 -1.2983 Td
(other)Tj
2.347 0 Td
(personal)Tj
3.6283 0 Td
(factors.)Tj
-4.7791 -1.2983 Td
(Finally,)Tj
3.1747 0 Td
(valid)Tj
2.1487 0 Td
(evidence)Tj
3.7133 0 Td
(on)Tj
1.2756 0 Td
(serious)Tj
3.0387 0 Td
(and)Tj
1.7292 0 Td
(fatal)Tj
1.9162 0 Td
(bleeding)Tj
3.634 0 Td
(attributable)Tj
4.8302 0 Td
(to)Tj
1.0261 0 Td
(aspirin,)Tj
3.2088 0 Td
(is)Tj
0.8504 0 Td
(urgently)Tj
-31.7421 -1.3039 Td
(required.)Tj
3.8607 0 Td
(An)Tj
1.457 0 Td
(increase)Tj
3.4696 0 Td
(in)Tj
1.0375 0 Td
(bleeding)Tj
3.6283 0 Td
(with)Tj
1.9956 0 Td
(age)Tj
1.542 0 Td
(has)Tj
1.542 0 Td
(been)Tj
2.126 0 Td
(well)Tj
1.8198 0 Td
(documented,)Tj
5.4709 0 Td
(but)Tj
1.5533 0 Td
(so)Tj
1.0885 0 Td
(also)Tj
1.7688 0 Td
(has)Tj
1.5421 0 Td
(an)Tj
-33.9021 -1.2982 Td
(increase)Tj
3.4695 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(benefits)Tj
3.3392 0 Td
(of)Tj
1.0148 0 Td
(aspirin)Tj
2.9877 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4684 0 Td
(balance)Tj
3.2371 0 Td
(between)Tj
3.5263 0 Td
(these)Tj
2.2564 0 Td
(outcomes)Tj
4.0875 0 Td
(needs)Tj
2.5058 0 Td
(to)Tj
1.0205 0 Td
(be)Tj
1.1508 0 Td
(evalu-)Tj
-34.2989 -1.2983 Td
(ated)Tj
1.9048 0 Td
(in)Tj
1.0318 0 Td
(different)Tj
3.6567 0 Td
(groups)Tj
2.9707 0 Td
(of)Tj
1.0148 0 Td
(subjects)Tj
3.3788 0 Td
(and)Tj
1.7292 0 Td
(patients.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 510.6897 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Supporting)Tj
5.537 0 Td
(information)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 493.6818 cm
BT
/F12 1 Tf
1 TL
-0.004 Tc
0 0 Td
(S1)Tj
1.2132 0 Td
(PRISMA)Tj
3.9288 0 Td
(Checklist.)Tj
/F5 1 Tf
-5.142 -1.2982 Td
(\(DOC\))Tj
/F12 1 Tf
0 -1.8992 Td
(S1)Tj
1.2132 0 Td
(Table.)Tj
2.8119 0 Td
(Aspirin)Tj
3.3902 0 Td
(treatment)Tj
4.3767 0 Td
(of)Tj
1.0658 0 Td
(cancer)Tj
2.931 0 Td
(in)Tj
1.0658 0 Td
(observational)Tj
5.8621 0 Td
(studies)Tj
3.1407 0 Td
(reported)Tj
3.8494 0 Td
(20152017.)Tj
/F5 1 Tf
4.9436 0 Td
(For)Tj
-34.6504 -1.2983 Td
(details)Tj
2.7779 0 Td
(of)Tj
1.0148 0 Td
(studies)Tj
2.9877 0 Td
(published)Tj
4.1215 0 Td
(before)Tj
2.7383 0 Td
(2015,)Tj
2.3527 0 Td
(see)Tj
1.423 0 Td
(our)Tj
1.6271 0 Td
(earlier)Tj
2.7609 0 Td
(report)Tj
2.7042 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(].)Tj
-24.5081 -1.3039 Td
(\(TIF\))Tj
/F12 1 Tf
0 -1.8992 Td
(S2)Tj
1.2132 0 Td
(Table.)Tj
2.8119 0 Td
(Association)Tj
5.0853 0 Td
(between)Tj
3.634 0 Td
(aspirin)Tj
3.1521 0 Td
(taking)Tj
2.8687 0 Td
(and)Tj
1.7915 0 Td
(metastatic)Tj
4.5354 0 Td
(spread.)Tj
/F5 1 Tf
-25.0921 -1.2983 Td
(\(TIF\))Tj
/F12 1 Tf
0 -1.8992 Td
(S1)Tj
1.2132 0 Td
(Fig.)Tj
1.7858 0 Td
(Flow)Tj
2.2507 0 Td
(diagram.)Tj
/F5 1 Tf
-5.2497 -1.3039 Td
(\(TIF\))Tj
/F12 1 Tf
0 -1.8992 Td
(S1)Tj
1.2132 0 Td
(File.)Tj
2.0126 0 Td
(The)Tj
1.8425 0 Td
(search)Tj
2.8799 0 Td
(strategy)Tj
3.532 0 Td
(to)Tj
1.0772 0 Td
(31st)Tj
1.9388 0 Td
(August)Tj
3.2258 0 Td
(2017.)Tj
/F5 1 Tf
-17.722 -1.2982 Td
(\(DOCX\))Tj
/F12 1 Tf
0 -1.8992 Td
(S2)Tj
1.2132 0 Td
(File.)Tj
2.0126 0 Td
(Quality)Tj
3.3618 0 Td
(grading)Tj
3.4526 0 Td
(of)Tj
1.0715 0 Td
(each)Tj
2.0919 0 Td
(paper,)Tj
2.863 0 Td
(with)Tj
2.0806 0 Td
(a)Tj
0.686 0 Td
(Newcastle-Ottawa)Tj
7.7952 0 Td
(score.)Tj
/F5 1 Tf
-26.6284 -1.304 Td
(\(DOCX\))Tj
/F12 1 Tf
0 -1.8992 Td
(S3)Tj
1.2132 0 Td
(File.)Tj
2.0126 0 Td
(Exploration)Tj
5.193 0 Td
(of)Tj
1.0658 0 Td
(heterogeneity.)Tj
/F5 1 Tf
-9.4846 -1.2982 Td
(\(DOCX\))Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 242.022 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Author)Tj
3.4771 0 Td
(Contributions)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 225.0141 cm
BT
/F12 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Conceptualization:)Tj
/F5 1 Tf
8.1523 0 Td
(Peter)Tj
2.2961 0 Td
(C.)Tj
1.1112 0 Td
(Elwood,)Tj
3.4866 0 Td
(Gareth)Tj
2.9877 0 Td
(Morgan,)Tj
3.668 0 Td
(Julieta)Tj
2.7439 0 Td
(Galante,)Tj
3.5433 0 Td
(Alison)Tj
2.8346 0 Td
(L.)Tj
0.9864 0 Td
(Weightman,)Tj
-30.6139 -1.3039 Td
(Marcus)Tj
3.2314 0 Td
(Longley,)Tj
3.6284 0 Td
(Malcolm)Tj
3.7927 0 Td
(Mason,)Tj
3.1861 0 Td
(Richard)Tj
3.3959 0 Td
(Adams,)Tj
3.2712 0 Td
(Sunil)Tj
2.2847 0 Td
(Dolwani,)Tj
3.8664 0 Td
(John)Tj
2.1316 0 Td
(Chia)Tj
2.1147 0 Td
(W.)Tj
1.4116 0 Td
(K.,)Tj
1.3436 0 Td
(Angel)Tj
-33.6583 -1.2982 Td
(Lanas.)Tj
/F12 1 Tf
-1.1962 -1.7972 Td
(Data)Tj
2.245 0 Td
(curation:)Tj
/F5 1 Tf
4.0138 0 Td
(Peter)Tj
2.2961 0 Td
(C.)Tj
1.1055 0 Td
(Elwood.)Tj
/F12 1 Tf
-9.6604 -1.8028 Td
(Formal)Tj
3.2711 0 Td
(analysis:)Tj
/F5 1 Tf
3.7474 0 Td
(Peter)Tj
2.296 0 Td
(C.)Tj
1.1112 0 Td
(Elwood,)Tj
3.4866 0 Td
(Janet)Tj
2.2507 0 Td
(E.)Tj
1.0148 0 Td
(Pickering,)Tj
4.2689 0 Td
(Gareth)Tj
2.9934 0 Td
(Morgan,)Tj
3.6624 0 Td
(Julieta)Tj
2.7439 0 Td
(Galante,)Tj
3.5489 0 Td
(Alison)Tj
-33.1991 -1.2983 Td
(L.)Tj
0.9864 0 Td
(Weightman.)Tj
/F12 1 Tf
-2.1826 -1.8028 Td
(Investigation:)Tj
/F5 1 Tf
5.9583 0 Td
(Peter)Tj
2.2961 0 Td
(C.)Tj
1.1112 0 Td
(Elwood.)Tj
/F12 1 Tf
-9.3656 -1.7972 Td
(Methodology:)Tj
/F5 1 Tf
5.998 0 Td
(Peter)Tj
2.2961 0 Td
(C.)Tj
1.1111 0 Td
(Elwood,)Tj
3.4866 0 Td
(Gareth)Tj
2.9877 0 Td
(Morgan,)Tj
3.6624 0 Td
(Julieta)Tj
2.7496 0 Td
(Galante,)Tj
3.5432 0 Td
(Alison)Tj
2.8347 0 Td
(L.)Tj
0.9864 0 Td
(Weightman,)Tj
5.1931 0 Td
(Delyth)Tj
-33.6527 -1.2982 Td
(Morris,)Tj
3.2201 0 Td
(Marcus)Tj
3.2258 0 Td
(Longley,)Tj
3.6283 0 Td
(John)Tj
2.1373 0 Td
(Chia)Tj
2.109 0 Td
(W.)Tj
1.4116 0 Td
(K.,)Tj
1.3437 0 Td
(Angel)Tj
2.5908 0 Td
(Lanas.)Tj
/F12 1 Tf
-20.8628 -1.8028 Td
(Project)Tj
3.2258 0 Td
(administration:)Tj
/F5 1 Tf
6.7464 0 Td
(Peter)Tj
2.296 0 Td
(C.)Tj
1.1112 0 Td
(Elwood.)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
31.7412 0 Td
(12)Tj
1.304 0 Td
(/)Tj
ET
endstream
endobj
420 0 obj
<>stream
endstream
endobj
421 0 obj
<>stream
endstream
endobj
422 0 obj
<>stream
endstream
endobj
423 0 obj
<>stream
endstream
endobj
424 0 obj
<>stream
endstream
endobj
425 0 obj
<>stream
endstream
endobj
426 0 obj
<>stream
endstream
endobj
427 0 obj
<>stream
endstream
endobj
428 0 obj
<>stream
endstream
endobj
429 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
430 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 344 0 R/Annots 431 0 R/Contents 432 0 R/TrimBox[0 0 612 792]>>
endobj
431 0 obj
[433 0 R 434 0 R 435 0 R 436 0 R 437 0 R 438 0 R 439 0 R 440 0 R 441 0 R 442 0 R 443 0 R 444 0 R 445 0 R 446 0 R 447 0 R 448 0 R 449 0 R 450 0 R 451 0 R 452 0 R 453 0 R 454 0 R 455 0 R 456 0 R 457 0 R 458 0 R 459 0 R 460 0 R 461 0 R 462 0 R 463 0 R 464 0 R 465 0 R 466 0 R 467 0 R 468 0 R 469 0 R 470 0 R 471 0 R 472 0 R]
endobj
433 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref001)>>
endobj
434 0 obj
<>/Border[0 0 0]/A 473 0 R>>
endobj
473 0 obj
<>
endobj
435 0 obj
<>/Border[0 0 0]/A 474 0 R>>
endobj
474 0 obj
<>
endobj
436 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref002)>>
endobj
437 0 obj
<>/Border[0 0 0]/A 475 0 R>>
endobj
475 0 obj
<>
endobj
438 0 obj
<>/Border[0 0 0]/A 476 0 R>>
endobj
476 0 obj
<>
endobj
439 0 obj
<>/Border[0 0 0]/A 477 0 R>>
endobj
477 0 obj
<>
endobj
440 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref003)>>
endobj
441 0 obj
<>/Border[0 0 0]/A 478 0 R>>
endobj
478 0 obj
<>
endobj
442 0 obj
<>/Border[0 0 0]/A 479 0 R>>
endobj
479 0 obj
<>
endobj
443 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref004)>>
endobj
444 0 obj
<>/Border[0 0 0]/A 480 0 R>>
endobj
480 0 obj
<>
endobj
445 0 obj
<>/Border[0 0 0]/A 481 0 R>>
endobj
481 0 obj
<>
endobj
446 0 obj
<>/Border[0 0 0]/A 482 0 R>>
endobj
482 0 obj
<>
endobj
447 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref005)>>
endobj
448 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref006)>>
endobj
449 0 obj
<>/Border[0 0 0]/A 483 0 R>>
endobj
483 0 obj
<>
endobj
450 0 obj
<>/Border[0 0 0]/A 484 0 R>>
endobj
484 0 obj
<>
endobj
451 0 obj
<>/Border[0 0 0]/A 485 0 R>>
endobj
485 0 obj
<>
endobj
452 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref007)>>
endobj
453 0 obj
<>/Border[0 0 0]/A 486 0 R>>
endobj
486 0 obj
<>
endobj
454 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref008)>>
endobj
455 0 obj
<>/Border[0 0 0]/A 487 0 R>>
endobj
487 0 obj
<>
endobj
456 0 obj
<>/Border[0 0 0]/A 488 0 R>>
endobj
488 0 obj
<>
endobj
457 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref009)>>
endobj
458 0 obj
<>/Border[0 0 0]/A 489 0 R>>
endobj
489 0 obj
<>
endobj
459 0 obj
<>/Border[0 0 0]/A 490 0 R>>
endobj
490 0 obj
<>
endobj
460 0 obj
<>/Border[0 0 0]/A 491 0 R>>
endobj
491 0 obj
<>
endobj
461 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref010)>>
endobj
462 0 obj
<>/Border[0 0 0]/A 492 0 R>>
endobj
492 0 obj
<>
endobj
463 0 obj
<>/Border[0 0 0]/A 493 0 R>>
endobj
493 0 obj
<>
endobj
464 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref011)>>
endobj
465 0 obj
<>/Border[0 0 0]/A 494 0 R>>
endobj
494 0 obj
<>
endobj
466 0 obj
<>/Border[0 0 0]/A 495 0 R>>
endobj
495 0 obj
<>
endobj
467 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref012)>>
endobj
468 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref013)>>
endobj
469 0 obj
<>/Border[0 0 0]/A 496 0 R>>
endobj
496 0 obj
<>
endobj
470 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref014)>>
endobj
471 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref015)>>
endobj
472 0 obj
<>/Border[0 0 0]/A 497 0 R>>
endobj
497 0 obj
<>
endobj
432 0 obj
[498 0 R 499 0 R 500 0 R 501 0 R 502 0 R 503 0 R 504 0 R 505 0 R 506 0 R 507 0 R 508 0 R 509 0 R 510 0 R 511 0 R 512 0 R 513 0 R]
endobj
498 0 obj
<>stream
q
0.83 0.64 0.02 0 k
281.7638 510.9165 m
447.8173 510.9165 l
h
f*
473.2724 510.9165 m
508.252 510.9165 l
h
f*
467.9433 488.4094 m
560.2394 488.4094 l
h
f*
221.4992 478.9417 m
243.326 478.9417 l
h
f*
268.8378 478.9417 m
303.7606 478.9417 l
h
f*
294.9732 446.9102 m
461.0268 446.9102 l
h
f*
486.4819 446.9102 m
521.4047 446.9102 l
h
f*
475.5969 424.4031 m
560.0126 424.4031 l
h
f*
221.4992 414.9354 m
295.4268 414.9354 l
h
f*
320.8819 414.9354 m
355.8047 414.9354 l
h
f*
522.0283 350.9291 m
571.9181 350.9291 l
h
f*
221.4992 341.4047 m
337.663 341.4047 l
h
f*
363.1181 341.4047 m
398.0976 341.4047 l
h
f*
221.4992 309.4299 m
252.0567 309.4299 l
h
f*
297.6945 286.9228 m
434.4945 286.9228 l
h
f*
459.9496 286.9228 m
494.9291 286.9228 l
h
f*
498.4441 264.4157 m
559.2756 264.4157 l
h
f*
221.4992 254.948 m
286.1291 254.948 l
h
f*
311.6409 254.948 m
346.5638 254.948 l
h
f*
295.8236 232.4409 m
461.8772 232.4409 l
h
f*
487.3323 232.4409 m
522.2551 232.4409 l
h
f*
242.9291 200.4094 m
408.9827 200.4094 l
h
f*
434.4378 200.4094 m
469.3606 200.4094 l
h
f*
221.4992 136.4031 m
252.0567 136.4031 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 694.3748 cm
BT
/F12 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Supervision:)Tj
/F5 1 Tf
5.3971 0 Td
(Peter)Tj
2.2904 0 Td
(C.)Tj
1.1111 0 Td
(Elwood.)Tj
/F12 1 Tf
-8.7986 -1.7971 Td
(Validation:)Tj
/F5 1 Tf
4.9209 0 Td
(Janet)Tj
2.2507 0 Td
(E.)Tj
1.0148 0 Td
(Pickering,)Tj
4.2689 0 Td
(Malcolm)Tj
3.7871 0 Td
(Mason,)Tj
3.1918 0 Td
(Richard)Tj
3.3902 0 Td
(Adams,)Tj
3.2711 0 Td
(Sunil)Tj
2.2847 0 Td
(Dolwani,)Tj
3.8721 0 Td
(John)Tj
2.1317 0 Td
(Chia)Tj
-33.1878 -1.2983 Td
(W.)Tj
1.4116 0 Td
(K.,)Tj
1.3436 0 Td
(Angel)Tj
2.5909 0 Td
(Lanas.)Tj
/F12 1 Tf
-6.5423 -1.8028 Td
(Writing)Tj
3.5602 0 Td
()Tj
0.7257 0 Td
(original)Tj
3.5036 0 Td
(draft:)Tj
/F5 1 Tf
2.5512 0 Td
(Peter)Tj
2.296 0 Td
(C.)Tj
1.1112 0 Td
(Elwood,)Tj
3.4866 0 Td
(Janet)Tj
2.2507 0 Td
(E.)Tj
1.0148 0 Td
(Pickering,)Tj
4.2689 0 Td
(Gareth)Tj
2.9877 0 Td
(Morgan,)Tj
3.668 0 Td
(Marcus)Tj
3.2258 0 Td
(Long-)Tj
-33.4542 -1.2982 Td
(ley,)Tj
1.5703 0 Td
(Sunil)Tj
2.2848 0 Td
(Dolwani,)Tj
3.8721 0 Td
(John)Tj
2.1316 0 Td
(Chia)Tj
2.1146 0 Td
(W.)Tj
1.406 0 Td
(K.,)Tj
1.3493 0 Td
(Angel)Tj
2.5852 0 Td
(Lanas.)Tj
/F12 1 Tf
-18.5101 -1.8029 Td
(Writing)Tj
3.5602 0 Td
()Tj
0.7257 0 Td
(review)Tj
2.9253 0 Td
(&)Tj
0.9355 0 Td
(editing:)Tj
/F5 1 Tf
3.4129 0 Td
(Janet)Tj
2.2507 0 Td
(E.)Tj
1.0148 0 Td
(Pickering,)Tj
4.2689 0 Td
(Gareth)Tj
2.9934 0 Td
(Morgan,)Tj
3.6623 0 Td
(Julieta)Tj
2.7439 0 Td
(Galante,)Tj
3.549 0 Td
(Alison)Tj
2.8346 0 Td
(L.)Tj
-33.681 -1.2982 Td
(Weightman,)Tj
5.1987 0 Td
(Malcolm)Tj
3.787 0 Td
(Mason,)Tj
3.1918 0 Td
(Richard)Tj
3.3902 0 Td
(Adams,)Tj
3.2712 0 Td
(Sunil)Tj
2.2847 0 Td
(Dolwani,)Tj
3.8721 0 Td
(John)Tj
2.1317 0 Td
(Chia)Tj
2.1089 0 Td
(W.)Tj
1.4117 0 Td
(K.,)Tj
1.3436 0 Td
(Angel)Tj
-31.9916 -1.2983 Td
(Lanas.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 544.4787 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(References)Tj
ET
Q
q
1 j
1 J
0 w
7.9999 0 0 7.9999 204.8881 530.9858 cm
BT
/F2 1 Tf
1 TL
-0.005 Tc
0 0 Td
(1.)Tj
/F0 1 Tf
2.0763 0 Td
(Antithrom)Tj
4.2095 0 Td
(botic)Tj
2.2961 0 Td
(Trialists')Tj
3.8126 0 Td
(Collaboration.)Tj
6.2647 0 Td
(\(2009\))Tj
3.0614 0 Td
(Aspirin)Tj
3.2173 0 Td
(in)Tj
0.978 0 Td
(the)Tj
1.5803 0 Td
(primary)Tj
3.5008 0 Td
(and)Tj
1.8568 0 Td
(secondar)Tj
4.0394 0 Td
(y)Tj
0.7157 0 Td
(preventi)Tj
3.4866 0 Td
(on)Tj
1.3111 0 Td
(of)Tj
1.0417 0 Td
(vascu-)Tj
-41.372 -1.1834 Td
(lar)Tj
1.304 0 Td
(disease:)Tj
3.8764 0 Td
(collaborative)Tj
5.726 0 Td
(meta-ana)Tj
4.1528 0 Td
(lysis)Tj
2.126 0 Td
(of)Tj
1.0418 0 Td
(individu)Tj
3.3094 0 Td
(al)Tj
0.9851 0 Td
(particip)Tj
3.1535 0 Td
(ant)Tj
1.5875 0 Td
(data)Tj
2.1331 0 Td
(from)Tj
2.1897 0 Td
(randomise)Tj
4.5851 0 Td
(d)Tj
0.7654 0 Td
(trials.)Tj
2.5653 0 Td
(Lancet)Tj
-39.5011 -1.1906 Td
(373:)Tj
2.1331 0 Td
(184918)Tj
3.8127 0 Td
(60.)Tj
0.83 0.64 0.02 0 k
1.5874 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.101)Tj
3.8197 0 Td
(6/S0140-67)Tj
5.0811 0 Td
(36\(09\)605)Tj
4.4717 0 Td
(03-1)Tj
0 g
2.1827 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(19482214)Tj
0 g
/F2 1 Tf
-33.5482 -1.6228 Td
(2.)Tj
/F0 1 Tf
2.0763 0 Td
(Battistoni)Tj
4.252 0 Td
(A,)Tj
1.1481 0 Td
(Mastrom)Tj
3.8339 0 Td
(arino)Tj
2.3882 0 Td
(V,)Tj
1.148 0 Td
(Volpe)Tj
2.7213 0 Td
(M.)Tj
1.311 0 Td
(\(2015\))Tj
3.0473 0 Td
(Reducing)Tj
4.3583 0 Td
(cardiovasc)Tj
4.6914 0 Td
(ular)Tj
1.8425 0 Td
(and)Tj
1.8496 0 Td
(cancer)Tj
3.1607 0 Td
(risk:)Tj
2.0126 0 Td
(how)Tj
2.0126 0 Td
(to)Tj
1.0347 0 Td
(address)Tj
-40.8122 -1.1906 Td
(global)Tj
2.8276 0 Td
(primary)Tj
3.5008 0 Td
(preventi)Tj
3.4867 0 Td
(on)Tj
1.311 0 Td
(in)Tj
0.978 0 Td
(clinical)Tj
3.1535 0 Td
(practice.)Tj
3.9331 0 Td
(Clin)Tj
1.8993 0 Td
(Cardiol.)Tj
3.8197 0 Td
(38:)Tj
1.5874 0 Td
(38739)Tj
3.267 0 Td
(4.)Tj
0.83 0.64 0.02 0 k
1.0417 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.100)Tj
3.8197 0 Td
(2/clc.)Tj
-40.0397 -1.1835 Td
(22394)Tj
0 g
2.9481 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(258735)Tj
3.267 0 Td
(55)Tj
0 g
/F2 1 Tf
-11.2607 -1.6299 Td
(3.)Tj
/F0 1 Tf
2.0763 0 Td
(Algra)Tj
2.5087 0 Td
(AM,)Tj
1.9843 0 Td
(Rothwe)Tj
3.3307 0 Td
(ll)Tj
0.6449 0 Td
(PM.)Tj
1.9843 0 Td
(\(2012\))Tj
3.0543 0 Td
(Effects)Tj
3.2386 0 Td
(of)Tj
1.0418 0 Td
(regular)Tj
3.2669 0 Td
(aspirin)Tj
3.104 0 Td
(on)Tj
1.311 0 Td
(long-term)Tj
4.3725 0 Td
(cancer)Tj
3.1678 0 Td
(incidence)Tj
4.3583 0 Td
(and)Tj
1.8567 0 Td
(metastas)Tj
3.9968 0 Td
(is:)Tj
-43.2216 -1.1835 Td
(a)Tj
0.7654 0 Td
(systematic)Tj
4.8756 0 Td
(comparison)Tj
5.3009 0 Td
(of)Tj
1.0346 0 Td
(evidence)Tj
4.1528 0 Td
(from)Tj
2.1898 0 Td
(observatio)Tj
4.5284 0 Td
(nal)Tj
1.5236 0 Td
(studies)Tj
3.3307 0 Td
(versus)Tj
3.1182 0 Td
(randomised)Tj
5.3575 0 Td
(trials.)Tj
2.5583 0 Td
(Lancet)Tj
-38.7358 -1.1905 Td
(Oncol.)Tj
3.2883 0 Td
(13:)Tj
1.5874 0 Td
(51852)Tj
3.2669 0 Td
(7.)Tj
0.83 0.64 0.02 0 k
1.0418 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.101)Tj
3.8197 0 Td
(6/S1470-20)Tj
5.0811 0 Td
(45\(12\)701)Tj
4.4717 0 Td
(12-2)Tj
0 g
2.1827 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(22440112)Tj
0 g
/F2 1 Tf
-35.1994 -1.6229 Td
(4.)Tj
/F0 1 Tf
2.0763 0 Td
(Mills)Tj
2.1757 0 Td
(EJ,)Tj
1.6511 0 Td
(Wu)Tj
1.7079 0 Td
(P,)Tj
1.1552 0 Td
(Alberton)Tj
3.8764 0 Td
(M,)Tj
1.3181 0 Td
(Kanters)Tj
3.6142 0 Td
(S,)Tj
1.1551 0 Td
(Lanas)Tj
2.8914 0 Td
(A,)Tj
1.1551 0 Td
(Lester)Tj
2.9551 0 Td
(R.)Tj
1.2048 0 Td
(\(2012\))Tj
3.0543 0 Td
(Low-dose)Tj
4.4788 0 Td
(aspirin)Tj
3.104 0 Td
(and)Tj
1.8567 0 Td
(cancer)Tj
3.1677 0 Td
(mortal-)Tj
-40.5216 -1.1905 Td
(ity:)Tj
1.4741 0 Td
(a)Tj
0.7653 0 Td
(meta-analy)Tj
4.8615 0 Td
(sis)Tj
1.4244 0 Td
(of)Tj
1.0417 0 Td
(random)Tj
3.3308 0 Td
(ized)Tj
2.0197 0 Td
(trials.)Tj
2.5654 0 Td
(The)Tj
1.9134 0 Td
(Amer)Tj
2.5795 0 Td
(J)Tj
0.7158 0 Td
(Med.)Tj
2.6291 0 Td
(125:)Tj
2.1331 0 Td
(56056)Tj
3.267 0 Td
(7.)Tj
0.83 0.64 0.02 0 k
1.0417 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.1016/)Tj
4.6418 0 Td
(j.)Tj
-41.8185 -1.1835 Td
(amjmed.201)Tj
5.4143 0 Td
(2.01.017)Tj
0 g
4.0394 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(22513195)Tj
0 g
/F2 1 Tf
-14.4993 -1.63 Td
(5.)Tj
/F0 1 Tf
2.0763 0 Td
(Burn)Tj
2.2961 0 Td
(J,)Tj
0.9922 0 Td
(Gerdes)Tj
3.4512 0 Td
(AM,)Tj
1.9771 0 Td
(Macrae)Tj
3.5009 0 Td
(F,)Tj
1.1055 0 Td
(Mecklin)Tj
3.5504 0 Td
(JP,)Tj
1.6441 0 Td
(Moeslein)Tj
4.1528 0 Td
(G,)Tj
1.2685 0 Td
(Olschwan)Tj
4.3158 0 Td
(g)Tj
0.7654 0 Td
(S,)Tj
1.1551 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2544 0 Td
(\(2013\))Tj
3.0543 0 Td
(Long-term)Tj
4.7056 0 Td
(effect)Tj
2.6291 0 Td
(of)Tj
-42.8602 -1.1834 Td
(aspirin)Tj
3.104 0 Td
(on)Tj
1.311 0 Td
(cancer)Tj
3.1678 0 Td
(risk)Tj
1.7504 0 Td
(in)Tj
0.9779 0 Td
(carriers)Tj
3.4938 0 Td
(of)Tj
1.0346 0 Td
(hereditary)Tj
4.5851 0 Td
(colorectal)Tj
4.415 0 Td
(cancer:)Tj
3.4512 0 Td
(an)Tj
1.311 0 Td
(analysis)Tj
3.7631 0 Td
(from)Tj
2.1897 0 Td
(the)Tj
1.5875 0 Td
(CAPP2)Tj
3.4583 0 Td
(rando-)Tj
-39.6004 -1.1906 Td
(mised)Tj
2.8418 0 Td
(controlled)Tj
4.4717 0 Td
(trial.)Tj
2.0693 0 Td
(Lancet)Tj
3.3874 0 Td
(378:)Tj
2.1331 0 Td
(20812087.)Tj
/F2 1 Tf
-16.9796 -1.6228 Td
(6.)Tj
/F0 1 Tf
2.0763 0 Td
(Rothwell)Tj
3.9828 0 Td
(PM,)Tj
1.9771 0 Td
(Price)Tj
2.4591 0 Td
(JF,)Tj
1.5945 0 Td
(Fowkes)Tj
3.6213 0 Td
(FG,)Tj
1.878 0 Td
(Zanchett)Tj
3.8268 0 Td
(i)Tj
0.4393 0 Td
(A,)Tj
1.1552 0 Td
(Ronca)Tj
2.8346 0 Td
(glioni)Tj
2.5016 0 Td
(MC,)Tj
2.0268 0 Td
(Tognoni)Tj
3.7701 0 Td
(G,)Tj
1.2685 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2012\))Tj
3.0544 0 Td
(Short-term)Tj
-38.6862 -1.1906 Td
(effects)Tj
3.1253 0 Td
(of)Tj
1.0417 0 Td
(daily)Tj
2.2252 0 Td
(aspirin)Tj
3.104 0 Td
(on)Tj
1.311 0 Td
(cancer)Tj
3.1678 0 Td
(incidence,)Tj
4.6417 0 Td
(mortality,)Tj
4.2095 0 Td
(and)Tj
1.8496 0 Td
(non-vascul)Tj
4.7481 0 Td
(ar)Tj
1.0984 0 Td
(death:)Tj
2.9481 0 Td
(analysis)Tj
3.763 0 Td
(of)Tj
1.0417 0 Td
(the)Tj
1.5875 0 Td
(time)Tj
-39.8626 -1.1835 Td
(course)Tj
3.1678 0 Td
(of)Tj
1.0417 0 Td
(risks)Tj
2.2394 0 Td
(and)Tj
1.8567 0 Td
(benefits)Tj
3.6638 0 Td
(in)Tj
0.978 0 Td
(51)Tj
1.311 0 Td
(random)Tj
3.3308 0 Td
(ised)Tj
2.0197 0 Td
(controll)Tj
3.1535 0 Td
(ed)Tj
1.3111 0 Td
(trials.)Tj
2.5653 0 Td
(Lancet)Tj
3.3875 0 Td
(379:)Tj
2.1331 0 Td
(16021612.)Tj
0.83 0.64 0.02 0 k
5.4071 0 Td
(https://)Tj
2.9551 0 Td
(doi.org/)Tj
-40.5216 -1.1905 Td
(10.1016/)Tj
3.8198 0 Td
(S0140-673)Tj
4.8047 0 Td
(6\(11\)6172)Tj
4.4717 0 Td
(0-0)Tj
0 g
1.6441 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9622 0 Td
(22440946)Tj
0 g
/F2 1 Tf
-19.7788 -1.6229 Td
(7.)Tj
/F0 1 Tf
2.0763 0 Td
(Gasic)Tj
2.7426 0 Td
(GJ,)Tj
1.7575 0 Td
(Gasic)Tj
2.7425 0 Td
(TB,)Tj
1.7575 0 Td
(Stewart)Tj
3.5646 0 Td
(CC.)Tj
1.9134 0 Td
(\(1968\))Tj
3.0615 0 Td
(Antimetast)Tj
4.6488 0 Td
(atic)Tj
1.7504 0 Td
(effects)Tj
3.1252 0 Td
(associat)Tj
3.6001 0 Td
(ed)Tj
1.311 0 Td
(with)Tj
1.9701 0 Td
(platele)Tj
2.8772 0 Td
(t)Tj
0.496 0 Td
(reduction.)Tj
4.5355 0 Td
(Pro-)Tj
-41.8539 -1.1905 Td
(ceeding)Tj
3.43 0 Td
(s)Tj
0.7157 0 Td
(of)Tj
1.0418 0 Td
(the)Tj
1.5874 0 Td
(National)Tj
3.8126 0 Td
(Academy)Tj
4.33 0 Td
(of)Tj
1.0417 0 Td
(Sciences)Tj
4.2095 0 Td
(of)Tj
1.0347 0 Td
(the)Tj
1.5874 0 Td
(United)Tj
3.0543 0 Td
(States)Tj
3.019 0 Td
(of)Tj
1.0417 0 Td
(America)Tj
4.0465 0 Td
(61:)Tj
1.5874 0 Td
(4652.)Tj
3.2244 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
-38.7641 -1.1835 Td
(5246932)Tj
0 g
/F2 1 Tf
-2.0763 -1.6229 Td
(8.)Tj
/F0 1 Tf
2.0763 0 Td
(Chan)Tj
2.5654 0 Td
(AT,)Tj
1.7646 0 Td
(Ogino)Tj
2.8418 0 Td
(S,)Tj
1.1551 0 Td
(Fuchs)Tj
2.9055 0 Td
(CS.)Tj
1.8638 0 Td
(\(2009\))Tj
3.0615 0 Td
(Aspirin)Tj
3.2173 0 Td
(use)Tj
1.8 0 Td
(and)Tj
1.8567 0 Td
(survival)Tj
3.5434 0 Td
(after)Tj
2.1897 0 Td
(diagnosis)Tj
4.3583 0 Td
(of)Tj
1.0418 0 Td
(colorectal)Tj
4.415 0 Td
(cancer.)Tj
-38.5799 -1.1905 Td
(JAMA)Tj
3.0757 0 Td
(302:)Tj
2.133 0 Td
(649658.)Tj
0.83 0.64 0.02 0 k
4.3158 0 Td
(https://d)Tj
3.5008 0 Td
(oi.org/10.100)Tj
5.7332 0 Td
(1/jama.20)Tj
4.3157 0 Td
(09.1112)Tj
0 g
3.7702 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9622 0 Td
(19671906)Tj
0 g
/F2 1 Tf
-31.8829 -1.6229 Td
(9.)Tj
/F0 1 Tf
2.0763 0 Td
(Langley)Tj
3.6568 0 Td
(RE,)Tj
1.8638 0 Td
(Burdett)Tj
3.3945 0 Td
(S,)Tj
1.1551 0 Td
(Tierney)Tj
3.4937 0 Td
(JF,)Tj
1.6016 0 Td
(Cafferty)Tj
3.6638 0 Td
(F,)Tj
1.1055 0 Td
(Parmar)Tj
3.4513 0 Td
(MK,)Tj
1.9771 0 Td
(Venning)Tj
3.8198 0 Td
(G.)Tj
1.2685 0 Td
(\(2011\))Tj
3.0614 0 Td
(Aspirin)Tj
3.2174 0 Td
(and)Tj
1.8496 0 Td
(cancer:)Tj
3.4512 0 Td
(has)Tj
-42.0311 -1.1905 Td
(aspirin)Tj
3.104 0 Td
(been)Tj
2.4024 0 Td
(overloo)Tj
3.2102 0 Td
(ked)Tj
1.8071 0 Td
(as)Tj
1.2615 0 Td
(an)Tj
1.311 0 Td
(adjuvan)Tj
3.43 0 Td
(t)Tj
0.496 0 Td
(therapy?)Tj
4.0394 0 Td
(Brit)Tj
1.7008 0 Td
(J)Tj
0.7087 0 Td
(Cancer)Tj
3.6071 0 Td
(105:)Tj
2.1331 0 Td
(11071113.)Tj
0.83 0.64 0.02 0 k
5.4071 0 Td
(https://d)Tj
3.5008 0 Td
(oi.org/10.)Tj
-38.1192 -1.1835 Td
(1038/bjc.2)Tj
4.5284 0 Td
(011.289)Tj
0 g
3.7701 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(218471)Tj
3.267 0 Td
(26)Tj
0 g
/F2 1 Tf
-17.1567 -1.6299 Td
(10.)Tj
/F0 1 Tf
2.6219 0 Td
(Elwood)Tj
3.4371 0 Td
(PC,)Tj
1.8709 0 Td
(Gallagher)Tj
4.4716 0 Td
(AM,)Tj
1.9843 0 Td
(Duthie)Tj
3.0544 0 Td
(GG,)Tj
2.0409 0 Td
(Mur)Tj
1.9205 0 Td
(LA,)Tj
1.7008 0 Td
(Morgan)Tj
3.5504 0 Td
(G.)Tj
1.2686 0 Td
(\(2009\))Tj
3.0614 0 Td
(Aspirin,)Tj
3.4866 0 Td
(salicylates,)Tj
5.0245 0 Td
(and)Tj
1.8567 0 Td
(cancer.)Tj
3.4441 0 Td
(Lan-)Tj
-42.1728 -1.1835 Td
(cet)Tj
1.7575 0 Td
(373:)Tj
2.126 0 Td
(13011309.)Tj
0.83 0.64 0.02 0 k
5.4072 0 Td
(https://doi.)Tj
4.5354 0 Td
(org/10.1016/S)Tj
6.1796 0 Td
(0140-6736\()Tj
5.0174 0 Td
(09\)60243-)Tj
4.4717 0 Td
(9)Tj
0 g
0.7653 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(193285)Tj
3.267 0 Td
(42)Tj
0 g
/F2 1 Tf
-39.1183 -1.6299 Td
(11.)Tj
/F0 1 Tf
2.6219 0 Td
(Rothwell)Tj
3.9828 0 Td
(PM,)Tj
1.9771 0 Td
(Wilson)Tj
3.1749 0 Td
(M,)Tj
1.3181 0 Td
(Price)Tj
2.4591 0 Td
(JF,)Tj
1.5945 0 Td
(Belch)Tj
2.6787 0 Td
(JF,)Tj
1.5945 0 Td
(Meade)Tj
3.2315 0 Td
(TW,)Tj
2.041 0 Td
(Mehta)Tj
2.9551 0 Td
(Z.)Tj
1.1056 0 Td
(\(2012\))Tj
3.0543 0 Td
(Effect)Tj
2.7426 0 Td
(of)Tj
1.0417 0 Td
(daily)Tj
2.2323 0 Td
(aspirin)Tj
3.104 0 Td
(on)Tj
1.311 0 Td
(risk)Tj
1.7433 0 Td
(of)Tj
-43.3421 -1.1835 Td
(cancer)Tj
3.1678 0 Td
(metastasis)Tj
4.7055 0 Td
(:)Tj
0.4961 0 Td
(a)Tj
0.7654 0 Td
(study)Tj
2.5724 0 Td
(of)Tj
1.0418 0 Td
(incident)Tj
3.6 0 Td
(cancers)Tj
3.6638 0 Td
(during)Tj
2.941 0 Td
(random)Tj
3.3307 0 Td
(ised)Tj
2.0197 0 Td
(controlled)Tj
4.4717 0 Td
(trials.)Tj
2.5583 0 Td
(Lancet)Tj
3.3945 0 Td
(379:)Tj
2.126 0 Td
(1591)Tj
-40.8547 -1.1906 Td
(1601.)Tj
0.83 0.64 0.02 0 k
2.6788 0 Td
(https://d)Tj
3.5008 0 Td
(oi.org/10.101)Tj
5.7331 0 Td
(6/S0140-67)Tj
5.0812 0 Td
(36\(12\)602)Tj
4.4717 0 Td
(09-8)Tj
0 g
2.1827 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(224409)Tj
3.2669 0 Td
(47)Tj
0 g
/F2 1 Tf
-32.5064 -1.6228 Td
(12.)Tj
/F0 1 Tf
2.6219 0 Td
(Lipton)Tj
2.8843 0 Td
(A,)Tj
1.1481 0 Td
(Scialla)Tj
3.0968 0 Td
(S,)Tj
1.1481 0 Td
(Harvey)Tj
3.3307 0 Td
(H,)Tj
1.1977 0 Td
(Dixon)Tj
2.7212 0 Td
(R,)Tj
1.2048 0 Td
(Gordon)Tj
3.4937 0 Td
(R,)Tj
1.1976 0 Td
(Hamilton)Tj
4.0891 0 Td
(R,)Tj
1.1976 0 Td
(et)Tj
1.0347 0 Td
(al.)Tj
1.2472 0 Td
(\(1982\))Tj
3.0544 0 Td
(Adjuvan)Tj
3.5433 0 Td
(t)Tj
0.489 0 Td
(antiplatelet)Tj
4.9536 0 Td
(therapy)Tj
-41.0319 -1.1906 Td
(with)Tj
1.9631 0 Td
(aspirin)Tj
3.1039 0 Td
(in)Tj
0.978 0 Td
(colo-rectal)Tj
4.748 0 Td
(cancer.)Tj
3.4442 0 Td
(J)Tj
0.7157 0 Td
(Medicine)Tj
4.3654 0 Td
(13:)Tj
1.5874 0 Td
(41942)Tj
3.267 0 Td
(9.)Tj
/F2 1 Tf
-26.7946 -1.6228 Td
(13.)Tj
/F0 1 Tf
2.6219 0 Td
(Lebeau)Tj
3.4938 0 Td
(B,)Tj
1.1551 0 Td
(Chasta)Tj
3.111 0 Td
(ng)Tj
1.3111 0 Td
(C,)Tj
1.2118 0 Td
(Muir)Tj
2.1331 0 Td
(JF,)Tj
1.5945 0 Td
(Vincent)Tj
3.4937 0 Td
(J,)Tj
0.9922 0 Td
(Massin)Tj
3.3378 0 Td
(F,)Tj
1.0984 0 Td
(Fabre)Tj
2.7922 0 Td
(C.)Tj
1.2047 0 Td
(\(1993\))Tj
3.0614 0 Td
(No)Tj
1.4741 0 Td
(effect)Tj
2.6291 0 Td
(of)Tj
1.0418 0 Td
(an)Tj
1.311 0 Td
(antiaggrega)Tj
5.1803 0 Td
(nt)Tj
-41.6271 -1.1906 Td
(treatment)Tj
4.3796 0 Td
(with)Tj
1.963 0 Td
(aspirin)Tj
3.104 0 Td
(in)Tj
0.9779 0 Td
(small)Tj
2.5158 0 Td
(cell)Tj
1.6795 0 Td
(lung)Tj
2.0694 0 Td
(cancer)Tj
3.1748 0 Td
(treated)Tj
3.274 0 Td
(with)Tj
1.9701 0 Td
(CCAVP16)Tj
4.7127 0 Td
(chemother)Tj
4.6488 0 Td
(apy.)Tj
2.0764 0 Td
(Results)Tj
3.5008 0 Td
(from)Tj
2.1898 0 Td
(a)Tj
-42.2366 -1.1835 Td
(randomiz)Tj
4.0394 0 Td
(ed)Tj
1.3111 0 Td
(clinical)Tj
3.1535 0 Td
(trial)Tj
1.793 0 Td
(of)Tj
1.0417 0 Td
(303)Tj
1.8567 0 Td
(patients.)Tj
3.9331 0 Td
(The)Tj
1.9134 0 Td
("Petites)Tj
3.5788 0 Td
(Cellules")Tj
4.0465 0 Td
(Group.)Tj
3.2315 0 Td
(Cancer)Tj
3.6071 0 Td
(71:)Tj
1.5874 0 Td
(17411745.)Tj
5.4072 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
-40.5004 -1.1905 Td
(8383578)Tj
0 g
/F2 1 Tf
-2.6219 -1.6229 Td
(14.)Tj
/F0 1 Tf
2.6219 0 Td
(Creagan)Tj
3.9828 0 Td
(ET,)Tj
1.7645 0 Td
(Twito)Tj
2.5725 0 Td
(DI,)Tj
1.4811 0 Td
(Johansson)Tj
4.9749 0 Td
(SL,)Tj
1.7008 0 Td
(Schaid)Tj
3.2244 0 Td
(DJ,)Tj
1.7008 0 Td
(Johnson)Tj
3.9331 0 Td
(PS,)Tj
1.8142 0 Td
(Flaum)Tj
2.9551 0 Td
(MA,)Tj
1.9772 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2544 0 Td
(\(1991\))Tj
3.0543 0 Td
(A)Tj
0.8788 0 Td
(randomized)Tj
-38.3106 -1.1905 Td
(prospective)Tj
5.2442 0 Td
(assessmen)Tj
4.9819 0 Td
(t)Tj
0.4961 0 Td
(of)Tj
1.0346 0 Td
(recombinant)Tj
5.6268 0 Td
(leukocyte)Tj
4.3725 0 Td
(A)Tj
0.8788 0 Td
(human)Tj
3.2315 0 Td
(interfe)Tj
2.7213 0 Td
(ron)Tj
1.6441 0 Td
(with)Tj
1.963 0 Td
(or)Tj
1.0913 0 Td
(without)Tj
3.3308 0 Td
(aspirin)Tj
3.1039 0 Td
(in)Tj
-39.7208 -1.1835 Td
(advanced)Tj
4.4788 0 Td
(renal)Tj
2.3953 0 Td
(adenocarc)Tj
4.5851 0 Td
(inoma.)Tj
3.1748 0 Td
(Journal)Tj
3.43 0 Td
(of)Tj
1.0417 0 Td
(Clin)Tj
1.9063 0 Td
(Oncol)Tj
3.0119 0 Td
(9:)Tj
1.0417 0 Td
(21042)Tj
3.267 0 Td
(109.)Tj
/F2 1 Tf
-30.9545 -1.6229 Td
(15.)Tj
/F0 1 Tf
2.6219 0 Td
(Liu)Tj
1.5237 0 Td
(JF,)Tj
1.5945 0 Td
(Jamieson)Tj
4.4291 0 Td
(GG,)Tj
2.041 0 Td
(Wu)Tj
1.7079 0 Td
(TC,)Tj
1.8142 0 Td
(Zhu)Tj
1.9205 0 Td
(GJ,)Tj
1.7575 0 Td
(Drew)Tj
2.5157 0 Td
(PA.)Tj
1.8142 0 Td
(\(2009\))Tj
3.0615 0 Td
(A)Tj
0.8787 0 Td
(prelimin)Tj
3.4229 0 Td
(ary)Tj
1.5874 0 Td
(study)Tj
2.5724 0 Td
(on)Tj
1.3111 0 Td
(the)Tj
1.5874 0 Td
(postopera)Tj
4.3654 0 Td
(tive)Tj
1.7504 0 Td
(sur-)Tj
-41.6555 -1.1905 Td
(vival)Tj
2.1757 0 Td
(of)Tj
1.0417 0 Td
(patients)Tj
3.6638 0 Td
(given)Tj
2.5583 0 Td
(aspirin)Tj
3.104 0 Td
(after)Tj
2.1897 0 Td
(resection)Tj
4.2024 0 Td
(for)Tj
1.3678 0 Td
(squamous)Tj
4.7622 0 Td
(cell)Tj
1.6795 0 Td
(carcinoma)Tj
4.7552 0 Td
(of)Tj
1.0417 0 Td
(the)Tj
1.5874 0 Td
(esophag)Tj
3.7631 0 Td
(us)Tj
1.2614 0 Td
(or)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
31.7412 0 Td
(13)Tj
1.304 0 Td
(/)Tj
ET
endstream
endobj
499 0 obj
<>stream
endstream
endobj
500 0 obj
<>stream
endstream
endobj
501 0 obj
<>stream
endstream
endobj
502 0 obj
<>stream
endstream
endobj
503 0 obj
<>stream
endstream
endobj
504 0 obj
<>stream
endstream
endobj
505 0 obj
<>stream
endstream
endobj
506 0 obj
<>stream
endstream
endobj
507 0 obj
<>stream
endstream
endobj
508 0 obj
<>stream
endstream
endobj
509 0 obj
<>stream
endstream
endobj
510 0 obj
<>stream
endstream
endobj
511 0 obj
<>stream
endstream
endobj
512 0 obj
<>stream
endstream
endobj
513 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
514 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 344 0 R/Annots 515 0 R/Contents 516 0 R/TrimBox[0 0 612 792]>>
endobj
515 0 obj
[517 0 R 518 0 R 519 0 R 520 0 R 521 0 R 522 0 R 523 0 R 524 0 R 525 0 R 526 0 R 527 0 R 528 0 R 529 0 R 530 0 R 531 0 R 532 0 R 533 0 R 534 0 R 535 0 R 536 0 R 537 0 R 538 0 R 539 0 R 540 0 R 541 0 R 542 0 R 543 0 R 544 0 R 545 0 R 546 0 R 547 0 R 548 0 R 549 0 R 550 0 R 551 0 R 552 0 R 553 0 R 554 0 R 555 0 R 556 0 R 557 0 R 558 0 R 559 0 R]
endobj
517 0 obj
<>/Border[0 0 0]/A 560 0 R>>
endobj
560 0 obj
<>
endobj
518 0 obj
<>/Border[0 0 0]/A 561 0 R>>
endobj
561 0 obj
<>
endobj
519 0 obj
<>/Border[0 0 0]/A 562 0 R>>
endobj
562 0 obj
<>
endobj
520 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref016)>>
endobj
521 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref017)>>
endobj
522 0 obj
<>/Border[0 0 0]/A 563 0 R>>
endobj
563 0 obj
<>
endobj
523 0 obj
<>/Border[0 0 0]/A 564 0 R>>
endobj
564 0 obj
<>
endobj
524 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref018)>>
endobj
525 0 obj
<>/Border[0 0 0]/A 565 0 R>>
endobj
565 0 obj
<>
endobj
526 0 obj
<>/Border[0 0 0]/A 566 0 R>>
endobj
566 0 obj
<>
endobj
527 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref019)>>
endobj
528 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref020)>>
endobj
529 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref021)>>
endobj
530 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref022)>>
endobj
531 0 obj
<>/Border[0 0 0]/A 567 0 R>>
endobj
567 0 obj
<>
endobj
532 0 obj
<>/Border[0 0 0]/A 568 0 R>>
endobj
568 0 obj
<>
endobj
533 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref023)>>
endobj
534 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref024)>>
endobj
535 0 obj
<>/Border[0 0 0]/A 569 0 R>>
endobj
569 0 obj
<>
endobj
536 0 obj
<>/Border[0 0 0]/A 570 0 R>>
endobj
570 0 obj
<>
endobj
537 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref025)>>
endobj
538 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref026)>>
endobj
539 0 obj
<>/Border[0 0 0]/A 571 0 R>>
endobj
571 0 obj
<>
endobj
540 0 obj
<>/Border[0 0 0]/A 572 0 R>>
endobj
572 0 obj
<>
endobj
541 0 obj
<>/Border[0 0 0]/A 573 0 R>>
endobj
573 0 obj
<>
endobj
542 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref027)>>
endobj
543 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref028)>>
endobj
544 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref029)>>
endobj
545 0 obj
<>/Border[0 0 0]/A 574 0 R>>
endobj
574 0 obj
<>
endobj
546 0 obj
<>/Border[0 0 0]/A 575 0 R>>
endobj
575 0 obj
<>
endobj
547 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref030)>>
endobj
548 0 obj
<>/Border[0 0 0]/A 576 0 R>>
endobj
576 0 obj
<>
endobj
549 0 obj
<>/Border[0 0 0]/A 577 0 R>>
endobj
577 0 obj
<>
endobj
550 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref031)>>
endobj
551 0 obj
<>/Border[0 0 0]/A 578 0 R>>
endobj
578 0 obj
<>
endobj
552 0 obj
<>/Border[0 0 0]/A 579 0 R>>
endobj
579 0 obj
<>
endobj
553 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref032)>>
endobj
554 0 obj
<>/Border[0 0 0]/A 580 0 R>>
endobj
580 0 obj
<>
endobj
555 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref033)>>
endobj
556 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref034)>>
endobj
557 0 obj
<>/Border[0 0 0]/A 581 0 R>>
endobj
581 0 obj
<>
endobj
558 0 obj
<>/Border[0 0 0]/A 582 0 R>>
endobj
582 0 obj
<>
endobj
559 0 obj
<>/Border[0 0 0]/A 583 0 R>>
endobj
583 0 obj
<>
endobj
516 0 obj
[584 0 R 585 0 R 586 0 R 587 0 R 588 0 R 589 0 R 590 0 R 591 0 R 592 0 R 593 0 R 594 0 R 595 0 R 596 0 R 597 0 R 598 0 R 599 0 R 600 0 R 601 0 R 602 0 R 603 0 R]
endobj
584 0 obj
<>stream
q
0.83 0.64 0.02 0 k
441.8079 707.6409 m
566.4189 707.6409 l
h
f*
221.4992 698.1165 m
245.537 698.1165 l
h
f*
270.9921 698.1165 m
305.9717 698.1165 l
h
f*
256.0252 634.1669 m
371.9055 634.1669 l
h
f*
397.3606 634.1669 m
432.2835 634.1669 l
h
f*
417.7701 602.1354 m
574.1291 602.1354 l
h
f*
245.2535 592.6677 m
280.1764 592.6677 l
h
f*
277.3984 493.115 m
423.9496 493.115 l
h
f*
449.4047 493.115 m
484.3843 493.115 l
h
f*
429.3921 429.1654 m
573.222 429.1654 l
h
f*
245.2535 419.6409 m
280.1764 419.6409 l
h
f*
533.4236 355.6346 m
569.7638 355.6346 l
h
f*
221.4992 346.1669 m
310.6205 346.1669 l
h
f*
336.0756 346.1669 m
371.0551 346.1669 l
h
f*
428.315 250.1291 m
574.8661 250.1291 l
h
f*
245.2535 240.6614 m
280.1764 240.6614 l
h
f*
260.3906 208.6299 m
416.7496 208.6299 l
h
f*
442.2047 208.6299 m
477.1276 208.6299 l
h
f*
221.4992 176.6551 m
336.0189 176.6551 l
h
f*
361.474 176.6551 m
396.3969 176.6551 l
h
f*
512.3906 154.148 m
547.3701 154.148 l
h
f*
299.7354 99.6661 m
446.2866 99.6661 l
h
f*
471.7417 99.6661 m
506.7213 99.6661 l
h
f*
0 g
1 j
1 J
0 w
7.9999 0 0 7.9999 221.4992 708.7181 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(adenoca)Tj
3.763 0 Td
(rcinoma)Tj
3.7205 0 Td
(of)Tj
1.0417 0 Td
(the)Tj
1.5803 0 Td
(cardia.)Tj
3.1678 0 Td
(Ann)Tj
1.9701 0 Td
(Surg)Tj
2.2961 0 Td
(Oncol)Tj
3.0118 0 Td
(16:)Tj
1.5874 0 Td
(13971402)Tj
4.904 0 Td
(.)Tj
0.83 0.64 0.02 0 k
0.496 0 Td
(https://doi.or)Tj
5.4143 0 Td
(g/10.1245/)Tj
4.6417 0 Td
(s10434-009-)Tj
-37.5947 -1.1905 Td
(0382-z)Tj
0 g
3.2244 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9622 0 Td
(19241108)Tj
0 g
/F2 1 Tf
-8.8086 -1.6229 Td
(16.)Tj
/F0 1 Tf
2.622 0 Td
(Coyle)Tj
2.7283 0 Td
(C,)Tj
1.2048 0 Td
(Cafferty)Tj
3.6708 0 Td
(FH,)Tj
1.8142 0 Td
(Rowley)Tj
3.4442 0 Td
(S,)Tj
1.1551 0 Td
(MacKenz)Tj
4.1032 0 Td
(ie)Tj
0.9779 0 Td
(M,)Tj
1.3252 0 Td
(Berkman)Tj
4.1599 0 Td
(L,)Tj
1.0417 0 Td
(Gupta)Tj
2.9056 0 Td
(S,)Tj
1.1551 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2016\))Tj
3.0543 0 Td
(Add-asp)Tj
3.6568 0 Td
(irin:)Tj
1.8 0 Td
(a)Tj
0.7653 0 Td
(phase)Tj
-41.2585 -1.1834 Td
(III,)Tj
1.3181 0 Td
(double-blind)Tj
5.3291 0 Td
(,)Tj
0.4961 0 Td
(placebo)Tj
3.6567 0 Td
(controlled)Tj
4.245 0 Td
(,)Tj
0.496 0 Td
(randomised)Tj
5.3575 0 Td
(trial)Tj
1.793 0 Td
(assessin)Tj
3.8197 0 Td
(g)Tj
0.7653 0 Td
(the)Tj
1.5875 0 Td
(effects)Tj
3.1252 0 Td
(of)Tj
1.0417 0 Td
(aspirin)Tj
3.0969 0 Td
(on)Tj
1.311 0 Td
(disease)Tj
3.6071 0 Td
(recur-)Tj
-41.0459 -1.1906 Td
(rence)Tj
2.6787 0 Td
(and)Tj
1.8567 0 Td
(survival)Tj
3.5434 0 Td
(after)Tj
2.1897 0 Td
(primar)Tj
2.778 0 Td
(y)Tj
0.7158 0 Td
(therapy)Tj
3.5008 0 Td
(in)Tj
0.9779 0 Td
(commo)Tj
3.2316 0 Td
(n)Tj
0.7653 0 Td
(non-metas)Tj
4.6489 0 Td
(tatic)Tj
2.0268 0 Td
(solid)Tj
2.2252 0 Td
(tumours.)Tj
4.0536 0 Td
(Contempora)Tj
5.4142 0 Td
(ry)Tj
1.0417 0 Td
(Clin)Tj
-41.6483 -1.1906 Td
(Trials)Tj
2.8417 0 Td
(51:)Tj
1.5874 0 Td
(5664.)Tj
/F2 1 Tf
-7.0511 -1.6228 Td
(17.)Tj
/F0 1 Tf
2.622 0 Td
(Baigent)Tj
3.5504 0 Td
(C.)Tj
1.2047 0 Td
(\(2016\))Tj
3.0544 0 Td
(Aspirin)Tj
3.2173 0 Td
(for)Tj
1.3677 0 Td
(disease)Tj
3.6072 0 Td
(preventi)Tj
3.4866 0 Td
(on:)Tj
1.5874 0 Td
(public)Tj
2.778 0 Td
(policy)Tj
2.7213 0 Td
(or)Tj
1.0913 0 Td
(personal)Tj
3.9827 0 Td
(choice?)Tj
3.6 0 Td
(Ann)Tj
1.9701 0 Td
(Int)Tj
1.3182 0 Td
(Med)Tj
2.3527 0 Td
(164:)Tj
-40.89 -1.1835 Td
(846847.)Tj
0.83 0.64 0.02 0 k
4.3157 0 Td
(https://)Tj
2.9552 0 Td
(doi.org/10.73)Tj
5.7331 0 Td
(26/M16-0)Tj
4.1528 0 Td
(576)Tj
0 g
1.8567 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(27064970)Tj
0 g
/F2 1 Tf
-24.6048 -1.6299 Td
(18.)Tj
/F0 1 Tf
2.622 0 Td
(Elwood)Tj
3.437 0 Td
(PC,)Tj
1.8709 0 Td
(Morgan)Tj
3.5504 0 Td
(G,)Tj
1.2685 0 Td
(Pickering)Tj
4.2591 0 Td
(JE,)Tj
1.6512 0 Td
(Galante)Tj
3.6638 0 Td
(J,)Tj
0.985 0 Td
(Weightman)Tj
5.2017 0 Td
(AL,)Tj
1.7008 0 Td
(Morris)Tj
2.948 0 Td
(D,)Tj
1.2118 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2016\))Tj
3.0544 0 Td
(Aspirin)Tj
3.2173 0 Td
(in)Tj
0.978 0 Td
(the)Tj
-41.294 -1.1835 Td
(treatment)Tj
4.3795 0 Td
(of)Tj
1.0418 0 Td
(cancer:)Tj
3.4441 0 Td
(reductions)Tj
4.748 0 Td
(in)Tj
0.978 0 Td
(metastatic)Tj
4.7126 0 Td
(spread)Tj
3.2174 0 Td
(and)Tj
1.8567 0 Td
(in)Tj
0.978 0 Td
(mortality:)Tj
4.2094 0 Td
(a)Tj
0.7654 0 Td
(systematic)Tj
4.8756 0 Td
(review)Tj
3.0544 0 Td
(and)Tj
1.8567 0 Td
(meta-)Tj
-40.1176 -1.1905 Td
(analyses)Tj
4.096 0 Td
(of)Tj
1.0418 0 Td
(publishe)Tj
3.6425 0 Td
(d)Tj
0.7654 0 Td
(studies.)Tj
3.6071 0 Td
(PLoS)Tj
2.6292 0 Td
(One)Tj
2.3031 0 Td
(11:)Tj
1.5874 0 Td
(e0152402.)Tj
0.83 0.64 0.02 0 k
4.8615 0 Td
(https://do)Tj
4.0465 0 Td
(i.org/10.1371)Tj
5.7331 0 Td
(/journal.pon)Tj
5.1237 0 Td
(e.01524)Tj
3.5433 0 Td
(02)Tj
0 g
-42.9806 -1.1835 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(270969)Tj
3.2669 0 Td
(51)Tj
0 g
/F2 1 Tf
-8.8582 -1.63 Td
(19.)Tj
/F0 1 Tf
2.622 0 Td
(Moher)Tj
3.0118 0 Td
(D,)Tj
1.2047 0 Td
(Liberati)Tj
3.43 0 Td
(A,)Tj
1.1551 0 Td
(Tetzlaff)Tj
3.4512 0 Td
(J,)Tj
0.985 0 Td
(Altman)Tj
3.2883 0 Td
(DG.)Tj
1.9771 0 Td
(\(2009\))Tj
3.0615 0 Td
(Preferred)Tj
4.3158 0 Td
(reporting)Tj
4.089 0 Td
(items)Tj
2.5724 0 Td
(for)Tj
1.3678 0 Td
(systematic)Tj
4.8756 0 Td
(reviews)Tj
3.5504 0 Td
(and)Tj
-42.3357 -1.1834 Td
(meta-ana)Tj
4.1527 0 Td
(lyses:)Tj
2.7355 0 Td
(the)Tj
1.5874 0 Td
(PRISMA)Tj
4.0111 0 Td
(statement.)Tj
4.8189 0 Td
(PLoS)Tj
2.6292 0 Td
(One)Tj
2.3102 0 Td
(6:)Tj
1.0417 0 Td
(e10000)Tj
3.267 0 Td
(97.)Tj
/F2 1 Tf
-29.1757 -1.63 Td
(20.)Tj
/F0 1 Tf
2.622 0 Td
(Wells)Tj
2.622 0 Td
(G,)Tj
1.2685 0 Td
(Shea)Tj
2.5158 0 Td
(B,)Tj
1.1551 0 Td
(O'Connell)Tj
4.5284 0 Td
(D,)Tj
1.2047 0 Td
(Robertson)Tj
4.7552 0 Td
(J,)Tj
0.9921 0 Td
(Peterso)Tj
3.3875 0 Td
(n)Tj
0.7653 0 Td
(J,)Tj
0.9922 0 Td
(Welch)Tj
2.9551 0 Td
(V,)Tj
1.1551 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2011\))Tj
3.0544 0 Td
(The)Tj
1.9204 0 Td
(Newcastle-)Tj
4.8615 0 Td
(Ottaway)Tj
-40.4294 -1.1834 Td
(Scale)Tj
2.6787 0 Td
(\(NOS\))Tj
3.0189 0 Td
(for)Tj
1.3678 0 Td
(assessin)Tj
3.8197 0 Td
(g)Tj
0.7653 0 Td
(the)Tj
1.5874 0 Td
(quality)Tj
3.0544 0 Td
(of)Tj
1.0347 0 Td
(nonrandomize)Tj
6.2221 0 Td
(d)Tj
0.7653 0 Td
(studies)Tj
3.3378 0 Td
(in)Tj
0.978 0 Td
(meta-ana)Tj
4.1528 0 Td
(lysis.)Tj
/F2 1 Tf
-35.4049 -1.6229 Td
(21.)Tj
/F0 1 Tf
2.622 0 Td
(Egger)Tj
2.8417 0 Td
(M,)Tj
1.3252 0 Td
(Smith)Tj
2.7355 0 Td
(GD,)Tj
1.9842 0 Td
(Altman)Tj
3.2812 0 Td
(DG.)Tj
1.9842 0 Td
(\(2001\))Tj
3.0544 0 Td
(System)Tj
3.2882 0 Td
(atic)Tj
1.7504 0 Td
(reviews)Tj
3.5504 0 Td
(in)Tj
0.978 0 Td
(health)Tj
2.8914 0 Td
(care:)Tj
2.4023 0 Td
(meta-analy)Tj
4.8615 0 Td
(sis)Tj
1.4244 0 Td
(in)Tj
0.978 0 Td
(context.)Tj
-39.331 -1.1905 Td
(2nd)Tj
1.8567 0 Td
(edition)Tj
3.1039 0 Td
(ed.)Tj
1.8071 0 Td
(London)Tj
3.267 0 Td
(:)Tj
0.7157 0 Td
(BMJ)Tj
2.204 0 Td
(Books.)Tj
/F2 1 Tf
-15.5764 -1.6229 Td
(22.)Tj
/F0 1 Tf
2.622 0 Td
(Bains)Tj
2.6787 0 Td
(SJ,)Tj
1.6441 0 Td
(Mahic)Tj
2.8418 0 Td
(M,)Tj
1.3252 0 Td
(Myklebus)Tj
4.1528 0 Td
(t)Tj
0.496 0 Td
(TA,)Tj
1.7646 0 Td
(Smastuen)Tj
4.656 0 Td
(MC,)Tj
2.0338 0 Td
(Yaqub)Tj
3.0615 0 Td
(S,)Tj
1.148 0 Td
(Dorum)Tj
3.1819 0 Td
(LM,)Tj
1.8638 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2016\))Tj
3.0544 0 Td
(Aspirin)Tj
3.2173 0 Td
(as)Tj
1.2543 0 Td
(second-)Tj
-40.6703 -1.1905 Td
(ary)Tj
1.5874 0 Td
(preventi)Tj
3.4866 0 Td
(on)Tj
1.311 0 Td
(in)Tj
0.978 0 Td
(patients)Tj
3.6638 0 Td
(with)Tj
1.963 0 Td
(colorectal)Tj
4.415 0 Td
(cancer:)Tj
3.4441 0 Td
(an)Tj
1.3111 0 Td
(unselected)Tj
4.9677 0 Td
(population-)Tj
4.8473 0 Td
(based)Tj
2.8985 0 Td
(study.)Tj
2.8488 0 Td
(J)Tj
0.7087 0 Td
(Clin)Tj
1.9063 0 Td
(Oncol)Tj
-40.3373 -1.1906 Td
(34:)Tj
1.5874 0 Td
(2501250)Tj
4.3583 0 Td
(8.)Tj
0.83 0.64 0.02 0 k
1.0417 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.1200)Tj
4.3654 0 Td
(/JCO.2015.6)Tj
5.5347 0 Td
(5.3519)Tj
0 g
3.2244 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9623 0 Td
(27247217)Tj
0 g
/F2 1 Tf
-31.1104 -1.6229 Td
(23.)Tj
/F0 1 Tf
2.622 0 Td
(Frouws)Tj
3.4512 0 Td
(MA,)Tj
1.9771 0 Td
(Bastiaannet)Tj
5.4143 0 Td
(E,)Tj
1.1551 0 Td
(Langle)Tj
2.9339 0 Td
(y)Tj
0.7157 0 Td
(RE,)Tj
1.8638 0 Td
(Chia)Tj
2.2394 0 Td
(WK,)Tj
2.0977 0 Td
(van)Tj
1.8 0 Td
(Herk-Suke)Tj
4.6488 0 Td
(l)Tj
0.4323 0 Td
(MP,)Tj
1.9843 0 Td
(Lemmen)Tj
3.8268 0 Td
(s)Tj
0.7157 0 Td
(VE,)Tj
1.8142 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2017\))Tj
-39.3664 -1.1834 Td
(Effect)Tj
2.7425 0 Td
(of)Tj
1.0417 0 Td
(low-dose)Tj
4.1457 0 Td
(aspirin)Tj
3.104 0 Td
(use)Tj
1.8071 0 Td
(on)Tj
1.311 0 Td
(survival)Tj
3.5434 0 Td
(of)Tj
1.0417 0 Td
(patients)Tj
3.6567 0 Td
(with)Tj
1.963 0 Td
(gastrointes)Tj
4.8048 0 Td
(tinal)Tj
2.0126 0 Td
(malignanc)Tj
4.4717 0 Td
(ies;)Tj
1.7504 0 Td
(an)Tj
1.311 0 Td
(observa-)Tj
-38.7073 -1.1906 Td
(tional)Tj
2.5582 0 Td
(study.)Tj
2.8489 0 Td
(British)Tj
2.948 0 Td
(J)Tj
0.7087 0 Td
(Cancer)Tj
3.6142 0 Td
(116:)Tj
2.126 0 Td
(405413.)Tj
/F2 1 Tf
-17.426 -1.6228 Td
(24.)Tj
/F0 1 Tf
2.622 0 Td
(Giampieri)Tj
4.422 0 Td
(R,)Tj
1.2048 0 Td
(Restivo)Tj
3.5008 0 Td
(A,)Tj
1.1551 0 Td
(Pusceddu)Tj
4.5922 0 Td
(V,)Tj
1.1551 0 Td
(Del)Tj
1.6866 0 Td
(Prete)Tj
2.5725 0 Td
(M,)Tj
1.3252 0 Td
(Maccaroni)Tj
4.7551 0 Td
(E,)Tj
1.1552 0 Td
(Bittoni)Tj
2.948 0 Td
(A,)Tj
1.1552 0 Td
(et)Tj
1.0346 0 Td
(al.)Tj
1.2544 0 Td
(\(2017\))Tj
3.0614 0 Td
(The)Tj
1.9134 0 Td
(role)Tj
1.8496 0 Td
(of)Tj
1.0418 0 Td
(aspi-)Tj
-41.783 -1.1906 Td
(rin)Tj
1.3039 0 Td
(as)Tj
1.2614 0 Td
(antitumor)Tj
4.0961 0 Td
(al)Tj
0.978 0 Td
(agent)Tj
2.6787 0 Td
(for)Tj
1.3678 0 Td
(heavily)Tj
3.2669 0 Td
(pretreated)Tj
4.6985 0 Td
(patients)Tj
3.6567 0 Td
(with)Tj
1.9701 0 Td
(metast)Tj
2.9551 0 Td
(atic)Tj
1.7505 0 Td
(colorectal)Tj
4.4149 0 Td
(cancer)Tj
3.1749 0 Td
(receiving)Tj
4.1386 0 Td
(cape-)Tj
-41.7121 -1.1835 Td
(citabine)Tj
3.5929 0 Td
(monotherapy)Tj
5.7402 0 Td
(.)Tj
0.4961 0 Td
(Clin)Tj
1.9063 0 Td
(Colorectal)Tj
4.6347 0 Td
(Cancer)Tj
3.6071 0 Td
(16\(1\):)Tj
2.785 0 Td
(3843.)Tj
0.83 0.64 0.02 0 k
3.2245 0 Td
(https://doi.)Tj
4.5354 0 Td
(org/10.1016/j)Tj
5.7332 0 Td
(.clcc.20)Tj
3.3307 0 Td
(16.07.011)Tj
0 g
-39.5861 -1.1905 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(275760)Tj
3.2669 0 Td
(95)Tj
0 g
/F2 1 Tf
-8.8582 -1.6229 Td
(25.)Tj
/F0 1 Tf
2.622 0 Td
(Shimoike)Tj
4.259 0 Td
(N,)Tj
1.2119 0 Td
(Fujikaw)Tj
3.3236 0 Td
(a)Tj
0.7654 0 Td
(T,)Tj
1.1055 0 Td
(Yoshimoto)Tj
4.8685 0 Td
(Y,)Tj
1.1552 0 Td
(Tanaka)Tj
3.5008 0 Td
(A.)Tj
1.1551 0 Td
(\(2016\))Tj
3.0544 0 Td
(Does)Tj
2.5157 0 Td
(antiplatelet)Tj
4.9607 0 Td
(therapy)Tj
3.4937 0 Td
(affect)Tj
2.6363 0 Td
(short-te)Tj
3.3307 0 Td
(rm)Tj
-41.3365 -1.1905 Td
(and)Tj
1.8567 0 Td
(long-term)Tj
4.3724 0 Td
(outcom)Tj
3.2245 0 Td
(es)Tj
1.2614 0 Td
(of)Tj
1.0417 0 Td
(patients)Tj
3.6568 0 Td
(undergoing)Tj
5.1236 0 Td
(surgery)Tj
3.5008 0 Td
(for)Tj
1.3678 0 Td
(colorectal)Tj
4.415 0 Td
(cancer?)Tj
4.4858 0 Td
(Surgical)Tj
3.763 0 Td
(radicality)Tj
4.089 0 Td
(ver-)Tj
-42.1585 -1.1835 Td
(sus)Tj
1.7504 0 Td
(periopera)Tj
4.1386 0 Td
(tive)Tj
1.7504 0 Td
(antiplatelet)Tj
4.7339 0 Td
(-related)Tj
3.5504 0 Td
(morbidi)Tj
3.2103 0 Td
(ty)Tj
0.9921 0 Td
(risks.)Tj
2.5158 0 Td
(Journal)Tj
3.437 0 Td
(of)Tj
1.0346 0 Td
(Gastroenter)Tj
5.2017 0 Td
(ol)Tj
0.9779 0 Td
(and)Tj
1.8567 0 Td
(Hepatol)Tj
3.6001 0 Td
(Res)Tj
2.1897 0 Td
(5:)Tj
-40.9396 -1.1906 Td
(19621969.)Tj
/F2 1 Tf
-2.622 -1.6228 Td
(26.)Tj
/F0 1 Tf
2.622 0 Td
(Restivo)Tj
3.4866 0 Td
(A,)Tj
1.148 0 Td
(Cocco)Tj
2.9977 0 Td
(IMF,)Tj
2.1969 0 Td
(Casula)Tj
3.2598 0 Td
(G,)Tj
1.2615 0 Td
(Scintu)Tj
2.9409 0 Td
(F,)Tj
1.0985 0 Td
(Cabras)Tj
3.3803 0 Td
(F,)Tj
1.0913 0 Td
(Scartozzi)Tj
4.2591 0 Td
(M,)Tj
1.3111 0 Td
(et)Tj
1.0275 0 Td
(al.)Tj
1.2473 0 Td
(\(2015\))Tj
3.0473 0 Td
(Aspirin)Tj
3.2031 0 Td
(as)Tj
1.2473 0 Td
(a)Tj
0.7583 0 Td
(neoadjuvan)Tj
5.0669 0 Td
(t)Tj
-44.0294 -1.1906 Td
(agent)Tj
2.6787 0 Td
(during)Tj
2.941 0 Td
(preoperati)Tj
4.415 0 Td
(ve)Tj
1.2543 0 Td
(chemoradiat)Tj
5.4071 0 Td
(ion)Tj
1.5237 0 Td
(for)Tj
1.3748 0 Td
(rectal)Tj
2.615 0 Td
(cancer.)Tj
3.4441 0 Td
(Brit)Tj
1.7008 0 Td
(J)Tj
0.7087 0 Td
(Cancer)Tj
3.6071 0 Td
(113:1133113)Tj
6.2788 0 Td
(9.)Tj
0.83 0.64 0.02 0 k
1.0417 0 Td
(https://)Tj
2.9551 0 Td
(doi.)Tj
-41.9459 -1.1835 Td
(org/10.1038/)Tj
5.5134 0 Td
(bjc.2015.33)Tj
5.074 0 Td
(6)Tj
0 g
0.7654 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(26372700)Tj
0 g
/F2 1 Tf
-16.9441 -1.6299 Td
(27.)Tj
/F0 1 Tf
2.622 0 Td
(Ventura)Tj
3.6638 0 Td
(L,)Tj
1.0417 0 Td
(Miccines)Tj
3.8197 0 Td
(i)Tj
0.4323 0 Td
(G,)Tj
1.2685 0 Td
(Barchielli)Tj
4.1953 0 Td
(A,)Tj
1.1481 0 Td
(Manneschi)Tj
4.9748 0 Td
(G,)Tj
1.2685 0 Td
(Puliti)Tj
2.3386 0 Td
(D,)Tj
1.2118 0 Td
(Mantellin)Tj
3.919 0 Td
(i)Tj
0.4323 0 Td
(P,)Tj
1.1551 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2544 0 Td
(\(2016\))Tj
3.0543 0 Td
(Does)Tj
2.5158 0 Td
(low-dose)Tj
-38.7357 -1.1835 Td
(aspirin)Tj
3.1039 0 Td
(use)Tj
1.8 0 Td
(for)Tj
1.3678 0 Td
(cardiovascul)Tj
5.4567 0 Td
(ar)Tj
1.0913 0 Td
(disease)Tj
3.6001 0 Td
(prevention)Tj
4.8047 0 Td
(reduce)Tj
3.2245 0 Td
(colorectal)Tj
4.415 0 Td
(cancer)Tj
3.1677 0 Td
(deaths?)Tj
3.7205 0 Td
(A)Tj
0.8787 0 Td
(comparison)Tj
5.3009 0 Td
(of)Tj
-41.9318 -1.1905 Td
(two)Tj
1.7504 0 Td
(cohorts)Tj
3.4441 0 Td
(in)Tj
0.985 0 Td
(the)Tj
1.5804 0 Td
(Florence)Tj
4.0464 0 Td
(district,)Tj
3.3308 0 Td
(Italy.)Tj
2.2961 0 Td
(In:)Tj
1.3181 0 Td
(Eur)Tj
1.7504 0 Td
(J)Tj
0.7157 0 Td
(Cancer)Tj
3.3875 0 Td
(Prev)Tj
2.2464 0 Td
(2016/11)Tj
3.5434 0 Td
(/16)Tj
1.5874 0 Td
(ed;)Tj
1.5874 0 Td
(2016.)Tj
/F2 1 Tf
-36.1915 -1.6229 Td
(28.)Tj
/F0 1 Tf
2.622 0 Td
(Gray)Tj
2.3598 0 Td
(RT,)Tj
1.8142 0 Td
(Cantwell)Tj
3.9827 0 Td
(MM,)Tj
2.1473 0 Td
(Coleman)Tj
4.1528 0 Td
(HG,)Tj
1.9771 0 Td
(Loughrey)Tj
4.3158 0 Td
(MB,)Tj
1.9772 0 Td
(Bankhead)Tj
4.6489 0 Td
(P,)Tj
1.148 0 Td
(McQuaid)Tj
4.167 0 Td
(S,)Tj
1.1551 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2544 0 Td
(\(2017\))Tj
3.0543 0 Td
(Evaluati)Tj
3.4867 0 Td
(on)Tj
-42.683 -1.1905 Td
(of)Tj
1.0417 0 Td
(PTGS2)Tj
3.4654 0 Td
(Expressio)Tj
4.3158 0 Td
(n,)Tj
1.0417 0 Td
(PIK3CA)Tj
3.7276 0 Td
(Mutation,)Tj
4.2662 0 Td
(Aspirin)Tj
3.2173 0 Td
(Use)Tj
1.9701 0 Td
(and)Tj
1.8567 0 Td
(Colon)Tj
2.7851 0 Td
(Cance)Tj
2.8346 0 Td
(r)Tj
0.5528 0 Td
(Survival)Tj
3.7063 0 Td
(in)Tj
0.978 0 Td
(a)Tj
0.7653 0 Td
(Population-)Tj
4.9607 0 Td
(Based)Tj
-41.4853 -1.1835 Td
(Cohort)Tj
3.1677 0 Td
(Study.)Tj
3.0189 0 Td
(Clin)Tj
1.8992 0 Td
(and)Tj
1.8567 0 Td
(Translat)Tj
3.7772 0 Td
(Gastro)Tj
2.9552 0 Td
(enterol)Tj
3.437 0 Td
(8:)Tj
1.0418 0 Td
(e91.)Tj
/F2 1 Tf
-23.7757 -1.6299 Td
(29.)Tj
/F0 1 Tf
2.622 0 Td
(Hua)Tj
2.0197 0 Td
(X,)Tj
1.1551 0 Td
(Phipps)Tj
3.2244 0 Td
(AI,)Tj
1.4315 0 Td
(Burnett-H)Tj
4.2095 0 Td
(artman)Tj
3.2882 0 Td
(AN,)Tj
1.8638 0 Td
(Adams)Tj
3.2882 0 Td
(SV,)Tj
1.8142 0 Td
(Hardikar)Tj
3.9331 0 Td
(S,)Tj
1.1551 0 Td
(Cohen)Tj
3.1111 0 Td
(SA,)Tj
1.8142 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2544 0 Td
(\(2017\))Tj
3.0543 0 Td
(Timing)Tj
3.1678 0 Td
(of)Tj
1.0417 0 Td
(aspi-)Tj
-41.868 -1.1835 Td
(rin)Tj
1.3039 0 Td
(and)Tj
1.8567 0 Td
(other)Tj
2.4591 0 Td
(nonsteroidal)Tj
5.563 0 Td
(anti-inflam)Tj
4.5213 0 Td
(matory)Tj
3.2315 0 Td
(drug)Tj
2.1827 0 Td
(use)Tj
1.8071 0 Td
(among)Tj
3.2245 0 Td
(patients)Tj
3.6638 0 Td
(with)Tj
1.963 0 Td
(colorectal)Tj
4.415 0 Td
(cancer)Tj
3.1677 0 Td
(in)Tj
0.9851 0 Td
(relation)Tj
-40.3444 -1.1906 Td
(to)Tj
1.0417 0 Td
(tumor)Tj
2.7354 0 Td
(markers)Tj
3.7772 0 Td
(and)Tj
1.8567 0 Td
(survival.)Tj
3.8198 0 Td
(J)Tj
0.7157 0 Td
(Clin)Tj
1.9063 0 Td
(Oncol)Tj
3.0048 0 Td
(35:)Tj
1.5874 0 Td
(28062813.)Tj
0.83 0.64 0.02 0 k
5.4071 0 Td
(https://do)Tj
4.0465 0 Td
(i.org/10.1200)Tj
5.7331 0 Td
(/JCO.2017.7)Tj
5.5276 0 Td
(2.3569)Tj
0 g
-41.1593 -1.1835 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(286176)Tj
3.2669 0 Td
(23)Tj
0 g
/F2 1 Tf
-8.8582 -1.6299 Td
(30.)Tj
/F0 1 Tf
2.622 0 Td
(Veitonma)Tj
4.1527 0 Td
(ki)Tj
0.9284 0 Td
(T,)Tj
1.1055 0 Td
(Murtola)Tj
3.4937 0 Td
(TJ,)Tj
1.6016 0 Td
(Talala)Tj
2.8843 0 Td
(K,)Tj
1.1551 0 Td
(Taari)Tj
2.4591 0 Td
(K,)Tj
1.1551 0 Td
(Tammela)Tj
4.33 0 Td
(T,)Tj
1.1055 0 Td
(Auvinen)Tj
3.763 0 Td
(A.)Tj
1.1552 0 Td
(\(2016\))Tj
3.0543 0 Td
(Non-stero)Tj
4.3158 0 Td
(idal)Tj
1.7433 0 Td
(anti-inf)Tj
2.9339 0 Td
(lam-)Tj
-41.3365 -1.1835 Td
(matory)Tj
3.2315 0 Td
(drugs)Tj
2.6787 0 Td
(and)Tj
1.8567 0 Td
(cancer)Tj
3.1678 0 Td
(death)Tj
2.6787 0 Td
(in)Tj
0.978 0 Td
(the)Tj
1.5874 0 Td
(Finnish)Tj
3.3804 0 Td
(Prostate)Tj
3.8905 0 Td
(Cancer)Tj
3.3875 0 Td
(Screen)Tj
3.111 0 Td
(ing)Tj
1.5237 0 Td
(Trial.)Tj
2.4023 0 Td
(PLoS)Tj
2.6292 0 Td
(One)Tj
2.3102 0 Td
(11:)Tj
-38.8136 -1.1905 Td
(e0153413.)Tj
0.83 0.64 0.02 0 k
4.8614 0 Td
(https://)Tj
2.9551 0 Td
(doi.org/10.13)Tj
5.7332 0 Td
(71/journal.p)Tj
5.1236 0 Td
(one.015)Tj
3.5434 0 Td
(3413)Tj
0 g
2.4023 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9694 0 Td
(271008)Tj
3.2669 0 Td
(76)Tj
0 g
/F2 1 Tf
-33.4773 -1.6229 Td
(31.)Tj
/F0 1 Tf
2.622 0 Td
(Murphy)Tj
3.5008 0 Td
(C,)Tj
1.2118 0 Td
(Turner)Tj
3.1181 0 Td
(N,)Tj
1.2048 0 Td
(Wong)Tj
2.7921 0 Td
(HL,)Tj
1.7575 0 Td
(Sinnath)Tj
3.3236 0 Td
(amby)Tj
2.6363 0 Td
(M,)Tj
1.3181 0 Td
(Tie)Tj
1.5874 0 Td
(J,)Tj
0.9851 0 Td
(Lee)Tj
1.8567 0 Td
(B,)Tj
1.1551 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2544 0 Td
(\(2017\))Tj
3.0543 0 Td
(Examinin)Tj
4.0394 0 Td
(g)Tj
0.7654 0 Td
(the)Tj
1.5874 0 Td
(impact)Tj
3.1181 0 Td
(of)Tj
1.0418 0 Td
(reg-)Tj
-42.3499 -1.1905 Td
(ular)Tj
1.8496 0 Td
(aspirin)Tj
3.1039 0 Td
(use)Tj
1.8071 0 Td
(and)Tj
1.8567 0 Td
(PIK3CA)Tj
3.7276 0 Td
(mutations)Tj
4.4859 0 Td
(on)Tj
1.311 0 Td
(survival)Tj
3.5434 0 Td
(in)Tj
0.9779 0 Td
(stage)Tj
2.6221 0 Td
(2)Tj
0.7653 0 Td
(colon)Tj
2.5654 0 Td
(cancer.)Tj
3.4441 0 Td
(Intern)Tj
2.7355 0 Td
(Med)Tj
2.1331 0 Td
(J)Tj
0.9354 0 Td
(47:)Tj
1.5874 0 Td
(8898.)Tj
0.83 0.64 0.02 0 k
-39.4514 -1.1835 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.111)Tj
3.8197 0 Td
(1/imj.1331)Tj
4.5284 0 Td
(2)Tj
0 g
0.7653 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(27800646)Tj
0 g
/F2 1 Tf
-20.1189 -1.6299 Td
(32.)Tj
/F0 1 Tf
2.622 0 Td
(Ratnasinghe)Tj
5.7331 0 Td
(LD,)Tj
1.7504 0 Td
(Graubard)Tj
4.3724 0 Td
(BI,)Tj
1.4316 0 Td
(Kahle)Tj
2.7283 0 Td
(L,)Tj
1.0418 0 Td
(Tangrea)Tj
3.8835 0 Td
(JA,)Tj
1.6441 0 Td
(Taylor)Tj
2.9551 0 Td
(PR,)Tj
1.8638 0 Td
(Hawk)Tj
2.6859 0 Td
(E.)Tj
1.1551 0 Td
(\(2004\))Tj
3.0543 0 Td
(Aspirin)Tj
3.2174 0 Td
(use)Tj
1.8 0 Td
(and)Tj
1.8567 0 Td
(mortal-)Tj
-41.1735 -1.1835 Td
(ity)Tj
1.2047 0 Td
(from)Tj
2.1898 0 Td
(cancer)Tj
3.1748 0 Td
(in)Tj
0.978 0 Td
(a)Tj
0.7653 0 Td
(prospectiv)Tj
4.4717 0 Td
(e)Tj
0.7654 0 Td
(cohort)Tj
2.9551 0 Td
(study.)Tj
2.8488 0 Td
(Anticance)Tj
4.3158 0 Td
(r)Tj
0.5457 0 Td
(Res)Tj
2.1898 0 Td
(24:)Tj
1.5874 0 Td
(31773184.)Tj
5.4071 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9623 0 Td
(15510608)Tj
0 g
/F2 1 Tf
-38.9837 -1.6229 Td
(33.)Tj
/F0 1 Tf
2.622 0 Td
(Hippisley-C)Tj
5.0102 0 Td
(ox)Tj
1.2615 0 Td
(J,)Tj
0.985 0 Td
(Coupland)Tj
4.4221 0 Td
(C.)Tj
1.2047 0 Td
(\(2017\))Tj
3.0544 0 Td
(Development)Tj
6.0095 0 Td
(and)Tj
1.8567 0 Td
(validation)Tj
4.3583 0 Td
(of)Tj
1.0417 0 Td
(risk)Tj
1.7433 0 Td
(prediction)Tj
4.4717 0 Td
(equations)Tj
4.4717 0 Td
(to)Tj
1.0418 0 Td
(esti-)Tj
-40.9326 -1.1905 Td
(mate)Tj
2.4094 0 Td
(survival)Tj
3.5434 0 Td
(in)Tj
0.985 0 Td
(patients)Tj
3.6567 0 Td
(with)Tj
1.963 0 Td
(colorectal)Tj
4.415 0 Td
(cancer:)Tj
3.4512 0 Td
(cohort)Tj
2.9481 0 Td
(study.)Tj
2.8488 0 Td
(Brit)Tj
1.6937 0 Td
(Med)Tj
2.1402 0 Td
(J)Tj
0.9355 0 Td
(357:)Tj
2.126 0 Td
(2497)Tj
2.4023 0 Td
(2522.)Tj
/F2 1 Tf
-38.1403 -1.6229 Td
(34.)Tj
/F0 1 Tf
2.622 0 Td
(Hamada)Tj
3.9401 0 Td
(T,)Tj
1.0985 0 Td
(Cao)Tj
2.0268 0 Td
(Y,)Tj
1.1551 0 Td
(Qian)Tj
2.2961 0 Td
(ZR,)Tj
1.8142 0 Td
(Masugi)Tj
3.3874 0 Td
(Y,)Tj
1.1551 0 Td
(Nowak)Tj
3.2244 0 Td
(JA,)Tj
1.6512 0 Td
(Yang)Tj
2.5158 0 Td
(J,)Tj
0.9921 0 Td
(et)Tj
1.0347 0 Td
(al.)Tj
1.2543 0 Td
(\(2017\))Tj
3.0615 0 Td
(Aspirin)Tj
3.2173 0 Td
(use)Tj
1.8 0 Td
(and)Tj
1.8567 0 Td
(colorectal)Tj
4.415 0 Td
(can-)Tj
-41.8963 -1.1905 Td
(cer)Tj
1.5874 0 Td
(survival)Tj
3.5433 0 Td
(according)Tj
4.4717 0 Td
(to)Tj
1.0417 0 Td
(tumor)Tj
2.7426 0 Td
(CD274)Tj
3.274 0 Td
(\(Programmed)Tj
6.2434 0 Td
(Cell)Tj
1.8992 0 Td
(Death)Tj
2.8488 0 Td
(1)Tj
0.7654 0 Td
(Ligand)Tj
3.1536 0 Td
(1\))Tj
1.0984 0 Td
(expression)Tj
4.9678 0 Td
(status)Tj
2.622 0 Td
(.)Tj
0.4961 0 Td
(J)Tj
0.7157 0 Td
(Clin)Tj
-41.4711 -1.1835 Td
(Oncol)Tj
3.0118 0 Td
(35:1836)Tj
3.5433 0 Td
(1844.)Tj
0.83 0.64 0.02 0 k
3.2245 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.120)Tj
3.8197 0 Td
(0/JCO.2016)Tj
5.2583 0 Td
(.70.7547)Tj
0 g
4.0465 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9622 0 Td
(28406723)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
31.7412 0 Td
(14)Tj
1.304 0 Td
(/)Tj
ET
endstream
endobj
585 0 obj
<>stream
endstream
endobj
586 0 obj
<>stream
endstream
endobj
587 0 obj
<>stream
endstream
endobj
588 0 obj
<>stream
endstream
endobj
589 0 obj
<>stream
endstream
endobj
590 0 obj
<>stream
endstream
endobj
591 0 obj
<>stream
endstream
endobj
592 0 obj
<>stream
endstream
endobj
593 0 obj
<>stream
endstream
endobj
594 0 obj
<>stream
endstream
endobj
595 0 obj
<>stream
endstream
endobj
596 0 obj
<>stream
endstream
endobj
597 0 obj
<>stream
endstream
endobj
598 0 obj
<>stream
endstream
endobj
599 0 obj
<>stream
endstream
endobj
600 0 obj
<>stream
endstream
endobj
601 0 obj
<>stream
endstream
endobj
602 0 obj
<>stream
endstream
endobj
603 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
604 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 344 0 R/Annots 605 0 R/Contents 606 0 R/TrimBox[0 0 612 792]>>
endobj
605 0 obj
[607 0 R 608 0 R 609 0 R 610 0 R 611 0 R 612 0 R 613 0 R 614 0 R 615 0 R 616 0 R 617 0 R 618 0 R 619 0 R 620 0 R 621 0 R 622 0 R 623 0 R 624 0 R 625 0 R 626 0 R 627 0 R 628 0 R 629 0 R 630 0 R 631 0 R 632 0 R 633 0 R 634 0 R 635 0 R 636 0 R 637 0 R 638 0 R 639 0 R 640 0 R 641 0 R 642 0 R 643 0 R 644 0 R 645 0 R 646 0 R 647 0 R 648 0 R 649 0 R 650 0 R 651 0 R 652 0 R 653 0 R 654 0 R 655 0 R 656 0 R 657 0 R 658 0 R 659 0 R 660 0 R 661 0 R 662 0 R]
endobj
607 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref035)>>
endobj
608 0 obj
<>/Border[0 0 0]/A 663 0 R>>
endobj
663 0 obj
<>
endobj
609 0 obj
<>/Border[0 0 0]/A 664 0 R>>
endobj
664 0 obj
<>
endobj
610 0 obj
<>/Border[0 0 0]/A 665 0 R>>
endobj
665 0 obj
<>
endobj
611 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref036)>>
endobj
612 0 obj
<>/Border[0 0 0]/A 666 0 R>>
endobj
666 0 obj
<>
endobj
613 0 obj
<>/Border[0 0 0]/A 667 0 R>>
endobj
667 0 obj
<>
endobj
614 0 obj
<>/Border[0 0 0]/A 668 0 R>>
endobj
668 0 obj
<>
endobj
615 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref037)>>
endobj
616 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref038)>>
endobj
617 0 obj
<>/Border[0 0 0]/A 669 0 R>>
endobj
669 0 obj
<>
endobj
618 0 obj
<>/Border[0 0 0]/A 670 0 R>>
endobj
670 0 obj
<>
endobj
619 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref039)>>
endobj
620 0 obj
<>/Border[0 0 0]/A 671 0 R>>
endobj
671 0 obj
<>
endobj
621 0 obj
<>/Border[0 0 0]/A 672 0 R>>
endobj
672 0 obj
<>
endobj
622 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref040)>>
endobj
623 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref041)>>
endobj
624 0 obj
<>/Border[0 0 0]/A 673 0 R>>
endobj
673 0 obj
<>
endobj
625 0 obj
<>/Border[0 0 0]/A 674 0 R>>
endobj
674 0 obj
<>
endobj
626 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref042)>>
endobj
627 0 obj
<>/Border[0 0 0]/A 675 0 R>>
endobj
675 0 obj
<>
endobj
628 0 obj
<>/Border[0 0 0]/A 676 0 R>>
endobj
676 0 obj
<>
endobj
629 0 obj
<>/Border[0 0 0]/A 677 0 R>>
endobj
677 0 obj
<>
endobj
630 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref043)>>
endobj
631 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref044)>>
endobj
632 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref045)>>
endobj
633 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref046)>>
endobj
634 0 obj
<>/Border[0 0 0]/A 678 0 R>>
endobj
678 0 obj
<>
endobj
635 0 obj
<>/Border[0 0 0]/A 679 0 R>>
endobj
679 0 obj
<>
endobj
636 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref047)>>
endobj
637 0 obj
<>/Border[0 0 0]/A 680 0 R>>
endobj
680 0 obj
<>
endobj
638 0 obj
<>/Border[0 0 0]/A 681 0 R>>
endobj
681 0 obj
<>
endobj
639 0 obj
<>/Border[0 0 0]/A 682 0 R>>
endobj
682 0 obj
<>
endobj
640 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref048)>>
endobj
641 0 obj
<>/Border[0 0 0]/A 683 0 R>>
endobj
683 0 obj
<>
endobj
642 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref049)>>
endobj
643 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref050)>>
endobj
644 0 obj
<>/Border[0 0 0]/A 684 0 R>>
endobj
684 0 obj
<>
endobj
645 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref051)>>
endobj
646 0 obj
<>/Border[0 0 0]/A 685 0 R>>
endobj
685 0 obj
<>
endobj
647 0 obj
<>/Border[0 0 0]/A 686 0 R>>
endobj
686 0 obj
<>
endobj
648 0 obj
<>/Border[0 0 0]/A 687 0 R>>
endobj
687 0 obj
<>
endobj
649 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref052)>>
endobj
650 0 obj
<>/Border[0 0 0]/A 688 0 R>>
endobj
688 0 obj
<>
endobj
651 0 obj
<>/Border[0 0 0]/A 689 0 R>>
endobj
689 0 obj
<>
endobj
652 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref053)>>
endobj
653 0 obj
<>/Border[0 0 0]/A 690 0 R>>
endobj
690 0 obj
<>
endobj
654 0 obj
<>/Border[0 0 0]/A 691 0 R>>
endobj
691 0 obj
<>
endobj
655 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref054)>>
endobj
656 0 obj
<>/Border[0 0 0]/A 692 0 R>>
endobj
692 0 obj
<>
endobj
657 0 obj
<>/Border[0 0 0]/A 693 0 R>>
endobj
693 0 obj
<>
endobj
658 0 obj
<>/Border[0 0 0]/A 694 0 R>>
endobj
694 0 obj
<>
endobj
659 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref055)>>
endobj
660 0 obj
<>/Border[0 0 0]/A 695 0 R>>
endobj
695 0 obj
<>
endobj
661 0 obj
<>/Border[0 0 0]/A 696 0 R>>
endobj
696 0 obj
<>
endobj
662 0 obj
<>/Border[0 0 0]/A 697 0 R>>
endobj
697 0 obj
<>
endobj
606 0 obj
[698 0 R 699 0 R 700 0 R 701 0 R 702 0 R 703 0 R 704 0 R 705 0 R 706 0 R 707 0 R 708 0 R 709 0 R 710 0 R 711 0 R 712 0 R 713 0 R 714 0 R 715 0 R 716 0 R 717 0 R 718 0 R 719 0 R]
endobj
698 0 obj
<>stream
q
0.83 0.64 0.02 0 k
497.2535 698.1165 m
558.085 698.1165 l
h
f*
221.4992 688.6488 m
312.378 688.6488 l
h
f*
337.8331 688.6488 m
372.7559 688.6488 l
h
f*
456.8315 656.6173 m
565.6819 656.6173 l
h
f*
221.4992 647.1496 m
261.6945 647.1496 l
h
f*
287.1496 647.1496 m
322.0724 647.1496 l
h
f*
221.4992 583.1433 m
338.6268 583.1433 l
h
f*
364.0819 583.1433 m
399.0614 583.1433 l
h
f*
326.8346 551.1685 m
446.6268 551.1685 l
h
f*
472.0819 551.1685 m
507.0047 551.1685 l
h
f*
376.611 487.1622 m
525.2031 487.1622 l
h
f*
221.4992 477.6378 m
256.422 477.6378 l
h
f*
548.7874 455.1307 m
572.485 455.1307 l
h
f*
221.4992 445.663 m
350.7591 445.663 l
h
f*
376.2142 445.663 m
411.1937 445.663 l
h
f*
312.378 346.1669 m
470.1543 346.1669 l
h
f*
495.6094 346.1669 m
530.5323 346.1669 l
h
f*
540.4535 323.6598 m
564.1512 323.6598 l
h
f*
221.4992 314.1354 m
346.8472 314.1354 l
h
f*
372.3024 314.1354 m
407.2252 314.1354 l
h
f*
411.6472 291.6283 m
442.2614 291.6283 l
h
f*
514.148 237.1465 m
549.0709 237.1465 l
h
f*
506.4945 214.6394 m
567.326 214.6394 l
h
f*
221.4992 205.115 m
286.1291 205.115 l
h
f*
311.6409 205.115 m
346.5638 205.115 l
h
f*
268.6677 173.1402 m
433.0772 173.1402 l
h
f*
458.5323 173.1402 m
493.4551 173.1402 l
h
f*
221.4992 141.1654 m
333.3543 141.1654 l
h
f*
358.8094 141.1654 m
393.789 141.1654 l
h
f*
496.4598 118.6583 m
557.2913 118.6583 l
h
f*
221.4992 109.1339 m
309.3165 109.1339 l
h
f*
334.7717 109.1339 m
369.6945 109.1339 l
h
f*
363.1181 86.6268 m
506.4378 86.6268 l
h
f*
531.8929 86.6268 m
566.8724 86.6268 l
h
f*
0 g
1 j
1 J
0 w
7.9999 0 0 7.9999 200.5228 708.7181 cm
BT
/F2 1 Tf
1 TL
-0.005 Tc
0 0 Td
(35.)Tj
/F0 1 Tf
2.622 0 Td
(Mc)Tj
1.5378 0 Td
(Menamin)Tj
4.2662 0 Td
(UC,)Tj
1.9205 0 Td
(Cardwell)Tj
4.0323 0 Td
(CR,)Tj
1.9205 0 Td
(Hughes)Tj
3.6 0 Td
(CM,)Tj
2.0339 0 Td
(Murray)Tj
3.2882 0 Td
(LJ.)Tj
1.5307 0 Td
(\(2017\))Tj
3.0544 0 Td
(Low-dose)Tj
4.4788 0 Td
(aspirin)Tj
3.1039 0 Td
(use)Tj
1.8071 0 Td
(and)Tj
1.8567 0 Td
(survival)Tj
3.5434 0 Td
(in)Tj
-41.9744 -1.1905 Td
(breast)Tj
2.9552 0 Td
(cancer)Tj
3.1677 0 Td
(patients:)Tj
3.9331 0 Td
(a)Tj
0.7654 0 Td
(nationwid)Tj
4.1386 0 Td
(e)Tj
0.7653 0 Td
(cohort)Tj
2.9552 0 Td
(study.)Tj
2.8488 0 Td
(Cancer)Tj
3.3874 0 Td
(Epidem)Tj
3.3308 0 Td
(iol)Tj
1.4173 0 Td
(47:)Tj
1.5803 0 Td
(2027.)Tj
0.83 0.64 0.02 0 k
3.2245 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.)Tj
-39.8838 -1.1835 Td
(1016/j.can)Tj
4.5284 0 Td
(ep.2016.12)Tj
4.9111 0 Td
(.008)Tj
0 g
2.133 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9694 0 Td
(28088656)Tj
0 g
/F2 1 Tf
-17.1639 -1.6228 Td
(36.)Tj
/F0 1 Tf
2.622 0 Td
(Shiao)Tj
2.7284 0 Td
(J,)Tj
0.9921 0 Td
(Thomas)Tj
3.7772 0 Td
(KM,)Tj
1.9843 0 Td
(Rahimi)Tj
3.274 0 Td
(AS,)Tj
1.8142 0 Td
(Rao)Tj
2.0197 0 Td
(R,)Tj
1.2118 0 Td
(Yan)Tj
1.9701 0 Td
(J,)Tj
0.9851 0 Td
(Xie)Tj
1.637 0 Td
(XJ,)Tj
1.6512 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2544 0 Td
(\(2017\))Tj
3.0543 0 Td
(Aspirin/an)Tj
4.3583 0 Td
(tiplatelet)Tj
3.8693 0 Td
(agent)Tj
2.6788 0 Td
(use)Tj
-40.3019 -1.1906 Td
(improves)Tj
4.2095 0 Td
(disease-fr)Tj
4.3087 0 Td
(ee)Tj
1.311 0 Td
(survival)Tj
3.5434 0 Td
(and)Tj
1.8567 0 Td
(reduces)Tj
3.7205 0 Td
(the)Tj
1.5803 0 Td
(risk)Tj
1.7504 0 Td
(of)Tj
1.0417 0 Td
(distant)Tj
3.1111 0 Td
(metastas)Tj
3.9969 0 Td
(es)Tj
1.2614 0 Td
(in)Tj
0.978 0 Td
(Stage)Tj
2.7921 0 Td
(II)Tj
0.7725 0 Td
(and)Tj
1.8567 0 Td
(III)Tj
1.0417 0 Td
(triple-nega)Tj
4.6276 0 Td
(-)Tj
-43.7602 -1.1906 Td
(tive)Tj
1.7504 0 Td
(breast)Tj
2.9481 0 Td
(cancer)Tj
3.1677 0 Td
(patients.)Tj
3.9402 0 Td
(Breast)Tj
3.0615 0 Td
(Cancer)Tj
3.3874 0 Td
(Res)Tj
1.9701 0 Td
(Treat)Tj
2.7425 0 Td
(161:)Tj
2.1331 0 Td
(463471.)Tj
0.83 0.64 0.02 0 k
4.3158 0 Td
(https://)Tj
2.9551 0 Td
(doi.org/10.10)Tj
5.7331 0 Td
(07/s1054)Tj
4.0394 0 Td
(9-)Tj
-42.1444 -1.1834 Td
(016-4081-)Tj
4.4717 0 Td
(8)Tj
0 g
0.7654 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(2800524)Tj
3.8126 0 Td
(5)Tj
0 g
/F2 1 Tf
-14.641 -1.6229 Td
(37.)Tj
/F0 1 Tf
2.622 0 Td
(McCarthy)Tj
4.4363 0 Td
(AM,)Tj
1.9842 0 Td
(He)Tj
1.4741 0 Td
(W,)Tj
1.4386 0 Td
(Regan)Tj
3.111 0 Td
(S,)Tj
1.1551 0 Td
(Chan)Tj
2.5654 0 Td
(AT,)Tj
1.7646 0 Td
(Moy)Tj
2.0835 0 Td
(B,)Tj
1.1551 0 Td
(Lafrate)Tj
3.2811 0 Td
(AJ,)Tj
1.6441 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2017\))Tj
3.0544 0 Td
(Impact)Tj
3.1819 0 Td
(of)Tj
1.0417 0 Td
(PIK3CA)Tj
3.7276 0 Td
(tumor)Tj
-39.3948 -1.1905 Td
(mutation)Tj
3.9898 0 Td
(on)Tj
1.311 0 Td
(the)Tj
1.5875 0 Td
(association)Tj
5.1307 0 Td
(of)Tj
1.0347 0 Td
(aspirin)Tj
3.1039 0 Td
(or)Tj
1.0914 0 Td
(NSAID)Tj
3.2386 0 Td
(use)Tj
1.8071 0 Td
(and)Tj
1.8567 0 Td
(time)Tj
2.0764 0 Td
(to)Tj
1.0417 0 Td
(breast)Tj
2.9552 0 Td
(cancer)Tj
3.1677 0 Td
(recurrence.)Tj
5.1874 0 Td
(J)Tj
0.7158 0 Td
(Clin)Tj
1.9063 0 Td
(Oncol)Tj
-41.2019 -1.1906 Td
(35)Tj
1.3111 0 Td
(suppl)Tj
2.5653 0 Td
(15211)Tj
3.267 0 Td
(521.)Tj
/F2 1 Tf
-9.7654 -1.6228 Td
(38.)Tj
/F0 1 Tf
2.622 0 Td
(Osborn)Tj
3.4512 0 Td
(VW,)Tj
2.0977 0 Td
(Chen)Tj
2.5654 0 Td
(SC,)Tj
1.8637 0 Td
(Weiner)Tj
3.3379 0 Td
(J,)Tj
0.9921 0 Td
(Schwartz)Tj
4.2662 0 Td
(D,)Tj
1.2118 0 Td
(Schrei)Tj
2.778 0 Td
(ber)Tj
1.6441 0 Td
(D.)Tj
1.2047 0 Td
(\(2016\))Tj
3.0544 0 Td
(Impact)Tj
3.1819 0 Td
(of)Tj
1.0417 0 Td
(aspirin)Tj
3.104 0 Td
(on)Tj
1.3039 0 Td
(clinical)Tj
3.1536 0 Td
(out-)Tj
-40.2523 -1.1835 Td
(comes)Tj
3.1252 0 Td
(for)Tj
1.3678 0 Td
(African)Tj
3.2811 0 Td
(American)Tj
4.3725 0 Td
(men)Tj
2.1331 0 Td
(with)Tj
1.9701 0 Td
(prostate)Tj
3.7701 0 Td
(cancer)Tj
3.1677 0 Td
(undergoing)Tj
5.1237 0 Td
(radiation.)Tj
4.252 0 Td
(Tumori)Tj
3.5079 0 Td
(102:)Tj
2.126 0 Td
(6570.)Tj
0.83 0.64 0.02 0 k
-38.1972 -1.1906 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.530)Tj
3.8197 0 Td
(1/tj.5000424)Tj
0 g
5.6269 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9622 0 Td
(26429642)Tj
0 g
/F2 1 Tf
-20.445 -1.6228 Td
(39.)Tj
/F0 1 Tf
2.622 0 Td
(Veitonma)Tj
4.1528 0 Td
(ki)Tj
0.9284 0 Td
(T,)Tj
1.1055 0 Td
(Murtola)Tj
3.4937 0 Td
(TJ,)Tj
1.6016 0 Td
(Maattanen)Tj
4.8685 0 Td
(L,)Tj
1.0347 0 Td
(Taari)Tj
2.4591 0 Td
(K,)Tj
1.1551 0 Td
(Stenman)Tj
4.167 0 Td
(UH,)Tj
1.9134 0 Td
(Tammela)Tj
4.3299 0 Td
(TL,)Tj
1.6512 0 Td
(et)Tj
1.0347 0 Td
(al.)Tj
1.2543 0 Td
(\(2015\))Tj
3.0614 0 Td
(Use)Tj
1.9701 0 Td
(of)Tj
1.0347 0 Td
(non-)Tj
-41.2161 -1.1906 Td
(steroidal)Tj
3.926 0 Td
(anti-inflam)Tj
4.5213 0 Td
(matory)Tj
3.2316 0 Td
(drugs)Tj
2.6787 0 Td
(and)Tj
1.8567 0 Td
(prostate)Tj
3.7701 0 Td
(cancer)Tj
3.1749 0 Td
(survival)Tj
3.5433 0 Td
(in)Tj
0.978 0 Td
(the)Tj
1.5874 0 Td
(Finnish)Tj
3.3803 0 Td
(prostate)Tj
3.7701 0 Td
(cancer)Tj
3.1748 0 Td
(screening)Tj
-39.5932 -1.1835 Td
(trial.)Tj
2.0693 0 Td
(Prostate)Tj
4.1103 0 Td
(75:)Tj
1.5803 0 Td
(13941402.)Tj
0.83 0.64 0.02 0 k
5.4072 0 Td
(https://doi.o)Tj
5.0811 0 Td
(rg/10.1002/pr)Tj
5.8465 0 Td
(os.23020)Tj
0 g
4.2591 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(26073992)Tj
0 g
/F2 1 Tf
-33.9451 -1.6299 Td
(40.)Tj
/F0 1 Tf
2.622 0 Td
(Zhou)Tj
2.4662 0 Td
(CK,)Tj
1.8638 0 Td
(Daugher)Tj
3.763 0 Td
(ty)Tj
0.9921 0 Td
(SE,)Tj
1.8142 0 Td
(Liao)Tj
2.0693 0 Td
(LM,)Tj
1.8638 0 Td
(Freedman)Tj
4.7127 0 Td
(ND,)Tj
1.9134 0 Td
(Abnet)Tj
2.7921 0 Td
(CC,)Tj
1.9205 0 Td
(Pfeiffer)Tj
3.3378 0 Td
(R,)Tj
1.2047 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2017\))Tj
3.0544 0 Td
(Do)Tj
1.474 0 Td
(aspirin)Tj
3.104 0 Td
(and)Tj
-40.6421 -1.1835 Td
(other)Tj
2.4591 0 Td
(NSAIDs)Tj
3.7276 0 Td
(confer)Tj
2.9551 0 Td
(a)Tj
0.7654 0 Td
(survival)Tj
3.5433 0 Td
(benefit)Tj
3.1678 0 Td
(in)Tj
0.9779 0 Td
(men)Tj
2.1331 0 Td
(diagnosed)Tj
4.7481 0 Td
(with)Tj
1.963 0 Td
(prostate)Tj
3.7701 0 Td
(cancer?)Tj
3.7205 0 Td
(A)Tj
0.8787 0 Td
(pooled)Tj
3.1607 0 Td
(analysis)Tj
3.763 0 Td
(of)Tj
-41.7334 -1.1905 Td
(NIH-AAR)Tj
4.0536 0 Td
(P)Tj
0.8858 0 Td
(and)Tj
1.8496 0 Td
(PLCO)Tj
2.9127 0 Td
(cohorts.)Tj
3.7205 0 Td
(Cancer)Tj
3.3874 0 Td
(Prev)Tj
2.2465 0 Td
(Research)Tj
4.6488 0 Td
(10:)Tj
1.5874 0 Td
(41042)Tj
3.267 0 Td
(0.)Tj
/F2 1 Tf
-31.1813 -1.6229 Td
(41.)Tj
/F0 1 Tf
2.622 0 Td
(Cardwell)Tj
4.0323 0 Td
(CR,)Tj
1.9205 0 Td
(Flahavan)Tj
4.2591 0 Td
(EM,)Tj
1.9772 0 Td
(Hughes)Tj
3.6071 0 Td
(CM,)Tj
2.0339 0 Td
(Coleman)Tj
4.1528 0 Td
(HG,)Tj
1.9771 0 Td
(O'Sullivan)Tj
4.6418 0 Td
(JM,)Tj
1.8142 0 Td
(Powe)Tj
2.6788 0 Td
(DG,)Tj
1.9771 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2014\))Tj
3.0544 0 Td
(Low-)Tj
-40.4224 -1.1905 Td
(dose)Tj
2.3528 0 Td
(aspirin)Tj
3.0969 0 Td
(and)Tj
1.8567 0 Td
(survival)Tj
3.5433 0 Td
(in)Tj
0.9851 0 Td
(men)Tj
2.133 0 Td
(with)Tj
1.9631 0 Td
(prostate)Tj
3.7771 0 Td
(cancer:)Tj
3.4442 0 Td
(a)Tj
0.7653 0 Td
(study)Tj
2.5725 0 Td
(using)Tj
2.5654 0 Td
(the)Tj
1.5803 0 Td
(UK)Tj
1.5945 0 Td
(Clinical)Tj
3.3662 0 Td
(Practice)Tj
3.7701 0 Td
(Research)Tj
-39.3665 -1.1835 Td
(Datalink.)Tj
4.0394 0 Td
(Cancer)Tj
3.3874 0 Td
(Causes)Tj
3.5505 0 Td
(Control)Tj
3.6071 0 Td
(25:)Tj
1.5874 0 Td
(3343.)Tj
0.83 0.64 0.02 0 k
3.2173 0 Td
(https://doi.or)Tj
5.4143 0 Td
(g/10.1007/)Tj
4.6417 0 Td
(s10552-013-)Tj
5.5135 0 Td
(0306-x)Tj
0 g
3.2244 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
-38.183 -1.1906 Td
(24310109)Tj
0 g
/F2 1 Tf
-2.622 -1.6228 Td
(42.)Tj
/F0 1 Tf
2.622 0 Td
(Downer)Tj
3.6071 0 Td
(MK,)Tj
1.9772 0 Td
(Allard)Tj
2.7284 0 Td
(CB,)Tj
1.8638 0 Td
(Preston)Tj
3.6142 0 Td
(MA,)Tj
1.9772 0 Td
(Gaziano)Tj
3.8835 0 Td
(JM,)Tj
1.8141 0 Td
(Stampfer)Tj
4.2166 0 Td
(MJ,)Tj
1.8142 0 Td
(Mucci)Tj
2.7921 0 Td
(LA,)Tj
1.7008 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2017\))Tj
3.0544 0 Td
(Regular)Tj
3.6567 0 Td
(aspirin)Tj
-40.9964 -1.1906 Td
(use)Tj
1.8071 0 Td
(and)Tj
1.8496 0 Td
(the)Tj
1.5875 0 Td
(risk)Tj
1.7504 0 Td
(of)Tj
1.0417 0 Td
(lethal)Tj
2.5583 0 Td
(prostate)Tj
3.7701 0 Td
(cancer)Tj
3.1677 0 Td
(in)Tj
0.978 0 Td
(the)Tj
1.5874 0 Td
(Physicians')Tj
5.1308 0 Td
(Health)Tj
3.0543 0 Td
(Study.)Tj
3.0119 0 Td
(Eur)Tj
1.7574 0 Td
(Urol)Tj
2.2323 0 Td
(72:)Tj
1.5875 0 Td
(821827)Tj
0.83 0.64 0.02 0 k
4.0394 0 Td
(https://)Tj
-40.9114 -1.1835 Td
(doi.org/10.10)Tj
5.726 0 Td
(16/j.eururo.2)Tj
5.5135 0 Td
(017.01.044)Tj
0 g
5.1378 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9622 0 Td
(28189429)Tj
0 g
/F2 1 Tf
-21.9615 -1.6299 Td
(43.)Tj
/F0 1 Tf
2.622 0 Td
(Bar)Tj
1.7433 0 Td
(D,)Tj
1.2048 0 Td
(Lavie)Tj
2.5583 0 Td
(O,)Tj
1.2614 0 Td
(Stein)Tj
2.452 0 Td
(N,)Tj
1.1976 0 Td
(Feferkorn)Tj
4.4292 0 Td
(I,)Tj
0.7654 0 Td
(Shai)Tj
2.1756 0 Td
(A.)Tj
1.148 0 Td
(\(2016\))Tj
3.0544 0 Td
(The)Tj
1.9134 0 Td
(effect)Tj
2.622 0 Td
(of)Tj
1.0347 0 Td
(metabolic)Tj
4.415 0 Td
(comorbid)Tj
4.0394 0 Td
(ities)Tj
1.9559 0 Td
(and)Tj
1.8496 0 Td
(commonly)Tj
-39.82 -1.1835 Td
(used)Tj
2.3528 0 Td
(drugs)Tj
2.6717 0 Td
(on)Tj
1.311 0 Td
(the)Tj
1.5874 0 Td
(prognosis)Tj
4.4717 0 Td
(of)Tj
1.0417 0 Td
(patients)Tj
3.6568 0 Td
(with)Tj
1.9701 0 Td
(ovarian)Tj
3.437 0 Td
(cancer.)Tj
3.4441 0 Td
(Eur)Tj
1.7504 0 Td
(J)Tj
0.7158 0 Td
(of)Tj
1.0346 0 Td
(Obs)Tj
2.0339 0 Td
(Gynec)Tj
3.0756 0 Td
(and)Tj
1.8567 0 Td
(Repr)Tj
2.3457 0 Td
(Biol)Tj
2.0693 0 Td
(207:)Tj
-40.8263 -1.1905 Td
(227231.)Tj
/F2 1 Tf
-2.622 -1.6229 Td
(44.)Tj
/F0 1 Tf
2.622 0 Td
(Matsuo)Tj
3.4512 0 Td
(K,)Tj
1.1552 0 Td
(Cahoon)Tj
3.6567 0 Td
(SS,)Tj
1.8142 0 Td
(Yoshihara)Tj
4.6417 0 Td
(K,)Tj
1.1552 0 Td
(Shida)Tj
2.7283 0 Td
(M,)Tj
1.3181 0 Td
(Kakuda)Tj
3.5576 0 Td
(M,)Tj
1.3181 0 Td
(Adachi)Tj
3.2244 0 Td
(S,)Tj
1.1551 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2016\))Tj
3.0544 0 Td
(Association)Tj
5.2441 0 Td
(of)Tj
1.0418 0 Td
(low-)Tj
-40.8122 -1.1905 Td
(dose)Tj
2.3528 0 Td
(aspirin)Tj
3.0969 0 Td
(and)Tj
1.8567 0 Td
(survival)Tj
3.5433 0 Td
(of)Tj
1.0418 0 Td
(women)Tj
3.3945 0 Td
(with)Tj
1.963 0 Td
(endometrial)Tj
5.3504 0 Td
(cancer.)Tj
3.4441 0 Td
(Obs)Tj
2.0339 0 Td
(Gyne)Tj
2.7992 0 Td
(128:)Tj
2.126 0 Td
(127137.)Tj
/F2 1 Tf
-35.6246 -1.6229 Td
(45.)Tj
/F0 1 Tf
2.622 0 Td
(Li)Tj
0.9709 0 Td
(JH,)Tj
1.6866 0 Td
(Wang)Tj
2.7851 0 Td
(Y,)Tj
1.148 0 Td
(Xie)Tj
1.63 0 Td
(XY,)Tj
1.8 0 Td
(Yin)Tj
1.6299 0 Td
(X,)Tj
1.148 0 Td
(Zhang)Tj
2.9977 0 Td
(L,)Tj
1.0276 0 Td
(Chen)Tj
2.5583 0 Td
(RX,)Tj
1.8567 0 Td
(et)Tj
1.0346 0 Td
(al.)Tj
1.2402 0 Td
(\(2016\))Tj
3.0473 0 Td
(Aspirin)Tj
3.2102 0 Td
(in)Tj
0.9638 0 Td
(combinatio)Tj
4.7481 0 Td
(n)Tj
0.7582 0 Td
(with)Tj
1.956 0 Td
(TACE)Tj
2.8488 0 Td
(in)Tj
0.9638 0 Td
(treat-)Tj
-42.0098 -1.1905 Td
(ment)Tj
2.4095 0 Td
(of)Tj
1.0417 0 Td
(unresecta)Tj
4.3158 0 Td
(ble)Tj
1.5236 0 Td
(HCC:)Tj
2.6292 0 Td
(a)Tj
0.7654 0 Td
(matched-p)Tj
4.6488 0 Td
(airs)Tj
1.8 0 Td
(analysis.)Tj
4.0394 0 Td
(American)Tj
4.3725 0 Td
(Journal)Tj
3.437 0 Td
(of)Tj
1.0418 0 Td
(Cancer)Tj
3.3874 0 Td
(Res)Tj
2.1898 0 Td
(6:)Tj
1.0417 0 Td
(21092116.)Tj
/F2 1 Tf
-41.2656 -1.6229 Td
(46.)Tj
/F0 1 Tf
2.622 0 Td
(Maddison)Tj
4.4788 0 Td
(P.)Tj
1.1551 0 Td
(\(2017\))Tj
3.0544 0 Td
(Effects)Tj
3.2386 0 Td
(of)Tj
1.0417 0 Td
(aspirin)Tj
3.104 0 Td
(on)Tj
1.311 0 Td
(small-cell)Tj
4.3016 0 Td
(lung)Tj
2.0693 0 Td
(cancer)Tj
3.1678 0 Td
(mortality)Tj
3.9331 0 Td
(and)Tj
1.8567 0 Td
(metastatic)Tj
4.7126 0 Td
(presenta)Tj
3.8197 0 Td
(tion.)Tj
-41.2444 -1.1835 Td
(Lung)Tj
2.4024 0 Td
(Cancer)Tj
3.6071 0 Td
(106:)Tj
2.1331 0 Td
(6769.)Tj
0.83 0.64 0.02 0 k
3.2173 0 Td
(https://doi.or)Tj
5.4143 0 Td
(g/10.1016/)Tj
4.6417 0 Td
(j.lungcan.2017.)Tj
6.6544 0 Td
(01.018)Tj
0 g
3.2245 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(28285696)Tj
0 g
/F2 1 Tf
-36.8861 -1.6299 Td
(47.)Tj
/F0 1 Tf
2.622 0 Td
(Kim)Tj
1.9205 0 Td
(S-A,)Tj
2.1402 0 Td
(Roh)Tj
2.0197 0 Td
(J-L,)Tj
1.8638 0 Td
(Kim)Tj
1.9205 0 Td
(S-B,)Tj
2.1401 0 Td
(Choi)Tj
2.2323 0 Td
(S-H,)Tj
2.1969 0 Td
(Nam)Tj
2.3032 0 Td
(SY,)Tj
1.8142 0 Td
(Kim)Tj
1.9134 0 Td
(SY.)Tj
1.8141 0 Td
(\(2018\))Tj
3.0615 0 Td
(Aspirin)Tj
3.2173 0 Td
(use)Tj
1.8001 0 Td
(and)Tj
1.8567 0 Td
(head)Tj
2.4023 0 Td
(and)Tj
1.8567 0 Td
(neck)Tj
2.2961 0 Td
(cancer)Tj
-40.7696 -1.1835 Td
(survival:)Tj
3.8197 0 Td
(an)Tj
1.3111 0 Td
(observatio)Tj
4.5283 0 Td
(nal)Tj
1.5237 0 Td
(study)Tj
2.5724 0 Td
(of)Tj
1.0418 0 Td
(11,623)Tj
3.2244 0 Td
(person-y)Tj
3.8197 0 Td
(ears)Tj
2.1331 0 Td
(follow-up)Tj
3.919 0 Td
(.)Tj
0.496 0 Td
(Int)Tj
1.3181 0 Td
(J)Tj
0.7158 0 Td
(Clin)Tj
1.8992 0 Td
(Oncol)Tj
3.0119 0 Td
(23:)Tj
1.5874 0 Td
(5258)Tj
0.83 0.64 0.02 0 k
2.948 0 Td
(https://)Tj
-39.8696 -1.1905 Td
(doi.org/10.10)Tj
5.726 0 Td
(07/s10147-017)Tj
6.5552 0 Td
(-1165-3)Tj
0 g
3.6 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9694 0 Td
(287259)Tj
3.2669 0 Td
(37)Tj
0 g
/F2 1 Tf
-24.7395 -1.6229 Td
(48.)Tj
/F0 1 Tf
2.622 0 Td
(Rosenberg)Tj
5.0245 0 Td
(L,)Tj
1.0417 0 Td
(Louik)Tj
2.5583 0 Td
(C,)Tj
1.2118 0 Td
(Shapiro)Tj
3.6 0 Td
(S.)Tj
1.1552 0 Td
(\(1998\))Tj
3.0543 0 Td
(Nonsteroid)Tj
4.7481 0 Td
(al)Tj
0.978 0 Td
(antiinflam)Tj
4.1953 0 Td
(matory)Tj
3.2315 0 Td
(drug)Tj
2.1898 0 Td
(use)Tj
1.8 0 Td
(and)Tj
1.8567 0 Td
(reduced)Tj
3.7701 0 Td
(risk)Tj
1.7433 0 Td
(of)Tj
-42.1586 -1.1905 Td
(large)Tj
2.3953 0 Td
(bowel)Tj
2.7851 0 Td
(carcinom)Tj
3.9827 0 Td
(a.)Tj
1.0417 0 Td
(Cancer)Tj
3.6071 0 Td
(82:)Tj
1.5875 0 Td
(23262333.)Tj
5.4071 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9622 0 Td
(9635524)Tj
0 g
/F2 1 Tf
-26.3907 -1.6229 Td
(49.)Tj
/F0 1 Tf
2.622 0 Td
(Sansbury)Tj
4.3725 0 Td
(LB,)Tj
1.7008 0 Td
(Millikan)Tj
3.4866 0 Td
(RC,)Tj
1.9134 0 Td
(Schroeder)Tj
4.7552 0 Td
(JC,)Tj
1.7008 0 Td
(Moorman)Tj
4.3796 0 Td
(PG,)Tj
1.9275 0 Td
(North)Tj
2.6292 0 Td
(KE,)Tj
1.8142 0 Td
(Sandler)Tj
3.6 0 Td
(RS.)Tj
1.8638 0 Td
(\(2005\))Tj
3.0614 0 Td
(Use)Tj
1.9701 0 Td
(of)Tj
1.0347 0 Td
(nonste-)Tj
-40.2098 -1.1905 Td
(roidal)Tj
2.6079 0 Td
(antiinflam)Tj
4.1953 0 Td
(matory)Tj
3.2386 0 Td
(drugs)Tj
2.6717 0 Td
(and)Tj
1.8567 0 Td
(risk)Tj
1.7504 0 Td
(of)Tj
1.0418 0 Td
(colon)Tj
2.5582 0 Td
(cancer)Tj
3.1749 0 Td
(in)Tj
0.9779 0 Td
(a)Tj
0.7654 0 Td
(popula)Tj
2.9339 0 Td
(tion-based,)Tj
5.0811 0 Td
(case-contro)Tj
5.1379 0 Td
(l)Tj
0.4322 0 Td
(study)Tj
2.5725 0 Td
(of)Tj
1.0417 0 Td
(Afri-)Tj
-42.0381 -1.1835 Td
(can)Tj
1.8071 0 Td
(American)Tj
4.1528 0 Td
(s)Tj
0.7158 0 Td
(and)Tj
1.8496 0 Td
(Whites.)Tj
3.5079 0 Td
(Amer)Tj
2.5795 0 Td
(J)Tj
0.7158 0 Td
(Epidem)Tj
3.3307 0 Td
(iol)Tj
1.4174 0 Td
(162:)Tj
2.126 0 Td
(548558.)Tj
/F2 1 Tf
-24.8246 -1.63 Td
(50.)Tj
/F0 1 Tf
2.622 0 Td
(Leitzmann)Tj
4.7481 0 Td
(MF,)Tj
1.9205 0 Td
(Stampfer)Tj
4.2165 0 Td
(MJ,)Tj
1.8071 0 Td
(Ma)Tj
1.5804 0 Td
(J,)Tj
0.985 0 Td
(Chan)Tj
2.5583 0 Td
(JM,)Tj
1.8071 0 Td
(Colditz)Tj
3.2103 0 Td
(GA,)Tj
1.9275 0 Td
(Willett)Tj
2.8843 0 Td
(WC,)Tj
2.1402 0 Td
(et)Tj
1.0346 0 Td
(al.)Tj
1.2473 0 Td
(\(2002\))Tj
3.0544 0 Td
(Aspirin)Tj
3.2102 0 Td
(use)Tj
1.7929 0 Td
(in)Tj
0.9709 0 Td
(relation)Tj
-41.0956 -1.1834 Td
(to)Tj
1.0418 0 Td
(risk)Tj
1.7433 0 Td
(of)Tj
1.0417 0 Td
(prostate)Tj
3.7772 0 Td
(cancer.)Tj
3.4441 0 Td
(Cancer)Tj
3.3875 0 Td
(Epidem)Tj
3.3307 0 Td
(iol)Tj
1.1976 0 Td
(Biomar)Tj
3.1111 0 Td
(kers)Tj
2.0835 0 Td
(Prev)Tj
2.4661 0 Td
(11:)Tj
1.5875 0 Td
(11081)Tj
3.2669 0 Td
(011.)Tj
2.1331 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(123765)Tj
3.267 0 Td
(16)Tj
0 g
/F2 1 Tf
-42.4704 -1.6229 Td
(51.)Tj
/F0 1 Tf
2.622 0 Td
(Fraser)Tj
3.0685 0 Td
(DM,)Tj
2.0339 0 Td
(Sulliva)Tj
2.8772 0 Td
(n)Tj
0.7654 0 Td
(FM,)Tj
1.9275 0 Td
(Thompson)Tj
4.8757 0 Td
(AM,)Tj
1.9842 0 Td
(McCowan)Tj
4.5993 0 Td
(C.)Tj
1.2047 0 Td
(\(2014\))Tj
3.0544 0 Td
(Aspirin)Tj
3.2173 0 Td
(use)Tj
1.8071 0 Td
(and)Tj
1.8496 0 Td
(survival)Tj
3.5505 0 Td
(after)Tj
2.1827 0 Td
(the)Tj
1.5874 0 Td
(diagno-)Tj
-40.5854 -1.1905 Td
(sis)Tj
1.4174 0 Td
(of)Tj
1.0417 0 Td
(breast)Tj
2.9551 0 Td
(cancer:)Tj
3.4442 0 Td
(a)Tj
0.7653 0 Td
(population-)Tj
4.8473 0 Td
(based)Tj
2.8914 0 Td
(cohort)Tj
2.9551 0 Td
(study.)Tj
2.8488 0 Td
(Brit)Tj
1.6938 0 Td
(J)Tj
0.7157 0 Td
(Cancer)Tj
3.6071 0 Td
(111:)Tj
2.1331 0 Td
(62362)Tj
3.267 0 Td
(7.)Tj
0.83 0.64 0.02 0 k
1.0417 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.)Tj
-41.0389 -1.1906 Td
(1038/bjc.2)Tj
4.5284 0 Td
(014.264)Tj
0 g
3.7701 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(249459)Tj
3.267 0 Td
(97)Tj
0 g
/F2 1 Tf
-17.1568 -1.6228 Td
(52.)Tj
/F0 1 Tf
2.622 0 Td
(Barron)Tj
3.1678 0 Td
(TI,)Tj
1.3819 0 Td
(Murphy)Tj
3.5008 0 Td
(LM,)Tj
1.8638 0 Td
(Brown)Tj
3.0118 0 Td
(C,)Tj
1.2047 0 Td
(Bennett)Tj
3.6142 0 Td
(K,)Tj
1.1552 0 Td
(Visvanath)Tj
4.3157 0 Td
(an)Tj
1.3111 0 Td
(K,)Tj
1.1551 0 Td
(Sharp)Tj
2.8418 0 Td
(L.)Tj
1.0417 0 Td
(\(2015\))Tj
3.0544 0 Td
(De)Tj
1.4811 0 Td
(novo)Tj
2.3457 0 Td
(post-diagnos)Tj
5.6197 0 Td
(is)Tj
-42.0665 -1.1835 Td
(aspirin)Tj
3.104 0 Td
(use)Tj
1.8 0 Td
(and)Tj
1.8567 0 Td
(mortality)Tj
3.9331 0 Td
(in)Tj
0.9851 0 Td
(wome)Tj
2.622 0 Td
(n)Tj
0.7654 0 Td
(with)Tj
1.9701 0 Td
(stage)Tj
2.622 0 Td
(I-III)Tj
1.6512 0 Td
(breast)Tj
2.9481 0 Td
(cancer.)Tj
3.4441 0 Td
(Cancer)Tj
3.3945 0 Td
(Epidem)Tj
3.3308 0 Td
(iol)Tj
1.1905 0 Td
(Biomarkers)Tj
5.1946 0 Td
(Prev)Tj
-40.8122 -1.1906 Td
(24:)Tj
1.5874 0 Td
(898904.)Tj
0.83 0.64 0.02 0 k
4.3087 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.1158/)Tj
4.6418 0 Td
(1055-9965.E)Tj
5.6268 0 Td
(PI-14-141)Tj
4.3158 0 Td
(5)Tj
0 g
0.7654 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(25791705)Tj
0 g
/F2 1 Tf
-32.2514 -1.6228 Td
(53.)Tj
/F0 1 Tf
2.622 0 Td
(Ljung)Tj
2.615 0 Td
(R,)Tj
1.2047 0 Td
(Sennerstam)Tj
5.5276 0 Td
(R,)Tj
1.2119 0 Td
(Mattsson)Tj
4.2165 0 Td
(F,)Tj
1.1055 0 Td
(Auer)Tj
2.2961 0 Td
(G,)Tj
1.2685 0 Td
(Lagergren)Tj
4.6914 0 Td
(J.)Tj
0.9921 0 Td
(\(2014\))Tj
3.0544 0 Td
(Anticoag)Tj
3.8197 0 Td
(ulant)Tj
2.3457 0 Td
(medication)Tj
4.9678 0 Td
(at)Tj
1.0417 0 Td
(time)Tj
2.0764 0 Td
(of)Tj
-42.435 -1.1906 Td
(needle)Tj
3.1607 0 Td
(biopsy)Tj
3.0543 0 Td
(for)Tj
1.3678 0 Td
(breast)Tj
2.9551 0 Td
(cancer)Tj
3.1677 0 Td
(in)Tj
0.978 0 Td
(relation)Tj
3.4299 0 Td
(to)Tj
1.0418 0 Td
(risk)Tj
1.7504 0 Td
(of)Tj
1.0346 0 Td
(lymph)Tj
2.8489 0 Td
(node)Tj
2.3953 0 Td
(metastasis)Tj
4.7055 0 Td
(.)Tj
0.4961 0 Td
(Int)Tj
1.3181 0 Td
(J)Tj
0.7158 0 Td
(Cancer)Tj
3.6071 0 Td
(135:)Tj
2.1331 0 Td
(23824)Tj
3.2669 0 Td
(1.)Tj
0.83 0.64 0.02 0 k
-43.4271 -1.1835 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.100)Tj
3.8197 0 Td
(2/ijc.2867)Tj
4.1954 0 Td
(1)Tj
0 g
0.7653 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(24346771)Tj
0 g
/F2 1 Tf
-19.7859 -1.6299 Td
(54.)Tj
/F0 1 Tf
2.622 0 Td
(Blair)Tj
2.1756 0 Td
(CK,)Tj
1.8709 0 Td
(Sweeney)Tj
4.2662 0 Td
(C,)Tj
1.2047 0 Td
(Anderson)Tj
4.4292 0 Td
(KE,)Tj
1.8142 0 Td
(Folsom)Tj
3.4512 0 Td
(AR.)Tj
1.8638 0 Td
(\(2007\))Tj
3.0543 0 Td
(NSAID)Tj
3.2386 0 Td
(use)Tj
1.8071 0 Td
(and)Tj
1.8567 0 Td
(survival)Tj
3.5434 0 Td
(after)Tj
2.1898 0 Td
(breast)Tj
2.948 0 Td
(cancer)Tj
-39.7137 -1.1835 Td
(diagnos)Tj
3.43 0 Td
(is)Tj
0.9283 0 Td
(in)Tj
0.978 0 Td
(post-meno)Tj
4.6488 0 Td
(pausal)Tj
3.1111 0 Td
(women.)Tj
3.6638 0 Td
(Breast)Tj
3.0685 0 Td
(Cancer)Tj
3.3874 0 Td
(Res)Tj
1.9701 0 Td
(Treat)Tj
2.7426 0 Td
(101:)Tj
2.1331 0 Td
(191197.)Tj
0.83 0.64 0.02 0 k
4.3087 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.)Tj
-39.7846 -1.1905 Td
(1007/s10)Tj
4.0394 0 Td
(549-006-9)Tj
4.4717 0 Td
(277-x)Tj
0 g
2.6788 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(168235)Tj
3.2669 0 Td
(08)Tj
0 g
/F2 1 Tf
-20.0481 -1.6229 Td
(55.)Tj
/F0 1 Tf
2.622 0 Td
(Assayag)Tj
3.9969 0 Td
(J,)Tj
0.985 0 Td
(Pollak)Tj
2.8914 0 Td
(MN,)Tj
2.0339 0 Td
(Azoulay)Tj
3.7134 0 Td
(L.)Tj
1.0417 0 Td
(\(2015\))Tj
3.0544 0 Td
(The)Tj
1.9205 0 Td
(use)Tj
1.8071 0 Td
(of)Tj
1.0346 0 Td
(aspirin)Tj
3.104 0 Td
(and)Tj
1.8567 0 Td
(the)Tj
1.5874 0 Td
(risk)Tj
1.7504 0 Td
(of)Tj
1.0347 0 Td
(mortality)Tj
3.9402 0 Td
(in)Tj
0.9779 0 Td
(patients)Tj
3.6568 0 Td
(with)Tj
-40.387 -1.1905 Td
(prostate)Tj
3.7701 0 Td
(cancer.)Tj
3.4512 0 Td
(J)Tj
0.7087 0 Td
(Urol)Tj
2.2394 0 Td
(193:)Tj
2.1331 0 Td
(12201)Tj
3.2669 0 Td
(225.)Tj
0.83 0.64 0.02 0 k
2.1331 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.101)Tj
3.8198 0 Td
(6/j.juro.2014)Tj
5.4 0 Td
(.11.018)Tj
0 g
3.5008 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9622 0 Td
(25463991)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
31.7412 0 Td
(15)Tj
1.304 0 Td
(/)Tj
ET
endstream
endobj
699 0 obj
<>stream
endstream
endobj
700 0 obj
<>stream
endstream
endobj
701 0 obj
<>stream
endstream
endobj
702 0 obj
<>stream
endstream
endobj
703 0 obj
<>stream
endstream
endobj
704 0 obj
<>stream
endstream
endobj
705 0 obj
<>stream
endstream
endobj
706 0 obj
<>stream
endstream
endobj
707 0 obj
<>stream
endstream
endobj
708 0 obj
<>stream
endstream
endobj
709 0 obj
<>stream
endstream
endobj
710 0 obj
<>stream
endstream
endobj
711 0 obj
<>stream
endstream
endobj
712 0 obj
<>stream
endstream
endobj
713 0 obj
<>stream
endstream
endobj
714 0 obj
<>stream
endstream
endobj
715 0 obj
<>stream
endstream
endobj
716 0 obj
<>stream
endstream
endobj
717 0 obj
<>stream
endstream
endobj
718 0 obj
<>stream
endstream
endobj
719 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
720 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 344 0 R/Annots 721 0 R/Contents 722 0 R/TrimBox[0 0 612 792]>>
endobj
721 0 obj
[723 0 R 724 0 R 725 0 R 726 0 R 727 0 R 728 0 R 729 0 R 730 0 R 731 0 R 732 0 R 733 0 R 734 0 R 735 0 R 736 0 R 737 0 R 738 0 R 739 0 R 740 0 R 741 0 R 742 0 R 743 0 R 744 0 R 745 0 R 746 0 R 747 0 R 748 0 R 749 0 R 750 0 R 751 0 R 752 0 R 753 0 R 754 0 R 755 0 R 756 0 R 757 0 R 758 0 R 759 0 R 760 0 R 761 0 R 762 0 R 763 0 R 764 0 R 765 0 R 766 0 R 767 0 R 768 0 R 769 0 R 770 0 R 771 0 R 772 0 R]
endobj
723 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref056)>>
endobj
724 0 obj
<>/Border[0 0 0]/A 773 0 R>>
endobj
773 0 obj
<>
endobj
725 0 obj
<>/Border[0 0 0]/A 774 0 R>>
endobj
774 0 obj
<>
endobj
726 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref057)>>
endobj
727 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref058)>>
endobj
728 0 obj
<>/Border[0 0 0]/A 775 0 R>>
endobj
775 0 obj
<>
endobj
729 0 obj
<>/Border[0 0 0]/A 776 0 R>>
endobj
776 0 obj
<>
endobj
730 0 obj
<>/Border[0 0 0]/A 777 0 R>>
endobj
777 0 obj
<>
endobj
731 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref059)>>
endobj
732 0 obj
<>/Border[0 0 0]/A 778 0 R>>
endobj
778 0 obj
<>
endobj
733 0 obj
<>/Border[0 0 0]/A 779 0 R>>
endobj
779 0 obj
<>
endobj
734 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref060)>>
endobj
735 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref061)>>
endobj
736 0 obj
<>/Border[0 0 0]/A 780 0 R>>
endobj
780 0 obj
<>
endobj
737 0 obj
<>/Border[0 0 0]/A 781 0 R>>
endobj
781 0 obj
<>
endobj
738 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref062)>>
endobj
739 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref063)>>
endobj
740 0 obj
<>/Border[0 0 0]/A 782 0 R>>
endobj
782 0 obj
<>
endobj
741 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref064)>>
endobj
742 0 obj
<>/Border[0 0 0]/A 783 0 R>>
endobj
783 0 obj
<>
endobj
743 0 obj
<>/Border[0 0 0]/A 784 0 R>>
endobj
784 0 obj
<>
endobj
744 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref065)>>
endobj
745 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref066)>>
endobj
746 0 obj
<>/Border[0 0 0]/A 785 0 R>>
endobj
785 0 obj
<>
endobj
747 0 obj
<>/Border[0 0 0]/A 786 0 R>>
endobj
786 0 obj
<>
endobj
748 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref067)>>
endobj
749 0 obj
<>/Border[0 0 0]/A 787 0 R>>
endobj
787 0 obj
<>
endobj
750 0 obj
<>/Border[0 0 0]/A 788 0 R>>
endobj
788 0 obj
<>
endobj
751 0 obj
<>/Border[0 0 0]/A 789 0 R>>
endobj
789 0 obj
<>
endobj
752 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref068)>>
endobj
753 0 obj
<>/Border[0 0 0]/A 790 0 R>>
endobj
790 0 obj
<>
endobj
754 0 obj
<>/Border[0 0 0]/A 791 0 R>>
endobj
791 0 obj
<>
endobj
755 0 obj
<>/Border[0 0 0]/A 792 0 R>>
endobj
792 0 obj
<>
endobj
756 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref069)>>
endobj
757 0 obj
<>/Border[0 0 0]/A 793 0 R>>
endobj
793 0 obj
<>
endobj
758 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref070)>>
endobj
759 0 obj
<>/Border[0 0 0]/A 794 0 R>>
endobj
794 0 obj
<>
endobj
760 0 obj
<>/Border[0 0 0]/A 795 0 R>>
endobj
795 0 obj
<>
endobj
761 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref071)>>
endobj
762 0 obj
<>/Border[0 0 0]/A 796 0 R>>
endobj
796 0 obj
<>
endobj
763 0 obj
<>/Border[0 0 0]/A 797 0 R>>
endobj
797 0 obj
<>
endobj
764 0 obj
<>/Border[0 0 0]/A 798 0 R>>
endobj
798 0 obj
<>
endobj
765 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref072)>>
endobj
766 0 obj
<>/Border[0 0 0]/A 799 0 R>>
endobj
799 0 obj
<>
endobj
767 0 obj
<>/Border[0 0 0]/A 800 0 R>>
endobj
800 0 obj
<>
endobj
768 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref073)>>
endobj
769 0 obj
<>/Border[0 0 0]/A 801 0 R>>
endobj
801 0 obj
<>
endobj
770 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref074)>>
endobj
771 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref075)>>
endobj
772 0 obj
<>/Border[0 0 0]/A 802 0 R>>
endobj
802 0 obj
<>
endobj
722 0 obj
[803 0 R 804 0 R 805 0 R 806 0 R 807 0 R 808 0 R 809 0 R 810 0 R 811 0 R 812 0 R 813 0 R 814 0 R 815 0 R 816 0 R 817 0 R 818 0 R 819 0 R 820 0 R 821 0 R 822 0 R 823 0 R]
endobj
803 0 obj
<>stream
q
0.83 0.64 0.02 0 k
221.4992 688.6488 m
373.1528 688.6488 l
h
f*
398.6079 688.6488 m
433.5874 688.6488 l
h
f*
548.3906 634.1669 m
572.1449 634.1669 l
h
f*
221.4992 624.6425 m
346.3937 624.6425 l
h
f*
371.8488 624.6425 m
406.8283 624.6425 l
h
f*
305.348 592.6677 m
465.222 592.6677 l
h
f*
490.6772 592.6677 m
525.6 592.6677 l
h
f*
295.3134 528.6614 m
446.9669 528.6614 l
h
f*
472.422 528.6614 m
507.4016 528.6614 l
h
f*
312.6047 483.6472 m
343.1622 483.6472 l
h
f*
297.5811 461.1402 m
406.4315 461.1402 l
h
f*
431.8866 461.1402 m
466.8094 461.1402 l
h
f*
401.8961 397.1339 m
567.9496 397.1339 l
h
f*
245.2535 387.6661 m
280.1764 387.6661 l
h
f*
467.6598 355.6346 m
548.1071 355.6346 l
h
f*
221.4992 346.1669 m
278.1921 346.1669 l
h
f*
303.7039 346.1669 m
338.6268 346.1669 l
h
f*
468.8504 323.6598 m
549.3543 323.6598 l
h
f*
221.4992 314.1354 m
289.7008 314.1354 l
h
f*
315.1559 314.1354 m
350.0787 314.1354 l
h
f*
366.1795 282.1606 m
532.2331 282.1606 l
h
f*
420.6047 250.1291 m
565.6819 250.1291 l
h
f*
245.2535 240.6614 m
280.1764 240.6614 l
h
f*
419.0173 218.1543 m
556.2709 218.1543 l
h
f*
221.4992 208.6299 m
250.3559 208.6299 l
h
f*
275.811 208.6299 m
310.7339 208.6299 l
h
f*
236.3528 186.1228 m
384.9449 186.1228 l
h
f*
410.4 186.1228 m
445.3228 186.1228 l
h
f*
237.2598 144.6236 m
381.8835 144.6236 l
h
f*
0 g
1 j
1 J
0 w
7.9999 0 0 7.9999 200.5228 708.7181 cm
BT
/F2 1 Tf
1 TL
-0.005 Tc
0 0 Td
(56.)Tj
/F0 1 Tf
2.622 0 Td
(Nagle)Tj
2.778 0 Td
(CM,)Tj
2.0339 0 Td
(Ibiebele)Tj
3.6496 0 Td
(TI,)Tj
1.3748 0 Td
(DeFazio)Tj
3.8835 0 Td
(A,)Tj
1.1551 0 Td
(Protani)Tj
3.3308 0 Td
(MM,)Tj
2.1472 0 Td
(Webb)Tj
2.7993 0 Td
(PM.)Tj
1.9771 0 Td
(\(2015\))Tj
3.0544 0 Td
(Aspirin,)Tj
3.4937 0 Td
(nonaspirin)Tj
4.741 0 Td
(nonstero)Tj
3.8197 0 Td
(idal)Tj
1.7434 0 Td
(anti-)Tj
-41.9815 -1.1905 Td
(inflammator)Tj
5.1379 0 Td
(y)Tj
0.7157 0 Td
(drugs,)Tj
2.9481 0 Td
(acetaminop)Tj
5.0811 0 Td
(hen)Tj
1.8567 0 Td
(and)Tj
1.8567 0 Td
(ovarian)Tj
3.43 0 Td
(cancer)Tj
3.1748 0 Td
(survival.)Tj
3.8197 0 Td
(Cancer)Tj
3.3874 0 Td
(Epidem)Tj
3.3308 0 Td
(iol)Tj
1.4173 0 Td
(39:)Tj
1.5803 0 Td
(196199.)Tj
0.83 0.64 0.02 0 k
-37.7365 -1.1835 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.101)Tj
3.8197 0 Td
(6/j.canep.2)Tj
4.8048 0 Td
(014.12.010)Tj
0 g
5.1378 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9623 0 Td
(25666512)Tj
0 g
/F2 1 Tf
-24.7608 -1.6228 Td
(57.)Tj
/F0 1 Tf
2.622 0 Td
(Fontaine)Tj
4.0394 0 Td
(E,)Tj
1.1551 0 Td
(McShane)Tj
4.3867 0 Td
(J,)Tj
0.985 0 Td
(Page)Tj
2.5158 0 Td
(R,)Tj
1.2047 0 Td
(Shackcloth)Tj
5.0316 0 Td
(M,)Tj
1.3181 0 Td
(Mediratta)Tj
4.3229 0 Td
(N,)Tj
1.2047 0 Td
(Carr)Tj
2.1331 0 Td
(M,)Tj
1.3181 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2010\))Tj
3.0543 0 Td
(Aspirin)Tj
3.2174 0 Td
(and)Tj
1.8567 0 Td
(non-smal)Tj
4.0394 0 Td
(l)Tj
-44.0791 -1.1906 Td
(cell)Tj
1.6866 0 Td
(lung)Tj
2.0694 0 Td
(cancer)Tj
3.1677 0 Td
(resections:)Tj
4.9748 0 Td
(effect)Tj
2.6292 0 Td
(on)Tj
1.311 0 Td
(long-term)Tj
4.3725 0 Td
(survival.)Tj
3.8197 0 Td
(Eur)Tj
1.7504 0 Td
(J)Tj
0.7087 0 Td
(Cardio-Thora)Tj
5.7898 0 Td
(cic)Tj
1.4173 0 Td
(Surg)Tj
2.5229 0 Td
(38:)Tj
1.5803 0 Td
(2126.)Tj
/F2 1 Tf
-40.4223 -1.6228 Td
(58.)Tj
/F0 1 Tf
2.622 0 Td
(Pastore)Tj
3.6142 0 Td
(AL,)Tj
1.7008 0 Td
(Palleschi)Tj
4.1386 0 Td
(G,)Tj
1.2685 0 Td
(Fuschi)Tj
3.1182 0 Td
(A,)Tj
1.1551 0 Td
(Silvestri)Tj
3.6567 0 Td
(L,)Tj
1.0347 0 Td
(Al)Tj
1.0984 0 Td
(Salhi)Tj
2.3953 0 Td
(Y,)Tj
1.1551 0 Td
(Costant)Tj
3.3875 0 Td
(ini)Tj
1.1976 0 Td
(E,)Tj
1.1481 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2543 0 Td
(\(2015\))Tj
3.0544 0 Td
(Can)Tj
2.0268 0 Td
(daily)Tj
2.2323 0 Td
(intake)Tj
2.8347 0 Td
(of)Tj
-42.513 -1.1906 Td
(aspirin)Tj
3.104 0 Td
(and/or)Tj
3.0047 0 Td
(statins)Tj
3.0615 0 Td
(influence)Tj
4.1386 0 Td
(the)Tj
1.5874 0 Td
(behavio)Tj
3.4299 0 Td
(r)Tj
0.5528 0 Td
(of)Tj
1.0417 0 Td
(non-mu)Tj
3.3308 0 Td
(scle)Tj
1.963 0 Td
(invasive)Tj
3.763 0 Td
(bladder)Tj
3.4867 0 Td
(cancer?)Tj
3.7205 0 Td
(A)Tj
0.8787 0 Td
(retrosp)Tj
3.0544 0 Td
(ective)Tj
-40.1177 -1.1835 Td
(study)Tj
2.5725 0 Td
(on)Tj
1.311 0 Td
(a)Tj
0.7654 0 Td
(cohort)Tj
2.9551 0 Td
(of)Tj
1.0347 0 Td
(patients)Tj
3.6638 0 Td
(undergoing)Tj
5.1236 0 Td
(transur)Tj
3.0544 0 Td
(ethral)Tj
2.6717 0 Td
(bladder)Tj
3.4866 0 Td
(resection.)Tj
4.4859 0 Td
(BMC)Tj
2.4165 0 Td
(Cance)Tj
2.8347 0 Td
(r)Tj
0.7724 0 Td
(15:)Tj
1.5875 0 Td
(120.)Tj
0.83 0.64 0.02 0 k
2.126 0 Td
(https://)Tj
-40.8618 -1.1905 Td
(doi.org/10.11)Tj
5.726 0 Td
(86/s12885-015)Tj
6.5552 0 Td
(-1152-x)Tj
0 g
3.5504 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9623 0 Td
(25877676)Tj
0 g
/F2 1 Tf
-21.4159 -1.6229 Td
(59.)Tj
/F0 1 Tf
2.622 0 Td
(Chae)Tj
2.5654 0 Td
(YK,)Tj
1.8142 0 Td
(Trinh)Tj
2.4591 0 Td
(L,)Tj
1.0417 0 Td
(Jain)Tj
2.0197 0 Td
(P,)Tj
1.1551 0 Td
(Wang)Tj
2.7922 0 Td
(X,)Tj
1.1551 0 Td
(Rozovski)Tj
4.2095 0 Td
(U,)Tj
1.2047 0 Td
(Wierda)Tj
3.3378 0 Td
(WG,)Tj
2.2111 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2544 0 Td
(\(2014\))Tj
3.0543 0 Td
(Statin)Tj
2.7355 0 Td
(and)Tj
1.8567 0 Td
(aspirin)Tj
3.1039 0 Td
(use)Tj
1.8001 0 Td
(is)Tj
0.9283 0 Td
(asso-)Tj
-41.7405 -1.1905 Td
(ciated)Tj
2.8347 0 Td
(with)Tj
1.9701 0 Td
(improved)Tj
4.2591 0 Td
(outcome)Tj
3.9969 0 Td
(of)Tj
1.0417 0 Td
(FCR)Tj
2.2465 0 Td
(therapy)Tj
3.5008 0 Td
(in)Tj
0.9779 0 Td
(relapsed/)Tj
4.0324 0 Td
(refractory)Tj
4.3795 0 Td
(chronic)Tj
3.3804 0 Td
(lymphocyt)Tj
4.4291 0 Td
(ic)Tj
0.9284 0 Td
(leukemia.)Tj
-37.9775 -1.1835 Td
(Blood)Tj
2.9481 0 Td
(123:)Tj
2.1331 0 Td
(1424142)Tj
4.3583 0 Td
(6.)Tj
0.83 0.64 0.02 0 k
1.0417 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.1182/)Tj
4.6418 0 Td
(blood-2013)Tj
4.904 0 Td
(-07-51710)Tj
4.4717 0 Td
(2)Tj
0 g
0.7653 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(24578497)Tj
0 g
/F2 1 Tf
-36.2695 -1.63 Td
(60.)Tj
/F0 1 Tf
2.622 0 Td
(Chae)Tj
2.5654 0 Td
(Y,)Tj
1.1551 0 Td
(Hong)Tj
2.5725 0 Td
(DS,)Tj
1.8638 0 Td
(Kim)Tj
1.9205 0 Td
(KH,)Tj
1.8638 0 Td
(Falchook)Tj
4.2094 0 Td
(GS,)Tj
1.9276 0 Td
(Piha-Pau)Tj
4.0394 0 Td
(l)Tj
0.4323 0 Td
(SA,)Tj
1.8142 0 Td
(Subbiah)Tj
3.8197 0 Td
(V,)Tj
1.1551 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2013\))Tj
3.0544 0 Td
(PIK3CA)Tj
3.7346 0 Td
(mutations,)Tj
-38.4239 -1.1834 Td
(aspirin)Tj
3.104 0 Td
(use)Tj
1.8 0 Td
(and)Tj
1.8567 0 Td
(mortality)Tj
3.9331 0 Td
(in)Tj
0.9851 0 Td
(patients)Tj
3.6567 0 Td
(with)Tj
1.963 0 Td
(women's)Tj
4.1032 0 Td
(cancers)Tj
3.6638 0 Td
(or)Tj
1.0913 0 Td
(colorectal)Tj
4.415 0 Td
(cancers)Tj
3.6638 0 Td
(treated)Tj
3.2811 0 Td
(in)Tj
0.978 0 Td
(early-phas)Tj
4.578 0 Td
(e)Tj
-43.0728 -1.1906 Td
(clinical)Tj
3.1465 0 Td
(trials.)Tj
2.5654 0 Td
(POSTER)Tj
4.2945 0 Td
(Epidem)Tj
3.3307 0 Td
(iology,)Tj
3.0544 0 Td
(Primary)Tj
3.6071 0 Td
(and)Tj
1.8567 0 Td
(Secondary)Tj
4.9252 0 Td
(Preven)Tj
3.1111 0 Td
(tion.)Tj
2.0764 0 Td
(Abstract)Tj
3.8339 0 Td
(No.)Tj
1.7575 0 Td
(1454)Tj
/F2 1 Tf
-40.1814 -1.6228 Td
(61.)Tj
/F0 1 Tf
2.622 0 Td
(Macfarlan)Tj
4.3158 0 Td
(e)Tj
0.7654 0 Td
(TV,)Tj
1.7645 0 Td
(Murchie)Tj
3.7135 0 Td
(P,)Tj
1.1551 0 Td
(Watson)Tj
3.5646 0 Td
(MC.)Tj
2.0339 0 Td
(\(2015\))Tj
3.0543 0 Td
(Aspirin)Tj
3.2174 0 Td
(and)Tj
1.8567 0 Td
(other)Tj
2.459 0 Td
(non-steroida)Tj
5.4568 0 Td
(l)Tj
0.4323 0 Td
(anti-inflam)Tj
4.5213 0 Td
(matory)Tj
3.2315 0 Td
(drug)Tj
-41.5421 -1.1906 Td
(prescript)Tj
3.763 0 Td
(ions)Tj
2.0197 0 Td
(and)Tj
1.8567 0 Td
(survival)Tj
3.5434 0 Td
(after)Tj
2.1898 0 Td
(the)Tj
1.5874 0 Td
(diagnos)Tj
3.4299 0 Td
(is)Tj
0.9284 0 Td
(of)Tj
1.0417 0 Td
(head)Tj
2.4024 0 Td
(and)Tj
1.8567 0 Td
(neck)Tj
2.2961 0 Td
(and)Tj
1.8567 0 Td
(oesopha)Tj
3.763 0 Td
(geal)Tj
2.0693 0 Td
(cancer.)Tj
3.4441 0 Td
(Cancer)Tj
3.3875 0 Td
(Epide-)Tj
-41.4358 -1.1835 Td
(miol)Tj
2.2394 0 Td
(39:)Tj
1.5803 0 Td
(10151022.)Tj
0.83 0.64 0.02 0 k
5.4072 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.101)Tj
3.8197 0 Td
(6/j.canep.2)Tj
4.8048 0 Td
(015.10.030)Tj
0 g
5.1378 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9622 0 Td
(26590503)Tj
0 g
/F2 1 Tf
-33.9876 -1.6299 Td
(62.)Tj
/F0 1 Tf
2.622 0 Td
(Gasic)Tj
2.7426 0 Td
(GJ,)Tj
1.7575 0 Td
(Gasic)Tj
2.7425 0 Td
(TB,)Tj
1.7575 0 Td
(Galanti)Tj
3.3378 0 Td
(N,)Tj
1.2047 0 Td
(Johnson)Tj
3.9331 0 Td
(T,)Tj
1.1056 0 Td
(Murphy)Tj
3.5008 0 Td
(S.)Tj
1.1551 0 Td
(\(1973\))Tj
3.0544 0 Td
(Platelet-tum)Tj
5.2441 0 Td
(or-cell)Tj
2.8843 0 Td
(interactions)Tj
5.237 0 Td
(in)Tj
0.9851 0 Td
(mice.)Tj
-40.6421 -1.1835 Td
(The)Tj
1.9205 0 Td
(role)Tj
1.8496 0 Td
(of)Tj
1.0418 0 Td
(platelet)Tj
3.1535 0 Td
(s)Tj
0.7158 0 Td
(in)Tj
0.9779 0 Td
(the)Tj
1.5875 0 Td
(spread)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(malignant)Tj
4.4787 0 Td
(disease.)Tj
3.8764 0 Td
(Internat)Tj
3.5505 0 Td
(J)Tj
0.7157 0 Td
(Cancer)Tj
3.6071 0 Td
(11:)Tj
1.5874 0 Td
(704718.)Tj
/F2 1 Tf
-35.9435 -1.6299 Td
(63.)Tj
/F0 1 Tf
2.622 0 Td
(Gasic)Tj
2.7426 0 Td
(GJ.)Tj
1.7575 0 Td
(\(1984\))Tj
3.0543 0 Td
(Role)Tj
2.2394 0 Td
(of)Tj
1.0417 0 Td
(plasma,)Tj
3.6638 0 Td
(platelet)Tj
3.1536 0 Td
(s,)Tj
0.9921 0 Td
(and)Tj
1.8568 0 Td
(endothe)Tj
3.5433 0 Td
(lial)Tj
1.4102 0 Td
(cells)Tj
2.1756 0 Td
(in)Tj
0.978 0 Td
(tumor)Tj
2.7425 0 Td
(metas)Tj
2.6788 0 Td
(tasis.)Tj
2.5158 0 Td
(Cancer)Tj
3.3945 0 Td
(Metas)Tj
2.6788 0 Td
(ta-)Tj
-42.6193 -1.1835 Td
(sis)Tj
1.4174 0 Td
(Rev)Tj
2.1897 0 Td
(3:)Tj
1.0418 0 Td
(99114.)Tj
3.7701 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(638614)Tj
3.267 0 Td
(4)Tj
0 g
/F2 1 Tf
-17.2773 -1.6228 Td
(64.)Tj
/F0 1 Tf
2.622 0 Td
(Gay)Tj
2.0339 0 Td
(LJ,)Tj
1.5307 0 Td
(Felding-Hab)Tj
5.3434 0 Td
(ermann)Tj
3.5575 0 Td
(B.)Tj
1.1551 0 Td
(\(2011\))Tj
3.0544 0 Td
(Contributi)Tj
4.1953 0 Td
(on)Tj
1.311 0 Td
(of)Tj
1.0417 0 Td
(platelets)Tj
3.8764 0 Td
(to)Tj
1.0347 0 Td
(tumour)Tj
3.2882 0 Td
(metastas)Tj
3.9969 0 Td
(is.)Tj
1.2047 0 Td
(Nature)Tj
3.1678 0 Td
(Reviews)Tj
-39.7917 -1.1906 Td
(Cancer)Tj
3.6071 0 Td
(11:)Tj
1.5874 0 Td
(123134.)Tj
0.83 0.64 0.02 0 k
4.3158 0 Td
(https://)Tj
2.9552 0 Td
(doi.org/10.10)Tj
5.7331 0 Td
(38/nrc30)Tj
3.8197 0 Td
(04)Tj
0 g
1.311 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9694 0 Td
(21258396)Tj
0 g
/F2 1 Tf
-28.9207 -1.6228 Td
(65.)Tj
/F0 1 Tf
2.622 0 Td
(Frouws)Tj
3.4512 0 Td
(MA,)Tj
1.9772 0 Td
(van)Tj
1.8071 0 Td
(Herk-Suke)Tj
4.6489 0 Td
(l)Tj
0.4323 0 Td
(MPP,)Tj
2.6433 0 Td
(Maas)Tj
2.6291 0 Td
(HA,)Tj
1.8638 0 Td
(Van)Tj
1.9701 0 Td
(de)Tj
1.3111 0 Td
(Velde)Tj
2.7283 0 Td
(CJH,)Tj
2.4095 0 Td
(Portielje)Tj
3.763 0 Td
(JEA,)Tj
2.3032 0 Td
(Liefers)Tj
3.1677 0 Td
(GJ,)Tj
1.7646 0 Td
(et)Tj
1.0347 0 Td
(al.)Tj
1.2543 0 Td
(\(2016\))Tj
-41.1594 -1.1906 Td
(The)Tj
1.9205 0 Td
(mortality)Tj
3.9331 0 Td
(reducing)Tj
3.9827 0 Td
(effect)Tj
2.6292 0 Td
(of)Tj
1.0417 0 Td
(aspirin)Tj
3.0969 0 Td
(in)Tj
0.9779 0 Td
(colorectal)Tj
4.4221 0 Td
(cancer)Tj
3.1678 0 Td
(patients:)Tj
3.9331 0 Td
(Interpreting)Tj
5.1874 0 Td
(the)Tj
1.5874 0 Td
(evidence.)Tj
4.4221 0 Td
(Cancer)Tj
-40.3019 -1.1835 Td
(Treat)Tj
2.5229 0 Td
(Rev)Tj
2.1898 0 Td
(55:)Tj
1.5874 0 Td
(12012)Tj
3.2669 0 Td
(7.)Tj
/F2 1 Tf
-12.189 -1.6299 Td
(66.)Tj
/F0 1 Tf
2.622 0 Td
(Rothwell)Tj
3.9827 0 Td
(PM,)Tj
1.9772 0 Td
(Algra)Tj
2.5087 0 Td
(A,)Tj
1.1551 0 Td
(Chen)Tj
2.5725 0 Td
(Z,)Tj
1.0984 0 Td
(Diener)Tj
3.1111 0 Td
(H-C,)Tj
2.2464 0 Td
(Norrving)Tj
3.926 0 Td
(B,)Tj
1.1552 0 Td
(Mehta)Tj
2.9551 0 Td
(Z.)Tj
1.1055 0 Td
(\(2016\))Tj
3.0544 0 Td
(Effects)Tj
3.2386 0 Td
(of)Tj
1.0417 0 Td
(aspirin)Tj
3.104 0 Td
(on)Tj
1.311 0 Td
(risk)Tj
1.7434 0 Td
(and)Tj
-41.287 -1.1835 Td
(severity)Tj
3.6071 0 Td
(of)Tj
1.0418 0 Td
(early)Tj
2.3457 0 Td
(recurrent)Tj
4.1527 0 Td
(stroke)Tj
2.8985 0 Td
(after)Tj
2.1898 0 Td
(transien)Tj
3.4866 0 Td
(t)Tj
0.4961 0 Td
(aschaemic)Tj
4.9181 0 Td
(attack)Tj
2.8489 0 Td
(and)Tj
1.8567 0 Td
(aschaemic)Tj
4.9252 0 Td
(stroke:)Tj
3.1748 0 Td
(time-cour)Tj
4.0961 0 Td
(se)Tj
-42.0381 -1.1905 Td
(analysis)Tj
3.763 0 Td
(of)Tj
1.0418 0 Td
(random)Tj
3.3307 0 Td
(ised)Tj
2.0197 0 Td
(trials.)Tj
2.5654 0 Td
(Lancet)Tj
3.3874 0 Td
(388:)Tj
2.1331 0 Td
(36537)Tj
3.267 0 Td
(5.)Tj
0.83 0.64 0.02 0 k
1.0417 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.1016/)Tj
4.6418 0 Td
(S0140-673)Tj
4.8047 0 Td
(6\(16\)3046)Tj
4.4717 0 Td
(8-8)Tj
0 g
-41.8822 -1.1835 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(272091)Tj
3.267 0 Td
(46)Tj
0 g
/F2 1 Tf
-8.8583 -1.6299 Td
(67.)Tj
/F0 1 Tf
2.622 0 Td
(Biondi-Zocc)Tj
5.1875 0 Td
(ai)Tj
0.9779 0 Td
(GG,)Tj
2.0481 0 Td
(Lotrion)Tj
2.9905 0 Td
(te)Tj
1.0418 0 Td
(M,)Tj
1.3252 0 Td
(Agostoni)Tj
4.0394 0 Td
(P,)Tj
1.1551 0 Td
(Abbate)Tj
3.3378 0 Td
(A,)Tj
1.1552 0 Td
(Fusaro)Tj
3.2811 0 Td
(M,)Tj
1.3252 0 Td
(Burzotta)Tj
3.8835 0 Td
(F,)Tj
1.1055 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2006\))Tj
3.0544 0 Td
(A)Tj
0.8787 0 Td
(systematic)Tj
-39.083 -1.1835 Td
(review)Tj
3.0544 0 Td
(and)Tj
1.8567 0 Td
(meta-ana)Tj
4.1528 0 Td
(lysis)Tj
2.1331 0 Td
(on)Tj
1.3039 0 Td
(the)Tj
1.5874 0 Td
(hazards)Tj
3.7205 0 Td
(of)Tj
1.0347 0 Td
(discontinu)Tj
4.415 0 Td
(ing)Tj
1.5236 0 Td
(or)Tj
1.0984 0 Td
(not)Tj
1.5804 0 Td
(adhering)Tj
4.0323 0 Td
(to)Tj
1.0417 0 Td
(aspirin)Tj
3.104 0 Td
(among)Tj
3.2315 0 Td
(50,279)Tj
-38.8704 -1.1906 Td
(patients)Tj
3.6567 0 Td
(at)Tj
1.0418 0 Td
(risk)Tj
1.7504 0 Td
(for)Tj
1.3677 0 Td
(coronary)Tj
4.0394 0 Td
(artery)Tj
2.7355 0 Td
(disease.)Tj
3.8764 0 Td
(Eur)Tj
1.7504 0 Td
(Heart)Tj
2.6291 0 Td
(J)Tj
0.9284 0 Td
(27:)Tj
1.5874 0 Td
(26672674.)Tj
0.83 0.64 0.02 0 k
5.4071 0 Td
(https://d)Tj
3.5009 0 Td
(oi.org/10.109)Tj
5.7331 0 Td
(3/)Tj
-40.0043 -1.1835 Td
(eurheartj/eh)Tj
5.2371 0 Td
(l334)Tj
0 g
2.0693 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(170530)Tj
3.2669 0 Td
(08)Tj
0 g
/F2 1 Tf
-16.1646 -1.6299 Td
(68.)Tj
/F0 1 Tf
2.622 0 Td
(Maulaz)Tj
3.3874 0 Td
(AB,)Tj
1.8142 0 Td
(Bezerra)Tj
3.6638 0 Td
(DC,)Tj
1.9205 0 Td
(Michel)Tj
3.0544 0 Td
(P,)Tj
1.1551 0 Td
(Bogoussl)Tj
4.0394 0 Td
(avsky)Tj
2.7426 0 Td
(J.)Tj
0.985 0 Td
(\(2005\))Tj
3.0614 0 Td
(Effect)Tj
2.7426 0 Td
(of)Tj
1.0417 0 Td
(discontinu)Tj
4.415 0 Td
(ing)Tj
1.5237 0 Td
(aspirin)Tj
3.1039 0 Td
(therap)Tj
2.778 0 Td
(y)Tj
0.7157 0 Td
(on)Tj
-42.1444 -1.1835 Td
(the)Tj
1.5874 0 Td
(risk)Tj
1.7434 0 Td
(of)Tj
1.0417 0 Td
(brain)Tj
2.3953 0 Td
(ischemic)Tj
4.0465 0 Td
(stroke.)Tj
3.1748 0 Td
(Archives)Tj
3.9898 0 Td
(of)Tj
1.0417 0 Td
(Neurolo)Tj
3.43 0 Td
(gy)Tj
1.4811 0 Td
(62:)Tj
1.5874 0 Td
(12171220.)Tj
0.83 0.64 0.02 0 k
5.4001 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.1001/)Tj
-36.3334 -1.1905 Td
(archneur.62.)Tj
5.5134 0 Td
(8.1217)Tj
0 g
3.2245 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(1608776)Tj
3.8126 0 Td
(1)Tj
0 g
/F2 1 Tf
-18.1418 -1.6229 Td
(69.)Tj
/F0 1 Tf
2.622 0 Td
(Rothwell)Tj
3.9827 0 Td
(PM,)Tj
1.9772 0 Td
(Cook)Tj
2.5158 0 Td
(NR,)Tj
1.9205 0 Td
(Gaziano)Tj
3.8835 0 Td
(JM,)Tj
1.8141 0 Td
(Price)Tj
2.4591 0 Td
(JF,)Tj
1.5945 0 Td
(Belch)Tj
2.6788 0 Td
(JFF,)Tj
2.2039 0 Td
(Ronca)Tj
2.8347 0 Td
(glioni)Tj
2.5016 0 Td
(MC)Tj
1.7575 0 Td
(et)Tj
1.0346 0 Td
(al.)Tj
1.2544 0 Td
(Effects)Tj
3.2386 0 Td
(of)Tj
1.0417 0 Td
(aspirin)Tj
3.104 0 Td
(on)Tj
-41.7972 -1.1905 Td
(risks)Tj
2.2394 0 Td
(of)Tj
1.0417 0 Td
(vascular)Tj
3.8765 0 Td
(events)Tj
3.1181 0 Td
(and)Tj
1.8567 0 Td
(cancer)Tj
3.1677 0 Td
(according)Tj
4.4788 0 Td
(to)Tj
1.0418 0 Td
(bodyw)Tj
2.8346 0 Td
(eight)Tj
2.3457 0 Td
(and)Tj
1.8567 0 Td
(dose:)Tj
2.6292 0 Td
(analysis)Tj
3.7559 0 Td
(of)Tj
1.0417 0 Td
(individual)Tj
4.2946 0 Td
(patient)Tj
-39.5791 -1.1835 Td
(data)Tj
2.1331 0 Td
(from)Tj
2.1898 0 Td
(randomise)Tj
4.5851 0 Td
(d)Tj
0.7653 0 Td
(trials.)Tj
2.5654 0 Td
(Lancet)Tj
3.1677 0 Td
(2018.)Tj
0.83 0.64 0.02 0 k
2.6788 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.101)Tj
3.8197 0 Td
(6/S0140-67)Tj
5.0812 0 Td
(36\(18\)311)Tj
4.4717 0 Td
(33-4)Tj
0 g
/F2 1 Tf
-39.494 -1.6299 Td
(70.)Tj
/F0 1 Tf
2.622 0 Td
(Ali)Tj
1.304 0 Td
(R,)Tj
1.2118 0 Td
(Toh)Tj
1.9134 0 Td
(H-C,)Tj
2.2465 0 Td
(Chia)Tj
2.2393 0 Td
(W-K.)Tj
2.4166 0 Td
(The)Tj
1.9205 0 Td
(ASCOLT)Tj
4.174 0 Td
(trial)Tj
1.8001 0 Td
(investigator)Tj
5.0173 0 Td
(s.)Tj
0.9851 0 Td
(\(2011\))Tj
3.0543 0 Td
(The)Tj
1.9205 0 Td
(utility)Tj
2.452 0 Td
(of)Tj
1.0417 0 Td
(Aspirin)Tj
3.2174 0 Td
(in)Tj
0.9779 0 Td
(dukes)Tj
2.8418 0 Td
(C)Tj
0.9284 0 Td
(and)Tj
-41.6626 -1.1835 Td
(high)Tj
2.0693 0 Td
(risk)Tj
1.7504 0 Td
(dukes)Tj
2.8418 0 Td
(B)Tj
0.8787 0 Td
(colorectal)Tj
4.415 0 Td
(cancer)Tj
3.9402 0 Td
(The)Tj
1.9205 0 Td
(ASCOLT)Tj
4.1811 0 Td
(study:)Tj
2.8418 0 Td
(study)Tj
2.5795 0 Td
(protocol)Tj
3.7064 0 Td
(for)Tj
1.3677 0 Td
(a)Tj
0.7654 0 Td
(randomiz)Tj
4.0394 0 Td
(ed)Tj
1.311 0 Td
(controlled)Tj
-38.6082 -1.1906 Td
(trial.)Tj
2.0693 0 Td
(Trials.)Tj
2.8985 0 Td
(2011;)Tj
2.8913 0 Td
(12:)Tj
1.5874 0 Td
(261.)Tj
2.1331 0 Td
(Published)Tj
4.5284 0 Td
(online)Tj
2.8276 0 Td
(2011)Tj
2.3953 0 Td
(Dec)Tj
1.9701 0 Td
(14.)Tj
0.83 0.64 0.02 0 k
1.5874 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.118)Tj
3.8197 0 Td
(6/1745-6215)Tj
5.5135 0 Td
(-12-261)Tj
0 g
-39.6358 -1.1835 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(221685)Tj
3.267 0 Td
(68)Tj
0 g
/F2 1 Tf
-8.8583 -1.6299 Td
(71.)Tj
/F0 1 Tf
2.622 0 Td
(Schmoll)Tj
3.7134 0 Td
(HJ.)Tj
1.7008 0 Td
(\(2018\))Tj
3.0544 0 Td
(FOCUS4:)Tj
4.5071 0 Td
(a)Tj
0.7654 0 Td
(new)Tj
2.0197 0 Td
(trial)Tj
1.8 0 Td
(design)Tj
3.1039 0 Td
(for)Tj
1.3678 0 Td
(evaluation)Tj
4.6914 0 Td
(of)Tj
1.0346 0 Td
(targeted)Tj
3.8268 0 Td
(drugs)Tj
2.6788 0 Td
(in)Tj
0.9779 0 Td
(colorectal)Tj
4.415 0 Td
(cancer?)Tj
-39.657 -1.1835 Td
(Lancet)Tj
3.1678 0 Td
(Gastroenter)Tj
5.2016 0 Td
(ology)Tj
2.5653 0 Td
(and)Tj
1.8568 0 Td
(Hepatolog)Tj
4.4716 0 Td
(y)Tj
0.7087 0 Td
(2018;)Tj
2.6788 0 Td
(3:1435.)Tj
0.83 0.64 0.02 0 k
4.0394 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.1016/)Tj
4.6418 0 Td
(S2468-125)Tj
4.8047 0 Td
(3\(17\))Tj
-39.5507 -1.1905 Td
(30402-8)Tj
0 g
3.8197 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(292548)Tj
3.267 0 Td
(88)Tj
0 g
/F2 1 Tf
-12.678 -1.6229 Td
(72.)Tj
/F0 1 Tf
2.622 0 Td
(Burn)Tj
2.2961 0 Td
(J,)Tj
0.9921 0 Td
(Mathers)Tj
3.7772 0 Td
(JC,)Tj
1.7008 0 Td
(Bishop)Tj
3.2174 0 Td
(DT.)Tj
1.8142 0 Td
(\(2013\))Tj
3.0614 0 Td
(Chemo)Tj
3.1677 0 Td
(prevention)Tj
4.8048 0 Td
(in)Tj
0.978 0 Td
(Lynch)Tj
2.8417 0 Td
(syndrome.)Tj
4.819 0 Td
(Fam)Tj
2.1968 0 Td
(Cancer)Tj
3.6071 0 Td
(12:707)Tj
-39.2743 -1.1905 Td
(718)Tj
0.83 0.64 0.02 0 k
1.8567 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.100)Tj
3.8198 0 Td
(7/s10689)Tj
4.0394 0 Td
(-013-9650)Tj
4.4716 0 Td
(-y)Tj
0 g
1.0418 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(23880960)Tj
0 g
/F2 1 Tf
-26.2348 -1.6229 Td
(73.)Tj
/F0 1 Tf
2.622 0 Td
(Shaw)Tj
2.6788 0 Td
(G,)Tj
1.2756 0 Td
(Oliver)Tj
2.785 0 Td
(T,)Tj
1.0985 0 Td
(Kealy)Tj
2.6787 0 Td
(R,)Tj
1.2048 0 Td
(Powles)Tj
3.3874 0 Td
(T,)Tj
1.1055 0 Td
(Hillman)Tj
3.4867 0 Td
(P,)Tj
1.1551 0 Td
(Cuzick)Tj
3.1677 0 Td
(J.)Tj
0.9922 0 Td
(\(2018\))Tj
3.0543 0 Td
(The)Tj
1.9205 0 Td
(PROVEN)Tj
4.1741 0 Td
(T)Tj
0.8291 0 Td
(study,)Tj
2.8488 0 Td
(a)Tj
0.7654 0 Td
(multicentre)Tj
-38.6082 -1.1905 Td
(double)Tj
3.1607 0 Td
(blind)Tj
2.2819 0 Td
(placebo)Tj
3.6496 0 Td
(controlled)Tj
4.4717 0 Td
(randomis)Tj
4.0394 0 Td
(ed)Tj
1.311 0 Td
(trial)Tj
1.793 0 Td
(to)Tj
1.0417 0 Td
(evaluate)Tj
3.9331 0 Td
(the)Tj
1.5803 0 Td
(effects)Tj
3.1253 0 Td
(of)Tj
1.0417 0 Td
(Vitamin)Tj
3.5008 0 Td
(D)Tj
0.9284 0 Td
(and)Tj
1.8567 0 Td
(aspirin)Tj
3.1039 0 Td
(on)Tj
1.3111 0 Td
(pro-)Tj
-42.1303 -1.1835 Td
(gression)Tj
3.926 0 Td
(of)Tj
1.0418 0 Td
(low)Tj
1.6937 0 Td
(risk)Tj
1.7433 0 Td
(prostate)Tj
3.7772 0 Td
(cancer)Tj
3.1677 0 Td
(during)Tj
2.941 0 Td
(active)Tj
2.7851 0 Td
(surveillanc)Tj
4.6276 0 Td
(e.)Tj
1.0417 0 Td
(European)Tj
4.4788 0 Td
(J)Tj
0.7157 0 Td
(Surgical)Tj
3.7631 0 Td
(Oncolog)Tj
3.6567 0 Td
(y)Tj
0.7157 0 Td
(2018;)Tj
2.6788 0 Td
(44:)Tj
-42.7539 -1.1906 Td
(S13)Tj
0.83 0.64 0.02 0 k
1.9701 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.101)Tj
3.8197 0 Td
(6/j.ejso.20)Tj
4.4717 0 Td
(17.10.126)Tj
0 g
/F2 1 Tf
-18.2977 -1.6228 Td
(74.)Tj
/F0 1 Tf
2.622 0 Td
(Elwood)Tj
3.43 0 Td
(PC,)Tj
1.8638 0 Td
(Morgan)Tj
3.5433 0 Td
(G.)Tj
1.2614 0 Td
(\(2014\))Tj
3.0473 0 Td
(Critical)Tj
3.2032 0 Td
(views)Tj
2.6716 0 Td
(in)Tj
0.9709 0 Td
(Gastroenter)Tj
5.2016 0 Td
(ology)Tj
2.5512 0 Td
(&)Tj
0.8717 0 Td
(Hepatolog)Tj
4.4717 0 Td
(y:)Tj
0.985 0 Td
(aspirin)Tj
3.0969 0 Td
(prophyl)Tj
3.2103 0 Td
(axis:)Tj
2.2323 0 Td
(put-)Tj
-42.6122 -1.1906 Td
(ting)Tj
1.8 0 Td
(gut)Tj
1.5874 0 Td
(bleeds)Tj
3.104 0 Td
(into)Tj
1.8 0 Td
(perspective)Tj
5.0245 0 Td
(.)Tj
0.496 0 Td
(Gastroen)Tj
4.0465 0 Td
(terol)Tj
2.1331 0 Td
(Hepatol)Tj
3.8197 0 Td
(10:)Tj
1.5874 0 Td
(613.)Tj
/F2 1 Tf
-28.0206 -1.6228 Td
(75.)Tj
/F0 1 Tf
2.622 0 Td
(Elwood)Tj
3.4371 0 Td
(PC,)Tj
1.8708 0 Td
(Morgan)Tj
3.5505 0 Td
(G,)Tj
1.2685 0 Td
(Galante)Tj
3.6638 0 Td
(J,)Tj
0.9921 0 Td
(Chia)Tj
2.2323 0 Td
(JW,)Tj
1.9347 0 Td
(Dolwan)Tj
3.2669 0 Td
(i)Tj
0.4323 0 Td
(S,)Tj
1.1551 0 Td
(Graziano)Tj
4.2095 0 Td
(JM,)Tj
1.8142 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2016\))Tj
3.0543 0 Td
(Systematic)Tj
5.0387 0 Td
(review)Tj
-40.2169 -1.1835 Td
(and)Tj
1.8567 0 Td
(meta-ana)Tj
4.1528 0 Td
(lysis)Tj
2.126 0 Td
(of)Tj
1.0418 0 Td
(randomis)Tj
4.0394 0 Td
(ed)Tj
1.311 0 Td
(trials)Tj
2.289 0 Td
(to)Tj
1.0417 0 Td
(ascertain)Tj
4.2024 0 Td
(fatal)Tj
2.0764 0 Td
(gastroin)Tj
3.4867 0 Td
(testinal)Tj
3.3307 0 Td
(bleeding)Tj
3.9189 0 Td
(events)Tj
3.1182 0 Td
(attribut)Tj
2.9976 0 Td
(able)Tj
2.0693 0 Td
(to)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
31.7412 0 Td
(16)Tj
1.304 0 Td
(/)Tj
ET
endstream
endobj
804 0 obj
<>stream
endstream
endobj
805 0 obj
<>stream
endstream
endobj
806 0 obj
<>stream
endstream
endobj
807 0 obj
<>stream
endstream
endobj
808 0 obj
<>stream
endstream
endobj
809 0 obj
<>stream
endstream
endobj
810 0 obj
<>stream
endstream
endobj
811 0 obj
<>stream
endstream
endobj
812 0 obj
<>stream
endstream
endobj
813 0 obj
<>stream
endstream
endobj
814 0 obj
<>stream
endstream
endobj
815 0 obj
<>stream
endstream
endobj
816 0 obj
<>stream
endstream
endobj
817 0 obj
<>stream
endstream
endobj
818 0 obj
<>stream
endstream
endobj
819 0 obj
<>stream
endstream
endobj
820 0 obj
<>stream
endstream
endobj
821 0 obj
<>stream
endstream
endobj
822 0 obj
<>stream
endstream
endobj
823 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
824 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 344 0 R/Annots 825 0 R/Contents 826 0 R/TrimBox[0 0 612 792]>>
endobj
825 0 obj
[827 0 R 828 0 R 829 0 R 830 0 R 831 0 R 832 0 R 833 0 R 834 0 R 835 0 R 836 0 R 837 0 R 838 0 R 839 0 R 840 0 R 841 0 R 842 0 R 843 0 R 844 0 R 845 0 R 846 0 R 847 0 R 848 0 R 849 0 R 850 0 R 851 0 R 852 0 R 853 0 R 854 0 R 855 0 R 856 0 R 857 0 R 858 0 R 859 0 R 860 0 R 861 0 R 862 0 R 863 0 R 864 0 R 865 0 R 866 0 R]
endobj
827 0 obj
<>/Border[0 0 0]/A 867 0 R>>
endobj
867 0 obj
<>
endobj
828 0 obj
<>/Border[0 0 0]/A 868 0 R>>
endobj
868 0 obj
<>
endobj
829 0 obj
<>/Border[0 0 0]/A 869 0 R>>
endobj
869 0 obj
<>
endobj
830 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref076)>>
endobj
831 0 obj
<>/Border[0 0 0]/A 870 0 R>>
endobj
870 0 obj
<>
endobj
832 0 obj
<>/Border[0 0 0]/A 871 0 R>>
endobj
871 0 obj
<>
endobj
833 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref077)>>
endobj
834 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref078)>>
endobj
835 0 obj
<>/Border[0 0 0]/A 872 0 R>>
endobj
872 0 obj
<>
endobj
836 0 obj
<>/Border[0 0 0]/A 873 0 R>>
endobj
873 0 obj
<>
endobj
837 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref079)>>
endobj
838 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref080)>>
endobj
839 0 obj
<>/Border[0 0 0]/A 874 0 R>>
endobj
874 0 obj
<>
endobj
840 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref081)>>
endobj
841 0 obj
<>/Border[0 0 0]/A 875 0 R>>
endobj
875 0 obj
<>
endobj
842 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref082)>>
endobj
843 0 obj
<>/Border[0 0 0]/A 876 0 R>>
endobj
876 0 obj
<>
endobj
844 0 obj
<>/Border[0 0 0]/A 877 0 R>>
endobj
877 0 obj
<>
endobj
845 0 obj
<>/Border[0 0 0]/A 878 0 R>>
endobj
878 0 obj
<>
endobj
846 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref083)>>
endobj
847 0 obj
<>/Border[0 0 0]/A 879 0 R>>
endobj
879 0 obj
<>
endobj
848 0 obj
<>/Border[0 0 0]/A 880 0 R>>
endobj
880 0 obj
<>
endobj
849 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref084)>>
endobj
850 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref085)>>
endobj
851 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref086)>>
endobj
852 0 obj
<>/Border[0 0 0]/A 881 0 R>>
endobj
881 0 obj
<>
endobj
853 0 obj
<>/Border[0 0 0]/A 882 0 R>>
endobj
882 0 obj
<>
endobj
854 0 obj
<>/Border[0 0 0]/A 883 0 R>>
endobj
883 0 obj
<>
endobj
855 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref087)>>
endobj
856 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref088)>>
endobj
857 0 obj
<>/Border[0 0 0]/A 884 0 R>>
endobj
884 0 obj
<>
endobj
858 0 obj
<>/Border[0 0 0]/A 885 0 R>>
endobj
885 0 obj
<>
endobj
859 0 obj
<>/Border[0 0 0]/A 886 0 R>>
endobj
886 0 obj
<>
endobj
860 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref089)>>
endobj
861 0 obj
<>/Border[0 0 0]/A 887 0 R>>
endobj
887 0 obj
<>
endobj
862 0 obj
<>/Border[0 0 0]/A 888 0 R>>
endobj
888 0 obj
<>
endobj
863 0 obj
<>/Border[0 0 0]/Dest(Lpone.0203957.ref090)>>
endobj
864 0 obj
<>/Border[0 0 0]/A 889 0 R>>
endobj
889 0 obj
<>
endobj
865 0 obj
<>/Border[0 0 0]/A 890 0 R>>
endobj
890 0 obj
<>
endobj
866 0 obj
<>/Border[0 0 0]/A 891 0 R>>
endobj
891 0 obj
<>
endobj
826 0 obj
[892 0 R 893 0 R 894 0 R 895 0 R 896 0 R 897 0 R 898 0 R 899 0 R 900 0 R 901 0 R 902 0 R 903 0 R 904 0 R 905 0 R 906 0 R 907 0 R]
endobj
892 0 obj
<>stream
q
0.83 0.64 0.02 0 k
514.6583 707.6409 m
575.4898 707.6409 l
h
f*
221.4992 698.1165 m
317.0835 698.1165 l
h
f*
342.5386 698.1165 m
377.4614 698.1165 l
h
f*
248.1449 666.1417 m
391.0677 666.1417 l
h
f*
416.5795 666.1417 m
451.5024 666.1417 l
h
f*
221.4992 583.1433 m
360.9071 583.1433 l
h
f*
386.3622 583.1433 m
421.285 583.1433 l
h
f*
221.4992 528.6614 m
256.422 528.6614 l
h
f*
475.7102 506.1543 m
510.6331 506.1543 l
h
f*
484.7244 483.6472 m
565.2283 483.6472 l
h
f*
221.4992 474.1228 m
282.3307 474.1228 l
h
f*
307.7858 474.1228 m
342.7087 474.1228 l
h
f*
410.1732 451.6157 m
544.3654 451.6157 l
h
f*
221.4992 442.148 m
256.422 442.148 l
h
f*
437.8394 374.6268 m
566.9858 374.6268 l
h
f*
221.4992 365.1591 m
239.0173 365.1591 l
h
f*
264.4724 365.1591 m
299.3953 365.1591 l
h
f*
481.7764 329.6693 m
562.2803 329.6693 l
h
f*
221.4992 320.1449 m
258.2362 320.1449 l
h
f*
283.6913 320.1449 m
318.6142 320.1449 l
h
f*
267.8173 288.1701 m
416.8063 288.1701 l
h
f*
442.2614 288.1701 m
477.2409 288.1701 l
h
f*
251.6598 265.663 m
419.074 265.663 l
h
f*
444.5291 265.663 m
475.0866 265.663 l
h
f*
0 g
1 j
1 J
0 w
7.9999 0 0 7.9999 221.4992 708.7181 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(preventive)Tj
4.748 0 Td
(low-dose)Tj
4.1457 0 Td
(aspirin:)Tj
3.3804 0 Td
(no)Tj
1.311 0 Td
(evidence)Tj
4.1457 0 Td
(of)Tj
1.0417 0 Td
(increased)Tj
4.4717 0 Td
(risk.)Tj
2.0268 0 Td
(PLoS)Tj
2.6292 0 Td
(One)Tj
2.3031 0 Td
(11:)Tj
1.5875 0 Td
(e016616)Tj
3.8126 0 Td
(6.)Tj
0.83 0.64 0.02 0 k
1.0417 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.)Tj
-42.0593 -1.1905 Td
(1371/journa)Tj
5.1803 0 Td
(l.pone.0)Tj
3.4866 0 Td
(166166)Tj
0 g
3.4938 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(2784624)Tj
3.8126 0 Td
(6)Tj
0 g
/F2 1 Tf
-21.5646 -1.6229 Td
(76.)Tj
/F0 1 Tf
2.622 0 Td
(Cea)Tj
2.0126 0 Td
(Soriano)Tj
3.5929 0 Td
(L,)Tj
1.0276 0 Td
(Lanas)Tj
2.8842 0 Td
(A,)Tj
1.1481 0 Td
(Soriano-G)Tj
4.4788 0 Td
(abarro)Tj
0 Tc
2.4094 0.0355 Td
()Tj
-0.005 Tc
0.6378 -0.0355 Td
(M,)Tj
1.3111 0 Td
(Garc)Tj
0 Tc
2.1189 0.0213 Td
()Tj
-0.005 Tc
0.2976 -0.0213 Td
(a)Tj
0.7583 0 Td
(Rodr)Tj
0 Tc
2.1047 0.0213 Td
()Tj
-0.005 Tc
0.2977 -0.0213 Td
(guez)Tj
2.3386 0 Td
(LA,)Tj
1.6937 0 Td
(Incidence)Tj
4.4079 0 Td
(of)Tj
1.0347 0 Td
(Upper)Tj
2.8842 0 Td
(and)Tj
1.8426 0 Td
(Lower)Tj
2.8842 0 Td
(Gas-)Tj
-42.1656 -1.1834 Td
(trointesti)Tj
3.7063 0 Td
(nal)Tj
1.5236 0 Td
(Bleeding)Tj
4.0323 0 Td
(in)Tj
0.978 0 Td
(New)Tj
2.1898 0 Td
(Users)Tj
2.7921 0 Td
(of)Tj
1.0418 0 Td
(Low-dose)Tj
4.4787 0 Td
(Aspirin,)Tj
3.4938 0 Td
(Clinical)Tj
3.3661 0 Td
(Gastroenter)Tj
5.2016 0 Td
(ology)Tj
2.5583 0 Td
(and)Tj
1.8567 0 Td
(Hepatolog)Tj
4.4717 0 Td
(y)Tj
-41.6908 -1.1906 Td
(\(2018\),)Tj
0.83 0.64 0.02 0 k
3.3307 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.101)Tj
3.8197 0 Td
(6/j.cgh.201)Tj
4.8048 0 Td
(8.05.061)Tj
0 g
4.0465 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(299083)Tj
3.2669 0 Td
(61)Tj
0 g
/F2 1 Tf
-30.2741 -1.6228 Td
(77.)Tj
/F0 1 Tf
2.622 0 Td
(Abraham)Tj
4.2165 0 Td
(NS,)Tj
1.8638 0 Td
(Hlatky)Tj
2.9552 0 Td
(MA,)Tj
1.9771 0 Td
(Antman)Tj
3.6142 0 Td
(EM,)Tj
1.9843 0 Td
(Bhatt)Tj
2.5229 0 Td
(DL,)Tj
1.7504 0 Td
(Bjorkman)Tj
4.3724 0 Td
(DJ,)Tj
1.7008 0 Td
(Clark)Tj
2.5087 0 Td
(CB,)Tj
1.8709 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2544 0 Td
(\(2010\))Tj
3.0543 0 Td
(ACCF/A)Tj
3.6213 0 Td
(CG/AHA)Tj
-40.3089 -1.1906 Td
(2010)Tj
2.4023 0 Td
(expert)Tj
2.9481 0 Td
(consensus)Tj
4.9252 0 Td
(document)Tj
4.5426 0 Td
(on)Tj
1.311 0 Td
(the)Tj
1.5803 0 Td
(concomitant)Tj
5.5276 0 Td
(use)Tj
1.8001 0 Td
(of)Tj
1.0417 0 Td
(proton)Tj
3.0047 0 Td
(pump)Tj
2.6788 0 Td
(inhibitors)Tj
4.1386 0 Td
(and)Tj
1.8567 0 Td
(thienopyri-)Tj
-37.7577 -1.1835 Td
(dines:)Tj
2.8346 0 Td
(a)Tj
0.7654 0 Td
(focused)Tj
3.6638 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0418 0 Td
(the)Tj
1.5874 0 Td
(ACCF/A)Tj
3.6213 0 Td
(CG/AHA)Tj
4.011 0 Td
(2008)Tj
2.4024 0 Td
(expert)Tj
2.9551 0 Td
(consens)Tj
3.6568 0 Td
(us)Tj
1.2614 0 Td
(document)Tj
4.5425 0 Td
(on)Tj
1.3111 0 Td
(reducing)Tj
3.9827 0 Td
(the)Tj
-40.8617 -1.1905 Td
(gastroint)Tj
3.763 0 Td
(estinal)Tj
3.0543 0 Td
(risks)Tj
2.2394 0 Td
(of)Tj
1.0418 0 Td
(antiplatelet)Tj
4.9606 0 Td
(therap)Tj
2.778 0 Td
(y)Tj
0.7158 0 Td
(and)Tj
1.8567 0 Td
(NSAID)Tj
3.2386 0 Td
(use.)Tj
2.0764 0 Td
(A)Tj
0.8787 0 Td
(Report)Tj
3.1748 0 Td
(of)Tj
1.0418 0 Td
(the)Tj
1.5803 0 Td
(American)Tj
4.3796 0 Td
(College)Tj
3.5362 0 Td
(of)Tj
1.0418 0 Td
(Cardi-)Tj
-41.3578 -1.1906 Td
(ology)Tj
2.5653 0 Td
(Founda)Tj
3.3308 0 Td
(tion)Tj
1.8 0 Td
(Task)Tj
2.3598 0 Td
(Force)Tj
2.7426 0 Td
(on)Tj
1.3039 0 Td
(Expert)Tj
3.0686 0 Td
(Consensus)Tj
5.1378 0 Td
(Document)Tj
4.4858 0 Td
(s.)Tj
0.9922 0 Td
(J)Tj
0.7157 0 Td
(Amer)Tj
2.5725 0 Td
(Coll)Tj
1.9063 0 Td
(Cardiol)Tj
3.5433 0 Td
(56:)Tj
1.5804 0 Td
(20512066.)Tj
/F2 1 Tf
-40.727 -1.6228 Td
(78.)Tj
/F0 1 Tf
2.622 0 Td
(Mo)Tj
1.5945 0 Td
(C,)Tj
1.2047 0 Td
(Sun)Tj
1.9701 0 Td
(G,)Tj
1.2685 0 Td
(Lu)Tj
1.311 0 Td
(ML,)Tj
1.8638 0 Td
(Zhang)Tj
3.0119 0 Td
(L,)Tj
1.0417 0 Td
(Wang)Tj
2.7921 0 Td
(YZ,)Tj
1.7646 0 Td
(Sun)Tj
1.9701 0 Td
(X,)Tj
1.1551 0 Td
(et)Tj
1.0418 0 Td
(al.)Tj
1.2543 0 Td
(\(2015\))Tj
3.0544 0 Td
(Proton)Tj
3.1181 0 Td
(pump)Tj
2.6788 0 Td
(inhibitors)Tj
4.1386 0 Td
(in)Tj
0.978 0 Td
(prevention)Tj
4.8047 0 Td
(of)Tj
-42.0168 -1.1835 Td
(low-dose)Tj
4.1457 0 Td
(aspirin-ass)Tj
4.7409 0 Td
(ociated)Tj
3.3875 0 Td
(upper)Tj
2.7283 0 Td
(gastroin)Tj
3.4867 0 Td
(testinal)Tj
3.3307 0 Td
(injuries.)Tj
3.5929 0 Td
(World)Tj
2.7851 0 Td
(J)Tj
0.7158 0 Td
(Gastroenter)Tj
5.2016 0 Td
(ol)Tj
1.1976 0 Td
(21:)Tj
1.5874 0 Td
(53825)Tj
3.267 0 Td
(392.)Tj
0.83 0.64 0.02 0 k
-40.1672 -1.1906 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.374)Tj
3.8197 0 Td
(8/wjg.v21.i17)Tj
5.7331 0 Td
(.5382)Tj
0 g
2.6717 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(25954113)Tj
0 g
/F2 1 Tf
-23.23 -1.6228 Td
(79.)Tj
/F0 1 Tf
2.622 0 Td
(Abraham)Tj
4.2165 0 Td
(NS.)Tj
1.8638 0 Td
(\(2016\))Tj
3.0544 0 Td
(Prevention)Tj
4.9181 0 Td
(of)Tj
1.0418 0 Td
(gastroin)Tj
3.4866 0 Td
(testinal)Tj
3.3307 0 Td
(bleeding)Tj
3.919 0 Td
(in)Tj
0.9779 0 Td
(patients)Tj
3.6567 0 Td
(receiving)Tj
4.1387 0 Td
(direct)Tj
2.622 0 Td
(oral)Tj
1.8496 0 Td
(anticoagu)Tj
4.2521 0 Td
(-)Tj
-43.3279 -1.1906 Td
(lants.)Tj
2.5653 0 Td
(Am)Tj
1.7079 0 Td
(J)Tj
0.7158 0 Td
(Gastro)Tj
2.9551 0 Td
(enterol)Tj
3.2174 0 Td
(suppl)Tj
2.785 0 Td
(3:)Tj
1.0418 0 Td
(212.)Tj
/F2 1 Tf
-17.6103 -1.6228 Td
(80.)Tj
/F0 1 Tf
2.622 0 Td
(Vreeburg)Tj
4.259 0 Td
(EM,)Tj
1.9843 0 Td
(Terwee)Tj
3.5008 0 Td
(CB,)Tj
1.8638 0 Td
(Snel)Tj
2.1827 0 Td
(P,)Tj
1.1551 0 Td
(Rauws)Tj
3.2316 0 Td
(EAJ,)Tj
2.3031 0 Td
(Bartelsman)Tj
5.2016 0 Td
(JFWM,)Tj
3.3591 0 Td
(Meulen)Tj
3.4371 0 Td
(JHP)Tj
2.0905 0 Td
(et)Tj
1.0347 0 Td
(al.)Tj
1.2543 0 Td
(\(1999\))Tj
3.0615 0 Td
(of)Tj
1.0346 0 Td
(the)Tj
-40.9538 -1.1906 Td
(Rockall)Tj
3.437 0 Td
(risk)Tj
1.7433 0 Td
(scoring)Tj
3.3874 0 Td
(system)Tj
3.3449 0 Td
(in)Tj
0.978 0 Td
(upper)Tj
2.7284 0 Td
(gastroint)Tj
3.763 0 Td
(estinal)Tj
3.0543 0 Td
(bleeding.)Tj
4.1954 0 Td
(Gut)Tj
2.0338 0 Td
(44:)Tj
1.5874 0 Td
(33133)Tj
3.267 0 Td
(5.Validation)Tj
5.3433 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
-38.8632 -1.1835 Td
(10026316)Tj
0 g
/F2 1 Tf
-2.622 -1.6299 Td
(81.)Tj
/F0 1 Tf
2.622 0 Td
(Anon)Tj
2.5157 0 Td
(\(2000\))Tj
3.0544 0 Td
(Prevention)Tj
4.9181 0 Td
(of)Tj
1.0418 0 Td
(pulmona)Tj
3.763 0 Td
(ry)Tj
1.0417 0 Td
(embolism)Tj
4.4292 0 Td
(and)Tj
1.8496 0 Td
(deep)Tj
2.4024 0 Td
(vein)Tj
2.0197 0 Td
(thrombosi)Tj
4.3158 0 Td
(s)Tj
0.7157 0 Td
(with)Tj
1.963 0 Td
(low)Tj
1.6938 0 Td
(dose)Tj
2.3456 0 Td
(aspirin:)Tj
3.3804 0 Td
(Pul-)Tj
-41.4499 -1.1835 Td
(monary)Tj
3.5008 0 Td
(Embolism)Tj
4.5425 0 Td
(Prevention)Tj
4.9182 0 Td
(\(PEP\))Tj
2.8488 0 Td
(trial.)Tj
2.0693 0 Td
(Lancet)Tj
3.3945 0 Td
(355:)Tj
2.126 0 Td
(12951302.)Tj
5.4072 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(107767)Tj
3.2669 0 Td
(41)Tj
0 g
/F2 1 Tf
-37.6655 -1.6299 Td
(82.)Tj
/F0 1 Tf
2.622 0 Td
(Brighton)Tj
3.8764 0 Td
(TA,)Tj
1.7645 0 Td
(Ekelboo)Tj
3.5434 0 Td
(m)Tj
1.0488 0 Td
(TA,)Tj
1.7646 0 Td
(Mann)Tj
2.6787 0 Td
(KMister,)Tj
3.8339 0 Td
(Gallus)Tj
3.0048 0 Td
(A,)Tj
1.1551 0 Td
(Ockelford)Tj
4.4363 0 Td
(P.)Tj
1.148 0 Td
(\(2012\))Tj
3.0614 0 Td
(Low-Dos)Tj
3.8765 0 Td
(e)Tj
0.7653 0 Td
(Aspirin)Tj
3.2174 0 Td
(for)Tj
1.3677 0 Td
(Prevent-)Tj
-40.5428 -1.1835 Td
(ing)Tj
1.5236 0 Td
(Recurren)Tj
4.0394 0 Td
(t)Tj
0.4961 0 Td
(Venous)Tj
3.5575 0 Td
(thromboe)Tj
4.1527 0 Td
(mbolism.)Tj
4.1599 0 Td
(New)Tj
2.1827 0 Td
(Engl)Tj
2.1898 0 Td
(J)Tj
0.7087 0 Td
(Med)Tj
2.3598 0 Td
(367:)Tj
2.126 0 Td
(19791987.)Tj
0.83 0.64 0.02 0 k
5.4072 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.105)Tj
3.8197 0 Td
(6/)Tj
-42.1373 -1.1905 Td
(NEJMoa1)Tj
4.3228 0 Td
(210384)Tj
0 g
3.4937 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9694 0 Td
(23121403)Tj
0 g
/F2 1 Tf
-13.4079 -1.6229 Td
(83.)Tj
/F0 1 Tf
2.622 0 Td
(Caine)Tj
2.7779 0 Td
(GJ,)Tj
1.7646 0 Td
(Stonelake)Tj
4.5922 0 Td
(PS,)Tj
1.8142 0 Td
(Lip)Tj
1.5236 0 Td
(GYH,)Tj
2.6362 0 Td
(Kehoe)Tj
3.0615 0 Td
(ST.)Tj
1.7646 0 Td
(\(2002\))Tj
3.0543 0 Td
(The)Tj
1.9205 0 Td
(hypercoa)Tj
4.0394 0 Td
(gulable)Tj
3.3733 0 Td
(state)Tj
2.3527 0 Td
(of)Tj
1.0418 0 Td
(maligna)Tj
3.4299 0 Td
(ncy)Tj
1.7575 0 Td
(patho-)Tj
-40.9042 -1.1906 Td
(genesis)Tj
3.6 0 Td
(and)Tj
1.8567 0 Td
(current)Tj
3.2811 0 Td
(debate.)Tj
3.4937 0 Td
(Neoplasia)Tj
4.7977 0 Td
(4\(6\):)Tj
2.2465 0 Td
(46547)Tj
3.2669 0 Td
(3.)Tj
0.83 0.64 0.02 0 k
1.0418 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.103)Tj
3.8197 0 Td
(8/sj.neo.79)Tj
4.8048 0 Td
(00263)Tj
0 g
2.948 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
-40.5711 -1.1834 Td
(12407439)Tj
0 g
/F2 1 Tf
-2.622 -1.6229 Td
(84.)Tj
/F0 1 Tf
2.622 0 Td
(Barbara)Tj
3.7134 0 Td
(L,)Tj
1.0417 0 Td
(Thomas)Tj
3.7843 0 Td
(G.)Tj
1.2685 0 Td
(\(2009\))Tj
3.0544 0 Td
(Venous)Tj
3.5575 0 Td
(thromboe)Tj
4.1528 0 Td
(mbolism)Tj
3.8834 0 Td
(in)Tj
0.978 0 Td
(cervical)Tj
3.5433 0 Td
(cancer.)Tj
3.4442 0 Td
(Lancet)Tj
3.1748 0 Td
(Oncol)Tj
3.0118 0 Td
(9:5460)Tj
3.5434 0 Td
(.)Tj
/F2 1 Tf
-44.7735 -1.6299 Td
(85.)Tj
/F0 1 Tf
2.622 0 Td
(Liebman)Tj
3.9827 0 Td
(HA,)Tj
1.8708 0 Td
(O'Conn)Tj
3.3308 0 Td
(ell.)Tj
1.4669 0 Td
(\(2016\))Tj
3.0615 0 Td
(Incidental)Tj
4.415 0 Td
(venous)Tj
3.3874 0 Td
(thromboe)Tj
4.1528 0 Td
(mbolismeve)Tj
5.2441 0 Td
(nts)Tj
1.5378 0 Td
(in)Tj
0.978 0 Td
(cancer)Tj
3.1677 0 Td
(patients:)Tj
3.9331 0 Td
(what)Tj
2.3032 0 Td
(do)Tj
-42.8318 -1.1835 Td
(we)Tj
1.474 0 Td
(know)Tj
2.5157 0 Td
(in)Tj
0.978 0 Td
(2016?)Tj
2.9481 0 Td
(Thromb)Tj
3.6212 0 Td
(Res)Tj
2.1898 0 Td
(140;)Tj
2.126 0 Td
(Suppl)Tj
2.7284 0 Td
(1;)Tj
1.0417 0 Td
(S18S20.)Tj
/F2 1 Tf
-22.2449 -1.6299 Td
(86.)Tj
/F0 1 Tf
2.622 0 Td
(Lyman)Tj
3.1748 0 Td
(GH,)Tj
1.9842 0 Td
(Khorana)Tj
3.9331 0 Td
(AA,)Tj
1.8142 0 Td
(Falanga)Tj
3.7631 0 Td
(A,)Tj
1.1551 0 Td
(Clarke-Pears)Tj
5.7331 0 Td
(on)Tj
1.311 0 Td
(D,)Tj
1.2119 0 Td
(Flowers)Tj
3.6638 0 Td
(C,)Tj
1.2047 0 Td
(Jahanzeb)Tj
4.4788 0 Td
(M,)Tj
1.3181 0 Td
(et)Tj
1.0417 0 Td
(al.)Tj
1.2544 0 Td
(\(2007\))Tj
3.0543 0 Td
(American)Tj
-40.0963 -1.1835 Td
(Society)Tj
3.4441 0 Td
(of)Tj
1.0417 0 Td
(Clinical)Tj
3.3662 0 Td
(Oncology)Tj
4.3795 0 Td
(guideline:)Tj
4.4009 0 Td
(recommenda)Tj
5.7473 0 Td
(tions)Tj
2.296 0 Td
(for)Tj
1.3678 0 Td
(venous)Tj
3.3874 0 Td
(thromboe)Tj
4.1528 0 Td
(mbolism)Tj
3.8835 0 Td
(prophyl)Tj
3.2102 0 Td
(axis)Tj
1.9701 0 Td
(and)Tj
-42.6475 -1.1905 Td
(treatment)Tj
4.3795 0 Td
(in)Tj
0.978 0 Td
(patients)Tj
3.6567 0 Td
(with)Tj
1.9701 0 Td
(cancer.)Tj
3.4441 0 Td
(J)Tj
0.7158 0 Td
(Clin)Tj
1.8992 0 Td
(Oncol)Tj
3.0118 0 Td
(25:)Tj
1.5874 0 Td
(5490550)Tj
4.3583 0 Td
(5.)Tj
0.83 0.64 0.02 0 k
1.0418 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.1200/)Tj
4.6418 0 Td
(JCO.2007.1)Tj
5.2583 0 Td
(4.)Tj
-42.357 -1.1835 Td
(1283)Tj
0 g
2.4023 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(179680)Tj
3.267 0 Td
(19)Tj
0 g
/F2 1 Tf
-11.2606 -1.63 Td
(87.)Tj
/F0 1 Tf
2.622 0 Td
(Elwood)Tj
3.437 0 Td
(P,)Tj
1.1551 0 Td
(Longley)Tj
3.6567 0 Td
(M.)Tj
1.3182 0 Td
(\(2010\))Tj
3.0614 0 Td
(My)Tj
1.5378 0 Td
(health:)Tj
3.1607 0 Td
(whose)Tj
3.0614 0 Td
(responsibility)Tj
5.6622 0 Td
(?)Tj
0.7654 0 Td
(A)Tj
0.8788 0 Td
(jury)Tj
1.8 0 Td
(decides.)Tj
3.8764 0 Td
(J)Tj
0.7157 0 Td
(Epidem)Tj
3.3308 0 Td
(iol)Tj
1.1976 0 Td
(and)Tj
1.8567 0 Td
(Comm)Tj
-40.4719 -1.1834 Td
(Health)Tj
3.274 0 Td
(64:)Tj
1.5874 0 Td
(761764.)Tj
/F2 1 Tf
-7.4834 -1.6229 Td
(88.)Tj
/F0 1 Tf
2.622 0 Td
(Sokol)Tj
2.6787 0 Td
(DK.)Tj
1.8638 0 Td
(\(2015\))Tj
3.0544 0 Td
(Update)Tj
3.3874 0 Td
(on)Tj
1.311 0 Td
(the)Tj
1.5874 0 Td
(UK)Tj
1.5945 0 Td
(law)Tj
1.6867 0 Td
(on)Tj
1.311 0 Td
(consent.)Tj
3.9402 0 Td
(Brit)Tj
1.6937 0 Td
(Med)Tj
2.1402 0 Td
(J)Tj
0.9283 0 Td
(350:)Tj
2.1331 0 Td
(h1481.)Tj
0.83 0.64 0.02 0 k
3.2245 0 Td
(https://do)Tj
4.0464 0 Td
(i.org/10.1136)Tj
5.7332 0 Td
(/)Tj
-42.3145 -1.1905 Td
(bmj.h148)Tj
4.0394 0 Td
(1)Tj
0 g
0.7653 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(25779588)Tj
0 g
/F2 1 Tf
-10.396 -1.6229 Td
(89.)Tj
/F0 1 Tf
2.622 0 Td
(Smith)Tj
2.7283 0 Td
(SG,)Tj
1.9276 0 Td
(Foy)Tj
1.8567 0 Td
(R,)Tj
1.1976 0 Td
(McGowan)Tj
4.656 0 Td
(J,)Tj
0.9779 0 Td
(Kobayash)Tj
4.3725 0 Td
(i)Tj
0.4252 0 Td
(LC,)Tj
1.7433 0 Td
(Burn)Tj
2.2961 0 Td
(J.)Tj
0.978 0 Td
(\(2017\))Tj
3.0473 0 Td
(General)Tj
3.7063 0 Td
(practitioner)Tj
5.067 0 Td
(attitudes)Tj
3.926 0 Td
(towards)Tj
3.6567 0 Td
(pre-)Tj
-42.5625 -1.1905 Td
(scribing)Tj
3.5929 0 Td
(aspirin)Tj
3.104 0 Td
(to)Tj
1.0417 0 Td
(carriers)Tj
3.4937 0 Td
(of)Tj
1.0418 0 Td
(Lynch)Tj
2.8417 0 Td
(Syndrom)Tj
3.9402 0 Td
(e:)Tj
1.0417 0 Td
(findings)Tj
3.6001 0 Td
(from)Tj
2.1898 0 Td
(a)Tj
0.7653 0 Td
(national)Tj
3.6497 0 Td
(survey.)Tj
3.3945 0 Td
(Fam)Tj
2.1968 0 Td
(Cancer)Tj
3.3875 0 Td
(2017;)Tj
2.8984 0 Td
(16)Tj
-42.1798 -1.1835 Td
(\(4\):50951)Tj
4.748 0 Td
(6.)Tj
0.83 0.64 0.02 0 k
1.0418 0 Td
(https://do)Tj
4.0464 0 Td
(i.org/10.1007)Tj
5.7332 0 Td
(/s10689-)Tj
3.8197 0 Td
(017-9986-)Tj
4.4717 0 Td
(9)Tj
0 g
0.7653 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9693 0 Td
(28434157)Tj
0 g
/F2 1 Tf
-30.2174 -1.63 Td
(90.)Tj
/F0 1 Tf
2.622 0 Td
(Kassirer)Tj
3.8268 0 Td
(JP.)Tj
1.6441 0 Td
(\(1994\))Tj
3.0614 0 Td
(Incorpor)Tj
3.6 0 Td
(ating)Tj
2.3457 0 Td
(patients')Tj
3.8693 0 Td
(preferences)Tj
5.4143 0 Td
(into)Tj
1.8 0 Td
(medical)Tj
3.6 0 Td
(decisions.)Tj
4.578 0 Td
(N)Tj
0.9354 0 Td
(Engl)Tj
2.1827 0 Td
(J)Tj
0.7158 0 Td
(Med)Tj
2.3527 0 Td
(330:)Tj
-39.9262 -1.1834 Td
(18956.)Tj
0.83 0.64 0.02 0 k
3.7701 0 Td
(https://)Tj
2.9551 0 Td
(doi.org/10.10)Tj
5.7331 0 Td
(56/NEJM)Tj
4.0536 0 Td
(19940630330)Tj
6.0024 0 Td
(2611)Tj
0 g
2.4024 0 Td
(PMID:)Tj
0.83 0.64 0.02 0 k
2.9622 0 Td
(8196734)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I1 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 239.4708 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Systematic)Tj
5.0457 0 Td
(review)Tj
3.0543 0 Td
(update)Tj
3.2244 0 Td
(of)Tj
1.0347 0 Td
(observation)Tj
5.0741 0 Td
(al)Tj
0.985 0 Td
(studies)Tj
3.3307 0 Td
(further)Tj
3.0615 0 Td
(supports)Tj
3.9898 0 Td
(aspirin)Tj
3.1039 0 Td
(role)Tj
1.8497 0 Td
(in)Tj
0.9779 0 Td
(cancer)Tj
3.1678 0 Td
(treatment)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.02039)Tj
4.089 0 Td
(57)Tj
0 g
2.0906 0 Td
(September)Tj
5.0386 0 Td
(25,)Tj
1.5874 0 Td
(2018)Tj
31.7412 0 Td
(17)Tj
1.304 0 Td
(/)Tj
ET
endstream
endobj
893 0 obj
<>stream
endstream
endobj
894 0 obj
<>stream
endstream
endobj
895 0 obj
<>stream
endstream
endobj
896 0 obj
<>stream
endstream
endobj
897 0 obj
<>stream
endstream
endobj
898 0 obj
<>stream
endstream
endobj
899 0 obj
<>stream
endstream
endobj
900 0 obj
<>stream
endstream
endobj
901 0 obj
<>stream
endstream
endobj
902 0 obj
<>stream
endstream
endobj
903 0 obj
<>stream
endstream
endobj
904 0 obj
<>stream
endstream
endobj
905 0 obj
<>stream
endstream
endobj
906 0 obj
<>stream
endstream
endobj
907 0 obj
<>stream
BT
66.402 0 Td
(17)Tj
ET
Q
endstream
endobj
9 0 obj
<>
endobj
908 0 obj
<>
endobj
911 0 obj
<>stream
MinionPro-It 9 `ab]+
W W X ' - 3 > H N T Z ` j q t { +2=CIU[cnz~
"(.9CIOU[elov|&-8>DPV^iuy &+/49@DGLPU[]_ahjmru|
&-4;BIPW^elsz
")07>ELSZahov} %,3:AHOV]dkry#/;JTey ! ( / 6 = D K R Y ` g n u |
$
+
2
9
@
G
N
U
\
c
j
q
x
'.5<CJQX_fmt{ #*18?FMT[bkry
"
)
0
7
>
E
J
O
W
d
q
v
$+29@GNU\cjqx '.5<CJQX_fmt{ #*18?FMT[bipw~
&-4;BIPW^elsz !(/6=DOVcpuz-B\v$<Tdy*5@Tanz!2>O_fmt{ #*18?FMT[bipw~(4@LZk{ "3EU_px!-?IUas $6BN\m
-:EQ]n}
%.7@IR[dmv!*3<ENW`ir{&/8AJS\enw ! * 3 < E N W ` i r { !!
!""commaaccentAbreveAmacronAogonekAEacuteCacuteCcaronCcircumflexCdotaccentDcaronDcroatEbreveEcaronEdotaccentEmacronEngEogonekGbreveGcircumflexGcommaaccentGdotaccentHbarHcircumflexIbreveIJImacronIogonekItildeJcircumflexKcommaaccentLacuteLcaronLcommaaccentLdotNacuteNcaronNcommaaccentObreveOhungarumlautOmacronOslashacuteRacuteRcaronRcommaaccentSacuteScedillaScircumflexScommaaccentTbarTcaronTcommaaccentUbreveUhungarumlautUmacronUogonekUringUtildeWacuteWcircumflexWdieresisWgraveYcircumflexYgraveZacuteZdotaccentIdotaccentabreveamacronaogonekaeacutecacuteccaronccircumflexcdotaccentdcarondcroatebreveecaronedotaccentemacronengeogonekgbrevegcircumflexgcommaaccentgdotaccenthbarhcircumflexibreveijimacroniogonekitildejcircumflexkcommaaccentlacutelcaronlcommaaccentldotnacutencaronncommaaccentobreveohungarumlautomacronoslashacuteracutercaronrcommaaccentsacutescedillascircumflexscommaaccenttbartcarontcommaaccentubreveuhungarumlautumacronuogonekuringutildewacutewcircumflexwdieresiswgraveycircumflexygravezacutezdotaccentkgreenlandiclongsnapostrophetonosdieresistonosAlphaBetaGammaDeltaEpsilonZetaEtaThetaIotaKappaLambdaMuNuXiOmicronPiRhoSigmaTauUpsilonPhiChiPsiOmegaAlphatonosEpsilontonosEtatonosIotatonosIotadieresisOmicrontonosUpsilontonosUpsilondieresisOmegatonosuni1FBBuni1F09uni1F0Duni1F0Buni1F0Funi1FB8uni1FBAuni1FBCuni1F89uni1F8Duni1F8Buni1F8Funi1F88uni1F8Cuni1F8Auni1F8Euni1F08uni1F0Cuni1F0Auni1F0Euni1FB9uni1FC9uni1F19uni1F1Duni1F1Buni1FC8uni1F18uni1F1Cuni1F1Auni1FCBuni1F29uni1F2Duni1F2Buni1F2Funi1FCAuni1FCCuni1F99uni1F9Duni1F9Buni1F9Funi1F98uni1F9Cuni1F9Auni1F9Euni1F28uni1F2Cuni1F2Auni1F2Euni1FDBuni1F39uni1F3Duni1F3Buni1F3Funi1FD8uni1FDAuni1F38uni1F3Cuni1F3Auni1F3Euni1FD9uni1FFBuni1F69uni1F6Duni1F6Buni1F6Funi1FFAuni1FFCuni1FA9uni1FADuni1FABuni1FAFuni1FA8uni1FACuni1FAAuni1FAEuni1F68uni1F6Cuni1F6Auni1F6Euni1FF9uni1F49uni1F4Duni1F4Buni1FF8uni1F48uni1F4Cuni1F4Auni1FECuni1FEBuni1F59uni1F5Duni1F5Buni1F5Funi1FE8uni1FEAuni1FE9alphabetagammadeltaepsilonzetaetathetaiotakappalambdanuxiomicronpirhosigmatauupsilonphichipsiomegaalphatonosepsilontonosetatonosiotatonosiotadieresisomicrontonosupsilontonosupsilondieresisomegatonosiotadieresistonosupsilondieresistonosuni03C2uni0374uni0375uni037Euni03D0uni03DAuni03DEuni03E0uni03F0uni1FBDuni1FBEuni1FC1uni1FCDuni1FCEuni1FCFuni1FDDuni1FDEuni1FDFuni1FEDuni1FEEuni1FFEuni1F00uni1F01uni1F02uni1F03uni1F04uni1F05uni1F06uni1F07uni1F10uni1F11uni1F12uni1F13uni1F14uni1F15uni1F20uni1F21uni1F22uni1F23uni1F24uni1F25uni1F26uni1F27uni1F30uni1F31uni1F32uni1F33uni1F34uni1F35uni1F36uni1F37uni1F40uni1F41uni1F42uni1F43uni1F44uni1F45uni1F50uni1F51uni1F52uni1F53uni1F54uni1F55uni1F56uni1F57uni1F60uni1F61uni1F62uni1F63uni1F64uni1F65uni1F66uni1F67uni1F70uni1F71uni1F72uni1F73uni1F74uni1F75uni1F76uni1F77uni1F78uni1F79uni1F7Auni1F7Buni1F7Cuni1F7Duni1F80uni1F81uni1F82uni1F83uni1F84uni1F85uni1F86uni1F87uni1F90uni1F91uni1F92uni1F93uni1F94uni1F95uni1F96uni1F97uni1FA0uni1FA1uni1FA2uni1FA3uni1FA4uni1FA5uni1FA6uni1FA7uni1FB0uni1FB1uni1FB2uni1FB3uni1FB6uni1FB7uni1FC2uni1FC3uni1FC4uni1FC6uni1FC7uni1FD0uni1FD1uni1FD2uni1FD3uni1FD6uni1FD7uni1FE0uni1FE1uni1FE2uni1FE3uni1FE4uni1FE5uni1FE6uni1FF2uni1FF3uni1FF4uni1FF6uni1FF7uni1FB4uni1FE7uniEFD5anoteleiauni03D1uni03D5uni03D6franclirapesetaEuroafii61289estimatedpartialdiffproductsummationuni2219radicalinfinityintegralapproxequalnotequallessequalgreaterequallozengeuni02C9uniEFEDuniEFEEuniEFF1uniEFF2uniEFF3uniEFF5uniEFF7AcuteCaronDieresisDieresisAcuteDieresisGraveGraveHungarumlautMacroncyrBrevecyrFlexdblGravecyrbrevecyrflexdblgravedieresisacutedieresisgraveuniF635uniF637uniF638uniF639uniF6DCuniF63AuniF63BuniF63CuniF63DuniF63EuniF63FuniF640uniF641uniF642uniF628uniF643uniF644uniF645uniF646uniF647uniF648uniF649uniF64AuniF64BuniF64CuniF64DuniF64EuniF64FuniF650uniF651uniF652uniF653uniF654uniF655uniF656uniF657uniF658uniF659uniF65AuniF65BuniF65CuniF65DuniF65EuniF65FuniF660uniF629uniF62AuniF62BuniF62CuniF62DuniF661uniF662uniF663uniF664uniF665uniF666uniF667uniF668uniF669uniF66AuniF66BuniF66CuniF62EuniF62FuniF630uniF631uniF632uniF66DuniF66EuniF66FuniF670uniF671uniF672uniF673uniF674uniF675uniF676uniF677uniF678uniF679uniF67AuniF67BuniF67CuniF67DuniF67EuniF67FuniF680uniF681uniF682uniF683uniF684uniF685uniF686uniF687uniF688uniF689uniF68AuniF68BuniF68CuniF68DuniF68EuniF68FuniF690uniF691uniF692uniF693uniF694uniF695uniF696uniF697uniF698uniF699uniF69AuniF69BuniF69CuniF69DuniF69EuniF69FuniF6A0uniF6A1uniF6A2uniF6A3uniF6A4uniF6A5uniF6A6uniF6A7uniF6A8uniF6A9uniF6AAuniF6ABuniF6ACuniF6ADuniF6AEuniF6AFuniF6B0uniF6B1uniF6B2uniF6B3uniF6B4uniF6B5uniF6B6uniF6B7uniF6B8uniF6B9uniF6BAuniF6BBuniF6BCuniF6BDuniF633c_hc_kc_tf_bf_f_bf_f_hf_f_kf_f_tf_hf_jf_f_jf_kf_ts_puniFB06T_hlongs_blongs_hlongs_ilongs_klongs_llongs_longsuniFB05longs_longs_ilongs_longs_la.ende.endm.endn.endr.endK.altR.altk.altcaron.altcommaaccent.altpeseta.altAlphaiotasub.altAlphaiotasubasper.altAlphaiotasubasperacute.altAlphaiotasubaspergrave.altAlphaiotasubaspertilde.altAlphaiotasublenis.altAlphaiotasublenisacute.altAlphaiotasublenisgrave.altAlphaiotasublenistilde.altEtaiotasub.altEtaiotasubasper.altEtaiotasubasperacute.altEtaiotasubaspergrave.altEtaiotasubaspertilde.altEtaiotasublenis.altEtaiotasublenisacute.altEtaiotasublenisgrave.altEtaiotasublenistilde.altOmegaiotasub.altOmegaiotasubasper.altOmegaiotasubasperacute.altOmegaiotasubaspergrave.altOmegaiotasubaspertilde.altOmegaiotasublenis.altOmegaiotasublenisacute.altOmegaiotasublenisgrave.altOmegaiotasublenistilde.altEuro.fittedcent.fittedcolonmonetary.fitteddollar.fittedflorin.fittedfranc.fittedlira.fittednumbersign.fittedsterling.fittedyen.fittedEuro.oldstylecolonmonetary.oldstyleestimated.oldstyleflorin.oldstylefranc.oldstylelira.oldstylenumbersign.oldstylesterling.oldstyleyen.oldstylefranc.taboldstylelira.taboldstyleorn.001orn.002orn.003orn.004orn.005orn.006orn.007orn.008orn.009orn.010orn.011orn.012orn.013orn.014orn.015orn.016orn.017orn.018orn.019orn.020orn.021orn.022orn.023A.swashB.swashC.swashD.swashE.swashF.swashG.swashH.swashI.swashJ.swashK.swashL.swashM.swashN.swashO.swashP.swashQ.swashR.swashS.swashT.swashU.swashV.swashW.swashX.swashY.swashZ.swashT_h.swashAacute.swashAbreve.swashAcircumflex.swashAdieresis.swashAgrave.swashAmacron.swashAogonek.swashAring.swashAtilde.swashCacute.swashCcaron.swashCcedilla.swashCcircumflex.swashCdotaccent.swashDcaron.swashDcroat.swashEacute.swashEbreve.swashEcaron.swashEcircumflex.swashEdieresis.swashEdotaccent.swashEgrave.swashEmacron.swashEng.swashEogonek.swashGbreve.swashGcircumflex.swashGcommaaccent.swashGdotaccent.swashHbar.swashHcircumflex.swashIJ.swashIacute.swashIbreve.swashIcircumflex.swashIdieresis.swashIdotaccent.swashIgrave.swashImacron.swashIogonek.swashItilde.swashJcircumflex.swashKcommaaccent.swashLacute.swashLcaron.swashLcommaaccent.swashLdot.swashNacute.swashNcaron.swashNcommaaccent.swashNtilde.swashOacute.swashObreve.swashOcircumflex.swashOdieresis.swashOgrave.swashOhungarumlaut.swashOmacron.swashOslash.swashOslashacute.swashOtilde.swashRacute.swashRcaron.swashRcommaaccent.swashSacute.swashScaron.swashScedilla.swashScircumflex.swashScommaaccent.swashTbar.swashTcaron.swashTcommaaccent.swashT_h.caronswashT_h.commaaccentswashUacute.swashUbreve.swashUcircumflex.swashUdieresis.swashUgrave.swashUhungarumlaut.swashUmacron.swashUogonek.swashUring.swashUtilde.swashWacute.swashWcircumflex.swashWdieresis.swashWgrave.swashYacute.swashYcircumflex.swashYdieresis.swashYgrave.swashZacute.swashZcaron.swashZdotaccent.swashafii10056T_h.caronT_h.commaaccentafii10048afii10074afii10075afii10082afii10192afii10062afii10194afii10193afii10102afii10071afii10041afii10076afii10085afii10103afii10051afii10039afii10037afii10079afii10061afii10059afii10047afii10067afii10049afii10148afii10033afii10094afii10080afii10022afii10145afii10063afii10027afii10070afii10054afii10109afii10036afii10065afii10055afii10068afii10086afii10064afii10096afii10050afii10146afii10077afii10097afii10069afii10107afii10101afii10043afii10078afii10024afii10073afii10089afii10092afii10147afii10087afii10081afii10029afii10083afii10026afii10019afii10032afii10046afii10072afii10021afii10030afii10098afii10038afii10017afii10040afii10042afii10105afii10052afii10057afii10025afii10034afii10053afii10832afii10058afii10018afii10044afii10110afii10020afii10095Rholenisafii10104afii10106afii10090afii10091afii10060afii10028afii10045afii10099afii10066afii10084afii10031afii10196afii10035afii10088afii10093Eth.swashafii10100uni0394afii10023afii10195uni2215uni021Aafii10108uni03BCuni00ADuni00A0uni03A9uni021Bafii10846afii61352afii10831Copyright 2000 Adobe Systems Incorporated. All Rights Reserved. U.S. Patents Des. 338,907 and 371,799.Minion is either a registered trademark or a trademark of Adobe Systems Incorporated in the United States and/or other countries.Minion Pro ItalicMinion Proq N s ^mTw6zgjTRC @ q
C
d
m
r$7
,
Q
c
!*D )d Gcw~!;FJ3%3@FP8ir3y1S_ju(/6:n . 9 C v !!/!5!`!h!!!!!"""@"g"t"|""""###W#\#h#n#v######$$ $&$,$3$:$K$U$r$$$$$$$$$% %%%5%D%]%h%o%v%%%%%%%%%%%& &&,&9&C&J&P&U&j&&&&&&&&&&&''''#'(':'L'Q'\'a'g'x'''''''''(((%(/(7(>(E(L([(j(w(~((((((((((((((())))!).)9)D)K)R)Y)`)f)k)o)t))))))))))))))**
****%*0*;*F*Q*\*g*r*}*****-
oFl\8Mgk^?ŜeQ[a`FpUI߹|{{|VsrocghpzvL##4/Jcݹ+!MWagpu
|;;.|;9hꖧovgtfstqon@Sm|}ĬD⋄DQnJs8*Tlb~wg8`F(;@§ŰY9kde:S!VtVl-ܲq
m
ބ}A98}@=
^98ԏڒ,`fhMhx{r/S#Qݟ9ʞJ+^VT\]xZ]Rmh
dn$d_JoDO(q
zm
ӇbjVy-}EVeF4)AKڑף
ڄ|>[tA_d}ʟɩ藿ΎwC{LZnXH;slz`Z?; :\o"T÷ķT`ź_j{xR{YvPwUBy
|s^`_ZNu[XUoaN{;iV`VsjaK]<_IZF"v,
b|bw`tgigxumjbisˎA{lW_ïknruxutnivry?y>x? rxǼiwi4wxηŻ6xyppvTyJyQ,|;7
^1؟svmdؓd
upՆ]oXy.]#m
vu|YWx.^h~_tWpy^Fy_pp͆SVQL
owÐˑ_Dm
{qtg`O_Rxo|TpgC]cwxz8REpzD掚˴k[uqlchkmXfjevrkpocjfq~z~|zhfsPfnwr
Wym{qhlb\2\)FWy:y1er}yo;ڕԑZhĚڰW-Änj~sypkWkuo_8lewߢۂ|ogYQZktY00=ZH<4 Eu{tzy{|wB/`J
aoAh{1~Ug^YoG=E)?XEݻd9N9&)^:<>