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[(1. )7.5(Int)5.9(e)0.1(r)-19.2(n)-2.3(ati)6.1(o)0.1(nal)6.1( L)25.6(y)0.2(me an)5.2(d Associ)6.1(a)-10(t)5.9(ed Di)6.1(sease)-7.4(s)3.1( )7.5(So)-7.4(ci)6.1(et)5.9(y \(ILA)-5.2(DS\))]TJ
/F1 1 Tf
10.02 0 0 10.02 34.2 632.3601 Tm
-0.0008 Tc
0.1999 Tw
[(IL)-10.7(ADS is an inter)13.8(d)5.2(isciplinar)-16.1(y organization of h)5.2(e)0(alth s)4.8(c)-2(ience)]TJ
T*
-0.0011 Tc
0.1164 Tw
[(pr)7.5(ofessionals establ)-5.6(ished in 1)]TJ
11.4251 0 TD
-0.0005 Tc
0.1158 Tw
[(999 to acco)6.5(mplish the follo)12.4(wing)]TJ
-11.4251 -1.1976 TD
-0.0012 Tc
0 Tw
[(objectiv)5.6(es:)]TJ
0 -1.497 TD
0.0179 Tc
0.2231 Tw
[()-444.4(A)-5.8(naly)-5.2(ze th)-6(e med)-6(i)-0.5(cal)-4.6( lit)-4.4(e)0.7(rat)-4.4(u)3(r)8.6(e)-5.3(, )6(po)-5.1(sitio)-5.1(n)-2( )6(st)-4.4(atements and)]TJ
0.8503 -1.1976 TD
-0.0013 Tc
0.0028 Tw
[(p)-21.2(r)-16.6(actice paramet)-5.7(e)-0.5(rs )6(r)7.3(e)-0.5(lated to L)48.7(y)-0.4(me and associated d)-19.2(i)-19.7(s)-25.6(e)-18.5(a)-16.5(s)-25.6(e)-18.5(s)]TJ
-0.8503 -1.497 TD
-0.0151 Tw
[( I)13.2(m)1.2(pr)7.2(o)17.5(v)5.5(e the management)-5.8( )6(of these )6(diseases )6(through e)5.4(v)5.4(a)-4.6(luat)-5.8(ion)]TJ
0.8503 -1.1976 TD
-0.0009 Tc
0.0024 Tw
[(of )6(established and inno)18(v)6(a)1.9(tiv)6(e)-0.1( therapies)]TJ
-0.8503 -1.497 TD
0.0089 Tc
0.0824 Tw
[()13.7( )12(E)12.1(d)14.9(u)5.9(c)7.7(ate a br)5.6(oad )-6(range )-6(of healthcar)11.6(e)-2.3( pr)5.6(o)15.9(v)-2.2(iders and ser)-18.4(v)3.8(e as)]TJ
0.8503 -1.1976 TD
0.0092 Tc
0.2498 Tw
[(an effectiv)10.1(e advocate )-6(for clin)]TJ
12.2335 0 TD
0.0086 Tc
0.2504 Tw
[(i)-3.9(c)1.4(ians)-3.7( s)-3.7(e)3.4(eking )-6(cost-effecti)-3.9(v)9.5(e)]TJ
-12.2335 -1.1976 TD
0.0098 Tc
-0.0023 Tw
[(stat)5.4(e-of-t)5.4(he-a)6.6(r)-11.5(t)-0.6( tr)12.5(eat)5.4(m)0.4(ent r)12.5(e)-1.4(gimens)]TJ
0 -1.497 TD
0.0159 Tc
0.1113 Tw
[(IL)-11.9(AD)5.5(S id)3.9(entifie)4.7(d)-2( th)4(e nee)4.7(d)-2( fo)4.9(r ne)-7.3(w and)3.9( expand)3.9(ed)3.9( guid)3.9(e-)]TJ
-0.8503 -1.1976 TD
0.0154 Tc
0.028 Tw
[(lines for)6.1( the diagno)4.4(sis a)6.2(n)-4.5(d tr)12.1(e)4.2(a)0.2(tment )6(of L)47.4(y)4.3(me )6(and asso)4.4(ciate)4.2(d)]TJ
T*
0.0151 Tc
0.1421 Tw
[(diseases. I)11.8(n)1.2( 2001, )-6(a wor)5.8(k)0.1(ing)6( )-6(pa)]TJ
13.2096 0 TD
0.0154 Tc
0.1418 Tw
[(r)-5.9(t)-1(y was form)6(ed to evaluate)]TJ
-13.2096 -1.1976 TD
0.0151 Tc
0.184 Tw
[(curr)11.8(ent practices and to encou)6.1(r)-0.2(age ne)-8.1(w standar)11.8(d)3.1(s of car)11.8(e)-2.1(.)]TJ
0 -1.2036 TD
0.0159 Tc
0.1473 Tw
[(This )-6(r)12.6(e)4.7(por)-11.4(t)5.5(, completed in )-6(N)32.4(o)]TJ
12.4311 0 TD
0.015 Tc
0.1542 Tw
[(v)9.9(e)-2.2(mber 2003, is intended )6(to)]TJ
-12.4311 -1.1976 TD
0.0525 Tw
[(ser)-18.4(v)9.8(e as a )6(r)11.6(e)-2.3(sour)5.6(ce )6(for physicia)]TJ
12.3653 0 TD
0.0153 Tc
0.0521 Tw
[(ns, public )6(health officia)6.1(l)-1.2(s )6(and)]TJ
-12.3653 -1.1976 TD
0.0158 Tc
0.2013 Tw
[(o)4.8(r)0.5(ganizatio)4.8(n)1.9(s )6(inv)4.7(o)4.8(lv)4.7(e)4.6(d)-2.1( )6(in t)5.4(h)-2.1(e)4.6( ev)10.7(aluation and tr)12.5(eat)5.4(m)0.4(ent )6(of)]TJ
T*
-0.032 Tc
0.0455 Tw
[(Ly)-43.1(m)-47.4(e)-49.2( d)-49.9(i)-44.5(s)-50.3(e)-43.2(a)-47.2(s)-50.3(e)-43.2(.)]TJ
/F5 1 Tf
7.98 0 0 9 34.2 393.32 Tm
0.0068 Tc
-0.0011 Tw
[(2. )7.5(Chr)18.5(o)0.2(ni)6.2(c L)25.7(y)0.3(m)-8.1(e)0.2( )7.5(di)6.2(sease:)8.6( a gr)18.5(o)15.2(w)2.3(ing epi)6.2(d)-2.4(em)-8.1(i)6.2(c)]TJ
/F1 1 Tf
10.02 0 0 10.02 34.2 380.3001 Tm
0.0177 Tc
0.2293 Tw
[(The C)-4.9(e)0.5(nte)-5.5(r)2.4(s for D)13.3(i)-0.7(se)-5.5(as)-6.6(e Cont)-4.6(r)8.4(o)-5.3(l and)-6.2( P)33.8(r)8.4(e)-5.5(v)6.6(ent)-4.6(i)-0.8(on \(C)-4.9(DC\))]TJ
T*
0.0184 Tc
0.0669 Tw
[(consider L)44.5(y)-4.7(me )-6(disease )-6(the)-4.8( fas)-5.9(t)2(est)-3.9( gro)13.4(w)1.8(ing v)7.3(e)-4.8(ctor-bo)-4.6(r)3.1(ne )-6(dis-)]TJ
T*
0.1329 Tw
[(ease in t)-4(h)0.4(e USA. B)18.5(y)-4.8( conser)-21(v)7.2(a)-2.9(tive es)-6(timat)-4(e)1.1(, t)-4(h)0.4(e number of)]TJ
T*
0.0192 Tc
0.2937 Tw
[(n)5.3(e)-10(w L)45.3(y)2.1(me disease in)5.3(fections per)-289.5(y)8.1(ear m)3.8(a)-2(y be ten)5.3( tim)3.8(e)-4(s)]TJ
T*
0.0182 Tc
0.109 Tw
[(higher th)-5.7(an t)-4.1(h)0.3(e 17,730 )-6(case)-5(s r)8.9(e)1(po)-4.8(rt)-4.1(ed )-6(to )-6(the)-5( CDC)-4.4( during)]TJ
T*
0.021 Tc
0 Tw
[(2)6(000)6( )]TJ
7.02 0 0 7.02 57.66 320.3004 Tm
-0.0035 Tc
[([1)-7.8(,2])]TJ
10.02 0 0 10.02 70.86 320.3001 Tm
0 Tc
(.)Tj
-2.8084 -1.1976 TD
-0.0011 Tc
0.0385 Tw
[(The pr)13.5(ev)5.8(al)-5.6(e)5.7(n)-3(ce )6(of chr)7.5(o)-0.1(nic L)42.9(y)-0.2(me d)4.9(i)-1.6(sease ranges fro)5.9(m)-4.5( )6(34% in)]TJ
-0.8503 -1.1976 TD
0.0804 Tw
[(a population-based, )5.9(r)7.5(e)-0.3(tro)5.9(s)-1.5(pectiv)5.8(e cohor)-10.4(t)0.5( study )]TJ
7.02 0 0 7.02 218.7 296.3004 Tm
0.0048 Tc
0 Tw
[([3)9.1(])]TJ
10.02 0 0 10.02 226.62 296.3001 Tm
0.0793 Tc
[( t)80.9(o)80.3( 6)82.3(2)82.3(%)79( i)84.8(n)77.4( a)]TJ
-19.2036 -1.1976 TD
-0.0026 Tc
0.04 Tw
[(s)-3(p)1.4(ec)-3.8(ia)-5.8(lty c)-3.8(l)-1.1(in)-4.5(i)-3.1(c)2.2( loc)-3.8(a)0.2(t)-7(e)4.2(d)-2.6( i)-3.1(n)1.4( a)-5.8(n)1.4( )]TJ
11.2335 0 TD
-0.0013 Tc
0.0387 Tw
[(ar)7.3(ea endemic for)-4.6( L)48.7(y)-0.4(me disea)-4.5(s)4.3(e )]TJ
7.02 0 0 7.02 267.54 284.3004 Tm
0.0048 Tc
0 Tw
[([4)9.1(])]TJ
10.02 0 0 10.02 275.46 284.3001 Tm
0 Tc
(.)Tj
-24.0778 -1.1976 TD
-0.001 Tc
0.0684 Tw
[(Clinic )-6(pat)-5.4(i)4.5(ents pr)7.6(esented with ar)]TJ
12.8144 0 TD
-0.0008 Tc
0.0682 Tw
[(thralgia, ar)-10.1(thritis, )-6(car)13.8(d)5.2(iac and)]TJ
-12.8144 -1.1976 TD
-0.0021 Tc
-0.0024 Tw
[(neurologic sympt)-6.5(o)-1.1(ms )]TJ
7.02 0 0 7.02 119.52 260.3004 Tm
-0.0038 Tc
0 Tw
[([4)-8.1(])]TJ
10.02 0 0 10.02 127.5 260.3001 Tm
0 Tc
(.)Tj
-8.4611 -1.1976 TD
-0.0014 Tc
0.0688 Tw
[(A widening)-4.5( arra)-4.6(y of c)-2.6(h)4.6(ronic p)-3.4(r)13.2(esen)-3.3(tations is associated with)]TJ
-0.8503 -1.1976 TD
-0.001 Tc
0.0624 Tw
[(the L)49(y)-0.1(me spirochete, )]TJ
/F4 1 Tf
8.4251 0.0003 TD
-0.0004 Tc
0.0678 Tw
[(Bo)4.4(rr)17.2(elia b)4.5(u)-1.4(rg)4.4(dor)-6.7(f)3.1(eri)]TJ
/F1 1 Tf
7.3952 -0.0003 TD
0.0005 Tc
0.0609 Tw
[(. Ther)15.1(e ar)21.1(e)13.3( )12(g)9.4(r)21.1(e)13.3(a)9.3(t)14.1( )12(c)11.3(h)12.5(a)9.3(l)14(-)]TJ
-15.8204 -1.1976 TD
-0.0076 Tc
0.033 Tw
[(l)5.9(e)5.2(nge)5.2(s)4( i)3.9(n)2.4( d)4.4(e)-0.8(t)6(e)5.2(rm)6.9(in)8.4(in)8.4(g o)5.3(p)2.4(t)6(i)-2.1(m)6.9(a)1.2(l)5.9( c)3.2(o)]TJ
12.521 0 TD
-0.0098 Tc
0.0352 Tw
[(st-eff)4.8(ectiv)9(e)-3( m)4.7(e)3(ans for )5.9(appr)10.8(op)6.2(ri-)]TJ
-12.521 -1.1976 TD
-0.0138 Tc
0.0812 Tw
[(at)-6.2(e dia)-5(g)-4.9(no)-6.8(sis,)-3.3( c)-3(l)-0.3(i)-8.3(n)2.2(i)-8.3(c)-3(al)-6.3( ma)-5(na)-5(g)-4.9(e)-1(me)-7(nt)-6.2( a)-5(n)2.2(d p)-3.8(u)-4.8(bl)-6.3(ic)-3( hea)-5(l)-6.3(th c)-3(o)-0.9(n)-3.8(t)-6.2(rol)-6.3( of)]TJ
T*
-0.013 Tc
-0.0154 Tw
[(L)49(y)-6.1(me)-6.2( disease )-5.9(through)-7(o)-0.1(ut)-5.4( t)-5.4(h)-1(e wo)-6(rl)]TJ
12.6707 0 TD
-0.0123 Tc
-0.0161 Tw
[(d. A)11.9(ddi)-6.8(tional )-5.9(proble)-5.5(ms i)-6.8(n)3.7(clud)-6.3(e)]TJ
-12.6707 -1.1976 TD
-0.0097 Tc
0.2567 Tw
[(t)3.9(h)2.3(e ide)3.1(n)0.3(tif)4.8(i)-4.2(ca)5.1(tio)3.2(n)0.3( and m)4.8(a)-0.9(na)5.1(ge)3.1(me)]TJ
13.1617 0 TD
-0.0106 Tc
0.2576 Tw
[(nt )-6(of tickborn)5.4(e coinfecti)-5.1(o)2.3(ns)]TJ
-13.1617 -1.1976 TD
-0.0118 Tc
0 Tw
(including )Tj
/F4 1 Tf
3.8204 0.0003 TD
-0.0093 Tc
[(Ehr)8.3(l)3.2(ic)5.3(hi)5.2(a)]TJ
/F1 1 Tf
3.3293 -0.0003 TD
-0.0105 Tc
(, )Tj
/F4 1 Tf
0.479 0.0003 TD
-0.0181 Tc
[(Ba)-5.2(b)-7.2(e)-7.4(s)-7.6(i)-9.6(a)]TJ
/F1 1 Tf
2.7365 -0.0003 TD
-0.0119 Tc
0.0014 Tw
( and )Tj
/F4 1 Tf
1.8802 0.0003 TD
-0.0115 Tc
0 Tw
[(B)6.6(a)-4.6(r)-5.8(t)-2.9(onella)]TJ
/F1 1 Tf
3.7365 -0.0003 TD
-0.0062 Tc
-0.0103 Tw
[( sp)9.8(ec)4.6(i)5.3(e)6.6(s)-6.6( )]TJ
7.02 0 0 7.02 224.64 176.3004 Tm
-0.0041 Tc
0 Tw
([5])Tj
10.02 0 0 10.02 232.62 176.3001 Tm
0 Tc
(.)Tj
/F5 1 Tf
7.98 0 0 9 34.2 153.32 Tm
0.0066 Tc
-0.0009 Tw
[(3. )7.5(The )7.5(need f)23.4(o)0(r n)5.1(e)15(w gui)6(d)-2.6(el)6(i)6(n)-2.4(es)]TJ
/F1 1 Tf
10.02 0 0 10.02 34.2 140.3001 Tm
0.0179 Tc
0.283 Tw
[(G)16.4(u)-3(ide)-5.3(l)1.4(ines o)-5.1(f)2.5( th)-6(e I)14.6(n)-2(fecti)-6.5(o)0.9(us)-6.4( )6(D)7.5(i)-0.5(sease S)9.9(o)0.9(ciet)-4.4(y of America)]TJ
0 -1.1976 TD
0.0186 Tc
0.1805 Tw
[(\(IDSA\) fall)-3.9( s)-5.7(h)0.7(or)-8.7(t )-6(of )-6(mee)-4.6(t)2.2(ing t)-3.7(h)0.7(e )-6(need)-5.3(s for )-6(diagnosis)-5.7( and)]TJ
T*
0.0201 Tc
0.0652 Tw
[(t)3.7(r)10.8(e)2.9(a)-1(tm)4.7(e)2.9(n)0.2(t )6(o)3.1(f)-1.3( indiv)3(i)1.7(dual)3.6(s w)3.5(i)1.7(th c)6.9(h)-3.8(r)10.8(o)-2.9(n)6.2(i)1.7(c L)46.2(y)3(me)2.9( )6(dise)2.9(ase)2.9( )]TJ
7.02 0 0 7.02 247.68 116.3004 Tm
-0.0041 Tc
0 Tw
([6])Tj
10.02 0 0 10.02 255.66 116.3001 Tm
0.0199 Tc
0.0594 Tw
(. The)Tj
-22.1018 -1.1976 TD
0.0793 Tc
0 Tw
[(l)62.8(a)58.1(t)62.9(e)56.1(s)61(t)62.9( I)58(D)62.9(S)59.3(A)61.6( G)71.8(u)64.4(i)54.9(d)61.4(e)62.1(l)62.8(i)54.9(n)65.4(e)56.1(s)61( \()58(2)64.3(0)58.3(0)64.3(0)58.3(\))58( f)63.9(a)58.2(i)60.9(l)56.8( t)62.9(o)62.3( t)57(a)58.1(k)64.3(e)62.1( i)54.9(n)65.4(t)57(o)62.3( a)58.1(c)60.1(c)60.1(o)62.3(u)58.4(n)65.4(t)57( t)62.9(h)55.4(e)]TJ
T*
0.0183 Tc
0.1928 Tw
[(compel)-4.2(li)-6.1(ng, peer-r)9(evie)-10.9(w)7.6(e)1.1(d, )-6(publishe)-4.9(d ev)-4.8(idence co)-4.7(nfirming)]TJ
T*
0.0176 Tc
0.2414 Tw
[(pe)-5.6(rs)-6.7(iste)-5.6(nt)-4.7(, r)8.3(e)0.4(curr)8.3(ent )-6(and )-6(r)14.3(e)-5.6(fractor)-21.7(y)0.5( )-6(L)43.7(y)0.5(me)-5.6( dise)-5.6(ase)-5.6( and)-6.3(,)-1.9( in)]TJ
T*
0.0186 Tc
0.0009 Tw
[(fact, deny its)-5.7( existence )]TJ
7.02 0 0 7.02 127.5 68.3004 Tm
0.0048 Tc
0 Tw
[([6)9.1(])]TJ
10.02 0 0 10.02 135.48 68.3001 Tm
0 Tc
(.)Tj
16.2036 64.6766 TD
0.0094 Tc
0.1657 Tw
[(T)4.7(h)-2.5(e)4.2( IDSA)93.5()76.7(s)3.1( sympto)4.4(matic appr)6.1(oache)4.2(s)-2.9( )5.9(to )5.9(L)41.4(y)4.3(me )5.9(dise)4.2(ase)4.2( ar)12.1(e)]TJ
-0.8503 -1.1976 TD
0.0074 Tc
0.06 Tw
[(limite)-3.8(d )-6(an)-6.5(d e)-3.8(x)8.3(clude)-3.8( many )-6(ind)-4.6(i)0.9(v)-3.7(i)]TJ
12.982 0 TD
0.009 Tc
0.0584 Tw
[(duals with persisting )-6(clinical)]TJ
-12.982 -1.1976 TD
0.0088 Tc
0.0765 Tw
[(and laborator)-18.5(y)3.7( evidence )6(of )6(active )]TJ
/F4 1 Tf
13.5928 0.0003 TD
0.0068 Tc
0.0785 Tw
[(B. bu)-6.2(rgd)-4.2(o)-0.4(r)-11.5(f)-1.7(e)-6.5(r)0.5(i)]TJ
/F1 1 Tf
5.4192 -0.0003 TD
0.0086 Tc
0.0767 Tw
[( infection. I)11.3(n)]TJ
-19.012 -1.1976 TD
-0.0004 Tc
0.0917 Tw
[(additi)5.1(on, physicians tr)14.2(eating )-6(i)5.1(n)-2.3(di)5.1(viduals wi)5.1(th)5.6( )-6(L)49.6(y)0.5(me and other)]TJ
T*
-0.0017 Tc
0.081 Tw
[(tick)-4.7(-bor)-5(ne infections r)12.9(e)-0.9(cognize )]TJ
12.3234 0 TD
-0.0013 Tc
0.0806 Tw
[(the )5.9(nee)5.5(d)-1.3( for ne)-6.5(w guideline)5.5(s)-1.6( to)]TJ
-12.3234 -1.1976 TD
-0.0006 Tc
-0.0039 Tw
[(better ser)-15.9(v)6.2(e )-6(the patient population )]TJ
7.02 0 0 7.02 424.62 656.3604 Tm
-0.0038 Tc
0 Tw
[([6)-8.1(])]TJ
10.02 0 0 10.02 432.6 656.3601 Tm
0 Tc
(.)Tj
-13.4491 -1.1976 TD
0.0072 Tc
0.1141 Tw
[(P)29.3(r)9.9(e)-4(v)2.1(i)-5.3(o)2.2(us)-5.1( guid)-4.8(el)-3.3(i)-5.3(n)-0.7(es)-5.1( for )-5.9(manage)-4(ment)-3.2( o)-3.8(f)-2.2( L)45.2(y)-3.9(me)-4( d)-4.8(i)0.7(s)-5.1(e)2(as)-5.1(e h)-4.8(a)-2(v)8.1(e)]TJ
-0.8503 -1.1976 TD
0.0085 Tc
0.1786 Tw
[(been published in the )]TJ
/F4 1 Tf
9.479 0.0003 TD
0.0122 Tc
0.1749 Tw
[(N)32.6(e)4.9(w)4.5( E)21.3(n)4.2(g)5(l)0.7(a)7.1(n)-1.8(d)7.2( J)40.8(o)5(urna)7.1(l )6(of)3.7( )6(M)17.9(e)4.9(di)8.8(cine)]TJ
/F1 1 Tf
13.6168 -0.0003 TD
0.0125 Tc
0.1686 Tw
[( in)]TJ
-23.0958 -1.1976 TD
0.0084 Tc
0.041 Tw
[(1990 b)5.4(y)3.3( )-6(Rahn )]TJ
7.02 0 0 7.02 349.5 620.3604 Tm
0.0048 Tc
0 Tw
[([7)9.1(])]TJ
10.02 0 0 10.02 357.48 620.3601 Tm
0.0074 Tc
0.048 Tw
(; in )Tj
/F4 1 Tf
1.6587 0.0003 TD
0.042 Tw
[(C)-5.3(o)0.2(nn)107.2()29.8(s)-0.1( C)18.7(u)-5.6(rr)19.1(en)-6.6(t Ther)25(ap)12.3(y)]TJ
/F1 1 Tf
9.0898 -0.0003 TD
0.0093 Tc
0.0401 Tw
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[(focusing on )-6(er)-18.6(ythema migrans, )-6(he)]TJ
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[(s)4.4(e)-0.4(r)7.4(o)-0.3(e)5.5(p)2.8(id)4.8(emi)4.3(o)-0.3(lo)5.7(gic)3.6( stud)4.8(ie)5.5(s. Ch)4.8(r)7.4(o)]TJ
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[(nic, )-6(persistent,)-4.5( r)11.6(e)-2.2(curr)11.6(ent an)-5(d)]TJ
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[(fat)-5.2(i)4.7(gue, cognitiv)6.1(e d)5.2(y)0.1(sfunction, headach)5.2(e)0(s, sleep disturbance)]TJ
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[(per)-4.6(i)4.2(pheral neur)7.3(opathy and sometimes motor)-4.6( )5.9(neuron disea)-4.5(s)4.3(e;)]TJ
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[(neur)8.5(opsy)12.8(ch)5.9(iatric)4.7( pr)14.5(esentations; )]TJ
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[(re)-17.3(l)-22.6(a)2.7(pse in )-6(the absence of another )-6(tickbite or er)-15.4(y)-5.3(t)1.5(hema migrans)]TJ
T*
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BT
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-12.1198 -1.1976 TD
-0.0015 Tc
0.2784 Tw
[(scription of antibiotics and th)]TJ
12.5269 0 TD
-0.0011 Tc
0.278 Tw
[(e use of measur)7.5(es to r)13.5(e)-0.3(duce)]TJ
-12.5269 -1.1976 TD
0.1282 Tw
[(adv)5.9(e)-0.2(rse ev)5.8(ents, e.g., emplo)11.9(y)-0.1(ing )]TJ
12.5569 0 TD
-0.0024 Tc
0.1296 Tw
[(a)-5.6(c)2.4(idophilus to repl)-6.9(ac)-3.6(e )-6(norma)-5.6(l)]TJ
-12.5569 -1.1976 TD
-0.0012 Tc
-0.0033 Tw
[(intestina)-4.4(l)0.3( f)-4.6(l)0.3(ora )-6(that )-6(is depleted b)7.8(y)-0.3( )-6(antibiotics.)]TJ
/F5 1 Tf
7.98 0 0 9 56.88 489.32 Tm
0.0067 Tc
-0.0085 Tw
[(6. The in)5.2(creasi)6.1(ng )-7.5(r)18.4(o)0.1(l)6.1(e)0.1( )-7.5(of pr)-19.2(i)6.1(m)-0.7(ar)-41.7(y c)-7.4(a)5(re)]TJ
/F1 1 Tf
10.02 0 0 10.02 56.88 476.3601 Tm
-0.0009 Tc
0.1102 Tw
[(Th)5.1(e primar)-22.2(y )6(car)7.7(e)-0.1( physic)3.9(ian has an)]TJ
13.7246 0 TD
-0.0006 Tc
0.1099 Tw
[( important role as the )6(first)]TJ
-13.7246 -1.1976 TD
-0.0013 Tc
0.0327 Tw
[(and at times, )6(the pr)-4.6(incipal medi)]TJ
12.4431 0 TD
[(cal contact for the )6(person with)]TJ
-12.4431 -1.2036 TD
-0.05 Tc
0.0515 Tw
[(Ly)-49.1(m)-47.4(e)-49.2( d)-50(i)-44.5(s)-50.4(e)-49.2(a)-47.2(s)-50.4(e)-49.2(.)]TJ
0.8503 -1.1976 TD
-0.0007 Tc
-0.0158 Tw
[(P)27.3(r)2(imar)-22(y car)7.9(e)0.1( ph)5.3(ysicians )-6(focus on)]TJ
12.497 0 TD
-0.0011 Tc
-0.0154 Tw
[( )-6(the r)7.5(e)-0.3(solution of )-6(symptoms,)]TJ
-13.3473 -1.1976 TD
-0.0017 Tc
0.1828 Tw
[(monitoring for)-5( side )-6(ef)-5.1(fects, )-6(maintenance or)-5( impr)6.9(o)11.2(v)5.2(ement )-6(of)]TJ
T*
-0.0013 Tc
0.0028 Tw
[(functional status and pr)13.3(even)]TJ
10.8623 0 TD
-0.001 Tc
0.0025 Tw
[(tio)6(n)-2.9( of r)13.6(e)-0.2(curr)7.6(ent)-5.4( )6(symptoms.)]TJ
-10.012 -1.1976 TD
-0.0008 Tc
0.134 Tw
[(These guidelines incorporate )6(t)-5.2(h)5.2(e evide)6(n)-2.7(ce )6(used b)8.2(y)0.1( primar)-16.1(y)]TJ
-0.8503 -1.1976 TD
-0.0009 Tc
0.0024 Tw
[(c)3.9(a)-4.1(r)13.7(e)-0.1( physic)3.9(ians )6(for th)5.1(e car)7.7(e)-0.1( )6(of)]TJ
11.3174 0 TD
-0.0011 Tc
-0.0034 Tw
[( patients )-6(with L)42.9(y)-0.2(me disease.)]TJ
/F5 1 Tf
7.98 0 0 9 56.88 369.32 Tm
0.0013 Tc
-0.0031 Tw
[(7.)-4.4( H)-10.4(i)0.7(g)-7.9(h)-7.7(lig)-7.9(h)-7.7(t)0.5(s )-7.5(o)-5.3(f)-4.4( g)-7.9(u)-7.7(id)-7.9(e)-5.3(l)0.7(i)-6.8(n)-0.2(e)-12.8(s)]TJ
/F1 1 Tf
10.02 0 0 10.02 56.88 356.3001 Tm
-0.0011 Tc
0.1403 Tw
[( S)8.9(i)4.4(nce )6(t)-5.5(h)4.9(er)7.5(e is curr)13.5(ently no definitiv)5.7(e)-0.3( test for L)42.9(y)-0.2(me disease,)]TJ
0.8503 -1.1976 TD
-0.0015 Tc
-0.015 Tw
[(l)-6(a)1.3(bora)-4.7(tor)-16.8(y)-0.6( r)7.1(e)-0.7(su)-4.5(lts shoul)-6(d)4.5( not be used )6(t)-5.9(o)-0.5( )6(ex)11.3(clude an individua)-4.7(l)]TJ
T*
-0.0007 Tc
0.0022 Tw
[(fr)7.9(om tr)7.9(e)6.1(a)-3.9(tment)]TJ
-0.8503 -1.497 TD
-0.0009 Tc
-0.0096 Tw
[()3.9( )-6(L)49.1(y)0(me disease is a )-6(c)3.9(l)0.6(ini)4.6(c)-2.1(al )-6(di)4.6(agnosis and tests should be )-6(used)5.1( )-6(to)]TJ
0.8503 -1.1976 TD
-0.0024 Tc
0.0039 Tw
[(su)-5.4(ppor)-11.7(t)-0.8( rat)-6.8(h)3.6(er)-5.7( )6(than)-4.3( su)-5.4(pers)]TJ
10.1377 0 TD
-0.0003 Tc
0.0018 Tw
[(ede the)6.5( ph)5.7(ysician)75.6()79(s judgment)]TJ
-10.988 -1.497 TD
-0.0015 Tc
0.0808 Tw
[( Th)4.5(e earl)-6(y )5.9(use of )5.9(antibiotics can pr)7.1(ev)5.4(ent persistent, r)13.1(e)-0.7(curr)13.1(ent)]TJ
0.8503 -1.1976 TD
0.0001 Tc
0.0014 Tw
[(and r)14.7(e)0.9(fractor)-15.2(y)1( L)50.1(y)1(me di)5.6(seas)5.7(e)]TJ
-0.8503 -1.497 TD
-0.0011 Tc
0.3739 Tw
[( )-5.9(The )-5.9(durat)-5.5(i)4.4(on of )-5.9(therapy should be guided by clinical)]TJ
0.8503 -1.1976 TD
0.0445 Tw
[(r)7.5(e)-0.3(sponse, rather than )6(by an arbi)]TJ
12.3593 0 TD
0.0444 Tw
[(trar)-16.3(y \(i.e., 30 day\) tr)7.6(eatment)]TJ
-12.3593 -1.1976 TD
0.0001 Tc
0 Tw
[(cours)5.7(e)]TJ
-0.8503 -1.497 TD
-0.0014 Tc
0.2484 Tw
[( The practice )6(of stopping )6(an)]TJ
12.4611 0 TD
-0.0005 Tc
0.2415 Tw
[(tibiotics to allo)12.4(w for delay)6.4(e)0.3(d)]TJ
-11.6108 -1.1976 TD
-0.0003 Tc
0.0377 Tw
[(r)8.3(e)0.5(co)18.6(v)6.6(e)0.5(r)-15.6(y)0.6( is not r)14.3(e)0.5(commend)5.7(ed for persi)5.2(s)-0.7(tent L)43.7(y)0.6(me di)5.2(sease. I)14.3(n)]TJ
T*
-0.0007 Tc
0.4094 Tw
[(t)-5.1(h)5.3(ese cases, it is r)7.9(e)0.1(asonable t)-5.1(o)0.3( continue tr)7.9(eatment for)]TJ
T*
-0.0016 Tc
0.2965 Tw
[(severa)-4.8(l)-251.6(m)1(onths af)-5(ter clinical )-6(and l)-6.1(a)1.2(bora)-4.8(tor)-16.9(y)-0.7( a)-4.8(b)1.4(nor)-4.9(m)1(alities)]TJ
T*
-0.0004 Tc
0.0019 Tw
[(hav)6.5(e)0.4( begun to r)14.2(e)0.4(solv)6.5(e and)5.6( sympto)6.6(ms)5.2( hav)6.4(e)0.4( d)5.6(i)-0.9(sappear)14.2(e)0.4(d)]TJ
/F5 1 Tf
9.6 0 0 10.02 56.88 154.3398 Tm
-0.006 Tc
0.001 Tw
[(Sect)-6(ion I)-7.2(I: Ne)21.5(w)6.5( presentat)-6(o)2.7(ns)]TJ
/F1 1 Tf
10.02 0 0 10.02 56.88 142.3401 Tm
-0.0016 Tc
0.2007 Tw
[(L)48.4(y)-0.7(me disease was )6(f)-5(i)3.9(r)-4.9(s)-2(t )6(descr)-4.9(i)-2.1(bed )6(in 19)-4.6(77 as )6()-6.1(L)48.4(yme ar)-10.9(thr)-4.9(i)-2.1(tis)40()]TJ
T*
-0.0011 Tc
0.1643 Tw
[(among )6(patients initially tho)5.9(u)-4.1(ght )]TJ
13.3054 0 TD
0.0001 Tc
0.1571 Tw
[(t)-4.3(o)7.1( )-6(hav)7(e)0.9( arthritis or juv)12.9(e)0.9(nile)]TJ
-13.3054 -1.1976 TD
0.0028 Tc
0.1544 Tw
[(r)5.5(h)2.8(e)3.6(u)5.8(m)5.4(a)5.6(to)3.8(i)8.3(d)2.8( a)5.6(r)-0.5(th)8.8(rit)4.4(i)8.3(s )]TJ
7.02 0 0 7.02 140.4 118.3404 Tm
-0.0042 Tc
0 Tw
([11])Tj
10.02 0 0 10.02 151.86 118.3401 Tm
-0.0011 Tc
0.1583 Tw
[(. I)25.5(t)0.5( was )6(later r)13.5(e)-0.3(named )6(L)42.9(yme )6(disease)29.6()]TJ
-9.479 -1.1976 TD
-0.0014 Tc
0.0987 Tw
[(follo)11.5(wing)-4.5( r)13.2(e)-0.6(cognition of a)-4.6( comb)]TJ
12.7545 0 TD
-0.0012 Tc
0.0985 Tw
[(ination )-6(of car)13.4(d)-1.2(iac, neur)7.4(ologic)]TJ
-12.7545 -1.1976 TD
-0.0008 Tc
0.0861 Tw
[(and rh)5.2(eumatologic pr)7.8(esentations,)]TJ
12.976 0 TD
-0.0013 Tc
0.0866 Tw
[( incl)-5.8(uding hear)-10.6(t block, men-)]TJ
-12.976 -1.1976 TD
0.0568 Tw
[(ingitis and Bell)12.1()77.9(s)-1.8( palsy)89.3(.)-2.9( F)33.6(o)-0.4(r mor)13.2(e)]TJ
12.6527 0 TD
-0.0023 Tc
0.0577 Tw
[( t)-6.7(h)3.7(a)-5.5(n)1.7( 10)-250.8(year)-5.6(s, var)-5.6(i)-2.8(able symp-)]TJ
-12.6527 -1.1976 TD
-0.0003 Tc
0.1754 Tw
[(tomatic c)4.5(o)0.7(nditi)5.2(o)0.7(ns hav)6.6(e)0.5( been r)14.3(e)0.5(cogni)5.2(z)5.4(ed in)3.7(cluding en)3.7(cep)3.7(h)-0.3(a-)]TJ
T*
-0.0012 Tc
0.0027 Tw
[(lopathy and )6(neur)7.4(opsy)11.7(ch)]TJ
9.2335 0 TD
-0.0015 Tc
0.003 Tw
[(iatric pr)7.1(esentations.)]TJ
/F5 1 Tf
7.98 0 0 9 312 717.32 Tm
0.0015 Tc
-0.0033 Tw
[(8. S)-4.8(y)-5(m)-13.4(p)-7.7(to)-5.1(m)-13.4(a)-7.7(ti)-6.6(c)-5.1( )-7.5(pre)-5.1(s)-2.1(e)-5.1(n)-7.5(ta)-15.2(tio)-12.6(n)]TJ
/F1 1 Tf
10.02 0 0 10.02 312 704.3601 Tm
-0.0009 Tc
-0.0216 Tw
[(V)88.3(a)1.9(riable symptomatic pr)13.7(esentation)]TJ
13.3054 0 TD
-0.0068 Tc
-0.0157 Tw
[(s)-7.2( h)-6.8(a)-4(ve)-6( b)-9.8(e)-6(en)-8.7( i)-7.3(n)-2.8(c)-8(r)1.8(ea)-10(s)-7.2(i)-1.3(n)-8.7(g)-3.9(l)-5.3(y)-5.9( d)-6.8(o)-5.8(c)-8(-)]TJ
-13.3054 -1.1976 TD
-0.0005 Tc
0.014 Tw
[(umented )6(in L)49.5(y)0.4(me)6.3( dise)6.3(ase, with)5.5( the best )6(example being )6(enceph-)]TJ
T*
-0.0011 Tc
0 Tw
(alopathy )Tj
7.02 0 0 7.02 348.36 680.3604 Tm
-0.0041 Tc
[([1)-8.4(2])]TJ
10.02 0 0 10.02 359.82 680.3601 Tm
0.0003 Tc
0.079 Tw
[(. E)9.4(n)-1.6(c)5.1(e)1.1(phalop)4.3(athi)5.8(c pr)14.9(esentation)4.3(s w)7.6(e)1.1(r)8.9(e)1.1( desc)5.1(ri)5.8(bed)6.3( )-6(i)5.8(n)]TJ
-4.7725 -1.1976 TD
-0.0009 Tc
0.0563 Tw
[(an initial )-6(c)3.9(o)0.1(hor)-10.2(t)0.7( of )-6(27 )-6(pati)4.6(ents as a symptom complex )-6(i)4.6(n)-2.8(c)3.9(l)-5.4(ud-)]TJ
T*
-0.0014 Tc
0.3442 Tw
[(ing )-6(memor)-16.7(y)-0.5( )-6(loss \()-4.8(81%\), f)-4.8(a)1.4(tigu)-4.4(e \()-4.8(74%\), headache )-6(\(48%\),)]TJ
T*
-0.0016 Tc
0.3324 Tw
[(depr)7(ession \(37%\), )6(sleep distur)-4.9(bance \(30%\) )6(a)-4.8(n)2.4(d )5.9(irr)-4.9(i)3.9(ta)-4.8(bility)]TJ
T*
-0.0013 Tc
-0.0212 Tw
[(\(26%\), often )-6(w)6(i)-1.8(thout)-5.7( objectiv)5.5(e markers )]TJ
7.02 0 0 7.02 465.9 632.3604 Tm
-0.0043 Tc
0 Tw
[([)-9.1(12])]TJ
10.02 0 0 10.02 477.36 632.3601 Tm
0.0002 Tc
-0.0226 Tw
[(. O)4.8(n)4.2(ly two)7.2( )-5.9(of the 27)]TJ
-16.503 -1.1976 TD
-0.0003 Tc
0.0138 Tw
[(patie)6.5(n)-2.2(ts pr)14.3(esented with obj)-4.8(e)6.5(ctiv)]TJ
12.2395 0 TD
-0.001 Tc
0.0205 Tw
[(e )6(findings on lumbar )6(punctur)13.6(e)-0.2(:)]TJ
-12.2395 -1.1976 TD
0.0324 Tw
[(one had )6(pleocytos)4.6(i)-1.5(s \(sev)5.8(en cells\) and a second )5.9(had an )6(antibody)]TJ
T*
-0.0008 Tc
-0.0037 Tw
[(index of gr)13.8(eater )-6(than )-6(one )]TJ
7.02 0 0 7.02 411 596.3604 Tm
-0.0041 Tc
0 Tw
[([12)-8.4(])]TJ
10.02 0 0 10.02 422.46 596.3601 Tm
0 Tc
(.)Tj
-10.1737 -1.1976 TD
0.0089 Tc
0.0884 Tw
[(N)31.4(e)3.7(ur)5.6(opsy)9.8(chiatric pr)11.6(esentations in acute)3.7( and chr)5.6(o)-2.1(nic L)46.9(y)-2.2(m)5.5(e)]TJ
-0.8503 -1.1976 TD
0.0094 Tc
0.2316 Tw
[(d)3.4(i)-3.1(sease hav)10.3(e)-1.8( been incr)12.1(easingly r)12.1(e)-1.8(cognize)4.2(d)-2.6( and can includ)3.4(e)]TJ
T*
-0.014 Tw
[(d)3.5(e)-1.7(pr)12.2(ession, )-6(anxiet)5.1(y and)3.5( rage )]TJ
7.02 0 0 7.02 425.04 560.3604 Tm
-0.0041 Tc
0 Tw
[([1)-8.4(3])]TJ
10.02 0 0 10.02 436.5 560.3601 Tm
0.0101 Tc
-0.0146 Tw
[(. Th)4.1(ese ar)12.8(e pr)6.8(e)4.9(s)-2.2(umabl)5.6(y)-1( r)6.8(e)4.9(late)4.9(d)]TJ
-12.4251 -1.1976 TD
0.0078 Tc
0.0057 Tw
[(to pers)-4.5(is)-4.5(tent infection )6(an)-6.1(d )6(are po)]TJ
13.018 0 TD
0.0097 Tc
0.0038 Tw
[(tentially )6(r)12.4(e)-1.5(v)4.6(e)4.5(rsible)4.5( w)5(i)-2.8(th ant)5.3(i)-2.8(-)]TJ
-13.018 -1.1976 TD
0.0089 Tc
0.268 Tw
[(biotics. N)31.4(e)-2.3(ur)5.6(opsy)9.8(chiatric sy)]TJ
11.4311 0 TD
[(m)5.5(p)0.9(toms may r)5.6(e)3.7(flect additional)]TJ
-11.4311 -1.1976 TD
0.008 Tc
0.1372 Tw
[(psy)8.9(c)0.8(h)-3.9(o)3(s)-4.3(o)-3(cial p)-6(r)4.7(oces)-4.3(ses i)-4.5(n)0.1(clud)-4(ing )-6(th)-3.9(e )-6(str)10.7(e)-3.2(ss)-4.3( of c)-5.2(o)3(pi)-4.5(ng with)-3.9( a)]TJ
T*
0.0064 Tc
0.0011 Tw
[(chroni)-6.1(c i)-6.1(l)-4.1(ln)-7.5(es)-5.9(s.)]TJ
0.8503 -1.1976 TD
-0.0012 Tc
0.3081 Tw
[(Asch and colleag)-4.3(ues f)-4.6(o)-0.2(und )-6(that )-6(mor)13.4(e)-0.4( )-6(than half)-4.6( of)-4.6( 21)-4.2(5)]TJ
-0.8503 -1.1976 TD
0.0506 Tw
[(patie)5.6(n)-3.1(ts in a L)42.8(y)-0.3(me-endemic r)13.4(e)]TJ
11.8144 0 TD
-0.0002 Tc
0.0496 Tw
[(gi)5.3(on had s)5.4(y)0.7(mptomati)5.3(c pr)8.4(esenta-)]TJ
-11.8144 -1.1976 TD
-0.0012 Tc
0.0865 Tw
[(tions of chr)7.4(o)-0.2(nic L)48.8(y)-0.3(me disease)5.6( )]TJ
7.02 0 0 7.02 431.82 476.3604 Tm
-0.0038 Tc
0 Tw
[([4)-8.1(])]TJ
10.02 0 0 10.02 439.8 476.3601 Tm
-0.0003 Tc
0.0796 Tw
[(. The )-6(pat)-4.7(i)5.2(ents pr)14.3(esented with)]TJ
-12.7545 -1.1976 TD
-0.0007 Tc
0.122 Tw
[(chro)6.3(nic fatigue, headaches and joint pai)4.8(n)-2.6( \(but not h)5.3(e)0.1(ad)5.3(aches)]TJ
0 -1.2036 TD
-0.0009 Tc
0.0024 Tw
[(alone\) in )6(t)-5.3(h)5.1(is r)13.7(e)-0.1(trospectiv)11.9(e cohor)-10.2(t)0.7( study)83.8(.)]TJ
/F5 1 Tf
7.98 0 0 9 312 429.32 Tm
0.014 Tc
-0.0083 Tw
[(9)10.1(.)8.3( )7.5(S)7.7(y)7.5(mp)4.8(t)13.2(o)7.4(ms)10.4( o)7.4(f)15.8( L)32.9(y)7.5(me)7.4( )7.5(d)4.8(i)13.4(se)7.4(a)4.8(s)10.4(e)]TJ
/F1 1 Tf
10.02 0 0 10.02 312 415.3401 Tm
0.4623 Tc
0 Tw
[(F)515.3(a)465.1(t)457.9(i)467.8(g)459.2(u)465.3(e)]TJ
0 -1.3713 TD
-0.0013 Tc
0.0028 Tw
[()-463.6(L)0.8(o)11.6(w)0( )6(grade fev)5.5(e)-0.5(rs, hot flashes)40.3()0.2( or chills)]TJ
0 -1.3653 TD
0.4623 Tc
-0.4608 Tw
[(N)490.8(i)461.8(g)465.2(h)462.3(t)463.9( s)467.9(w)469.6(e)463.1(a)459.1(t)463.9(s)]TJ
T*
-0.4668 Tw
[(S)478.2(o)463.3(r)471(e)463.1( t)463.9(h)462.3(r)471(o)463.3(a)459.1(t)]TJ
0 -1.3713 TD
-0.0006 Tc
-0.0039 Tw
[()-462.9(S)33.3(wollen glands)]TJ
0 -1.3653 TD
0.4623 Tc
-0.4668 Tw
[(S)490.2(t)463.9(i)461.8(f)464.9(f)458.9( n)460.4(e)463.1(c)467.1(k)]TJ
T*
-0.0009 Tc
0.2599 Tw
[()-463.2(M)18.9(igrating ar)-10.2(thralgias, stiffn)]TJ
11.9401 0 TD
-0.0015 Tc
0.2605 Tw
[(ess )-6(and, less commonl)-6(y)89.2(,)-3( f)-4.9(r)1.2(ank)]TJ
-11.0898 -1.1976 TD
-0.0032 Tc
0 Tw
[(ar)-6.5(t)-7.6(h)2.8(r)-6.5(i)-3.7(tis)]TJ
-0.8503 -1.3713 TD
0.4623 Tc
[(M)500(y)463.2(a)459.1(l)463.8(g)465.2(i)461.8(a)]TJ
0 -1.3653 TD
-0.0006 Tc
0.0021 Tw
[()-462.9(C)6.8(hest pai)4.9(n)-2.5( )6(and palpitations)]TJ
0 -1.3772 TD
0.4623 Tc
-0.4608 Tw
[(A)480.5(b)459.3(d)468.3(o)463.3(m)464.9(i)461.8(n)460.4(a)465.1(l)463.8( p)466.3(a)459.1(i)467.8(n)460.4(,)466.8( n)460.4(a)465.1(u)465.3(s)461.9(e)463.1(a)]TJ
T*
-0.0009 Tc
0 Tw
[()-463.2(D)18.6(ia)-4.1(rrhea)]TJ
T*
-0.001 Tc
-0.0035 Tw
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T*
-0.0024 Tc
-0.0021 Tw
[(persistent)-6.8( inf)-5.8(e)-1.6(ct)-6.8(ion)-4.3( mec)-3.6(h)-2.4(an)-4.3(ism.)]TJ
/F5 1 Tf
7.98 0 0 9 34.2 117.32 Tm
0.0061 Tc
-0.0004 Tw
[(12. Se)22(v)17.2(e)-0.5(r)-19.8(i)5.5(t)5.3(y)-0.4( of )7.5(chr)17.8(o)-0.5(ni)5.5(c L)25(y)-0.4(m)-8.8(e)-0.5( disease)]TJ
/F1 1 Tf
10.02 0 0 10.02 34.2 104.3001 Tm
-0.0003 Tc
0.0796 Tw
[(F)40.7(o)0.7(r patients with chr)8.3(o)0.7(nic L)43.7(y)0.6(me di)]TJ
13.515 0 TD
-0.0006 Tc
0.0799 Tw
[(sease, )-6(the quality )-6(of li)4.9(fe has)]TJ
-13.515 -1.1976 TD
-0.0019 Tc
0.207 Tw
[(been ev)5(al)-6.4(uated in a cl)-6.4(inical )]TJ
11.5868 0 TD
-0.0006 Tc
0.2057 Tw
[(trial sponso)6.4(r)8(e)0.2(d b)8.4(y)0.3( the )6(N)27.9(a)2.2(tional)]TJ
-11.5868 -1.1976 TD
-0.0011 Tc
0.0745 Tw
[(I)13.5(n)2.9(stitu)-4.1(t)0.5(es of)-4.5( H)14.5(e)-0.3(alth )-5.9(\(NIH\) )-5.9(u)-4.1(s)4.5(in)]TJ
12.485 0 TD
-0.0008 Tc
0.0801 Tw
[(g a standar)13.8(d)5.2(iz)4.9(ed )5.9(ques)4.8(tionnair)7.8(e)]TJ
7.02 0 0 7.02 34.2 68.3004 Tm
-0.0042 Tc
0 Tw
([23])Tj
10.02 0 0 10.02 45.66 68.3001 Tm
0.1871 Tc
[(.)191.6( )-6(T)188.4(h)187.1(e)187.9( q)187.1(u)190.1(a)183.9(l)188.6(i)186.6(t)188.7(y)188( o)188.1(f)183.7( l)182.6(i)192.6(f)183.7(e)187.9( o)188.1(f)183.7( t)188.7(h)187.1(e)187.9( )-6(1)190.1(0)190.1(7)184.1( i)186.6(n)185.2(d)193.1(i)186.6(v)188(i)186.6(d)187.1(u)190.1(a)189.9(l)188.6(s)186.7( )-6(w)188.4(i)186.6(t)188.7(h)187.1( c)185.9(h)187.1(r)195.7(o)188.1(n)191.1(i)186.6(c)]TJ
24.3174 64.6766 TD
-0.0009 Tc
0.0563 Tw
[(L)49.1(y)0(me disease was worse than that of patients with T)114.2(y)0(pe 2 dia-)]TJ
0 -1.1976 TD
-0.0015 Tc
0.009 Tw
[(betes or )-6(a r)7.1(e)-0.7(cent hear)-10.8(t at)-5.9(tack, an)]TJ
12.4611 0 TD
-0.0017 Tc
0.0092 Tw
[(d )-6(equiv)5.2(a)-4.9(lent )-6(to that of patients)]TJ
-12.4611 -1.1976 TD
-0.0009 Tc
0.188 Tw
[(with congestiv)5.9(e)-0.1( heart failur)7.8(e or osteoar)-10.2(t)0.7(hritis. M)24.9(o)0.1(r)7.7(e)-0.1(o)18(v)5.9(er)61.6(, the)]TJ
T*
-0.0008 Tc
0.0143 Tw
[(av)6.1(erage L)49.2(y)0.1(me dise)6(ase )6(duration of)]TJ
12.6707 0 TD
-0.0002 Tc
0.0077 Tw
[( 4.7)-248.7(y)6.7(ears in )-6(subjects enr)8.4(o)0.8(lling)]TJ
-12.6707 -1.1976 TD
-0.0009 Tc
0.1102 Tw
[(in the study emphasiz)10.8(ed the chr)7.7(o)0.1(nic natur)7.8(e)-0.1( of the condition.)]TJ
T*
-0.001 Tc
0.1342 Tw
[(F)34(i)-1.5(nal)-5.5(l)0.5(y)89.7(,)-2.5( the failur)7.6(e of )-6(1)-243.5(m)-4.4(o)6(n)-2.9(th of )-6(i.v)77.7(.)-2.5( ceftriax)5.8(one follo)11.9(w)6.3(e)-0.2(d b)8(y)]TJ
T*
-0.0007 Tc
-0.0217 Tw
[(2)-249.2(m)1.9(onths of o)6.3(r)-4(al do)6.3(xy)12.2(cy)12.2(cline delineated the )6(potential)-5.2( )6(fo)6.3(r )6(a )6(poor)]TJ
T*
-0.0011 Tc
0.0026 Tw
[(outcome in )6(chr)7.5(o)-0.1(nic L)48.9(y)-0.2(me disease )]TJ
7.02 0 0 7.02 419.76 632.3604 Tm
-0.0041 Tc
0 Tw
[([25)-8.4(])]TJ
10.02 0 0 10.02 431.22 632.3601 Tm
0 Tc
(.)Tj
/F5 1 Tf
9.6 0 0 10.02 289.32 608.3597 Tm
-0.0041 Tc
-0.0009 Tw
[(Se)4.6(ctio)4.7(n III: Dia)5.9(g)5.9(n)2.1(os)4.7(tic)4.7( c)4.7(o)-1.6(nc)4.6(e)4.7(r)-21.6(ns)]TJ
/F1 1 Tf
10.02 0 0 10.02 289.32 596.3601 Tm
-0.0198 Tc
0.0333 Tw
[(The )6(most im)-5.3(por)-11.2(t)-0.2(ant )6(method for pr)]TJ
13.1198 0 TD
-0.0187 Tc
0.0262 Tw
[(ev)6.1(enting chr)7.9(o)0.2(nic L)43.3(y)0.1(me )-6(d)5.3(i)-1.2(sease)]TJ
-13.1198 -1.1976 TD
0.0099 Tc
-0.0024 Tw
[(i)27.4(s)3.6( r)6.6(e)4.7(co)4.9(gnition of th)3.9(e early)4.8( )-6(m)6.5(a)]TJ
11.479 0 TD
0.0083 Tc
0.0052 Tw
[(nifestations of the d)8.3(i)13.8(s)7.9(e)9.1(a)11.1(s)7.9(e)27.1(.)]TJ
/F5 1 Tf
7.98 0 0 9 289.32 561.32 Tm
0.0072 Tc
-0.0015 Tw
[(13.)9( Atypi)6.6(c)0.6(al)6.6( ear)-11.1(l)-0.9(y )7.5(present)6.4(a)-9.5(t)6.4(i)6.6(ons)]TJ
/F1 1 Tf
10.02 0 0 10.02 289.32 548.3601 Tm
0.0089 Tc
0.0405 Tw
[(Early L)46.9(y)-2.2(m)5.5(e)-2.3( disease classically pr)]TJ
12.7126 0 TD
0.0096 Tc
0.0398 Tw
[(esents with)3.6( a single)4.4( er)-17.7(y)4.5(t)-0.8(he)4.4(ma)]TJ
-12.7126 -1.1976 TD
0.0089 Tc
0.0345 Tw
[(migrans \(EM)4.7( or bullseye)27.7()4.4(\) rash. The EM rash may be absent)]TJ
T*
0.0096 Tc
0.2374 Tw
[(in o)16.6(v)4.5(er )6(50% )6(of L)47.6(y)-1.5(m)6.2(e)-1.6( d)3.6(i)-2.9(sease case)4.4(s, h)3.6(o)10.6(w)4.9(e)4.4(v)4.5(e)-1.6(r)6.3( )]TJ
7.02 0 0 7.02 483.06 524.3604 Tm
-0.0043 Tc
0 Tw
[([)-9.1(25])]TJ
10.02 0 0 10.02 494.52 524.3601 Tm
0.0117 Tc
0.2353 Tw
[(. P)45.7(a)2.5(t)7.3(i)-0.8(en)3.8(ts)]TJ
-20.479 -1.1976 TD
0.009 Tc
0.0404 Tw
[(should b)6(e)-2.2( made awar)5.7(e of the )6(si)]TJ
12.3473 0 TD
0.0092 Tc
0.0402 Tw
[(gnificance of a range of rashes)]TJ
-12.3473 -1.1976 TD
0.01 Tc
-0.0025 Tw
[(be)4.8(y)4.9(o)-1(nd)4( th)4(e )6(cla)6.8(s)-2.3(s)3.7(i)-2.5(c)2.8( EM)5.8(, )6(inc)2.8(l)-0.5(ud)4(ing m)6.6(u)1(lti)3.5(p)-4(l)5.5(e)-1.2(, flat, )6(rais)3.7(ed)4( or )6(blis)3.7(-)]TJ
T*
0.0095 Tc
0.1656 Tw
[(tering rashes. Central )]TJ
9.1737 0 TD
0.0112 Tc
0.1699 Tw
[(cl)6.7(eari)4.7(ng)8.1( wa)8(s )6(abse)6(nt)6.8( i)4.7(n)3.3( o)18.2(v)12.1(er )5.9(half )5.9(of )6(a)]TJ
-9.1737 -1.1976 TD
0.0089 Tc
-0.0074 Tw
[(series )-6(of EM rashes )]TJ
7.02 0 0 7.02 367.02 476.3604 Tm
-0.0042 Tc
0 Tw
([26])Tj
10.02 0 0 10.02 378.48 476.3601 Tm
0.0081 Tc
-0.0066 Tw
[(. )-6(Rashes)-4.2( can)-5.8( also mi)-4.4(mi)-4.4(c )-6(other )-6(common)]TJ
-8.8982 -1.1976 TD
0.0092 Tc
0.0701 Tw
[(pr)11.9(esentations including a )5.9(spide)4(r)-0.1( bit)4.8(e)-2(, ringw)4.5(o)-1.8(rm, o)4.2(r)-0.1( cellul)4.7(i)-3.3(tis.)]TJ
0 -1.2036 TD
0.0068 Tc
0.0246 Tw
[(One)-4.4( )6(s)-5.5(e)1.6(ri)-5.7(es)-5.5( )5.9(o)-4.2(f)-2.6( el)-3.7(e)-4.4(v)7.7(e)-4.4(n)-1.1( EM rash)-5.1(es)-5.5( )6(w)-3.9(a)-2.4(s mis)-5.5(d)0.8(iagn)-7.1(os)-5.5(ed)-5.2( )5.9(and)-5.2( )6(t)-3.6(r)9.5(e)-4.4(a)-2.4(t)-3.6(e)-4.4(d)]TJ
0 -1.1976 TD
0.0097 Tc
0.0337 Tw
[(as ce)4.5(llulitis, with al)5.2(l ele)4.5(v)4.6(en pa)]TJ
11.8263 0 TD
[(tients sh)3.6(o)10.6(w)4.9(ing clinical ev)4.5(id)3.6(ence)]TJ
-11.8263 -1.1976 TD
0.007 Tc
0.0065 Tw
[(of L)45(y)1.9(me)-4.2( )6(d)-5(i)0.5(s)-5.3(e)1.8(as)-5.3(e progres)-5.3(s)0.7(i)-5.5(o)2(n )]TJ
7.02 0 0 7.02 401.16 428.3004 Tm
-0.0042 Tc
0 Tw
([27])Tj
10.02 0 0 10.02 412.62 428.3001 Tm
0 Tc
(.)Tj
-11.4551 -1.1976 TD
-0.0194 Tc
0.1347 Tw
[(P)8.6(h)-1.4(y)-6.6(s)-1.8(icia)-4.6(ns )6(s)-7.8(h)-1.4(ou)-4.4(ld b)-4.4(e)-0.6( aw)-6.1(ar)7.2(e t)-5.8(h)-1.4(at)-5.8( fe)-12.6(wer)-4.8( tha)-4.6(n)-3.4( )6(5)-4.4(0)-4.4(%)4.2( of)-4.8( al)-5.9(l L)42.6(y)-0.6(m)-4.9(e)]TJ
-0.8503 -1.1976 TD
-0.0181 Tc
-0.0163 Tw
[(dise)-5.3(ase)-5.3( )6(pati)-6.6(ents r)8.5(e)0.7(call)-4.6( a t)-4.5(i)-0.6(ckbit)-4.5(e)0.7( )]TJ
7.02 0 0 7.02 404.82 404.3004 Tm
-0.0041 Tc
0 Tw
[([28)-8.4(])]TJ
10.02 0 0 10.02 416.28 404.3001 Tm
-0.0173 Tc
-0.0171 Tw
[(. Early )6(L)44.7(y)1.5(me dis)-5.7(e)1.5(as)-5.7(e should)-5.3( )6(also)]TJ
-12.6707 -1.1976 TD
0.0554 Tc
0 Tw
[(b)76.4(e)68.2( c)72.2(o)74.3(n)71.4(s)73(i)72.9(d)73.4(e)68.2(r)82(e)74.2(d)73.4( i)72.9(n)71.4( a)70.2(n)77.4( e)68.2(v)80.2(a)70.2(l)74.9(u)70.4(a)76.2(t)69(i)72.9(o)74.3(n)71.4( o)74.3(f)69.9( )122.7(o)74.3(f)69.9(f)70(-)76(s)67(e)74.2(a)76.2(s)67(o)74.3(n)143.3()74.8( )-6(o)74.3(n)71.4(s)73(e)74.2(t)69( w)74.7(h)73.4(e)74.2(n)71.4( f)70(l)74.9(u)70.4(-)76(l)68.9(i)72.9(k)70.3(e)]TJ
T*
-0.0162 Tc
0.1255 Tw
[(symp)5.8(toms, fev)8.6(e)2.6(r an)5.8(d )6(chills occur )]TJ
12.9222 0 TD
-0.0175 Tc
0.1268 Tw
[(in t)-3.9(h)0.5(e summer and fal)-4(l)2(. Earl)-4(y)]TJ
-12.9222 -1.1976 TD
0.1806 Tw
[(r)9.2(e)1.4(cogniti)-5.9(o)1.5(n of at)-3.8(ypical)-3.9( e)-4.6(a)3.4(rly)-4.5( L)44.6(y)1.4(me dis)-5.8(e)1.4(ase pr)9.2(es)-5.8(entatio)-4.5(n)-1.4( is )-6(mos)-5.8(t)]TJ
T*
-0.0177 Tc
0.0012 Tw
[(likel)-4.2(y)1.1( t)-4.1(o)1.2( occur w)-4.4(h)0.3(en the)-4.9( pat)-4.1(i)-0.2(ent has been ed)-5.7(ucate)-4.9(d)0.3( on thi)-6.2(s)-0.1( topic.)]TJ
/F5 1 Tf
7.98 0 0 9 289.32 333.32 Tm
0.007 Tc
-0.0013 Tw
[(14.)8.8( Ne)15.4(w chr)18.7(o)0.4(ni)6.4(c L)25.9(y)0.5(me)-7.1( )7.5(di)6.4(sease )7.5(present)6.2(a)-9.7(t)6.2(i)6.4(ons)]TJ
/F1 1 Tf
10.02 0 0 10.02 289.32 320.3001 Tm
-0.0008 Tc
0.0502 Tw
[(A detailed histor)-16.1(y )-6(may )-6(be helpful )-6(for )-6(sugge)6(s)-1.2(ting a diagnosi)4.7(s )-6(of)]TJ
T*
-0.0003 Tc
0.1156 Tw
[(c)4.5(h)-0.3(ronic)4.5( )-6(L)49.7(y)0.6(me )-6(di)5.2(sease. H)21.3(e)0.5(adac)4.5(he, stiff ne)6.5(ck, sleep disturbance)]TJ
T*
-0.0014 Tc
0.0029 Tw
[(and )-6(pr)7.2(ob)-4.4(lems with memor)-16.7(y)-0.5( a)-4.6(n)2.6(d concentr)-4.7(ation )-6(ar)7.2(e finding)-4.5(s)-1.7( fr)7.2(e-)]TJ
T*
-0.001 Tc
-0.0214 Tw
[(quentl)-5.5(y associated with neur)7.6(ologic L)43(y)-0.1(me dise)5.8(ase. )-5.9(O)9.6(t)0.6(her )-5.9(clues )-5.9(to)]TJ
T*
0.2121 Tw
[(L)49(y)-0.1(me )-6(d)5(i)-1.5(sease )-6(h)5(a)-4.2(v)5.8(e)-0.2( been identified, )-6(although these hav)5.9(e)-0.2( not)]TJ
T*
0.1343 Tw
[(been consistently pr)7.5(esent in )]TJ
11.4192 0 TD
-0.0008 Tc
0.134 Tw
[(each patient: numbness and tin-)]TJ
-11.4192 -1.1976 TD
-0.0009 Tc
0.0323 Tw
[(gling, )-6(muscle twitching, photos)4.7(en)]TJ
13.1257 0 TD
-0.0008 Tc
[(sitivity)83.9(, hyperacusis, t)-5.2(i)4.7(nnitus,)]TJ
-13.1257 -1.1976 TD
-0.0005 Tc
-0.004 Tw
[(lightheadedness and depr)14.1(ession.)]TJ
0.8503 -1.1976 TD
-0.0204 Tc
0.2195 Tw
[(M)29.3(o)-1.5(st patients diagno)4.5(se)4.3(d )6(wit)5.2(h)-2.4( )]TJ
11.8802 0 TD
-0.0191 Tc
0.2182 Tw
[(ch)4.9(r)7.5(o)-0.2(n)2.9(i)4.4(c )6(L)48.9(y)-0.3(me)5.6( d)4.9(i)-1.6(s)4.5(e)-0.4(as)4.5(e h)4.9(a)1.7(v)5.7(e)5.6( an)]TJ
-12.7305 -1.1976 TD
-0.0202 Tc
0.0277 Tw
[(i)3.3(n)1.8(dol)5.2(e)-1.4(nt ons)3.4(e)-1.4(t and v)10.6(a)0.6(riable)4.5( )-6(co)4.7(ur)]TJ
11.8683 0 TD
[(se. N)32.4(e)-1.3(ur)6.5(o)4.8(l)-0.6(ogi)3.4(c)-3.3( and)3.9( )-6(rh)3.9(eum)6.4(a)0.7(tolo)4.8(gic)]TJ
-11.8683 -1.1976 TD
-0.0207 Tc
0.136 Tw
[(symptoms ar)11.9(e characteristic, and )]TJ
12.6587 0 TD
-0.0192 Tc
0.1345 Tw
[(i)4.3(n)2.8(cr)13.4(eas)4.4(e)-0.4(d)4.8( se)5.5(v)5.6(e)-0.4(ri)4.3(ty)5.6( )-6(o)5.7(f)1.3( sy)5.6(mptoms)]TJ
-12.6587 -1.1976 TD
-0.0204 Tc
0.1476 Tw
[(o)4.5(n)-4.4( wake)4.3(ning is )-6(com)6.1(m)0.1(on. )-6(N)32.1(e)4.3(ur)6.2(opsy)16.4(chiatric sy)4.4(mptoms alone ar)12.2(e)]TJ
T*
-0.0237 Tc
0.1809 Tw
[(m)-3.2(o)1.2(re o)-4.8(f)-3.2(t)-4.1(e)1(n )-6(se)-4.9(en i)-6.2(n)-1.7( ch)-5.7(ro)-4.8(nic t)-4.1(h)-5.7(a)-2.9(n)]TJ
12.5689 0 TD
-0.0206 Tc
0.1778 Tw
[( acute L)47.4(y)4.2(me disease. Although)]TJ
-12.5689 -1.1976 TD
-0.0208 Tc
0.0941 Tw
[(many st)4.8(udies hav)10(e)-2( found that such)]TJ
13.1497 0 TD
-0.0205 Tc
0.0939 Tw
[( clinical featur)6.1(es ar)12.1(e )6(often )6(not)]TJ
-13.1497 -1.1976 TD
-0.0212 Tc
0.0107 Tw
[(unique )-6(to L)46.8(y)-2.4(me )-6(disease, the striki)]TJ
12.2455 0 TD
-0.0208 Tc
0.0103 Tw
[(ng association of musculoskeletal)]TJ
-12.2455 -1.1976 TD
-0.0206 Tc
0.0281 Tw
[(and neur)6(o)4.3(p)-4.6(sy)10.2(chiatric sy)4.2(mptom)5.9(s)-3(, the )6(v)4.2(a)0.2(riability )6(of t)5(h)-2.6(e)4.1(s)-3(e )6(sy)4.2(mptoms)]TJ
T*
-0.0213 Tc
-0.0011 Tw
[(and )-5.9(their r)5.3(e)3.4(curr)11.3(ent )-5.9(natur)11.3(e)-2.5( may )-5.9(suppor)-6.7(t)-1.7( a )-5.9(diagnosis of the disease.)]TJ
/F5 1 Tf
7.98 0 0 9 289.32 105.32 Tm
0.0008 Tc
0.0049 Tw
[(15)-10.6(. Th)-8.2(e)-5.8( lim)-14.1(it)-7.5(a)-8.4(t)0(i)-7.3(o)-5.8(ns)-10.3( )7.5(o)-5.8(f)-4.9( p)-8.4(h)29.4(y)-5.7(s)-10.3(ic)-5.8(a)-8.4(l)0.2( f)17.6(i)-7.3(nd)-8.4(in)-8.2(g)-8.4(s)]TJ
/F1 1 Tf
10.02 0 0 10.02 289.32 92.3001 Tm
-0.0002 Tc
0.1454 Tw
[(A c)4.6(o)0.8(mpr)14.4(e)0.6(hens)5.4(iv)6.7(e phys)5.4(ical exami)5.3(n)-2.1(ation s)5.4(h)-0.2(ould)5.8( )-6(be per)-9.5(f)2.4(ormed)5.8(,)]TJ
T*
-0.0009 Tc
0.0024 Tw
[(with special at)-5.3(tention to neur)7.7(ol)]TJ
12.0539 0 TD
-0.0006 Tc
0.0021 Tw
[(ogic, rheumatologic and)5.4( )-6(c)4.2(a)2.2(r)14(d)-0.6(iac)]TJ
-12.0539 -1.1976 TD
-0.0009 Tc
0.0024 Tw
[(symptoms assoc)3.9(i)-1.4(ated)5.1( with )6(L)43.1(y)0(me )6(disease.)]TJ
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/F5 1 Tf
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/GS1 gs
0 Tc
0 Tw
[(ILA)6.7(DS guidel)6.7(ines f)20(or L)26.7(yme dis)6.7(ease)]TJ
/F1 1 Tf
7.98 0 0 7.98 56.88 30.3802 Tm
0.0005 Tc
[(www)74(.futur)9.2(e-dr)-5.8(u)-6.3(g)2.9(s.c)-5.5(o)5.3(m)]TJ
/F6 1 Tf
8.64 0 0 9 545.64 30.3803 Tm
-0.0105 Tc
(S7)Tj
ET
56.88 45.26 498.9 0.48 re
f
BT
/F1 1 Tf
10.02 0 0 10.02 65.4 716.3601 Tm
-0.0213 Tc
0.0048 Tw
[(Physical findings ar)11.3(e n)-5.3(o)3.6(nspecifi)]TJ
11.4431 0 TD
-0.0206 Tc
0.0041 Tw
[(c and )6(often normal, but ar)-6(thritis,)]TJ
-12.2934 -1.1976 TD
-0.0213 Tc
-0.0071 Tw
[(meningitis and Bell)10.1()76(s)2.3( palsy may so)]TJ
12.3234 0 TD
-0.0207 Tc
-0.0077 Tw
[(met)4.9(i)-3.2(mes be noted. A)45.4(v)4.1(ailable data)]TJ
-12.3234 -1.1976 TD
0.076 Tw
[(suggest that o)4.3(b)0.4(jectiv)4.2(e e)4.1(v)-1.8(ide)4.1(n)-4.6(ce)4.1( alone )6(is inadequate to)4.3( make)4.1( tr)12(eat-)]TJ
T*
-0.0191 Tc
0.0086 Tw
[(m)7.4(e)-0.3(n)2.9(t)0.5( de)5.6(ci)4.4(si)4.4(on)2.9(s)4.5(,)-2.6( be)5.6(caus)4.5(e a s)4.5(i)-1.6(gn)2.9(i)4.4(f)1.4(ic)]TJ
12.1617 0 TD
-0.0212 Tc
0.0107 Tw
[(ant number of )-6(chronic L)46.8(y)-2.4(me dis-)]TJ
-12.1617 -1.1976 TD
-0.0217 Tc
0.1549 Tw
[(eas)-4.1(e)3( c)-4.9(a)-0.9(ses may )6(occ)-4.9(u)-0.7(r in s)-4.1(y)3.1(mptoma)]TJ
13.2874 0 TD
-0.0204 Tc
0.1536 Tw
[(tic patients witho)4.5(u)0.6(t obj)5.1(e)-1.6(ctiv)10.4(e)]TJ
-13.2874 -1.1976 TD
-0.0211 Tc
0.0046 Tw
[(featur)11.5(es on examination or confirmator)-18.4(y)-2.3( )6(laborator)-18.4(y)-2.3( )6(testing.)]TJ
0.8503 -1.1976 TD
-0.0011 Tc
0.2182 Tw
[(F)45.9(a)1.7(ctors other than physical f)-4.5(i)4.4(ndings, )6(su)-4.1(ch as a histor)-22.4(y of)]TJ
-0.8503 -1.1976 TD
0.0685 Tw
[(potential )24(exposur)13.5(e)-0.3(, )24(kno)11.8(w)0.2(n )18(tickbites, )18(rashes)-13.4( o)-18.1(r)-16.4( s)-13.4(y)-18.2(m)-16.5(p)-15.1(t)-17.5(o)-18.1(m)-16.5(s)-13.4( c)-20.3(o)-12.1(n)-21(-)]TJ
T*
0.0163 Tc
0.1948 Tw
[(siste)5.1(n)-3.6(t with the)5.1( )-6(ty)5.2(pical multisystem)6.9( )-6(pr)13(esentatio)5.3(n)-3.6( of L)48.3(y)-0.8(me)]TJ
T*
0.0176 Tc
0.0797 Tw
[(d)5.6(i)-0.8(se)6.4(as)5.3(e, must also)6.6( be c)4.4(o)0.6(ns)5.3(id)]TJ
11.4072 0 TD
0.0165 Tc
0.0808 Tw
[(er)7.2(ed)4.5( in d)4.5(e)-0.7(termining wh)4.6(ether)19.2( )23.9(a)19.3(n)]TJ
-11.4072 -1.1976 TD
-0.0009 Tc
-0.0036 Tw
[(i)4.6(n)-2.8(divi)4.6(dual patient is )-6(a )-6(cand)]TJ
10.4072 0 TD
0.0024 Tw
[(id)5.1(ate )6(for ant)-5.3(i)4.6(biot)-5.3(ic therapy)89.8(.)]TJ
/F5 1 Tf
7.98 0 0 9 56.88 573.32 Tm
0.0064 Tc
-0.0007 Tw
[(16. Sen)4.9(s)-4.7(i)5.8(t)5.6(ivi)5.8(t)-1.9(y )7.5(li)5.8(mit)5.6(a)-2.8(ti)5.8(ons of )7.5(test)5.6(in)4.9(g)]TJ
/F1 1 Tf
10.02 0 0 10.02 56.88 560.3601 Tm
-0.0166 Tc
0.078 Tw
[(T)134.4(r)4(eatment deci)-5.1(sions should not )6(be)]TJ
13.024 0 TD
-0.0156 Tc
0.071 Tw
[( based r)5(o)3.3(utinely or )-6(ex)9.2(clusiv)9.2(ely)]TJ
-13.024 -1.1976 TD
-0.0172 Tc
0.2882 Tw
[(on l)-3.7(a)3.6(bo)-4.3(rat)-3.6(o)1.7(r)-20.5(y)-4.3( fi)-5.7(ndings )]TJ
7.02 0 0 7.02 150.42 548.3604 Tm
-0.0038 Tc
0 Tw
[([)-8.6(2)0.5(,25])]TJ
10.02 0 0 10.02 167.16 548.3601 Tm
-0.0146 Tc
0.2856 Tw
[(. T)4.7(h)-2.6(e)4.2( tw)4.7(o)4.3(-)0(tier )6(diagno)4.3(stic cr)6(it)5(eria,)]TJ
-11.006 -1.1976 TD
-0.0165 Tc
0 Tw
[(r)10.1(e)2.3(q)-4.5(u)4.5(i)-5(r)4.1(i)-5(n)-0.5(g both a positive ELISA and wes)-4.9(t)3.1(ern blot, )-6(lacks )-6(sens)-4.9(itivi)-5(t)3.1(y)]TJ
T*
-0.015 Tc
0.0584 Tw
[(a)5.8(n)1(d leav)9.8(es a significant nu)6(mber of)]TJ
12.8623 0 TD
-0.017 Tc
0.0604 Tw
[( indi)-5.5(vid)-5(u)4(als with L)45(y)-4.2(me)-4.2( dis)-5.4(e)1.8(ase)]TJ
-12.8623 -1.1976 TD
-0.0175 Tc
0.0849 Tw
[(und)-5.5(i)0(agnose)-4.7(d and untr)9.1(e)-4.7(a)-2.7(te)-4.7(d )]TJ
7.02 0 0 7.02 162.96 512.3604 Tm
-0.0042 Tc
0 Tw
[([29)-8.5(,)-2.1(30])]TJ
10.02 0 0 10.02 183.18 512.3601 Tm
-0.0165 Tc
0.0839 Tw
[(. )6(These d)-4.5(i)1(agnostic criteri)-5(a)4.3( wer)10.1(e)]TJ
-12.6048 -1.1976 TD
0.1079 Tw
[(intended to impr)10(o)14.3(ve the s)-5(p)-0.6(ecifi)-5.1(c)0.2(ity of tests to aid)-4.6( )6(i)-5.1(n)-0.6( identifying)]TJ
T*
-0.0181 Tc
0.0855 Tw
[(w)7.2(e)-5.3(ll)-4.6(-defi)-6.6(n)-2.1(ed L)43.9(y)0.7(me )6(d)-6.1(i)-0.6(se)-5.3(as)-6.5(e )]TJ
10.0539 0 TD
-0.0168 Tc
0.0782 Tw
[(cas)-5.2(e)2(s)-5.2( for r)9.8(e)-4(search)-4.8( studies )]TJ
7.02 0 0 7.02 253.26 488.3604 Tm
-0.0043 Tc
0 Tw
[([)-9.1(31])]TJ
10.02 0 0 10.02 264.72 488.3601 Tm
-0.016 Tc
0.0834 Tw
(. Though)Tj
-20.7425 -1.1976 TD
-0.0142 Tc
0.0097 Tw
[(a)6.6(r)0.4(bitrar)6.4(il)5.3(y ch)3.8(osen, th)3.8(e)4.6(s)-2.6(e)4.6( crit)5.4(er)6.4(ia h)3.8(a)]TJ
12.7066 0 TD
-0.0156 Tc
0.0111 Tw
[(v)9.2(e)-2.8( been used as)]TJ
5.6527 0 TD
-0.0152 Tc
0.0107 Tw
[( rigid diagnostic)]TJ
-18.3593 -1.1976 TD
-0.0172 Tc
0.1624 Tw
[(be)-4.4(nchmarks)-5.6( )6(that hav)7.6(e)-4.4( )6(pr)9.4(e)-4.4(v)7.6(e)-4.4(n)-1.2(te)-4.4(d indi)-5.7(vi)-5.7(duals with L)44.8(y)1.6(me dis)-5.6(e)1.6(ase)]TJ
0 -1.2036 TD
-0.0144 Tc
0.0518 Tw
[(f)6.1(r)6.2(om)6.1( )-6(o)4.5(b)0.6(ta)6.4(ining tr)12.2(e)4.4(a)0.4(tm)6.1(ent)5.2(.)-3.9( D)17.1(i)-2.9(a)6.4(g)0.5(nosis o)4.5(f)0.2( )-6(L)53.6(y)-1.6(me)4.4( disease)4.4( )-6(b)12.5(y)-1.5( tw)4.9(o-t)5.2(i)-2.9(e)4.4(r)]TJ
0 -1.1976 TD
-0.001 Tc
0.1103 Tw
[(c)15.8(o)17.9(nfirmation fails to )-6(detect )-6(up)]TJ
12.0898 0 TD
-0.0004 Tc
0.1097 Tw
[( )-6(to 90%)5.3( )-6(of cases and does not)]TJ
-12.0898 -1.1976 TD
-0.0157 Tc
-0.0008 Tw
[(d)-9.7(i)-16.2(s)-16.1(t)-14.1(i)-16.2(n)-11.7(g)-18.8(u)-12.7(ish betw)9.6(een acute, )-6(chr)4.9(o)]TJ
11.7725 0 TD
-0.0166 Tc
0.0001 Tw
[(ni)-5.1(c, or resolved infection )]TJ
7.02 0 0 7.02 268.74 428.3004 Tm
-0.0041 Tc
0 Tw
[([21)-8.4(])]TJ
10.02 0 0 10.02 280.2 428.3001 Tm
0 Tc
(.)Tj
-21.4371 -1.1976 TD
-0.001 Tc
0.0205 Tw
[(The C)6.4(D)0.6(C considers a )6(w)6.3(e)-0.2(stern )6(blot )6(posit)-5.4(i)4.5(v)5.8(e)-0.2( if )6(at )6(least 5 of )6(10)]TJ
-0.8503 -1.1976 TD
-0.0016 Tc
-0.0089 Tw
[(I)7.1(g)1.3(G bands )-6(or 2 of)-5( 3 IgM bands ar)7(e positive )]TJ
7.02 0 0 7.02 225 404.3004 Tm
-0.0042 Tc
0 Tw
([31])Tj
10.02 0 0 10.02 236.46 404.3001 Tm
-0.0021 Tc
-0.0024 Tw
[(. H)19.5(o)10.8(w)5.2(e)-1.3(v)4.7(e)-1.3(r)60.4(,)-3.6( )6(other)]TJ
-17.9222 -1.1976 TD
-0.0024 Tc
0.1117 Tw
[(def)-5.8(i)-2.9(nitions for)-5.7( west)-6.8(ern b)-5.4(l)-0.9(ot c)-3.6(o)]TJ
12.012 0 TD
-0.001 Tc
0.1103 Tw
[(nfirmation hav)5.8(e)-0.2( been pr)7.6(oposed)]TJ
-12.012 -1.1976 TD
-0.0014 Tc
0.0927 Tw
[(to impro)17.5(v)5.5(e the test sensitivit)-5.8(y )]TJ
7.02 0 0 7.02 177.3 380.3004 Tm
-0.0043 Tc
0 Tw
[([30,)-10.7(323)-8.6(6])]TJ
10.02 0 0 10.02 207.96 380.3001 Tm
-0.0004 Tc
0.0917 Tw
[(. I)14.2(n)-2.3( fact, s)5.2(e)0.4(v)6.4(e)0.4(ral studies)]TJ
-15.0778 -1.1976 TD
-0.0007 Tc
0.1519 Tw
[(s)4.9(h)-0.7(o)12.2(w)6.6(ed that sensitivi)4.8(t)-5.1(y)6.2( )-6(and )-6(s)4.9(p)-2.7(ec)4.1(ificity for both the IgM and)]TJ
T*
-0.0027 Tc
-0.0018 Tw
[(IgG)-4.2( )6(wester)-6(n blot ra)-5.9(nge from )6(9)-5.7(2)0.3( )]TJ
12.4251 0 TD
-0.001 Tc
-0.0095 Tw
[(to )-6(96% when only )-6(two specific)]TJ
-12.4251 -1.1976 TD
-0.0023 Tc
0.0038 Tw
[(bands ar)6.3(e positive )]TJ
7.02 0 0 7.02 127.74 344.3004 Tm
-0.0041 Tc
0 Tw
[([3)-8.4(436)-8.4(])]TJ
10.02 0 0 10.02 149.7 344.3001 Tm
0 Tc
(.)Tj
-8.4132 -1.1976 TD
-0.0129 Tc
0.0863 Tw
[(Lum)-4.3(b)-3.9(ar)-4.3( pu)-3.9(nct)-5.3(u)-3.9(r)13.7(e)-6.1( ha)-4.1(s )-5.9(al)-5.4(so b)-3.9(e)-0.1(e)-6.1(n)]TJ
12.1078 0 TD
-0.0106 Tc
0.084 Tw
[( )-5.9(disappointing as a diagnostic)]TJ
-12.9581 -1.1976 TD
-0.0118 Tc
0.0253 Tw
[(tes)-6.2(t)1.8( t)-4.2(o)1.1( r)-9.1(u)-2.8(l)-4.3(e)1( out)-4.2( concomitant ce)-5(nt)-4.2(ral)-4.3( ner)-21.1(v)7(ous s)-6.2(y)1(ste)-5(m)2.7( )-6(infect)-4.2(ion. I)8.8(n)]TJ
T*
-0.0114 Tc
0.0368 Tw
[(L)50.6(y)-4.5(me disease, ev)7.4(aluatio)-4.4(n)4.6( of )5.9(cer)9.2(e)1.4(br)]TJ
12.8204 0 TD
-0.0092 Tc
0.0287 Tw
[(o)3.7(s)2.4(pina)5.6(l fl)4.3(uid is u)5.8(n)0.8(r)11.4(e)3.6(liab)5.8(le)3.6( fo)3.7(r a)]TJ
-12.8204 -1.1976 TD
-0.0101 Tc
0.2092 Tw
[(diag)4.8(nosis of)4.5( )-6(encephalop)5.9(athy an)]TJ
12.3413 0 TD
-0.0123 Tc
0.2114 Tw
[(d )-6(ne)-5.5(uropathy)-5.4( because)-5.5( o)-5.3(f)2.3( )-6(poor)]TJ
-12.3413 -1.1976 TD
-0.0112 Tc
-0.0113 Tw
[(sensitivity \(see S)10.7(e)1.6(ction II.8\). F)35.8(o)]TJ
11.6647 0 TD
-0.0101 Tc
-0.0124 Tw
[(r examp)5.9(le, pleocyto)]TJ
7.2874 0 TD
-0.0113 Tc
-0.0112 Tw
[(sis was pr)9.3(esent)]TJ
-18.9521 -1.1976 TD
-0.0116 Tc
0.079 Tw
[(in )6(o)-4.6(n)4.4(l)-4.1(y)1.3( one of 27 )6(pati)-6.1(ents \(sensit)-4(i)-0.1(vit)-4(y)1.2( 3%\) )6(and wit)-4(h)0.4( )6(o)-4.6(n)-1.6(ly seven)]TJ
T*
-0.0113 Tc
0 Tw
(cells )Tj
7.02 0 0 7.02 75.12 260.3004 Tm
-0.0043 Tc
[([)-9.1(12])]TJ
10.02 0 0 10.02 86.58 260.3001 Tm
-0.0123 Tc
0.0258 Tw
[(. The ant)-4.7(i)-0.8(bo)-5.3(dy )6(inde)-5.5(x )6(w)-5(a)2.5(s po)-5.3(siti)-6.8(v)6.5(e)0.5( )6(\(>1\) )6(in only one )6(o)-5.3(f)2.3( 27)]TJ
-2.9641 -1.1976 TD
0.0197 Tw
[(pat)-4.6(i)-0.7(ents \(se)-5.4(n)3.8(s)-6.6(i)-0.7(tiv)-5.3(i)-0.7(ty)-5.3( )6(3%\) )]TJ
7.02 0 0 7.02 150.42 248.3004 Tm
-0.0041 Tc
0 Tw
[([1)-8.4(2])]TJ
10.02 0 0 10.02 161.88 248.3001 Tm
-0.0106 Tc
0.0121 Tw
[(. An index is the ratio betw)8.7(een L)45.4(y)2.2(me)]TJ
-10.479 -1.1976 TD
-0.0126 Tc
0.0081 Tw
[(EL)-4.5(ISA anti)-7.1(bo)-5.6(dies )6(i)-7.1(n)3.4( the)-5.8( )6(spinal)-5.1( )]TJ
11.7305 0 TD
-0.011 Tc
0.0005 Tw
[(fluid and L)45(y)1.9(me ELISA antibodie)-4.2(s)]TJ
-11.7305 -1.1976 TD
-0.012 Tc
0.0854 Tw
[(in the)-5.2( ser)-9.3(u)-3(m. Th)-6(e pr)8.6(o)-5(p)-2(osed i)-6.5(n)4(d)-6(ex of 1.3 )-5.9(would be e)-5.2(x)0.8(pect)-4.4(ed t)-4.4(o)]TJ
T*
0.0016 Tw
[(have even worse se)-5.3(nsitiv)-5.3(ity)84.6(.)]TJ
0.8503 -1.1976 TD
-0.0005 Tc
0.002 Tw
[(S)9.5(e)0.3(v)6.4(e)0.3(ral additional tests )-6(for )-6(L)43.5(y)6.4(me disease hav)6.3(e)0.3( )-6(been ev)6.4(aluated.)]TJ
-0.8503 -1.1976 TD
-0.0015 Tc
0.1287 Tw
[(Th)4.5(ese incl)-6(ude antigen )-6(captur)7.1(e,)]TJ
12.2036 0 TD
-0.001 Tc
0.1282 Tw
[( ur)-4.3(ine a)-4.2(n)3(tigen and polymer)-4.3(a)1.8(se)]TJ
-12.2036 -1.1976 TD
-0.0015 Tc
0.009 Tw
[(chain )6(r)7.1(e)-0.7(action. Each ha)-4.7(s )6(a)-4.7(d)4.5(va)-4.7(nta)-4.7(g)1.4(es and disa)-4.7(dva)-4.7(n)2.5(ta)-4.7(ges )6(in )6(t)-5.9(e)-0.7(rms)]TJ
T*
0.0004 Tc
-0.0109 Tw
[(of)3( con)4.4(v)7.3(en)4.4(ienc)5.2(e, cos)6(t)-4(,)4.9( as)6(say s)6(t)-4(a)3.2(n)4.4(da)3.2(r)15(d)0.4(iza)3.2(t)2(ion)4.4(,)-1.1( av)13.2(aila)3.2(b)3.4(i)-0.1(lity an)4.4(d r)9(e)1.2(li-)]TJ
T*
-0.001 Tc
0.0444 Tw
[(ability)83.7(.)-2.5( )6(These tests)4.6( r)7.6(e)-0.2(main )6(an option )6(to identify people at high)]TJ
T*
-0.0014 Tc
0.1526 Tw
[(risk f)-4.8(o)-0.4(r persist)-5.8(e)5.4(nt, r)7.2(e)-0.6(cu)-4.4(rr)7.2(ent )-6(and r)7.2(e)-0.6(fr)-4.7(actor)-16.7(y)-0.5( L)42.6(y)-0.5(me disease bu)-4.4(t)]TJ
T*
-0.0012 Tc
0.0027 Tw
[(h)4.8(a)-4.4(v)5.7(e)-0.4( )6(not been stand)4.8(a)-4.4(r)13.4(d)4.8(ized.)]TJ
/F5 1 Tf
7.98 0 0 9 56.88 105.32 Tm
0.0076 Tc
-0.0019 Tw
[(1)3.7(7)3.7(.)1.9( Ser)19.3(o)1(neg)-16.6(a)-1.6(t)6.8(i)-0.5(v)26.2(e)1( L)26.5(y)1.1(m)-7.3(e)1( )7.5(dis)4(e)1(as)4(e)]TJ
/F1 1 Tf
10.02 0 0 10.02 56.88 92.3001 Tm
-0.0011 Tc
0.0385 Tw
[(A patient who )6(has tested )6(ser)7.5(o)-0.1(negativ)5.8(e)-0.3( may hav)5.8(e)-0.3( )6(a )6(clinical pr)7.5(es-)]TJ
T*
-0.0017 Tc
0.0751 Tw
[(entation consist)-6.1(e)-0.9(nt with L)48.3(y)-0.8(me )-5.9(di)]TJ
12.9521 0 TD
-0.0007 Tc
0.0741 Tw
[(sease, especially if ther)7.9(e is no)]TJ
-12.9521 -1.1976 TD
-0.0012 Tc
0.0027 Tw
[(evidence to indicat)-5.6(e)-0.4( )6(another illness.)]TJ
26.3114 64.6766 TD
-0.0034 Tc
0.1187 Tw
[(Alt)-7.8(h)2.6(ou)-6.4(gh)-3.4( )6(man)-5.3(y)-2.5( )6(i)-3.9(n)-5.3(di)-3.9(v)-2.5(i)-3.9(d)-3.4(u)-0.4(als)-3.8( do not ha)-6.6(ve)-2.6( )6(c)-4.6(o)-2.4(nfi)-3.9(r)-0.7(m)-6.8(a)-0.6(tor)-18.7(y)-2.5( se)-2.6(ro-)]TJ
-0.8503 -1.1976 TD
-0.0007 Tc
0.1818 Tw
[(logic )5.9(tests, sur)-16(v)6.1(eillance studies )5.9(sho)12.2(w)0.6( )6(t)-5.1(h)5.3(at )6(t)-5.1(h)5.3(ese patients may)]TJ
T*
-0.0015 Tc
0.2964 Tw
[(have a)-4.7( similar)-4.8( r)-4.8(i)4(sk)-4.5( of )-6(developin)-3.4(g)1.4( )-6(persistent,)-3( )-6(r)13.1(e)-0.7(c)-2.7(u)1.5(r)-4.8(r)13.1(en)-3.4(t a)-4.7(n)2.5(d)]TJ
T*
-0.0009 Tc
-0.0096 Tw
[(r)13.7(e)-0.1(fractor)-16.2(y)0( )-6(L)49.1(y)0(me disease compar)7.7(ed with the ser)7.8(o)0.1(positiv)5.9(e)-0.1( popula-)]TJ
T*
-0.0011 Tc
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[(cally)4.5( ill )6(indiv)4.5(i)-2.9(duals )]TJ
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[(chroni)-4.6(c illness)-4.4(.)0.4( )]TJ
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[(B. burgdor)-9.2(f)0.6(eri,)]TJ
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[(Ly)-49.1(m)-41.4(e)-49.2( d)-50(i)-44.5(s)-50.3(e)-43.2(a)-47.2(s)-50.3(e)-43.2( )]TJ
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[(Th)6.7(e Inter)-20(na)-6.7(t)6.7(ional L)26.7(yme and)6.7( Associated Disea)6.7(ses Society)]TJ
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0.1652 Tw
[(r)12.6(e)-1.3(fracto)4.9(r)-17.4(y)-1.2( e)4.7(v)4.8(en in the)4.7( face)4.7( of)]TJ
12.0838 0 TD
0.0091 Tc
0.166 Tw
[( antibiotic therapy)87.8(,)-4.4( evalua)5.9(tion)]TJ
-12.0838 -1.1976 TD
-0.0012 Tc
-0.0033 Tw
[(and )-6(tr)7.4(eatment must be pr)7.4(ompt and )-6(aggr)7.4(essiv)5.6(e)-0.4(.)]TJ
/F5 1 Tf
7.98 0 0 9 34.2 657.32 Tm
0.0062 Tc
-0.008 Tw
[(21. )-7.5(Pr)17.9(om)-8.7(pt use)-7.9( of )-7.5(anti)5.6(bi)5.6(ot)5.4(ics)]TJ
/F1 1 Tf
10.02 0 0 10.02 34.2 644.3601 Tm
-0.0009 Tc
0.1102 Tw
[(A)5.3(l)-5.4(though no w)6.4(e)-0.1(ll designed studies h)5.1(a)-4.1(v)5.9(e)-0.1( )6(been carri)4.6(e)-0.1(d out, the)]TJ
T*
-0.0011 Tc
0.0445 Tw
[(av)5.7(ailable data suppor)-10.4(t the pr)7.5(ompt)]TJ
13.1737 0 TD
-0.0007 Tc
0.0441 Tw
[( )-6(use of )-6(antibiotics to pr)13.9(ev)6.1(ent)]TJ
-13.1737 -1.1976 TD
-0.0023 Tc
0.0397 Tw
[(chron)-4.2(i)-2.8(c )-6(L)47.7(y)-1.4(me di)-2.8(s)-2.7(e)-1.5(as)-2.7(e.)-3.8( Anti)-2.8(bi)-2.8(oti)-2.8(c)]TJ
12.6527 0 TD
-0.0009 Tc
0.0383 Tw
[( therapy may need t)-5.3(o)0.1( be )-6(initi-)]TJ
-12.6527 -1.1976 TD
-0.0007 Tc
0.122 Tw
[(ated upon suspicio)6.3(n of the diagnosis, e)6.1(v)6.2(en witho)6.3(u)-3.7(t definitiv)6.1(e)]TJ
T*
-0.0009 Tc
0.0623 Tw
[(pr)7.7(oof)13.7(. N)33.6(e)-0.1(ither the opt)-5.3(i)4.6(mal antibiotic dose nor the)5.9( )-6(duration of)]TJ
T*
-0.0015 Tc
0.015 Tw
[(therapy )6(has been stand)4.5(a)-4.7(r)13.1(d)4.5(ized, bu)]TJ
13.0659 0 TD
-0.0013 Tc
0.0148 Tw
[(t )6(l)-5.8(i)4.2(mited data suggest a bene-)]TJ
-13.0659 -1.1976 TD
-0.0009 Tc
0.0144 Tw
[(fit fr)7.7(om incr)7.7(eased )6(dosages and )6(lo)]TJ
12.6108 0 TD
-0.0012 Tc
0.0147 Tw
[(nger tr)7.4(eatment, comparable to)]TJ
-12.6108 -1.1976 TD
-0.0009 Tc
0.0383 Tw
[(the data )-6(on t)-5.3(uber)7.7(c)-2.1(ulosis and lepr)7.7(osy which ar)7.7(e cau)-3.9(s)4.7(ed by simi-)]TJ
T*
-0.0036 Tw
[(larly slo)12(w)0.4(-gr)7.7(o)12(wing )-6(pathogens )]TJ
7.02 0 0 7.02 148.98 548.3604 Tm
-0.0041 Tc
0 Tw
[([25)-8.4(])]TJ
10.02 0 0 10.02 160.44 548.3601 Tm
0 Tc
(.)Tj
/F5 1 Tf
7.98 0 0 9 34.2 525.32 Tm
0.0087 Tc
-0.0105 Tw
[(2)4.8(2)4.8(.)3( )-7.5(Ch)7.2(oos)5.1(i)8.1(ng an ant)7.9(i)0.6(b)7(i)0.6(ot)7.9(i)8.1(c)]TJ
/F1 1 Tf
10.02 0 0 10.02 34.2 512.3601 Tm
-0.0009 Tc
0.0802 Tw
[(I)13.7(n)3.1( acut)-5.3(e )5.9(L)43.1(y)0(me d)5.1(i)-1.4(sease, )5.9(t)-5.3(h)5.1(e choice)]TJ
13.1377 0 TD
-0.0008 Tc
0.0801 Tw
[( of antibiotics should be )5.9(tai-)]TJ
-13.1377 -1.1976 TD
-0.0007 Tc
0.0022 Tw
[(lor)13.9(e)0.1(d t)-5.1(o)0.3( the individual and take into )-6(account the sev)6.1(e)0.1(rity of the)]TJ
T*
-0.0013 Tc
-0.0032 Tw
[(disease as well as the )6(patient)18.3()84(s ag)-4.4(e,)]TJ
12.9162 0 TD
-0.0019 Tc
-0.0026 Tw
[( abil)-6.4(it)-6.3(y )6(to tolerate side effects,)]TJ
-12.9162 -1.1976 TD
-0.0006 Tc
0.0979 Tw
[(c)4.2(l)0.9(inic)4.2(al featur)8(es)5(, allergy )-6(pro)6.4(f)-4(ile, )-6(c)4.2(o)0.4(morbidi)4.9(t)1(ies, prior expos)5(u)-3.6(r)14(e)0.2(,)]TJ
T*
-0.0013 Tc
0.0028 Tw
[(epidemiologic setting )6(and cost.)]TJ
0.8503 -1.2036 TD
-0.0011 Tc
0.0505 Tw
[(Conv)5.7(ersely)83.6(, persistent and r)13.5(e)-0.3(fractor)-16.4(y)-0.2( L)48.9(y)-0.2(me disease tr)7.5(eatment)]TJ
-0.8503 -1.1976 TD
0.0006 Tc
-0.0171 Tw
[(is)6.2( )-6(mor)15.2(e)1.4( li)6.1(kely to inc)5.4(l)2.1(ud)6.6(e )-6(i)6.1(n)-1.3(trav)]TJ
11.6766 0 TD
-0.0011 Tc
-0.0154 Tw
[(enous and/or intr)]TJ
6.6946 0 TD
0.0011 Tc
-0.0176 Tw
[(am)3.7(u)4.1(s)0.7(cu)4.1(la)3.9(r a)3.9(n)-0.8(ti-)]TJ
-18.3713 -1.1976 TD
-0.0016 Tc
0.0151 Tw
[(biotics. )6(The choices depend in pa)]TJ
12.9401 0 TD
0.015 Tw
[(rt on the patient)18.1()77.8(s r)7.1(e)-0.7(sponse to)]TJ
-12.9401 -1.1976 TD
-0.0022 Tc
0.0756 Tw
[(ant)-6.6(i)3.3(b)-5.2(i)-2.7(ot)-6.6(ic therapy )6(a)-5.4(n)1.8(d on the su)]TJ
12.6826 0 TD
-0.0014 Tc
0.0748 Tw
[(ccess of antibiotics in tr)7.2(eating)]TJ
-12.6826 -1.1976 TD
-0.0009 Tc
0.0024 Tw
[(other L)49.1(y)0(me d)5.1(i)-1.4(sease pat)-5.3(i)4.6(ents )6(\(see)5.9( bel)-5.4(o)12(w)6.4(\))-4.3(.)]TJ
0.8503 -1.1976 TD
-0.0119 Tc
0.0793 Tw
[(T)-4.6(h)0.1(erapy)-5( )6(usual)-4.4(l)1.6(y st)-4.3(ar)-9.2(t)-4.3(s)-0.3( wit)-4.3(h)0.1( )6(o)-4.9(r)2.7(al ant)-4.3(i)-0.4(biot)-4.3(ics, and some exper)-9.2(t)-4.3(s)]TJ
-0.8503 -1.1976 TD
-0.0114 Tc
0.1925 Tw
[(r)9.2(e)1.4(commend high dosages. The choi)-5.9(ce of )6(antibiotic the)-4.6(r)3.2(apy is)]TJ
T*
-0.009 Tc
0.0105 Tw
[(g)5.9(u)0(ided )6(b)6(y)3.9( w)10.3(e)3.8(ig)5.9(hing t)4.6(h)3(e)3.8( gr)11.6(e)3.8(a)-0.2(t)4.6(e)3.8(r a)5.8(c)1.8(tiv)3.8(i)2.5(ty)3.8( o)3.9(f)-0.4( )6(intr)5.6(av)9.8(en)7(ou)6(s an)7(tibio)3.9(t)-1.4(ics)]TJ
T*
-0.0126 Tc
0.1818 Tw
[(in the ce)-5.8(nt)-5(ral)-5.1( ne)-5.8(r)-15.9(v)0.2(ous)-7( syst)-5(em against)-5( the l)-5.1(o)12.3(w)6.7(e)-5.8(r co)-5.6(st and)-6.6( )6(e)-5.8(a)2.2(s)-7(y)]TJ
T*
-0.0093 Tc
-0.0012 Tw
[(a)5.5(d)2.7(ministr)5.3(a)-0.5(t)4.3(i)2.2(on o)3.6(f)5.3( or)5.3(al )6(ant)4.3(i)-3.8(b)5.7(i)2.2(ot)4.3(ics fo)3.6(r )]TJ
/F4 1 Tf
13.8802 0.0003 TD
-0.0122 Tc
0.0017 Tw
[(B. burgdor)-12.5(f)-2.7(er)-6.5(i)]TJ
/F1 1 Tf
5.0659 -0.0003 TD
0 Tc
0 Tw
(.)Tj
/F5 1 Tf
7.98 0 0 9 34.2 321.32 Tm
0.007 Tc
-0.0013 Tw
[(23. Oral)6.4( ant)6.2(i)-1.1(bi)6.4(ot)6.2(ic )7.5(opti)6.4(ons)]TJ
/F1 1 Tf
10.02 0 0 10.02 34.2 308.3001 Tm
-0.0009 Tc
0.0503 Tw
[(F)40.1(o)0.1(r many L)43.1(y)0(me disease patients, ther)7.7(e is no clear adv)5.9(a)1.9(ntage of)]TJ
0 -1.1976 TD
-0.0013 Tc
0.0148 Tw
[(par)7.3(e)-0.5(nteral therapy)83.4(.)3.2( Along w)6(i)-1.8(th )]TJ
11.988 0 TD
-0.0002 Tc
0.0137 Tw
[(co)6.8(st considerations)5.4( and )6(pr)14.4(essur)8.4(e)]TJ
-11.988 -1.1976 TD
-0.0015 Tc
0.0509 Tw
[(to tr)7.1(eat )-6(pat)-5.9(i)4(ents with L)42.5(y)-0.6(me dise)]TJ
12.3832 0 TD
-0.0012 Tc
0.0566 Tw
[(ase with the )6(least inter)-16.5(v)5.6(ention,)]TJ
-12.3832 -1.1976 TD
-0.0011 Tc
0.0026 Tw
[(ther)13.5(e is)4.5( gro)11.8(w)0.2(i)4.4(n)-3(g inter)7.5(e)-0.3(st )6(in)]TJ
10.2395 0 TD
[( )6(the use of )6(oral therapy)83.6(.)]TJ
-9.3892 -1.1976 TD
0.0089 Tc
0.1064 Tw
[(F)31.9(i)-3.6(rst-line )6(dr)-6.4(ug therapies for )]TJ
11.509 0 TD
0.0094 Tc
0.0999 Tw
[(L)47.4(y)4.3(me disease may )-6(include \(in)]TJ
-12.3593 -1.1976 TD
0.3752 Tw
[(alphabetical or)18.1(der)6.2(\))]TJ
7.7425 0 TD
0.0069 Tc
0.3838 Tw
[(:)-6.6( )6(oral amoxici)-5.6(l)-3.6(li)-5.6(n, az)-5.3(ith)-5(r)3.6(omy)7.8(c)-0.3(in)-7( )]TJ
7.02 0 0 7.02 253.44 248.3004 Tm
-0.0042 Tc
0 Tw
[([39)-8.5(41])]TJ
10.02 0 0 10.02 275.4 248.3001 Tm
0 Tc
(,)Tj
-24.0719 -1.1976 TD
0.0094 Tc
[(cefur)6.1(o)10.4(xime )]TJ
7.02 0 0 7.02 81.84 236.3004 Tm
-0.0043 Tc
[([)-9.1(42])]TJ
10.02 0 0 10.02 93.3 236.3001 Tm
0.0081 Tc
0.1311 Tw
[(,)-5.4( clarithromy)15(c)-5.1(in )]TJ
7.02 0 0 7.02 161.7 236.3004 Tm
-0.0041 Tc
0 Tw
[([43)-8.4(])]TJ
10.02 0 0 10.02 173.16 236.3001 Tm
0.0114 Tc
0.1278 Tw
[(,)3.9( do)12.4(xy)18.3(cy)18.3(cl)6.9(in)3.5(e )6(and)5.4( te)6.2(trac)4.2(y-)]TJ
-13.8683 -1.1976 TD
0.0072 Tc
0.0482 Tw
[(cl)-3.3(ine)-4(.)-0.3( Th)-4.7(es)-5.1(e ant)-3.2(i)0.7(bi)-5.3(ot)-3.2(ic)-6(s have )6(s)-5.1(i)0.7(mi)-5.3(lar fav)8.1(o)-3.8(rabl)-3.3(e r)9.9(e)2(s)-5.1(u)-1.8(l)-3.3(t)-3.2(s )6(i)-5.3(n)-0.7( )6(co)-3.8(m-)]TJ
T*
0.0434 Tc
0 Tw
[(p)35.4(a)34.2(r)34.1(a)34.2(t)33(i)36.9(v)38.3(e)38.2( t)33(r)34.1(i)36.9(a)34.2(l)32.9(s)31.1( o)38.4(f)34( e)32.2(a)34.2(r)34.1(l)38.9(y)32.3( L)81.4(y)32.3(m)40(e)32.2( d)37.4(i)30.9(s)37.1(e)32.2(a)34.2(s)37.1(e)32.2(.)35.9( I)46.1(n)35.5( o)32.4(n)35.5(e)32.2( )6(s)31.1(t)33(u)34.4(d)37.4(y)116.1(,)35.9( a)34.2(z)37.2(i)30.9(t)39(h)31.5(r)40.1(o)38.4(m)34(y)32.3(-)]TJ
T*
0.0098 Tc
-0.0083 Tw
[(cin perform)6.4(e)-1.4(d )-6(slightl)5.3(y)-1.3( less w)5.1(e)4.6(ll )]TJ
12.3533 0 TD
0.0104 Tc
-0.0089 Tw
[(wh)4.4(en co)5.4(mpar)13.1(ed)4.4( )-6(t)6(o)-0.6( amo)5.4(x)5.3(icil)5.9(lin)]TJ
-12.3533 -1.1976 TD
0.0073 Tc
0.1319 Tw
[(and dox)-3.8(y)14.2(c)-5.9(y)14.2(cli)-5.2(n)-0.6(e.)-6.2( )6(H)16.9(o)8.3(weve)-3.9(r)63.9(,)-6.2( )6(th)-4.6(e e)-3.9(fficac)-5.9(y)2.2( of az)-4.9(ithromy)14.2(c)-5.9(in was)]TJ
T*
0.0094 Tc
0.2915 Tw
[(under)12.1(e)-1.8(stim)6(ated because the an)]TJ
12.9102 0 TD
0.2914 Tw
[(tibiotic w)4.8(a)0.3(s )6(only giv)4.4(e)4.3(n for)]TJ
-12.9102 -1.1976 TD
0.0084 Tc
0 Tw
[(10)-258.1(days )]TJ
7.02 0 0 7.02 66.72 164.3004 Tm
-0.0041 Tc
[([39)-8.4(])]TJ
10.02 0 0 10.02 78.18 164.3001 Tm
0 Tc
(.)Tj
-3.5389 -1.1976 TD
-0.0002 Tc
0.0017 Tw
[(One stud)5.8(y has suggested)5.8( th)5.8(at or)]TJ
12.2814 0 TD
-0.0016 Tc
0.0031 Tw
[(al)-6.1( doxy)11.3(cy)11.3(cl)-6.1(ine \(10)-4.6(0)1.4( mg twice)]TJ
-13.1317 -1.1976 TD
-0.002 Tc
0.0454 Tw
[(da)-5.2(ily for)-5.3( 30)-5( days\) )-6(is )-6(as ef)-5.4(fectiv)]TJ
11.7725 0 TD
-0.0008 Tc
0.0502 Tw
[(e as )6(intrav)6(enous )6(ceftriax)6(one \(2 g)]TJ
-11.7725 -1.1976 TD
-0.0004 Tc
0.0498 Tw
[(d)5.6(a)-3.6(ily for 30 days\) in )-6(early )]TJ
10.3473 0 TD
-0.0008 Tc
0.0502 Tw
[(disseminated L)43.2(y)0.1(me disease )]TJ
7.02 0 0 7.02 244.26 128.3004 Tm
-0.0043 Tc
0 Tw
[([)-9.1(40])]TJ
10.02 0 0 10.02 255.72 128.3001 Tm
0.0015 Tc
0.0539 Tw
[(. T)134.6(w)2.8(o)]TJ
-22.1078 -1.1976 TD
-0.0007 Tc
0.2178 Tw
[(E)20.4(u)2.3(ropean studies hav)6.2(e)0.1( demonstrated )-6(s)4.9(i)-1.2(milar effic)4.1(a)-3.9(c)4.1(y)0.2( )-6(o)6.3(f)-4.1( oral)]TJ
T*
0.1399 Tw
[(d)5.3(o)6.3(xy)12.2(cy)12.2(cline and par)13.9(e)0.1(nteral penicillin and)5.3( )-6(ceftriax)6.1(one )-6(in early)]TJ
T*
-0.05 Tc
0.0515 Tw
[(Ly)-49.1(m)-47.4(e)-49.2( d)-50(i)-44.5(s)-50.4(e)-49.2(a)-53.2(s)-44.4(e)-49.2( )]TJ
7.02 0 0 7.02 86.52 92.3004 Tm
-0.0042 Tc
0 Tw
[([44)-8.5(,)-2.1(45])]TJ
10.02 0 0 10.02 106.74 92.3001 Tm
0 Tc
(.)Tj
-6.3892 -1.1976 TD
-0.021 Tc
-0.0134 Tw
[(Ther)11.6(e ar)5.6(e )-6(no )-6(studies comparing or)]TJ
12.509 0 TD
-0.0135 Tw
[(al )-6(with intrav)9.9(enous antibiotics)]TJ
-13.3593 -1.1976 TD
-0.0208 Tc
0.0043 Tw
[(for persistent, r)11.8(e)-2(curr)11.8(ent )6(and )6(r)11.8(e)-2(fractor)-18.1(y)4( L)47.2(y)4(me)-20( )-18(d)-14.8(i)-21.3(s)-21.2(e)-20(a)-18(s)-21.2(e)-20(.)]TJ
/F5 1 Tf
7.98 0 0 9 289.32 717.32 Tm
0.0072 Tc
-0.0015 Tw
[(24.)9( In)5.7(tra)20.6(v)25.9(e)-6.9(n)5.7(ous an)5.7(ti)6.6(bi)6.6(oti)6.6(c)0.6( opt)6.4(i)6.6(ons)]TJ
/F1 1 Tf
10.02 0 0 10.02 289.32 704.3601 Tm
0.0183 Tc
0.1928 Tw
[(I)27(t)-4( )6(is common)4.4( practice to cons)6(ider in)4.4(trav)7.2(enous antibiotics)]TJ
T*
0.0178 Tc
0.0496 Tw
[(upon failur)14.5(e)-5.4( of )-6(oral medications in pat)-4.5(i)-0.6(ent)-4.5(s)-0.5( with )-6(persistent,)]TJ
T*
0.018 Tc
0.0554 Tw
[(r)8.7(e)0.8(curr)14.7(ent )-5.9(or )-5.9(r)8.7(e)0.8(fractor)-21.3(y)0.9( )-5.9(L)50(y)0.9(me disease, and as t)-4.3(h)0.1(e first )-5.9(line o)-5(f)]TJ
T*
-0.0017 Tc
0.1349 Tw
[(t)-18.1(h)-19.6(e)-18.9(r)-23(a)-16.9(p)-21.6(y)-18.8( )-30(f)-17.1(o)-18.7(r)-23( )-30(c)-20.9(e)-18.9(r)-5(t)-6.1(ain c)-2.9(o)-0.7(nditions,)-3.2( \(i.e.)-3.2(,)-3.2( enc)-2.9(e)-0.9(phalitis,)-3.2( mening)-4.8(itis,)]TJ
T*
-0.0006 Tc
0.0201 Tw
[(optic )24(neuritis,)-20.1( j)-17.1(o)-17.6(i)-19(n)-20.5(t)-17( e)-17.8(f)-16(f)-22(u)-15.5(s)-18.9(i)-19.1(o)-17.6(n)-20.5(s)-18.9( a)-15.8(n)-20.5(d)-18.5( h)-18.5(e)-17.8(a)-15.8(r)-27.9(t)-17( b)-21.6(l)-17.1(o)-17.6(c)-19.8(k)-15.6(\))-21.9(.)]TJ
0.8503 -1.1976 TD
0.086 Tw
[(I)19.9(d)-0.7(eally)84(, the )-6(intrav)6.1(e)6.1(n)-2.6(ous antibiotic should )-6(be selected on the)]TJ
-0.8503 -1.1976 TD
-0.001 Tc
0.1642 Tw
(basis of )Tj
/F4 1 Tf
3.4072 0.0003 TD
-0.0021 Tc
0 Tw
[(in)-249.6(vit)-5.5(r)3.6(o)]TJ
/F1 1 Tf
2.7485 -0.0003 TD
-0.0003 Tc
0.1635 Tw
[( )-6(s)5.3(e)0.5(nsi)5.2(t)1.3(ivity tes)5.3(t)-4.7(i)5.2(n)-2.2(g or clinic)4.5(al experience )]TJ
7.02 0 0 7.02 515.64 632.3604 Tm
-0.0041 Tc
0 Tw
[([1)-8.4(01])]TJ
10.02 0 0 10.02 530.64 632.3601 Tm
0 Tc
(.)Tj
-24.0838 -1.1976 TD
-0.0017 Tc
-0.0207 Tw
[(I)12.9(n)-3.6(travenous antibiotics ar)6.9(e al)-6.2(so j)-6.2(u)1.3(stified )-5.9(b)7.3(y)-0.8( concern f)-5.1(o)-0.7(r penetra)-4.9(-)]TJ
T*
-0.0012 Tc
0.0027 Tw
[(tion into the )6(cent)-5.6(ral ner)-22.5(v)5.6(ous )6(system )]TJ
7.02 0 0 7.02 429.96 608.3604 Tm
-0.0041 Tc
0 Tw
[([15)-8.4(])]TJ
10.02 0 0 10.02 441.42 608.3601 Tm
0 Tc
(.)Tj
-14.3293 -1.1976 TD
0.0095 Tc
0.1237 Tw
[(U)36.9(n)1.6(t)5.1(i)-3(l r)12.2(e)-1.7(cently)88.2(, ceftriax)4.4(o)4.5(n)1.6(e, )-6(cefo)4.5(taxime and penicillin )-6(w)10.8(e)-1.7(r)12.2(e)]TJ
-0.8503 -1.1976 TD
0.0084 Tc
0.1129 Tw
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-0.0006 Tc
0.1398 Tw
[(i)4.9(n)-2.5( general and gastr)8(o)0.4(intestinal )]TJ
12.3413 0 TD
0.0004 Tc
0.1448 Tw
[(pr)9(oble)7.2(ms)6( in )6(par)-8.9(t)2(ic)5.2(ular)62.9(. A)18.6(c)-0.8(ido-)]TJ
-12.3413 -1.1976 TD
-0.001 Tc
-0.0035 Tw
[(philus has )6(r)7.6(e)-0.2(po)6(r)-10.3(t)0.6(edly r)7.6(e)-0.2(d)5(u)-4(ced the )6(incidence of )]TJ
/F4 1 Tf
17.9222 0.0003 TD
-0.0019 Tc
-0.0026 Tw
[(C. diffic)-5.2(ile)]TJ
/F1 1 Tf
3.8922 -0.0003 TD
-0.0024 Tc
-0.0021 Tw
[( coli)-2.9(ti)-2.9(s)]TJ
-21.8144 -1.1976 TD
-0.001 Tc
0.0025 Tw
(and non-)Tj
/F4 1 Tf
3.5329 0.0003 TD
-0.0003 Tc
0.0018 Tw
[(C.)4.2( difficile)]TJ
/F1 1 Tf
3.8982 -0.0003 TD
-0.001 Tc
-0.0035 Tw
[( antibiotic-r)7.6(elated )-6(d)5(i)-1.5(arrhea.)]TJ
-6.5808 -1.2036 TD
-0.0002 Tc
0.0137 Tw
[(S)9.8(e)0.6(rious )6(adv)6.7(e)6.6(rse )6(effec)4.6(t)1.4(s of )6(antibiotics, h)5.8(o)12.7(w)7.1(e)0.6(v)6.6(e)0.6(r)56.4(,)4.3( w)7.1(e)0.6(r)14.4(e)0.6( less)5.4( c)4.6(o)0.8(m-)]TJ
-0.8503 -1.1976 TD
-0.001 Tc
-0.0215 Tw
[(mon than pr)13.6(evious estimates. I)13.6(n)-2.9( a )]TJ
13.1257 0 TD
-0.0007 Tc
-0.0218 Tw
[(r)7.9(e)0.1(c)4.1(e)0.1(nt clinical tri)4.8(a)-3.9(l of chr)7.9(o)0.3(nic)]TJ
-13.1257 -1.1976 TD
[(L)49.3(y)0.2(me disease, the o)18.2(v)6.2(erall )-6(serious )]TJ
12.4731 0 TD
-0.0012 Tc
-0.0213 Tw
[(adv)5.6(e)-0.4(rse ev)5.7(ent rate was )-6(3% )-6(aft)-5.6(e)-0.4(r)]TJ
-12.4731 -1.1976 TD
-0.0014 Tc
0.0688 Tw
[(thr)13.2(e)-0.6(e)-252.1(m)1.2(onths of ant)-5.8(i)4.1(biot)-5.8(ics, in)]TJ
11.8743 0 TD
-0.0004 Tc
0.0618 Tw
[(cluding 1)-248.9(m)2.2(onth of intrav)6.4(enous)]TJ
-11.8743 -1.1976 TD
-0.0015 Tc
0 Tw
[(ant)-5.9(i)4(b)-4.5(i)4(ot)-5.9(ics )]TJ
7.02 0 0 7.02 101.52 404.3004 Tm
-0.0041 Tc
[([2)-8.4(3])]TJ
10.02 0 0 10.02 112.98 404.3001 Tm
-0.0007 Tc
0.1998 Tw
[(. )6(Clinicians w)6.6(h)-0.7(o h)5.3(a)-3.9(v)6.2(e)0.1( )6(experienc)4.1(e)0.1( wi)4.8(th h)5.3(i)-1.2(gher-)]TJ
-5.5988 -1.1976 TD
-0.0012 Tc
0.0087 Tw
[(dose )-6(antibiotic therapy must ba)]TJ
12.1557 0 TD
-0.0009 Tc
0.0144 Tw
[(lance )6(t)-5.3(h)5.1(e benefit)-5.3( )6(of h)5.1(i)-1.4(gher drug)]TJ
-12.1557 -1.1976 TD
-0.0007 Tc
0.2118 Tw
[(lev)6.2(e)0.1(ls )6(achiev)6.2(ed w)6.6(i)-1.2(th this )6(t)-5.1(h)5.3(erapy against the modest )6(risk of)]TJ
T*
-0.0039 Tw
[(gastro)6.4(intestinal and other side effec)4.2(t)1(s.)]TJ
0.8503 -1.1976 TD
-0.0008 Tc
0.0143 Tw
[(R)9.5(e)0(sear)7.8(ch )6(is needed )6(to determine )6(t)-5.2(h)5.2(e added )6(benefits of higher)]TJ
-0.8503 -1.1976 TD
-0.0003 Tc
0.0018 Tw
[(d)5.7(o)0.7(ses of antibi)5.2(otics )6(in )6(chr)8.3(o)0.7(nic L)49.7(y)0.6(me d)5.7(i)-0.8(sease.)]TJ
/F5 1 Tf
7.98 0 0 9 56.88 321.32 Tm
0.0061 Tc
-0.0004 Tw
[(29. Durat)5.3(i)-2(on )7.5(of t)5.3(h)-2.9(era)-18.1(p)12(y)]TJ
/F1 1 Tf
10.02 0 0 10.02 56.88 308.3001 Tm
-0.0018 Tc
0.0931 Tw
[(B)10.4(e)-1(c)-3(a)1(u)-4.8(s)3.8(e )-6(of)-5.2( the disa)-5(ppoin)-3.7(ting )-6(lo)]TJ
12.4072 0 TD
-0.001 Tc
0.0923 Tw
[(ng-term outcome with short)-5.4(e)-0.2(r)]TJ
-12.4072 -1.1976 TD
0.1762 Tw
[(courses of antibiotics, the prac)]TJ
12.3473 0 TD
-0.0014 Tc
0.1765 Tw
[(tice of st)-5.8(opping antibiotics to)]TJ
-12.3473 -1.1976 TD
-0.0011 Tc
0.2062 Tw
[(allo)11.8(w for a delay)5.8(e)-0.3(d r)7.5(e)-0.3(co)17.8(v)5.8(e)-0.3(r)-16.4(y)-0.2( is no )-6(longer r)13.5(e)-0.3(commended for)]TJ
T*
-0.0007 Tc
0.0441 Tw
[(pat)-5.1(i)4.8(ents )6(with persistent, r)13.9(e)0.1(curr)13.9(ent )6(and r)13.9(e)0.1(fractor)-16(y)0.2( L)49.3(y)0.2(me disease.)]TJ
T*
-0.0001 Tc
0.0735 Tw
[(R)16.2(e)0.7(po)6.9(r)-9.4(t)1.5(s s)5.5(h)-0.1(o)12.8(w)1.2( failur)14.5(e rates of )6(3062% )6(within 3)-248.6(y)12.7(ears )6(of )6(short-)]TJ
T*
-0.0005 Tc
0.1277 Tw
[(course t)-4.9(r)14.1(eat)-4.9(m)2.1(ent )-6(using antibiotics thought )-6(to be effectiv)6.4(e)6.3( )-6(for)]TJ
T*
-0.05 Tc
0.0275 Tw
[(Ly)-49.1(m)-47.4(e)-49.2( d)-50(i)-50.5(s)-44.4(e)-49.2(a)-53.2(s)-50.4(e)-49.2( )]TJ
7.02 0 0 7.02 108.78 236.3004 Tm
-0.0032 Tc
0 Tw
[([)-8(3)1.1(,4,1)-7.5(2])]TJ
10.02 0 0 10.02 130.68 236.3001 Tm
-0.001 Tc
-0.0215 Tw
[(. Conv)5.9(ersely for neurologic complicat)-5.4(i)4.5(ons of)]TJ
-7.3653 -1.1976 TD
0.1463 Tw
[(L)48.9(y)-0.2(me disease, )-6(d)4.9(o)-0.1(ubling the leng)]TJ
12.8563 0 TD
0.1462 Tw
[(th of intrav)5.8(enous ceftriax)5.8(one)]TJ
-12.8563 -1.1976 TD
-0.0006 Tc
0.0021 Tw
[(tr)14(eatment)-5( from 2 to )-6(4)-249.1(w)6.7(eeks impr)]TJ
13.0539 0 TD
-0.0004 Tc
0.0079 Tw
[(o)18.5(v)6.4(ed the )6(succe)6.4(ss rate from )6(66)]TJ
-13.0539 -1.1976 TD
-0.0009 Tc
-0.0036 Tw
(to 80% )Tj
7.02 0 0 7.02 88.2 200.3004 Tm
-0.0039 Tc
0 Tw
[([)-8.7(12,51)-8.2(])]TJ
10.02 0 0 10.02 108.42 200.3001 Tm
0 Tc
(.)Tj
-4.2934 -1.1976 TD
-0.0124 Tc
0.0139 Tw
[(T)-5.1(h)-0.4(e m)-3.8(a)2.4(na)-3.6(ge)-5.6(ment)-4.8( of ch)-6.4(r)8.2(o)-5.4(nic L)43.6(y)-5.5(me di)-6.9(sea)-3.6(s)-0.8(e mu)-3.4(st)-4.8( be)-5.6( individu)-3.4(a)-3.6(l)1.1(-)]TJ
-0.8503 -1.1976 TD
-0.0123 Tc
0.0198 Tw
[(ized, since pat)-4.7(i)-0.8(ents)-6.7( )6(wil)-4.8(l)1.2( v)6.5(a)-3.5(r)-21.6(y)0.5( )6(accor)8.3(d)-0.3(ing to)-5.3( )6(se)-5.5(v)6.5(e)0.5(rity)-5.4( )6(o)-5.3(f)2.3( pr)8.3(e)-5.5(s)-0.7(entat)-4.7(i)-0.8(on)]TJ
T*
-0.0124 Tc
0.0019 Tw
[(and r)8.2(e)0.4(s)-6.8(p)3.6(o)-5.4(n)3.6(s)-6.8(e)0.4( to)-5.4( pr)8.2(e)-5.6(v)0.4(ious t)-4.8(r)8.2(eatme)-5.6(n)-2.4(t.)]TJ
0.8503 -1.1976 TD
0.0092 Tc
0.1779 Tw
[(Concurr)11.9(e)-2(nt risk )-6(factors \(i.e., )]TJ
12.1677 0 TD
0.0089 Tc
0.1842 Tw
[(coinfecti)-3.6(o)3.9(ns)-3.4(, pr)11.6(evi)-3.6(o)3.9(us)-3.4( )6(tr)11.6(eat-)]TJ
-13.018 -1.1976 TD
0.0099 Tc
0.1533 Tw
[(m)6.5(e)-1.3(nt failu)6.9(r)6.6(e)4.7(s)-2.4(, fr)6.6(e)4.7(q)-2.1(ue)4.7(nt)5.5( )-6(r)12.6(e)-1.3(l)5.4(a)0.7(pses)3.6(, )-6(ne)4.7(ur)6.6(olo)4.9(g)0.8(ic)2.7( inv)4.8(o)4.9(lv)4.8(e)4.7(m)0.5(ent, or)]TJ
T*
0.0112 Tc
0.3196 Tw
[(pr)13.9(ev)6.1(io)6.2(us use of co)6.2(r)-10.1(t)6.8(ic)4(os)4.9(ter)7.9(o)6.2(id)]TJ
12.515 0 TD
0.0094 Tc
0.3214 Tw
[(s\) or evidence )-6(of unusually)]TJ
-12.515 -1.1976 TD
0.0083 Tc
0.0112 Tw
[(sev)9.2(e)-2.9(r)11(e)-2.9( L)46.3(y)-2.8(me di)-4.2(sease sh)-3.6(ould lead to the in)-5.6(itiati)-4.2(on of )6(p)-5.7(r)5(olonged)]TJ
T*
0.0093 Tc
0.2377 Tw
[(and/or intrav)10.2(enous )-6(antibio)4.3(t)-1.1(ic tr)12(eatme)4.1(n)1.4(t. )-6(P)7.4(h)-2.6(y)4.2(s)-3(icians shoul)4.8(d)]TJ
T*
0.0085 Tc
0.0289 Tw
[(always assess the patient)22.1()75.8(s r)11.2(e)-2.7(sp)]TJ
11.8922 0 TD
0.0101 Tc
0.0273 Tw
[(o)5.1(n)2.2(se)4.9( to )6(tr)12.8(eatm)6.7(ent be)4.9(for)12.8(e)-1.1( decid-)]TJ
-11.8922 -1.1976 TD
0.0089 Tc
0.7471 Tw
[(ing on )6(appr)5.6(opriate duration of therapy )6(\(i.e.,)-262.1(w)10.2(e)-2.3(eks)]TJ
T*
0.0086 Tc
0 Tw
[(v)9.5(e)-2.6(rsus)-261.2(months\).)]TJ
/F5 1 Tf
7.98 0 0 9 312 717.32 Tm
0.0065 Tc
-0.0008 Tw
[(30. Empi)5.9(r)-19.4(i)5.9(c t)5.7(r)3.2(ea)-10.2(t)5.7(m)-0.9(e)-7.6(n)5(t)]TJ
/F1 1 Tf
10.02 0 0 10.02 312 704.3601 Tm
-0.001 Tc
0.0025 Tw
[(The impor)-10.3(t)0.6(ance )-6(of )-6(est)-5.4(a)1.8(blishing )-6(the diagnosis )-6(of L)43(y)-0.1(me disease is)]TJ
T*
[(heigh)5(t)-5.4(ened in l)-5.5(i)4.5(ght of incr)7.6(easing)]TJ
12.4311 0 TD
[( concern about )-6(antibiotic o)17.9(v)5.8(er-)]TJ
-12.4311 -1.1976 TD
0.0007 Tc
-0.0052 Tw
[(u)3.7(s)0.3(e. Af)3.3(ter)3.4( an)4.7( ap)4.7(pr)9.3(op)4.7(ri)6.2(ate his)6.3(t)-3.7(or)-14.6(y)85.4(,)5.2( )-6(p)4.7(h)0.7(ysi)6.2(c)-0.5(a)3.5(l)2.2( )-6(exa)3.5(m)3.3(in)4.7(atio)7.7(n a)3.5(n)-1.2(d la)3.5(b-)]TJ
T*
-0.0012 Tc
0.1883 Tw
[(orat)-5.6(o)5.8(r)-22.5(y testing ar)13.4(e complet)-5.6(e)-0.4(d, )]TJ
12.491 0 TD
(empiric antimicrobial therapy)Tj
-12.491 -1.1976 TD
-0.0009 Tc
0.0383 Tw
[(sh)5.1(ould )6(be initiated on the)5.9( bas)4.7(i)-1.4(s of )6(clinical c)3.9(l)-5.4(ues, the )6(sev)5.9(e)-0.1(rity of)]TJ
T*
0.0144 Tw
[(the )6(patient)18.7()78.4(s acute ill)-5.4(n)3.1(ess, und)5.1(e)-0.1(rlying disease and)5.1( the )6(like)5.9(l)-5.4(i)4.6(hood)]TJ
T*
-0.0018 Tc
0 Tw
(of )Tj
/F4 1 Tf
1.0778 0.0003 TD
-0.0004 Tc
0.0498 Tw
[(B. burgdor)-12.7(f)3.1(er)5.3(i)]TJ
/F1 1 Tf
5.2575 -0.0003 TD
-0.0013 Tc
0.0507 Tw
[( infec)3.5(t)0.3(ion. )-6(T)6(h)-1.3(e IL)-11.2(ADS working )-6(gr)7.3(oup r)7.3(e)-0.5(com-)]TJ
-6.3353 -1.1976 TD
-0.0009 Tc
0.4216 Tw
[(mends that empiric tr)13.7(eatment be consider)13.7(ed r)7.7(o)0.1(utine )6(for)]TJ
T*
-0.0008 Tc
0.0023 Tw
[(patie)6(n)-2.7(ts w)6.5(i)-1.3(th a likely diagnosis )6(of )6(L)43.2(y)0.1(me )6(disease.)]TJ
/F5 1 Tf
7.98 0 0 9 312 585.32 Tm
0.0043 Tc
0.0014 Tw
[(31. P)22.9(e)-9.8(r)-14(s)-6.8(isten)-4.7(t)-4( )7.5(L)23.2(y)-2.2(m)-10.6(e)-2.3( disea)-4.9(s)0.7(e)]TJ
/F1 1 Tf
10.02 0 0 10.02 312 572.3601 Tm
-0.0194 Tc
0.1287 Tw
[(P)56.5(e)-0.6(rsistent L)48.6(y)-0.6(m)-4.9(e)5.3( )-6(disease )-6(is m)-4.9(o)-0.5(r)13.2(e)-0.6( r)7.2(e)-0.7(sist)-5.8(ant)-5.8( to tr)7.2(eatm)-4.9(ent and mor)7.2(e)]TJ
T*
-0.019 Tc
0.0444 Tw
[(likely to )5.9(pr)7.6(oduce a )5.9(r)7.6(e)-0.2(lapse. Although persistent )5.9(L)43(y)-0.2(me )5.9(disease may)]TJ
T*
0.0685 Tw
[(r)13.5(e)-0.3(solv)5.7(e )-6(wit)-5.5(h)4.9(out additional)-5.6( therapy)83.6(,)3.3( )-6(many exper)-10.5(ts bel)-5.6(i)4.4(ev)5.7(e )-6(that t)-5.5(h)4.9(is)]TJ
T*
-0.0033 Tw
[(condit)-5.5(ion should be tr)7.5(eated with r)7.5(e)-0.3(peated)4.9( )-5.9(and pr)7.5(olonged ant)-5.5(i)4.4(biot-)]TJ
T*
-0.0162 Tc
-0.0122 Tw
[(ic)6.6(s. P)11.8(h)1.8(y)2.6(s)1.4(ic)6.6(ia)4.6(ns sh)7.8(o)2.7(u)-1.2(l)3.3(d)1.8( e)2.6(x)2.6(t)3.4(e)2.6(n)5.8(d)1.8( t)3.4(h)1.8(e)2.6( d)1.8(u)4.8(ra)4.6(t)3.4(i)1.3(o)2.7(n)5.8( o)2.7(f)-1.6( a)4.6(n)-0.2(t)3.4(i)1.3(b)4.8(i)1.3(o)2.7(t)3.4(ic)6.6(s t)3.4(o)2.7( pr)4.4(event)]TJ
T*
-0.0124 Tc
0.0019 Tw
[(or)-3.8( d)-6.4(e)0.4(l)-4.9(a)2.4(y)-5.5( r)8.2(e)-5.6(cu)-3.4(rrent)-4.8( a)-3.6(n)-2.4(d r)8.2(e)-5.6(fr)-3.8(a)-3.6(c)-1.6(t)-4.8(o)0.5(r)-21.7(y)0.4( )-6(L)43.6(y)0.4(m)-3.8(e)0.4( d)-6.4(i)-0.9(se)-5.6(as)-6.8(e.)]TJ
/F5 1 Tf
7.98 0 0 9 312 489.32 Tm
0.006 Tc
-0.0003 Tw
[(32. Recurr)10.2(ent )7.5(L)24.9(y)-0.5(m)-8.9(e)-0.6( disease)]TJ
/F1 1 Tf
10.02 0 0 10.02 312 476.3601 Tm
-0.0011 Tc
0.0625 Tw
[(D)6.4(e)-0.3(spite )6(pr)7.5(e)5.7(v)-0.2(ious antibiotic tr)13.5(eatment)-5.5(,)3.4( L)48.9(y)-0.2(me disease h)4.9(a)-4.3(s )6(a pro-)]TJ
T*
-0.0015 Tc
0.009 Tw
[(pensity )-6(for r)7.1(e)-0.7(lapse and )-6(r)13.1(e)-0.7(quir)7.1(es )-6(ca)-4.7(r)13.1(e)-0.7(f)-4.9(u)1.5(l fol)-6(l)0(o)11.4(w)-0.2(-up for)-268.3(y)5.4(ear)-4.8(s)4.1(. The)]TJ
0 -1.2036 TD
-0.0011 Tc
0.0864 Tw
[(data suggest that failur)13.5(e to er)]TJ
11.497 0 TD
-0.0007 Tc
0.08 Tw
[(adicate the )-6(organism may be the)]TJ
-11.497 -1.1976 TD
-0.002 Tc
0.0933 Tw
[(r)12.6(e)-1.2(a)-5.2(s)-2.4(on f)-5.4(o)-1(r )-6(a r)6.6(e)-1.2(curr)6.6(ence )-6(of)-5.4( symptoms )]TJ
7.02 0 0 7.02 459.66 440.3004 Tm
-0.0041 Tc
0 Tw
[([1)-8.4(2])]TJ
10.02 0 0 10.02 471.12 440.3001 Tm
-0.0017 Tc
0.093 Tw
[(. E)-4.5(a)1.1(rly )-6(and ag)-4.8(gr)6.9(essive)]TJ
-15.8802 -1.1976 TD
-0.0012 Tc
0.0746 Tw
[(tr)7.4(eatment )6(with ant)-5.6(i)4.3(biot)-5.6(ics )6(is indicated for )6(r)7.4(e)-0.4(curr)7.4(ent L)42.8(y)-0.3(me )6(dis-)]TJ
T*
-0.0011 Tc
0.278 Tw
[(ease. )-6(Th)4.9(e )-6(ultimat)-5.5(e)-0.3( impact fr)7.5(om r)7.5(e)-0.3(tr)7.6(eating each episode)5.7( )-6(of)]TJ
T*
-0.0008 Tc
0.0023 Tw
[(r)13.8(e)0(curr)13.8(ent )6(L)43.2(y)0.1(me d)5.2(i)-1.3(sease is curr)7.8(entl)-5.3(y )6(unclear)61.7(.)]TJ
/F5 1 Tf
7.98 0 0 9 312 381.32 Tm
0.0048 Tc
0.0009 Tw
[(33. Refrac)-9.3(tor)-36.1(y)-9.2( )7.5(L)23.7(y)-1.7(m)-10.1(e)-1.8( disease)]TJ
/F1 1 Tf
10.02 0 0 10.02 312 368.3001 Tm
-0.0021 Tc
0.0455 Tw
[(R)14.2(e)-1.3(f)-5.5(r)0.6(actor)-17.4(y)-1.2( L)41.9(y)-1.2(me disea)-5.3(s)-2.5(e )-6(is )-6(a de)]TJ
12.1078 0 TD
-0.0007 Tc
0.0441 Tw
[(v)6.1(a)2.1(stating condition th)5.3(at usually)]TJ
-12.1078 -1.1976 TD
-0.001 Tc
0.0504 Tw
[(affects )-6(patients with persistent symptomatology and long-t)-5.4(erm)]TJ
T*
-0.0004 Tc
0.0678 Tw
[(di)5.1(sability)84.3(. P)33.6(r)8.3(ompt and aggr)14.2(essiv)6.5(e)0.4( )6(ins)5.2(t)1.2(itution of antibi)5.1(otic )6(th)5.6(er-)]TJ
T*
-0.0009 Tc
0.1461 Tw
[(apy )6(may )6(be essential to pr)7.7(ev)6(ent r)7.7(e)-0.1(fractor)-22.2(y)0( )6(disease. I)7.8(n)3.1(cr)13.7(easing)]TJ
T*
-0.0001 Tc
0.0914 Tw
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-0.0119 Tc
0.0254 Tw
[( L)44.1(y)1(me)-5.1( )6(d)-5.9(i)-0.4(sease hav)6.9(e)0.9( r)8.7(e)0.9(comme)-5.1(n)4.1(de)-5.1(d)]TJ
-11.5808 -1.1976 TD
-0.0091 Tc
-0.0134 Tw
[(t)4.5(h)2.9(at)4.5( an)6.9(tibio)3.8(t)4.5(ics )5.9(be)3.7( disco)3.8(n)0.9(tin)6.9(u)-0.1(e)3.7(d)2.9( af)5.5(te)3.7(r )5.9(30)5.9( day)3.7(s)2.5( )5.9(of)5.5( t)4.5(r)11.5(ea)5.7(tm)5.4(e)3.7(n)0.9(t. )5.9(C)4.3(o)-2.1(m)5.4(-)]TJ
T*
-0.0108 Tc
0.162 Tw
[(plicating the d)-4.8(e)2(cision )-6(to stop an)]TJ
12.7784 0 TD
-0.0114 Tc
0.1626 Tw
[(tibiot)-3.8(ics i)-5.9(s)0.2( t)-3.8(h)0.6(e fact )-6(that )-6(some)]TJ
-12.7784 -1.1976 TD
-0.0117 Tc
0.1629 Tw
[(pat)-4.1(i)-0.2(ents pr)8.9(e)-4.9(s)-0.1(ent wi)-6.2(th dis)-6.1(e)1.1(ase r)8.9(e)1.1(curr)14.9(e)-4.9(n)-1.7(ce aft)-4.1(e)1.1(r the r)8.9(e)-4.9(sol)-4.2(u)3.3(t)-4.1(i)-0.2(on of)]TJ
T*
-0.0113 Tc
0.2583 Tw
[(their initial L)44.7(y)1.6(me disease symp)]TJ
12.5389 0 TD
-0.0115 Tc
0.2585 Tw
[(toms)-5.9(. This is cons)-5.9(istent with)]TJ
-12.5389 -1.1976 TD
-0.0098 Tc
0.0173 Tw
[(inco)3.1(m)4.7(p)0.2(le)3(t)3.8(e)-3( a)5(n)0.2(tib)5.2(i)-4.3(o)3.1(t)3.8(ic the)3(r)-1.2(ap)6.2(y)80.9(.)0.7( Al)3.7(tho)3.1(u)-0.8(g)5.1(h)2.2( the)3( op)6.2(tim)4.7(a)-1(l t)3.8(i)1.7(me)3( t)3.8(o)-2.8( dis-)]TJ
T*
-0.011 Tc
0.0664 Tw
[(continue antibiotics is unkno)13.9(w)2.3(n,)]TJ
12.5569 0 TD
-0.0108 Tc
0.0662 Tw
[( it appears to be dependen)5.2(t on)]TJ
-12.5569 -1.1976 TD
-0.0119 Tc
0.0493 Tw
[(the)-5.1( )6(e)-5.1(x)0.9(te)-5.1(nt of )6(s)-6.3(y)1(mpt)-4.3(o)1(mato)-4.9(logy)84.8(, th)-5.9(e pat)-4.3(i)-0.4(ent)19.6()79.4(s)-6.3( )6(pr)8.7(ev)-5.1(ious r)8.7(e)0.9(sponse t)-4.3(o)]TJ
T*
-0.0121 Tc
0.0016 Tw
[(ant)-4.5(i)-0.6(bi)-6.6(otics)-6.5( and t)-4.5(h)-0.1(e o)12.8(v)6.7(eral)-4.6(l r)8.5(e)-5.3(sponse t)-4.5(o)0.8( the)-5.3(r)2.5(apy \(see bel)-4.6(o)12.8(w\).)]TJ
0.8503 -1.1976 TD
-0.0007 Tc
0.4034 Tw
[(Rather )-6(than an arbitrar)-16(y 30-day )-6(tr)13.9(eatment )-6(course, the)]TJ
-0.8503 -1.1976 TD
0 Tc
0.2231 Tw
[(pati)5.5(ent)19.6()79.3(s c)4.8(l)-4.5(i)5.5(n)-1.9(ic)4.8(al r)8.6(e)0.8(s)5.6(p)-2(onse shou)]TJ
12.4072 0 TD
-0.0011 Tc
0.2242 Tw
[(ld guide )-5.9(duration of t)-5.5(h)4.9(erapy)83.6(.)]TJ
-12.4072 -1.1976 TD
-0.0008 Tc
0.2418 Tw
[(P)45.2(a)2(t)-5.2(i)4.7(ents must t)-5.2(h)5.2(er)7.8(efor)7.8(e be car)7.8(e)0(ful)-5.3(l)0.7(y ev)6(aluated )-6(for )-6(persistent)]TJ
T*
-0.0011 Tc
0.0026 Tw
[(infection befor)7.5(e)-0.3( a d)4.9(e)-0.3(cisi)4.4(on )6(is made to )6(withhold )6(therapy)83.6(.)]TJ
0.8503 -1.1976 TD
-0.0005 Tc
0.1397 Tw
[(The decis)5.1(i)-1(on to disco)6.5(n)-2.4(tinue an)]TJ
12.485 0 TD
-0.0009 Tc
0.1401 Tw
[(tibiotic)3.9(s should )-6(be made )-6(i)4.6(n)]TJ
-13.3353 -1.1976 TD
-0.0011 Tc
0.2182 Tw
[(consultat)-5.5(i)4.4(on )6(with the)5.7( patient )]TJ
12.2695 0 TD
[(and sho)5.9(u)-4.1(ld )6(take into )6(account)]TJ
-12.2695 -1.1976 TD
0.0804 Tw
[(such fact)-5.5(ors as the fr)7.5(equency and duration of persistent infec-)]TJ
T*
0.1642 Tw
[(tion, fr)7.6(equency of r)7.6(e)-0.2(curr)7.6(ence, pr)7.6(obability of r)13.6(e)-0.2(fractor)-16.3(y)-0.1( L)43(y)-0.1(me)]TJ
T*
-0.0005 Tc
0.02 Tw
[(d)5.5(i)-1(sease, gains with antibiotics)5.1(,)-2( )]TJ
11.8802 0 TD
-0.0009 Tc
0.0263 Tw
[(the import)-5.3(ance )5.9(to the )5.9(patient of)]TJ
-11.8802 -1.1976 TD
-0.0012 Tc
0.0027 Tw
(discontinuing antibiotics and po)Tj
12.497 0 TD
-0.002 Tc
-0.0025 Tw
[(t)-6.4(e)-1.2(ntial )-6(for)-5.3( car)6.6(e)-1.2(ful)-6.5( f)-5.4(o)5(l)-6.5(l)-0.5(o)10.9(w)-0.7(-up)14(.)]TJ
13.8144 64.6766 TD
-0.0159 Tc
-0.0066 Tw
[(The ideal )-6(approach would )-6(be to )]TJ
12.018 0 TD
-0.015 Tc
-0.0074 Tw
[(continu)6(e)-2.2( thera)5.8(p)1(y for L)47(y)-2.1(m)5.5(e)-2.2( dis-)]TJ
-12.8683 -1.1976 TD
-0.0141 Tc
-0.0263 Tw
[(e)4.7(a)0.7(se unt)5.5(i)-2.6(l)5.4( )-6(t)5.5(h)-2.1(e)4.7( L)47.9(y)-1.3(m)6.4(e)-1.3( spir)12.5(och)3.9(e)-1.3(t)5.5(e)-1.3( is e)4.7(r)0.5(ad)3.9(icat)5.5(ed)3.9(. U)37.3(n)1.9(fo)4.8(rtunat)5.5(el)5.4(y th)3.9(er)12.5(e)4.6( is)]TJ
T*
-0.0146 Tc
0.04 Tw
[(curr)12(e)4.2(n)1.4(tl)4.9(y no t)5(e)-1.8(st av)10.2(ailabl)4.9(e to)4.3( de)4.2(te)4.2(rmine)4.2( this point )]TJ
7.02 0 0 7.02 477.72 692.3604 Tm
-0.0041 Tc
0 Tw
[([25)-8.4(])]TJ
10.02 0 0 10.02 489.18 692.3601 Tm
-0.0141 Tc
0.0396 Tw
[(. Th)3.9(e)4.7(r)12.5(efo)4.8(r)12.5(e,)]TJ
-19.9461 -1.1976 TD
-0.0131 Tc
0.0266 Tw
[(t)6.5(h)-1.1(e)5.7( cl)6.4(in)8.9(ic)3.7(i)4.4(a)1.7(n mus)4.5(t)6.5( )-6(r)13.5(e)5.7(ly)5.7( )-6(o)5.8(n)2.9( th)4.9(e fa)7.7(c)3.7(t)0.5(or)7.5(s o)5.8(u)1.9(tl)6.4(ine)5.6(d)4.9( )-6(a)7.7(b)1.9(o)17.8(v)11.7(e to)5.8( de)5.7(c)3.7(i)-1.6(d)4.9(e)5.7( )-6(o)5.8(n)]TJ
T*
-0.015 Tc
-0.0015 Tw
[(t)4.6(h)-3(e)3.8( le)3.8(ngth of an)7(tibio)3.9(t)-1.4(ic ther)]TJ
10.2156 0 TD
-0.0157 Tc
-0.0008 Tw
[(apy for chr)4.9(o)-2.8(nic L)46.3(y)-2.8(m)4.8(e)-2.9( disease.)]TJ
/F5 1 Tf
7.98 0 0 9 289.32 645.32 Tm
0.0077 Tc
-0.002 Tw
[(3)3.8(8)-3.7(.)9.5( Alt)6.9(e)1.1(r)-18.2(n)-1.3(ati)7.1(v)18.8(e )7.5(ant)6.9(i)7.1(biot)6.9(i)7.1(c)1.1(s)]TJ
/F1 1 Tf
10.02 0 0 10.02 289.32 632.3601 Tm
-0.0009 Tc
0.1341 Tw
[(Ther)13.7(e is compelling )6(evide)5.9(n)-2.8(ce )6(that L)49.1(y)0(me d)5.1(i)-1.4(sease can )6(r)7.8(e)-0.1(sult in)]TJ
0 -1.1976 TD
-0.0008 Tc
-0.0157 Tw
[(serious and potentially )-6(r)13.8(e)0(fractor)-16.1(y)0.1( )]TJ
12.8204 0 TD
-0.0007 Tc
[(illness. U)26.7(s)4.9(e )-6(of alternativ)6.2(e anti-)]TJ
-12.8204 -1.1976 TD
-0.0009 Tc
0.1701 Tw
[(biotics t)-5.3(o)0.1( tr)7.8(eat early L)43.1(y)0(me disease with er)-22.2(ythe)5.9(ma migrans is)]TJ
T*
-0.0013 Tc
0.0028 Tw
[(generally not)-5.7( )6(indicated unle)]TJ
10.7126 0 TD
-0.0001 Tc
0.0016 Tw
[(ss c)4.7(o)0.9(infec)4.7(t)-4.5(i)5.4(o)0.9(n )6(is suspected.)]TJ
-9.8623 -1.1976 TD
-0.0114 Tc
0.0848 Tw
[(The IL)-9.3(AD)-3.9(S W)74.4(o)1.5(r)9.2(k)-2.5(ing )6(G)23(r)3.2(oup )6(bel)-3.9(i)0.1(eves that)-3.8( )6(t)-3.8(h)0.6(e risk of )6(al)-3.9(terna-)]TJ
-0.8503 -1.1976 TD
-0.0119 Tc
-0.0165 Tw
[(tive ant)-4.3(i)-0.4(bio)-4.9(t)1.7(ics)-6.3( )6(is acceptabl)-4.4(e)0.9( in )6(s)-6.3(e)0.9(le)-5.1(cted L)44.1(y)0.9(me disease pat)-4.3(i)-0.4(ent)-4.3(s)-0.3( )6(pr)8.7(e-)]TJ
T*
-0.0107 Tc
0.4673 Tw
[(sentin)5.3(g with chr)9.9(o)2.2(nic L)45.3(y)-3.8(m)3.8(e)2.1( disease. Alter)3.9(n)-0.7(ative antibiotics)]TJ
T*
-0.0111 Tc
0.1204 Tw
[(include les)-5.5(s)0.5( )6(common)4.9(ly used )6(oral )]TJ
12.982 0 TD
-0.0114 Tc
0.1147 Tw
[(antibi)-5.9(otics)-5.8( \(cefixime, cefdinir)57.1(,)]TJ
-12.982 -1.1976 TD
-0.0124 Tc
0.1037 Tw
[(me)-5.6(tronidazol)-4.9(e\) and i)-6.9(n)3.6(t)-4.8(r)2.2(av)6.4(e)-5.6(n)-2.4(ous)-6.8( ant)-4.8(i)-0.9(bi)-6.9(otics)-6.8( \(i)-6.9(mipenem, azithro-)]TJ
T*
-0.0112 Tc
0.0606 Tw
[(my)7.6(cin\). The r)9.4(o)-4.2(le of alternativ)7.6(e antibiotics in lo)7.7(w-risk patients is)]TJ
T*
-0.0116 Tc
-0.0109 Tw
[(less cer)-8.9(t)2(ain and ther)9(e is less consens)-6(u)3.4(s wi)-6.1(thin th)-5.6(e W)80.1(o)1.3(rki)-6.1(n)4.4(g G)22.8(r)9(oup)]TJ
T*
-0.0121 Tc
0.0016 Tw
[(as)-6.5( to w)-4.8(h)-0.1(et)-4.5(her the po)-5.1(tent)-4.5(ial)-4.6( be)-5.3(nefi)-6.6(ts out)-4.5(w)7.2(eigh t)-4.5(h)-0.1(e risks)-6.5(.)]TJ
/F5 1 Tf
7.98 0 0 9 289.32 477.32 Tm
0.0061 Tc
-0.0004 Tw
[(39.)7.9( T)5(h)-2.9(era)-25.6(p)19.5(y f)22.9(o)-0.5(r )7.5(co)-8(i)5.5(n)-2.9(f)7.9(ecti)5.5(o)-0.5(n)]TJ
/F1 1 Tf
10.02 0 0 10.02 289.32 464.3601 Tm
0.0092 Tc
0.0342 Tw
[(Thera)6(p)-4.8(y for polymicr)5.9(obial infect)]TJ
13.018 0 TD
0.0081 Tc
0.0413 Tw
[(i)-4.4(o)-2.9(n )6(in L)46.1(y)3(me )6(d)-3.9(i)1.6(s)-4.2(e)2.9(as)-4.2(e is a )6(rap-)]TJ
-13.018 -1.2036 TD
0.009 Tc
0.25 Tw
[(idly changing)5.9( ar)5.7(ea of clinical practice )]TJ
7.02 0 0 7.02 453.36 452.3004 Tm
-0.0043 Tc
0 Tw
[([)-9.1(25])]TJ
10.02 0 0 10.02 464.82 452.3001 Tm
0.0072 Tc
0.2518 Tw
[(.)-6.3( U)34.6(n)-0.7(comp)-6.8(li)-5.3(cated)]TJ
-17.515 -1.1976 TD
0.0086 Tc
-0.0071 Tw
[(L)46.6(y)-2.5(m)5.2(e)-2.6( disease may be managed wi)]TJ
13.1257 0 TD
0.0065 Tc
-0.005 Tw
[(th)-5.4(o)-4.5(u)-2.5(t ad)-5.5(dr)9.2(e)-4.7(s)-5.8(si)-6(ng coi)-6(n)-1.4(fe)-4.7(ct)-3.9(io)-4.5(n)]TJ
-13.1257 -1.1976 TD
0.0088 Tc
0.1843 Tw
[(b)5.8(y)3.7( means of standar)11.5(d)-3.2( )6(oral or par)5.5(e)3.6(nteral antibiotic therapy)81.5(.)]TJ
T*
0.0096 Tc
0.0937 Tw
[(S)13.6(o)-1.4(m)6.2(e)-1.6( but not all exper)-5.7(t)-0.8(s )6(r)6.3(e)4.4(co)]TJ
11.9581 0 TD
0.0088 Tc
0.0945 Tw
[(mmend thera)5.6(p)-5.2(y for )6(subclinical)]TJ
-11.9581 -1.1976 TD
0.0073 Tc
-0.0238 Tw
[(or )-6(chroni)-5.2(c coin)-6.6(fecti)-5.2(o)2.3(n)-6.6( wi)-5.2(th )]TJ
/F4 1 Tf
10.9461 0.0003 TD
0.0095 Tc
0 Tw
[(Ehr)15.2(l)-2(ichia)]TJ
/F1 1 Tf
3.515 -0.0003 TD
0.0135 Tc
(, )Tj
/F4 1 Tf
0.491 0.0003 TD
-0.0002 Tc
[(Ba)-11.3(b)-7.3(e)-13.5(s)-7.7(i)-9.6(a)]TJ
/F1 1 Tf
2.8802 -0.0003 TD
0.0072 Tc
-0.0237 Tw
[( or )]TJ
/F4 1 Tf
1.3054 0.0003 TD
-0.0002 Tc
0 Tw
[(Ba)-11.3(r)-12.5(t)-9.6(o)-13.4(n)-8.2(e)-7.5(l)-11.7(l)-5.7(a)]TJ
/F1 1 Tf
3.9282 -0.0003 TD
0.011 Tc
-0.0275 Tw
[( on)]TJ
-23.0659 -1.1976 TD
0.0102 Tc
0.0691 Tw
[(th)4.2(e )5.9(basi)3.7(s )5.9(of t)5.8(h)-1.7(ei)3.7(r be)5(lie)5(f)0.8( th)4.2(at )5.9(r)6.9(e)5(spons)3.9(e)-1(s)3.9( ar)12.9(e m)6.8(o)-0.8(r)12.9(e)-1( pr)6.9(o)5.2(m)0.8(pt w)5.5(i)-2.3(th)]TJ
T*
0.0097 Tc
-0.0022 Tw
[(this appr)6.4(o)4.7(a)0.5(ch.)]TJ
0.8503 -1.1976 TD
-0.0015 Tc
0.1647 Tw
[(The dose, duratio)5.5(n)-3.4( and type of tr)7.1(eatment for coinfections)]TJ
-0.8503 -1.1976 TD
-0.0009 Tc
-0.0215 Tw
[(hav)6(e)-0.1( not )-5.9(been )-5.9(defined. P)27.1(ublished r)7.7(e)-0.1(por)-10.2(t)0.7(s of coinfe)5.9(ction )-5.9(ar)7.8(e )-5.9(lim-)]TJ
T*
-0.0011 Tc
0.0804 Tw
[(ited to a smal)-5.6(l number of )-6(patients tr)7.5(e)5.7(a)-4.3(ted in ope)5.7(n)-3(-label, non-)]TJ
T*
0 Tc
0.0674 Tw
[(randomiz)11.7(ed stud)6(ies. D)13.5(o)7(xy)12.9(c)4.8(y)12.9(cl)]TJ
11.6407 0 TD
-0.0006 Tc
0.068 Tw
[(ine has)5( )-6(been indi)4.9(cated for )]TJ
/F4 1 Tf
10.479 0.0003 TD
-0.0031 Tc
0 Tw
[(Eh)-7.1(r)14.5(l)-2.6(i)-6.5(-)]TJ
-22.1198 -1.1976 TD
-0.0023 Tc
[(chi)-5.7(a)]TJ
/F1 1 Tf
1.5329 -0.0003 TD
-0.0007 Tc
0.1938 Tw
[(. A r)7.9(e)0.1(ce)6.1(ntly publi)4.8(s)-1.1(hed randomiz)11(ed trial determined)5.3( )-6(that)]TJ
-1.5329 -1.1976 TD
-0.0017 Tc
0.1828 Tw
[(tr)6.9(eatment of )-6(sev)5.1(e)-0.9(r)6.9(e)-0.9( )]TJ
/F4 1 Tf
8.0719 0.0003 TD
-0.0061 Tc
0 Tw
[(Ba)-5.2(b)-7.2(e)-1.4(s)-7.6(i)-3.6(a)]TJ
/F1 1 Tf
2.8024 -0.0003 TD
0 Tc
( )Tj
/F4 1 Tf
0.4371 0.0003 TD
-0.0036 Tc
[(mic)-6.9(r)2.1(oti)]TJ
/F1 1 Tf
2.6407 -0.0003 TD
-0.0011 Tc
0.1822 Tw
[( with the combination )-6(of)]TJ
-13.9521 -1.1976 TD
-0.0015 Tc
0.2186 Tw
[(ato)11.4(v)5.3(aquone )-6(and )-6(azithromy)11.3(c)3.3(in was )-6(as eff)-4.9(e)-0.7(ctive a)-4.7(s)-1.9( the u)-4.5(s)4.1(e )-6(of)]TJ
T*
-0.0013 Tc
0.0028 Tw
[(standa)-4.5(r)13.3(d)4.7( ora)-4.5(l)0.2( )6(t)-5.7(h)4.7(er)-4.6(apy with )6(clindam)-4.7(y)17.5(cin and )6(quinine )]TJ
7.02 0 0 7.02 492.2401 284.3004 Tm
-0.0043 Tc
0 Tw
[([)-9.1(55])]TJ
10.02 0 0 10.02 503.7 284.3001 Tm
0 Tc
(.)Tj
-20.5449 -1.1976 TD
0.0073 Tc
0.072 Tw
[(Th)-4.6(e d)-4.7(e)2.1(c)-5.9(i)0.8(s)-5(i)0.8(o)-3.7(n)-0.6( t)-3.1(o)2.3( us)-5(e al)-3.2(t)-3.1(e)2.1(rnat)-3.1(i)-5.2(v)]TJ
11.8982 0 TD
0.0093 Tc
0.07 Tw
[(e antibiotics should be )5.9(based)]TJ
-12.7485 -1.1976 TD
0.01 Tc
0.0933 Tw
[(o)5(n)-3.9( th)4(e ind)4(i)-2.5(v)4.9(i)-2.5(d)4(u)1(al cas)3.7(e)-1.2(, inc)2.8(l)-0.5(ud)4(ing a )-6(c)2.8(a)0.8(r)12.7(e)-1.2(ful as)3.7(ses)3.7(s)3.7(m)0.6(ent of th)4(e)]TJ
T*
0.0104 Tc
0.0929 Tw
[(pati)3.9(ent)18()83.7(s ris)4.1(k)1.4( )-6(fa)7.2(cto)5.4(r)1.1(s and pers)4.1(on)]TJ
12.7904 0 TD
0.0098 Tc
0.0935 Tw
[(al pr)6.5(e)4.6(f)0.4(er)12.5(ences. P)43.8(a)0.6(tie)4.6(n)1.9(ts man-)]TJ
-12.7904 -1.1976 TD
0.0079 Tc
0.1672 Tw
[(aged)-4.1( in)-6( this)-4.4( way mus)-4.4(t)3.5( )-6(be c)-5.3(a)-1.3(r)10.6(e)-3.3(fully selec)-5.3(t)-2.5(ed)-4.1( and )-6(con)-6(s)1.6(id)-4.1(er)10.6(ed)]TJ
T*
0.0099 Tc
0.1233 Tw
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T*
-0.0171 Tc
0.0004 Tw
[(M)34.9(G)23.2(E)20.2(,)-7.1( W)109.6(e)5.6(i)-6.8(n)14.6(ste)5.6(i)-6.8(n)14.6( A)12.6(.)-0.4( )-6.7(L)62.6(y)7.6(m)23.2(e)5.6( d)5.2(i)-0.1(se)5.6(a)6.9(s)-0.8(e)5.6(:)-0.4( )-6.7(a)6.9(n)14.6( )]TJ
T*
-0.0166 Tc
0.0066 Tw
[(in)15.1(fec)10.1(t)-2.9(io)9.4(u)15.4(s)-0.3( a)7.4(n)15.1(d)12.4( p)10.4(o)16.1(stin)15.1(fec)10.1(t)-2.9(io)9.4(u)8.7(s)6.4( s)6.4(y)1.4(n)15.1(d)12.4(r)8.7(o)9.4(m)30.4(e)-0.6(. )]TJ
/F4 1 Tf
14.74 0 TD
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0 Tw
(J. )Tj
-14.74 -1.1667 TD
-0.0349 Tc
[(Rh)-6.6(e)-15.6(u)-5.6(ma)-10.9(t)-17.6(o)-8.9(l)-22.2(.)]TJ
/F1 1 Tf
4.0133 0 TD
-0.0267 Tc
0.0167 Tw
[( )6.7(21,)-10( 4)6.6(5445)6.6(6 \()-6.7(1994)6.6(\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 34.2 543.3198 Tm
0 Tc
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(5)Tj
/F1 1 Tf
9 0 0 9 49.8 543.32 Tm
-0.015 Tc
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0 -1.1667 TD
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T*
-0.0177 Tc
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[(in)14(fec)9(t)-4(io)8.3(u)14.3(s)-1.4( th)10.6(r)7.6(e)5(a)6.3(t)2.6(.)-7.7( )]TJ
/F4 1 Tf
6.3733 0 TD
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[(C)15.8(l)-4.2(in)10.8(. I)24.1(n)10.8(fect. D)28.8(i)-5.6(s.)]TJ
/F1 1 Tf
5.9 0 TD
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[( 3)23.3(2)16.7(, )]TJ
-12.2733 -1.1667 TD
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[(8)6.6(97928)6.6( \()-6.7(2001)6.6(\))-13.4(.)]TJ
/TT6 1 Tf
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/F1 1 Tf
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/F4 1 Tf
T*
-0.0203 Tc
0.0036 Tw
(et al)Tj
/F1 1 Tf
1.48 0 TD
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0.0057 Tw
[(.)-5.7( )-6.7(P)39.9(r)-3.7(a)-5.1(c)4.3(t)-8.7(i)-5.4(ce gui)-5.4(d)-0.1(el)-8.7(i)-5.4(n)9.3(es)-6.1( )-6.7(f)-5.7(o)3.6(r t)-8.7(h)12.6(e)-6.4( treat)-8.7(m)24.6(ent )]TJ
-1.48 -1.1667 TD
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0.0065 Tw
[(o)16.2(f)0.2( L)56.5(y)8.2(m)30.5(e)6.2( d)12.5(i)0.5(se)6.2(a)7.5(s)-0.2(e)6.2(.)-6.5( )6.7(T)16.8(h)18.5(e )6.7(I)14.8(n)8.5(fe)6.2(c)10.2(t)-2.8(io)9.5(u)8.8(s)6.5( D)36.8(i)0.5(se)6.2(a)7.5(s)-0.2(e)6.2(s)-0.2( )]TJ
T*
-0.0228 Tc
0.0061 Tw
[(S)19.5(o)3.2(ci)-5.8(et)-9.1(y of)-6.1( A)6.9(m)24.2(eri)-12.5(c)3.9(a)-5.5(.)-6.1( )]TJ
/F4 1 Tf
7.3067 0 TD
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0.0006 Tw
[(C)15.4(l)-4.6(in)10.4(.)-7.3( I)23.7(n)10.4(fect. )-6.7(D)28.4(i)-6(s)]TJ
/F1 1 Tf
5.66 0 TD
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(. )Tj
-12.9667 -1.1667 TD
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0.01 Tw
[(3)6.6(1)0(\()-13.4(S)29(uppl)-13(.)-10( 1\))-13.4(,)-10( 114 \()-6.7(2000\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 34.2 442.8198 Tm
0 Tc
0 Tw
(7)Tj
/F1 1 Tf
9 0 0 9 49.8 442.82 Tm
-0.0112 Tc
-0.0055 Tw
[(R)27.1(a)12.8(h)17.1(n)20.5( )-6.7(D)48.8(W)155.5(,)5.5( M)47.5(a)12.8(la)12.8(w)22.1(i)5.8(s)5.1(t)9.1(a)6.1( S)17.8(E)19.5(. L)61.8(y)13.5(m)35.8(e)11.5( )-6.7(d)17.8(i)5.8(s)5.1(e)11.5(a)12.8(s)5.1(e)11.5(:)-1.2( )]TJ
T*
-0.0283 Tc
0.0183 Tw
[(re)-5.6(c)-8.3(o)-2.3(m)18.7(m)12(e)-5.6(n)3.4(da)-11(t)-8(i)-11.3(ons)-5.3( f)-11.6(o)-2.3(r)-9.6( )6.7(di)-18(agnos)-12(i)-11.3(s)-12( and )]TJ
T*
-0.0223 Tc
0 Tw
[(treatm)18(en)9.4(t)-8.6(.)-5.6( )]TJ
/F4 1 Tf
3.98 0 TD
-0.0277 Tc
-0.0223 Tw
[(A)21.6(nn.)-11( I)13.3(n)0(t)-10.4(e)-8.4(r)-20(n)0(.)-11( )-6.7(M)39.6(e)-8.4(d)]TJ
/F1 1 Tf
6.12 0 TD
-0.0267 Tc
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[(.)-16.7( 114)6.6(,)-16.7( 4724)6.6(81 )]TJ
-10.1 -1.1667 TD
0 Tw
[(\()-6.7(199)6.6(1\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 34.2 397.8198 Tm
0 Tc
(8)Tj
/F1 1 Tf
9 0 0 9 49.8 397.82 Tm
-0.0425 Tc
0.0058 Tw
[(F)42.2(e)0.2(d)6.5(e)-6.5(r H)16.8(M)29.5( )-6.7(Jr)56.2(.)-12.5( )-6.7(D)30.8(i)-5.5(f)-5.8(f)-12.5(eren)9.2(ce)-6.5(s)-6.2( are)-6.5( voi)-5.5(c)-2.5(ed b)10.8(y)-4.5( t)-8.8(w)17.5(o )]TJ
T*
-0.0401 Tc
0.0034 Tw
[(L)52.9(y)4.6(m)26.9(e)-4.1( cam)20.2(p)6.9(s )-6.7(at)-6.4( a C)15.9(o)5.9(nn)11.6(ect)-6.4(i)-3.1(cu)5.2(t)-6.4( p)6.9(u)5.2(b)6.6(l)-6.4(i)-9.8(c)6.6( )-6.7(h)8.2(e)2.6(ari)-9.8(n)11.6(g)5.9( )]TJ
T*
-0.0462 Tc
0.0095 Tw
[(on)5.5( )-6.7(i)-9.2(n)-1.2(s)-9.9(u)5.8(r)-14.2(a)-2.2(nce)-10.2( c)-6.2(o)13.1(v)5.8(e)-10.2(r)-7.5(a)-2.2(g)-6.9(e)-3.5( of)-16.2( L)46.8(y)-1.5(m)14.1(e)-3.5( )-6.7(di)-15.9(s)-9.9(e)-3.5(as)-9.9(e)-10.2(.)-9.5( )]TJ
/F4 1 Tf
T*
-0.092 Tc
0 Tw
[(Pe)-52.7(d)-44.7(i)-60.7(a)-48(t)-54.7(r)-57.7(i)-54(c)-60.7(s)]TJ
/F1 1 Tf
3.1667 0 TD
-0.0467 Tc
0.01 Tw
[( 105\()-13.4(4 P)15.6(t)-13( 1\))-13.4(,)-10( )-6.7(855857 \()-13.4(2000\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 34.2 352.8198 Tm
0 Tc
0 Tw
(9)Tj
/F1 1 Tf
9 0 0 9 49.8 352.82 Tm
-0.0175 Tc
0.0008 Tw
[(B)27.5(u)14.5(rra)6.5(sca)6.5(n)14.2(o)8.5( )-6.7(JJ)7.5(.)-7.5( L)55.5(y)7.2(m)22.8(e)5.2( d)11.5(i)-7.2(s)5.5(e)5.2(as)5.5(e. I)7.2(n)14.2(: )]TJ
/F4 1 Tf
11.8867 0 TD
-0.0403 Tc
0 Tw
[(Co)-21(n)-12.6(n)94(s)-25( )]TJ
-11.8867 -1.1667 TD
-0.0202 Tc
0.0035 Tw
[(C)32.5(u)9.1(rr)14.1(en)7.5(t T)13.8(h)8.1(er)27.5(ap)14.5(y)]TJ
/F1 1 Tf
5.7533 0 TD
-0.0177 Tc
0.0077 Tw
[(. W)35.6(B)20.6( S)24.6(a)-0.4(u)14.3(n)14(d)4.6(e)5(rs)5.3( C)25(o)8.3(m)22.6(p)9.3(a)6.3(n)14(y)87(,)-7.7( )]TJ
-5.7533 -1.1667 TD
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0.0167 Tw
[(P)42.3(A)9.6(,)-10( U)19.3(S)-4.4(A)9.6( )6.7(14014)6.6(3 \()-6.7(199)6.6(7\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 34.2 318.3198 Tm
-0.0032 Tc
0 Tw
(10)Tj
/F1 1 Tf
9 0 0 9 49.8 318.32 Tm
-0.0232 Tc
0.0132 Tw
[(K)18.5(i)-12.9(sh)5.1( M)28.8(A)13.1(.)-13.2( )6.7(G)30.5(u)2.1(i)-6.2(d)5.8(e to )6.7(dev)8.8(e)-0.5(l)-9.5(o)2.8(pm)23.8(ent o)9.5(f)-6.5( )]TJ
T*
-0.0174 Tc
0.0007 Tw
[(p)16.3(r)1.3(ac)9.3(tice)5.3( gu)14.6(id)4.9(e)5.3(l)-3.7(in)14.3(es)5.6(.)-7.4( )]TJ
/F4 1 Tf
7.1933 0 TD
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0.0067 Tw
[(C)16(l)2.6(i)-5.4(n)11(. I)24.3(n)11(fec)8(t)-6(. )6.7(D)22.3(i)-5.4(s)]TJ
/F1 1 Tf
5.6667 0 TD
-0.0267 Tc
0.01 Tw
[(.)-10( 32,)-16.7( )]TJ
-12.86 -1.1667 TD
0.0167 Tw
[(8)6.6(51854)6.6( \()-6.7(2001)6.6(\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 34.2 283.8198 Tm
-0.0032 Tc
0 Tw
(11)Tj
/F1 1 Tf
9 0 0 9 49.8 283.82 Tm
-0.0232 Tc
0.0065 Tw
[(S)32.5(t)-9.5(eere A)19.8(C)19.5(,)-13.2( M)35.5(a)0.8(l)-9.5(a)0.8(w)10.1(i)-6.2(s)-6.9(t)-2.9(a)-5.9( S)5.8(E)7.5(,)-6.5( )-6.7(S)25.8(n)8.5(y)8.1(d)5.8(m)17.1(a)0.8(n)8.5( )-6.7(D)23.5(R)8.5(,)-6.5( )]TJ
T*
-0.0108 Tc
-0.0059 Tw
[(S)31.5(h)17.5(o)15.2(p)16.2(e)11.9( R)20.9(E)26.5(, A)25.5(n)14.2(d)18.2(i)6.2(m)29.5(a)13.2(n)20.9( )-6.7(W)115.9(A)25.5(, R)34.2(o)15.2(s)5.5(s)12.2( )-6.7(M)41.2(R)27.5(, S)38.2(t)9.5(e)5.2(e)11.9(le)11.9( )]TJ
T*
-0.0165 Tc
0.0065 Tw
[(F)14.8(M)35.5(. L)56.5(y)8.2(m)30.5(e)6.2( a)7.5(r)-4.5(th)18.5(riti)-6.2(s: )6.7(an)15.2( )6.7(ep)17.2(i)-6.2(d)12.5(e)6.2(m)30.5(i)-6.2(c)10.2( o)9.5(f)0.2( )]TJ
T*
-0.0123 Tc
-0.0044 Tw
[(o)20.4(l)1.4(ig)13.7(o)13.7(a)11.7(rti)4.7(c)7.7(u)19.7(l)1.4(a)5(r)6.4( a)11.7(r)-0.3(th)16(r)6.4(i)4.7(ti)4.7(s)4( in)19.4( c)7.7(h)16(ild)16.7(r)19.7(e)10.4(n)12.7( a)11.7(n)12.7(d)16.7( )]TJ
T*
-0.0141 Tc
-0.0026 Tw
[(a)9.9(d)14.9(u)17.9(lts in)10.9( th)14.2(r)17.9(e)8.6(e C)21.9(o)18.6(n)10.9(n)17.6(e)8.6(c)5.9(t)6.2(i)-3.8(c)12.6(u)11.2(t)6.2( )-6.7(c)5.9(o)18.6(m)26.2(m)32.9(u)11.2(n)17.6(it)6.2(ie)8.6(s)8.9(.)-4.1( )]TJ
/F4 1 Tf
T*
-0.0171 Tc
0.0004 Tw
[(A)32.2(r)-9.4(th)11.2(riti)-5.8(s R)16.9(h)4.6(eu)12.2(m)]TJ
/F1 1 Tf
5.6667 0 TD
-0.0267 Tc
0.01 Tw
[(.)-16.7( 20,)-10( )-6.7(7)6.6(17 \()-13.4(1)6.6(977\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 34.2 217.8198 Tm
-0.0032 Tc
0 Tw
(12)Tj
/F1 1 Tf
9 0 0 9 49.8 217.82 Tm
-0.0169 Tc
0.0002 Tw
[(L)16.1(o)9.1(g)9.1(i)0.1(gia)7.1(n)8.1( E)13.8(L)16.1(, )-6.7(K)24.8(a)0.4(p)16.8(l)-3.2(an)14.8( R)14.8(F)147.8(,)-6.9( S)32.1(t)3.4(ee)5.8(r)15.1(e)5.8( )-6.7(A)32.8(C)19.1(. )]TJ
0 -1.1667 TD
-0.0317 Tc
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[(C)11(h)-3.4(r)-6.4(o)-5.7(ni)-21.4(c)-11.7( ne)-9(u)-6.4(r)-6.4(o)-5.7(l)-18(o)-5.7(g)-5.7(i)-14.7(c)-11.7( m)15.3(a)-14.4(ni)-14.7(f)-15(e)-15.7(s)-8.7(t)-18(a)-7.7(t)-11.4(i)-21.4(o)-5.7(ns)-15.4( o)-5.7(f)-15( L)41.3(y)-7(m)15.3(e)-9( )]TJ
T*
-0.0265 Tc
0 Tw
[(di)-9.5(s)-10.2(e)-3.8(as)-10.2(e)-3.8(.)-9.8( )]TJ
/F4 1 Tf
2.9333 0 TD
-0.0174 Tc
0.0074 Tw
[(N)21.6(.)-0.7( )6.7(E)28.6(n)10.3(g)4.6(l)-4.7(. J. M)49.9(e)1.9(d)]TJ
/F1 1 Tf
5.6 0 TD
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0.01 Tw
[(.)-16.7( 323)6.6(,)-16.7( 1438)6.6(1444 )]TJ
-8.5333 -1.1667 TD
0 Tw
[(\()-6.7(199)6.6(0\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 34.2 172.8198 Tm
-0.0032 Tc
(13)Tj
/F1 1 Tf
9 0 0 9 49.8 172.82 Tm
-0.0162 Tc
0.0062 Tw
[(F)61.8(a)7.8(llo)9.8(n)15.5( B)15.5(A)20.1(, N)53.5(i)-5.9(e)6.5(l)-2.5(d)12.8(s)6.8( JA)20.1(. L)56.8(y)8.5(m)30.8(e)6.5( d)12.8(i)0.8(se)6.5(a)7.8(s)0.1(e)6.5(:)-6.2( )6.7(a)7.8( )]TJ
T*
-0.0251 Tc
0.0151 Tw
[(n)6.6(e)-2.4(urop)8.6(s)-8.8(y)12.9(c)-5.1(hi)-14.8(atr)-6.4(i)-14.8(c i)-8.1(l)-11.4(l)-11.4(n)-0.1(ess)-8.8(.)-15.1( )]TJ
/F4 1 Tf
8.9133 0 TD
-0.0493 Tc
0.0326 Tw
[(Am)-7(.)-39.3( J)-29.3(.)-39.3( P)9.4(s)-34(y)-23.3(c)-31.3(h)-21(i)-38(a)-18.6(t)-38.6(r)-48.3(y)]TJ
/F1 1 Tf
5.9867 0 TD
0 Tc
0 Tw
( )Tj
-14.9 -1.1667 TD
-0.0267 Tc
0.0167 Tw
[(1)6.6(51,)-10( 157)6.6(11583)6.6( \()-6.7(1994)6.6(\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 34.2 138.3198 Tm
-0.0032 Tc
0 Tw
(14)Tj
/F1 1 Tf
9 0 0 9 49.8 138.32 Tm
-0.0308 Tc
0.0208 Tw
[(T)115.9(y)-12.8(l)-17.1(e)-8.1(ws)-14.5(ka)-6.8(-)-17.5(W)35.9(i)-20.5(e)-8.1(r)-12.1(z)-13.8(b)-4.1(a)-6.8(no)8.5(ws)-14.5(ka)-6.8( S,)-14.1( C)11.9(h)-2.5(m)9.5(i)-13.8(e)-8.1(l)-17.1(e)-14.8(w)2.5(s)-7.8(k)-8.8(i)-13.8( )]TJ
T*
-0.0259 Tc
0.0159 Tw
[(T)127.4(.)-9.2( L)7.1(i)-15.6(m)21.1(i)-15.6(t)-5.6(a)-1.9(t)-12.2(i)-8.9(on)5.8( of)-9.2( )6.7(s)-9.6(e)-3.2(rol)-12.2(ogi)-8.9(c)-5.9(a)-1.9(l)-12.2( t)-5.6(e)-3.2(s)-9.6(t)-12.2(i)-8.9(n)5.8(g f)-9.2(o)0.1(r)-7.2( )]TJ
T*
-0.017 Tc
0.0003 Tw
[(L)62.7(y)7.7(m)23.3(e)5.7( b)9.7(o)9(rr)8.3(e)5.7(l)-3.3(io)9(sis: )-6.7(e)5.7(v)15(a)7(l)-3.3(u)8.3(a)7(tio)9(n)14.7( )-6.7(o)9(f)-0.3( E)13.7(L)16(IS)12(A)12.7( a)7(n)8(d)12( )]TJ
T*
-0.0259 Tc
0.0092 Tw
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T*
-0.0146 Tc
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[(c)12.1(u)10.7(lt)5.7(u)10.7(r)17.4(e)8.1( m)32.4(e)8.1(th)13.7(o)11.4(d)14.4(s. )]TJ
/F4 1 Tf
6.3933 0 TD
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0.0013 Tw
[(W)40(i)-6.7(en)9.7( K)18.3(l)-5.3(i)-6.7(n)9.7( W)106.7(o)1.3(c)6.7(h)3.7(en)9.7(sch)10.3(r)]TJ
/F1 1 Tf
7.8933 0 TD
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0 Tw
(. )Tj
-14.2867 -1.1667 TD
-0.0267 Tc
0.0167 Tw
[(1)6.6(14,)-10( 601)6.6(605 )6.7(\()-6.7(2002\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 34.2 72.3198 Tm
-0.0032 Tc
0 Tw
(15)Tj
/F1 1 Tf
9 0 0 9 49.8 72.32 Tm
-0.0253 Tc
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/F4 1 Tf
11.1533 0 TD
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[(Am)-20.3(.)-39.3( J)-36(.)-39.3( M)11.3(e)-36.7(d)]TJ
/F1 1 Tf
4.08 0 TD
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(. )Tj
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/TT6 1 Tf
6.96 0 0 6.96 204.3 717.3198 Tm
0.0054 Tc
0 Tw
(16)Tj
/F1 1 Tf
9 0 0 9 219.84 717.32 Tm
-0.0239 Tc
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[(B)21.1(a)-6.6(tt)-10.2(agl)-10.2(i)-6.9(a)-6.6( )6.7(H)15.4(R)14.4(,)-7.2( A)12.4(l)-10.2(varez)-6.9( )6.7(G)16.4(,)-13.9( M)54.8(e)-1.2(r)-5.2(c)2.8(au A)12.4(,)-7.2( F)47.4(a)0.1(y M)28.1(,)-7.2( )]TJ
T*
-0.0263 Tc
0.0096 Tw
[(C)9.7(a)-2.3(m)14(p)7.4(odni)-9.3(c)-6.3(o M)25.7(.)-16.3( P)36(s)-3.3(y)5(c)0.4(hi)-16(at)-6(r)-14.3(i)-9.3(c)-6.3( )]TJ
T*
-0.0153 Tc
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[(sy)9.4(m)25(p)18.4(to)10.7(m)31.7(a)8.7(to)10.7(lo)10.7(g)10.7(y)9.4( as)7.7(so)10.7(c)4.7(i)1.7(a)8.7(t)-1.6(e)7.4(d)13.7( w)18(i)1.7(th)13( )]TJ
T*
-0.0235 Tc
0.0068 Tw
[(pres)-7.2(u)8.5(m)16.8(p)10.2(t)-9.8(i)-6.5(v)1.8(e L)49.5(y)1.2(m)16.8(e)-0.8( d)5.5(i)-13.2(sea)-6.2(s)-0.5(e:)-13.5( C)12.5(l)-9.8(i)-6.5(n)1.5(i)-6.5(c)-3.5(al)-9.8( )]TJ
T*
-0.0231 Tc
0 Tw
[(evi)-6.1(d)5.9(ence.)-13.1( )]TJ
/F4 1 Tf
3.6 0 TD
-0.0185 Tc
0.0018 Tw
[(J.)-8.5( S)19.2(p)2.8(ir)9.2(o T)48.8(ick)9.5( )-6.7(D)27.2(i)-7.2(s)]TJ
/F1 1 Tf
5.86 0 TD
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0.0167 Tw
[(.)-10( 7,)-10( )6.7(2225 )]TJ
-9.46 -1.1667 TD
0 Tw
[(\()-13.4(2)6.6(000\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 204.3 651.3198 Tm
0.0054 Tc
(17)Tj
/F1 1 Tf
9 0 0 9 219.84 651.32 Tm
-0.0172 Tc
0.0005 Tw
[(C)18.8(o)8.8(rsa)6.8(r)8.1(o)8.8( L)9.1( I)14.1(n)7.8(tra)6.8(m)23.1(u)14.8(s)-0.9(cu)14.8(la)6.8(r )-6.7(B)27.8(i)-0.2(cilli)-6.9(n)14.5( )-6.7(fo)15.5(r )]TJ
T*
-0.0266 Tc
0.0166 Tw
[(per)-7.9(s)-10.3(i)-9.6(s)-10.3(t)-12.9(e)-3.9(nt)-12.9( )6.7(pedi)-9.6(a)-9.3(t)-6.3(r)-7.9(i)-16.3(c L)46.4(y)-1.9(m)20.4(e)-3.9( di)-9.6(s)-10.3(e)-3.9(as)-10.3(e.)-9.9( )]TJ
T*
-0.0256 Tc
0.0089 Tw
[(P)30.1(r)-0.3(oc)-5.6(eedi)-8.6(n)-0.6(gs)-9.3( of)-8.9( t)-11.9(h)2.7(e 9t)-11.9(h I)5.7(n)6.1(t)-11.9(e)-2.9(r)-6.9(n)6.1(a)-8.3(t)-5.3(i)-15.3(o)7.1(nal)-11.9( )]TJ
T*
-0.0218 Tc
0.0051 Tw
[(C)14.2(o)4.2(n)9.9(f)-5.1(eren)9.9(ce )-6.7(o)10.9(n)3.2( L)51.2(y)2.9(m)18.5(e)0.9( B)9.9(o)4.2(rr)10.2(el)-8.1(i)-11.5(o)4.2(si)-11.5(s )-6.7(&)22.9( O)26.5(t)-1.5(h)6.5(e)-5.8(r )]TJ
T*
-0.026 Tc
0.0093 Tw
[(T)47.3(i)-15.7(ck-)-12.7(b)0.7(o)6.7(r)-14(ne D)27.3(i)-15.7(sor)6(d)3(er)-7.3(s)-9.7( )-6.7(\()-6(199)7.3(9\))-12.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 204.3 595.8198 Tm
0.0054 Tc
0 Tw
(18)Tj
/F1 1 Tf
9 0 0 9 219.84 595.82 Tm
-0.026 Tc
0.0093 Tw
[(C)10(i)-9(m)14.3(m)21(i)-15.7(n)5.7(o M)19.3(A)10.3(,)-9.3( )-6.7(A)23.7(c)-6(ca)-8.7(r)6(d)3(o S.)-16( Lo)6.7(ng-)-6(t)-12.3(er)-7.3(m)21( )]TJ
T*
-0.0149 Tc
-0.0018 Tw
[(tr)17.1(ea)9.1(t)5.4(m)25.4(e)7.8(n)16.8(t o)11.1(f)1.8( c)5.1(h)13.4(r)10.4(o)11.1(n)16.8(i)-4.6(c)5.1( L)58.1(y)9.8(m)32.1(e)7.8( )-6.7(a)9.1(r)-2.9(th)13.4(ritis w)18.4(i)2.1(th)20.1( )]TJ
T*
-0.0287 Tc
-0.0213 Tw
[(be)-6(n)-3.7(z)-5(a)-4.7(t)-15(hi)-11.7(ne)-12.7( pe)-6(ni)-18.4(ci)-18.4(l)-15(l)-15(i)-11.7(n)-3.7(.)-12( )]TJ
/F4 1 Tf
8.0333 0 TD
-0.0277 Tc
-0.0223 Tw
[(A)28.3(nn.)-17.7( Rhe)-8.4(u)1.6(m)8(.)-11( D)11.3(i)-16.4(s)]TJ
/F1 1 Tf
6.0533 0 TD
-0.0167 Tc
-0.0266 Tw
[(. 5)16.6(1)10(,)-6.7( )]TJ
-14.0867 -1.1667 TD
-0.0267 Tc
0.01 Tw
[(1007)6.6(1008 \()-13.4(1)6.6(992\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 204.3 550.8198 Tm
0.0054 Tc
0 Tw
(19)Tj
/F1 1 Tf
9 0 0 9 219.84 550.82 Tm
-0.0155 Tc
-0.0012 Tw
[(F)55.8(a)8.5(llo)10.5(n)16.2( )-6.7(B)22.8(A)14.2(, T)124.5(a)8.5(g)3.8(e)7.2(r F)142.5(,)1.2( K)26.2(e)7.2(ilp)11.5( J, )-6.7(W)111.2(e)7.2(iss N)27.5(,)1.2( )]TJ
T*
-0.025 Tc
-0.0383 Tw
[(Li)-8(ebo)14.3(w)8.3(i)-8(t)-11.3(z M)27(R)6.7(,)-8.3( F)39.7(e)-9(i)-8(n)6.7( L,)-8.3( Li)-8(egner)-6.3( K)10(.)-8.3( R)20(e)-2.3(peat)-11.3(ed )]TJ
T*
-0.0205 Tc
0.0105 Tw
[(an)11.2(ti)-10.2(b)6.2(i)-3.5(o)5.5(t)-0.2(i)-10.2(c)6.2( treat)-6.8(m)26.5(ent in)11.2( c)6.2(h)7.8(ro)12.2(nic )6.7(L)52.5(y)4.2(m)19.8(e)2.2( )]TJ
T*
-0.0265 Tc
0 Tw
[(di)-16.2(s)-10.2(e)-3.8(as)-10.2(e)-3.8(.)-9.8( )]TJ
/F4 1 Tf
2.9267 0 TD
-0.0175 Tc
-0.0125 Tw
[(J. S)20.2(p)3.8(iro)8.5( T)56.5(i)-6.2(ck)10.5( D)21.5(i)0.5(s)]TJ
/F1 1 Tf
5.8133 0 TD
-0.0264 Tc
-0.0036 Tw
[(.)-9.7( 6,)-9.7( )-6.7(9)6.9(4102 \()-6.4(1999)6.9(\))-13.1(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 204.3 505.8198 Tm
0.0054 Tc
0 Tw
(20)Tj
/F1 1 Tf
9 0 0 9 219.84 505.82 Tm
-0.0175 Tc
0.0075 Tw
[(L)8.8(a)6.5(w)22.5(r)7.8(e)5.2(n)14.2(ce)5.2( C)25.2(,)-7.5( )6.7(L)15.5(i)-7.2(p)9.5(t)2.8(o)8.5(n)14.2( R)20.8(B)14.2(, L)15.5(o)21.8(w)15.8(y)7.2( )6.7(F)13.8(D)22.5(, C)25.2(o)21.8(y)7.2(l)-3.8(e)5.2( )]TJ
0 -1.1667 TD
-0.0246 Tc
0.0146 Tw
[(PK)10.4(.)-7.9( S)17.7(e)-1.9(ronegat)-10.9(i)-7.6(v)7.4(e)-1.9( ch)10.4(r)-5.9(o)8.1(ni)-7.6(c )6.7(rel)-10.9(a)-0.6(ps)-8.3(i)-7.6(n)0.4(g )]TJ
T*
-0.0252 Tc
0 Tw
[(neu)6.8(r)0.1(obor)-6.5(rel)-11.5(i)-8.2(os)-8.9(i)-8.2(s)-8.9(.)-8.5( )]TJ
/F4 1 Tf
6.3067 0 TD
-0.0527 Tc
0.036 Tw
[(Eu)-23.4(r)21.6(.)-36( N)13(e)-33.4(u)-23.4(r)-31.7(o)-26.7(l)]TJ
/F1 1 Tf
4.1133 0 TD
-0.0267 Tc
0.0167 Tw
[(.)-10( 35)6.6(,)-16.7(113)6.6(117 )]TJ
-10.42 -1.1667 TD
0 Tw
[(\()-13.4(1)6.6(995\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 204.3 460.8198 Tm
0.0054 Tc
(21)Tj
/F1 1 Tf
9 0 0 9 219.84 460.82 Tm
-0.012 Tc
0.0153 Tw
[(Ca)-8(m)15(e)-9.3(r)-6.7(o)-6(n D)8(J)-7(.)-15.3( )-6.7(M)46.7(o)-6(ni)-15(t)-18.3(o)0.7(r)-13.3(i)-21.7(ng)-6( L)41(y)-7.3(m)15(e)-9.3( di)-15(s)-15.7(e)-9.3(a)-8(s)-9(e)-9.3( )]TJ
T*
-0.0025 Tc
0.0058 Tw
[(i)-12.2(n)9.2( th)5.8(e co)10.2(m)17.8(m)24.5(u)9.5(n)2.5(i)-5.5(t)-2.2(y F)42.2(i)-12.2(rst )-6.7(sur)-17.2(v)9.5(ei)-5.5(l)-8.8(l)-8.8(a)1.5(n)9.2(c)-2.5(e )]TJ
T*
0.005 Tc
0.005 Tw
[(d)14(a)9(ta)9(b)18.3(a)9(se)7.7( )6.7(se)7.7(n)16.7(t)5.3(in)10(e)7.7(l)5.3( h)20(e)7.7(a)9(lth)20( s)8(i)2(te)7.7(. )6.7(P)40.7(r)10.3(o)17.7(c)5(e)7.7(e)7.7(d)14(in)16.7(g)11(s)1.3( )]TJ
T*
-0.0047 Tc
0.008 Tw
[(of)-8( the 12th A)11.6(n)7(nu)7.3(al)-11( I)6.6(n)7(t)-11(e)-2(rnati)-7.7(o)1.3(n)7(a)-0.7(l)-11( )]TJ
T*
0.0027 Tc
0.0006 Tw
[(S)11.7(c)2.7(ie)5.4(n)14.4(t)-3.6(ific)9.4( )-6.7(C)25.4(o)8.7(n)14.4(f)-0.6(e)5.4(r)14.7(e)5.4(n)14.4(ce)5.4( o)8.7(n)14.4( L)55.7(y)7.4(m)29.7(e)5.4( D)36(i)-0.3(se)5.4(a)6.7(s)5.7(e)5.4( )]TJ
T*
-0.0078 Tc
0.0111 Tw
[(and O)27.2(t)-14.1(h)7.2(e)-5.1(r)-9.1( )-6.7(S)27.9(p)-0.8(i)-10.8(r)-2.5(oche)-5.1(t)-7.5(a)-3.8(l)-14.1( a)-10.5(n)3.9(d T)45.5(i)-10.8(ck-)-14.5(B)10.5(or)-9.1(ne)-5.1( )]TJ
T*
0.0025 Tc
0.0008 Tw
[(D)35.8(i)-0.5(so)15.2(r)14.5(d)11.5(e)5.2(r)1.2(s \(1)9.2(9)15.8(9)9.2(9)9.2(\))2.5(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 204.3 384.3198 Tm
0.0054 Tc
0 Tw
(22)Tj
/F1 1 Tf
9 0 0 9 219.84 384.32 Tm
-0.0167 Tc
[(F)54.6(a)7.3(llo)9.3(n)15( )-6.7(B)21.6(A)13(, K)38.3(o)9.3(ch)11.6(e)6(v)15.3(ar JM)35.3(, )-6.7(G)30.3(a)7.3(ito)9.3( A)19.6(,)-6.7( N)46.3(i)0.3(e)6(l)-3(d)12.3(s)-0.4( )]TJ
T*
-0.0306 Tc
-0.0127 Tw
[(J)-12.3(A)5.7(.)-20.6( The)-7.9( )-6.6(und)-8.3(e)-7.9(rdi)-13.6(a)-6.6(g)-11.3(n)1.1(o)-4.6(s)-14.3(i)-13.6(s)-14.3( o)-4.6(f)-13.9( )-6.6(ne)-7.9(u)-5.3(r)-5.3(o)-4.6(ps)-7.6(yc)-3.9(hi)-20.3(a)-6.6(t)-16.9(r)-11.9(i)-13.6(c)-10.6( )]TJ
T*
-0.0243 Tc
0.0076 Tw
[(L)48.7(y)0.4(m)16(e)-1.6( di)-14(se)-8.3(as)-8(e i)-7.3(n)0.7( chi)-7.3(l)-10.6(dren)7.4( )-6.7(an)7.4(d adul)-10.6(ts)-8(.)-7.6( )]TJ
/F4 1 Tf
T*
-0.0091 Tc
-0.0009 Tw
[(P)49.6(s)6.2(y)16.9(c)8.9(h)12.6(i)8.9(a)14.9(t)8.2(r)65.2(.)7.6( C)30.2(l)3.6(i)8.9(n)18.6(. )6.7(N)56.6(o)16.9(rt)8.2(h)19.2( A)46.9(m)]TJ
/F1 1 Tf
9.16 0 TD
-0.0267 Tc
0.0167 Tw
[(.)-10( 2)6.6(1)0(,)-16.7( )6.7(693)6.6(703 )]TJ
-9.16 -1.1667 TD
0 Tw
[(\()-13.4(1)6.6(998\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 204.3 328.8198 Tm
0.0054 Tc
(23)Tj
/F1 1 Tf
9 0 0 9 219.84 328.82 Tm
-0.0169 Tc
0.0002 Tw
[(K)18.1(l)-3.2(e)5.8(m)23.4(p)16.8(n)8.1(e)5.8(r)1.8( M)35.1(S)5.4(, )-6.7(H)62.4(u)8.4( L)102.8(T)136.4(, )-6.7(E)47.1(v)8.4(a)7.1(n)14.8(s J )]TJ
/F4 1 Tf
11.4533 0 TD
-0.0203 Tc
0.0036 Tw
(et al)Tj
/F1 1 Tf
1.48 0 TD
-0.01 Tc
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[(. T)150(w)23.3(o)22.7( )]TJ
-12.9333 -1.1667 TD
-0.0142 Tc
-0.0025 Tw
[(c)5.8(o)11.8(n)17.5(t)-0.5(r)11.1(o)11.8(lle)8.5(d)14.8( tria)9.8(ls )-6.7(o)18.5(f)-4.2( a)9.8(n)10.8(t)6.1(i)2.8(b)12.5(i)-3.9(o)11.8(t)6.1(ic)5.8( )-6.7(t)6.1(r)11.1(e)8.5(a)9.8(t)6.1(m)26.1(e)8.5(n)17.5(t in)17.5( )]TJ
T*
-0.0199 Tc
0.0032 Tw
[(p)7.1(a)4.1(t)-6.2(i)-2.9(ents w)13.4(i)-2.9(t)-6.2(h)8.4( p)7.1(e)2.8(rsisten)11.8(t)0.4( )-6.7(sym)27.1(p)7.1(to)6.1(m)20.4(s)-3.6( and)9.1( a )]TJ
T*
-0.0253 Tc
0.0086 Tw
[(hi)-15(st)-11.6(or)-20(y )-6.7(of)-8.6( L)47.7(y)-0.6(m)21.7(e)-9.3( di)-15(sea)-8(s)-2.3(e.)-15.3( )]TJ
/F4 1 Tf
8.9133 0 TD
-0.01 Tc
-0.0067 Tw
[(N)29(.)6.7( )-6.7(E)42.7(n)17.7(g)5.3(l)9.3(. J)10(.)0( M)57.3(e)9.3(d)]TJ
/F1 1 Tf
5.6067 0 TD
-0.0167 Tc
0 Tw
(. )Tj
-14.52 -1.1667 TD
-0.0267 Tc
0.0167 Tw
[(345,)-10( 8)6.6(592 )6.7(\()-13.4(2)6.6(001\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 204.3 273.3198 Tm
0.0054 Tc
0 Tw
(24)Tj
/F1 1 Tf
9 0 0 9 219.84 273.32 Tm
-0.0222 Tc
0.0055 Tw
[(D)31.1(i)-11.9(n)9.5(e)0.5(rm)24.8(a)-4.9(n)9.5( )-6.7(H)23.8(,)-5.5( )-6.7(S)33.5(t)-8.5(eere A)20.8(C)20.5(.)-12.2( L)50.8(y)2.5(m)18.1(e)0.5( d)6.8(i)-11.9(sea)-4.9(s)0.8(e )]TJ
T*
-0.0162 Tc
-0.0005 Tw
[(as)6.8(so)9.8(cia)7.8(t)-2.5(e)6.5(d)12.8( w)17.1(i)0.8(th)12.1( fi)-5.9(b)17.1(r)2.5(o)16.5(m)24.1(y)8.5(a)7.8(lg)9.8(i)-5.9(a)7.8(. )]TJ
/F4 1 Tf
10.76 0 TD
-0.0277 Tc
0.011 Tw
[(A)21.6(nn.)-11( I)13.3(n)0(t)-17(e)-8.4(r)-13.4(n)0(.)-11( )]TJ
-10.76 -1.1667 TD
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0 Tw
[(Me)-41.4(d)]TJ
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10.0333 0 TD
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[(12,)-10( 16)6.6(09161)6.6(4 \()-6.7(200)6.6(3\))-13.4(.)]TJ
/TT6 1 Tf
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T*
-0.0266 Tc
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/F4 1 Tf
11.8667 0 TD
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[(Am)-7(.)-39.3( J)-29.3(.)-39.3( )]TJ
-11.8667 -1.1667 TD
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[(Me)-41.4(d)]TJ
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6.96 0 0 6.96 204.3 169.8198 Tm
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T*
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6.4667 0 TD
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[(5635)6.6(67 \()-6.7(200)6.6(0\))-13.4(.)]TJ
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6.96 0 0 6.96 204.3 124.8198 Tm
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T*
-0.022 Tc
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T*
-0.0224 Tc
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T*
-0.0256 Tc
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[(vect)-11.9(or)53.1(.)-15.6( )]TJ
/F4 1 Tf
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6.96 0 0 6.96 204.3 69.3198 Tm
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/F1 1 Tf
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T*
-0.0461 Tc
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18.9 73.1667 TD
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/F1 1 Tf
5.2533 0 TD
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-15.46 -1.1667 TD
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[(53,)-10( 1)6.6(78183)6.6( \()-6.7(1998)6.6(\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 374.34 682.8198 Tm
0.0054 Tc
0 Tw
(30)Tj
/F1 1 Tf
9 0 0 9 389.94 682.82 Tm
-0.0316 Tc
0.0216 Tw
[(T)41.7(i)-14.6(l)-17.9(t)-17.9(o)-5.6(n )6.7(R)33.4(C)11.1(,)-21.6( )6.7(Sa)-7.6(nd M)20.4(N)11.4(,)-14.9( M)33.7(a)-7.6(n)-6.6(a)-7.6(k M)20.4(.)-14.9( T)8.4(h)-3.3(e)-8.9( )]TJ
T*
-0.0249 Tc
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[(W)101.8(e)-2.2(s)-8.6(t)-4.6(er)-6.2(n i)-14.6(m)22.1(m)15.4(u)7.1(no)7.8(bl)-11.2(ot)-11.2( f)-8.2(o)1.1(r)-6.2( L)48.1(y)-0.2(m)15.4(e)-2.2( di)-14.6(se)-8.9(as)-8.6(e:)-8.2( )]TJ
T*
-0.0109 Tc
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[(d)18.1(e)11.8(te)11.8(r)7.8(m)36.1(in)20.8(a)13.1(t)2.8(i)6.1(o)15.1(n)20.8( )-6.7(o)15.1(f)5.8( s)5.4(e)11.8(n)20.8(s)5.4(it)9.4(iv)14.4(i)6.1(t)2.8(y)93.8(,)5.8( s)5.4(p)16.1(e)11.8(c)9.1(i)6.1(f)5.8(ic)15.8(it)9.4(y)13.8( )-6.7(a)13.1(n)20.8(d)18.1( )]TJ
T*
-0.0209 Tc
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[(interp)6.1(reti)-10.6(v)11.1(e)1.8( c)5.8(r)-2.2(i)-10.6(t)-0.6(eri)-10.6(a)3.1( w)19.1(i)-3.9(t)-7.2(h)7.4( )6.7(use )6.7(o)5.1(f)-4.2( )]TJ
T*
-0.015 Tc
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/F4 1 Tf
T*
-0.0171 Tc
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[(C)15.6(l)2.2(i)-5.8(n)10.6(. I)23.9(n)17.2(fect)-6.4(. )6.7(D)21.9(i)0.9(s)]TJ
/F1 1 Tf
5.6667 0 TD
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-5.6667 -1.1667 TD
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0 Tw
[(\()-6.7(1997\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 374.34 606.3198 Tm
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(31)Tj
/F1 1 Tf
9 0 0 9 389.94 606.32 Tm
-0.0349 Tc
0.0249 Tw
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T*
-0.0145 Tc
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[(p)12.5(e)8.2(rfo)11.5(r)4.2(m)25.8(a)9.5(n)17.2(c)5.5(e)8.2( an)17.2(d)14.5( in)17.2(te)8.2(rp)12.5(r)17.5(e)8.2(ta)9.5(tio)11.5(n)17.2( )-6.7(fr)10.8(o)11.5(m)32.5( )-6.7(t)5.8(h)13.8(e)8.2( )]TJ
T*
-0.0251 Tc
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[(s)-8.8(e)-2.4(c)-5.1(o)7.6(nd nat)-4.8(i)-14.8(on)6.6(al)-11.4( )-6.7(conf)-8.4(er)6.9(ence)-9.1( on)6.6( )-6.7(ser)-6.4(o)7.6(l)-11.4(ogi)-14.8(c)-5.1( )]TJ
T*
-0.0164 Tc
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[(d)12.6(i)-6.1(a)7.6(g)9.6(n)15.3(o)9.6(sis o)16.3(f)0.3( L)56.6(y)8.3(m)30.6(e)6.3( d)12.6(i)0.6(se)6.3(a)7.6(s)-0.1(e)6.3(.)-6.4( )]TJ
/F4 1 Tf
9.72 0 TD
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0 Tw
(MMWR)Tj
/F1 1 Tf
3.02 0 TD
-0.01 Tc
[( 4)16.7(4)23.3(, )]TJ
-12.74 -1.1667 TD
-0.0267 Tc
0.01 Tw
[(590)6.6(591 \()-13.4(1)6.6(995\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 374.34 550.8198 Tm
0.0054 Tc
0 Tw
(32)Tj
/F1 1 Tf
9 0 0 9 389.94 550.82 Tm
-0.0167 Tc
[(T)143.3(r)8.6(e)6(v)15.3(e)6(j)-3.7(o)9.3( R)61.6(T)130(, )-6.7(K)25(r)2(au)15.3(se)6( P)12.3(J)1.6(, )-6.7(S)25.6(i)-6.4(k)12(a)7.3(n)8.3(d)12.3( V)19.3(K)18.3(, )]TJ
T*
-0.0233 Tc
[(S)5.7(c)-3.3(hri)-6.3(e)-0.6(f)-13.3(e)-0.6(r M)28.7(E)7.4(,)-6.6( R)41.7(y)1.4(an R)15(,)-6.6( Lepo)9.4(re T)123.4(,)-6.6( P)59(o)2.7(r)-11.3(t)-9.6(er W)143.4(,)-6.6( )]TJ
T*
-0.0201 Tc
0.0034 Tw
[(D)26.6(e)2.6(n)11.6(n)4.9(is D)19.9(T)133.2(.)-10.1( E)43.9(v)5.2(al)-6.4(uati)-9.8(o)12.6(n)4.9( o)5.9(f)-3.4( )-6.7(tw)13.2(o)12.6(-)-6.8(test)-6.4( )]TJ
T*
-0.0167 Tc
0.0067 Tw
[(se)6(r)8.6(o)9.3(d)12.3(i)0.3(ag)9.3(n)15(o)9.3(sti)-6.4(c)10( m)30.3(e)6(th)11.6(o)9.3(d)12.3( )6.7(fo)9.3(r e)6(a)7.3(rly)8( )6.7(L)56.3(y)8(m)23.6(e)6( )]TJ
T*
-0.0176 Tc
0.0009 Tw
[(d)11.4(i)-7.3(s)5.4(e)5.1(as)5.4(e in)7.4( clin)7.4(ica)6.4(l)-3.9( p)9.4(r)1.1(a)6.4(c)2.4(ti)-7.3(ce)5.1(. )]TJ
/F4 1 Tf
9.8067 0 TD
-0.0145 Tc
-0.0022 Tw
[(J. I)26.5(n)13.2(fe)4.8(ct. D)24.5(i)3.5(s)]TJ
/F1 1 Tf
4.4067 0 TD
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(. )Tj
-14.2133 -1.1667 TD
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0.01 Tw
[(179,)-10( 93193)6.6(8 )-6.7(\()-6.7(199)6.6(9\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 374.34 484.8198 Tm
0.0054 Tc
0 Tw
(33)Tj
/F1 1 Tf
9 0 0 9 389.94 484.82 Tm
0.0032 Tc
0.0001 Tw
[(A)19.5(g)9.2(u)8.5(e)12.5(r)8.5(o)9.2(-R)28.2(o)15.9(s)-0.5(e)5.9(n)14.9(fe)5.9(ld)12.2( M)35.2(E)13.9(, N)52.9(o)22.5(w)23.2(a)7.2(k)11.9(o)22.5(w)23.2(s)-0.5(k)11.9(i)0.2( )-6.7(J)8.2(,)-6.8( )]TJ
T*
0.0024 Tc
0.0009 Tw
[(M)54.4(c)9.1(K)24.1(e)5.1(n)14.1(n)14.1(a)6.4( D)22.4(F)147.1(, C)18.4(a)6.4(rb)15.7(o)8.4(n)14.1(a)6.4(r)7.7(o)8.4( C)18.4(A)18.7(, W)109.1(o)8.4(rm)29.4(se)11.7(r )]TJ
T*
0.0028 Tc
0.0005 Tw
[(G)23.1(P)185.1(. S)18.5(e)5.5(r)8.1(o)15.5(d)11.8(i)-6.9(a)6.8(g)8.8(n)14.5(o)15.5(sis in)7.8( e)5.5(a)6.8(rly)7.5( )-6.7(L)62.5(y)7.5(m)29.8(e)5.5( )-6.7(d)11.8(i)-0.2(s)5.8(e)5.5(a)6.8(s)-0.9(e)5.5(.)-0.5( )]TJ
/F4 1 Tf
T*
0.0019 Tc
0.0081 Tw
[(J. C)21.2(l)-5.4(in)9.6(. )6.7(M)42.6(icr)9.6(ob)14.6(i)-6.8(o)7.9(l)]TJ
/F1 1 Tf
6.6 0 TD
-0.0067 Tc
0.01 Tw
[(.)-10( 31)6.6(,)-16.7( 30)6.6(90)6.6(309)6.6(5 )]TJ
-6.6 -1.1667 TD
0 Tw
[(\()-6.7(199)6.6(3\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 374.34 429.3198 Tm
0.0054 Tc
(34)Tj
/F1 1 Tf
9 0 0 9 389.94 429.32 Tm
-0.0176 Tc
0.0009 Tw
[(H)35.1(a)-0.3(rris N)25.4(.)-7.6( A)18.7(n)7.4( u)7.7(n)14.1(d)11.4(e)5.1(rstan)14.1(d)11.4(i)-7.3(n)14.1(g)8.4( o)8.4(f)-0.9( )-6.7(la)6.4(b)9.1(o)8.4(ra)6.4(to)8.4(r)-18.9(y)7.1( )]TJ
T*
-0.0159 Tc
0.0059 Tw
[(te)6.8(s)7.1(t)-2.2(in)9.1(g)10.1( )6.7(fo)10.1(r L)63.8(y)2.1(m)31.1(e)6.8( d)13.1(i)1.1(se)6.8(a)8.1(s)0.4(e)6.8(.)0.8( )]TJ
/F4 1 Tf
9.12 0 TD
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0.003 Tw
[(J. )-6.7(S)18(p)8.3(i)-8.4(r)8(o T)54.3(i)-8.4(ck D)19.3(i)-1.7(s)]TJ
/F1 1 Tf
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[(.)-16.7( 40,)-10( )-6.7(46)6.6(8469 \()-6.7(1996\))-6.7(.)]TJ
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[( et)-230(a)10(l)-1.3(.)]TJ
/F1 1 Tf
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[( C)25.6(o)8.9(m)23.2(p)16.6(ariso)8.9(n)14.6( o)15.6(f)-0.4( iv)74.9(. )]TJ
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T*
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/F4 1 Tf
T*
-0.0723 Tc
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/F1 1 Tf
3.5267 0 TD
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[( )-6.7(44)6.6(,)-16.7( 1203)6.6(1207 \()-6.7(1994\))-6.7(.)]TJ
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T*
-0.0242 Tc
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/F4 1 Tf
13.8667 0 TD
-0.0393 Tc
0 Tw
[(Cl)-26.6(i)-21.3(n)-11.6(.)-29.3( )]TJ
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0.031 Tw
[(In)-20(f)-33.4(e)-28.4(c)-29.7(t)-30.4(.)-37.7( D)-8.7(i)-29.7(s)]TJ
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3.6133 0 TD
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[(.)-10( 28,)-10( )-6.7(56)6.6(9574 \()-6.7(1999\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 56.88 481.8198 Tm
-0.0032 Tc
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0 -1.1667 TD
[(D)36.9(a)7.6(tt)3.9(w)16.9(y)8.3(le)6.3(r R)15.3(J)1.9(. )-6.7(N)59.9(e)-0.4(w)16.9( c)3.6(h)11.9(e)6.3(m)30.6(o)9.6(t)-2.7(h)11.9(e)6.3(ra)7.6(p)10.6(e)6.3(u)15.6(t)-2.7(ic)3.6( )]TJ
T*
-0.0234 Tc
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T*
-0.0172 Tc
0 Tw
[(b)16.1(o)8.8(rr)8.1(e)5.5(l)-3.5(io)8.8(sis.)-7.2( )]TJ
/F4 1 Tf
4.18 0 TD
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/F1 1 Tf
6.66 0 TD
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[(. 5)16.7(3)16.7(9)23.3(, )]TJ
-10.84 -1.1667 TD
-0.0267 Tc
0.0167 Tw
[(3)6.6(5236)6.6(1 \()-6.7(1988)6.6(\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 56.88 426.3198 Tm
-0.0032 Tc
0 Tw
(47)Tj
/F1 1 Tf
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T*
-0.0312 Tc
0.0145 Tw
[(C)11.5(a)-7.2(m)9.1(p)-4.2(od)-8.9(n)-6.2(i)-14.2(c)-11.2(o)-5.2( M)20.8(.)-21.2( P)31.1(s)-14.9(y)6.8(c)-11.2(hi)-14.2(a)-7.2(t)-17.5(r)-12.5(i)-14.2(c)-11.2( )]TJ
T*
-0.0203 Tc
0.0036 Tw
[(sym)20(p)6.7(to)5.7(m)26.7(a)-3(to)5.7(l)-6.6(o)5.7(g)5.7(y)4.4( asso)5.7(ciat)-6.6(ed)8.7( w)13(i)-3.3(t)-6.6(h)8( )]TJ
T*
-0.0238 Tc
0.0071 Tw
[(p)9.9(r)1.5(es)-7.5(u)8.2(m)16.5(pti)-13.5(v)8.2(e L)49.2(y)0.9(m)16.5(e)-1.1( d)5.2(i)-13.5(s)-7.5(e)-1.1(as)-7.5(e:)-7.1( )-6.7(cl)-10.1(i)-13.5(n)7.9(i)-6.8(c)-3.8(al)-10.1( )]TJ
T*
-0.0249 Tc
0 Tw
[(evi)-7.9(d)4.1(ence)-8.9(.)-8.2( )]TJ
/F4 1 Tf
3.6 0 TD
-0.0176 Tc
0.0009 Tw
[(J. S)20.1(p)3.7(iro)8.4(l)-4.9(. )-6.7(T)56.4(ick D)21.4(i)0.4(s)]TJ
/F1 1 Tf
6.3267 0 TD
-0.0267 Tc
0.01 Tw
[(.)-16.7( 7,)-10( )-6.7(22)6.6(25 )]TJ
-9.9267 -1.1667 TD
0 Tw
[(\()-6.7(200)6.6(0\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 56.88 360.3198 Tm
-0.0032 Tc
(48)Tj
/F1 1 Tf
9 0 0 9 72.48 360.32 Tm
0.0029 Tc
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T*
-0.0035 Tc
0.0068 Tw
[(P)18.8(h)4.8(ys)-7.2(i)-6.5(c)3.2(i)-6.5(a)-6.2(n)8.2( pr)8.5(ef)-6.8(er)8.5(en)8.2(ces )-6.7(i)-6.5(n)8.2( t)-9.8(h)4.8(e)5.8( )-6.7(d)5.5(i)-6.5(agn)8.2(o)2.5(si)-13.2(s )]TJ
T*
-0.0028 Tc
0.0061 Tw
[(an)8.9(d)6.2( treatm)24.2(en)8.9(t)-9.1( of)-6.1( L)50.2(y)8.5(m)17.5(e)-0.1( d)6.2(i)-5.8(s)-6.5(e)-0.1(ase i)-12.5(n)8.9( th)5.5(e )]TJ
T*
-0.0025 Tc
0.0058 Tw
[(U)56.8(n)9.2(i)-5.5(t)-8.8(ed)6.5( S)26.5(t)-2.2(ates)-6.2(.)-5.8( )]TJ
/F4 1 Tf
5.62 0 TD
0.0031 Tc
0 Tw
[(I)24.1(n)10.8(fe)9.1(ction)]TJ
/F1 1 Tf
3.2267 0 TD
-0.0067 Tc
0.01 Tw
[( 2)6.6(4)0(,)-10( )-6.7(1)6.6(82)6.6(186)6.6( )]TJ
-8.8467 -1.1667 TD
0 Tc
0 Tw
[(\(1)13.3(9)6.7(9)6.7(6)13.3(\).)]TJ
/TT6 1 Tf
6.96 0 0 6.96 226.98 717.3198 Tm
0.0054 Tc
(49)Tj
/F1 1 Tf
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-0.0165 Tc
-0.0002 Tw
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T*
-0.0172 Tc
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T*
-0.0115 Tc
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[(G)35.5(o)14.5(ld)17.5(s)4.8(m)35.5(it)8.8(h)16.8( )-6.7(D)35.2(P)190.8(. L)61.5(y)13.2(m)28.8(e)11.2( a)12.5(r)-6.2(t)8.8(h)16.8(r)7.2(i)5.5(ti)5.5(s)4.8( in)20.2( )-6.7(c)15.2(h)16.8(ild)17.5(r)20.5(e)4.5(n)20.2(.)5.2( )]TJ
T*
-0.0258 Tc
0.0091 Tw
[(An)5.9( or)-13.8(t)-12.1(h)2.5(op)7.9(e)-9.8(d)3.2(i)-8.8(c)-5.8( per)-7.1(s)-9.5(pect)-12.1(i)-8.8(v)-0.5(e.)-9.1( )]TJ
/F4 1 Tf
10.0133 0 TD
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0.0078 Tw
[(J. B)16.5(o)8.2(n)9.9(e)1.5( J)35.5(o)8.2(i)-6.5(n)9.9(t )]TJ
-10.0133 -1.1667 TD
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0.0301 Tw
[(Su)-24.1(r)-25.8(g)-24.8(.)-36.8( Am)]TJ
/F1 1 Tf
3.2867 0 TD
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0.01 Tw
[(.)-16.7( 69,)-10( 9699 \()-6.7(1987\))-6.7(.)]TJ
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6.96 0 0 6.96 226.98 661.8198 Tm
0.0054 Tc
0 Tw
(50)Tj
/F1 1 Tf
9 0 0 9 242.52 661.82 Tm
-0.0167 Tc
0.0067 Tw
[(W)110(e)6(i)-6.4(s)6.3(s L)16.3(M)35.3(.)-6.7( )6.7(B)28.3(a)7.3(b)10(e)6(sio)9.3(s)-0.4(is in)15( h)11.6(u)15.3(m)23.6(a)7.3(n)15(s)-0.4(: a)7.3( )]TJ
0 -1.1667 TD
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[(t)-9.3(r)9(ea)-5.7(tm)17.3(en)8.7(t)-9.3( revi)-6(e)-7(w)83.7(.)-13( )]TJ
/F4 1 Tf
6.5133 0 TD
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0 Tw
[(E)22.6(x)3.3(p)11.3(e)2.6(r)-9(t)0.6( O)26.6(p)11.3(i)-5.4(n)11(. )]TJ
-6.5133 -1.1667 TD
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[(Pha)-7.7(r)-17.4(mac)-13.7(o)-12.4(t)-14.4(h)-3.4(e)-12.4(r)]TJ
/F1 1 Tf
4.8333 0 TD
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[(.)-16.7( )6.7(3,)-10( 1)6.6(10911)6.6(15 \()-6.7(2)0(0)6.6(02\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 226.98 627.3198 Tm
0.0054 Tc
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(51)Tj
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9 0 0 9 242.52 627.32 Tm
-0.017 Tc
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0 -1.1667 TD
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0.0136 Tw
[(S)25.4(u)1.7(cces)-7.3(s)-7.3(f)-6.9(u)8.4(l)-9.9( treat)-9.9(m)23.4(en)8.1(t)-9.9( )6.7(of)-6.9( L)49.4(y)1.1(m)23.4(e)-0.9( )]TJ
T*
-0.0174 Tc
0.0007 Tw
[(e)5.3(n)7.6(c)9.3(e)-1.4(p)16.3(h)10.9(alo)8.6(p)9.6(a)6.6(t)-3.7(h)10.9(y)7.3( w)15.9(i)-0.4(th)10.9( iv)74.6(. )-6.7(ce)5.3(ftri)-7.1(a)6.6(x)14.6(o)8.6(n)14.3(e. )]TJ
/F4 1 Tf
13.34 0 TD
-0.015 Tc
0 Tw
(J. )Tj
-13.34 -1.1667 TD
-0.04 Tc
0.0233 Tw
[(In)-12.3(f)-25.7(e)-20.7(c)-22(t)-22.7(.)-30( Di)-22(s)]TJ
/F1 1 Tf
3.6133 0 TD
-0.0267 Tc
0.01 Tw
[(.)-16.7( 180,)-10( 37738)6.6(3 )-6.7(\()-6.7(199)6.6(9\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 226.98 582.3198 Tm
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(52)Tj
/F1 1 Tf
9 0 0 9 242.52 582.32 Tm
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0 -1.1667 TD
0.0029 Tc
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T*
-0.0056 Tc
0.0089 Tw
[(borrel)-11.9(i)-8.6(osi)-8.6(s)-9.3( r)-6.9(a)-1.6(n)6.1(d)3.4(om)21.4(i)-8.6(z)-1.9(ed com)21.4(p)1.4(ar)-6.9(i)-8.6(s)-9.3(on)6.1( of)-8.9( )]TJ
T*
-0.0044 Tc
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[(cef)-7.7(t)-4.1(r)-5.7(i)-7.4(ax)7.6(on)7.3(e and p)9.3(e)-1.7(ni)-7.4(ci)-14.1(ll)-10.7(i)-7.4(n)0.6(.)-7.7( )]TJ
/F4 1 Tf
10.2333 0 TD
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[(La)-6.2(nc)-12.2(e)-4.2(t)]TJ
/F1 1 Tf
2.44 0 TD
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( )Tj
-12.6733 -1.1667 TD
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0.01 Tw
[(119)6.6(11)6.6(194)6.6( \()-13.4(1)6.6(988)6.6(\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 226.98 526.8198 Tm
0.0054 Tc
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(53)Tj
/F1 1 Tf
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-0.0018 Tc
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T*
-0.0007 Tc
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[(A)22.3(C)22(. )-6.7(T)146(r)4.6(eatm)19.6(e)8.6(n)4.3(t o)5.3(f)-4( re)8.6(fracto)5.3(r)-15.4(y)4( ch)7.6(ro)12(nic)6( )]TJ
T*
-0.0004 Tc
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T*
0 Tw
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/F4 1 Tf
5.36 0 TD
0.0018 Tc
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[(A)31.1(r)-3.9(thritis R)9.1(h)10.1(eu)11.1(m)]TJ
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5.9533 0 TD
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[(.)-10( 34,)-10( )]TJ
-11.3133 -1.1667 TD
[(105)6.6(61)6.6(060)6.6( \()-13.4(1)6.6(991)6.6(\))-6.7(.)]TJ
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6.96 0 0 6.96 226.98 471.3198 Tm
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(54)Tj
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9 0 0 9 242.52 471.32 Tm
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[(P)50.8(a)5.8(via)5.8( C)24.5(S)10.8(.)-8.2( )6.7(C)37.8(u)7.1(rr)13.8(en)13.5(t a)5.8(n)13.5(d )6.7(n)13.5(o)21.1(v)13.8(e)4.5(l th)10.1(erap)15.5(i)-7.9(e)4.5(s )6.7(fo)7.8(r )]TJ
T*
-0.073 Tc
0.0563 Tw
[(Ly)-48.3(m)-32.7(e)-50.3( d)-44(i)-62.7(s)-50(e)-57(a)-49(s)-50(e)-57(.)-56.3( )]TJ
/F4 1 Tf
5.1867 0 TD
-0.0107 Tc
-0.006 Tw
[(E)22(x)16(p)10.6(e)8.6(rt)6.6( )-6.7(O)39.3(p)10.6(i)7.3(n)17(. I)30.3(n)17(v)22(e)8.6(st)6.6(i)7.3(g)11.3(. D)28.3(r)3.6(u)18.6(g)4.6(s)]TJ
/F1 1 Tf
10.0333 0 TD
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( )Tj
-15.22 -1.1667 TD
-0.0267 Tc
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[(12,)-10( 10)6.6(03101)6.6(6 \()-6.7(200)6.6(3\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 226.98 436.8198 Tm
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/F4 1 Tf
12.0333 0 TD
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[(et al)]TJ
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0 Tw
(. )Tj
-13.52 -1.1667 TD
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T*
-0.0236 Tc
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[(t)-9.9(r)8.4(ea)-6.3(tm)16.7(en)8.1(t)-9.9( of)-6.9( babes)-7.3(i)-13.3(o)9.1(s)-7.3(i)-13.3(s)-0.6(.)-13.6( )]TJ
/F4 1 Tf
8.78 0 TD
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[(N)29(.)6.7( )-6.7(E)42.7(n)17.7(g)12(l)2.7(. J)10(.)0( M)57.3(e)9.3(d)]TJ
/F1 1 Tf
5.6067 0 TD
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(. )Tj
-14.3867 -1.1667 TD
-0.0267 Tc
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[(343,)-10( 1)6.6(45414)6.6(58 )6.7(\()-13.4(2)0(0)6.6(00\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 226.98 391.8198 Tm
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0 Tw
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/F4 1 Tf
11.68 0 TD
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[(et al)]TJ
/F1 1 Tf
1.4867 0 TD
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(. )Tj
-13.1667 -1.1667 TD
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T*
-0.019 Tc
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/F4 1 Tf
9.7733 0 TD
-0.01 Tc
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[(N)29(.)6.7( E)42.7(n)17.7(g)12(l)2.7(. )6.7(J)10(.)6.7( M)57.3(e)9.3(d)]TJ
/F1 1 Tf
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(. )Tj
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[(312,)-10( 8)6.6(69874)6.6( \()-6.7(1985)6.6(\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 226.98 346.8198 Tm
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(57)Tj
/F1 1 Tf
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T*
-0.014 Tc
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[(S)35(t)-0.3(u)18(d)15(y)90.7(.)-4( )6.7(A)22.3( d)15(o)12(u)18(b)12.7(le)8.7(-)6(b)12.7(lin)17.7(d)15( p)19.7(l)-0.3(ac)12.7(e)8.7(b)12.7(o)12(-)6(c)6(o)12(n)17.7(t)-0.3(r)11.3(o)12(lle)8.7(d)15( )]TJ
T*
-0.0148 Tc
-0.0019 Tw
[(ran)16.9(d)14.2(o)11.2(m)32.2(iz)15.5(e)7.9(d)7.5( c)5.2(l)-1.1(in)16.9(ic)11.9(al tria)9.2(l )-6.7(e)7.9(v)17.2(a)9.2(l)-1.1(u)10.5(a)9.2(tin)16.9(g)11.2( )-6.7(t)5.5(h)13.5(e)7.9( )]TJ
T*
-0.0178 Tc
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T*
-0.0248 Tc
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T*
-0.0267 Tc
0 Tw
(2000.)Tj
/TT6 1 Tf
6.96 0 0 6.96 397.02 717.3198 Tm
0.0054 Tc
(58)Tj
/F1 1 Tf
9 0 0 9 412.62 717.32 Tm
-0.0226 Tc
0.0059 Tw
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T*
-0.014 Tc
0.004 Tw
[(S)35(t)6.3(u)11.3(d)15(y)90.7(.)2.7( A)22.3( d)15(o)18.7(u)11.3(b)12.7(le)8.7(-)6(b)12.7(lin)11(d)15( )6.7(p)13(l)-0.3(a)10(c)6(e)8.7(b)12.7(o)12(-)6(c)6(o)12(n)17.7(t)-0.3(r)11.3(o)12(lle)8.7(d)15( )]TJ
T*
-0.0108 Tc
0.0008 Tw
[(r)7.9(a)13.2(n)14.2(d)18.2(o)15.2(m)36.2(iz)19.5(e)11.9(d)18.2( c)15.9(l)2.9(in)20.9(ic)15.9(a)13.2(l)2.9( t)9.5(r)7.9(ia)13.2(l )6.7(e)11.9(v)14.5(a)13.2(l)2.9(u)14.5(a)13.2(t)9.5(i)-0.5(n)20.9(g)15.2( t)9.5(h)17.5(e)11.9( )]TJ
T*
-0.0167 Tc
0 Tw
[(e)6(ffi)-6.4(c)10(a)0.6(c)10(y)8( )-6.7(o)9.3(f)0( o)9.3(r)2(a)7.3(l)-3( )-6.7(a)7.3(m)30.3(o)16(x)8.6(i)-6.4(c)3.3(illin)8.3( fo)9.3(r se)6(ro)16(p)10.3(o)9.3(sitiv)15.3(e)-0.7( )]TJ
T*
-0.0277 Tc
0.0177 Tw
[(and )6.7(s)-11.4(e)-5(rone)-5(g)-8.4(a)-3.7(t)-7.4(i)-17.4(ve)-5( L)52(y)-9.7(m)19.3(e)-5( di)-10.7(s)-11.4(e)-5(as)-11.4(e)-5(.)-11( E)9.6(n)4(rol)-14(l)-14(m)12.6(e)-5(n)4(t)-7.4( )]TJ
T*
-0.0256 Tc
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[(s)-9.3(i)-8.6(nce 20)7.7(01.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 397.02 651.3198 Tm
0.0054 Tc
0 Tw
(59)Tj
/F1 1 Tf
9 0 0 9 412.62 651.32 Tm
-0.0164 Tc
0.0064 Tw
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T*
-0.0198 Tc
0.0031 Tw
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T*
-0.0242 Tc
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[(t)-10.5(o)15.1(w)15.8(a)-0.2(r)7.8(d)-1.9( )6.7(L)48.8(y)0.5(m)22.8(e)-1.5( di)-7.2(s)-7.9(e)-1.5(as)-7.9(e i)-7.2(n)7.5( an)7.5( en)7.5(de)-8.2(m)22.8(i)-7.2(c ar)7.8(ea)-6.9(.)-7.5( )]TJ
/F4 1 Tf
T*
-0.0327 Tc
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[(Cl)-13.4(i)-21.4(n)-5(.)-16( P)39.3(e)-13.4(d)-5.4(i)-14.7(a)-8.7(t)-15.4(r)]TJ
/F1 1 Tf
4.52 0 TD
-0.0267 Tc
0.0167 Tw
[(.)-16.7( )6.7(33,)-10( 1)6.6(30134)6.6( \()-6.7(1994)6.6(\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 397.02 606.3198 Tm
0.0054 Tc
0 Tw
(60)Tj
/F1 1 Tf
9 0 0 9 412.62 606.32 Tm
-0.0174 Tc
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0 -1.1667 TD
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T*
-0.0258 Tc
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[(di)-15.5(sea)-8.5(s)-2.8(e i)-8.8(n)-0.8( )6.7(a po)6.9(pul)-12.1(a)-1.8(t)-5.5(i)-15.5(on-)-5.8(b)0.9(as)-9.5(ed cohor)-13.8(t)-12.1(.)-9.1( )]TJ
/F4 1 Tf
13.7133 0 TD
-0.0393 Tc
0 Tw
[(Cl)-26.6(i)-21.3(n)-11.6(.)-29.3( )]TJ
-13.7133 -1.1667 TD
-0.04 Tc
0.03 Tw
[(In)-12.3(f)-25.7(e)-20.7(c)-22(t)-22.7(.)-23.3( Di)-22(s)]TJ
/F1 1 Tf
3.6133 0 TD
-0.0267 Tc
0.0167 Tw
[(.)-10( 29,)-10( )6.7(6946)6.6(95 \()-6.7(199)6.6(9\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 397.02 561.3198 Tm
0.0054 Tc
0 Tw
(61)Tj
/F1 1 Tf
9 0 0 9 412.62 561.32 Tm
-0.1333 Tc
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[(Wa)-109.3(h)-105(l)-119.6(b)-106.6(e)-110.6(r)-114.6(g)-107.3( P)62.4(,)-116.6( G)-73(r)-114.6(a)-109.3(n)-101.6(l)-119.6(u)-108(n)-101.6(d)-104.3( )-6.7(H)-87.3(,)-116.6( )-6.7(N)-63.6(y)-108.6(m)-86.3(a)-109.3(n)-108.3( D)-93.3(,)-116.6( )]TJ
0 -1.1667 TD
-0.0144 Tc
0.0044 Tw
[(P)54.6(a)9.6(n)17.3(e)1.6(liu)17.6(s)1.9( J, )6.7(S)21.3(e)8.3(p)12.6(p)12.6(a)9.6(la)9.6( I)10.3(.)-4.4( )6.7(T)145.6(r)10.9(e)8.3(a)9.6(tm)32.6(e)8.3(n)10.6(t)5.9( o)18.3(f)-4.4( )6.7(la)9.6(te)8.3( )]TJ
T*
-0.0228 Tc
0.0128 Tw
[(L)50.2(y)1.9(m)24.2(e)-0.1( borr)9.2(el)-9.1(i)-12.5(o)3.2(si)-12.5(s.)-12.8( )]TJ
/F4 1 Tf
6.4267 0 TD
-0.0185 Tc
0.0018 Tw
[(J.)-8.5( I)22.5(n)9.2(f)-4.2(e)0.8(ct)]TJ
/F1 1 Tf
2.7267 0 TD
-0.0267 Tc
0.01 Tw
[(.)-16.7( 29,)-10( )-6.7(2)6.6(55261)6.6( )]TJ
-9.1533 -1.1667 TD
0 Tw
[(\()-6.7(1994\))-6.7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 397.02 516.3198 Tm
0.0054 Tc
(62)Tj
/F1 1 Tf
9 0 0 9 412.62 516.32 Tm
-0.0163 Tc
-0.0004 Tw
[(D)37(o)9.7(n)15.4(t)-2.6(a)7.7( S)12.7(T)130.4(. )-6.7(T)137(e)6.4(tra)7.7(c)3.7(y)21.7(c)3.7(lin)8.7(e)6.4( th)12(e)6.4(r)2.4(a)7.7(p)10.7(y)8.4( fo)9.7(r )-6.7(c)10.4(h)12(r)9(o)9.7(n)8.7(i)0.7(c)3.7( )]TJ
T*
-0.073 Tc
0.063 Tw
[(Ly)-48.3(m)-26(e)-50.3( d)-44(i)-56(s)-56.7(e)-50.3(a)-49(s)-56.7(e)-50.3(.)-63( )]TJ
/F4 1 Tf
5.18 0 TD
-0.0171 Tc
0.0071 Tw
[(C)15.6(l)-4.4(in)10.6(. I)23.9(n)10.6(fec)7.6(t)-6.4(. D)28.6(i)-5.8(s)]TJ
/F1 1 Tf
5.6667 0 TD
-0.0156 Tc
0.0056 Tw
[(. 2)17.7(5)11.1(\(S)40.1(u)9.7(p)11.4(p)11.4(l)-1.9(. )]TJ
-10.8467 -1.1667 TD
-0.027 Tc
0.0103 Tw
[(1\))-7(,)-17( S52S56 \()-7(1997\))-7(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 397.02 481.8198 Tm
0.0054 Tc
0 Tw
(63)Tj
/F1 1 Tf
9 0 0 9 412.62 481.82 Tm
-0.01 Tc
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[(R)35(e)12.7(i)7(d)19( )-6.7(M)42(C)26(,)6.7( S)12.3(c)16.7(h)18.3(o)16(e)12.7(n)15( R)68.3(T)143.3(, E)47.3(v)22(a)14(n)15(s)13( )-6.7(J)8.3(,)6.7( )-6.7(R)41.7(o)16(s)6.3(e)12.7(n)21.7(b)16.7(e)12.7(r)8.7(g)16( )]TJ
T*
-0.0238 Tc
0.0138 Tw
[(JC)18.9(,)-13.8( )6.7(H)35.5(o)2.2(r)-18.5(w)9.5(i)-6.8(t)-10.1(z R)14.5(I)-5.8(.)-7.1( T)16.2(h)4.5(e consequ)8.2(e)-1.1(nce)-7.8(s)-0.8( of)-7.1( )]TJ
T*
-0.0231 Tc
0.0131 Tw
[(o)16.2(v)8.9(er)8.9(d)5.9(i)-12.8(agn)8.6(o)2.9(s)-6.8(i)-6.1(s)-6.8( an)8.6(d)5.9( o)22.9(v)2.2(er)-11.1(treat)-9.4(m)23.9(ent o)9.6(f)-13.1( )6.7(L)49.9(y)1.6(m)23.9(e)-0.4( )]TJ
T*
-0.0242 Tc
-0.0191 Tw
[(di)-13.9(sea)-6.9(s)-1.2(e:)-14.2( an)7.5( obs)-7.9(e)-1.5(r)-25.5(v)7.8(at)-10.5(i)-7.2(o)1.8(n)7.5(a)-6.9(l s)-7.9(t)-10.5(u)7.8(d)4.8(y)80.5(.)-14.2( )]TJ
/F4 1 Tf
11.36 0 TD
-0.0277 Tc
-0.0156 Tw
[(A)21.6(nn.)-11( I)13.3(n)0(t)-10.4(e)-8.4(r)-20(n)0(.)-11( )]TJ
-11.36 -1.1667 TD
-0.0673 Tc
0 Tw
[(Me)-48(d)]TJ
/F1 1 Tf
1.5867 0 TD
-0.0267 Tc
0.0167 Tw
[(.)-16.7( )6.7(128,)-10( 3)6.6(54362)6.6( \()-6.7(1998)6.6(\))-13.4(.)]TJ
/TT6 1 Tf
6.96 0 0 6.96 397.02 426.3198 Tm
0.0054 Tc
0 Tw
(64)Tj
/F1 1 Tf
9 0 0 9 412.62 426.32 Tm
-0.0263 Tc
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[(S)22.7(t)-6(ee)-10.3(r)5.7(e)-3.6( A)23.4(C)9.7(,)-9.6( T)113.7(a)-2.3(yl)-12.6(or)-7.6( )6.7(E,)-9.6( M)45.7(c)0.4(H)46.4(u)-1(gh )6.7(G)14(L)6.7(,)-16.3( )]TJ
0 -1.1667 TD
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