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[(Neu)14.7(robo)18.3(t)-319.7(too)16.4(l)-319.7(\()4.2(ht)15.9(tps)15.2(://)14.7(neu)18(robo)18.3(t)15.4(.in)13(cf)14.9(.or)20.7(g/\))13.8(.)-319.1(Rel)15.6(eas)14.4(e)-324.4(1)0(.)16.5(1)-322(of)-311.5(the)-314.8(dat)20.3(a-)]TJ
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[(base)-200.1(was)-201.5(us)12.4(ed)-203.8(\(se)14.2(e)-210.6(Sup)15.5(ple)14(men)14.5(ta)13.5(ry)-204(Tex)11.9(t)-212.2(for)-199.8(det)20.3(ails)15.6(\).)-201(Bas)12.1(ic)-207.8(su)12.4(mm)12.9(ary)]TJ
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[(sta)12.8(tis)17.5(tic)16.3(s)-278.9(for)-263(po)13.6(pul)16.4(ati)16.3(on)-270.9(cha)15.6(rac)13(te)13.5(ris)12.6(tic)16.3(s)-272.6(are)-265.2(list)20.3(ed)-273.3(in)-268.6(Ta)11.4(ble)-264.2(1.)]TJ
1.1128 -1.1128 TD
[(We)-313.2(decided)-311.4(to)-312.9(use)-305.6(only)-311.9(those)-315(GOSe)-309.2(observations)-315.5(obtained)-306.2(be-)]TJ
-1.1128 -1.1065 TD
[(tween)-401.7(injury)-399.7(and)-399.3(18)-397.4(months)-397.8(post-injury,)-395.4(because)-405.8(extremely)-396.4(late)]TJ
0 -1.1128 TD
[(follow-ups)-259.5(were)-255.4(considered)-263.1(uninformative)-253.2(for)-256.7(the)-257.9(index)-256.9(follow-up)]TJ
T*
[(time)-201.7(point)-201.6(of)-197.6(6)-201.8(months)-195.5(post-injury.)-199.4(This)-205.4(led)-194.7(to)-205.4(a)-197.9(total)-201.7(of)-197.6(8185)-200.4(GOSe)]TJ
T*
[(observations)-347.1(of)-349.4(the)-340.1(study)-350.5(population)-344.7(being)-345.4(available)-346.1(for)-345.2(the)-346.4(ana-)]TJ
0 -1.1065 TD
[(lyses.)-281.2(For)-277.9(1151)-276.3(\(34%\))-276.8(individuals,)-276.5(GOSe)-277.5(observations)-283.9(at)-277.3(180)]TJ
/F6 1 Tf
24.9502 0 TD
()Tj
/F4 1 Tf
.7208 0 TD
(14)Tj
-25.671 -1.1128 TD
[(days)-311.5(post-)-302.6(injury)-311.2(were)-306(available,)-311.1(and)-304.5(2394)-307.9(\(72%\))-308.4(individuals)-305.2(had)]TJ
T*
[(GOSe)-245.9(observations)-239.6(within)-246.4(the)-238.9(per-protocol)-242.5(window)-241.6(of)-241.9(58)-238.8(months)]TJ
T*
[(post-injury.)-439.6(The)-437(distribution)-435.3(of)-437.9(GOSe)-435.6(sampling)-434.9(times)-436.4(and)-437.2(both)]TJ
0 -1.1065 TD
[(absolute)-206.2(and)-197(relative)-201.4(frequencies)-204.4(of)-197.6(the)-201(respective)-200(GOSe)-201.7(categories)]TJ
0 -1.1128 TD
[(are)-410.6(shown)-400.4(in)-407.7(Figure)-403(1.)-400.8(True)-407.6(observation)-403.3(times)-404.8(were)-407.1(mapped)-403.8(to)]TJ
T*
[(categories)-313.8(by)-302.5(rounding)-306.2(to)-306.5(the)-308.5(closest)-309(time)-302.9(point;)-306.3(for)-307.2(example,)-311.5(the)]TJ
T*
[()54.8()0(6)-324.1(months)55.3()-324.6(category)-326.1(contains)-326.3(observations)-328.1(up)-321.5(to)-319.2(9)-328.3(months)-322(post-)]TJ
0 -1.1065 TD
[(injury.)-427.9(Thus,)-425.6(the)-422.3(gures)-425.5(include)-426.8(a)-425.6(small)-430(proportion)-419.4(of)-425.3(GOSe)-429.3(1)]TJ
0 -1.1128 TD
[(representing)-199.2(patients)-197.5(who)-197.8(died)-194.2(between)-200.8(6)-195.5(and)-190.6(9)-195.5(months)-195.5(post-injury.)]TJ
/F9 1 Tf
0 -2.7315 TD
[(Imputation)-334.8(methods)]TJ
/F4 1 Tf
1.1128 -1.7514 TD
[(We)-496.6(compared)-496.3(LOCF)-497.7(to)-496.2(a)-495.1(MICE)-492.7(panel)-499.6(regression)-498.4(approach)]TJ
-1.1128 -1.1128 TD
[(\(multiple)-216.3(imputation)-219.5([MI]\),)-213.9(an)-216.4(MM,)-212(a)-216.9(G)0(P)-215.9(regression,)-216.8(and)-209.6(an)-216.4(MSM.)]TJ
0 -1.1065 TD
[(For)-284.3(all)-287.2(model-based)-285.1(approaches)-286.8(we)-289.3(additionally)-284.6(explored)-285.8(variants)]TJ
0 -1.1128 TD
[(including)-212.4(the)-207.3(key)-209.6(IMPACT)]TJ
/F6 1 Tf
11.2421 0 TD
(=)Tj
/F4 1 Tf
.7208 0 TD
[(2)-208.2(predictors)-210.4(as)-211.3(covariates.)]TJ
6.7246 0 0 5.9768 512.5605 360.7936 Tm
(7)Tj
8.9663 0 0 8.9663 517.8329 356.8251 Tm
[(These)-212.1(are)]TJ
-22.8384 -1.1128 TD
[(age,)-189.7(Glasgow)-187.9(Coma)-179.4(Scale)-190.8(\(GCS\))-186.4(motor)-184.8(score,)-186.1(pupil)-182.6(reactivity)-185.5(\(0,)-181.6(1,)]TJ
T*
[(2\),)-447.1(hypoxia,)-442.2(hypotension,)-439.2(Marshall)-443.4(computed)-444.8(tomography)-444(\(CT\))]TJ
0 -1.1065 TD
[(classication,)-491.2(traumatic)-488.9(subarachnoid)-483.4(hemorrhage,)-488.2(epidural)-485.8(he-)]TJ
0 -1.1128 TD
[(matoma,)-287.8(glucose,)-281.4(and)-279.2(hemoglobin.)]TJ
/F9 1 Tf
0 -2.7315 TD
(LOCF)Tj
/F4 1 Tf
1.1128 -1.7515 TD
[(Because)-353.6(LOCF)-345.9(is)-345.7(widely)-352.3(used)-349.4(to)-344.5(impute)-346.2(missing)-352(outcomes)-344.8(in)]TJ
-1.1128 -1.1128 TD
[(TBI)-302.8(studies,)]TJ
6.7246 0 0 5.9768 357.4487 270.822 Tm
(6,7,9)Tj
8.9663 0 0 8.9663 373.6062 266.7968 Tm
[(it)-297.9(served)-302.9(as)-299.8(the)-302.1(comparator)-299.7(method.)-300.8(Here,)-302.6(LOCF)]TJ
-6.7529 -1.1065 TD
[(was)-391.1(dened)-379.9(as)-388.3(the)-384.3(last)-382.7(GOSe)-385(observation)-390.7(before)-380.2(the)-384.3(imputation)]TJ
0 -1.1128 TD
[(time)-397.7(point)-391.3(of)-393.6(180)-396.9(days)-393.7(post-injury.)-395.4(LOCF)-390.2(is)-396.2(not)-394.6(a)-393.9(model-based)]TJ
T*
[(method)-278.9(and,)-282.1(by)-277.2(denition,)-277.2(only)-280.3(permits)-279.9(the)-276.9(imputation)-276.4(of)-279.8(a)-280.1(GOSe)]TJ
T*
[(value)-227.7(for)-231.4(subjects)-226.3(for)-225(whom)-226.2(at)-226.8(least)-226.6(one)-228.6(value)-227.7(was)-226.7(available)-232.3(within)]TJ
0 -1.1065 TD
[(the)-485.5(rst)-485(180)-485.4(days)-482.2(post-)-485.9(injury.)-484.9(We)-483.9(accounted)-483.5(for)-484.3(this)-487.8(lack)-481.1(of)]TJ
0 -1.1128 TD
[(complete)-425.9(coverage)-419.4(under)-419.9(LOCF)-421.8(by)-416.3(performing)-423.9(all)-420(performance)]TJ
T*
[(comparisons)-258.6(including)-256.7(LOCF)-257.4(only)-255(on)-258.3(the)-251.6(subset)-258.8(of)-254.5(individuals)-260.9(for)]TJ
0 -1.1065 TD
[(whom)-283.1(a)-280.1(LOCF-imputed)-282.7(value)-284.6(could)-282.2(be)-279.6(obtained.)]TJ
/F9 1 Tf
0 -2.7378 TD
[(Model-based)-334.7(methods)]TJ
/F4 1 Tf
1.1128 -1.7451 TD
[(Model-based)-358.2(imputation)-352.3(approaches)-356.3(offer)-349.2(richer)-358.9(output)-352.9(\(prob-)]TJ
-1.1128 -1.1128 TD
[(abilistic)-540.2(imputation,)-538.6(multiple)-536.6(imputation\))-537.8(and)-538.4(may)-535.6(reduce)-544.4(the)]TJ
T*
[(LOCF-inherent)-207.9(bias.)-210.9(We)-199.4(compared)-211.8(the)-201(performance)-211.7(of)-204(four)-199.3(model-)]TJ
T*
[(based)-281.8(approaches)-286.8(with)-281.3(that)-280.4(of)-279.8(LOCF.)]TJ
1.1128 -1.1065 TD
[(Th)20.1(e)-197.9(M)0(I)16.6(C)14.7(E)-201.7(r)0(e)21.2(g)0(r)17.3(e)0(s)22.7(s)0(i)21.1(o)13.1(n)-201.8(a)0(p)23.9(p)13.1(ro)17.3(ac)21.4(h)-201.8(\()-71.7(M)12.4(I)0(\))-187.6(i)0(s)-193.9(a)-197.9(st)21.1(an)17.5(d)13.1(a)0(r)21.3(d)-201.8(ap)23.8(p)13.1(r)0(o)17.3(a)0(c)21.4(h)-201.8(t)15.4(o)-201.8(M)12.4(I)]TJ
-1.1128 -1.1128 TD
[(th)15.9(at)-353.2(d)13.1(e)0()18.9(n)13.1(es)-350.4(re)21.2(gr)17.3(es)22.7(si)21.1(o)13.1(n)-366.2(mo)22.7(d)13.1(e)0(l)19.8(s)-361.1(fo)17.3(r)-362.5(e)0(a)21.4(c)0(h)-355.5(m)15.9(is)21.1(si)21.1(ng)-353.1(va)17.5(ri)26(ab)17.5(l)15.4(e)-368.7(i)15.4(n)-366.2(a)-362.3(m)0(a)20.3(-)]TJ
T*
[(tr)19.6(ix)22.2(.)]TJ
6.7246 0 0 5.9768 327.3448 91.1621 Tm
(17)Tj
8.9663 0 0 8.9663 336.6424 87.137 Tm
[(B)14.7(y)-296.7(it)18.2(er)21.2(at)19.8(i)15.4(n)0(g)-283.6(o)0(v)19.9(e)0(r)-288.6(e)0(a)21.4(c)0(h)-286(v)13.1(ar)21.2(ia)19.8(b)13.1(l)0(e)-283.7(t)0(h)22.3(a)0(t)-290(c)0(o)23.9(n)13.1(ta)19.8(in)22.2(s)-297.9(m)0(i)18.7(s)0(s)23.9(i)0(n)22.3(g)-296.7(v)13.1(a)0(l)19.8(u)13.1(es)22.7(,)]TJ
-2.6303 -1.1065 TD
[(an)17.5(d)-372.6(r)0(e)21.2(s)0(a)22.7(m)0(p)22.7(l)0(i)24.5(n)0(g)-365.8(m)15.9(is)21.1(si)21.1(n)13.1(g)-372.6(va)17.5(l)15.4(u)0(e)17.5(s)-367.4(fr)21.1(om)-363(th)22.2(e)-375(c)0(o)23.8(r)0(r)21.1(e)0(s)22.7(p)13.1(on)20(d)13.1(i)0(n)22.2(g)-372.6(re)21.2(g)13.1(r)0(e)14.9(s)0(s)23.9(i)0(o)22.2(n)]TJ
0 -1.1128 TD
[(mo)16.4(d)13.1(e)0(l)-416.5(w)0(h)23(i)0(l)24.6(e)-431.9(h)13.1(o)13.1(l)0(d)22.3(i)0(n)22.2(g)-429.5(al)19.8(l)-427.2(o)13.1(th)22.3(er)-415(v)13.1(a)0(r)21.2(i)0(a)19.8(b)0(l)22.3(e)0(s)-419.9()14.6(xe)17.5(d)13.1(,)-426.5(a)-425.6(s)0(t)21.1(e)0(a)21.4(d)0(y)19.9(-)0(s)22.5(t)0(a)19.8(t)0(e)-416.5(c)0(a)21.4(n)]TJ
T*
[(ul)15.9(t)15.4(i)0(m)18.7(a)0(t)19.8(e)0(l)26.2(y)-549.6(b)13.1(e)-552(re)21.3(ac)21.4(h)13.1(e)0(d)23.8(,)-553(an)23.9(d)-543.3(a)-552(se)22.7(t)-547.3(o)13.1(f)-552.2(i)15.4(mp)22.7(ut)15.9(ed)-532.6(d)13.1(a)0(t)19.8(a)-552(se)22.7(ts)-535.4(ca)21.4(n)-549.6(b)13.1(e)]TJ
/F3 1 Tf
-27.9978 77.2217 TD
(456)Tj
45.3479 0 TD
[(KUNZMANN)-334(ET)-338.7(AL.)]TJ
ET
endstream
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BT
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8.9663 0 0 8.9663 59.7543 256.592 Tm
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0 Tc
0 Tw
[(ge)17.5(n)13.1(e)0(r)21.2(a)0(t)19.8(e)0(d)23.9(.)-230.5(B)14.7(e)0(c)15.1(a)0(u)23.9(s)0(e)-217.6(o)13.1(ur)-216.6(go)19.9(al)-220.4(i)15.4(s)-228.3(si)21.1(n)13.1(g)0(l)22.2(e)-229.6(im)18.7(p)13.1(u)13.1(t)0(a)19.8(t)0(i)18.2(o)13.1(n)13.1(,)-230.5(we)-213.4(re)14.9(d)13.1(u)13.1(c)0(e)21.4(d)-227.1(th)22.2(e)-229.5(s)0(e)22.7(t)]TJ
0 -1.1128 TD
[(of)-425.3(im)25(pu)19.9(te)19.8(d)-429.5(v)0(a)17.5(l)0(u)22.2(e)0(s)-419.9(t)0(o)-426.7(a)-431.9(p)13.1(r)0(e)14.9(d)13.1(ic)19.8(t)15.4(i)0(o)22.2(n)-435.8(b)13.1(y)-435.8(ta)19.8(k)13.1(i)0(n)22.2(g)-435.8(t)15.4(h)0(e)-425.1(m)0(o)22.7(s)0(t)-421.5(f)0(r)21.1(e)0(q)17.5(u)13.1(en)23.9(tl)18.2(y)]TJ
T*
[(im)18.7(p)13.1(u)0(t)22.2(e)0(d)-425.1(G)16.2(OS)18.1(e)-431.9(v)13.1(al)19.8(u)13.1(e)0(.)-422.2(T)0(h)20.1(e)-431.9(fr)21.1(eq)23.9(ue)17.5(n)13.1(c)0(y)-418.8(d)0(i)22.2(s)0(t)21.1(r)0(i)19.6(b)13.1(ut)22.2(io)22.3(n)-435.8(o)13.1(f)-432.1(t)0(h)22.3(e)-431.9(im)25(pu)19.9(te)19.8(d)]TJ
0 -1.1065 TD
[(GO)19.7(Se)-177.1(v)13.1(a)0(l)19.8(u)13.1(es)-179.7(ca)21.4(n)-182.9(b)0(e)-178.5(u)13.1(se)16.3(d)-182.9(a)0(s)-173.3(p)0(r)17.3(o)13.1(b)13.1(a)0(b)17.5(i)15.4(li)18.2(st)21.1(ic)-176.2(p)13.1(r)0(e)21.2(d)13.1(ic)19.8(ti)18.2(o)13.1(n)-182.9(in)-180.1(v)13.1(e)0(r)21.2(y)-182.9(mu)16.4(ch)-172.2(th)22.2(e)]TJ
0 -1.1128 TD
[(sa)16.3(m)15.9(e)-242.2(wa)20.5(y)-239.8(a)0(s)-230.3(t)15.4(he)-229.1(pr)17.3(o)13.1(b)13.1(a)0(b)17.5(i)15.4(li)18.2(st)21.1(i)15.4(c)-242.2(o)13.1(u)0(t)22.3(p)0(u)19.9(t)-237.5(of)-229.2(o)13.1(t)0(h)22.2(e)0(r)-231.7(m)0(o)22.7(d)13.1(el)19.8(-b)23.7(as)16.3(ed)-229.1(m)15.9(e)0(t)19.8(h)0(o)19.9(d)13.1(s.)]TJ
T*
[(To)-245.4(in)22.2(co)17.5(rp)23.7(o)13.1(r)0(a)21.2(t)0(e)-252.1(t)15.4(he)-248(lo)22.2(n)13.1(g)0(i)22.2(t)0(u)22.2(d)0(i)22.2(n)0(a)17.5(l)-256.4(as)22.7(p)13.1(e)0(c)21.4(t)-262.8(o)13.1(f)-255(GO)19.7(S)14.6(e)0(,)-251.4(w)16.2(e)-261.2(j)0(o)22.2(i)0(n)22.2(t)0(l)24.6(y)-258.8(im)25(pu)19.9(te)19.8(d)]TJ
T*
[(GO)19.7(Se)-259.3(at)-258.4(2)-271.4(w)0(e)20.5(e)0(k)17.5(s)0(,)-256.5(3)-271.4(mo)22.7(n)13.1(t)0(h)22.2(s)0(,)-262.9(6)-265.1(mo)22.7(nt)22.2(hs)18.8(,)-268.5(a)0(n)17.5(d)-265.1(12)-258.3(mo)22.7(nt)22.2(hs)-259.4(jo)22.3(in)22.2(tl)18.2(y)13.1(.)-268.5(Th)20.1(is)]TJ
0 -1.1065 TD
[(me)20.3(an)17.5(s)-323.2(t)0(h)22.2(a)0(t)-315.3(t)0(h)22.2(e)-330.7(GO)26(Se)-316.2(at)-315.3(2)-328.3(w)0(e)20.5(e)0(k)23.9(s)0(,)-319.8(3)-322(mo)22.7(nt)22.2(hs)18.8(,)-325.4(a)0(n)23.9(d)-328.3(1)13.1(2)-328.3(mo)22.7(n)13.1(t)0(h)22.3(s)-329.5(ac)21.4(t)-326(a)0(s)]TJ
0 -1.1128 TD
[(co)17.5(v)13.1(a)0(r)21.2(i)0(a)19.8(t)0(e)19.8(s)-266.3(in)-256(th)22.3(e)-273.8(r)0(e)21.2(g)13.1(re)21.2(ss)17.6(i)15.4(o)0(n)-258.3(m)0(o)22.7(d)0(e)17.5(l)-269.1(fo)23.7(r)-267.7(t)0(h)22.3(e)-273.8(6)13.1(-)0(m)20.1(o)13.1(n)13.1(t)0(h)-262.3(G)16.2(OS)18.1(e.)]TJ
1.1128 -1.1128 TD
[(MM)-190.1(are)-189.3(a)-191.6(widely)-187.9(used)-191.3(approach)-189.3(in)-186.4(longitudinal)-193.7(data)-190.3(analysis)-188.4(and)]TJ
-1.1128 -1.1128 TD
[(model)-209.9(individual)-209.6(deviations)-215.5(from)-209.1(the)-207.3(population)-211.9(mean)-208.7(trajectory.)]TJ
6.7246 0 0 5.9768 292.1385 160.9511 Tm
(18)Tj
8.9663 0 0 8.9663 59.7543 147.0047 Tm
[(The)-228.4(MM)-221.7(used)-223(for)-225(the)-226.3(GOSe)-220.6(imputation)-225.8(incorporates)-224.5(time)-227(as)-223.9(a)-223.2(non-)]TJ
T*
[(linear)-379.3(covariate)-376.3(via)-378(a)-375(spline)-375.4(to)-376.1(be)-374.5(able)-373.6(to)-376.1(capture)-377.2(the)-378(non-linear)]TJ
T*
[(dynamics)-231(of)-222.9(GOSe)-233.3(over)-224.4(time)-227(in)-224.3(the)-226.3(population.)-227.5(The)-228.4(MM)-228(was)-226.7(tted)]TJ
0 -1.1065 TD
[(using)-496(Bayesian)-500.1(methods)-494.6(to)-489.9(allow)-498.2(for)-490.6(the)-498.2(inclusion)-491.8(of)-494.8(patient-)]TJ
0 -1.1128 TD
[(specic)-323.8(quadratic)-317(random)-321.8(effect)-317(\(see)-322.8(Supplementary)-317.2(Text)-320.4(for)-313.6(de-)]TJ
T*
[(tails\).)-315.4(An)-312.1(alternative)-313.8(non-linear)-310.4(regression)-315.1(model)-311(for)-307.2(longitudinal)]TJ
T*
[(data)-278.8(is)-276.1(GP,)-275.7(which)-272.9(allows)-277.6(exible)-273.6(modelling)-279.2(of)-273.5(both)-274(the)-276.9(individual)]TJ
0 -1.1065 TD
[(GOSE)-414(trajectories)-418.3(and)-411.9(the)-416(population)-414.3(mean)-411.1(in)-414(a)-412.9(Bayesian)-417.9(non-)]TJ
0 -1.1128 TD
[(parametric)-382(way.)]TJ
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T*
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T*
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T*
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T*
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T*
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T*
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s
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BT
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(0)Tj
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(300)Tj
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(600)Tj
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ET
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ET
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f
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s
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Q
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s
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s
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s
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s
Q
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s
Q
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f
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s
Q
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f
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s
Q
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s
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71.214 0 l
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s
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f
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s
Q
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s
Q
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s
Q
BT
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(2 weeks)Tj
ET
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f
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s
Q
BT
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(3 months)Tj
ET
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f
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s
Q
BT
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(6 months)Tj
ET
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f
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s
Q
BT
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(12 months)Tj
ET
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0 2.087 l
S
Q
BT
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(1345678)Tj
ET
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0 2.087 l
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0 2.087 l
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0 2.087 l
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0 2.087 l
S
Q
BT
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(1345678)Tj
ET
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[(965\).)-370.3(Both)-373.5(the)-378(raw)-373.6(count)-370.7(and)-374(the)-378(relative)]TJ
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