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[(i)158.6(n)158.6(f)167.5(e)154(c)152(t)153.4(i)158.6(o)170.7(n)166.6(s)158.2(.)-0.8(B)164.4(l)158.7(o)149.7(o)149.7(d)0(s)152.2(a)168(m)177.6(p)165.7(l)158.7(e)159(sf)148.5(r)171.3(o)170.7(m)158.9()149.7()0.2(s)163.3(t)153.4(r)158.2(a)177(yc)156(a)178(t)158.5(se)159(n)158.6(r)171.3(o)165.7(l)153.6(l)158.7(e)154(di)158.6(nat)153.5(r)158.2(a)178(p)158.6(-)158.3(n)162.6(e)159(u)170.7(t)164.5(e)159(r)182.3(-)158.3(r)171.3(e)163(l)158.7(e)153(a)162(s)150.2(e\()158.3(T)158.3(N)158.8(R)158.3(\))-0.3(p)170.7(r)171.3(o)158.7(g)153.8(r)158.2(a)168(mi)158.6(nn)162.6(o)170.7(r)148.2(t)152.4(h)162.6(e)159(r)152.2(nI)197.5(t)152.5(a)153.9(l)165.7(y)0.3(w)167.1(e)159(r)171.3(e)0.4(e)159(x)158.8(a)168(m)158.6(i)158.6(n)162.6(e)154(d)0(w)156(i)170.7(t)152.4(h)]TJ
T*
0.0004 Tc
[(co)12.6(n)23.5(v)8.7(en)19.4(t)-4.8(i)0.4(o)12.5(n)3.4(al)-183.2(PCR)-181.6(f)9.3(o)12.5(r)-182.7(t)-5.8(h)4.4(e)-181.9(p)12.5(r)13.1(e)0.8(s)-8(e)0.8(nce)-182.9(o)12.6(f)]TJ
/F1 1 Tf
14.8161 0 TD
0.0032 Tc
[(Ba)25.5(b)7.4(e)10.7(s)13(i)7.2(a)-180.3(m)20.3(i)7.2(c)2.8(r)21.9(o)15.5(t)12.1(i)]TJ
/F4 1 Tf
6.173 0 TD
-0.0094 Tc
[(an)-5.4(d)]TJ
/F1 1 Tf
1.6833 0 TD
-0.0005 Tc
[(C)34.3(y)-15.2(t)9.4(a)15.7(uxzoo)9.8(n)-186.2(f)9.5(e)15.1(l)12.6(i)-4.5(s)]TJ
/F4 1 Tf
6.5755 0 TD
-0.0001 Tc
[(D)9.2(N)38.3(A.)-183.6(N)25.2(o)-182.7(s)-6.5(a)9.3(m)18.9(p)7(le)-182.4(\(.%\))-183.1(t)5.8(e)0.3(st)5.8(ed)-182.7(p)-9.1(o)0(si)12(t)-5.3(i)6.9(v)8.2(e)-183.4(f)8.8(o)12(r)]TJ
/F1 1 Tf
16.931 0 TD
0.0004 Tc
[(C.)-183.2(f)10.4(e)16(l)13.5(i)-3.6(s)]TJ
/F4 1 Tf
2.5495 0 TD
-0.0007 Tc
[(,)-183.2(w)-7.3(hilst)]TJ
/F1 1 Tf
-48.7282 -1.1674 TD
-0.0098 Tc
[(B.)-211.4(m)7.3(i)-5.8(c)-10.2(r)8.9(oti)]TJ
/F4 1 Tf
4.0039 0 TD
-0.0001 Tc
[(D)9.2(N)38.3(A)-201.4(w)0.4(as)-201.2(det)5.8(e)-4.7(c)-6.7(t)5.8(ed)-201.8(in)-199.9(tw)8.4(o)-200.7(s)-6.5(a)9.3(m)18.9(p)7(l)0(es)-201.2(\(.%\).)-200.7(B)-20.4(o)11(t)-6.3(h)-199.8(inf)8.8(ec)-6.7(t)5.8(e)-4.7(d)-200.8(c)-2.7(a)19.3(t)-0.2(s)-201.2(w)8.4(er)12.6(e)-201.4(i)-0.1(n)-199.9(g)8.2(o)-9(o)-9(d)-200.8(c)6.4(l)0(inical)-201.8(co)12(ndi)12(t)-5.3(io)12(n)-200.9(a)9.3(nd)-200.8(r)12.6(e)-4.7(co)16.1(v)8.2(e)0.3(r)12.6(e)-4.7(d)-201.8(w)8.4(el)-5.1(l)-200.8(f)-10.2(r)12.6(o)12(m)-199.9(t)-6.3(he)]TJ
-4.0039 -1.1664 TD
0 Tc
[(neu)12.1(t)5.9(er)-6.4(in)8(g)-263.7(s)4.7(ur)7.6(g)8.3(e)0.4(r)-29.5(y)73.6(.)-263.8(O)0.2(ne)-263.6(o)12.1(f)-264.1(t)-6.2(h)4(es)-8.4(e)-263.6(t)-3.1(w)8.5(o)-263.9(ca)19.4(ts)-264.4(had)-264(a)-264.6(t)-5.2(r)-6.4(i)12(p)7.1(le)-262.6(co)12.2(inf)8.9(ec)-6.6(t)-5.2(i)0(o)12.1(n)-265(wi)12(t)-6.2(h)]TJ
/F1 1 Tf
28.1397 0 TD
0.0032 Tc
[(Ba)25.5(b)7.4(e)10.7(s)13(i)7.2(a)-262.6(m)20.3(i)7.2(c)2.8(r)21.9(o)15.5(t)12.1(i)]TJ
/F4 1 Tf
6.0736 0 TD
0 Tc
(,)Tj
/F1 1 Tf
0.4908 0 TD
0.0037 Tc
[(Ca)19.9(n)10.7(d)16.9(i)7.7(d)7.8(a)26(t)12.6(us)]TJ
/F4 1 Tf
4.8089 0 TD
-0.0012 Tc
[(M)30.6(y)7.1(co)9.9(p)5.9(l)-4.1(asma)-265.8(haemo)10.9(min)17.8(u)10.9(t)8.7(um,)]TJ
-39.513 -1.1664 TD
-0.0094 Tc
[(an)-5.4(d)]TJ
/F1 1 Tf
1.7425 0 TD
-0.0115 Tc
[(A)18.1(n)-4.5(apl)-7.4(a)-11.3(sm)-4.4(a)-256.2(p)-1.3(h)-4.4(a)4.7(g)-11.1(o)-7.2(c)-22(y)-26.2(tophi)-6.5(lum)]TJ
/F4 1 Tf
11.4165 0 TD
-0.0002 Tc
[(.)-244(E)19.8(vidence)-243.7(p)11.9(r)12.5(e)0.2(s)-8.6(e)0.2(n)18.8(t)5.7(ed)-243.1(in)-242.1(t)-6.4(h)-0.2(is)-242.5(st)9.7(ud)6.9(y)-241.8(i)-0.2(ndica)19.2(t)5.7(es)-243.5(t)-6.4(h)2.8(a)19.2(t)-242.2(t)-6.4(h)3.8(e)-242.7(b)6.9(lo)-9.1(o)-9.1(d)-242.1(b)-9.1(o)11.9(r)-6.6(n)3.8(e)-242.7(p)11.9(r)12.5(o)10.9(t)5.7(o)5.9(zoa)9.2(n)7.8(s)]TJ
/F1 1 Tf
30.6008 0 TD
0.0032 Tc
[(Ba)25.5(b)7.4(e)10.7(s)13(i)7.2(a)-241.5(m)20.3(i)7.2(c)2.8(r)21.9(o)15.5(t)12.1(i)]TJ
/F4 1 Tf
6.2934 0 TD
-0.0094 Tc
[(an)-5.4(d)]TJ
/F1 1 Tf
-50.0532 -1.1664 TD
-0.0005 Tc
[(C)34.3(y)-15.2(t)9.4(a)15.7(uxzoo)9.8(n)-271.5(f)9.5(e)15.1(l)12.6(i)-4.5(s)]TJ
/F4 1 Tf
6.7441 0 TD
0 Tc
[(a)9.4(r)12.7(e)-267.6(n)4(o)11.1(t)-268.1(widel)7.1(y)-267.7(dist)-5.2(r)-6.4(i)4(b)11.2(u)12.1(t)5.9(e)-4.6(d)-267(i)0(n)-267(s)4.7(t)-5.2(r)-0.4(a)18.4(y)-266.7(ca)19.4(t)-268.1(p)-9(o)11.1(p)11.1(u)-5(la)19.4(t)-5.1(i)0(o)12.1(n)8(s)-268.4(i)0(n)-267(M)6.7(ila)9.4(n)0(,)-267.9(n)4(o)12.1(r)-10.4(t)-6.2(h)4(er)-6.4(n)-267(I)38.9(t)-6.2(a)-4.7(l)7.1(y)73.6(,)-267.8(a)9.4(nd)-267(t)-6.2(h)3(a)19.4(t)-268.1(t)-6.2(h)4(e)-266.6(s)-0.4(igni ca)9.4(n)4(ce)-268.6(o)12.1(f)-267.1(ca)19.4(ts)-268.4(as)-267.4(a)]TJ
-6.7441 -1.1674 TD
-0.0123 Tc
[(re)-11.9(s)-20.7(e)-11.9(r)-41.8(v)-4(oi)-12.3(r)-239.5(h)-8.3(o)-12.2(s)-7.6(t)-238.3(f)-3.4(or)]TJ
/F1 1 Tf
7.1185 0 TD
-0.0098 Tc
[(B.)-238.5(m)7.3(i)-5.8(c)-10.2(r)8.9(oti)]TJ
/F4 1 Tf
4.0581 0 TD
-0.0012 Tc
[(in)-228.1(t)-7.4(h)-1.2(is)-228.4(a)8.2(r)11.5(e)-6.8(a)-228.7(is)-227.4(limi)10.8(t)4.7(e)-5.8(d)4.9(.)]TJ
/F2 1 Tf
11.9551 0 0 11.9551 50.58 244.272 Tm
0 Tc
[(1.)-250.3(Introduction)]TJ
/F4 1 Tf
9.9626 0 0 9.9626 50.58 224.382 Tm
-0.0007 Tc
[(M)25.8(e)-0.3(m)8.9(b)-9.4(er)5.3(s)-483.8(o)10.6(f)-481.6(t)-7.4(he)-480.9(o)10.6(r)11.7(der)-482.5(P)8.5(i)-1(r)11.7(o)9.7(p)6.6(l)-3.4(asmida)-481.3(\(s)4.9(uc)5.8(h)-483(a)2(s)-482(t)-7.4(he)-481.8(g)7.5(e)-0.3(nera)]TJ
/F1 1 Tf
0 -1.141 TD
0.0028 Tc
[(Ba)24.8(b)6.4(e)10.7(s)12.8(i)6.6(a)]TJ
/F4 1 Tf
3.3461 0 TD
-0.009 Tc
[(an)-5.8(d)]TJ
/F1 1 Tf
1.8393 0 TD
-0.0352 Tc
[(Cy)-50.3(t)-25.4(a)-18.6(u)-35.2(x)-35.6(z)-38.2(o)-31.3(o)-25(n)]TJ
/F4 1 Tf
4.713 0 TD
-0.0117 Tc
[(\))-347.8(a)-2.7(re)-347.3(a)7.2(p)0.1(i)-12(c)-11.5(om)6.9(p)-4.4(l)-11.6(e)-11.3(x)-11.3(a)-2.7(n)-347.3(p)0.1(rot)-5.7(o)-5.8(z)-11.8(o)-17.5(a)-11.7(.)-345.6()-8.5(e)-19.4(y)]TJ
-9.8984 -1.141 TD
-0.0004 Tc
[(li)6.5(v)7.3(e)-452.6(in)-452.5(t)-7.1(h)3.3(e)-452.6(b)7.1(lo)-9.8(o)-9.8(d)-452.6(cel)-5.8(l)2.4(s)-452.8(o)10.9(f)-452.4(v)7.3(er)-10.6(t)5.6(e)2.7(b)11.6(r)-0.7(a)18.5(t)5.6(es)-453.7(a)8.6(n)2.8(d)-451.7(a)8.6(r)12(e)-452.6(t)-6.2(r)-0.7(a)8.6(n)7.3(smi)11(t)9.2(t)5.6(e)-5.4(d)]TJ
T*
0.0008 Tc
[(b)-7.9(e)1.2(tw)9.2(een)-181.2(h)4.5(os)6.4(ts)-179.6(b)17.4(y)-180.7(t)-5(i)0.5(c)7.3(k)0.8(s)-179.6(a)9.8(nd)-178.6(co)11.2(u)-4.8(l)0.9(d)-179.5(a)-4.7(ls)-7.1(o)-179.4(b)-7.9(e)-179.5(t)-5(ra)9.8(n)8.5(s)1(mi)12.2(t)10.4(t)6.8(ed)-177.6(b)17.4(y)-180.7(ia)19.7(t)-5(r)13.2(o-)]TJ
T*
0.0001 Tc
[(g)8.3(e)0.5(nic)-305.9(\()0.1(e)6.8(.)0.4(g.,)-307.6(b)7.6(lo)-9.3(o)-9.3(d)-305.7(t)-5.7(r)-0.2(a)9.1(n)7.8(sf)-6.5(usio)11.4(n\))-302.5(a)9.1(n)3.3(d)-304.8(c)0.3(o)11.4(n)7.8(g)8.3(e)0.5(ni)11.5(t)-6.6(a)-5.4(l)-303.4(t)-5.7(ra)9.1(n)7.8(s)0.3(mis)5.7(s)0.3(io)11.4(n.)]TJ
T*
-0.0007 Tc
[(Emer)7.1(g)-6.1(i)-1(n)7(g)-263.5(dis)-8.6(e)-6.6(as)-8.6(es)-265.2(ca)18.2(us)-8.6(e)-5.7(d)-265(b)15.9(y)-265.3(s)-8.6(o)10.6(me)-264.1(o)10.6(f)-263.9(t)-7.4(h)3(es)-8.6(e)-264.1(p)11.1(ir)11.7(o)9.7(p)6.6(lasm)7.1(s)-264.3(p)-9.7(os)-8.6(e)]TJ
T*
-0.0022 Tc
[(he)-8.1(a)-7.7(l)9.6(t)-8.9(h)-227.9(r)-8.8(i)0.2(sks)-227.8(f)6.5(o)9.1(r)-228.3(ma)6.8(n)-228.5(a)6.8(nd)-228.5(o)8.2(t)-8.9(her)-227.4(a)6.8(nima)-7.7(ls)-227.8([)]TJ
0 g
16.0015 0 TD
0 Tc
()Tj
0 0 0 1 k
0.3379 0 TD
0.0001 Tc
(].)Tj
/F1 1 Tf
-14.8397 -1.3415 TD
0.0028 Tc
[(Ba)24.8(b)6.4(e)10.7(s)12.8(i)6.6(a)-310.3(m)20.1(i)6.6(c)2.7(r)21.9(o)14.8(t)11.7(i)]TJ
/F4 1 Tf
6.1204 0 TD
-0.0005 Tc
[(,)-311.8(a)-310.4(b)-5.6(a)7.6(b)-9.2(e)-0.1(sia)-6(l)-311.2(p)-5.9(a)8.5(rasi)10.9(t)5.5(e)-310(o)10.8(f)-310.7(r)11.9(o)-9.9(den)18(ts,)-310(h)2.3(as)-311(b)-9.2(e)-5.5(en)]TJ
-7.62 -1.141 TD
0.4201 Tc
[(i)419.8(d)420.5(e)420.5(n)438.6(t)414.3(i)419.8( )420.3(e)415.1(da)422.8(st)413.4(h)423.8(e)0.4(c)417.6(a)439(u)422.6(s)412.2(eo)431.4(fm)423.3(o)431.4(r)432.5(et)413.4(h)422.9(a)429.1(n\012)408.7()410.8()-1.1(c)417.6(a)422.8(s)412.2(e)420.5(so)431.4(fh)439.2(u)419.9(m)422.4(a)429.1(n)]TJ
T*
0.0001 Tc
[(ba)8.2(b)-8.6(e)0.5(siosis)-466.7(since)-466.5()10.2()-6.1()9.1()41.8(,)-466.6(ca)19(usin)7.8(g)-466(d)0.5(is)-7.8(e)-5.8(a)2.8(s)-7.8(e)-466.5(ra)9.1(n)7.8(g)-5.3(in)7.8(g)-466(f)-10.2(r)12.5(o)11.4(m)-464.6(m)-0.3(i)-5.6(l)0.2(d)]TJ
T*
-0.0105 Tc
[(t)-4.5(o)-396.7(s)-18.4(e)-18.2(ve)-10.1(re)-397.6(i)-10.8(n)-396.7(n)-8.2(a)8.4(tu)-10.7(re)-394.9([)]TJ
0 g
8.5595 0 TD
0 Tc
()Tj
0 0 0 1 k
0.4643 0 TD
0.0007 Tc
[(].)-386.5(P)32.5(e)1.1(nnisi)-385.3(et)-386.3(al)7.1(.)-386.5(\()0.7()-5()-8.6(\))-384.1([)]TJ
0 g
10.0726 0 TD
0 Tc
(\012)Tj
0 0 0 1 k
0.4517 0 TD
-0.0003 Tc
[(])-387(i)-0.6(den)18.2(t)-6.1(i)-0.6( e)-5.3(d)]TJ
-19.5481 -1.141 TD
0.3035 Tc
[(s)303.7(i)303.2(xb)311(l)303.6(o)294.1(o)294.1(d)-0.5(s)297.4(a)312.5(m)322.1(p)310.8(l)303.6(e)303.9(sf)293.3(r)315.9(o)314.8(mo)319.3(w)301(n)306.7(e)298.5(d)0.4(p)294.5(e)303.9(tc)301(a)322.4(t)303.2(sf)293.3(r)315.9(o)314.8(ms)295.6(o)313.9(u)315.1(t)296.8(h)307.2(e)303.9(r)296.9(nI)342.8(t)296.8(a)298(l)310.8(y)]TJ
T*
0.001 Tc
[(\(S)7(ici)-4.7(l)8.3(y\))-252.8(t)-5.7(h)3.8(a)19.9(t)-251.4(t)7(e)1.4(s)6.6(t)7(ed)-254.2(p)-8(o)0.6(si)12.4(t)-4.8(i)7.9(v)8.7(e)-250.6(f)9.7(o)12.3(r)]TJ
/F1 1 Tf
12.2833 0 TD
0.0028 Tc
[(Ba)24.8(b)6.4(e)10.7(s)12.8(i)6.6(a)-253.4(m)20.1(i)6.6(c)2.7(r)21.9(o)14.8(t)11.7(i)]TJ
/F4 1 Tf
6.3174 0 TD
-0.0102 Tc
[(an)-7(d)-262.7(p)1.6(rop)-19.2(o)-10.6(s)-18.1(e)-15.2(d)]TJ
-18.6007 -1.141 TD
-0.0117 Tc
[(t)-18.4(h)-8.9(a)7.2(t)-237.9(c)-14.2(a)7.2(t)-12(s)-239.1(m)-12.1(i)-12(g)-18.9(h)7.4(t)-237.9(b)-20.4(e)-238.9(a)-238.5(re)-11.3(s)-19.6(e)-11.3(r)-40.9(v)-4(oi)-12(r)-237.8(f)-3(or)-236.9(t)-18.4(h)-11.6(i)-9.3(s)-238.2(p)-17.1(a)-2.7(r)-12(a)-9(s)-11.5(i)-0.3(t)-5.7(e)-5(.)]TJ
1.4996 -1.2412 TD
0.2556 Tc
[(D)248.9(o)255.2(g)255.6(s)0.2(a)264.6(n)258.8(dc)253.1(a)274.5(t)255.3(sl)255.7(i)262.5(v)263.3(ei)255.3(nc)262.1(l)255.7(o)255.2(s)247.7(e)-1.5(p)267.4(r)268(o)271.4(x)256(i)255.3(m)255.2(i)267(t)252.5(yt)261.6(op)246.6(e)250.6(o)266(p)262.9(l)255.7(ea)264.6(n)258.8(d)0.4(h)258.4(a)273.6(v)263.3(e)]TJ
-1.4996 -1.141 TD
-0.0012 Tc
[(o)10.1(\015)5.3(en)-366.6(b)-9.9(e)-6.2(en)-366.6(p)10.6(r)11.2(o)9.2(p)-10.2(os)-9.1(e)-6.2(d)-363.9(as)-365.9(e)7.8(e)-6.2(c)-8.2(t)-7(i)5.7(v)6.5(e)-364.9(s)-9.1(e)-0.8(n)17.3(t)-7(inel)-364.3(a)7.8(n)-1.7(ima)-6.7(l)1.6(s)-364.1(t)4.8(o)-365.7(a)1.5(s)4.4(s)-9.1(es)4.4(s)]TJ
25.8998 19.4117 TD
-0.0008 Tc
[(t)-7.5(h)2.9(e)-200(r)-7.4(isk)-199.5(o)10.5(f)-199.9(h)18.3(uma)8.2(n)-200(inf)7.9(e)-5.8(c)-7.8(t)-6.6(io)10.5(n)-198.2(w)-3.3(i)10.6(t)-7.5(h)-199.4(t)-6.6(ic)5.7(k-b)-9.5(o)10.5(r)-7.4(n)2.4(e)-198.2(d)-0.4(is)-8.7(e)-6.7(a)1.9(s)-8.7(e)-0.4(s)-201.1([)]TJ
0 g
21.1272 0 TD
0 Tc
()Tj
0 0 0 1 k
0.4969 0 TD
-0.0005 Tc
[(].)-200.7(is)]TJ
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