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Marianne S. Muhlebach, Bryan T. Zorn, Charles R. Esther, Joseph E. Hatch, Conor P. Murray, Lidija Turkovic, Sarath C. Ranganathan, Richard C. Boucher, Stephen M. Stick, Matthew C. Wolfgang
Initial acquisition and succession of the cystic fibrosis lung microbiome is associated with disease progression in infants and preschool children
www.plospathogens.org
www.plospathogens.org
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0 g
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1.1111 0 Td
(several)Tj
2.9367 0 Td
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(24)Tj
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(countries)Tj
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(visits)Tj
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([)Tj
0.83 0.64 0.02 0 k
(25)Tj
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(].)Tj
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1.1112 0 Td
(the)Tj
1.4683 0 Td
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3.0217 0 Td
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(infants)Tj
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(and)Tj
1.7291 0 Td
(young)Tj
2.7212 0 Td
(children)Tj
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(is)Tj
0.8447 0 Td
(not)Tj
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(recommended)Tj
6.0377 0 Td
([)Tj
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(26)Tj
0 g
(];)Tj
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3.8381 0 Td
(a)Tj
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(recent)Tj
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(trial)Tj
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(the)Tj
1.4683 0 Td
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(and)Tj
1.7292 0 Td
(Canada)Tj
3.2598 0 Td
(showed)Tj
-32.9837 -1.3039 Td
(that)Tj
1.7744 0 Td
(children)Tj
3.5603 0 Td
(less)Tj
1.6101 0 Td
(than)Tj
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(6)Tj
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(an)Tj
1.2019 0 Td
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(two)Tj
1.7121 0 Td
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1.3833 0 Td
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4.0025 0 Td
(respiratory)Tj
4.5921 0 Td
(symptoms)Tj
4.3597 0 Td
([)Tj
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(27)Tj
0 g
(].)Tj
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3.1181 0 Td
(inflammation)Tj
5.6976 0 Td
(in)Tj
1.0374 0 Td
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1.4117 0 Td
(can)Tj
1.6214 0 Td
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(detected)Tj
3.566 0 Td
(within)Tj
2.8176 0 Td
(the)Tj
1.4684 0 Td
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1.8028 0 Td
(few)Tj
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(months)Tj
3.2825 0 Td
(to)Tj
1.0262 0 Td
(years)Tj
2.2677 0 Td
(of)Tj
1.0148 0 Td
(life,)Tj
-34.0949 -1.3039 Td
(despite)Tj
3.0387 0 Td
(the)Tj
1.4683 0 Td
(absence)Tj
3.3392 0 Td
(of)Tj
1.0148 0 Td
(clinically)Tj
3.7814 0 Td
(diagnosed)Tj
4.2803 0 Td
(infection)Tj
3.7927 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(29)Tj
0 g
(].)Tj
1.7348 0 Td
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5.6182 0 Td
(increased)Tj
3.9969 0 Td
(inflam-)Tj
-33.8001 -1.2983 Td
(mation)Tj
3.0954 0 Td
(and)Tj
1.7291 0 Td
(structural)Tj
4.0762 0 Td
(lung)Tj
2.0126 0 Td
(disease)Tj
3.016 0 Td
(occurs)Tj
2.8346 0 Td
(in)Tj
1.0318 0 Td
(children)Tj
3.5603 0 Td
(with)Tj
1.9956 0 Td
(CF)Tj
1.4117 0 Td
(despite)Tj
3.0387 0 Td
(the)Tj
1.4683 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(prophylactic)Tj
-31.8158 -1.2982 Td
(antibiotics)Tj
4.3993 0 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(33)Tj
0 g
(].)Tj
3.5433 0 Td
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1.7801 0 Td
(underlying)Tj
4.6035 0 Td
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2.3867 0 Td
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1.0148 0 Td
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5.6976 0 Td
(in)Tj
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(CF)Tj
1.4116 0 Td
(remains)Tj
3.4413 0 Td
(contro-)Tj
-34.333 -1.2983 Td
(versial)Tj
2.7779 0 Td
(and)Tj
1.7291 0 Td
(may)Tj
1.9276 0 Td
(reflect)Tj
2.6929 0 Td
(undiagnosed)Tj
5.3574 0 Td
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3.7927 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7405 0 Td
(29)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3946 0 Td
(34)Tj
0 g
(],)Tj
1.7348 0 Td
(altered)Tj
2.948 0 Td
(immune)Tj
3.6227 0 Td
(function)Tj
3.6283 0 Td
([)Tj
0.83 0.64 0.02 0 k
(35)Tj
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(,)Tj
0.83 0.64 0.02 0 k
1.7405 0 Td
(36)Tj
0 g
(],)Tj
-35.087 -1.3039 Td
(or)Tj
1.0941 0 Td
(a)Tj
0.6576 0 Td
(response)Tj
3.7304 0 Td
(to)Tj
1.0262 0 Td
(mucus)Tj
2.8799 0 Td
(obstruction)Tj
4.8359 0 Td
([)Tj
0.83 0.64 0.02 0 k
(37)Tj
0 g
(].)Tj
-13.0279 -1.2983 Td
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1.3379 0 Td
(better)Tj
2.5455 0 Td
(understand)Tj
4.7849 0 Td
(the)Tj
1.474 0 Td
(microenvironment)Tj
7.8179 0 Td
(in)Tj
1.0374 0 Td
(very)Tj
1.9219 0 Td
(young,)Tj
2.948 0 Td
(clinically)Tj
3.7758 0 Td
(stable,)Tj
2.7155 0 Td
(CF)Tj
1.4117 0 Td
(subjects,)Tj
-32.9667 -1.2983 Td
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1.3266 0 Td
(applied)Tj
3.1521 0 Td
(sensitive)Tj
3.6283 0 Td
(molecular)Tj
4.2179 0 Td
(detection)Tj
3.9345 0 Td
(methods)Tj
3.685 0 Td
(to)Tj
1.0261 0 Td
(characterize)Tj
5.0287 0 Td
(the)Tj
1.474 0 Td
(microbiome)Tj
5.1306 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(lower)Tj
-35.087 -1.3039 Td
(airways)Tj
3.2144 0 Td
(using)Tj
2.3811 0 Td
(cross-sectional)Tj
6.0945 0 Td
(BAL)Tj
2.0069 0 Td
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3.3732 0 Td
(obtained)Tj
3.7247 0 Td
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(infants)Tj
2.9593 0 Td
(and)Tj
1.7178 0 Td
(preschoolers)Tj
5.2497 0 Td
(who)Tj
1.9276 0 Td
(under-)Tj
-34.8432 -1.2982 Td
(went)Tj
2.1713 0 Td
(bronchoscopy)Tj
5.879 0 Td
(as)Tj
1.0148 0 Td
(part)Tj
1.8368 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(Australian)Tj
4.388 0 Td
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4.8472 0 Td
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2.2961 0 Td
(Surveillance)Tj
5.0626 0 Td
(Team)Tj
2.5115 0 Td
(for)Tj
1.3833 0 Td
(Cystic)Tj
-33.8794 -1.2983 Td
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3.3902 0 Td
(\(AREST)Tj
3.5206 0 Td
(CF\))Tj
1.7518 0 Td
(study.)Tj
2.6135 0 Td
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1.7801 0 Td
(early)Tj
2.1544 0 Td
(CF)Tj
1.4059 0 Td
(lower)Tj
2.4548 0 Td
(airways)Tj
3.2258 0 Td
(microbiome)Tj
5.1307 0 Td
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1.7008 0 Td
(analyzed)Tj
3.702 0 Td
(in)Tj
1.0375 0 Td
(relation)Tj
-33.8681 -1.3039 Td
(to)Tj
1.0261 0 Td
(antibiotic)Tj
4.0365 0 Td
(prophylaxis,)Tj
5.1137 0 Td
(BAL)Tj
2.0239 0 Td
(markers)Tj
3.4979 0 Td
(of)Tj
1.0148 0 Td
(inflammation)Tj
5.6976 0 Td
(and)Tj
1.7291 0 Td
(structural)Tj
4.0762 0 Td
(lung)Tj
2.0126 0 Td
(disease,)Tj
3.2428 0 Td
(measured)Tj
-33.4712 -1.2983 Td
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1.1792 0 Td
(chest)Tj
2.2563 0 Td
(computed)Tj
4.2633 0 Td
(tomography)Tj
5.125 0 Td
(\(CT\),)Tj
2.3981 0 Td
(to)Tj
1.0261 0 Td
(elucidate)Tj
3.7928 0 Td
(the)Tj
1.4683 0 Td
(evolution)Tj
3.9968 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(lower)Tj
2.4492 0 Td
(airways)Tj
3.2258 0 Td
(micro-)Tj
-33.6697 -1.2983 Td
(biome)Tj
2.7439 0 Td
(with)Tj
1.9955 0 Td
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3.0388 0 Td
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1.0261 0 Td
(disease)Tj
3.016 0 Td
(progression.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 339.0236 cm
BT
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1 TL
-0.0033 Tc
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0 -1.5023 Td
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2.7543 0 Td
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4.7622 0 Td
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1.8662 0 Td
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Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 303.9874 cm
BT
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1 TL
-0.004 Tc
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1.3379 0 Td
(examine)Tj
3.6 0 Td
(the)Tj
1.4683 0 Td
(early)Tj
2.1487 0 Td
(lower)Tj
2.4547 0 Td
(airways)Tj
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1.6384 0 Td
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1.3266 0 Td
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2.3925 0 Td
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6.4686 0 Td
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2.211 0 Td
(46)Tj
1.1679 0 Td
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1.4116 0 Td
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3.6056 0 Td
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1.0374 0 Td
(age)Tj
1.5421 0 Td
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-33.63 -1.2983 Td
(approximately)Tj
5.9753 0 Td
(3.5)Tj
1.3947 0 Td
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3.2825 0 Td
(to)Tj
1.0261 0 Td
(five)Tj
1.6554 0 Td
(years)Tj
2.2621 0 Td
(with)Tj
1.9956 0 Td
(a)Tj
0.6576 0 Td
(median)Tj
3.2371 0 Td
(age)Tj
1.5421 0 Td
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1.0148 0 Td
(1.95)Tj
1.8765 0 Td
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2.262 0 Td
(and)Tj
1.7291 0 Td
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(interquartile)Tj
-31.1128 -1.3039 Td
(range)Tj
2.4604 0 Td
(\(IQR\))Tj
2.6079 0 Td
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1.0148 0 Td
(1.134.06)Tj
4.0421 0 Td
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1.4003 0 Td
(subjects)Tj
3.3789 0 Td
(were)Tj
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(diagnosed)Tj
4.2803 0 Td
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2.0013 0 Td
(CF)Tj
1.4116 0 Td
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3.4412 0 Td
(newborn)Tj
3.8098 0 Td
(screen-)Tj
-34.4577 -1.2983 Td
(ing.)Tj
1.7234 0 Td
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3.4072 0 Td
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(intubated)Tj
4.0535 0 Td
(during)Tj
2.9254 0 Td
(CT)Tj
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(and)Tj
1.7291 0 Td
(bronchoscopy)Tj
5.8734 0 Td
(to)Tj
1.0261 0 Td
(control)Tj
3.1181 0 Td
(breathing)Tj
4.0592 0 Td
(and)Tj
1.7291 0 Td
(avoid)Tj
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(aspi-)Tj
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(ration.)Tj
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1.576 0 Td
(Australian)Tj
4.3937 0 Td
(clinical)Tj
3.0728 0 Td
(care)Tj
1.8765 0 Td
(standards,)Tj
4.3086 0 Td
(all)Tj
1.1452 0 Td
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3.5546 0 Td
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1.9956 0 Td
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1.4116 0 Td
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1.4514 0 Td
(prescribed)Tj
4.4107 0 Td
(amoxicillin-)Tj
-32.0653 -1.3039 Td
(clavulanic)Tj
4.2235 0 Td
(acid)Tj
1.8709 0 Td
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(antibiotic)Tj
4.0422 0 Td
(prophylaxis)Tj
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2.9253 0 Td
(the)Tj
1.474 0 Td
(first)Tj
1.8028 0 Td
(two)Tj
1.7122 0 Td
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1.6724 0 Td
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2.7496 0 Td
(samples)Tj
-31.6514 -1.2983 Td
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(obtained)Tj
3.736 0 Td
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3.3789 0 Td
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1.7064 0 Td
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2.2677 0 Td
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4.2406 0 Td
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3.3789 0 Td
(showed)Tj
3.2541 0 Td
(clinically)Tj
-33.1991 -1.2983 Td
(defined)Tj
3.2258 0 Td
(infection)Tj
3.7927 0 Td
(\(i.e.,)Tj
1.9219 0 Td
(BAL)Tj
2.0239 0 Td
(cultures)Tj
3.4015 0 Td
(showed)Tj
3.2485 0 Td
(a)Tj
0.6577 0 Td
(density)Tj
3.101 0 Td
(of)Tj
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0 Tc
1.0148 0 Td
()Tj
/F8 1 Tf
-0.004 Tc
(10)Tj
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 441.0708 204.4346 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(5)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 446.8535 200.0125 cm
BT
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1 TL
-0.004 Tc
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(colony)Tj
2.9083 0 Td
(forming)Tj
3.4866 0 Td
(units/ml)Tj
3.617 0 Td
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(recognized)Tj
4.5864 0 Td
(pathogen\).)Tj
4.5071 0 Td
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5.6409 0 Td
(subjects)Tj
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(homozygous)Tj
5.3063 0 Td
(and)Tj
1.7348 0 Td
(22)Tj
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(subjects)Tj
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(zygous)Tj
2.948 0 Td
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1.3833 0 Td
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1.474 0 Td
(F508del)Tj
3.3676 0 Td
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2.6475 0 Td
(mutation.)Tj
4.1442 0 Td
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1.9389 0 Td
(subject)Tj
3.0161 0 Td
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1.7121 0 Td
(two)Tj
1.7064 0 Td
(other)Tj
2.3527 0 Td
(CFTR)Tj
2.6418 0 Td
(mutations.)Tj
4.5071 0 Td
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1.3946 0 Td
(sub-)Tj
-35.2343 -1.2983 Td
(jects)Tj
1.9843 0 Td
(were)Tj
2.1203 0 Td
(seen)Tj
1.9785 0 Td
(routinely)Tj
3.8608 0 Td
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1.1849 0 Td
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0.6519 0 Td
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1.4117 0 Td
(nutritionist)Tj
4.7792 0 Td
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1.7291 0 Td
(recommended)Tj
6.0376 0 Td
(a)Tj
0.652 0 Td
(high)Tj
2.0069 0 Td
(fat)Tj
1.2416 0 Td
(diet)Tj
1.7404 0 Td
(with)Tj
1.9956 0 Td
(enzyme)Tj
-33.3748 -1.2983 Td
(supplementation.)Tj
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