%PDF-1.3 % 2 0 obj <> endobj 15 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 25 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 10 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 21 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 30 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 29 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 31 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 17 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 22 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 18 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 26 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 36 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 35 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 5 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 3 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 16 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 6 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 28 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 34 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 7 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 8 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 14 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 27 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 19 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 33 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 20 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 1 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 9 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 23 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 12 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 24 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 54/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5TR Ɩf !\!Y\ !p)P endstream endobj 11 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 37 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 13 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 32 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 53/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0q-Br44C@B 9 s (P endstream endobj 4 0 obj <>>>/Subtype/Form/BBox[0 0 612 792]/Matrix [1 0 0 1 0 0]/Length 55/FormType 1/Filter/FlateDecode>>stream xs w3T04PI2P0T5T0P02S04S  @$P5 )1 endstream endobj 38 0 obj <>stream 3B2 Total Publishing System 7.51o/W 2010-10-28T12:39:10-07:00 2010-10-05T00:13:42+05:30 application/pdf untitled Acrobat Distiller 8.1.0 (Windows) uuid:9b593326-9a59-473a-b26b-d8d8c324d3e5 uuid:11ecb035-588e-4f6a-b13a-a1573749bd91 endstream endobj 39 0 obj <>stream x+| endstream endobj 40 0 obj <>stream xS**T0T0BiU!D. _e1 endstream endobj 41 0 obj <>stream x+| endstream endobj 42 0 obj <>stream xS**T0T0BiUD* : endstream endobj 43 0 obj <>stream x+| endstream endobj 44 0 obj <>stream xS**T0T0Bih] D. pa endstream endobj 45 0 obj <>stream x+| endstream endobj 46 0 obj <>stream xS**T0T0Bil])D. qgj endstream endobj 47 0 obj <>stream x+| endstream endobj 48 0 obj <>stream xS**T0T0Bid]%D. rs endstream endobj 49 0 obj <>stream x+| endstream endobj 50 0 obj <>stream xS**T0T0Bid]D. qdj endstream endobj 51 0 obj <>stream x+| endstream endobj 52 0 obj <>stream xS**T0T0Bil]D. pa endstream endobj 53 0 obj <>stream x+| endstream endobj 54 0 obj <>stream xS**T0T0Bih]D. r^j endstream endobj 55 0 obj <>stream x+| endstream endobj 56 0 obj <>stream xS**T0T0BiUD* 8 endstream endobj 57 0 obj <>stream x+| endstream endobj 58 0 obj <>stream xS**T0T0BiU)D* 9V endstream endobj 59 0 obj <>stream x+| endstream endobj 60 0 obj <>stream xS**T0T0Bid]1D. pa endstream endobj 61 0 obj <>stream x+| endstream endobj 62 0 obj <>stream xS**T0T0Bih] 9D. qaj endstream endobj 63 0 obj <>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/XObject<>/Font<>>>/Thumb 75 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 76 0 obj <>/ProcSet[/PDF/Text/ImageB]/XObject<>/Font<>>> endobj 65 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.9663 0 0 8.9663 62.022 567.1558 Tm 0 0 0 rg 0 Tc 0 Tw [(consider)-323.7(how)-323.9(well)-324.7(current)-328.3(measures)-324(of)-325.7(MCC/CC)-324.9(serve)-325(as)-323.3(a)]TJ 0 -1.2266 TD [(biomarker)-336(for)-332.7(airways)-333.1(disease)-337.3(and)-334.7(its)-334.1(treatment.)]TJ 1.1128 -1.2203 TD [(The)-512.1(MCC)-511.3(apparatus)-517.2(is)-510.7(a)-511.7(well-coordinated)-520.6(system)-510.8(con-)]TJ -1.1128 -1.2203 TD [(sisting)-315.1(of)-319.4(airway)-312.8(secretory)-319.3(cells)-317.4(and)-315.7(submucosal)-315.9(glands)-318.7(that)]TJ 0 -1.2266 TD [(produce)-368.8(a)-366.2(sol)-368(and)-372.6(gel)-368.3(\(or)-364.3(mucus\))-374.4(uid)-365(layer)-368.5(on)-366.6(the)-370.5(airway)]TJ 0 -1.2203 TD [(surface,)-403.8(and)-404.2(ciliated)-398.5(cells)-405.9(that)-402.2(propel)-401.6(the)-402.1(mucus)-405.5(out)-402.9(of)-401.6(the)]TJ T* [(lung)-411(toward)-412.7(the)-414.7(mouth)]TJ 6.7246 0 0 5.9768 157.833 505.3605 Tm (\(1\))Tj 8.9663 0 0 8.9663 169.2283 501.392 Tm [(\(Fig.)-414.1(1\).)-407.6(In)-416.5(health,)-411.5(this)-413.4(system)-409.6(is)]TJ -11.9566 -1.2203 TD [(effective)-358.7(at)-347.7(clearing)-355.7(mucus)-355(and)-347.3(associated)-358.4(bacteria)-348.8(and)-353.7(tox-)]TJ 0 -1.2266 TD [(ins)-286.4(from)-286(our)-283(lungs.)-288.8(However,)-286.7(in)-285.1(a)-284(variety)-287.5(of)-281.4(airway)-287.5(diseases)]TJ 0 -1.2203 TD [([e.g.,)-399.2(cystic)-394(brosis)-396.4(\(CF\),)-400.5(chronic)-398(bronchitis)-402.2(\(CB\),)-392.7(and)-397.9(asth-)]TJ T* [(ma])-358(this)-356.5(apparatus)-359.2(becomes)-352.9(dysfunctional,)-364.5(which)-359(may)-349.3(lead)]TJ 0 -1.2266 TD [(to)-433.2(further)-430.6(exacerbation)-439.2(of)-433.2(airway)-426.6(inammation)-437.9(and)-429.5(an)-426.5(in-)]TJ 0 -1.2203 TD [(creasing)-410.4(reliance)-414.4(on)-404.5(CC)-411.3(to)-407.9(remove)-412.6(secretions)-410.9(from)-412.5(the)-408.4(air-)]TJ T* [(ways.)-736.9(Eventually,)-743.6(CC)-740.1(may)-741.3(also)-734.3(become)-743.6(compromised,)]TJ 0 -1.2266 TD [(leaving)-457.6(patients)-465.2(with)-457.9(little)-454(defense)-463.1(to)-458.5(the)-459(accumulation)-460.5(of)]TJ 0 -1.2203 TD [(bacteria)-506.8(on)-499.3(airway)-502.5(surfaces.)-506.3(Consequently,)-508.5(there)-510.2(are)-499.6(con-)]TJ T* [(tinuing)-399.5(efforts)-398.1(to)-395.3(develop)-403.2(therapeutic)-401.9(aerosols)-397.5(that)-395.9(may)-393.5(be)]TJ T* [(delivered)-652.8(to)-648.2(the)-648.7(airways)-642.9(to)-648.2(enhance)-653.7(both)-643.3(MCC/CC)-653.7(in)]TJ 0 -1.2266 TD [(compromised)-338.6(patients.)]TJ 1.1128 -1.2203 TD [(MCC/CC)-318.6(rates)-324.4(can)-318.3(be)-320.5(measured)-319.4(in)-316.7(humans)-322.7(by)-318.7(assuming)]TJ -1.1128 -1.2203 TD [(that)-566.6(a)-562.3(nonpermeating,)-567(inhaled)-560(marker)-565.5(depositing)-567.5(on)-562.6(the)]TJ 0 -1.2266 TD [(airway)-293.8(surface)-299.7(moves)-299.5(out)-295.5(of)-294.1(the)-300.9(lung)-290.9(at)-297.2(the)-294.6(same)-301.8(rate)-291.4(as)-298(the)]TJ 0 -1.2203 TD [(airway)-243.3(secretions)-246.5(in)-247.2(which)-245.2(it)-244.3(is)-238.8(immersed.)-246.7(The)-246.6(most)-242.4(common)]TJ T* [(technique)-414(is)-409.5(to)-407.9(use)-413.6(inhaled,)-411.2(radiolabeled)-409(\(Tc99m\))-410.8(particles,)]TJ 0 -1.2266 TD [(aqueous)-491.2(or)-490.3(dry,)-491.6(that)-490.7(upon)-489.4(deposition)-496.3(in)-487.5(the)-490.6(lung)-493.2(can)-489(be)]TJ 0 -1.2203 TD [(followed)-542.4(by)-533.6(a)-543.3(gamma)-536(camera)-533.9(to)-540.7(determine)-539.5(their)-545.4(rate)-538(of)]TJ T* [(egress)-627.2(from)-627.5(the)-629.7(lung)-626(\(Fig.)-629.1(2\).)-622.5(After)-628.9(inhalation)-630(of)-629.2(these)]TJ 0 -1.2266 TD [(markers,)-468.6(retention)-469.8(of)-464.8(activity)-467.2(in)-462.2(the)-465.3(lung)-467.9(\(as)-462.9(a)-467.4(percent)-466.6(or)]TJ 0 -1.2203 TD [(fraction)-421.1(of)-420.6(initial)-415.8(deposition\))-427.2(is)-415.8(monitored)-418.8(as)-418.1(a)-416.8(function)-425.6(of)]TJ T* [(time)-279.7(over)-276(a)-271.4(period)-276.8(of)-281.4(up)-274.6(to)-275.1(24)-169.7(h)-275.3(t)0(o)-275.1(determine)-280.2(clearance)-276.9(rates.)]TJ /F4 1 Tf 27.9978 53.1377 TD [(State)-339.8(of)-330.2(the)-334.7(Art)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(Many)-328.6(recent)-332.4(studies)-333.4(of)-325.7(MCC)-327.9(rely)-331(upon)-325(the)-332.6(nebulized)-328.4(de-)]TJ -1.1128 -1.2203 TD [(livery)-366.9(of)-357.3(Technetium)-365.9(sulfur)-362.8(or)-357.6(albumin)-361.1(colloid)-366.2(aerosols.)]TJ 6.7246 0 0 5.9768 537.7321 702.3683 Tm (\(26\))Tj 8.9663 0 0 8.9663 313.0582 687.4014 Tm [(These)-538.6(radiopharmaceuticals)-544.5(are)-537.6(easy)-529.9(to)-540.7(label)-535.7(and)-537(handle)]TJ T* [(\(labeling)-730.9(efciencies)-734.3(of)]TJ /F10 1 Tf 11.6152 0 TD (>)Tj /F5 1 Tf .7714 0 TD [(98%\),)-731.2(having)-729.5(been)-728.4(developed)]TJ -12.3866 -1.2203 TD [(principally)-251.8(for)-244.2(liver)-242.3(scanning)-245.8(by)-242.8(i.v.)-244.1(injection)-248.8([e.g.,)-241.2(CIS-Sulfur)]TJ 0 -1.2266 TD [(Colloid)-620(Kits)-621.4(\(CIS-US,)-617.8(Inc.,)-617.6(Bedford,)-622.8(MA\)].)-617.4(The)-619.6(colloidal)]TJ 0 -1.2203 TD [(particles)-452.2(are)-449(submicronic)-447.1(in)-449.5(size)-446.9(and)-448.5(dispersed)-444(in)-449.5(isotonic)]TJ T* [(saline)-396.9(for)-389.6(nebulization,)-395(forming)-392.2(larger)-388.1(polydisperse)-396.1(aerosol)]TJ T* [(particles)-300.5(\(36)]TJ /F11 1 Tf 5.9752 0 TD (m)Tj /F5 1 Tf .5501 0 TD [(m)-294.7(MMAD\))-298(that)-294.7(are)-297.3(inhaled.)-297.4(There)-297.7(is)-295.7(minimal)]TJ -6.5252 -1.2266 TD [(observed)-531.2(Tc99m)-523.7(penetration)-533.9(into)-528.6(the)-528.6(bloodstream,)]TJ 6.7246 0 0 5.9768 522.8786 614.7211 Tm (\(7\))Tj 8.9663 0 0 8.9663 535.2943 610.6959 Tm (sug-)Tj -24.7858 -1.2203 TD [(gesting)-365.2(that)-364.2(the)-364.2(colloidal)-362.9(particles)-363.7(stay)-359.8(dispersed)-368.1(in)-361(the)-357.8(air-)]TJ T* [(way)-486.1(surface)-489.4(uid)-485.1(for)-490.8(measures)-482.1(of)-490.1(MCC)-486(over)-484.7(the)-490.6(time)-482(of)]TJ 0 -1.2266 TD [(observation)-278.8(\(024)-169.2(h\).)-272.3(For)-273.5(many)-276.8(years)-271.4(a)-271.4(few)-280.2(laboratories)-272(have)]TJ 0 -1.2203 TD [(used)-435.5(solid)-425.1(Tc99m,)-431.8(polystyrene)-433.2(or)-427.1(iron)-427.7(oxide)-428.7(particles)-433.2(gen-)]TJ T* [(erated)-718(by)-717(spinning)-719.8(disks)]TJ 6.7246 0 0 5.9768 421.6818 559.899 Tm (\(811\))Tj 8.9663 0 0 8.9663 445.9464 555.9305 Tm [(to)-711.4(measure)-721.1(MCC.)-716.5(These)]TJ -14.8209 -1.2266 TD [(methods)-248.7(allow)-251.2(for)-244.2(strict)-252.4(control)-246.9(of)-249.8(monodisperse)-245.1(particle)-248.6(size)]TJ 0 -1.2203 TD [(and)-480.1(tight)-480.2(binding)-474.6(of)-477.5(the)-478(label)-472.5(to)-477.5(the)-478(particles.)-480.4(Unlike)-477.7(the)]TJ T* [(colloidal)-641.1(particles,)-644.8(these)-637.3(particles)-641.9(are)-638.7(delivered)-640.2(as)-639.4(large)]TJ 0 -1.2266 TD (\(36)Tj /F11 1 Tf 1.9917 0 TD (m)Tj /F5 1 Tf .5501 0 TD (m\))Tj /F6 1 Tf 1.4479 0 TD (dry)Tj /F5 1 Tf 1.6376 0 TD [(particles)-256.2(during)-250.3(inhalation.)-259.9(These)-247.8(methods)-255(have)]TJ -5.6274 -1.2203 TD [(been)-488.1(particularly)-492.1(useful)-488.5(over)-484.7(the)-490.6(years)-486.4(for)-484.5(assessing)-490.2(lung)]TJ T* [(clearance)-314.8(for)-313.8(a)-309.3(range)-317.7(of)-306.7(particle)-318.1(sizes)-309.1(and)-315.7(for)-307.4(understanding)]TJ T* [(regional)-340.2(deposition)-338.2(in)-329.4(the)-338.9(lung.)]TJ 6.7246 0 0 5.9768 438.6896 483.1936 Tm (\(12,13\))Tj 8.9663 0 0 8.9663 323.0361 468.2267 Tm [(Although)-248.4(most)-248.7(centers)-245.2(use)-249.2(Tc99m,)-242.1(longer-lived)-247.2(isotopes)-247.4(of)]TJ -1.1128 -1.2203 TD (I)Tj 6.7246 0 0 5.9768 316.0629 461.2534 Tm (123)Tj 8.9663 0 0 8.9663 328.3086 457.2849 Tm [(and)-239.8(In)]TJ 6.7246 0 0 5.9768 353.5936 461.2534 Tm (111)Tj 8.9663 0 0 8.9663 365.8393 457.2849 Tm [(have)-243.8(also)-241.1(been)-241.5(used.)-236.1(Regardless)-245.4(of)-237.2(isotope)-246.1(used)]TJ -5.8866 -1.2203 TD [(to)-502.8(tag)-497.6(the)-496.9(particles,)-499.4(it)-497.2(is)-498(important)-496.6(to)-502.8(check)-493.1(for)-503.5(potential)]TJ 0 -1.2266 TD [(leaching)-269.9(of)-262.5(the)-263(label)-257.5(from)-267.1(the)-263(particle.)-264.1(For)-260.8(example,)-259.8(Venticoll)]TJ 0 -1.2203 TD [(\(colloidal)-546.7(albumin\))-538.6(leakage)-536(in)-538(vitro)-545.7(is)]TJ /F10 1 Tf 18.2479 0 TD (<)Tj /F5 1 Tf .7714 0 TD [(0.1%/24)-163.7(h,)-543.7(while)]TJ /F6 1 Tf -19.0193 -1.2203 TD [(in)-265.5(vivo)]TJ /F5 1 Tf 2.7947 0 TD [(:)-262.2(7)0(%)-260.4(was)-255.4(recovered)-266.1(in)-259.8(urine)-261.8(within)-268.9(24)-163.4(h.)]TJ 6.7246 0 0 5.9768 494.8723 417.4298 Tm (\(14\))Tj 8.9663 0 0 8.9663 508.3085 413.4613 Tm [(Most)-262.6(likely)]TJ -21.7761 -1.2266 TD (the)Tj /F6 1 Tf 1.8589 0 TD [(in)-499.5(vivo)]TJ /F5 1 Tf 3.5219 0 TD [(leaching)-497.5(derives)-495.9(from)-494.7(the)-496.9(gastrointestinal)-502.4(\(GI\))]TJ -5.3808 -1.2203 TD [(tract)-303.9(because)-302.9(earlier)-305(studies)-301.7(using)-304.9(Tc-human)-298.8(serum)-304.3(albumin)]TJ T* [(have)-256.5(shown)-252.8(3%)-247.7(blood)-256.8(uptake)-253.6(from)-248.1(the)-256.7(lungs)-248(but)-252.8(15%)-253.6(uptake)]TJ T* [(from)-336.6(radiocolloid)-337.8(via)-332.6(the)-338.9(GI)-329.7(tract.)]TJ 1.1128 -1.2266 TD [(Controlled)-412.3(inhalation)-415.1(of)-407.9(the)-414.7(radiolabeled)-409(aerosols)-416.5(is)-409.5(rec-)]TJ -1.1128 -1.2203 TD [(ognized)-452.8(as)-443.4(an)-445.5(important)-446(factor)-445.8(for)-446.5(targeting)-453.1(the)-446.4(bronchial)]TJ T* [(airways)-516.5(and)-511.7(improving)-511.2(intrasubject)-518.8(repeatability)-514.4(of)-515.4(MCC)]TJ 0 -1.2266 TD [(measures.)-611.5(The)-600.6(breathing)-607.8(patterns)-607.8(employed)-606.8(by)-603.2(different)]TJ 0 -1.2203 TD [(laboratories)-518.6(are)-505.9(quite)-515.5(varied,)-509.8(but)-512.1(each)-514.2(strives)-507.5(to)-515.4(produce)]TJ T* [(sufcient)-442.7(airway)-439.3(versus)-441.6(alveolar)-440.2(deposition)-439.4(to)-439.5(provide)-435.6(for)]TJ 0 -1.2266 TD [(measure)-291.1(of)-294.1(MCC)-290(over)-288.6(a)-290.4(24-h)-287.4(period.)-292.4(In)-290(each)-286.6(case)-290.9(the)-288.3(subject)]TJ 0 -1.2203 TD [(is)-460.1(trained)-459.4(to)-458.5(perform)-465(the)-459(breathing)-462.3(maneuvers)-459.6(usually)-457.6(by)]TJ T* [(following)-456(a)-454.8(visual)-452.6(and/or)-455(audio)-452.8(signal.)-448.6(Some)-454(laboratories)]TJ 0 -1.2267 TD [(have)-370.3(subjects)-360.8(breathe)-368.7(the)-364.2(radioaerosol)-367.8(continuously)-369(as)-361.2(sub-)]TJ 0 -1.2203 TD [(jects)-454.8(control)-449.2(their)-450.6(tidal)-452.7(ow)-450(and)-448.5(rate)-449.5(of)-452.2(breathing,)-452.6(for)-446.5(ex-)]TJ ET q 238.992 0 0 110.211 61.965 622.034 cm /Im1 Do Q BT /F7 1 Tf 8.9663 0 0 8.9663 61.8519 605.3101 Tm [(FIG.)-469.6(1.)]TJ /F5 1 Tf 4.2237 0 TD [(Airway)-466.4(epithelial)-473.9(components)-473.8(of)-464.8(the)-465.3(mucociliary)]TJ -4.2237 -1.1128 TD [(clearance)-333.8(system.)]TJ ET q 1 i 142.526 234.028 m 471.685 234.028 l 471.685 84.019 l 142.526 84.019 l W n q 329.399 0 0 150.009 142.526 84.019 cm /Im2 Do Q Q BT /F7 1 Tf 8.9663 0 0 8.9663 62.022 67.2378 Tm [(FIG.)-298.9(2.)]TJ /F5 1 Tf 4.0593 0 TD [(Left:)-297.6(initial)-295.7(gamma)-295.8(camera)-300(deposition)-300.2(scan.)-297.3(Right:)-303.5(20-min)-294.8(postdeposition)-306.2(scan)-294.3(illustrating)-304(clearance)-302.2(of)-294.1(particles)-300.4(up)]TJ -4.0593 -1.1128 TD [(the)-338.9(trachea.)]TJ /F4 1 Tf 0 77.2217 TD (262)Tj 46.3849 0 TD [(BENNETT)-338(ET)-338.7(AL.)]TJ ET endstream endobj 67 0 obj <>stream AdobedC        s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?Nlٳf͛6y͚9!uL_[$w>~6vxSikO4ڕMiDjjGκ?8$?/;GHާ=1iZ~g|M]b/0 pkw̾T޻-Ky:K( 'PujVhy_i;X)O%/c_2yj[v!!BMqf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lq&?n{kzH& 8zzw-.yf =0ު İ{W&-gWau={X"tg13J ?-ܦ?$~CQߛ[5^$8WOȏZV[o͗ ,38c1Ppgo<4."Ӧi#ZJ8'Kߔy~+=zn+]h%͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lϼ"O<&QʗJ78ӓ-&f=X\oNNgY7@_HnVKFDf(z˜qb.r8ՔnYEw?1_ MڄpC`xa|:-J wn}dG $f͛6lٳf͛6lEu`>I-PUU$Mi aڜTJ Iy ¥5@4$zL!mRd"r#٭7뉟̟&Б@T8ۯ(Cn=H&+qo NVt6mU@`⼔TcFK"e%9U$̚0-8<>2dW ɥi(*|y:צ&/o&)% UHy 4OQzr6&BÃ4fD #}'Q[~x61Qg,x>?;+!9qp}B.v6F_Q> /Uş'7n;ն2Z@(Y7 8d !íb4tƧ甜90^ݞ9; [&jI5G. .fx@})y)|5PN3W~#bl&P[:wVߝ]Z6V%r^BDMR=EX>[Xhޖ@-:T4s*7wġ@NE\$+Q?1`:G 2W4c|ClkۥfpCȦ Os+Jn";bYCjC~.o]5CwCݏ=j1~uiSʀ2"ɩ[-Rrb@8Ӗ,:󿕮߄: m~ШߧL6@ L#8O#u/:^7^[O/#YX?TEGaI4ʽb9_`?1?0esʾb9?;?='V?H_I 5n1S|_{_:^Kޕ ɩ;i>?lձ4z裳津>#ƃ86]啥̷=*F/ݲͳy(f݋NӴꞰٰ֮5;e+_ՊN6?-ƴwGN8HҘ:V2̅˫zR4>rqDk8ӊ&i} XE&)q嘯 ӧ)RR(HbwwRWWrC[Ӎب[z q3?: SlޙdXRdvgBE,UlI6;AUb1k9SEt,ŸN\r2hmo:&GiP?kA/#ґ„BBSK0n&tvrbv^Ah=: 7[';ZS q^tck|U53AnBX(cz.߽냡OH^3Cy08;L10+EBhrnumí]i%Up}2XIAϠ8~oi7&k6Rd zr`?dNF>,⻊&.<֚EXb3U'}3^d(q"*(;6lٳf͛6lٳf͛#ve4i>1M?,ڞyj(wIuy,sHbCmۏ u^ 5i%FSsߗj bMKF0a (q)/9 Sḛ,-fI=2ޫ@~zb8XVAeb^jA\xGjSlqIQoVI RF$T}c |&?d95RAb!چf$m㑠?P|,V)bbfG f_Hbi"eP Vi%1J)H*k0l\G~k2V/ĄՁ&µijXiRWT5 4(FFYZ TiDU?;e-ԱسǺ'ճՊI\#qڲY6ԑ҅m(;MIJ>7ũC6@g?;Зfic¨6sBYFa!WRH) L JYG'$xSomJTp;L{oWzOi~*-zpdZ-=3p_ӐG3Uvo}[f/?#”fz yu3Fa+ߍ0KGynH#q +7#O侄oEqAz…8;{`H?%R]T*̦jn@Gզ*[xR7&C *eӑ6tOkuBzxP Q֣| 2*[\]A~@?=0TЬ;odT*:\*.#Pg2"[sN.̑炯'Y?0?4KZ޲3`Vq6ߔLd?)&wIzP:&Cnw'הe0ФF@kQ˞˅"7@}Z;cPrʾT:|G~K#J ahu$+nqI|冒o>)7eoL =wpv<:mIs;+Tor#kk[S]tbʉ$VV?{~HDCK7?زU_쓋ZxԞ0yMze}2~kGK7H"Hd1Ȇ9~~UR'MFg [:"ܶ^uśQL+|}6@ծ2VSds*?*5--hWZ/-5Za`ex*^鷨 ep ~Dkt%16ެ|&=uMM%^ٸ^,)qTV /o1'ꬶ]%X^m?/dㅭ??t Y1τ}Iǿ埙^>WoFdc ppWv0wRHF^{#DQȒS-.B"X#hHzLASI'rQ,7ɏ|[I58YޜjCd}CG{!5"I"*@ {ⶺw+kuA,q)"jىMp]ȱZ+rJdž@縕!1Id`wf4cdIqZnGnd;Vc!73JI"ܛň O?t:`_S_Gd&A)cӎX4$yL{[d(Qz?zz=:嗂;x}(tg!yEuSƿ`vk~Unn'i>HjS#z}1qs c0ʾo]V=+^tMVi}d}Hmݔj0]ů4済4sG+ F|&uZ:tYU#sRޟ<7Y5k1*J5=մ (>;nd༫!$WI"^鸢//?{s=XB"NG($݉cU֕6%΍mn /jb^Rԯ/,g[DWIGu8ʓ7ZUQ`To ˽b/:au1{bT ^?^cZʑ۳nk{aiuyNsÒȔ={?(wud9 SZdͯ!wak*Xi=?Cu{3j62I<\I!:ӢE)ŌI!Vi5f )GU(Λ@M*ޚ\vJ[zq5ͳ&ޅQ}NNwEu`>g>ܪ+s~uDg,luYo پl_/.WOݕݾ`{9"֟b[*m`+K`4`}.k[AR@وys ̷u*iPW o#o+QjG̚kwyiG&e;jYՙDOu4s84$ti᷀KHaT\/A- *^[[nMv"NKˀv}_ˉuGTmR;Ԍ1m E vu>[|]kTЄCV[ɲ&8eO(Ei'l(󯝼yCz~EYZevz DgT}=v/ |=sG=dFx^EC/1~^y>htHv\\hX P@?Nsi|mm5@jqw +ʣ~l H~Xk:q{"S`ʥraXYzm1ZFňDTrm$+-'^Ѽcs ^C>%:%ޗ2dB*=0S[ vn+R pVgcg^\D7%:ҧx?=54+|t\xc4CǮRżbu"2Y8iE?^]9Q ۦ; pbiHVz ݉A`p^,t3=qntX1ۑnY랾b)UU޳5Kja[Gxg1kKzEZN'\ Mpcr`I -l,ố)Pӑ m> >v,OJ׬5+?ԇŶ2lZ}ЙZ8A _PP&?F<OWfg2ҟRh!dG;Xe.n?uvҬe@tĝlů>TErR7uorGxP zd_zp`)K폕`gZE"()cљPUx@NΛiw]igIz|? jv'ƣ%ƙ4 ]@j(د?ĺ@Y@Q^$k[yjuMׅ aJ\3Q ؏yg@ NH@ڣ+ɯ,\HC8N&6۾z֟@go+>+z4wT؉D;#cKEI,]E2 !oܶC iS;[ i Yvr}s8Z=ִt[yi䄢l^)cvu\OIF rŐ{w{]8zҍAߙu˷i%T%SS\3GBH/xuu} C*W+hm kYЎ`S:75*w16Cx?ﵠ}UH2lFMK*@In|vmi#XHk=y6u{Ŧ\IyaVWs55a<E=k #b$RNkA t v̷"K%44O7]pA @MonV%"}5e=?VU,YѢ$4Օ7'yN{Ѕ7+)#e?f́+?<<6e45E>lo$NkSTU  wUbX.Zhhw1X<VU$}Ŵ5dk(^M+^47З*12|EF=S]fU~B:}[ ܎Ţ\ڥ.5RkӭGOsjW1,sE뗾]FtzWɎ&wJ -hONSn4M;eZ~kOv޾=Wk56ifz֟38+M'c".fpn3mas+{- {ݡƥڂu$xgnߘk2-b"duM*?K5k~Tv\w6szF5hGx2CkrCK*~Cq[ŸLƂt_(\]\\{!_VD[If͛6l#{?KExbA5Vڛxu0Zej"7O㓋kk;YN²1=1psNlRI\Kgj+uuGyroaN=3}Ņy8E{Dw"~w4j)4ԯ {צb o·/ֽ~nGJtOFkNѮ)Y$1_PPՄx{l)ݾy"彑."?#SJCihNPȐthh)1~;ާޭJ7AֵeFUO >ѫB!lXZڰ3%Qٰ̰pO˾kПK$.ڹڪyس޳߰f#<:iZ=&q QBD1EUfo9GMii7 $k,S 䕥9q+VsEq,U(Q"R%H}&{e|RF/dI嵅j^5ֲ}c jp ZF}pXm$q.^M'E;/^ XSW<[i\JHe*:1RAփ#=>)ҧ?Y@#QCtR tݽvn.C7ټ9eSOf5XtYo&,k=kVbIJ6lٳf͛6E?2Z6v.eZzĨXрl=m/uQeiەq?̑$RzctBYv{ ZrIr%DkϬ}4cLP4T%TtÏ1Y\\Av2 K̻fAJ~o,iHu9;s~u?o+OP?kxp8vW_?_튟[zeڧ_ڦ ޟn~ӗC:>P5پ_>?k̟X][KHp8zF1 dֵm>9#Ӽ{[[XYQOZW}չd͞wҴ4$mbkʤn]`{d~cy'5G$zRg~pOg{v0_%@=G0?6jKm1n(X)p* UoB;`aN-JS:}5FV`wt2R q^m63CGC13y'4f͛6lٳf͛ _3-)dmJH9+,ju72ۺƔdGIWtmB])0.żLґ؊eِǨE4d= V4H̿W,KjW`{ca/^[gaĊ?x;ih\pVsxpȆI~L!R:]0QWGV֢4TV>QEIyKq\#H3_4fd$ Wchr`*Iҡ59n~LB{=N[sTc.@  (w JF^4q-e2}3oZP{emOaS3Wz^,; |S!3TuENJ֡T*D\ŖM%ҋ1"tumdLyOLp@I>Yy\z=Jnխ|zt JWJ~Ts Ko2(tTF>s2x:՗G*!0>u4+I `)*]fsf͛6lٳf͛6C?4R?<-Cՠ|Wo uYir?}(UVQY4@=M$5K[y?zPQ\w04xPP MiZ| d"܀=~vK"YJ6OH6X2gO͐;v=D/$Wm*Jʻp( }HSq͏kצy8VYm*\AF)BP  oy6|.KX-iXd: ϧʍly?E%ҚհǙ&(M'$#hr1)則}?Ƴ\^8~)?n^cbET4`d~ |":ڜ:x-?/]Ҟ}ͻmQۦr1/6*Uj<ݿ..c4Eѵ&7SrQւ_z`:vt"֫Z~e!7=J[6lٳf͛6lٰ_`4me^JFƇ}g5) u#j pjv^Y46ws+:5Cᜌi G7چ//+NܿۮJ^F$_\<)/lz,S;Sl?dExUe<ǧM $@˦|E"P'&j1!*1+*i(@[ڿ<7`媉{xB ߷\.t-g[h>qB&GbxǥGߙ?1_K{w;9>!PRfO\_٦&kضoK9St~zQ=9ŽiZ'ӿZ(5ʭ[Sn?Oտ%`\yFVia wp>.ttfCOY V#A2NP^a=CXqQpA%qszTcG{i~apÍVE&1\iCQ̑C -  xוk^)zۦ-/@A* (;ˏ#:Nwkw}n 'jxl=#(?/?+jfM6VޤRNgsЌ#oT"fERʢ)m4kice#-aR]$ռw]u$M7GV'V;ScˣiZ=ƹJcӢ<"-iOHǎr1~jWM4 SifuďS!ȭf <{ۯߟZQSӷx`o,NpR>*ɧ8<ӧGiܔ+<@&'[| ]:^!v&h+Xihq >) s>؋Ϸ7Nҟڙ4/F͛6ٳ͛6?4ֶٱ`;S5?k.z 1Fȁ=Su \E-<+V]3E&ٞ纪,K 3K N؈{`GWv0hHwC-(J۩0j\LQ 8!~<r-_ϚE.P_Z7Zג?h<=>:iɧH *9ӏpg':jO ]nmM{?KhR(  }Y$ާEĻ_Ui=>կ~ŵ~7M*<vQڧj}ؓ[{V,/بcM{Wӭ= K )o5)ZP7ږhT( pC |oƃ@`2#+-[w_zZwV%(Ot8gm +qQEJUxK.,rT~\֥lH@x*Z7+nO 8siVZMe9h"X7PtQL*Zu4 пO1(4z %~VW,^naQxj?x^"|Y3q>G`I5=zs%qo[dT&\]ȧ#4 `&,ɉ.MY'ܟ~Y[x> o>=;/6ڳͣG.ٛ3;Vr?yRóeҮղ$:󠧶.7ծw <[twUmk{ղ.ԟ (8~;+;N_V,dk^SC11[($տ6^٥ /߃S=]5n}Puۗуc7_RҐj*\N;:So8uIFIIXGgC%N6[4GIb=FߗQ֟W;1dҲк=8!ŃG|}p=w@uO3}h&dڃ=?gλ򧈯Lѩ>JP+R8Vg:ǐ|,-J?krre6lٳf͛6lٲ wu"GZRz ]ikmڟOڴM*LertQv4,L6UnN\Ң*45I'ڋ7\z`@ߙZT[oOk:XAa(v_JV1 4?Ia}䚱PPԍ}KK 6S@pG5%?8&?:~k)quC1#̯|7Ӽp>Gqiym#4S)q *emZۈG~n]oH󦇧JM 6N LM@<ӪkzVZ!2AΏn"+"vkp2PѼ9?$Z +(yJJJLљ+8?E4# Zr?e*kZѷ%yYAG,EhӮZ'˫A>M 'ՔIPL6e4f9C\?_Z?3m!ЕZ"V0[#|C]}O1FL{lYO'?mڼҢl/妺a*+0"9N3H;sLBO&0յejֽw=9_RAԧjZ>gyX ˏPN=):o].pmV䧮JtMfR*M=@ƻ@=oFޡ~^ú}FAá#co_So2z}ƼG=|#`z!( ǼLj$` 0:UU}BFu;2y+$`1T9 8(m`ЖG{bj[ΫRMqo(inKx@Ӡ1`'?!hE}@t$C6 VCZ9_/.pg?_ZqOjvo)hZez0%,?p~~lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6W8}^>B_7+ ݺ3-c0>w>)*їٳ*0o<*dImq qSo2cMiR̖\Ьo6lٳcHя͛6lٳf͛6lٳf͛6lٰ^o|۽Ycf٘Q14 獮-?C%ɔͨXհԺϳ2P<6#-SĦ$N 6y{od fH% b۶<4ȱB#Uܝ;>hZ򾥯[`̖! zᕏۍTh!hRy0Z"\څ 5Q3tWuRTnXT9/iqZӗ:ŗ6{7mi&O]Hj23$|[jNks?&lٳf͛6lljVv>T&縂) fE .9ƥͥ:sW rӳ<sL]>󱰰YD᳢Hҹٳ͛6ٳ͛6ٳ͛6ٳ͛6;%n6n-(xֱ*{8OOny6}]7lj45.V̿)$:ijݹʳ'<*V?ǣ?lFr}?_×3\_Կ(t8-W6%90,+›xd~=le\jzr'+E_M3Y+ZkP ٮknT|AY-W~a[cn$>o=?㱷5^ܰ/ʸN䳧>?8­x¶=2.eӤwȾ4+?1󴳿ߵ=t/QB|qĺ/ŧ>IuNbW8tV {8SV1鮷qGeAe?-rhc`J;G;txFY}*3}E$~˨a"ٳf͛6lٳf͛6lٳf͛6lٰ=ơio=䟙PGdk*OJ+GPIOh:ZIt±]{)8pf;I3#4%ȑӗ6L]C'F-֣zvZѦf34 2RPJz>!yyּҜӴYYJZeIi%thƴE"[so,)%L,n$RQYoh`;z*Q c-:aUZGQvp!h8}ޘ,6$1/َ5 F0xU YR#I،SD OH.d-b1kTxS$xgq%J!+v^v \j+oۉRk 8׾ڷbmD'cjt%֟ӆvt,[[CգER.Mӭdy-maI?xT-P+3f͛6lٳg(ںӤ)zkoh \nZNj/^@`GnRyٛ)*K?lzyz BFg֥[{DQ~^~4d=OoZCpk2FjJf͛6lٳf͛6lٳf͛6l؅H"1Vv4̵̽KPk= =(NLq]C]N}IΌ< O(kCcHt;׬BDS HB}zv)9Elj, +n*zU󮙯DOzwlٳf͔̪ 1I^giRG%+ioY׼{+ByGFUk0%^/98v,k )]XP{ؽzf;r}{KtI)"WVNv\y |U ?ѯ,voO|f͛6lٳf$ƼѨM3i7 1\RBCpR S$6Ҷ+]$AAZ'#я6Wz~ՠytR+F,p[ʠ"AXlٳf͛6lٳf͛6lٳf͛6r7kzƭW !8I+ֽB(kbٶXu*P`kD)NcеfyҭIG<,9MzʋˍY>Imyz}i?FTWV8Z;4iqFOz}8ﭴۡ%@ *mr=kEv f͛6A45l:iESjrA)ilQ[U6xh^4xS^bX2%Tm1]DA!FT'r{`Rݭn$>F22+J !Z]/$aXԄS67N0%H|Cq!~olٳffURBܓ!etk}5Eظ?SV5.FkHi_m˦z!TYT򵸤LnosW(_H.DWs$ArG a?eu5Rd9 Uٜ'&S iJ_r̪^B:>*gF|辜9N ٳf͛6lٳf͛6lٳf͛5}'^&vp1iup'}YwQ_COVIlᅯ[FH*ҕ qp f.}}EE-д$IDM4{sk`H4r KT2"}8ž[[H-B^ dzqٜ)ucNx/ d@u Bhqìmp2Z?M3~OD^؛lٳfiNQE&(vМ經’4&pVH"Esڴi[DZyƤ/hh "bos&k6#d(8X\/5 v;'Ƹ;IwV6/Wr'Lѱ&w riE@4t4 x8EUc%˿u.u1lt($ pު%f͛9YBI[SMS'[2Kp}8qQS#^ z6vI:Ių0bnz4V֫Ist"ȖY/kD~p~+ݜj2YZGTDksH1[WFb6Mxh}Ĕz2+S/0~9C>&lٳf͛6lٳf͛6lٳf#nY“gxHc%KFO`Ƭ'ZmiQ]{ -1o1.m VuKd*qe;ѶZhY59ۻjkx #4끵+/N;{XZq<"V !AA΋5yipT%L|Zq*C.DxՉ'LTEh@ȱԝPQCÌٳf͈_X_ZkrHe]Or4~\jd55ݏQwA;֩yE["JRY2wF&#~7Wc $?YZnsN."r 4B[{29h$<.RcP|0,O"FܣV!k" F!G @lMK0s9Xﵕkܟ"*(UUxe͛6l^iMF;Ց&)ǥT`ҞC[9Ru⧋ó;K'I^ B>2߲ mJXLGO廙vd@Ld\8c "m%͔޷bfIa$ž86.tfXDhf_r?:td!c; aW :APGϋqrv۸8|ER}{Y})( ZԊӾthf-$L#-~mtٳf͛6lٳf͛6lٳf̀uW{;u=YRoQtVPU88= FyG /qO*Ga+eV#X(yIgcM YߩpP4m . Sŭ4GUz5hHHc4n<{m"}C?Lf͛6lوctKI-sJ^h dR{MbM0Cm[km]?cqjTur*~(k5Ѣ`W2S(?vJt-PDޕc3͛6lٳg>L Zi@r&?hg:]*6rC'PЊxmkZݕZO,d+o /NoJadF]]MvXX'eyH26|q!Ռ֭g̶Rr1ob}ArXAխC$q))2Jه6,Y}B_,PF.f͛6lٳf͛6l endstream endobj 68 0 obj <>stream AdobedC       9 s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?lٳf͛6lYyf͛6lٳf͛6lٳf͛6lٳf͞']hsjʼ|^lٳf͛6V^l {f˩'|<3ǰڸkjR6lٳee͛6lٳf͛6lٳf͛6lٳf͛|ٲm6lَlYyfdX49ߵo^ ?>yf͛6ʲ۲;.+wf*#/"oH)#0'cS|k1jWVlٳf͛6{#pP w*0I9t͛6lٲFn҃ u꣈>s:c~JH`|1PI!'$4Ñ;1{Q \$o((v+L@[nQA 1+L;t͕/6lٳf͛6ljWj'3JAmm{G#֜xwQ2j)#n@r$*5eb)"gLANî_ikZs + x1TIco.%ܻS+6lٳf͘? ڷr?.Lٳf͛6l̹Q8ZBG|s^ŧBN.;Zn撱\2FYygYV-$V0j· ]1#c, (Sl|U^i/>? NGvE1cs W~6lٳf͛6lٳf͛6lٱH׶[3TW>fj!()㎈Y_҃:w껍#O/A^uqQͥ"HjmlbUW3|  N.-Ϥ_1ApUH:v3"DLs=P͛6lٳg? ڷr?.Lٻeejcm !N8 "bASƎgk}LzV t Y!ᶂH⌯b0UEjW e.?Ğr'aA,*_|BZ׮6und6pК *F[GNܬٳf͛6lٳf͕(#\i)Lĕ\ooLKy,B I%Yv "(]~#_g{i kw+2vGeXov2CW }Lz?ֿj%T{v7ejS.hإI;'nC]$ 8.AȎꪴޘ#3jcgHΑ[΅9`G,Ȇ$#Otl%/Rm6Y=?!?V 8yV>v \闫k|->1۶1؜J(6lٳg? ڷr?.A6V^l5MW>&1zXu=pbbhy?%yNo0Ɩ)$̟XhQ# Fɮ-x{w=)X/JO bkO_*9*0esK4>wTQG$Jz O?/4IѲԲ2۳oɱЭYA%>^Υ.wV.KW#wkK2"򫚷ӆޥ[T؝ȥs%ZBCJdqC]ʾ?Ec? b,+6lٳg? ڷr?.Lٲb+^1ʻ ^\T(kP  żHPAuv͝).+zwbQ53>à9I 6jL"eq0v (N[b!HQx2lXiUԣ>{`6RݎvSŁ9RwO{Ff85^%SvWMUOo/'56bWFnev Oq;(Ӡ9mfiB#w~ @ZL͛6lٳf͛6lnvB-2KEgqh.n#i‚Ρ5 dP~\/6lٳ UXʍsrօ~Or 1^폞aXSiw1rF);íê_}xE>X>g@~XP FVUvIo,DrqC1Y4I&2=J도̡~l@<1Ģ^2isHX}0L9 eŕ ިi=AS$jqA0XʡLٳf͛6lٳf͘cɩ 2ʓ(0_BVVG+AO*lk l-|iBlu5Bl .vzuvfu0'+Gl>5oFFdCY^V?W &5כ i.4( X){m2E,vՍK5INEnEAWZ„S2Re= z1=|ߗc=A:-s4FMWu5{<̿/anܱ1-QS1 . YȏfYUCq br'ALfV^lY@5k;'@ˁ/+/6l|_@ˉ{J"XTDרO,W%wTTd &'iIu.Gk;xdC:e&x} )R>0ռks.ՍQ㑋/@צhҠ@G9F_;ayq6 X49X-xፔ5[5LnXx^S_ `/Lލ`  4r!!.ZPo9@SX(kC; mrhNVlٲf͛6lٱG~xpBZL`4ؚi(i(KN+(%ym{}/)^ #)**w=NyOyZ Χ CʿEVNųgO7Q$x~3)$[d*+J2՞q%XE0+p9NYQLѱ-yI58 UJrn۶fj'әiVXkN\= ])Lc'M[!lj^{y[U& ڹ=y̞Sj$k/# }VY-DRTN( `b8ysz4ILƔ͛6lٳfƝr"⮭^DvR0B*H tyv!@x~xK4<:r$X9&:baOGƱJYn`|3t+3`i_h\GsxH޲sv&zֵydc:T\ 1u _=©/pU>Ǎg?u'Sp$A\h&hH{gҴ*cy (jTu!|Ӵ!,M;tQ8$:Np4LbRGL%;WP>qT]W 96l@5k;'@ˁ/6lٳb1x?h{x弪;x9zPxcݮ*X>?gAycټ=_ 5ȍK?GY ،?:mG5lznK39o#ŎT;+-$"ƛ^6T`-_ g,<ݍݬPUTPg-5hIzS$1W+LW綣.A<Ā!5ƥI>T H?˚)$*ׯbOlMPaf6lٳf͛6W\ޞ8/ <fgVz`kY aᵝuWE1DM__\&+bߤyn?g 5K++?UGP$:DUyiXXHvƣ~ه@!S\&N/|kSXYU$a̲=%~bL<7?p+ ^s^iA%blK}i>eb皘7=zd?7Z.3/eyw{&y#D=Iy8OZE>\NJ~L"ћ6lYy@5k;'@ˁ/6V^ljqN i-zlp,[MYK_ö$^Ya[dcL|U_4"XTX 逼a~I]Ȝ +l-i UH|.qM>4ʚ//Htҹ)n؜x W2o|U=FPF}b\k1cS9`S,W6lٳf͛0Ŕik:0I?oH:˷ lqqQ+D11k8mXL\}-iݔRxӾk:rU&gc9xbf:TֵNmOҸj>Aʠ|e4@@.857͚}qK!,#-ۗGHō\ik^dZHn$e1ҨiJ/m>Eu$ȟ눈䉛u1'G!GCƾ͛6lG?CCVU` s闛-TƪEI"=.YO  <*f МY-8P{)!mc * <"O`ۍ2Rl)6r֪m+ L5#HV$'=-z1#w,ԭw=jʩ JmF FV@Wh˒^?F5F'gDAԲ1;kn&Ea;0}FNo_K;1 Y^84w f'sf͛6lٳf͘ S;8ELVUqJo=hl9xobS!o&ܨ3SSuckIbe+%Ej\(bp3zt|DL仞JNb|qH\V1n7 Xð; e3M'1^FLu;LmkcAKWV ӞUSb։N\^Hfm(~֘d4.f!-)t_Fٳf͛=8O(mcP~տy$p:e͛6aZ}_xjxĎ z|UͨS\2QC;["!e-`(4=qXZ&0y{wMoHLkFVj͛6lٳf͛+/:eP+11R:VP;C8pnGy?`brT,>parhp6i &\)^!ixjUddw®lL1YUJ?"FWcBٙ:w8& zV|+_ QT(R]\v "&[3mQPGbN Ă?T;ȊBi\L Oe\+Nd?7;YXSR<0?*mLI7r(E))O{.JW6l@5k;'@˅闛6lQ=M0K8p 8ŭT^aj^89wes4lY(в܅i"N n%foٺ֞lijI_xnيծ) d1 N0L(ꄀ:ahob\$_7~:`Py l"oڧl]"oUfNH%{ 1f͛6V^lٳc*ڽp]t|5.Bd GRFw5clim!M0C%KS|MY^8ִMCF TzDĉ閻V ,H CW">}zKvò t;f)eY~LRVZ"7Kj<1+h uXCX؄K; 76V^l@5k;'@ˁe͛6ai+'i%ͤ lmOS`2}nҟRo 5_z"ָ*g7/l<)|q%^w퉻9?U9iml8Vq@lw?y1H Ď#,NS 9´/X+4qE!)W?hwWbTǦ36V^lٳf͛,!SP>ꄢt2"=)߾_z`.OfǨE#ҝߋmO }|ro#qlL\UhFQr 1H0[#-вae J9{uM:@.n$4L_Hsq[1u0FA3r $=O\Z[tI ,mz3f͛6{#pP w*0I9t͛6lز9;Ɲx" SAr24Su:*oL~M>^?2Ddp}0L&!W FDV:}c-7GCX XIƪH?PJ"] 82$OC~Yl-MNtǼlD}nI1h]AG i=5N#Q8&Mvȭ"'{sjڣz\a30>Y/#'9RィX4U~`jvǫHg:x7 Ȱ-S.UdNJ8qc#*D&*͛6lG?CCVU` s闛6lٱwA.:9 J1Jv%? ɣ+0۬@65Vl@Z q AZb&J61 Ju#l=a[ 'u$6oV+&4ma{srawjzl\Ř6V^lٳf͖pS|kbʰӯéWP v1'e.E>>Q.XiDşiU'zλ5;('TFY6 )N̳Um-`%1Ұ1zAq$TTYٸ]$r=q[[->"X,>0CL|r'ʃ)9f͛+=8O(mcP~տy$p: yf͂ma{*EvǼ~8cLEt;{bw낮=e8q9-Pr z\yYyf\#2l~ v8߶&!5'|V*|FL4оRnXHfKNcS!zޙ|kMI|4}V}.tIn.WuI\Āo0k1ֽ{桥seԝPӡĪQָ摚*`fj efͶlٳf͛6V^a5OlqxLt<|1TMIdڌW3&8d;+'h 9z2Sk;Y!7.5#TiSP+lqkJ )%jcY6l٩6lٳf͘? ڷr?.Lٲb;:,Uw|Ø}+ %1wvVOXC yRx@i܀ﲇJo/z椒JpŸ");y^ եdI+BlD'jf C,; aǩ@SS)Tfe-S0yfre͛6lٳf_,r jH;WFnM)]01/(hîzs3ǘ+E/n[j6'Y`kÊųNihR{0<}p>6'lJf:cNldlf͍2f͛6lG?CCVU` s3e͏VaQ3Lpţe|}u/ɸ/fX& '3JoiJ+F ,J{iq?&kZ  $RkӇxH&t~4ĝF$)qi9e319Y>٫5Nj\ٳf͛6lٳee1E V}e*z&+MCf{o0;n)OK݁+ƀtܼiA!v3|y.g C/ohwyH%FC?Fc ď\ٻ;lٲePf͛6lٳk? w[9WOϗ^lٳf МW&>~|k߾Z@bTY?,0 UA4dgv}Fͣ'@Kzt?=7#NekUcLv=CYWfݫͪr{g~iV-Zy9\/T's@nMVk76lٳf͛6lٳf͛6{#pP w*0I9ty6l٫VcHSV T1мE?SLNcJ"IgNA7ߓ-CG2M_Q)sV&[}\fs6u5돮f͛6lٲf6lٳf͛lٳf͛6a2\'hh,u-gՈwWM4"Hn!=e u=*]v8]ۋӹ{JMq'ƪA6lٳf͛7|ٳf͛6lٳg? ڷr?.A6lٻec Y84?v @uyBամX UdZ?=;\>|rQmM?A/7~]hV7)2dqj:Vk#$(q@9Grf͛6lٳf6^lٳf͞']hsjʼ|^lٳff@|u^lz ey+DW6ц ԬbH;^APxژmP\}rq#du>b+nJDO0y1N2 j%Fb+Vlٳee͛/6lG?CCVU` s闛6lٳeS6 1dng 8NpEc 遱8ekyEhV:B%N-kƞW pG#zIP݉—5&,iL^yf͛6lYyf͕/6lٳf͛6ljick!thDDPэ;YiፒJx>9_>\6lٳf͛6lٳf͛=8O(mcP~տy$p: YyeTvYhvC}cWaT"MpF:WPu^VדY]-{?MA#us)´rf͛6lٳf͛6lYyf͛6lٳv͛6lR)V@FP%Z(˹(2f͛6lٳf͛6lٳf͛6{#pP w*0I9t͗6lܱsQb97 N$ Pw/!% 8T$yYf͛6lYyf͛6lٳf͘eeَnYg7l]3sxeeea+1훶^V^l0͛=8O(mcP~տy$p: 6VY z*(}ağ_3X9f͛l6a1͘ef/o svrg endstream endobj 77 0 obj <>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/XObject<>/Font<>>>/Thumb 80 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 81 0 obj <>/ProcSet[/PDF/Text/ImageB]/XObject<>/Font<>>> endobj 78 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.9663 0 0 8.9663 59.7543 725.7825 Tm 0 0 0 rg 0 Tc 0 Tw [(ample,)-592.8(xed)-596.1(rates)-596.2(of)-591.3(500)-162.9(mL/sec)-598.4(and)-593.9(25)-587.1(breaths/min.)]TJ 6.7246 0 0 5.9768 291.1747 729.751 Tm (\(2\))Tj 8.9663 0 0 8.9663 59.7543 714.8408 Tm [(Daviskas)-391.1(et)-392.4(al.)]TJ 6.7246 0 0 5.9768 118.9417 718.8093 Tm (\(4,15,16\))Tj 8.9663 0 0 8.9663 146.948 714.8408 Tm [(uses)-389.6(a)-391.5(closed)-389.2(breathing)-392.8(circuit)]TJ 6.7246 0 0 5.9768 269.2913 718.8093 Tm (\(17\))Tj 8.9663 0 0 8.9663 283.8614 714.8408 Tm (and)Tj -24.9945 -1.2266 TD [(controls)-260.8(the)-256.7(tidal)-256.6(volume)-258.8(\(450)-163.4(mL\),)-256.9(inhalation)-257(rate)-259.8(\(1)-164.4(sec\))-260.2(and)]TJ 0 -1.2203 TD [(exhalation)-492.4(rate)-493.8(\(2)-164.4(sec\))-487.8(that)-490.7(are)-487(measured)-490.1(and)-492.8(reproduced.)]TJ T* [(Others)-514.6(have)-509.4(subjects)-518.8(perform)-509.3(single)-515.6(breath)-507.9(maneuvers)-516.5(at)]TJ 0 -1.2266 TD [(controlled)-518.9(volume)-511.7(and)-511.7(ow,)-509.8(e.g.,)-512.6(Hasani)-513.1(et)-512.5(al.)]TJ 6.7246 0 0 5.9768 256.3653 674.9856 Tm [(\(8,18)-10.4(,19\))]TJ 8.9663 0 0 8.9663 285.5054 670.9604 Tm (has)Tj -25.1778 -1.2203 TD [(subjects)-291.2(inhale)-285.1(single,)-284.6(small)-283.7(tidal)-288.3(volumes)-285.4(\(450)-163.4(mL\))-285.6(followed)]TJ T* [(by)-495.7(a)-499(short)-495.5(3-sec)-500(breathhold,)-498.2(and)-492.8(Scheuch)-498.3(et)-499.9(al.)]TJ 6.7246 0 0 5.9768 257.9527 653.0455 Tm (\(10,11\))Tj 8.9663 0 0 8.9663 281.8771 649.077 Tm (uses)Tj -24.7732 -1.2266 TD [(bolus)-367.5(technology)-372.1(to)-363.6(deliver)-371.7(shallow)-369.8(boluses)-362.4(of)-370(aerosol)-364.6(dur-)]TJ 0 -1.2203 TD [(ing)-302.2(a)-303(single)-300.6(breath)-305.6(also)-298(followed)-308.5(by)-299.7(a)-296.7(breath)-305.6(old.)-303.1(Mortensen)]TJ T* [(et)-417.7(al.)]TJ 6.7246 0 0 5.9768 79.8236 620.1636 Tm (\(5,6\))Tj 8.9663 0 0 8.9663 96.2645 616.1951 Tm [(does)-411.7(not)-417.6(control)-411.3(inhalation)-421.4(ow)-412.1(rates)-412.9(or)-414.5(volumes)]TJ -4.072 -1.2203 TD [(per)-495.1(se,)-497.3(but)-499.4(rather)-491.5(have)-496.7(subjects)-499.9(perform)-496.6(slow)-496.1(inhalations)]TJ 0 -1.2266 TD [(followed)-403.3(by)-400.9(a)-397.9(forced)-404.5(exhalation,)-400.5(the)-402.1(latter)-402.9(likely)-398.7(providing)]TJ 0 -1.2203 TD [(good)-341.8(intrasubject)-348.1(reproducibility)-348.6(and)-341(efcient)-345.1(airway)-344.4(depo-)]TJ T* (sition.)Tj 1.1128 -1.2266 TD [(Once)-321.8(sufcient)-328.9(radiolabeled)-320.5(particles)-325.7(are)-322.6(deposited)-325.1(in)-323.1(the)]TJ -1.1128 -1.2203 TD [(lungs,)-598.6(subjects)-601(either)-595.9(sit)-593.3(against)-600.2(or)-591.5(lie)-595(beneath/above)-603(a)]TJ T* [(gamma)-390.6(camera)-388.5(to)-388.9(measure)-385.9(clearance)-390.7(from)-393.5(the)-389.5(lungs.)-390(Early)]TJ 0 -1.2266 TD [(studies)-251.2(employed)-246.4(single-crystal)-253.4(detectors)-248.1(positioned)-256(over)-244.4(the)]TJ 0 -1.2203 TD [(subjects)-710.4(torso)-703.5(to)-705.1(monitor)-706.7(particle)-710.1(movement)-704.1(from)-703.3(the)]TJ T* (lungs.)Tj 6.7246 0 0 5.9768 83.6787 510.5762 Tm (\(12,13\))Tj 8.9663 0 0 8.9663 105.5622 506.6077 Tm [(But)-270.4(most)-267.7(investigators)-275(now)-267(use)-268.1(a)-265.1(gamma)-264.1(camera)]TJ -5.1089 -1.2203 TD [(and)-322(planar)-317.8(imaging)-319.9(to)-319.4(characterize)-321.8(both)-320.9(regional)-321.3(deposition)]TJ 0 -1.2266 TD [(and)-277.8(clearance)-270.6(of)-275.1(the)-275.6(inhaled)-269.2(particles.)-278.1(Most)-275.2(investigators)-275(use)]TJ 0 -1.2203 TD [(a)-366.2(single-head)-363.8(gamma)-365.3(camera)-363.2(that)-364.2(allows)-366.4(them)-361.7(to)-363.6(take)-364.7(pos-)]TJ T* [(terior)-343.2(or)-332.3(anterior)-339.8(planar)-336.8(images.)-337.9(However,)-337.3(due)-333(to)-338.4(the)-338.9(struc-)]TJ 0 -1.2266 TD [(ture)-268(of)-268.8(the)-269.3(respiratory)-268.3(tract,)-268.9(a)-265.1(more)-266.5(accurate)-271.9(measurement)-267.1(of)]TJ 0 -1.2203 TD [(the)-389.5(transport)-383.7(of)-382.6(the)-383.1(radiolabeled)-390(mucus,)-383.2(which)-384.3(corrects)-383.8(for)]TJ T* [(the)-490.6(movement)-489.2(of)-490.1(mucus)-487.7(over)-484.7(time)-488.3(away)-485.6(or)-484(closer)-494.4(to)-483.8(the)]TJ 0 -1.2266 TD [(detector,)-565.8(is)-561.3(done)-559.2(by)-558.9(taking)-559.5(dynamic)-560.8(anterior)-567.4(and)-556(poste-)]TJ 0 -1.2203 TD [(rior)-456.6(images)-448.8(and)-454.8(then)-449.7(creating)-453.8(a)-454.8(geometric)-451.1(mean)-455.6(image)-447.5(of)]TJ T* [(the)-749.9(two.)]TJ 6.7246 0 0 5.9768 96.1511 400.9889 Tm (\(4,15,16,20\))Tj 8.9663 0 0 8.9663 135.7795 397.0204 Tm [(This)-744.7(requires)-745.3(either)-747.7(a)-739.3(rotating)-748.7(single)]TJ -8.479 -1.2266 TD (head)Tj 6.7246 0 0 5.9768 79.0299 390.0471 Tm [(\(15,16,21,22)-11.7(\))]TJ 8.9663 0 0 8.9663 119.2818 386.0219 Tm [(or)-439.8(a)-435.8(dual-head)-443.6(gamma)-441.2(camera.)]TJ 6.7246 0 0 5.9768 247.918 390.0471 Tm (\(4\))Tj 8.9663 0 0 8.9663 259.5401 386.0219 Tm [(The)-442.6(dual-)]TJ -22.2819 -1.2203 TD [(head)-366.2(gamma)-359(camera)-363.2(has)-364.6(the)-364.2(advantage)-358.2(that)-364.2(dynamic)-364.8(ante-)]TJ T* [(rior)-266.9(and)-265.1(posterior)-266.4(images)-259.2(are)-265.7(taken)-266.9(simultaneously)-264.2(while)-264.9(the)]TJ T* [(subject)-340.5(lies)-330.7(in)-335.7(the)-332.5(supine)-339.6(position.)]TJ 1.1128 -1.2266 TD [(It)-274.5(is)-276.7(recognized)-275.6(that)-275.7(the)-275.6(measured)-275.1(clearance)-276.9(from)-273.4(the)-275.6(lung)]TJ -1.1128 -1.2203 TD [(is)-618.2(highly)-623.4(dependent)-621.3(on)-619.5(regional)-618.4(deposition)-622.7(in)-620.2(the)-623.4(lung)]TJ T* [(\(Fig.)-287.6(3\),)-281.1(that)-288.4(is,)-279.6(the)-288.3(more)-285.5(proximal)-283(the)-282(deposition)-287.6(of)-287.8(particles)]TJ 0 -1.2266 TD [(occurs)-447.3(in)-443.2(the)-440(bronchial)-444.2(airways)-440.6(the)-446.4(more)-437.2(rapidly)-446(particles)]TJ 0 -1.2203 TD [(will)-366.3(leave)-364(the)-364.2(lungs.)-364.7(Controlling)-363.8(particle)-368.7(size)-364.7(characteristics)]TJ T* [(and)-277.8(inhalation)-282.3(patterns)-279(in)-272.5(patients)-281.8(is)-276.7(an)-274.8(attempt)-278(to)-275.1(minimize)]TJ 28.0042 48.8887 TD [(intrasubject)-259.6(variability)-257.9(in)-253.5(regional)-258(particle)-261.2(deposition.)-258.9(On)-259.3(the)]TJ 0 -1.2203 TD [(other)-367.6(hand,)-366.3(intersubject)-373.8(variability)-371.7(in)-367.3(regional)-371.8(deposition)-369.8(is)]TJ 0 -1.2266 TD [(affected)-407.7(by)-407.2(variation)-406.2(in)-405.3(airway)-401.3(and)-410.6(lung)-404.7(sizes)-403.9(between)-407.9(in-)]TJ 0 -1.2203 TD [(dividuals.)-294.3(For)-298.7(either)-298.7(case,)-293.8(intra-)-298.9(or)-300.6(intersubject)-297.9(comparisons,)]TJ T* [(it)-484.5(is)-485.4(recognized)-490.6(by)-483.1(most)-489(that)-484.4(an)-483.4(index)-486.2(of)-490.1(initial,)-488.3(regional)]TJ 0 -1.2266 TD [(deposition)-319.2([e.g.,)-317(central/peripheral)-320.8(\(C/P\))-321.6(ratio)-316.8(as)-310.6(illustrated)]TJ 0 -1.2203 TD [(in)-329.4(Fig.)-331.4(3])-335.1(is)-327.3(required)-336(to)-332(include)-336.5(as)-329.6(a)-334.6(covariate)-328.9(in)-335.7(analyses)-335.4(of)]TJ T* [(particle)-330.8(clearance)-327.5(from)-330.3(the)-326.2(lungs.)-333.1(To)-328.2(accomplish)-327.7(this)-331.2(a)-328.3(clear)]TJ 0 -1.2266 TD [(denition)-427.7(of)-420.6(the)-427.4(lung)-423.7(is)-428.5(required)-424.5(to)-426.9(prepare)-427.1(regions)-420.7(of)-426.9(in-)]TJ 0 -1.2203 TD [(terest)-293.6(\(ROIs\))-302.5(\(Fig.)-294(3\))-297.2(that)-294.7(can)-293(be)-295.2(overlayed)-299(on)-297(the)-294.6(deposition)]TJ T* [(image)-340(to)-344.7(calculate)-341.5(regional)-346.5(deposition.)-347.4(Currently,)-340(investiga-)]TJ T* [(tors)-245.5(use)-249.2(transmission)-252.8(scans)-251.4(of)-243.5(the)-250.3(lung)]TJ 6.7246 0 0 5.9768 461.2534 609.2219 Tm [(\(4,15)-10.4(,16\))]TJ 8.9663 0 0 8.9663 488.0692 605.2534 Tm [(or)-243.7(radioisotopic)]TJ -19.7654 -1.2266 TD [(gas)-397.3(ventilation)-406.9(scans)-403.1(\(Fig.)-401.5(4\))-404.6(\(either)-406.7(Xenon)-405.7(133)-396.9(or)-401.8(Krypton)]TJ 0 -1.2203 TD (81m\))Tj 6.7246 0 0 5.9768 330.5196 587.2817 Tm [(\(3,6,23)-10.7(\))]TJ 8.9663 0 0 8.9663 355.9747 583.3132 Tm [(to)-477.5(outline)-482.8(the)-471.6(lung)-480.6(regions,)-474.2(and)-480.1(in)-474.8(some)-475.8(cases)]TJ -5.033 -1.2203 TD [(normalize)-250.7(deposition)-256(images)-252.8(to)-249.8(lung)-253(area/volume.)-258(The)-252.9(lung,)]TJ 0 -1.2266 TD [(usually)-356.5(the)-357.8(right,)-356.9(is)-352.6(divided)-358.2(into)-357.9(either)-355.6(two)-358.9(regions)-357.5(\(central)]TJ 0 -1.2203 TD [(and)-271.5(peripheral\))]TJ 6.7246 0 0 5.9768 371.792 554.3998 Tm (\(2\))Tj 8.9663 0 0 8.9663 381.9401 550.4313 Tm [(or)-275.4(three)-269.9(regions)-275.3(\(central,)-275.7(intermediate,)-274(and)]TJ -7.9289 -1.2203 TD (peripheral\).)Tj 6.7246 0 0 5.9768 356.5983 543.4581 Tm (\(4,6,24\))Tj 8.9663 0 0 8.9663 320.8251 528.4912 Tm [(Using)-456.7(the)-459(ROIs)-459.6(dened)-454.8(by)-457.8(transmission)-461.4(or)-458.7(gas)-460.5(images,)]TJ -1.1128 -1.2203 TD [(retention)-305.4(as)-304.3(a)-296.7(function)-311.8(of)-300.4(time)-305(is)-302(determined)-302.2(from)-305(total)-303.9(lung)]TJ T* [(counts)-489.1(in)-487.5(sequential)-491.5(images)-486.8(\(usually)-489.7(12)-169.3(min)-485(acquisitions\))]TJ T* [(acquired)-523.9(from)-520(16)-169.3(h.)-518.5(To)-524.3(avoid)-521.7(interference)-530(from)-520(stomach)]TJ 0 -1.2266 TD [(counts,)-327.6(many)-327.4(times)-331.6(only)-330.3(the)-332.5(right)-328.7(lung)-328.8(is)-327.3(used)-328(for)-332.7(retention)]TJ 0 -1.2203 TD [(versus)-251.9(time)-260.7(measures.)-251.1(Many)-259(investigators)-256(also)-253.7(obtain)-254.4(a)-258.8(static)]TJ T* [(image)-460.2(the)-465.3(following)-468.7(day)-462.2(as)-468.7(an)-464.5(estimate)-464.2(of)-464.8(24-h)-464.5(retention.)]TJ 0 -1.2266 TD [(Because)-288.8(the)-294.6(Tc99m)-289.7(has)-288.7(a)-290.4(half-life)-293(of)-287.8(only)-292.3(6)-170.2(h)-287.9(the)-294.6(static)-289.1(image)]TJ 0 -1.2203 TD [(at)-366.7(24)-169.7(h)-370.1(i)0(s)-371.6(acquired)-372.1(for)-370.7(a)-372.6(longer)-375.1(period)-371.7(\(e.g.,)-367.6(1030)-168.3(min\),)-374.6(de-)]TJ T* [(pending)-562.7(on)-562.6(the)-560.2(initial)-561.3(activity,)-565(to)-566(obtain)-557.9(better)-568.6(counting)]TJ 0 -1.2266 TD [(statistics)-333.7(relative)-337.1(to)-338.4(background)-333.1(radiation.)-335.5(Later)-332.4(time)-336.6(points)]TJ 0 -1.2203 TD [(of)-237.2(acquisition)-244.4(are)-246.7(generally)-240.6(too)-240(noisy)-243(by)-242.8(planar)-242(imaging)-237.7(to)-243.5(be)]TJ T* [(reliable.)-460.5(Finally,)-461.5(some)-463.1(investigators)-464.7(either)-469.5(incorporate)-463.3(vol-)]TJ 0 -1.2266 TD [(untary)-338.6(coughing)-338.7(maneuvers)]TJ 6.7246 0 0 5.9768 423.3259 390.0471 Tm (\(3,25\))Tj 8.9663 0 0 8.9663 442.4314 386.0219 Tm [(or)-338.6(attempt)-341.2(to)-332(assess)-339.8(the)-338.9(ef-)]TJ -14.6755 -1.2203 TD [(fect)-430.1(of)-426.9(spontaneous)-434.9(cough)-428.5(for)-433.9(separate)-426.3(measures)-431.5(of)-433.2(cough)]TJ T* [(clearance)-378.1(\(CC\))-374.3(during)-376.8(the)-376.8(period)-378(of)-376.3(monitoring)-376.6(lung)-373.1(reten-)]TJ T* (tion.)Tj 6.7246 0 0 5.9768 328.4786 357.1653 Tm (\(4\))Tj 8.9663 0 0 8.9663 320.8251 342.1983 Tm [(There)-582.3(are)-588.1(clearly)-586.3(potential)-590.3(advantages)-587.2(of)-585(using)-583.1(three-)]TJ -1.1128 -1.2203 TD [(dimensional)-249.1(\(3D\))-248.5(imaging)-250.3(to)-249.8(measure)-253.2(clearance,)-248.2(especially)-250.2(in)]TJ T* [(better)-574.9(denition)-579.4(of)-572.3(regional)-580.5(airway)-572(deposition/clearance.)]TJ 0 -1.2266 TD [(Although)-254.7(the)-250.4(feasibility)-252.3(of)-249.8(using)-254.3(both)-251.3(single)-250(photon)-254.4(emission)]TJ 0 -1.2203 TD [(computed)-353.5(tomography)-352.5(\(SPECT\))]TJ 6.7246 0 0 5.9768 438.633 302.3432 Tm (\(26,27\))Tj 8.9663 0 0 8.9663 461.2534 298.3748 Tm [(and)-353.7(positron)-357.7(emission)]TJ -16.7747 -1.2203 TD [(tomography)-270.3(\(PET\))]TJ 6.7246 0 0 5.9768 383.9243 291.4015 Tm [(\(28)-10.1(\))]TJ 8.9663 0 0 8.9663 397.4739 287.433 Tm [(has)-269.8(been)-273.2(demonstrated,)-274.2(there)-276.2(has)-269.8(been)]TJ ET q 359.95 0 0 168.265 124.894 93.94 cm /Im3 Do Q BT /F7 1 Tf 8.9663 0 0 8.9663 59.7543 77.159 Tm [(FIG.)-298.9(3.)]TJ /F5 1 Tf 4.0593 0 TD [(Left:)-303.9(schematic)-301.4(illustrating)-304(faster)-305.9(clearance)-302.2(for)-301.1(peripherally)-306.4(\()]TJ /F7 1 Tf 26.5752 0 TD (A)Tj /F5 1 Tf .7714 0 TD [(\))-297.6(versus)-308.8(centrally)-299.3(\()]TJ /F7 1 Tf 8.1882 0 TD (B)Tj /F5 1 Tf .6702 0 TD [(\))-297.6(deposited)-306.1(particles.)-303.4(Right:)-303.5(lung)]TJ -40.2643 -1.1065 TD [(morphometry)-270.8(and)-265.1(regions)-268.9(of)-262.5(interest:)-271.8(central)-266(\()]TJ /F7 1 Tf 20.2396 0 TD (C)Tj /F5 1 Tf .7208 0 TD [(\),)-262.6(which)-264.1(includes)-268.2(the)-269.3(largest)-269.1(bronchial)-267.1(airways,)-260.1(and)-265.1(peripheral)-273.1(\()]TJ /F7 1 Tf 27.9662 0 TD (P)Tj /F5 1 Tf .6007 0 TD [(\),)-268.9(excluding)]TJ -49.5274 -1.1128 TD [(those)-336.6(largest)-338.6(airways.)]TJ /F4 1 Tf 0 77.228 TD [(MUCOCILIARY)-339.2(AND)-337.2(COUGH)-337(CLEARANCE)]TJ 53.0113 0 TD (263)Tj ET endstream endobj 79 0 obj <>stream AdobedC       _ s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?Nlٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6luVAl= O<{=G*zTig9_3Pկxi&m,o 9+vr 8*:AKHED1qJl90i_&?I_&?%+CraO+9,j_&%㔿MKWRf?%R6W R92vq#o9:W+؋S0]l9]e0m!'zz6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6x+'?<l` Ңa Sڙh-z@$ze뛖Z*{rHq',6ZSខ]k7rZ*U0.jv&8 E^" zh/$2nzoʐ]vodVya 6Ǘ^CxL!w¯27y\w|w'W`w۷nC,7J <" O:-L5}IӤPַ \M3HdJΧ=sOӰ0 hfS#lF2#e4&WXӮjNhJ꺰K<5:l Y|=FUQpO ./n>w{<Ŕ`=TQ)Ȏ!2[\/[M?GԬxn=uo4VfRÏO/O%k֓}KNΑZ;[$Ee ƻr9sf͛6lٳf)Gk;9o4Vji:uq_[1J?$َZ_.qIi#6Jrc_:vlٳf͛6lϟ~hɱ6\tͶ94ZҴ2 >=r<>٩倱aϖƊ5Գ!۳vw.龳@җњ!<$ׯ@~y]fwdBe;HPlh0x<_A%L)ce|KC>w V#R5ME6P?wg5#b\jOIAsR;W ߘ>--4VBIwy̋ɐ:? S|t똵\ܹ{%ڶl?oa˵2YizbyQ֛tmT}7PO+jxj9 Ls vP*8Q=R^7Q#|$hUŰa}jt# n^O{U[n^ȷ<5K# !#1ʆb-Q+4뎭NrOb0Ŏ,}eϢfM?VIKIedHDFF[ ;#Zim!ꩦAb y˘ܼK+lj3'O^;/lڿ赱5[?>3^??|ՠ$ڰڼC-F㰭q3&<7w厥Gˡ:ƁM뎢z1o](34L6MvIc$y ge\yrLeo$qVU¸s}:5oI#b<ߣ;bnFSN"1&-%@OS4).yr--` 0 1idBhXNܰ 3O@7zǯxQ6ajڤvҰoVUJq//hwr[]JM)/ￆG<ýF-TS(S0+Zg6Zm[uWZno c~%^MݞeIx~apȶ:=3Մ=v#5tL]Z*I25b>⻥+ڽN^Mq)帿ڋ׶7l>̷ֹ5Kk،1֔,(7#7'>ϢĞZo̸?鬕>I048C߮˯8>zZu=ձ𐪻ՅN51ϯ>!o곧jB<;jp*Gl.OmRث."IB=mq ͼwxPUA3f͛6lٳfĮpDvNs/,#n@UTي|6-&<è˫K)!K;DS ru+Llnmf5!Sᅟ1yz%ү=F7ST'nK-N]>vLדoA:e֝yQI+P^ bh7\*H*wn͛6lF[pBvBy^hVMA娨ACmrYukUESL@ r2~mL#xz ;vZg|[FVxj@bQZxe~Xi+,:,jK)bƘ/,ʰyijqTxk;kXIo2סS͛6lٳg>q3&<3Jli~e72ɨY5.o|]kTG'Nl(7?BhXks,6-Ac.+F8F {|kCu#]X\1,uIL7ZAzpZWe ktƋ"^nog`9vK.n|a)?w%jB~CO/֤]FHUېy#JĻ4^}|Ah^Y s}ur7*w85$8T"pwɍij{I_kl?[[Kk)DGb]QMRŔK*8O2{mB}Tajd>#`~y"[Ǻ*[*A~ymkƿWԬ7{yKML,P:]0MFH!YњmF#Oz ѐ%Bېq6ۧӔNbEF4ԝ5;u:ZEG3lٳf͍To~oAEB)XH9L]k֙3f͛6lٳe3*f (ܓg,UϞoHg.P$NI#5`lO#&1IqJYqmb3~~yfH,ZdXnCތjA-`~3vM>x;th2CWM~f(j[*jgq%B i:6LfXn5qm#Sw&7i)ʿ-"Mq7(>=״1Fl!ܜH|p95XVRF DW;^Xj=5 CDcpEe"O@{#>[T=r`p_ȧ(eB(G`i;\/tݯ"GB0%i^BW| )ծ#\~k~>#I#1K$Pֻuǐ|_KмaNɫ egH½gT͛66oSZO~w <Ӧa%,wJ#i-52'YWӮM;_\2LN jGìٳf͛6l矛ycA`5]Lge?ot; GEX E1Gt$cAH5f3X3Cr5HOҸge棬irr;_2g6B1ui[_-iFF`yFm.: "f[ `SB(A7$Yç^ Vm)-.Sӓ2תhm#3\sxfTi YW$HLkD:whѱ ];18t,23FԪާ [!]i ggmzO1;9;>.k; ;Fđsϸ@;v[}Lm;~92Y![(5'.. eY8;oֶqb (=5qo6/˸f{jS]ya1ÓX$cgx/OBlk~aUrC$nU87տ7cĴN$9_#?Q벲/ʲnس鳾ɱʲ;AI/Ө*/#ۨ P^zH+};x:sTK,&%9Q:a yf͛6S3'8ߔy[~;;[Sl24bVk)=8 [sÊ2 Q q]5u9ܼ~=:WG;?1?c+J6ݽ/$Wqْh#>= v8_O uBH!-6xu'e;EX͘N@<\N+h+==N,H1B?Nwߜ9j`e^T&>9.ƨ(%?%)̞WaJu Xcy mV\76y{6a2\r0Ǩh`'H -| d)y MpQӖC obW2u//܍Nvh-cQSïIi2wH&U.ʩW#j6%•-[rվ':Ҵ Bd%b&i.A2hʤgGzLVֲ}STbEK|㰳]R..#ZX@1Od$yUcn.BPUG"`RU 鉱{yMol[9z6XG]8쮒Q{! ?YYcoQ߼APx?+O6X\.ku~_0C-\hOZgY͛66_S]irjJTrkUGt/\j[5{i5!r?@?|ArC~7fS،>ӯ.!:?|*6ί6ٳ_ܰZ̶ى67sgfDݡju-c?.EuZ)f|d6lٳg:К]Jhyo\4V$ Tu:ǼRd&Xg<4tMzrp (գ%ۈNBot3* K/qYDCQMb vHcB`մ=SN1%u;Fr˙,.%'Нf$Fj2]"+ ˕_0T0*(2'3+o{TTF"$+G~MN~_iǓ[il~mA'ԦHWIJ$R>@bҴ 2=6 y {/4*-AW%SsEPđD#@ES(xRb3y2;msɌKv?_Ӕ{.t>ѣ;ص*jǮm޵IJ8e8ڱ%͛<?60F#T_1ߵlqnh#h*h:?T@.hv't?0iwӵպk`d6bjt:$^={gRҴ-[֓dV8}4 =r(ڕޟh% FqPzv׺C{Tfa,:v)JSKgQƣCOʏ.= VB8g6&X2«6enT?q6_OO>>5xVz'@s|?]cqṋV:g#cQty%ſ9K9Ol|5  {r4`)o|^\ dk=7=5*%jn)gH'o ZU E)>iJ5(z0gѨ-vA0N*03jVQ=RA 6J><ӨEwإh+pAqsܲzՓtNt c!7-&kF 7`C\~gꫥRk[kѵhוr÷\G|ass }R+cX"y;/&_:lٱt՜q8TNkŇ@s0i=/Ӷv  `[xC$Uy=9YA *[xO0q-?HΩQTsf]8[N Rhc&>4˝gM{ʶ{X4pD$2WkbyI/PJ{e]8FHI$d syNMY"K8ʼd9}d`h%kH3 4y'|p$v],$Qȟl[[A qI k=_5t&kA \BzSE(~/!_Ib?Jp>D͛6lWN?4xWLn0VXw⻜:򽶜mj L祥д=gNk(" ANZ44!.wf'2%y7QX L7ϭ07α,nbK6-!PS./(k&dʁ;pI&Gj0BpUkؗmiNq0_inWdN7lQE͢2hH)T&ym.8>tCt=~+yh^|voё궉| Hي;{)]jW7! K?,?ޡijb[pg8gΟCŦElO;A?j"SڹO+mu-$]HC7"ѱ$8ˋW@j1{&S%m-rTƵڽI <O{NHBM̽ .'-.v/ д/JO|$,VgZP{_2ȸHw'ڹ5?0ZVM;\T(kGqpNz|yoPtd4qL2Ӵ9'Rzl}):)0pys[~n t 3^%đyFBQ3F2y%jWAo; /W%pK!wd-Bҳ crTؙ)w*ҽ9a7a։Su3ntC ΆX4LΊQU=2;xTXDN IqO3洸IΉ9 5ުB:: [Ǯ0$bNqFMCgb!F 6lٳg>q3&;~Ν]6{#HSr_qo6BH %ᢒw~^[ɀX3L:L!YmnEd5Ss;ɥIo1jȪPliKks]j@9,9ݠ/{x.u[[;}6R;)CՄ$ a͵3^Qa/2?u-z:pE4z`+M;wrjP.TQTZ'֟Fj[\ NAeQXTZ9ȿ1&UՁzS!$cE*H+^WϷ%EP> 5M4Sv"$ 8lff U YՠZFc!Zz©mFj:&ugN!k FP?llI0Y[Ԁ(PH$CLv'%>}MTr VyrF;);}{@f&4M`ưmyRR{)!%P}S1ɐt9m+6edBmδ E?4,KuakC#[ۛ[[>W’\lu8w˼*wKҵ*j_+io(O *NKXJ'1S]+[hhbUUPbce?8㹫yտQ憀.8ēlހ?λ`O|kUjVk 6E1c//Ia)/zI 뺺S`_^K7|61.*x:flٳ~jM2y7'S~=r"! NC3Cn1ʗ24BV(Uw+_UU[{A>:_07}(b04$;GPճ]-)8'.?0<`\~.5OzH/ح?dmԂ'bHj#ꗞOjSȳw}|^*D5Q:s͆>!3]鍸wq;>yMFA$`?ʝUVMjwrM}os еOD]>?Z;,lc!SEƗ=ec %7w6k[$F >rVYɦlٳf~|GgM-4菈4lԑ$OƵqfAgsgͤ/e"5DƁҼᷜ$3=2@`H.ZWi o njĒ=P,6(s4<Ī2ʹIhZ2-Ae靘j DU4!z^[1Ylc*/&%w `"ޝ?ͪP̥%xOö g˷Nu]NfksԚv"ntn)PXE:1i/Sޥwˡkz{2ڬ=|i~`'.aAЏuNgظNþyFs/"NE ?@N*EarYepz 8<..Bb^cki OUF#LcX+j{Ԍ*&3/ qKC֗-@~0PL>ڕϦ7ɷb'1Ł#ԩkͱ5ӴWϕ`?+󳦘|61<{Iv#`[oq ~2]ڇR>g>߻u5u %+;?T{[9&ޯ>Hh*}-'^A־^X.M.xnHk*OHnYfVq6,|^UosFSс~qK>ygerOס^&lyg>Vk:ݥ[NMғ[~W~cC.Hn6~aOX>̲.+R&g1̊+O=mJ: ď݊lGTƣ68yTzamT90킴-wS7uy.M  \|iOΚ-4HiTlوEAEΟj1S6àI$$тt;-kVC%ǖļ?z"ąxŪ[qH|\ \êF-s !=o6lٳ_?8c Q⣧Z`'CNywDolC"Sz2zZ3Ǣg 5Tpo,o WE8#SZ . HZ.7N h#Cև!&?o.n%1Z).<Ȳz|.c%G|=3Y,| ޻}yNwlޓ 8oo7n$uekچêR;;C#w>xn稔zvA>Z̫ˉ ガgӑX*kQJ QO7W3i Fـ_|w֕*8f=H"\gomz#oJ棍zP9 ܔjqWHǯ0"=`eS&ZNb>幡!fߖ˜֡Ӥ-𰪻7|<ɧH5z0ٽK h#SCNm%gb %'yZuIc J=("?/ϢGmk6i^g4 ,KUMc%#H%Xg_Wב\Cd*mٳcf?8㉯ͿsgυO:@Dp]4H C3++(e5R*^lʿ3_ {`%#vF*K/CMGOn};'X&2:$>|h-ܰiEcPf͛6lٱ;[kW$0\6A(?6lٳg>q3&hb\-*^IQWPwaBQ"NvO4Ȇz6VpYڂEIߗ|Wc> 'j Qe/p8:Vf$ilrFڼ3+1Yy_WyOi㬇e|r]4 BgOr2UBAHyE^a5ɼPnY?1<` |(3Z=>^"4zS#Q8@]FV!{h*r7jbVtguBi#MsyR 7Z0W=8|@ӵ\_= 33Ey3JMN($oQ+645c:߶=Wm>%ke#%(㈔) r1+TvJp’soIv?FkglxQY *F#FŮ.[ੴ[^w &QAhOpaz4#^r9[˫Fљ; kTz0dѼEKt zhfi_ 26aQ# 9+SI>L~haa勍a>'Re\ܤ&i(S#F÷\y"[\Wh)u-.Xt5-kXHaP +R;lٱt՜oqRO9 ֚ y1H$uYu#Kc/!iw07Q{Cc ٳgf-}1|{"lpt?&yDv7>r/Ƶٳ͛6ٳ͛6ٳ͛6ٳ͛<?60Cc` <0vKHY Q*M;gwZԢx$$D҃Wl7 y(x +㹼G(ԉb+yn5d "5f nOMk,i#}G6Tڱ_8Ǥ[Ӛ0̦|94M /LOG&A {uϖX,ի=287$,zG3SMtJH.qbL-! o7/P9kyܚ?G'-M0Gi.{Q"axͤvD WJ/GV^' ε8,5ښR?՞%֦|y -15&~GVOl V=/]$ir^Jvژa"tnR<ujkX^׮ҕm3̺-c>mù[i$һVx$p>irjlf۵r A}weKS^Kq 侺7q#54_aUx/kvVy^5;F5ۣf͛7OY׌t_ XNv4TyC˞z@!i:j7Y]$pH/6lؕݥ嬶1)IbaUe;Fp-Q./f/wji4sgiѵ3Z ˄P~]nlٳf͛6lٳf͛6lٳf͛6lٳf~|GgM/ЁM(GX9tx!۳Nx䣳ﳧքMܒǯb14lNˈ!d?ϰՑ%-<46-zW%ͱ-jEuIM^lO$l pރj-noO#mt9ebSR+G&n, އ z]QWfx+ <˧ZC#h3GqYZPrsH ^  mޣ<ᦳevʴğlr$p+ΩL2\ңlŤ:UNx!C,#ߘ,zrܣk"AQ]j_ݢA+A2OHɿ|JN6 @ʆKlZՊm]L׾~(ڹ-K.r Cp5z9shwrVӦ/5Y^H۬3$Ȣ[iΧur-H?ZW"?:}Q,SfAũϢy+P:KOfgCjm/pZDbyzt4Y 졕hY)$i$1"tQ6lO38"sfbG-7oؔn=Oϯ6;{F9 §@͛6lJKkky8OS(uIu*E&{/h {R~԰w3OͺXu}Ok0~7tq،8͛6lٳf͛6lٳf͛6lٳf͛6lWN?4xL}7Cn9L Ӧw4= P*B):V.on']zp4zZ,f(ѵh\x kV].?ҁHE>pS8} } : &ƋԮBw\gW[=-9O%֒zWOY)Z ]~]u*)[[ђO4ޙ.Mחt$MJIhK ;j`ҵJb[sȯ}cO=-#4PpeIksn>]6Yqg|A,Gm~TVtٌhḂH؃BiM׷.XGLQzd;Q=Z'L~MH+&f+'%qKŁB sAvOl v R e#Cָgc= $Pm b[bYoN]?Kb7ȞꚨSvԮ$(:7QħqF&<[E3j8 F0mNaYZxO$T.K`Ya%` X#">lއi-v!ɳPŲzˏϢ҇OȚ߾dbDʙ<|eaMcX\+YXjM^ziSIȃ1:lyo̺Zizh3j_ޅb4uӾ_PgW:2%M~Vn}OArm>?W7#ӯʟ)ON;vRB$S9ㄑqgj NvٳjN<~_ UD dgcf͛)]J8 (wh5."ʳ'ְډ#´"V9ƅVf9NK-3L7\9ob)C5;3~[F|E(^7F kebPxb2+Bİ\xJdK(EB=E1X5;B+d;Lqkq*jE=-|Z; CBpLVPuZtGOB$1[}`^R}j3yۗK:ΦEglӵճF[w1w)p$~2=+;\>w鞳ӄښH7,ƒ͜/'7º1['0n79F9<?.GikBCS&Aho•S'jי.SIx1Vq?,>sAo1i93fȟ#gn=m:~;/ cִ=NݾВ/7 +ٳf͛9sf͛6lٳf͛6lٳf͛6lٳf~|GgMtgjPEI܊djοwo`nGpT6k=7Hڄ3۩-xízƫw_w)Fsw_H 1r aYRbD^EjRksX .5GnH0 W0VTSzZawAN^\ǧNdܢҵG7Vn&΍#QAZH-iH}/VMr޽w,ŧBe?%?/WP?Vxw4Y幂p=yT^,翙>ᵎѭڮ+ҎyJ[2ČGV<ev Gr(9nuKe^ VJ[s* iC;0k6)Z:qrf<{+ҒW쑋X[zhgm&Q'ԧLVx?,gbZpA9?Z`Fy6E h. iwowkճ H^*+6lٳd7B3աU6>!2|+{DvdV9'睎;IV{yT4r 1lٳf͛6lٳf͛6lٳf͛6lWN?4x7ȳG6oiX'NBY 2nzSh 2x㊻`{FХԶ%zP*u5xMaZt+e҅\v92HUe'bw⿜_ն9ɿ&vl[ipD%xGE} ,5L9{x Sr*k8B;EywCYnỿF$;L~t&I};hx_yrɽ'WH{ }ڕ^0. jGE:>mٳܱ谨ߗאAdzٲo c f6}-:fredbcۍ:avjضNb6w""[ H쓾!tYBMA]cgh]N$w_ $`xJ~G4Gzx~Թ ׏Eιs麆m[[]jvH}YYa >=:g˚(t+Fѵʬz]寥KFnۖeL뙳f|+8i/5E?;flٰޑwj1 #hSC^ҵ[Z)m& 7cfjEa͛6lٳ` oBu:];UaGE >bk>m,КO HX-w$BK;/|٠yO[.\Hep6lٳf͛6lٳf͛6lٳf͞ &/ 9֕ywJިwk'6VvHU JAFX`hăV#y^܈Gҝ~i[ܣD8zmG̲Tz|PBXjoG?:%S[-6\:` \wC[CFY͔z*:.nJb<,Xďw ʥe,z甿6%$ҵ5'̷6r?mj'F|e5l?T!!Š [QuT:lA+!X1cCɯI{3w1'dtdʟ:_G51/ *JS'm ] o ySxwE\ȴg+|ymrW?aKh%\׍O]K,''\t|U@> zoskHϡ)":nos[ʩ"*H8kIT װzj +-啕ZV:;rK.ë`%%}V~Iɧ[{1}὜rPG1%I!lHUeǸs"?N8+M12}4J>sSœ&u5Û+}U4 K6𪍅{>VQI!VO)9쌌~eJoSv.KwGڊ%3~Yaae$^˧Eirchf (VR sf͛)|q?;WS6lٳ~pyS5ymO:lgwh^Ca<~6fuفٳf͛66Xb&TF㋣ br4~O^rkW_2}Iim9N;ʿyVxsR ڪmC4SFHU]MA6lٳf͛6lٳf͛6lٳ_?8cXiZֶ``xo&ELvѠ"3S mm>)ߝ `gI)*Db u3U>0i]k\XA$al @ýNDhF64>7AZz~u!o-o5ly)\zf:gyVHӅ^h*hxKvHWsl2sjma#!+HH鐯2H=Mhrea]OL ] ˜ ~O$4'6ۻ[p$6yE^ 9%x\ wRAF:$Fޘ1 k nNdlR+Hd?& tGFGV"}q+]K?U1I-[ 3֠)>7Ee~~g= wG%$XXʴ+,2,\$vwQ.F.yd6lٳgǔ%yO?y2/R 7d3'yvaɞrѼۡëirrAIb?n7iv#sf͛6lٰ;Hך~Y!F3'~g_sP:?Dz?=<] Ckp(cL6`et!1Lٳf͛6l6lٳf͛6lWN?4x?)Km:"2ШQ $>0Z1ڧtYfQj =goun&j!U4k' 1 #4ž, jZ|ZbG$M].TS|u:e)<lRLUJRXo!3zX!4݆rO4htJARA MԮCG' ~ώj~] ft@ڞ9旧鱁Ϋ?<(>[c,H};OCH4`(zgtl%խyړ;g"$E%9qڹ 3q|3rfW ;+\ ,&I//OqCΓɩkk `QDF#sh-"YI=k$kp(CokJ#Y.csm\_/jI,Fdj r=}Oie8;x]E.I3Н/vxFACMjܕ#&"K'ߴ):D&wpBf7= rdu0V};%*zkњOTzSOU"P:"Ls^INqy~ \@7/+]:6j6ba-atI0cdiYA0I?o|xڍ^6gk/ #_,]d;UQc6lOO|#6lٳe2V=9gRyѴ_jzBtPN"W43hjTki&unñm6lٳf͛#g|I)p,qwc+w]l:m$Pv=>."Γ).??͛6?<||c? !NXJ39Iu9k_:/eii hn |ٳf͛6lϟ~hɱo %+exCCFm%`Bロ4|21-Z4K{a pWY FkZ[]V~l3PRHaU('Ƕs =Z Q=xٛ3\]cSvoFpr0>ˢ!W>8%6/c*n6;(<ώ' :b^C]ZL`hVb(8%זe޸̥S` |kK44S 8c@FZz@yXV j3pKi-* VxZkl-ѽDu뿯F40L֧r0rBK0޹c|DSKUnKGu\"OTMUv9ؓiwE[&}j[sA-Rӂr YoL\i%]S`8e3kx!8eF F\*qdfKYhwla0a >_:u ON޹^$/1{oQyCWs\,8 *mIۥ7;ں݅fF2um RC$Nq*20A.ecWJH5 7I-,'@[\Lb.'ogx͛6S}'A??vٳf͛,QME*WFgo}<6ǖ?d{6t$y@󎐺0b(.mib~P6lٳf͛6lVZEt8ʡ^Auȿ(^Mtf:":?; טN{}RHJ/˒zu򬒆76[PLtLW2iMhPdOF1%7HEyB_/C^ݛGKٍ*!]89XMB'ξ]G?.ɣ!-$o!B2|a]:lٳf͛6lWN?4x΍8 7n`BvsyIi`F1[7j>$-1ݬjaTv6pҼ#M0=U-@,l-#3[%T;TmfI@3యD~`foN$qЁq{S:܄Qg>>V5 4]'Q"`i/ZZS['yG"=B 2LVPo"i1A4?jCVbBaL,* -vo!#w-+1[(0+O .3Hm*-E3/buڅHЭS,xFe%x04ڵO.jzu -An/db2ODGZsFt\ٳe7?,?į_*vg;~lٳf͛1T9QZn:}K37*WN\n>kțJE>O'f͛6lٳf͌e5qבzSR?Dzm7!b?=; B6Yӌxsc:[|)#iϮ$Z?喩2 Jt . LZ^B&;I"`ٳf͛6lٳ_?8c&?MU^j- 5D.yY`ww]g T\}gRl|pⴅ3RfV#}cDmm0\`U󰵰6ѥ&֧jn'*2Q;Z-;=᳾6>U7'+tSŽ pVd/.'pB'GW1Xʏ%2ϗTPMNd> >'%Zӥ@c*߶ 4ỈOM+mԖ]\*T[mg۽޴82;Ka|%>p9Χko&G$cDlm演' Ë/Kcf[SG Em>I{V~ vCqe>4t86}H;r[ټ wv)F{g4 p8UiM\D|XkBΫo9sR2Ō`56=7cG7(=~ďyҝi&ٳfpC[ +Q6lٳf͛9y̞_;㷽a-?bZ}#cϐ~4_O柶}Ou@A;;ٳf͛6lٳf͛65 B<-y?4nP(_!ubOl$Fx0ЂX9ēκQywV4kf E^,XiNT!-eFQ>FՕ2ʷ͛6N?4xΥ#i^o䰿ZߒFѐFhy7Pʴ]E".ʲ-/d?O/&G>SĵR:;CkJ[a[yϸ@TeQᜯ̟x*f'a0Vz,m{[Ko ޴|$J$wdz E˰CZ6ken lMw [к*'¾y5;`cff;q , ,S[{ q]A˶=xLaBuҮt˹-nc `+u2;5r (I,ݰQh,||1Kk|mt+xkXA遯l{ߘtKIT,>;am$L;={XĖ76NO FJC=xt{_,ϭ\iZe oko%BfC;g?_ZyKKc􆥥Cive̒XyUEH9ݳf͘9?&J?3 6lٳf͛6l>Zla%7uXrҟ"-Ie/ԅKWSӗv 3W~[V%wP HΝWf͛6lٳf͛6lٳeS_sAԐzF~Y\^%A4lZ!pk R#Bcf͛<?63?^@X@.T =ڙkoMMs'z \/&?6S3r6]?zծXZ6q2oȁMx΅qnb[mӾcno|/.`h;P3%ğS1P Ǿ|s_Ix}KxJ8 o&yԴь |EĀ{a榚S jivw%"-%QBpV֫''epz{w_G)ĝ)V[˶{ťNIlae͈Txg3~\q1ʋՙ@/]>-Gp3޳#M-l#&ݹ/t%^a԰³)؎‹=RZMg3Ʋ]Ki 9`뚍RA4XbodD@fzg <:0c?;lٳf͛6lٱѴRxQA9G"mP:גo֯RζYm(]&I`MnK6ʵuo/˾a[Șn z6͛6lٳf͛6l$W;h.ǩæ[ܹ '$p9woxdkhՂ5ޙ'͛6lٳf͞ )Y>KEgQq"=)Bm&[QrM̲(xo-y7R/&hك=( $][]/t.{w2y-m/_.kc3wVxoח埪^O$b6:V sqq,GyGB4 }b<2Ui^Wl󐷖\:/` |k9T֙-HҬ'nVcMdV]~J߉t8a,b?'`6Pg6;G u.udZ^֓#]]I!qn= :>S..Fg%ًdtxgi-%hH4n5=RƓ0ssᐭuZf6s {2֭.-bYzt)t bN>&:w=WM,a D7_\CM:^iֈ~P "Ij6WvAhъWҒRT0ڵa)-c:#'LS'<42@zo^XHg}ļ鿙~=tzzscdCMBRq$ބt/&~W9V_iZbhvrjw ċևSQ\ԤW1<9\5^]d^"UzӾK]WN&+sC~CF|էq"rf-և!FMs/?KBl/Q7y V6qt_:"ޝs)pUZkiiqt_YTr7tˤų}3Dx()ڞ4Ö=*P'S-_նeh^mase$F|ymy/rwz1,z\sJ({pV _=>]m}Jp(fD!daPcǮ |ujqmoLYyT3$7JJf͛8g>H(6lٳf͛6lٳf͛6b+1Dz]cڒӠ3~O~WܤՋ7/WR͏FoʙETO'9vqGe ڡiq3 P韶???utHQq8^ŸRk8Tm=8}Cu}F~T˖W.K$o(#K|>͛6lϯ~iɱ7RyHoRye8.|~^rKֵIr=]\NShז=[i`|ݎC@ $0* |zlWJoO&GM(_ū`I[_==vٳfpP6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͞ 5`HC4{vC?}qumn`]W^->O]jB' u/1jϥ,/o۸Ҳv;|]O3i2Q?RGĔQυiˏZWjWMĵFs Վ9=Տ?F#W2Y}-͛6lu+L/aW>&gXFvoǓe#Mݗy7v_>?qD7ɿ{\&#_&Gs|WH>y,GrI^$SY&1NeO̟2?}e#[; hu/4/@?+V_j\?/?g#WyW?7OG[uj\gˏ,j\a`?8?-OO0Zo/0Z u3W_wL6c+WooL6c7m?o]0+avVi3 c[z ϯT^M+j{p#FMqo1_` 95:wr1(`h;Lsf͛6x+'?<l`$j4->a[oT:?z3GNf2 RjAFŰQ7w_oP:^PlNh"P s EpDn<+ [9MͻiItFޝH8Kk55z}jZW'׏Ӟ{Ӧԧk8HJ9o+ڦ[3u>yj ZkJC\'=JŨ ֟,?Yi +<R6{#Zӯ[K;ڼ&?Ks׏D&iS*~aok|zfϾ6E`NF3N* D17Su幒H&/CM/طfzQb1)ߔU.>^eШ~QPϿ\r3P*~PJ~r8+Pq>~W?()Oя,-P ,;S7j5Λ#K ZF(d%?'S8oU'SU?'~'o/o/o/8:O(()?0(? (36'ϟyZ]?p-ڡ14*yyoO/uVkhy* -Z/O* {?sʂ^\'W?7/O* {?rJ_'ʅ?__g ^\"ϗ?3t{/hFc\K9f͛6x+'?<l`/-{[Tӵ5Jt:pz6֗qw%^C#uv_\oDq Ƹ7zݼjҬѡ=A o=jfguk$fezP YuKD`1d^SZ 5VjSֶ'b:aVuʼn%8]`x@TmQHsVa7y/%S(+hZF/A1;QrMŮ`6\_;LXӮ5XkMPDN ~9+/,AA\\K1=)+HԴQO7X]/(UJW<q$D%X:껹 w <aԊw9k5:0ee5O]V #&5&f)OKF35̟Nf[0_5I5 Y$M @yhzcX M|:cvԜeA9G}eT֙tzL8]=rĤR%2#]94[jkĮ--.B cFHĊx⹳f`y1|'X>S SB ٳf͛6lٳf㶂9HTy7jx♳f͛6lٳ\ٳf͛6lٳfilٳf͞ _2.3ţׁB*= 1^뙤UOߍ{3< ,I V fkF5ż= b'`!_l|0̐Ճ[%mጺ;Nh=-K~jDvoj]h }GA ^C)=CjgH7hEzDC1\`2+Ǫ\jq(<~=zgLdDG-Hh)8պ⿫EȁL:Λ711fw¯;7 gpu9z70-'?Q渊5qaC7]cM0 7iE:߆,b[s)*:g|ٳf͞~Vy}fdlTk: S{gsf͛6lٳf̀<ܚzŬ.-L)9RĪs&]E^3iYL8Nwٳf͞ &X*uf}<0/G? $s2+_zv2ķ?,c8W獸e0 OӚ?6$~A>ݱ]՛)7<ëVpΡhkRZ%OZ<\Jƭ Rf|VZ[د$֮-2,ĖCqb8,UI/03ykWԛWI[;bޤ@Z G53yb-|?ru'^~@aU'rf|-'?(uKr{$X?MFToTp{d͖>T>G=.i`Xi6eԧ^Půgex"9QgoL9xZb˹MM[,eԵfKu-VaK, ]B_)PycO,dHnmc=%,!<aϾ368UycO֙-d֠X$ig j` ?)~Fں,ӮE儬vl"x|*7kZq&=S_um4}icUHTWq?V)*D'2-)lB_0ZAqsjeR'm&:x ^=")%鶱q!ڕX-'',o!&ݮ`nA7TI^(_SPm_cqc*\X,{w A,)xһeZKE$zpWH"z&Yk:/Ol_X^O&Mcq$YeQؘx"ߙ=7Tt)m)}6[Yӝ@8]kTjTMa: S>̲-cffzQ ԓ͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛? endstream endobj 82 0 obj <>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/XObject<>/Font<>>>/Thumb 86 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 87 0 obj <>/ProcSet[/PDF/Text/ImageB]/XObject<>/Font<>>> endobj 83 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.9663 0 0 8.9663 62.022 528.5479 Tm 0 0 0 rg 0 Tc 0 Tw [(little)-277(work)-281.4(following)-279(up)-274.6(these)-283.2(proof-of-principle)-281.8(studies,)-279.4(and)]TJ 0 -1.2203 TD [(the)-269.3(advantages)-271(of)-275.1(3D)-266.5(data)-268.1(have)-269.1(yet)-270.3(to)-268.8(be)-269.9(fully)-272.5(explored.)-269.1(One)]TJ T* [(disadvantage)-536.8(of)-534.4(these)-536.1(3D)-538.4(methodologies)-537.5(is)-536(the)-534.9(increased)]TJ 0 -1.2266 TD [(radiation)-237.7(dose)-234.6(to)-237.2(patients)-237.6(compared)-231.7(to)-237.2(2D)-234.9(methods.)-232.6(The)-233.9(total)]TJ 0 -1.2203 TD [(effective)-263.9(doses)-261.2(estimated)-264.9(by)-255.4(investigators)-262.3(for)-263.2(2D)-260.1(measures)-260.8(of)]TJ T* [(MCC)-321.6(using)-317.5(Tc99m)-315(labeled)-323.6(insoluble)-320.9(markers)-320.3(is)-314.7(in)-323.1(the)-319.9(range)]TJ T* [(of)-344.7(0.020.7)-344.3(mSv)-344.5(\(or)-345.4(270)-345.8(mRem\))-347.5(associated)-345.7(with)-350.5(depositing)]TJ 0 -1.2266 TD [(from)-361.9(220)-168.8(MBq)-360.3(\(or)-364.3(50500)-167.8(uCi\))-359.6(in)-361(the)-364.2(lungs.)-364.7(These)-361.6(effective)]TJ 0 -1.2203 TD [(doses)-375(are)-373.2(considered)-377.2(acceptable)-373.9(by)-369.2(comparison)-378.9(\(1\))-373.5(to)-370(other)]TJ T* [(radiological)-266.4(procedures,)-266.1(for)-263.2(example,)-266.1(as)-260.1(low)-267.2(as)-260.1(a)-258.7(single)-269(chest)]TJ 0 -1.2266 TD [(X-ray)-439.3(and)-442.2(much)-444.2(less)-442.3(than)-436.7(a)-442.1(chest)-440.6(CT)-439.5(scan,)-442.7(and)-442.2(\(2\))-443.1(to)-439.5(the)]TJ 0 -1.2203 TD [(average)-548.5(annual)-554.5(radiation)-547.5(dose)-550.8(that)-553.9(subjects)-550.5(receive)-554(from)]TJ T* [(natural)-628.1(sources)-626.3(\(about)-622.3(2.5)-166.3(mSv\).)-626.1(SPECT)-625.7(imaging)-623.4(is)-624.5(per-)]TJ 0 -1.2266 TD [(formed)-270(with)-268.3(a)-271.4(deposited)-268.2(activity)-271.2(of)-268.8(between)-275.2(20)-264.6(and)-271.5(100)-169.3(MBq)]TJ 0 -1.2203 TD [(of)-237.2(Tc99m,)-235.7(giving)-235(rise)-239.4(to)-237.2(effective)-238.6(doses)-242.2(estimated)-239.6(between)-237.2(0.3)]TJ T* [(and)-328.4(1.6)-166.3(mSv.)-322.2(If)-325.1(low)-324.1(resolution)-329.6(CT)-325.6(is)-327.3(also)-323.3(performed)-328.8(then)-329.6(an)]TJ T* [(additional)-338.4(dose)-335.8(of)-332(0.8)-166.3(mSv)-331.9(is)-333.6(delivered.)]TJ /F4 1 Tf 0 -2.447 TD [(Moving)-336.3(Forward)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(On)-480.6(the)-484.3(second)-490.2(day)-481.1(of)-483.8(the)-484.3(workshop)-486.2(the)-484.3(attendees)-488.4(dis-)]TJ -1.1128 -1.2203 TD [(cussed)-360.2(the)-357.8(following)-354.8(series)-360.7(of)-351(questions)-359.9(that)-357.9(need)-360.3(to)-351(be)-358.4(ad-)]TJ 0 -1.2267 TD [(dressed)-641.4(to)-641.9(better)-644.5(understand,)-644.9(improve,)-641.8(and)-638.2(standardize)]TJ 0 -1.2203 TD [(MCC/CC)-337.6(methodologies.)]TJ /F12 1 Tf 0 -2.447 TD [(1.)-501.1(Does)-333.6(the)-334.8(choice)-331.7(of)-336.7(inhaled)-332.2(radiolabeled)-338.2(marker)]TJ 0 -1.2203 TD [(affect)-335.1(the)-334.8(measured)-328.9(clearance?)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(It)-559(has)-554.3(been)-557.7(a)-555.9(topic)-563.8(of)-553.3(some)-558(research)-561.1(and)-556(controversy)]TJ -1.1128 -1.2203 TD [(whether,)-239.9(once)-233(deposited)-242.9(on)-233.8(the)-231.4(airway)-236.9(surface,)-239.4(the)-231.4(geometric)]TJ T* [(size,)-298(shape,)-292.9(or)-294.3(solubility)-300.8(of)-294.1(the)-294.6(radiomarkers)-298.2(inuences)-293.3(their)]TJ 0 -1.2266 TD [(rate)-285.1(of)-275.1(clearance)-283.2(by)-280.7(MCC.)-280.3(Obviously,)-281(if)-282.2(solutes)-282.5(are)-284.6(too)-277.9(small)]TJ 0 -1.2203 TD [(\(e.g.,)-487.8(DTPA\))-481.8(their)-488.5(clearance)-485.5(rates)-482.4(will)-486.4(also)-487.7(be)-478.5(affected)-489.9(by)]TJ T* [(their)-425.3(ability)-424.1(to)-420.6(pass)-427.1(through)-421.2(the)-427.4(airway)-420.3(epithelium.)]TJ 6.7246 0 0 5.9768 272.6361 181.8708 Tm (\(29\))Tj 8.9663 0 0 8.9663 287.4897 177.9023 Tm (But)Tj -25.1462 -1.2266 TD [(solutes)-491.2(as)-487.7(small)-486(as)-487.7(albumin)-487.5(\(m.w.)-486(66)-163.4(K,)-492.6(0.6)-166.3(nm)-481.5(molecular)]TJ 0 -1.2203 TD (size\),)Tj 6.7246 0 0 5.9768 82.0913 159.9306 Tm (\(30\))Tj 8.9663 0 0 8.9663 96.4346 155.9622 Tm [(and,)-362.9(at)-366.7(the)-364.2(other)-367.6(extreme,)-363.9(56)]TJ /F11 1 Tf 13.6385 0 TD (m)Tj /F5 1 Tf .5501 0 TD [(m)-364.3(solid)-361.9(particles)-370(of)]TJ -18.0266 -1.2203 TD (polystyrene)Tj 6.7246 0 0 5.9768 108.2267 148.9889 Tm [(\(19)-10.1(,23\))]TJ 8.9663 0 0 8.9663 131.6409 145.0204 Tm [(and)-435.9(Teon)]TJ 6.7246 0 0 5.9768 175.5779 148.9889 Tm (\(30,31\))Tj 8.9663 0 0 8.9663 198.9354 145.0204 Tm [(have)-439.8(been)-431.2(used)-435.5(for)-433.9(mea-)]TJ -15.2698 -1.2266 TD [(sures)-415.6(of)-407.9(MCC.)-413(In)-410.2(between)-414.3(these)-416(extremes)-412.9(are)-411.1(the)-414.7(colloidal)]TJ 0 -1.2203 TD [(particles)-338.4(of)-338.4(sulfur)-337.5(or)-338.6(albumin)-335.8(that)-339(are)-335.2(in)-335.7(the)-338.9(range)-336.7(of)-338.4(50)-169.7(nm)]TJ T* [(to)-547(0.5)]TJ /F11 1 Tf 2.8263 0 TD (m)Tj /F5 1 Tf .5564 0 TD (m)Tj 6.7246 0 0 5.9768 100.1763 116.107 Tm [(\(3,4,6,15,1)-11.4(6\))]TJ 8.9663 0 0 8.9663 139.748 112.1385 Tm [(and)-543.3(the)-553.8(more)-544.7(dense)-551.3(23)]TJ /F11 1 Tf 11.6911 0 TD (m)Tj /F5 1 Tf .5564 0 TD [(m)-541.3(geometric)]TJ -20.9162 -1.2203 TD [(diameter)-554.7(iron)-554.2(oxide)-555.1(\(Fe)]TJ 6.7246 0 0 5.9768 161.5181 99.6661 Tm (3)Tj 8.9663 0 0 8.9663 164.8629 101.1968 Tm (O)Tj 6.7246 0 0 5.9768 171.8929 99.6661 Tm (4)Tj 8.9663 0 0 8.9663 175.2377 101.1968 Tm [(\))-556.9(particles.)]TJ 6.7246 0 0 5.9768 218.381 105.1653 Tm (\(11\))Tj 8.9663 0 0 8.9663 234.4251 101.1968 Tm [(Particle)-558.4(size)-554.3(de-)]TJ -19.228 -1.2266 TD [(pendence)-282(for)-282.1(MCC)-283.7(has)-276.1(been)-285.8(studied)-278.1(with)-280.9(ambiguous)-281.8(results)]TJ 0 -1.2203 TD [(between)-262.5(laboratories.)-268.6(Some)-264.3(data)-261.7(have)-262.8(suggested)-262.7(that)-263.1(there)-263.6(is)]TJ T* [(a)-410.5(slow)-413.9(cleared)-416.8(fraction)-414.8(of)-414.2(deposited)-419.9(particles)-414.3(from)-412.5(the)-414.7(tra-)]TJ 0 -1.2266 TD [(cheobronchial)-240.8(airways)-238.2(that)-244.1(increases)-236.5(with)-243(decreasing)-236.2(particle)]TJ 27.9978 52.556 TD (size.)Tj 6.7246 0 0 5.9768 330.2928 532.5731 Tm (\(10\))Tj 8.9663 0 0 8.9663 344.5794 528.5479 Tm [(This)-359(seems)-360.4(especially)-357.7(evident)-365(for)-358(dry,)-358.8(ultrane)-359.6(par-)]TJ -3.5155 -1.2203 TD [(ticles;)-466.2(for)-459.2(example,)-462.1(Moller)-464.5(et)-455.6(al.)]TJ 6.7246 0 0 5.9768 444.6424 521.5746 Tm (\(32\))Tj 8.9663 0 0 8.9663 459.8361 517.6061 Tm [(showed)-460.9(approximately)]TJ -16.37 -1.2203 TD [(75%)-645.6(retention)-653.1(of)-648.2(ultrane)-644.2(particles)-648.2(\(100-nm)-651.7(median)-645.5(di-)]TJ 0 -1.2266 TD [(ameter\))-498(deposited)-495.8(in)-500.1(the)-490.6(tracheobronchial)-500.8(region)-495.3(by)-495.7(shal-)]TJ 0 -1.2203 TD [(low)-298.8(bolus)-297.9(methodology)-303.2(at)-297.2(24)-169.7(h)-294.2(postinhalation.)-303.7(However,)-299.4(for)]TJ T* [(larger)-539.9(particles,)-537.3(recent)-541.1(experimental)-543(evidence)-534.4(from)-538.9(Smith)]TJ T* [(et)-594.7(al.)]TJ 6.7246 0 0 5.9768 334.7149 466.8093 Tm (\(33\))Tj 8.9663 0 0 8.9663 351.0991 462.8408 Tm [(showed)-587.4(no)-594.2(difference)-592.2(in)-588.6(tracheobronchial)-595.6(clear-)]TJ -4.2427 -1.2266 TD [(ance)-299.3(among)-292.2(humans)-297.4(for)-294.8(particles)-300.5(with)-293.5(geometric)-293.1(sizes)-296.4(of)-294.1(1.2)]TJ 0 -1.2203 TD [(versus)-245.6(5)]TJ /F11 1 Tf 3.7495 0 TD (m)Tj /F5 1 Tf .5501 0 TD [(m,)-240.8(but)-233.9(the)-237.7(same)]TJ /F6 1 Tf 7.1639 0 TD (d)Tj /F5 1 Tf 6.7246 0 0 5.9768 420.3212 439.4267 Tm (ae)Tj 8.9663 0 0 8.9663 428.9952 440.9007 Tm (\(5)Tj /F11 1 Tf .9864 0 TD (m)Tj /F5 1 Tf .5501 0 TD [(m\))-238.3(so)-238(as)-234.8(to)-243.5(deposit)-240(similarly)]TJ -14.4668 -1.2203 TD [(in)-329.4(the)-326.2(TB)-322.1(airways.)-323.4(Very)-324(ne)-328.8(and)-322(ultrane)-328(colloidal)-325(particles)]TJ 0 -1.2266 TD [(in)-411.6(solution)-411.2(\(e.g.,)-405.6(sulfur)-407.1(colloid)-410.4(and)-404.2(albumin\))]TJ 6.7246 0 0 5.9768 493.7384 422.9857 Tm [(\(6,34)-10.4(\))]TJ 8.9663 0 0 8.9663 513.5242 418.9605 Tm [(appear)-407(to)]TJ -22.3578 -1.2203 TD [(clear)-268.5(at)-259.2(similar)-262.6(or)-262.7(faster)-267.9(rates)-261.1(as)-266.4(larger)-261.7(dry)-261(particles)]TJ 6.7246 0 0 5.9768 514.1479 411.9873 Tm [(\(1012)-10.7(,30,31\))]TJ 8.9663 0 0 8.9663 313.0582 397.0771 Tm [(and)-322(do)-315.6(not)-316.5(have)-319.7(the)-319.9(high)-318.2(24-h)-312.7(retentions)-325.7(observed)-316.2(with)-318.8(dry)]TJ 0 -1.2266 TD [(carbon)-250.3(or)-243.7(metallic)-247.6(ultrane)-245.8(particles.)]TJ 6.7246 0 0 5.9768 456.6046 390.1039 Tm (\(32,35\))Tj 8.9663 0 0 8.9663 478.318 386.0786 Tm [(On)-240.4(the)-250.4(other)-247.5(hand,)]TJ -18.4313 -1.2203 TD [(there)-529.2(have)-528.3(not)-531.4(been)-526.1(direct)]TJ /F6 1 Tf 12.9493 0 TD [(in)-524.8(vivo)]TJ /F5 1 Tf 3.5851 0 TD [(clearance)-523.5(comparisons)]TJ -16.5344 -1.2203 TD [(between)-357.4(these)-359.1(various)-357.7(types)-355.2(of)-357.3(particles.)-354(Sulfur)-360(colloid)-353.5(par-)]TJ T* [(ticles)-406.4(\(mean)-399.2(size)-402.6(200)-169.3(nm\))-399.8(and)-397.9(nonaggregated)-405.2(albumin)-399(\(0.6-)]TJ 0 -1.2266 TD [(nm)-234.9(molecular)-235.8(size\))-238.7(delivered)-235.5(by)-230.1(microspray)-238.8(nozzle)-236.2(in)-234.5(a)-233.5(small)]TJ 0 -1.2203 TD [(volume)-499.1(\(6)]TJ /F11 1 Tf 4.8054 0 TD (m)Tj /F5 1 Tf .5564 0 TD [(L\))-490.3(of)-496.4(saline)-498(solution)-499.7(to)-490.1(large)-494.9(airways)-497.5(of)-496.4(dogs)]TJ -5.3618 -1.2203 TD [(shows)-604.8(rapid)-596.1(clearance,)]TJ 6.7246 0 0 5.9768 408.529 324.3401 Tm (\(36\))Tj 8.9663 0 0 8.9663 424.97 320.3716 Tm [(with)-603.4(sulfur)-596.8(colloid)-600.1(completely)]TJ -12.4814 -1.2267 TD [(clearing)-343.1(the)-338.9(airways)-339.4(by)-337.6(24)-163.4(h.)]TJ 6.7246 0 0 5.9768 427.4077 313.3983 Tm (\(7\))Tj 8.9663 0 0 8.9663 438.1794 309.3731 Tm [(There)-335.7(were)-343.6(some)-336.7(differences)]TJ -13.9547 -1.2203 TD [(observed)-309.9(in)-304.1(1-h)-300.5(clearance)-308.5(kinetics)-306.7(between)-306.8(the)-307.3(sulfur)-305.9(colloid)]TJ T* [(particles)-483.8(and)-486.4(molecular)-482.4(albumin,)-477.8(with)-483.2(the)-478(latter)-485.1(having)-482.9(a)]TJ 0 -1.2266 TD [(larger)-287(slow-clearing)-289.5(phase.)-286.6(It)-280.8(appears)-288.2(that)-288.4(small)-283.7(solutes)-282.5(may)]TJ 0 -1.2203 TD [(disperse)-314.5(more)-310.8(completely)-309.9(in)-304.1(the)-313.6(airway)-306.5(surface)-312.4(uid)-308.1(and)-309.4(be)]TJ T* [(retained)-326.5(for)-313.8(longer)-324.5(periods)-316.1(than)-322.9(particles)-319.4(that)-320(may)-317.6(associate)]TJ 0 -1.2266 TD [(more)-393(readily)-387.6(with)-394.7(the)-389.5(mucus.)-389.5(It)-388.3(is)-390.5(also)-392.8(not)-392.3(clear)-388.6(what)-390.7(role)]TJ 0 -1.2203 TD [(airway)-521.5(macrophages)-521.9(may)-513.6(play)-521(in)-512.8(particle)-520.4(clearance)-523.5(from)]TJ T* [(the)-408.4(airways.)-405.6(Sulfur)-410.6(colloid)-404.1(particles)-407.9(have)-408.2(been)-405.9(found)-403(asso-)]TJ T* [(ciated)-486.2(with)-483.2(macrophages)-483.9(in)-481.1(induced)-487.7(sputum)-484(samples)-485(fol-)]TJ 0 -1.2266 TD [(lowing)-373.4(inhalation,)]TJ 6.7246 0 0 5.9768 385.7385 203.811 Tm (\(37\))Tj 8.9663 0 0 8.9663 400.1385 199.7858 Tm [(about)-368.9(30%)-367.4(of)-363.7(those)-374.6(collected,)-368.7(but)-366.7(it)-370.7(is)]TJ -9.712 -1.2203 TD [(not)-379.7(clear)-376(whether)-376.1(this)-381.8(association)-377.8(affects)-374.5(their)-381(rate)-373.6(of)-376.3(clear-)]TJ T* [(ance)-337.2(from)-336.6(the)-332.5(airways.)]TJ 1.1128 -1.2266 TD [(So)-393.3(the)-395.8(question)-402.8(remains)-391.6(as)-392.8(to)-395.3(what)-397(the)-395.8(appropriate)-396.9(par-)]TJ -1.1128 -1.2203 TD [(ticle)-367.1(is)-358.9(to)-357.3(be)-364.7(used)-359.7(for)-358(MCC)-359.5(measures,)-364.9(one)-360.1(that)-364.3(mimics)-356.9(bac-)]TJ T* [(terial/viral)-309.5(clearance,)-311.4(tracks)-309.2(mucus)-304.4(movement,)-308.7(or)-307(tracks)-309.2(the)]TJ 0 -1.2266 TD [(clearance)-359.1(of)-351(the)-357.8(airway)-350.7(surface)-356.6(uid)-352.3(as)-354.9(a)-353.6(whole?)-351.9(With)-354.2(new)]TJ 0 -1.2203 TD [(particle)-356(engineering)-355.3(processes)-355.6(\(e.g.,)-348.7(nanotechnology\))-356.4(it)-351.8(may)]TJ T* [(be)-320.5(possible)-315.3(to)-313.1(develop)-321(particles)-319.4(of)-313.1(controlled)-316.5(size)-320.4(and)-309.4(shape)]TJ T* [(that)-307.3(when)-305.5(deposited)-306.1(on)-303.3(airway)-306.5(surfaces,)-303.9(\(1\))-304(accurately)-305.1(track)]TJ 0 -1.2266 TD [(the)-490.6(movement)-482.8(of)-490.1(mucus)-481.4(from)-488.4(the)-484.3(lung)-486.9(and)-486.4(\(2\))-481(allow)-485.2(for)]TJ 0 -1.2203 TD [(multimodal)-493.4(imaging)-484.3([e.g.,)-487.8(SPECT,)-489.5(PET,)-484.5(or)-484(magnetic)-488.6(reso-)]TJ T* [(nance)-523.9(imaging)-522.2(\()-82.7(MRI\)])-518.2(provided)-527.2(that)-516(they)-526.7(can)-514.3(be)-522.8(labeled)]TJ 0 -1.2266 TD [(appropriately)-499.7(for)-497.1(each)-495.3(technique\).)-499.6(Although)-501.3(we)-494.7(approach)]TJ ET q 1 i 102.387 732.245 m 511.937 732.245 l 511.937 594.482 l 102.387 594.482 l W n q 409.55 0 0 137.764 102.387 594.482 cm /Im4 Do Q Q BT /F7 1 Tf 8.9663 0 0 8.9663 62.0787 577.7006 Tm [(FIG.)-330.5(4.)]TJ /F5 1 Tf 4.0909 0 TD [(Transmission)-331.2(\(from)-337.1(a)-328.3(Tc99m)-334(ood)-327.7(source\),)-337.5(Xenon133)-328.4(equilibrium,)-336.6(and)-328.4(deposition)-338.2(image)-327.4(\(aerosol)-339.8(of)-332(Tc99m-sulfur)]TJ -4.0909 -1.1128 TD [(colloid\))-335(in)-335.7(the)-332.5(same)-339.7(healthy,)-333.7(nonsmoking)-336.8(adult.)]TJ /F4 1 Tf -.0063 20.2902 TD (264)Tj 46.3849 0 TD [(BENNETT)-338(ET)-338.7(AL.)]TJ ET endstream endobj 84 0 obj <>stream AdobedC       U s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?Yh17[o6Q,d$ޝ: {;덱fԿi+WxCJR;3D5q+lkt aST J3\\PusS)v'Ajc`8eR,8k\is+^UcEd$W-#0L/͎ NzpSfJg?7)'YfZcPI19[@\t4%kE|2!YmDS,#.)qcSPqIX 9-7:1:7(!##Ͱȱ8՟(38>'y8=Nٯy26Ʊ HU`ybt@B*>LQ"C*J *1^;tf pJVNdoҘqw,1)Nm6}n%'hT/թ@W0gtRxۑaniInyr|FɩExZdOR\XS=wV*3`YoZ J>ɾz+΢$` HUV;V,:pǡM6#-pұ W? $z|<0TVp Xt'_ae굮R"n mn" ̾_4<1ދצn=Sc+]p3͖:㌛Rm&W 6?W *>XS'wqdڍ SSS U L&JIN[jJ-W4ڙb{xU{W٪F5kHޙ+м-r\3۩K|<ڸOyh@c]} Z׶%?;cС)/v\tzvl Rjx`fgiyvدL@ hNBz㾱l^[KX~rOVlWj61ʝp 8}b!E]ƍ~/&"*WQsu)0w]] Pɹfu%wi2˥$ɔTiL`}^{G* 깩8)? 9qk>q])n]!IF#iװ\LFk) $Ħ3vs9EW2M"g* tkev ӭ|-+am;b{ߦVdX8Y{ںq1uD5Mupl+z{F> ?1/²,c9#^ܧ'yr7&1<1rz伈1T@:np-ŹZP`^&9e(0"g>>)⳾<#[+=(o lƕ2u8P:f[A=ɶhm&W 6?W mλcCLQ4 8z%ŌQpKf1#e;J4%CTV2fn tiOܻf0&oH4{kGՇ.ja;VDM NS;fhA-qP>izR!~syJ,(p::wŋ:y 3=pe2@KxhFdAln'~ AÙl_Ҷ<09LiT@EmjU׆m)cb:FGjC;naS#͹Su=Rɾhf W6 Io\#sm815;Z)8oLc--Pj΅8 F}Q67rh [M|qPlzc̟ zp3P~3!m|.l9~9b qTb,3lUh1eNI5k,@ژ]r55y P/|>8/.3_HP+2HN !Abmhi]yð8Kz$p$9Mcʠ\F4"}=7ɕ¯͏n5C>|I5N4P7KP)B3zVw9bgZ)*8VSű)ݢc `^qOIyq5!"f%ml:a2ջ`iJި,%#N3ʀ ج N[xc4,ծ]Ì8P[SXG! 68բ8O J%˶[Ĩ .%b1Φ>8:ٽ8h>enm(;1a6jRD_S4jeNͪ(NHY" D[=DAl&Oa]Æ]ک n2q=ѐ`1PwY\ڋUp)f>/S|wI'o"tЉM \"I`X-$}YhEbRjj9 '0&e 3[l7˲A |B),C[:ɸcÛtYG2s˫{$aH',aZ)'n "b)y ~ r˾hLgs_l^[{ 1aQ$6mF 'L5K0cś:5!wJq9'HSс8EUkR%˞:mLelZ#ŀ~X4adp- px\+J ڸBۋ B 6服1".$Izȵ,s?Eto+_+lk|"pSc^1 'F1꠯,Fs]狓mLVOMq+Ts^/G(ZbCPq D4"F*ъn) o=?r܂y}+]:Yn!q+'+*)v=ʦ`iLNI%j1w!*p0A*Tl d%zS.>(J@|I",+$%Qd%aDjllWP\0aS `؞ā Sk Hor_1}<0&j C6E*7N4 <mCP,Y@+\)Pڸ >Yv. wX,GiS!+Ҙ3 ͅC'Mr)Mogq7g'rLL[h֞]i-8:}X&M5.ct)9'aݽj:e0ҽIcEL()>i06*=!Sޘb RW\X/<;`wҤmۥpdQP@ZN@s 1kڊ9<3Icq4fi#c^L&sӊ\Zi  )C^W5u&zbnhr|s?Eto+_+lk|(:f18j}*lZD  (qW`{`8C^08"fC68E؊WȱЂ1],E?J{ࢤIT]uv|q!uY7v\BFءQ?낁~iN»ꦟjP&Dh+"qB?сeW-\Pm=?lO`*$WN⵺KC^8gK#R5ǷH}-A$n:H Z-8JAq jsvlz wN K0hOWj`G2N/nc\GZX wQHGna[BGNUwgPW4H$Ol mb=0oL3ӵr*}d3Z=InFh)\#zޣH#O@KP*]^4ż+=qNW周ӌtΊ ҃ũ ^;G:;8q w ȂvSzq/O[?/ռFw'<0mȦq6mCա ( pp|Up}oD AraoM8-л5kg ێ} A5< l__uyCjdkof7-ȷ+n/=q\W2)ZAgI5ˋ~M}h lL9( vĚ*kN(06epc%Pϟ7Mu8& s?:5Es\7ug~q-Lv/(@`@tl k1)j@Ϧ9S(][W m=b}cާ.‹$(FfyOlJ&,Ri/te V T^z| Íi چ]C (wS#ˈKƝ{g ]r3We17#go)+ \*_c_3ͦCHJJbڃQXprz(z % 1{ cN\1K"S6XdqJⶖwL|$Z|iL/dec\iSz/\{;7ŠhAsY\^!$+{b"0}P z`[sKGrƒQ덌FQg~eQ>;`P{4~@ Nq;doќ5b'C!* ˅jRTo )}Y˰|uRM?=qT1=&iHDOݩiGA׮_ME튵x;dH෥jv#Qz8`j@J;l/,\L"1uQL]^z])aL:M&YD֢;YHvlb\L8]_Ԝ%Zo4w%}y+cZ W1x q}.n5BhN鶷_)58Ab6Up D)S\٫k!7Mc Rwgl)ʭPkUapv0X-ܐlpQ #h+B*:e0 ewWF`5Cឡ1B\1"?@gȿnoO & iJ5s UHS$N˰&amno'o!im. T[GM?Q(8+U y%@E0FX}'wH9T|[b.'Jw*܇|29}H4>X}Fc[ Q4)`%V8*>P:c Q@>XWmQ $^T'|!@US7V(v?zjA`i밨ICQ}<7ɕ¯͏n5C>|O `4^AoTçLV4X:þ*NwW20mpH[xGanAU_x ViEb(G/=Ҧ8_lN奴u@ \Z;u3W=F%,^2NM;dVGZtMc .XTvu*l\\@=iycמ\`kˊCL:dKAnOonA^aad#nlaHkX G'h[ P^ +n0IH;`bA[Iħ_*&\JMd=[ ZJZayvԕӅ`lZ\FMv醰ȩ v/Ⱦ>@L۾ñʾaQ8ɀ𰿙ʱ#!*k޸wssJGT$+ a1UTt lq ;Lc% GDž?dg~!ny^,3P\zNp+ZS4!x EޔM!t2r/!`kvR9VnN!GL^䬁iǹՑj2Q[œ,*q)/Jrޘ[p_| t=E)d+H h;ٵ ! 67Z.٭EQN<Cc }7thib%)\sHkVpmn* n[؞Yq*^(Pu !i?Eto+_+lk|'a# A֘GHL[~15.*naJ(t6JbNlsWNiF.(>#C=$#J%ʎuLK4΁#2VFWӥ1K+(XE@sN9-|af/ j /! 1FD<=!fH,^ա_:wq#6]əpA:^O?rG=2FD*m2BxTܯ vfmG҂k,;QۭO`1ĶNqf?9&Mktx#_PoEo0b7Zz_QWza17"axGu]vTaTWgZ=B+ 5Q)~?zb, - $.qTEQ}*$`ۼv2uW .,-Ha=VKY{ v_M[!bq -y;N2+"_2+3^!~ t$Bd"J L@GI?!Dg5>傴<3Ѫ\1r @ᵫDe۬Ӆ {dLV->0fN) ƁpNӣS$Kac|Al]>OH1sͦn-+ FZ8 1L8Yp7'bqP g+K(ZXR0T1siURE@mŤojpXUbJo!: FV 5J\/R1Dt /,*P8<fN4Z$ +XsiMzO)Ym&W 6?W v.A_~U6\ld~^2I:k4KnkbQ"-㹉a"c@k"̞}ᅥ.A.~.*OZmk&p{  EDcb6>wn[]Cc$V!2̚?\+y:{%v#aZ>-B(4QŽۏkIoRF csEI\'/E˯|0 a 5Z\neJSev"im!UV+`:oL uT#̠^/?k\9(Ӭ}6Kj2Gn'0F+spuGHfnkֲJ!ɩ\#- l)eA9FB8mD >~,cLɚ|=Fh]@Ju I 0PPzRB}\d@=R|@8EKٸ-\BJ՚M11O7_ZQQz:Ĝa[>:Ws_.70~hSl CvWD` [M7UIʾQBR|25y}qapbD,.uDx ˝9|)[ b_Yvrm| 9?dn} ? gsȟk`&<^9`i6~;SYÍΘHyS\i%؜?hH*`rOhw =zi^HĆ =RH%Z0ÿ4hzS|Y`PJ!-zUV4' /_b09r|4)ڙ$ hFa(:NE˺L#㒝JPmOqɤߕhN[aD&XoaWIc,rV'jd }.ljp<ʤro~m&W 6?W w 7'iL/ ޹h)m\P ?IP!OwZ_GKCKIڬ|2wO}F&ZٗNX: M(@q }-Tjq(N!t/=8'@?N)-Z0٥OI> V[ݺ3򿗭Z; "j>ط.5G"ܖ+Đ(޸\$5յ婲G䳢զ&/##Jm'<O T-rlp-7I VIi)op( "9F *{zGS/\ \|KMWJA8` .`7w2I Qy ^jd&˜O2ĀQ UbM=p rkݏ+st¥eIrZF*HPI$&Rkz0C7AaᆋiD{m AZҹ._.\#ƴ:S #c4Hj˂[&ZMb$tVûONKs!2 g֘iNꐨ+lpzفC@:0:*~š8׌s_H2j>B5I-.)س1^7TT߅ \I[޽r4N韔ѿL~lwcoiU2I9Pa^nY UEŞXz1ү"MpԐއ?` ^#KlHO^Kp="a)=0XqP$]j0(.^Aox0tlI/O)PR:{ 3TKo)aOOlhrrE & M%k&L kK: |b-Yy{oV_7P[0<. 0酏hQDnc_MzjuZɒ_՞X't 7X} w,^ʍuPNis5գЇr[oK[j=p:e:9Ҽ#0l5D^%N^M ЃɘR4ƍ)J!"I ޸ K ~eȁ#jS]xgAm\3@#>KnJoi?CUq` \7WR\T661:|\8淨S9圖k.=yhV2pݿ GLA'&.6'I` 0S_?Eto+_+lk|9O|9t2폋*(MO!Yxk1r0faM %lsR\ 9/i; ALH {Mw1f|_is,kSy>;=^U#a_I۰$ohF> `nYnZoჼZBx)sI qMjV4 Q"=^ؤSHv/W^_F8,bա+IxJ:eʭ.WV5 /%iuڹH4uTR% 倭|+۵>>é7ea16޻itP/d>=!^=\kZ>$aE×'i.;a[&-֘6/Z(.̚FI43붂^8g9 ktli]w a.-iO\IlcYHȾ#I10+Vq§np˺ƘWDa z{W[ 0vrqmޢxd}d?O{fUA"qulꐗr|F|XY~>^E{WUbҞ8Aʱr4!3Ì9IοF {ƈ{DҌl4j'(AALE n{K4L+.*?`[$ާ!J yvX7T!T^#lwY5"H3}NeRCW"7 W ';y.kOϥ^SWFo2Uƿgϝ À>؀Tdz1p=<6_, ;ڄsJRa~Z)HtN>(1{O1 C\ŵO4 (-`,_l+6zıAqM*&Ii^`{`&ǜ̥ȢREpZ%Ȯd궋}ۻ\Jl [2\wX<ŴO73ۿ:4!̒Bf: ~󷟁iG:wyԔjXYtx)m ~`{aҧl֬l+_2=OW ndlUF1㫆LSÔA@vë-GM[S 3l&v?v‹!x,uМZ B]}fHF5{aߞ.Rb*ݦBfmFu:TBh6t;=:Ux1Ghdh(MY"_C,iL׫!+lyA?,!FI0 s|r[$Y.A:B /PXrZ4aΕ6E}fj$bҬ[.f/T#I/#EsSN۸-ijIۋI<<3^wH$hyD|g ὤor=Ÿ!W o 545Fa5. oWlv QԿw/̮ۭ[OioҽaA/XSW,ݻ9>vƗkX Ȫ7]5 Qi3^ǶM?V{q,p~'#bxl\Kq$]ؚ[Oʴ*HUN+Cu b*hrEjHH$dHBW|.z*|:;i!PzL8^@~- -1$!a,p9|u펥 H8KZ|)(w8,͸P3k{Cq!_凌XdF9ZpX>\hہK|(06ep_%Pϟ8.qGӃ- mˏlSMF7T+W_k2o nŠ-Bmm14޸EǫGF줚\y;ɞa7bMb%-T9%:Oi=պ.9CLOϓoc^#*GS98짷%8}]m텒FFp;cCHvĚ~2cI/$O>۳5I&S+#K<[ >fWaW|z_4dP!ayNU-]ssyW[v␹RA=&@kBrIZd]\ U_k}wnƵ!\ؒԮ⭧\El,GF=0en?g=9\+ziMpx?AD+L5G(,څ&yv 2}Q]Ia 52FpNM6̞8$;W+QmTM>Ó Oq ңfZuH޸]^MlǨNn.Iv;ao_f.?֥9&2)۱Ȱ9k5pE5J>㥚J<@ޡ  2 X$YcVQKS45jx{iHwdR6&%V?*A6rmM򟖴D\H|BXb1 O >qv0*It3@8:/e0%{Q2&0u#:*Kp"&G5"[=Fg .0b0#?,_?Eto+_+lk|1,9ƃz?Mӥr & 9. ӑjs4}̡+ĞCGg\]E*gF/v>RB~%!9Mq_AM %aQ05(7гGOM%˭ )1h$+iڎrOS|ǢhqO\ yn9 i^[,<)~ck7AA N$Z28}rBPDaUw&,jCK.Ev9HcX51ZqR90]iuZ`tq\[Pb^'}/|ͥIhF5l{IV2$mH;Sr Sj,^*=LÐ) ༐S]Uhb|b+B$_{~^޽]I(K߮s0:%c<٢60UBz@vlerfu}PON}UXSCEB-m ' \Z#I04Y6ם>wAB~[g[ҿ3,/%G~a 9[LNO"{eudsMN}ż0BTbn%V6ɤ[}VuH[ mRQ)l3o<նfBZn ȅÃB8 Ҙ'Jd0tkJ2FfBVGJ ӥ@$ t1|-a W!yX"]4R#J^|S,etWF@m}En{ VuATuMCY;?` )TKg#SL97w@Le8A]5*)SgQXI^9 3,ϲ/)jyKNؼ"#*]t>L6й|[ϥ%\ΏugvM SH^ ZUjYJT5O#j[$]$"W=cE -@D Z5!tK;[Rҹ;jK%Qk=뉹1I[:q R;dv~'U| %H_ V}"7ɕ¯͏n5C>|c1T|E-`lQOɏkHykaV0cl)!gj2^.#&͍UJbחVScF PyZޝ،:ЮWFgþu84>ALޏKcNЬtZLDc.~7q/+A{p)k3ݝB #>r2|w| 0nm@+|`bB?F}MgwBbRWsFw}@um{ Ϊ9嗔-]YCv֏eQy|z+yg`߸ lohs{`<4|~Mk~pfזH1*{f5~lFܭ" 9j}!|mwb&, 05"Zlח$lrڲ}St.u9G$*1זЅI*{Z(:m(6E|u?.ZGca}wEY: tT 8`GMkA˻I>3u*X}F.e AFGba;!36]MIJ bO=>&$ӶL%zJ+a0G2%tDƇ$BZ't7E[y> Tl .sy%Ƨ dМwCb*ztl4F党%$ GL迺#r7,^f}yNfUpolm"1儾g63"F9\&-Y<5x ș/} 3/Kl=qL;ҮJm^Wh_5ӭITS:O.8*8H,zO,ϥ~S[Fo2UƿgϛFim#v X&bk7NZ?Y1ᶝ4){s݅LXҘw_,XE{m4T6| 6nT&|Vyzid 3DcY">BmjװD,kP fA1Ĵ0;d:D$HXRΊVP|pTU4[Xc P_Uĕ,]bs4pqyV OcA!aYΝ)*Nww^KY"QU~᭭]ۯ#@r0c'-p%+X'#qJ@N#"R@)%Any0u zwX Kb|1m*#NY ~lP(9O6B-^Jz򻽜bO#+N/x0 Mn#C:,:EVT:0}] "ݖ/p=eCmӯ Ljztb_L l t+TrvcvmC4\ -~ en!ka FˊXycQjUw㐎;}9 =S8؟^!be+\D\Qn6ԸGfuJ18g?V]&FwG戯EFtHKyHG`pͬ9W SLG`i~kSwYe4ZĶ.fko. !9no9r<찺,FT'9vF?eFu4@^ȝ豺ӟJ(06epc%Pϟ9=H@#zb7F9yJj%ieDpzOo,\Q;5{-&|Lj>dzҼԸB9d[x4&Wc <|ע |L}tO/>[µASGPI2ۦ?3_/aQȌVsqs!==)1ԡhl~&_\WָSϙ ^Sd sv+}"uy)P3^BmásZlt.5(Rs{ѵk_11^0M ԌōrYi%P1F|bnmn5{RYb@1*N:VRX-(:F.*]!SI"ZJk1+-JDû rH;f?#]WW J$?cTn7P=IGo>zl|,zmjzhQ)lzF4-̻ioH+"ؘZ.}S [v C^@ey7=F7y>8qd,Qh0KY˩GI! [sM TI̶Mpwxo.X_7Q7%W5V%e‹{b G`rSleP 2Ae`#;wȅ7R ">D:$Pq20  ꏄta]} I źI2l'w$7*T g_/yI"3L<l#y䕨LVL+Ϥ7Nxv3Wl}zɯa|Ny pU\NIPY+\ꚢ#TLOY )@0k(tCIeAE;c쯮$V<0T+pd-B $o 0ɏa1|*XVcw@p0:qu;iqjx}R~0aVڕQŲ%խ55-,PBbǾV虜[h=\ͪvLmS! s$!["ڲH.HsRa,:H}"7ɕ¯͏n5C>|TG@rؒf"`&a4jv~^iF(Ϩ+W[ZX=ŻVT\/TK4ýT܇CL1t**:o1_UoӇ/ ޹dI`Sc!&}ZaH푍Sz%[a‡vi- |)1@ӈ?0C*raMZ[ORǧLJy 1GLmel$±";?hZ[8'9|.<(Xx ,ᴸ6 "kOFRBN^Nv=qKt^\`O^Jҙ5-\!bW% 2^QZdNA ]<6SJŔ\4za䚜rۭ\gtlSi|5; n"Ĕ9t,T1p?,y\jq`hj7)D|tqFCTVM{OJ1 tPD;zd5xF |dZ/.;7lJ`@|PE*=>ek @ryY- j2'&-B^=@P@()CIϪhLǦ5T!MG(1ANԦ|G怯|a182 Ij@|rI4|lWm|ܱU lHeS鿧"ؿ4M|9z:23k%̈!pQap^ZRP&՟H|(06epc%Pϟ9`\ODr[Ta <:M90ȺBk/2 /]} ~x:g-@,~YZCPͩyX!'$/G:Bp?+&}z`}]?GJ .hr+M`'^9K1HHQll-cZ򴺝 |yFS 8q^#'G;Ԥ}ı"WRHzDt熰ʲ˷<7/,/ƤѽEuSV*q%kω{W-EѮ#ic(?T\e샸8_2z`^3ɜHq퍒9jlji nD]?LuHZ:+zCY݊f:vx;mO8P7‰bVP6H /*PI2'7]R]Bmd m|]AU5Zo4XƧ/K@=H w%Pn3Z[)I{7h>h)Bg3rz}Bo>3ei69UON#uPiR2mpZu=홃ёvڇ^׾I!\GwYPd";ot3Z8gsX$^QP#,݈`]J;I%QpǾEPSD kzzW/U$6tvQq,lp)$"ëxjGpP:\r[J0MBE4kЀI)Iӄd0IKoN~ z.`%SEE:Ws[kqw70:W gGa'O3/^d':,yd#TӴ(9c\G ,#F5D;wq>Rm>m&W 6?W ye:q7 Qm  }F]/K4K\+Narٖ6`[/u8Ui,T7B0O枩w h"Fs TH& wW/LMhiu^[bg0 O=\&7m $rf-Fh 1oP]W\?򵝽RLBh'U &}ajK<ܣrƎH0T(T`!{s1Tc$l5+88>\ pkffec75xzW2%ܩ!.,Li%4LHoh0Ejn([&z٤H(k&i[[*Kr#joZy0ۺʬ$VfPIHZ4JB tZ ʖ7 ׶C!gudN$qGd"#:ݿq|//y@g4E|O +)W$j~I|dNLl(3ުZiQ)ѹtoiK6OC^U5 4 ]Z%w-l&;yܐq+$ 2;ZG 8k٤ E;0HJoQjVkEo|0jH4*zBkprB[S=BM3{us^jcbp0U),QМ&n ޕ*C8poZ6E2Ki~&Op/bcFsrDRN&Y =^؀OE(06epc%Pϟ7R#P"YW5Ԓ4hzy(RWZLjԽGk6jmAL67=%A)OגߖE-)+#.0[x5 IGHe=Q^Լp9=ۛY" ?k|&ԭ"Ԗӣyx%^',M*;`ߞt8ek xu,'tDw'i4Ʒ'' n~>V%¿<9ޅi4o 2nW9. e鯤F >U2J Jtg3@L Jt֞%\?.8?Q=S0 W)$MW8$8=FF.\O> s[fۉݶ\BSII1{#;y'sBU[,:p]5ԖH4(]Tm:ر`b@M+Im";a-&ݾ5lKqFt8R:{ʝisYf~jhsͧ"[z藉R .BFOu5BLpI'zN'$kHj"%U[;~-Jc,0W>*=|up# $z'/!2JATр<}fj쫧\U=pF%c$Jkaw21 SE&]&U( "c3~Ò@5$"L"-W:b~1O+h+/嗛?]ʒF( %廨E@0R[ӭ1bi:9;sR[iO);gd M4R@;dm^YKM:! T2Y˟0˨=ɘkCv`ƅv41'F$瑘i1?3NbcޘG$3 \k*|q;W / KҗI4pI -OS1(7 \*/) Z 0+Rh0Uq01}.IcI!Yj5xa}QhѼ ⳁ :i/xsRh17Ԧ>_> D#r7<#= M[&y@8^E~><#&Dz8oZݰt!4 5 \׾neo0QM0{]dRKbG=TAF9[OlRE-Z[h-К P2˧]1=-4 ThP}]:Em`~*"ZĢ'#}|0{; %wv Rr!t.Rrm{M׽q4(U~[d@q)v~= 9.ap&oMEQ!,;1'Ҡyz ȴ4ޯǽ6kdsސ M. u 1+u«KCUqva|=#DQ#gWzm:r8x} IwJb֕LZvޘK!=+MWqEKóƇ*C!~f*E'CȽ޸޼ "kg$Џd INT&ʻTO[ Z,h1k'w! ]e;VԚEUNuo7L o.Mzx@??`g31iM>c%p-j+ҙ4Ɇ?G!x8wNZO#:VS_"oa8Y/`~XQ# IR#_pV7%PdSS2/c<#|,w,=ecny"h,kLwQ/־'ҵ-@V ӂqO(F|K[m-$ r7A.Ԯ8BRn@=,|_~Ǫ[ڿ, w*e+z`[!ߎfnoLTg /)CkmɕŸ͏n5C>|PgWj|n>ucgמIt4)#~E ɯ[Ț]֝kt.rhEE2s&q#Hb7^++ih_mܭ4%}>ybo/z`!O[1e~|r%)Ow;K*;Adb+8ޟ&;һ%\N)S^1HԦش:pz>Y/ 2[hl 4 6 -N8c 4ǪIsj$qj ᗘ0JliչT+j)53Pl/Hg_@ޘfkLmNQjX9ѤTSy# íi"UII>˾3HRN޻, Y^Y 84W·]j춷v<* LYZ^xkza\DE݅{e隝ĥP tjO@(#42[xq=# .!{bdhK ^Wj)p =ȑ/$B"ŊćwZHhpZ|ڜW5rn{`noՑ.fGpKW8ZNѓ5-FK{(0ukGۖнSǵwŷ& WiKj(?Fw?H%FHqJz#;y#sFZM'pEd>΅WDW ?Iq۹ڿLƕA ,o-$L)M=gL{hV̅p~2`4PWzںPQz`;+CvcB1{ - |$kUtzi,J6IUG*Ԯ" Ttf*QL7"k:D>pQN;uËbF^0IO{Iޥ(cL%qkvm홗i:+~/mU'i$0'iQI،&$ w2jȣtZ-;Ǻr H pCZv}7ɕ¯͏n5C>|¨H ^n $ntYwɇ&-7JjZg|$mL]Bѳ= :GѵM"ud=2iB{᷑ePfp!f}bk;v(B|ͥP*PCmtK5A HX1a *0\{+p-zX :x X8niָ7H_u11Cm<RbrHAod\77lM0<\+_l$x^UR+R9UϮw:w0(rqw]*/+% ŧ_Fn5;W%6"Li}l1&#W@mto>3yfה\!)L/=+m&gXG=8 \,!` o\%$pU~ʚ~ zi@7'ެo8g4aA#W+[6[yh#j]⯧"851CZ#|3EZd,XlVH.4jQ(7E"n߮?PXns퇇 au;.J{`=f]P1 RGlo~jMGL }go r g6V}7ɕ¿jʰmz~gϞ:% -S"ɦeocavjxU֛{<ԭa>lǦNeb+}15#7NYZm#C~t u]K{_ܺEĬ4:KYԑ򏗮nTMr_&l-4?9ㅭt5^hF-Y/F4H^ jkL/MbMq4'mZL(f>!5F ֞; L&H /w [pb $Rs+Qጟ]leBzVio:ܚSIvj&S$f$6ݮʦwFpH#l,ҥYk%уv$lSikR݉q~2=|rE{Ji5~Rź`h5Scu|/'£jb؎5'|,ub6LV9⴦FS$.:8qLo%H|][WݙR]#ŧK ۈSNH8%a? alsRQ4=="/#ƘokqL@zw:ʴ)n>ߨя*/ \)_c_3l*eHC$=h7R QmA'&{;Z:ZY"^-aYk[% Ԏ9&7ԘömjM9eQ|,xl]+3Ʃ $]M'RF=AY_[uL0KAeoRumމb &>6f3d(i -ɬu4N|ioZ평]^6ab{0<,nDW%V?ukgz-е [|<9ap?>n??\gYIꝶH-T}+;?SƽB61Hv#-uoT <㵽ZXcRrW9,CzcLĘa](Lmwl-9+J=ǩ'~ SXw8#0UW%ͩC]NC(Il~,[:fK$jiL4ZCu#91\do<1Dkj Y}d!xnt,omᒵk$v<^IM_os菕)Vipc%Pϟ=Hzjz/4Vduʖ^Caҕÿ5'or~:|G'SBMӵ{@tbgnKĄ -4>JK<@_zފQ>겟⟼|s\KԍkF$sCyN+vtXBѱo\mkAd]8@d»&w,ޫq[g+˾-sl$'l|K6J~-j>[zoNS|jSa#PhDL~,.*Ggx#k}rif8^_WOM8˙"hO=?6T|n ikFHBzԤ@7.U2-K 5bGf1G`&8 nU]sw֞N ~|1KQ4I/cpMJUS!K3HS3+Lt7!q(H=p"NV~TqKY ZBӖ q0rz\i35z<8";`kBR|H'J`11ր!viB@ L[ӍL3Sz0V7֤v. ,+ޟP6iT/Z5ϤDY̝ɭ1L]"ŤԏLjjuX"(˽s,50ہqXo79\zE1K 9[>̞>莸ֵ2ܰ0Ԕ_᳦$ϳ߫>yQ`J7>̨<󌷰v냴soϩ`"ß+fk=FsC;DBqZwۋ}zAQ^RΩt#zcRj)Ln|W羨-{4E8gKhK *| /#]/Op,FԦ!LI^g1>e \369W1kR R:\^*,,]|CZ׏ս.=sNծ].v"4qIq S o^0 )DPp Dzz6OCL)iRx\lrs5)ysSڸ],R'AFT/$uftaw=5̄ɱ^UPiF|YXҠnmS\'aV.TóxsbN0(5isJrbw+Q Ar4@H~I 5.9h$P~ |r:rȑ}D43doixIpuprkj- Ӂg#YsuN)ͫao`!STc/PՑD/)H0FĤ`HU$x戱!` 1Kw.~zS !&qo)0BHq Y&~pz8/1C XKH.BE8q@5?!U?qrj'D endstream endobj 88 0 obj <>/XObject<>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/Font<>>>/Thumb 91 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 92 0 obj <>/ProcSet[/PDF/Text]/Font<>>> endobj 89 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.9663 0 0 8.9663 59.7543 725.7825 Tm 0 0 0 rg 0 Tc 0 Tw [(methodologies)-265.6(to)-262.5(improve)-259.5(on)-259.1(markers)-263.3(for)-256.9(MCC)-258.4(measure,)-262.4(we)]TJ 0 -1.2203 TD [(have)-401.9(to)-395.3(be)-396.3(realistic)-403.8(as)-392.8(to)-401.6(what)-397(we)-393.5(can)-400.5(have)-395.6(patients)-402(safely)]TJ 0 -1.2266 TD [(inhale)-278.8(for)-275.8(such)-277.2(measurements.)-277.7(Thus)-274.6(we)-279.7(should)-274.6(make)-273.3(similar)]TJ 0 -1.2203 TD [(efforts)-353.9(towards)-344.5(comparisons)-348.6(of)-344.7(particles)-351(currently)-348.9(used)-347(and)]TJ T* [(approved)-350.8(for)-345.4(these)-352.7(measures.)-345.9(Some)-352.8(suggestions)-346.7(for)-351.7(making)]TJ 0 -1.2266 TD [(crosslaboratory)-340.3(comparisons)-336(are)-335.2(presented)-338.7(further)-335.8(below.)]TJ /F12 1 Tf 0 -3.054 TD [(2.)-501.1(How)-326.2(do)-325(we)-323.4(best)-321.7(target)-325.9(deposition)-320.7(to)-324.1(the)-328.5(airways)-319.6(of)]TJ 0 -1.2203 TD [(interest)-335.1(with)-336.5(inhalation)-337.1(patterns)-329.9(and)-335.7(aerosol)-332.4(size?)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(All)-387.8(agree)-390.1(that)-389.5(deposition)-388.8(in)-386.3(bronchi)-390.5(and)-385.3(bronchioles)-391.7(air-)]TJ -1.1128 -1.2203 TD [(ways)-367.3(should)-369.4(be)-364.7(maximized)-366.7(with)-369.4(minimal)-362.7(deposition)-369.8(in)-367.3(the)]TJ 0 -1.2266 TD [(alveoli)-386.6(where)-391.2(MCC)-384.8(is)-384.2(not)-386(present.)-389.3(But)-390.5(\(1\))-386.1(how)-387.2(do)-385.1(we)-380.9(best)]TJ 0 -1.2203 TD [(achieve)-290.8(that)-282(goal)-282.1(and)-284.1(\(2\))-285(do)-284(we)-279.7(care)-290.2(what)-283.2(the)-282(distribution)-287.7(of)]TJ T* [(deposition)-420.4(is)-409.5(along)-412(the)-414.7(bronchial)-412.5(tree?)-411.2(As)-413.7(discussed)-412.4(previ-)]TJ 0 -1.2266 TD [(ously,)-465.2(each)-470(investigator)-469.7(has)-459.5(different)-473.4(approaches)-464.3(to)-464.8(maxi-)]TJ 0 -1.2203 TD [(mizing)-884.5(airway)-881.9(versus)-884.2(alveolar)-889.1(deposition.)-884.9(Ultimately,)]TJ T* [(comparison)-404.2(of)-395.3(deposition)-401.4(indices)-399.6(\(described)-401.2(further)-405.3(below\))]TJ 0 -1.2266 TD [(and)-265.1(clearance)-270.6(rates)-267.5(through)-263.1(24)-169.7(h)-262.6(between)-268.8(laboratories)-272.1(would)]TJ 0 -1.2203 TD [(be)-257.2(useful)-254.5(for)-250.5(assessing)-256.3(the)-256.7(optimum)-251.2(approaches)-255.7(for)-256.9(targeting)]TJ T* [(the)-655(airways.)-645.8(Each)-650.1(laboratory)-651.1(should)-647.7(also)-652.1(determine)-653.3(in-)]TJ T* [(trasubject)-492.9(repeatability)-489.1(of)-490.1(their)-488.5(measures)-488.4(of)-490.1(MCC,)-482.6(an)-489.8(im-)]TJ 0 -1.2266 TD [(portant)-501.9(element)-497.8(for)-497.1(its)-498.5(use)-495.8(as)-494(a)-492.7(biomarker)-500.4(of)-490.1(therapeutic)]TJ 0 -1.2203 TD (effects.)Tj 1.1128 -1.2203 TD [(Based)-322.9(on)-328.6(mean)-322.8(retentions)-325.7(at)-322.4(2)-170.2(h)-319.5(in)-329.4(healthy)-324.4(adult)-324(subjects,)]TJ -1.1128 -1.2266 TD [(it)-370.7(appears)-364.1(that)-370.6(the)-364.2(technique)-369.7(of)-370(Mortensen)-371(et)-367.1(al.,)]TJ 6.7246 0 0 5.9768 256.6487 455.8109 Tm [(\(6,38)-10.4(\))]TJ 8.9663 0 0 8.9663 276.0944 451.7857 Tm (incor-)Tj -24.1282 -1.2203 TD [(porating)-534.6(rapid)-526.6(forced)-530.9(exhalations,)-534.6(may)-526.3(provide)-530.5(the)-528.6(most)]TJ T* [(large)-412.7(airway)-414(deposition,)-410.7(that)-414.8(is,)-412.4(deposition)-414.1(at)-411(sites)-411.2(of)-414.2(ow)]TJ 0 -1.2266 TD [(limitation)-264.9(during)-256.7(exhalation.)-261.4(The)-259.2(greatest)-259.6(control)-259.5(is)-257.8(probably)]TJ 0 -1.2203 TD [(provided)-362.8(by)-362.9(the)-364.2(method)-361.2(of)-363.6(Scheuch)-365.5(et)-360.8(al.)]TJ 6.7246 0 0 5.9768 227.5086 411.9306 Tm [(\(10,1)-10.4(1\))]TJ 8.9663 0 0 8.9663 250.2424 407.9621 Tm [(where)-365.9(abso-)]TJ -21.245 -1.2203 TD [(lute)-435.2(volumes,)-433.7(ows,)-435.3(and)-429.5(bolus)-437(depths)-433.1(normalized)-437(to)-433.2(lung)]TJ 0 -1.2266 TD [(volumes)-241.1(are)-240.4(controlled)-240.7(by)-236.5(positive)-247.6(pressure)-240.5(ventilation)-242.5(of)-237.2(the)]TJ 0 -1.2203 TD [(subject)-498.6(with)-495.9(single)-496.6(breaths.)-493.2(The)-499.5(AKITA)-491.3(technology)-498.6(\(Acti-)]TJ T* [(veaero\))-339.1(provides)-335.8(a)-334.6(potential)-337.4(commercial)-332.4(tool)-332(to)-338.4(achieve)-335(this)]TJ T* [(controlled)-284.9(breathing)-279(and)-271.5(aerosol)-282.4(delivery.)-277.9(One)-271.9(disadvantage)]TJ 0 -1.2266 TD [(of)-275.1(the)-269.3(device,)-268.5(however,)-271.2(may)-267.1(be)-269.9(its)-270.9(limitation)-271.2(on)-271.7(inhaled)-269.2(ow)]TJ 0 -1.2203 TD [(rates)-438.2(\()]TJ /F13 1 Tf 2.8516 0 TD ()Tj /F5 1 Tf .7714 0 TD [(250)-162.9(mL/sec\))-434.5(and)-435.9(the)-433.7(fact)-429.7(that)-433.8(exhalation)-435.5(is)-434.8(uncon-)]TJ -3.623 -1.2203 TD [(trolled.)-333(By)-323.6(incorporating)-335.6(breathholds)-332.2(at)-322.5(end)-328.8(inhalation)-332.8(with)]TJ 0 -1.2266 TD [(this)-236.3(device,)-236.9(there)-238.3(is)-232.5(little)-239.1(aerosol)-231.8(left)-238.3(to)-237.2(deposit)-233.6(in)-234.5(the)-237.7(airways,)]TJ 0 -1.2203 TD [(but)-347.7(breathholding)-348.6(will)-341(also)-348.6(enhance)-343.9(deposition)-350.8(in)-342(the)-345.2(smal-)]TJ T* [(lest)-340.3(airways)-333.1(where)-334.3(particles)-338.4(reside.)]TJ 1.1128 -1.2266 TD [(The)-404.6(second)-401.7(question,)-405.8(which)-396.9(airways)-402.6(are)-404.8(most)-400.5(important)]TJ -1.1128 -1.2203 TD [(to)-439.5(target,)-438.3(assumes)-444.9(that)-433.8(we)-437.8(might)-439.3(affect)-442.7(the)-440(distribution)-439.5(of)]TJ T* [(particle)-583.7(deposition)-584.8(along)-576.4(the)-579.1(airway)-578.4(tree)-582.7(with)-578.1(breathing)]TJ T* [(patterns)-512.9(or)-509.3(particle)-514.1(size.)-506.7(One)-505.8(of)-509.1(the)-509.6(more)-513.1(innovative)-511.2(ap-)]TJ 0 -1.2266 TD [(proaches)-299.1(to)-300.4(specically)-296.9(target)-296.3(the)-294.6(small)-296.3(airways)-295.1(of)-294.1(the)-300.9(lungs)]TJ 0 -1.2203 TD [(is)-365.3(that)-364.2(of)-363.6(Anderson)-369.9(et)-360.8(al.,)]TJ 6.7246 0 0 5.9768 162.8787 225.6377 Tm (\(30\))Tj 8.9663 0 0 8.9663 177.222 221.6693 Tm [(where)-359.6(by)-362.9(using)-368.1(large)-362.1(particles)]TJ -13.1011 -1.2203 TD (\(6)Tj /F11 1 Tf .9927 0 TD (m)Tj /F5 1 Tf .5501 0 TD [(m\))-649.3(and)-644.5(extremely)-647.2(slow)-647.9(inhalations)-650.3(\(40)-163.9(mL/sec\))-649.5(they)]TJ -1.5428 -1.2267 TD [(predict)-375(particles)-376.3(will)-372.6(escape)-374.3(deposition)-376.1(by)-375.6(impaction)-371.8(in)-373.6(the)]TJ 0 -1.2203 TD [(upper)-700.2(airways)-693.5(and)-695.1(large)-697.3(bronchi)-700.4(but)-695.4(penetrate)-701.1(to)-692.4(the)]TJ T* [(smaller)-360.1(bronchioles)-353.8(for)-358(deposition)-357.2(by)-350.3(sedimentation.)-363.1(Model)]TJ 0 -1.2266 TD [(predictions)-404.9(also)-405.5(suggested)-401.8(that)-402.2(the)-402.1(slow)-407.6(ow)-399.4(would)-398(allow)]TJ 0 -1.2203 TD [(near)-446.1(complete)-447.4(deposition)-452(in)-443.2(the)-446.4(small)-441.7(airways)-446.9(before)-444.4(par-)]TJ T* [(ticles)-526.5(could)-528.4(reach)-521.3(the)-528.6(alveolar)-522.4(region.)-529.8(Their)-522.7(experimental)]TJ 0 -1.2266 TD [(comparisons)-532(with)-521.2(tidal)-528.5(breathing)-525.6(of)-521.7(similar)-528.2(size)-522.7(particles)]TJ 0 -1.2203 TD [(conrmed)-572.4(that)-566.6(signicantly)-573.6(greater)-568.3(clearance)-567.7(of)-572.3(particles)]TJ T* [(was)-464(observed)-468(beyond)-460.5(the)-465.3(24-h)-464.5(retention)-469.8(measurement)-463.1(for)]TJ T* [(the)-300.9(slow)-293.8(inhalation)-294.9(versus)-302.5(tidal)-294.6(breathing)-297.9(approach.)-295.3(Bennett)]TJ 0 -1.2266 TD [(et)-373.4(al.)-372.7(\(unpublished)-374.8(observations\))-375.4(have)-370.3(been)-374.3(making)-366.9(similar)]TJ 0 -1.2203 TD [(comparisons)-702.7(of)-698.8(MCC)-694.7(as)-696.3(measured)-698.8(after)-696.6(rapid)-697.3(shallow)]TJ T* [(breathing)-449.7(\(500)-163.4(mL/sec)-446.7(at)-442.6(30/min\))-443.3(of)-445.8(5)]TJ /F11 1 Tf 17.8243 0 TD (m)Tj /F5 1 Tf .5564 0 TD [(m)-440.2(particles)-445.9(versus)]TJ -18.3807 -1.2267 TD [(slow)-502.4(inhalation)-497.2(\(80)-170.2(mL/sec\))-497.7(of)-502.8(9.5)]TJ /F11 1 Tf 15.9906 0 TD (m)Tj /F5 1 Tf .5501 0 TD [(m)-497.1(nebulized)-499.1(particles.)]TJ 11.4634 74.5598 TD [(Initial)-420.7(results)-419.6(conrm)-417.7(those)-425.2(of)-414.2(Anderson)-426.8(et)-417.7(al.,)]TJ 6.7246 0 0 5.9768 502.5826 729.751 Tm [(\(30)-10.1(\))]TJ 8.9663 0 0 8.9663 517.4361 725.7825 Tm [(but)-417.2(also)]TJ -23.0407 -1.2203 TD [(show)-445.4(enhanced)-441.7(MCC)-448.1(during)-440(the)-446.4(rst)-448.1(few)-444.6(hours)-445.8(of)-439.5(obser-)]TJ 0 -1.2266 TD [(vation)-497.3(post)-499.1(deposition,)-499.2(suggesting)-498.7(enhanced)-498.6(large)-501.3(airway)]TJ 0 -1.2203 TD [(deposition)-287.6(as)-285.4(well)-286.8(for)-288.5(the)-282(slow)-287.5(inhalation)-288.6(method.)-288.2(Targeting)]TJ T* [(deposition)-464.6(of)-464.8(the)-465.3(radiolabeled)-465.9(particles)-464.8(to)-464.8(the)-465.3(small)-467(bron-)]TJ 0 -1.2266 TD [(chiole)-328.6(airways)-326.8(of)-325.7(the)-332.5(lungs)-323.8(may)-330.3(be)-326.8(especially)-326.1(advantageous)]TJ 0 -1.2203 TD [(for)-294.8(studying)-300.1(MCC)-302.6(in)-297.8(patients)-300.8(with)-293.5(early)-298.9(lung)-303.5(disease)-299.3(as)-291.7(it)-301.2(is)]TJ T* [(generally)-411.3(agreed)-405.8(that)-408.5(many)-409.5(airway)-407.6(diseases)-408.1(begin)-407.7(in)-405.3(these)]TJ 0 -1.2266 TD [(airways)-484.8(\(e.g.,)-481.4(CF\))-485.6(bronchiolar)-485.6(region)-488.9(of)-483.8(the)-484.3(lung.)-483.5(If)-483.1(large)]TJ 0 -1.2203 TD [(airway)-907.2(deposition)-913.6(dominates)-915.6(in)-904.8(such)-915.8(patients,)-910.7(MCC)]TJ T* [(may)-387.2(appear)-394.4(to)-395.3(be)-390(relatively)-395.6(normal,)]TJ 6.7246 0 0 5.9768 457.1148 620.1636 Tm (\(39\))Tj 8.9663 0 0 8.9663 471.7416 616.1951 Tm [(while)-391.3(the)-389.5(MCC)-397.5(de-)]TJ -17.9444 -1.2203 TD [(fect)-328.9(in)-329.4(small)-327.9(airways)-333.1(may)-324(be)-333.1(disguised,)-327.8(as)-329.6(may)-324(the)-332.6(effect)-335.6(of)]TJ 0 -1.2266 TD [(the)-345.2(experimental)-353.3(therapy)-351.2(on)-347.6(this)-350.1(region)-349.8(of)-351(the)-351.5(lung.)-344.4(On)-354.2(the)]TJ 0 -1.2203 TD [(other)-601.6(hand,)-600.2(there)-605(may)-595.8(be)-605(therapies)-598.1(or)-604.1(situations)-605.7(where)]TJ T* [(MCC)-486(in)-487.5(the)-490.6(larger)-489.3(airways)-491.2(is)-491.7(of)-483.8(primary)-494.7(interest,)-493.1(for)-484.5(ex-)]TJ 0 -1.2266 TD [(ample,)-226.1(a)-233.5(drug)-224.5(that)-231.5(stimulates)-236.6(or)-224.8(inhibits)-232.2(glandular)-233.9(secretions.)]TJ 0 -1.2203 TD [(In)-309(these)-314.8(cases)-311.1(a)-303(targeting)-314(strategy)-314.7(such)-308.8(as)-310.6(that)-313.7(of)-306.7(Mortensen)]TJ T* [(et)-379.7(al.)]TJ 6.7246 0 0 5.9768 330.5763 543.4581 Tm [(\(6,14,3)-10.7(8,39\))]TJ 8.9663 0 0 8.9663 366.9731 539.4896 Tm [(that)-383.2(targets)-379.8(the)-383.1(largest)-382.9(airways)-383.7(may)-380.9(be)-377.4(best.)]TJ -5.1469 -1.2266 TD [(Finally,)-619.6(regardless)-627.6(of)-622.9(targeting)-623.8(methodology)-625.7(sufcient)]TJ -1.1128 -1.2203 TD [(activity)-385(should)-388.4(be)-390(deposited)-388.3(with)-388.4(inhalation)-389.8(to)-388.9(provide)-391.4(for)]TJ T* [(accurate)-512.2(24-h)-508.7(retentions,)-518.3(by)-508.4(which)-510.7(time)-513.6(Tc99m)-511(will)-511.7(have)]TJ T* [(decayed)-672.9(four)-681.9(half-lives.)-676.9(Moreover,)-679.4(the)-674(accuracy)-679.9(of)-673.5(this)]TJ 0 -1.2266 TD [(measure)-474.5(is)-472.7(critical)-477.7(for)-471.8(being)-477.2(able)-468.9(to)-477.5(calculate)-474.3(the)-478(tracheo-)]TJ 0 -1.2203 TD [(bronchial)-393.6(clearance)-397(or)-389.2(retention)-393.9(where)-397.5(24-h)-394.9(retention)-393.9(is)-390.5(as-)]TJ T* [(sumed)-774.5(to)-781(primarily)-779.9(represent)-779(alveolar)-781.6(deposition)-780.8(\(i.e.,)]TJ 0 -1.2266 TD [(subtracting)-436.2(24-h)-432.8(retention)-438.1(from)-437.8(previous)-435.3(retention)-438.2(values\).)]TJ 0 -1.2203 TD [(This)-422.2(assumption)-429.9(may)-418.8(not)-423.9(always)-427.2(be)-421.6(valid,)-424.2(however,)-422.9(espe-)]TJ T* [(cially)-254.1(in)-253.5(airways)-250.9(disease)-255.1(such)-258.3(as)-253.7(CF)-251.2(or)-256.4(non-CF)-254.9(bronchiectasis)]TJ 0 -1.2266 TD [(where)-296.4(the)-300.9(bronchial)-298.7(airways)-295.1(have)-300.7(not)-297.5(completely)-297.3(cleared)-303(by)]TJ 0 -1.2203 TD [(24)-163.4(h.)]TJ 6.7246 0 0 5.9768 328.6487 411.9306 Tm [(\(40)-10.1(,41\))]TJ 8.9663 0 0 8.9663 351.7794 407.9621 Tm [(It)-407.3(is)-409.5(agreed)-405.8(that)-402.2(longer)-406.7(static)-409.2(acquisitions)-410.1(are)-404.8(re-)]TJ -4.5651 -1.2203 TD [(quired)-335.4(\(up)-338.3(to)-338.4(30)-169.7(min\))-340.1(at)-335.1(24)-169.7(h)-332.2(t)0(o)-338.4(provide)-340.8(better)-341(counting)-341.1(sta-)]TJ 0 -1.2266 TD [(tistics)-332.4(for)-339.1(comparison)-334.7(to)-338.4(background)-333.1(radiation.)]TJ /F12 1 Tf 0 -3.054 TD [(3.)-501.1(Characterization)-335.2(of)-330.4(initial)-335.4(deposition)-339.7(pattern)]TJ 0 -1.2203 TD [(\(C/P,)-332.4(PI,)-333.8(Skew,)-337(other\)?)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(All)-318.3(investigators)-325.6(recognize)-329.6(that)-320(the)-326.2(measured)-319.4(clearance)-327.5(is)]TJ -1.1128 -1.2203 TD [(a)-239.8(function)-248.6(of)-243.5(initial)-245.1(deposition)-249.7(pattern)-246.1(in)-247.2(the)-244(lung)-246.6(\(Fig.)-243.4(3\))-240.2(and)]TJ 0 -1.2266 TD [(consequently)-239.1(measure)-240.5(some)-235.5(index)-239.6(of)-237.2(regional)-239.1(deposition)-243.3(that)]TJ 0 -1.2203 TD [(will)-239.8(reect)-237.2(airway)-236.9(versus)-245.6(alveolar)-237.8(deposition.)-239.9(Figure)-241.9(5)-239.8(shows)]TJ T* [(data)-299.7(from)-298.7(Mortensen)-301.5(et)-297.5(al.)]TJ 6.7246 0 0 5.9768 416.1826 291.4015 Tm (\(6\))Tj 8.9663 0 0 8.9663 426.5573 287.433 Tm [(illustrating)-304(the)-300.9(correlation)-301.1(of)-300.4(%)]TJ -12.9051 -1.2266 TD [(retention)-267.4(at)-265.5(2)-163.9(h)-269(with)-261.9(penetration)-274.6(index)-264.9(\(PI,)-266.1(which)-264.1(is)-264.1(a)-265.1(ratio)-266.2(of)]TJ 0 -1.2203 TD [(activity)-239.6(in)-234.5(peripheral)-241.5(to)-237.2(central)-240.7(region)-236(normalised)-242.8(for)-237.9(volume)]TJ T* [(differences,)-489(inverse)-496.3(of)-483.8(C/P)-491.4(in)-487.5(Fig.)-489.5(3\))-486.8(in)-487.5(a)-486.4(large)-488.6(group)-491.1(of)]TJ T* [(healthy)-299.1(adult)-298.7(subjects.)]TJ 6.7246 0 0 5.9768 399.1747 247.5779 Tm (\(6\))Tj 8.9663 0 0 8.9663 409.5495 243.6094 Tm [(Are)-299.2(the)-300.9(various)-300.8(indices)-298.5(comparable)]TJ -11.0082 -1.2266 TD [(and/or)-290.6(should)-287.3(there)-295.2(be)-288.8(a)-284(standard)-295.4(index)-290.2(that)-288.4(can)-293(be)-288.8(used)-290.1(to)]TJ 0 -1.2203 TD [(compare)-443.7(clearance)-441.3(between)-445.9(different)-448.1(studies)-447.2(and)-442.2(laborato-)]TJ T* [(ries?)-320.9(Because)-326.7(the)-319.9(actual)-326.1(borders)-322.6(of)-325.7(the)-319.9(lungs)-323.8(are)-322.6(likely)-322.8(to)-325.7(be)]TJ 0 -1.2267 TD [(underestimated)-298.5(with)-293.6(the)-294.6(deposition)-300.2(scan)-294.3(alone,)-296.6(the)-294.6(rst)-296.3(step)]TJ 0 -1.2203 TD [(in)-835.2(assessing)-838(regional)-839.7(deposition)-837.7(is)-839.5(dening)-836.3(the)-838.4(lung)]TJ T* [(boundaries.)-269.4(As)-261.9(discussed)-266.9(above,)-269.5(this)-267.9(can)-261.4(be)-269.9(done)-262(with)-268.3(either)]TJ 0 -1.2266 TD [(a)-397.9(gas)-403.6(or)-395.5(transmission)-404.5(scan)-401.8(\(Fig.)-401.5(4\).)-401.2(Equilibrium)-406.3(scans)-396.8(with)]TJ 0 -1.2203 TD [(Xe133)-413.7(are)-417.4(more)-411.9(likely)-417.7(to)-414.2(dene)-413.9(the)-421.1(whole)-415.9(lung)-411(than)-417.7(short)]TJ T* [(half-life)-381.5(\(13)-163.9(sec\))-380.3(Kr)-382.9(81m)-376(scans,)-380.8(which)-378(provide)-385.1(a)-372.6(measure)-385.9(of)]TJ 0 -1.2266 TD [(ventilated)-387.5(lung.)-382.3(Although)-387.5(either)-387.3(may)-387.2(sufce)-384.7(in)-386.3(the)-383.1(healthy)]TJ 0 -1.2203 TD [(lung,)-502.5(poorly)-502.4(ventilated)-507.6(regions)-502.9(in)-506.4(the)-503.3(diseased)-504.7(lung)-505.9(may)]TJ T* [(make)-431.4(gas)-435.2(scans)-441.1(less)-436(reliable.)-435.3(In)-435.5(such)-435.3(cases,)-440.5(a)-429.5(transmission)]TJ T* [(scan)-427.1(is)-428.5(probably)-432.1(better)-429.5(at)-429.9(dening)-431.6(the)-433.7(edges)-432.2(of)-426.9(the)-433.7(whole)]TJ 0 -1.2266 TD [(lung.)-312.8(Figure)-317.8(6)-315.7(illustrates)-319.1(how)-311.3(even)-320.1(a)-315.7(Xenon)-317.2(133)-314.7(equilibrium)]TJ 0 -1.2203 TD [(scan)-465.1(in)-462.2(a)-461.1(mild)-462.9(CF)-459.8(patient)-463.9(may)-463.1(tend)-462(to)-464.8(underestimate)-466.2(the)]TJ T* [(edges)-444.8(of)-445.8(the)-440(lung)-449(compared)-446.7(to)-439.5(a)-448.4(transmission)-448.8(scan)-439.8(in)-443.2(the)]TJ 0 -1.2267 TD [(same)-333.4(individual;)-344.2(in)-335.7(this)-337.5(case,)-338(the)-345.2(upper)-339.8(right)-335(lung)-341.5(is)-333.6(poorly)]TJ /F4 1 Tf -28.0042 77.228 TD [(MUCOCILIARY)-339.2(AND)-337.2(COUGH)-337(CLEARANCE)]TJ 53.0113 0 TD (265)Tj ET endstream endobj 93 0 obj <>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/XObject<>/Font<>>>/Thumb 97 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 98 0 obj <>/ProcSet[/PDF/Text/ImageB]/XObject<>/Font<>>> endobj 94 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.9663 0 0 8.9663 62.022 465.9023 Tm 0 0 0 rg 0 Tc 0 Tw [(ventilated.)-377.8(On)-379.5(the)-376.8(other)-374(hand,)-378.9(the)-376.8(transmission)-379.2(scan)-376.5(is)-371.6(less)]TJ 0 -1.2266 TD [(likely)-386.1(to)-388.9(normalize)-383.5(for)-389.6(volume)-385.2(differences)-391.2(between)-389(the)-383.1(dif-)]TJ 0 -1.2203 TD [(ferent)-276.7(regions)-268.9(of)-268.8(the)-275.6(lung)-271.9(in)-266.2(the)-275.6(way)-264.8(an)-274.8(equilibrium)-270.4(gas)-270.8(scan)]TJ T* [(will)-416.9(if)-415(the)-421.1(lung)-417.4(is)-415.8(fully)-418(ventilated.)-422(A)-418.7(good)-417.6(comparison)-416.9(be-)]TJ T* [(tween)-403.6(these)-403.3(two)-403.2(methods)-406.8(in)-398.9(both)-403.1(healthy)-406.6(subjects)-405(and)-404.2(pa-)]TJ 0 -1.2266 TD [(tients)-337.9(with)-331.5(airways)-339.4(disease)-330.9(would)-334.8(be)-333.1(useful)-336.7(to)-332(better)-341(dene)]TJ 0 -1.2203 TD [(the)-509.6(limitations/advantages)-521.3(of)-509.1(each.)-510.8(But)-510.7(if)-509.8(all)-512.4(laboratories)]TJ T* [(could)-338.7(measure)-341.7(a)-334.6(C/P)-339.6(or)-338.6(PI)-338.6(based)-336.9(on)-341.3(a)-340.9(transmission)-341.3(scan)-338.6(of)]TJ 0 -1.2266 TD [(the)-263(lung)-265.6(\(the)-263.5(easiest)-265.2(and)-265.1(most)-261.4(accessible)-271.2(method)-260(for)-263.2(dening)]TJ 0 -1.2203 TD [(the)-389.5(lung\),)-389.1(and)-391.6(dene)-388.6(the)-389.5(right)-391.9(lung)-392.1(regions)-389.1(the)-389.5(same)-390.3(way,)]TJ T* [(then)-392.8(crosscomparisons)-398.3(between)-395.3(laboratories)-392.2(\(or)-389.6(within)-395.3(lab-)]TJ 0 -1.2266 TD [(oratories)-631.3(for)-623.6(different)-631.5(patient)-634.6(cohorts\))-624.5(of)-629.2(retention)-634.2(as)-626.8(a)]TJ 0 -1.2203 TD [(function)-337.1(of)-338.4(C/P)-333.3(or)-332.3(PI)-338.6(by)-331.3(analysis)-339(of)-332(covariance)-337.4(\(e.g.,)-336(Fig.)-331.4(5\))]TJ T* [(could)-553.7(be)-554.4(easily)-549.7(made.)]TJ 6.7246 0 0 5.9768 154.6582 327.4015 Tm (\(6\))Tj 8.9663 0 0 8.9663 167.3007 323.433 Tm [(For)-558(instance)-554.6(such)-555.4(a)-549.6(comparison)]TJ -11.7416 -1.2203 TD [(would)-334.8(then)-335.9(allow)-339.8(us)-331.5(to)-338.4(determine)-337.1(if)-332.8(there)-339.5(are)-335.2(differences)-334.3(in)]TJ 0 -1.2266 TD [(MCC)-479.7(measures)-475.8(associated)-478.5(with)-476.9(particle)-482.5(type)-474(as)-475(discussed)]TJ 0 -1.2203 TD [(above,)-364.3(for)-370.7(example,)-367.2(sulfur)-362.8(colloid)]TJ 6.7246 0 0 5.9768 197.348 294.5196 Tm (\(3,4\))Tj 8.9663 0 0 8.9663 213.3921 290.5511 Tm [(versus)-365.7(polystyrene)]TJ 6.7246 0 0 5.9768 288.3401 294.5196 Tm (\(8,9\))Tj 8.9663 0 0 8.9663 62.022 279.6094 Tm [(versus)-511.2(iron)-503.6(oxide.)]TJ 6.7246 0 0 5.9768 136.3464 283.5779 Tm [(\(1012)-10.7(\))]TJ 8.9663 0 0 8.9663 162.085 279.6094 Tm [(Ilowite)-507.1(et)-506.2(al.)]TJ 6.7246 0 0 5.9768 214.9228 283.5779 Tm (\(42\))Tj 8.9663 0 0 8.9663 230.5133 279.6094 Tm [(reported)-514.6(such)-504.8(an)]TJ -18.7917 -1.2266 TD [(analysis)-294.7(to)-294.1(determine)-299.2(if)-294.9(the)-294.6(retention)-299(vesus)-301.8(C/P)-289.1(relationship)]TJ 0 -1.2203 TD [(differed)-504.2(for)-503.5(different)-511.3(particle)-501.5(types)-507(used)-505.1(within)-502.8(the)-503.3(same)]TJ T* [(laboratory.)-249.4(The)-246.6(denition)-256.9(of)-243.5(size)-250.8(and)-246.2(location)-255.5(of)-243.5(regions,)-252.9(that)]TJ 27.9978 53.4286 TD [(is,)-304.9(C)-297.3(versus)-308.8(P,)-295.1(should)-306.2(be)-301.5(standardized)-301.4(for)-301.1(such)-302.5(comparisons)]TJ 0 -1.2203 TD [(to)-338.4(be)-333.1(made)-335.1(across)-333.7(laboratories.)]TJ 1.1128 -1.2266 TD [(Regional)-293.2(deposition)-293.9(as)-291.7(dened)-296.7(by)-287(specic)-292.2(regions)-294.2(may)-292.3(be)]TJ -1.1128 -1.2203 TD [(useful)-418.9(as)-418.1(an)-413.9(index)-416.6(of)-414.2(large)-412.7(bronchial)-418.9(airways)-415.3(versus)-416.3(small)]TJ T* [(airways)-415.3(and)-416.9(alveoli,)-414.8(but)-417.2(other)-411.9(distribution)-420.5(indices)-418.6(that)-414.8(are)]TJ 0 -1.2266 TD [(not)-442.9(dependent)-444.3(on)-442.4(specic)-444(regions)-439.7(of)-439.5(interest)-446(may)-437.8(provide)]TJ 0 -1.2203 TD [(more)-481.5(sensitive)-482(measures)-475.8(of)-477.5(airway)-477.2(deposition)-483.6(and)-473.8(its)-479.5(ho-)]TJ T* [(mogeneity.)-360.7(For)-355.7(example,)-354.6(the)-357.8(coefcient)-359.8(of)-357.3(skew)-355(for)-358(the)-357.8(his-)]TJ 0 -1.2266 TD [(togram)-460.7(distribution)-458.4(\(counts/pixel)-465.1(vs.)-460.2(number)-456.3(of)-458.5(pixels\))]TJ 6.7246 0 0 5.9768 541.077 642.1038 Tm [(\(43)-10(\))]TJ 8.9663 0 0 8.9663 313.0582 627.1368 Tm [(within)-553.4(the)-547.5(whole)-548.7(lung)-550.1(ROI)-546.8(increases)-546.3(with)-552.8(increased)-548(fre-)]TJ 0 -1.2203 TD [(quency)-379.5(of)-376.3()80.3(hot)-375.2(spots)79.4()-381.3(i)0(n)-373.6(the)-376.8(lung.)-376(These)-380.6(hot)-379.7(spots)-374(are)-379.5(pre-)]TJ T* [(sumed)-287.7(due)-282.5(to)-281.4(increased)-282.4(deposition)-287.6(within)-281.5(bronchial)-286.1(airways)]TJ 0 -1.2266 TD [(throughout)-552.2(the)-547.5(lung)-543.8(so)-547.9(that)-547.6(skew)-544.7(is)-548.6(independent)-546(of)-547(the)]TJ 0 -1.2203 TD [(specic)-368.1(region)-362.5(within)-363.7(the)-364.2(lung)-360.5(\(e.g.,)-361.3(C)-360.6(vs.)-365.4(P\).)-358.8(To)-366.2(determine)]TJ T* [(skew,)-667.8(frequency)-665.1(distribution)-673.4(histograms)-666.2(are)-664(constructed)]TJ 0 -1.2266 TD [(from)-248.1(the)-250.4(deposition)-249.7(images,)-249.4(with)-249.3(the)-250.4(number)-247.6(of)-249.8(pixels)-245.7(with)-249.3(a)]TJ 0 -1.2203 TD [(given)-315.5(count)-317.1(value)-314.9(\(expressed)-313.5(as)-317(a)-309.3(percentage)-318.6(of)-313.1(total)-310.3(pixels\))]TJ T* [(on)-360.2(the)-351.5(y-axis)-352.8(and)-353.7(the)-357.8(count)-355(values)-354.1(on)-353.9(the)-357.8(x-axis.)-353.5(These)-355.3(his-)]TJ 0 -1.2266 TD [(tograms)-278.6(are)-272(then)-272.7(analyzed)-272(for)-275.8(skew)-272.8(\(a)-271.9(measure)-272.1(of)-275.1(histogram)]TJ 0 -1.2203 TD [(symmetry,)-331.7(the)-326.2(third)-327.2(moment)-330.5(about)-331(the)-326.2(mean)-329.2(of)-325.7(histogram\).)]TJ T* [(Heterogeneity)-386.5(of)-376.3(deposition)-382.4(increases)-381.9(with)-375.7(increasing)-379.4(skew)]TJ T* [(\(i.e.,)-259.2(more)-260.2(pixels)-258.4(with)-261.9(high)-255(counts/pixel\))-262.8(and,)-261.7(like)-258(C/P)-257.4(or)-256.4(PI,)]TJ 0 -1.2266 TD [(has)-295.1(been)-292.1(found)-289.2(to)-294.1(correlate)-291.3(with)-293.5(retention,)-295.6(that)-294.7(is,)-286(decreased)]TJ 0 -1.2203 TD [(retention)-343.3(at)-335.1(any)-329.8(time)-336.6(with)-331.5(increasing)-341.4(skew.)]TJ 6.7246 0 0 5.9768 486.3683 477.6943 Tm [(\(43)-10.1(\))]TJ 8.9663 0 0 8.9663 323.0361 462.7841 Tm [(Finally,)-290.8(three-dimensional)-304.5(multimodality)-293.2(imaging)-288.3(enables)]TJ -1.1128 -1.2266 TD [(more)-443.5(accurate)-436.3(characterisation)-447.2(of)-433.2(the)-440(initial)-441.1(distribution)-439.5(of)]TJ 0 -1.2203 TD (aerosol.)Tj 6.7246 0 0 5.9768 343.4456 444.8125 Tm (\(44\))Tj 8.9663 0 0 8.9663 357.9023 440.844 Tm [(It)-382(provides)-380(both)-384.1(an)-375.9(improved)-382.6(description)-386(of)-376.3(the)]TJ -5.0014 -1.2203 TD [(spatial)-274.8(deposition)-268.6(of)-268.8(aerosol)-269.7(and)-265.1(the)-269.3(possibility)-270.5(of)-268.8(estimating)]TJ 0 -1.2266 TD [(deposition)-471(by)-464.1(airway)-458.2(generation.)-469.8(Associated)-467.7(3D)-462.5(lung)-461.6(vol-)]TJ 0 -1.2203 TD [(ume)-536.3(scans)-542.3(from)-532.6(transmission)-543.6(SPECT)-537.1(or)-534.6(CT)-534.3(are)-537.6(also)-538.3(fre-)]TJ T* [(quently)-295.7(obtained)-288.9(in)-291.5(these)-289.5(studies.)-292(All)-286.7(these)-289.5(data)-287(should)-293.6(help)]TJ 0 -1.2266 TD [(in)-335.7(interpreting)-337.9(clearance)-340.1(rate)-335.7(measurements.)]TJ /F12 1 Tf 0 -2.6746 TD [(4.)-501.1(Period)-339.1(of)-330.4(MCC/CC)-338.9(observation/imaging?)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(The)-442.6(period)-447.5(for)-446.5(assessing)-446(MCC/CC)-438.8(postradioaerosol)-449.6(de-)]TJ -1.1128 -1.2203 TD [(position)-310(depends)-302.7(on)-303.3(the)-300.9(aims)-299.1(of)-306.7(the)-300.9(study,)-304.3(the)-300.9(isotope)-303(used,)]TJ 0 -1.2266 TD [(and)-499.1(the)-496.9(initial)-498(activity)-498.8(deposited.)-498.7(The)-493.1(latter)-497.8(is)-498(limited)-492.1(by)]TJ 0 -1.2203 TD [(radiation)-389.5(safety,)-388.4(that)-389.5(is,)-387.1(minimum)-390.2(levels)-388.3(of)-388.9(activity)-385(are)-385.8(de-)]TJ T* [(sired)-539.6(to)-534.4(reduce)-535.3(radiation)-541.2(doses)-533.1(to)-540.7(subjects.)-534.4(As)-540.2(discussed)]TJ 0 -1.2266 TD [(above,)-351.7(most)-349.9(all)-348(laboratories)-354.2(use)-350.3(the)-345.2(short)-350.1(half-life)-356.2(Tc99m)-346.6(as)]TJ 0 -1.2203 TD [(the)-269.3(radiolabel)-273.3(but)-265.5(some)-267.1(have)-269.1(utilized)-274.1(Indium)-263.9(111)-270.4(\(half-life)-268.2(of)]TJ T* [(2.2)-356(days\))]TJ 6.7246 0 0 5.9768 348.9448 272.8629 Tm [(\(30,3)-10.4(1\))]TJ 8.9663 0 0 8.9663 371.6786 268.8944 Tm [(to)-357.3(allow)-352.4(measures)-362(of)-357.3(MCC)-353.2(over)-358.2(a)-359.9(longer)-356.1(pe-)]TJ -6.5379 -1.2203 TD [(riod)-307.2(of)-306.7(time,)-307.9(assuming)-309.6(that)-307.3(sufcient)-309.9(activity)-309.1(is)-302(still)-309.6(residing)]TJ 0 -1.2266 TD [(in)-323.1(ciliated)-316.3(airways)-320.4(at)-316.1(these)-321.1(later)-313.9(time)-317.6(points.)-325.6(Although)-317.9(none)]TJ ET q 1 i 101.82 212.939 m 512.107 212.939 l 512.107 83.792 l 101.82 83.792 l W n q 410.527 0 0 129.146 101.82 83.792 cm /Im5 Do Q Q BT /F7 1 Tf 8.9663 0 0 8.9663 61.7952 67.0677 Tm [(FIG.)-330.5(6.)]TJ /F5 1 Tf 4.0909 0 TD [(Transmission)-337.5(\(from)-337.1(a)-328.3(Tc99m)-334(ood)-334(source\),)-337.5(Xenon133)-334.7(equilibrium,)-336.6(and)-328.4(deposition)-338.2(image)-333.7(\(aerosol)-333.4(of)-338.4(Tc99m-sulfur)]TJ -4.0909 -1.1128 TD [(colloid\))-335(in)-335.7(the)-332.5(same)-339.7(CF)-333.4(adult.)]TJ ET q 238.992 0 0 206.589 62.249 525.657 cm /Im6 Do Q BT /F7 1 Tf 8.9663 0 0 8.9663 62.0787 508.8755 Tm [(FIG.)-602.4(5.)]TJ /F5 1 Tf 4.3628 0 TD [(The)-607(association)-605.4(between)-610.3(penetration)-603.4(index)-606.3(and)]TJ -4.3628 -1.1065 TD [(lung)-430(retention)-438.1(at)-429.9(2)-170.2(h)0(,)-429.9(analyzed)-430.1(by)-432.5(simple)-430.8(linear)-434.2(regression)]TJ 0 -1.1128 TD (\()Tj /F6 1 Tf .3225 0 TD (n)Tj /F13 1 Tf .7208 0 TD ()Tj /F5 1 Tf .9358 0 TD [(62\))-334.6(\(6\).)]TJ /F4 1 Tf -1.9854 29.0727 TD (266)Tj 46.3849 0 TD [(BENNETT)-338(ET)-338.7(AL.)]TJ ET endstream endobj 96 0 obj <>stream AdobedC        W s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?^*”ǭF(l?zHm5 qy}Ra2ʡ %*cbR(Nda^<J[RZXkF8r +hKrdl_QdY`٭*~,uy+w0Pؾ(lmas]zc/ؖE6[<[ڋ$nPJƇN5j1H oew-jib~.XXnRӁo\1z彌h`0=i8??5U=7s'oR0bxوzzN*~"Uh|"+xbJ84lĞ!$_L,Ƙ"ՂȠe(7\UU!E;S\w--6]6GLݰ/" 2Jޘ8#;q!OSz| T+Y%t^a.Qj^mLZLc0N=̗&|l^ *)ģӏ>:kI$ `z`۝:&汮ZP#k +`{$وPaOa$6rN8@<ǿ8닻`4wŔ6q-jS108W|h|[ W0BN8bJ ;mTl1˜WHB}t2CC8,E1-bYT;:?ϩy* ?$XdY3iC (N_ފ٭(ƘDqTQL qI"CiKKΙ=q}? M OϾعds04k3xcco\/xQQ2n$ \`=3z_86Rۘ5>]CV+ޠR 1Wାqݝ#T#~l]@輫or=UJ)o+NN-u ۠U{}aBN vjvSZg$HUoIPiMM |$x:<-W/Xbg4PRЅF.OBBR"*;+f-ztB +N2imL&$6jF+ ef2*n1yd[˷&5Iuu f6rD!"ڥhhr$] #nMZ=\zfO0 ]ZVYTOΏs/6RQZa]Ż-C-)({ 9}obܙ>5n[u5nUJ()QXꌚ%G9MZf(j*Gᅲy5HUW| {kl AzEwˡCf㐱~g/}0L\ԍTZԜ&ʂWk6RgJŨ%/M}% '.}kj5]r2q%7KS5myZ)L3K#V=1/u #n!#-8zH\@+ٛn:a|K*6- **g +ᦓ (b0ӄxE E2{q֘^ViY'TKM|LJ#qV'kyTa㓁G=8[K+\g(;z'Ƈ:gob-3M 'HlUjw5ʄ쁶lb`j{p.u jL}j?X Kvߗj^30}XMdYշ<>0n$)YcAz.jśm',aզR$UOk\|3ķ#r03-z\)a톙iM>w3XR?t{0^DmK'vkiu"jqhR%h>,Ul?yӁi }Fᦶ;cbARz<'1FOQ"~A9Ht3nYE鞧&P46-ViOBm6y3ǬkEbek#6メIe!\'H8Op: Ѝ9W0Ei/$bNr$!\XmInljUHv*ਢ yR8 [A4~mٔB6nʎ=X6ZN\:l45` qyōHQkO1QT_Z=xWQx3 |='x"XλLuޡ%lb<Vz;SFC >.ܣOW-Ɍg) ZcZGHTָ -ѿkh+3Px$~Ǿi dYp;SrkP*GLdRI}ZCnm +O_IlU;c4咪Sp1KM5/.>犊چñ԰7۲<} qX H1BtPl8q ,<@{ŭ'>UP7,e;*-ܯ[\>zWI4(IZ\H ^怐0z=զIy70]3δGAYN= V"W$FOv (=yDR9`-ZU ךoX#B3yu4o([k v*>")fu j߁}3YhOl7ֵcsj yk~V>בV:G^Yűv;gcsr1Hӡl#C귢v|}T nXqىMQ1%*p<@H4pTtK i>4^<,52`ꎇ[V.mU@z}06l v=F@a;7SBN>+H؇Is2 2dc`}(g_]"Ꮋkй>Iѱҹ!aO4ᑸᴔ>&;bi)ppldnUWyecaj*Ss˓s>.ŕE8Tv{o Sˍƍq~#YV?Y벜GXl&גx_@j=+u.d?Ҳzhs5WdGRF{*('hzpjjF1Luъhz/9 fX\dzspkit56S碳ΟI<φb%R5#^9  Op+c" (>=4*gJ8%K58_/WXs*^W4Wa(| rz{xԈ԰f X 2᥼QL0$^qAAe,3?.@;Xb4uRlQ'ۆhn1MƮkdf8CǦ$TLAW brWG[2dY3gZPNV\kRZE4!R|#zֳQtIl 7Qa`Yo40%[!7ޫr]Ǚ!ȃ !Fm'sm kLjm ashpTBkG7Pr{ugk\ƅE@r43$j*+ CW8(<|)!#IU{ ]Ŕ'\|,ǰ8ΞRt_ҶY+X5M8,)\u87ZbN,~ dUNQW][Q9<WjY"ގ69釷є2TTG,j9Eܓ1jW<2IMRS$4܌<:mį1Wv$8rkr3MARmY/ڡȶO=ԱE'j`yh p=9I4iT\I0t&ObwtR1L;2Cǖ//BC]ԝnW6PXG-6Y"+ Su/ҁfSèۼ+b}cSC[%11qVȬUg_Gp0D$6<]HN FÐ29$70*Ubuld+}ZZ";_(45si__wD pBU@NJw4a?c%1j68>ɻlF{wb*y!9&5Kxׇ#%Q'sĞ۫8f 0jvBW ]\NBn3EbX${n%I0JJ9 mXllzǬ4'痩2 /Q!m^*̩ ܂hWcRGS/=w΀0(Aώ V֟c>&?洳K1T5ݝ=++$!)ڎ٥?>ٲL<*yBA?F3˾܍/7}}%H@rև^c8f5wۊȷp7@:$qZ[-yS,;V|_$P5:4&p,Z ޣx 2E]dW~ɭ緧5S/Ïel[Ź {8iJfM>б+˹1`ˡl IזkhFjˡ8tL%q?D,^bV¿0صhQsO|.!5_JkwovЈP d2[## /M~\h[Ti -87ϥM#|<{򂭿fROv6?VzJҬu-:: )W|}2E(AfOnX*7j3ǫq4\uWW5W F)yGyk/0YƪRf#ZYJߨ~vO­WzG+IT#tm%Pwb|`0AP*2/;34-b փ[(X`Dz㌸ q)c }BC8ҕξGSmY%`HdsJW%`u#i8lt> KWZIp=<0 Tct̮(+L^]Tבbъ?g)HuĊZ ?u^<6{/Xq:F TXQG+a:]XSBzmާ;-:7#%20_^-m;b2%(Gе )VC}8|畃g/zZiS7mDKt'a ĥYwc5w mf ʻ 9K? TH˚KZ}d}3LG=Ab>{$0ܕB^>unSqfԿ}UW`"K+PI1Č# ۾Jm\` 䦍i#$}QO e]іoLv S N6oɧ|2[GP>܏%FMA폶kjpnhOŋG2QҸ]zq DV{c`0:"ƛdO?Nf$3^r_ʃO-h?xFhfp\}[M8zb K\1df4'eyݍl`E '5N_PK]?B=0J/JT4 }zW6RZ`]^E[QUkssre%"ћHzeI%5}%ՌQ#5Sϫ߭k $7>j(Us0^ZrT@C-ѹߓnFKt_,[Q}~Fex`:m1 ^"|#o [e^@O\yEI8Kq\Rj ,10:ZV⻂78]$b2dt#!cobS隔Tǥs[Qk>*/m X)5dj.v=NxΨ6fv/Ƶ9V ({hb9ؑ\upK7n;gO_7[CkPLftd-%~a`]7Jie?Αybht}q@>ȮG$wI$ =裉QԮw%"9<\8қ`J;U8q 1"Z,ZQMji_=3J^iĶK>8RӸXç0TI rkR7 dO'Fn~ҝ`BebP^ɣ3O ֋, vavr5;YdWQ#.,%wýJQyf8=_IB^NbSشI.؄3a=p[Ckរ=16moMiCI@G#,5ڹ"(fnjmoܥLYGlhq FHykPE06~+88Ukff jt#3]RxםˍKS1|0m:c L+_덊dkݐ1zlqHO*2X_+Oo,eanksD 4ȖOY^[Ou 1!@::`&$h\/E|0Q[95˜zL>#u_hC>g$Rߒ:ڎ[ ?2,{$b23AV᥄ ¤TLS4FZZy׎on`Q ~F>0U[j|>/Ztz(pyC%u_!q@z$AN9x=pIm&M{Z[;'9Anc ,)\aq9]i-WO$~+04H _m7 ؁!Em,F*ڜq]Tuv,ZJ OtsmXn; mfY_1Au=T(Ŷ'"#dbݎ4"WBuȲrEcn#Go a:Ħ EmJdE#M1YM=:DbbBfon9!d,QB=nt'+VqH"Zo-LgoF)jasExAQ!QcJ=0E힧,jm*h{dNZWfцG w"3 58mHShOSl(dt#.t Ka厡k%CJᵭŝˈ^puVÃ5hڇ  M. -"mjOnl٫w&=yql[^MXUv# "N cN>Kx~@'iW v^aҹT5ܾȧ~!9N"Ge*\+^uS=%8v.kOa/MHgYI/YBL+K`M+}M(@gn5pZ؊n!7Xp}2i݀,j)` X c|u0Y tS,'׸?_0HuweƄ\ޕ2a!\gaƕ (pG"XNrR R(Uwo.$ ?\Edb &ͧEErKuCN :Ƹs|1VTCm#-bAN4q3q r r~IL:>Ef!PW4(1~4 lk\WC0mK"̱AJ/*#!Myr@R~ )&{ ?QBRV^D4Χɿ-PO;no7ӡ>r#ձҺ[#%\P n{I乗Vo6; 9zZNVo5^'Қ}nDSt=65@fi^J֏JAF)oZ̨jX~Nak=hH9֡w+ pwQ\/qaW!}J կՒdkH6F V8I.i5F[c{l픛vi\:ŷζ4ڒe!(9Գ݂ӶĥrM9C<- j@+Fjh+wUڸU)ޥ=ܚƊFNJ?1{kuU5̧Rs&2î)hh?9ټBYi^FhLiа'4W2GrF1b_NOSl}p]+HW4(j( }`eCҸ7ˋoi4((iԒ#"W˜_spdhB-F ZDTB@Lt qMʝGU"zv&*#7! |0x=ia=dpo7.H4[΍Q c@ zUO|0%^5x+\-*s5e /5'3^;R-f-;z 2i䋮!̄tXS2j1 (Bc)M4A]z q8wmz^#aZv- $\^A$7X:専9V#S~_˦/+' >VL^ r•"WBVx"fSӖAx>\#Ҫ`ezu'kFz[qa.z qMY_a_%xCɞBb)^1FdV4pOOiP[, 7ǖIJLS5K5q#lLj^dYK]!Dzj#..Ȋ~6c],V9' t.K5ң74Imu:<0 c@aEW-aA!j2 =1R#Tlv07Z2]k+^qPi!d˭-S-7خ]%RI(LIaѵAR~CyrJxf䠝vDI#ȣ,xe{eZm25K#/-29sFf# 1 m#2э\ xȨQnUq J>E7h>*{<7wj\rL 2piig,i`sOlKqspѰI DǍv5ɾ}gTrW<פ*Dާ a6pw/dˋelqMoDtYC C}\\,$4߀ﴫh^(heEo Ir9{ٵ$HB=#C{k@탥&d1;+,XPx rx )DF1zT`,E d=pQi_H]ŧ Qj^Yv‘%SmE+}Nꌊw9ZMngbrekq-cnpSK2 D}j[؜8_Y@G(dೊBSrzaXmy^VpJJȮLum3QLmliz U0 i Ѿy%k*9ifBMiHf<{a尵m8 ٱ i==8}sk&=v3o<,qeg @0\xd\j1J@W:AmnFv1Gt\@-z;Fn!7çNir.uTG ݲgZ*x9涷*pH Vuh)tx:kۡ댎:;a M8qw]Z\F.KpAZﭵ# wIRzl`_o$wn}'&X!ќ( w = 0-&K%2Z4X&nm S\Ozw2#3hDpa[61e;aMJסT`j r5ul2,`|ތHѤAOrY"+IVC1mA] rDrw^m[;5h2k7|Ǣp1z + %#1bp4y׆F6QjF-c%er4\^Z: Y @;dv5uy>d%+ X LK+qm99͢$]\"D~۾`>ΰɴw8?bڳܶو|ٳ-ɱmkMڵ&zgAC{I7f32?L3VUC`xaXSOZbtJuZL;=hXtRVvN,)/^RmOao(A"jxU~O( m!eq# $S"~E ~6}Y5ӇIP@l{dB0PqD NH w«~'ojkH69ZVumO[hc>%njC"  c\VK! -Z(B>y7_*$~{ihuTB80o1eXz;O=j.բ:; E.*=%[hќrŪNW7lOaPFZ)|[G.Ͱ??Ư@/4ޛh r_T%!j ;'VzX7߱$۲ԳژjNcȏ-9T Q:U;bo9lio(@jۣn |;[e 82կ#VC?A-@:V@~!kȷ͔*&q-'@B = y2\ⱐJ?Ii3&bi1B8Eܭ@N.-I}QGހamx~v/vIOXZ5 ސ)4YgQ ":7I!쩧kH˶،!NXŌJ)ý1-^rZ;aVS!WӮ8t(v!_EdکZ +6yI2GyF i$?gpC(/vafNyZeC0mtYtũe ;텗Iȶ@emeTA#B/0 &22R gVi5׭=hc>-ɰ¾ʲѱLUđ.9'+h8!<z:1>߈>Sl!A'p7P0)&jMއms.eiDWM$nޚN]}FCR?~AWIvw7e%]+MUh~#8uJqFTIin 6qTnAj밉.ed_D b@:Hթ#ØZfk?ٌn-&,6#{|pJ9pJm4Lb|YP[8 oi9n-P0,%R1Vԡxd&̷;S'W^AQNDmH̩Gcj¤cp꣦_ږiӳoL[MxE~:uK++$S":7REFuzJOLm ݍ3E<GzOpI_MO֕o;iiCIMn-abZd۬,=1ZoZen,>ңF힣Ar@rQwZLlXc5a|NĚcM֓=*2f7k]Fw!޻(T zC; (ծYksSJ%gT¯M$G/*vVQT$6WYHȁ.þ|$Rx=F'm`O):^]U}1-ӑ lv1ʐCӕweѭt_ڒӻ@$-ȸ3,)epݲ+a'Q,҇"^mͳAS 1Zʩ4NCL,S$q f7G9'KuYIgq6[|;i'{KKS\fL4I4r~M4U8q$GM鸛w¯-]irj.%WƘG>jfD*呋{Q$|M+Qa{q: ^XL85xC 0FoCcƟ ђm#ZHoN?2T B6:8]$zx9ۼ4[+WU e0 G"~rߗ#,~yWP+~% <.M~,-Tʑ)P8d>_(4w|Nyq&fVDw匓Kn ~Wpl-Cq ҏލmOʌlh0D1va\hm<&$,}n##gӴ&$kC4#,r%0VOL14MH9~7n}#k nUփ Rxo-^gur)ژ.(-~jp{baeLz a xxبm+9xa~0I f:YVDA~? ~yNk2Jkt OΛ`':rߕ2qmyCT^Y$HkR>WC#/ ~Eu+,)(X:CQE hL9X>1OXef%%RKe TvíOM@C\?D j~ŭ[;iͿL~4WE@MêI'E(0 O(_G Xz~Oy'V!N0%nӭaU^.##j$2 ϣ+*6Ԯ+c˛Bb?Lyn[{'2!<2V֖*Uæt] PC)+^|m$DEMUZےZ{e,R勴N8Y YIEݜZi1^Ǚ 5A}N([5JcM jO3N< 7415!GgnEfB=-!\;m.X,-F: #UqZgo/STGN nj^|Я5iNXFM,iZ'OO*a,OXfu]3[>ialN2i5_O|pdxάghĿmk ,}G B Y?2Zen*0kgjY-cXmՑEȇ߸Z}1s]Iq+w\kgӔJㇸʎcs"%5è`')򖡧&oq|K`Au"|˯y>ҭ Ti2-]?܈6q8**M'YgQ5_p>Y4SA =1Bs;i)]㉁bGa 6yh=zȠ7g3+=ܗzq1G» 0\B!CPd5Icc:\9waA];xG|,OQ-"*LlIp.G)Lh6Mo ][q}+ ɦu+(N~0XO/T>ۮEudD;=!ka-#hkȱq$CͤhdCNŸI^i B+µ2 olIvԊ`@=I9-޴zSIfȴZaOS <8W*1y>ٴI4ۛP<Dž4__J.ι-S˚ Sw@~>3tnje~j#mro M[6-GEfQ\\i!Hקp+~2Ӵ4XHg5xptf{[unWj?fr?k隣J]? j]AhŴcn4yykZt֮P35rpV-&+͌g惶]S'yjZm']F>8p[]qq +S9Sxu޹.Q!0J|Ɏi j掣|, QTpNY su*zL/ (>nuYn%!,۶!+k7V6vCLkEq:Չ+C"zU VGekz@/\,BwU,r{ ƙ<ёMB/  -uGկGN"cS 5㎀#G僼a[۱7cW IT+^5m-B 7wv]9 mG|SfRiSAu -9ԟ&zLR q%wxUEn%(wo,Rc]Y 7?/z$`8/[:qrfvHu O1d#Pd;iMA{ ub<2Q om#(Php˽jf(5>OALLkI.oCit E 3ꖾgY7%mg-jYnV4"(bV0;y{Ѡ@MCq5DE{SN.uY@bnpq/6"r96 %O#q, zOkаi[NU'5(-&`K4^Olm=?t#ǂ 5{y)ONW; Wl%7Ep!A)#Ilѡd pSǎ >`:^DbѨs" aብ@h6NNOVNHyJpen +\mc>xFel1˥F5dRermu)Vt3xW f,'Cm( 7b͵"BZ !0ACn"O֗s>O򽦯s/c\fok'{rOgg=fS#z MLݼxdKa$_JwvM4+ V03mL~G%~+Ѝzx VXGRdLV9{@w\GkzmА=>>l3"C5op=Kee@lr{ #k۴XZ@z+- <0EӟźR0PM+kFI*Z @Dv?Nk~]X-sR0tZIШ[: #6k F]511HnMmV,riF#ߗ-ﵘuJRە [ʁ&64ᶥ[oU3Fjd܌sgQ 1]5nf#F*Cima9GgPM0>c4?]OWB\$ٵV'cN##Wt$v8بlP0-&G]iҭ!{zhdz5 URMeլF' mB# OL2Ӯb}ᘽXFVzX{W@6P]MT|'|Y5o'kd^mľC^b GCw~ BeT-{sq!xE=BP +:tv2t4Q#p&F6D+]㉍ԆJԒjEx fm41PsU!"izȇEw4iWYe(=(p&;XP}tO-ջY,3h[[gpJS' *2E%rTAuRz|5Yg]K}OI:V¿L+mcӴ^)Y 2N# v60T[n&%[bC ~9b/c(Ὰ,^\{Ic)ӧ|eFLjڕ}bB-@s&ˆלC>>Τᾱ4Ჹݴ9¶ٻ尨;#Xm:Dȭj7É-2βϳ捎1ΰŹC9<)73Z꾬Ttaq,RJ?-$(u؏7zN~SPgltn!`y8fpG}XZ)9"of8w,#ɼ*o=~6[>aƘֆ.r] _KgJ/YSᡯ3TZI(bBPqKUlnZqQJ|Y|ѩߍy(z{R}{X⮁z52>,亐OȀݰ/3 KvM늆"57xs"=G| e/m]Lg_&uɠi,^tzQ==qJa}m-މ>33߰Я(Շ0?6܉u⹳$糦<3 'y{%9g.u$O!.,ocZ=7+.J܊wqw %arMJ`k.5& @rr vpb-h"r.$IcBs_:_nYGV9*)~ML[YB#|a:sF--"[xkky#Am !zd'5g !dz΃ Q\)9lfFsTt/9jJ@չֳM"J"VT.?ʖ4`0MMRjҟ<]_Dy3򭭢ݱY>:\"1p8ccVXw8yhr+@/u+TO Ejm hkP-aðg|eγs bM\L̊`2O N=*iS J5&!0&|Q ;Tn0$0[ۤ tؼ.VN: ̼jC߶Hm> .ɉѬu %iE)fYy[!:Ձ؝=qh3MzI_G`Y5nM͖@ܝkN#\cl As+US`pD׀ 4鹡8fDѽX[S14.fPV) RqtgUQ|gプ#;ys#o*yljPg,p5Yi:n|R(7lfXsA.n&sKHfTԠN9Z^Z0#:twN~pM_L0owӧqtibjO]v+ }#K.a|0ϧaaA$B -)sa qh)FK.7 ;WvҬ }g(۵*v8BV-ǩ a%hmmF[SѵM" +UvyTShZ\vr4`$y6me'}0Ua]R6]h1 lQ{ u4)a[Kb?6JG@OizՍ킨b=Gƶg=򮮌Jv5"[]>ϕ#݈浫h׮5!ڭc!d^k9 %n طOZ/ϧ*9ʓָ7cCGg|HuK[TGSL躽ݦ.7ATS#MvxabkWHtozI7Zey4xwUVjZ\:V䀵6`M̪4r2ykS\'M|JN Eb?us^SZuz10.k:'4>+omZ?~hi9 W8{U.9Դ3i|~ޚc7{W|68EYˢ[@ o$Vi:HjM\'NEcx#V(e'b\BFX3_y'ӬtөGPx.֕u&o2( :򏝿-l%%-BY~嫻;HٙHI `慩\HP(Ǖ 1ZkOgRiFGf4p otrx'. ["76GGjz"(dʺ/.e䭰?Xy|):~mR6F t%j,]iwU)hԮ"t+2A&jP~XIZ<4'yE+b]k .jرgja.W| .#.`#*r+X$Ykûg`m{pnژkijocfnS+/QakÇZblհnm9H w^__I {@RȀwpX u5kr4yWͺBm*GI2yW8t[KVUPjdKP_OէtbGͨNq v4WvM!}#mJIudk ͻmUN=:u둝{PF|b含*Ns}];;# +?T;ǩ JqMbMh)t{KCxp. !`#X!H?t&C滬%R\iZΡj GU@$>]G>6 zap6ԋuۍZMy@(@劾}t_QL ]zt5h@vȵƦ ̋:jvZQ`"35;S"z!w'+b:a|3yl+N sr򥵊2,Iqdƙ1i=3˙h}*B򍷘`5Ԋ*/Ǚ[T UԵU^;W|oy> rpڣjJ!S y\$^kHfaS":|vqc[/Ҵ?0iQ_K1OiiU"]|s*|1MjRder5 -pt:|j5Ӛ:O;DNG]ë}E'X`sA5hkqxԎ$m@UU`o}rvi-r,"Wr8_8]M?NH/;8cda\d֣JIp[Ym`(4m |l+75N;W ` :Kd8ٍzW5*GB9εNT1JWw=se5u[x8OTr'i2GՖVcMյ-} Uj;#ɾ[Uxy"EͮmYѪ$/]_$_lM #o8_hn-Yd /Pz$K_TKV^؄qJjH*ƴ5?ִjvCf*pn<%ɮ![栔5kL4&E# +9; p{4M@s+(|<{mXD,wq@j`MIek ԮÐT; ({o'")L\ ]$H/`1%s [jJ!JaIg>^Un'vuǾ6eW= 8zMv3DXVqt}BYPWj3vZLffF[l.Z=KKzjIth >_S]a&u,%mY\#".B} }rMi 9%b$z}$| `Ǻiҁ`0]= }6e&Ulu[ߡ½jOHsjTjDeީ8"{`ܕz5qOjz4~7hڀOĞؓk=6,MuoN_qsrʘ+ױȳQ"nnN]nm5qkB-w~v/mX>S 4fX]=:dbWVj'^/̶0zN[uMr+ee{q b~\eީtTTM)QE[4?8ѢG8ChPJe܌UڴdSZxQYw'F!q+aeUlJx+lZWڨ۝9m~͈9cm?Ih T}F" >czq~$bRM I`6R"97m9㲐Mr9F{u_5i "[`8.uWl MҔ+46v<]4+iwbҔ\LS+uRWw7&]LhXFik8Hօa[` ~OY񒮧Z2[8_jf 5}DugH}N/0\Y 뎲-[pdJ'ϨuA^3[vȎ".;K:r3E9'Q䆶|%?xZj0s2;kXzfcUly^%-FpHL<=)FrjL+:=ݠ + ޸egk(#lkמZ>W߯z{x*8e 7B77(OY|ⓩ"]JI4#O4ն)/T<$l:vJt EIcIjh_ `é&Q$?d η? iݓuڽ:c2`'.:.yN>ؕ 1+r% u ߯~3蟧fe&"uvKSA=6 ݺd_̽JN3 6"<ڐF?Wڠayk"ڻ:׵fYDx!RaW3~g7T1#2jrD#ӯRreⴲafx&u9*ѫᆾaK+x"}VAuwAЌ ɯF-5D*4Pq™iLF@>1+;̈<^KaF9m='a`]DO $ "?$Hԓ{n7VOm_QK++ 'RƯn{ޘisn $+?*xan$~[v'l*Pz0 ,5YeS99(TA3y;VysQKy3ˠu&&y$ 0We[oTk8MmtK2.VM@uo_5UNK08{ 0bx6M!%\uC+@#=1[&ӈ?ԃŷ8ag;fe-#.aL1`vA;5H<7 5-Ҙ4_փ إ pgVI'}j\g#nyCҘk#ox$'+q, alҎd6lnN wrWG[2dYRБ .f 8l0ӭd25AS х]e5_GR1~գAZ 7Yl4fqh·a$k8 |2I,ًPa55"1'Ffj)!ӓn)5)\Z7hJޤ+37u+Ue yrm#d%i뿆CR|^j%CƁ{v!SNXqk|~=78ȄiORks$;^ysT_&&y؀ ,O9 00)%;F+cQS5C)A 3\ v䳬;eqY2>>7*Pm.!29F= aml]8_Oj4١Z}_^>7_%㡯>>!l7˵泦8"$#A5.棾T¸EOഡ-w팰چΫ1.ڿ>$H츿2S"-׮.Ѵ>ɡ#"%D<7@pP*Y ))Gi]Eɫ$mƌjy/񭫔?yju/ HwbEisNm Nw'SnF@p(ɥ16 0"+@k{5, Xr-v;Lu546@'qNbhHf$Gjn9:p, .Ы0N2zv9sCq%b^Nzz,B9 =3,*-HsNSHRi ֔:/Ӎ;}sIiONx` UwK^T鑙Aҹyr /zƂ2'8~v]3? Ӯ 8kO_\ZoSoR;v}Cӯb=!ҹM֘oe#zqTprc<9__W6y3b=l=2jzމJw2⟵bBG.˼E|oߦ's/jt3zj`7O/^S~^0/mZe_ˁ.ϝOl\ci AӮ2?_꧍==ο 1o?^?30z7ژC`G/#<dvf&3&r^?u]={dY}hp*\n^xMpm=e^{[zf p}SRZz^qX4Y3'/ڨmǗ=EZJmM5i? ?I_׆^a/G0s/=g+S._-TW˟# )cwO\zӾ0DcIW+˿PL"X4pqzL_+K`S=i ~'O|7BM7G/߀5Z6yOF6UiZ~jq5^ endstream endobj 95 0 obj <>stream AdobedC        s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?Nl7Cߒ-h ws#UۇXPPs+y󕷘˶6zmK1~ IpGm+m?m6;Iy{$}D+6fsMjuͨNW0͙y[xfd{.?*T<{ak 䖏 ,ip( ?%yY/|$qC|3J5ٶErG6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳfͅ>aΝ 4_5;oI{bJ5_qf5N}J=GP.mTm6e]!b$^lӋH3T.dJƟd4ҥHmJ)EQMhwigip}K U,B؞9זd_GoкoIf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6l\/&46u<ٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͜˰? +r΋]P?lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛9{p?()8 PzMڻӣs\%rK{7#mK+ёr{8o'y|nY$4.B*@ۀ은Ji͛6lٳf͛6lٳf͛6lٳf͜H|q9fNcڿս4,>:~lٳf͛6lٳf͛6lٳf͛6lٳf͛6ycq1| 1za[տ_X#ea#|_?vKݵhZInxzJf V^%f͛6lٳf͛6lٳf͛6lٳg+g퉦ě:lٳf͛6ln*Z :v2S~nI lckpV-†0z?7L/+;{3IJr<ٳf͛6llR* "uGRmcf͛6lʞCKyЉKhyu>w#~X~myKIB{bOgx*ٔ6lٳfT_?|_Yi~/2jļ}.\.d6lٳf޿hZ|}c\:ƃڬw> ilxuƍdt3MȀ*w']m/ڛcӎ2(n.e9f͛6lٳfimʹM/C$~f͛6lٳfk:Sk>j2][JƦI"R>/psC PЋ1(H@UTP(6leU,,@ Ϛou;y #D*7#&w"+rZ?v囩c[eck4,B!~9oᖿQ;[RYUt dfF~^lٳfiMyͷ"T_Kܸk9_HD''u?mWњZY;C0R9|>h֕"?<2&{[mvRd*>⢾&ٳf̀u>Q >鬮- PUd_u&w.o;?{ۿ&$TV]oD4k[Mo^AoW7RT@0'f͛#n-o0kVub L3((%jBJ"׼Ln>ˤP;ʜ?Kن=>W݂PKL63O?q鷡<2q8_O1Xi}+P<|^W,9pB~Yٳf͛6lٳfi\ޘCKh}<Η6lٳf͛6lٳf͞K5/FVG䵤+=zyͺƃKwi^V(d 9JU Av9p #i wYbBt_;6G]Id75=c=8py)5SC/-8/wW Jf͛ 5cAX[լ/_[8KvC -m`TeѰtuaPPA)6l71jYc$*g;oӦ@d?x?.|}ʡ-X }%UgD'z0'1<9 XD\ˁrT,ѷR+/#BZ@Ŧڍ.nYԵXpS3 e2/qlٳf͛6lٳfeF?!Y2.(5:oaE7F_yO=1thRmfh沘3~Ȍ{Ӿz_Zl^aﾪvѼH7V4Egw^Gg͛6lٳ~X|WݴCr^0DڼXIɩ޵8a/Շ1?[x.U* Jgǵ-SM줾ԮᲳV[(@u/&w ;7jCoa #cbaux Egnޘػ(#`O^oH,oGlWBjʠVV;6lٳf͘ze8yeu(ԳT I2obmj=N҇BGAM6:&d^w?_etr?c~fj֗vLXdZ ::Oߙ3QGou%طEmq̕^U':lٲDVUfhO/6C5_k}O1]ZڤYT>˵2z/Y9sf͛6lٲ~[^kvWzQ=rHلMEF(i]Siu .\iINxb')*ezr?3%XDۡ%wfc/H)w^XR A93f͛6lٳfƤq!($ ;;6lٳg(#|M>/ͥ3!.\IvU!C?^h Ǚ8/uH-664h\"M8~y޳~;ZK5ѠgxdsWeVVj)hDuc' ;L3$vQɉcb.|az-KO׭dǨYA:JxԈې t8A_#jkE$\^I5Bk_j#?"1/|]x.+JIF~zɷ#dbsƱyIdRXY1LzsC/b<Χ4 2M!FENxhy.F'OZy=jޔڝ׺}amjIb%$Phw_>t~soO?nf]BTXV=.%iTg4K+M0~hE]^ r3\u?3ҍ"?CqH#\,~rRF|Kg"d[r^iyS_""(TP e͛6lٳf͛6lٳf͛6lٳfsހ fTҭ^7 {sU?/ww4|w|ߛUնyp$(bnQLX- V=圗qA˸vD-z,H&IV~W>Z]I-4?}}(Y Fe@UɃ*aUaBpsRf}NMvhK]c/Kl,h\1gJXIj :jף<| DYU>~lٳf͛6lٳf͛6lٳf͛6lf$_yJ f͛6lٳa/<'S`[=> gscMYO;Mmzc=T*Y~!Zѳf́u[[.cmqqCp+XЪ\*/?*s$[W`\i)}ѭ }"Q]jҎ"Y@;rj#^gcg]J*=JQj{L?.k{%xJH 8e٪)-9?=,/!",Z~ݾc7矟,AW|Vuz0ېZ~FbkW{mK,B5͝1ݙb+uΓ)k:zh Rzo݉8m CԼsywL85 mfe9Pƌ:u 8.̾h1ig*M%IEFD|\SSҙ<~\PV-ia\.B]o#alٳΟ?h}֟,^ c2"&jcnFJaccz@,2e ,k;>k-F->'9*Y*"v' W/HߖY󄾉w vp='/؍}Ow_F%nӴ}"(.V^wuCd?ɏś$k-{PM[VgCh/#zIBi/roȟk-CWҴkO& VJWALw?H44R+ʼ h}9ۗ>MAҾ9g!k5^xU߄0n PnMZ(C? =?gX{b֔5ȉC*K # - nZ)˿0w7Wcsw[i HƮC.懩ڙ٭mm-aA,PƽU 1\ٳf͛6lٳf͛6lٳf͛6lٳf5U=v\ٳf͛6lٳg|8nϜMYKox^I!gA+)jV-3VӼr6zt^;л%ڛU݋;͞E󝗜|ϦEvE-U72n5˷8&`DW_MuGsFK{Jn⣈uH(Qc5 h6lٳ~{~B~f^[ݍ7 bu/r1JؒUM5"#4:I.H뺐UQ%2JGU|3f͛6lٳf͛6lٳf͛6lٳg:c\k^pinV*Ou;!G:bAMJFiXk}B][ʪQ3FSPFOf͛8ތI<=vLٳf͛6lٳfȧ5.Ck[;t*(Pޒz 6.5&t^C鰨Rxz99 WriT}J% WNGe=~|/XG96^f+rv-$Uy>%</.Ԛϖ#Q #EOvΡ8Qk^uMvQ {~bW }GQ\sο_/,A5o/.)ؤt$0⼔PnIg59d-oCGXkL%:ϞtO3xԵ;M+U]Kex(kE lvNZ41ފ0MB[5Xt2,.Rnv/yG[Ht &Jbe!GN\;W ?^yԯQڛL55}7ZuX%51$2۪!y~ѓˍ&HK!V+xi azw>??֚ W:H[W@`'a?E$DN9܆~n~ZX~b23}V:X]ҸWXxe<˸mΑpda1<J#ޙ<ٳf͛6lٳf͛6lٳf͛6lٳf͜ӏu/#_>\+-T{VqL4/4y\Ə)&{]e&J9*͛6lebT=`6lٳf͛6s/&Q}5$ %%8܊> #Z{qʭ湸ײ "Klm^E/Ir]R3B[mo/o:k{.Fk1h7*V6Pi\lٳdAi=Bьnf29=7a8o'7QyQԣ0]B2_ӯvʽt/)yPZTdS/!^bԮ8}6lٳf͛6lٳf͛6lٳf͛6lٳf͑_2~aZhhN^MmB03hB͑᧖9.f/vCR8`i8 OSյYSR`m㇏2doPqïD??=mz>i}Ny!{;PeA"zT"^@U={w>q_,|#[]u ` UԐxʩ˵vޙ4k(914 y \jMɴt*$ڔn-|fK9-yȐhAcԵKeހ1")YuS8sZݤBg Еjn ٳf͛6lٳf͛6lٳf͛97cVyޥ'eӄwVaixh1I^;2VySJ,5SD{VRx.OQO,05 6ƙ0͘TSA_ŀi]|Nlg־&]y͛6lٳf͛6lٳd[_>Hս>gVꅍ)cNAdEEi[Ɓ&-'AOBf?if$?_g\f \j`P@f5݇Nנӯ<OiwTHHxw ~N~_y zo$2HoZBT{]д{G{uo1\۽@e>wt8COʏ!yf>YҒkIik^-dd!}4q{mR ,l,i_<t.X%c#FFwr@yfO8/^q$|d0pdu/ +&游ޘ-WrKc^BTR|f͛6lٳf͛6lٳf͛6lȼ{K]n^.4CQX'Do-_H@ R֔9%ƛPu=Jo,gUHc#uVXWv5lm|)<-_*yv_Ϥ2ɴ3*E:&ǥK;Oմ-ԧԶ~hZʴ%:3zdzҤdzqխNٯ<~gTm8"G.[Ԑ3mGN3f͛6lٳf͛6lٲQom4m9{B vbYEkƵחI#O$zCR@ɷz].}nyD0DEdn93͑?2~[:ީ.{ujWXL xsn.p bZg.Fttt?і3]͈Yd wW$&hzE-hV(ԓN-V䟒 kW~B+Hљ<噗~ο6lٳf͛6lٳf͛iVc1A=9#/VSh,^0|-ϣ_K|[MB45JI ]ZŽ\\JY**Rƀ__|nkCqeIxFM:wwzVxvp\ #K9ab(Q#@@l~lٳf͛6lٳf͛6lٳf͛6lٳfM.+]b'CnlR-3-NAq1UvmA0/{&uky--Ӟ;ArS6lǭmBTB]vٳf͛6lٳf͛6lٰ|D*6zMNTҵM8eVAgM*V ˏ,Iq-;]okB)_NgC1Z:i͛6lٳf͛6lٳf͛6lٳf͛6lٳgZoyH{=bSpb0w$:ITVR -Xy6kkww&6)g>'$$*jѰᓴٳ=[Ě`Û6ٳ͛6ٳ$ұ#ݍՒO3r,_/&̨+/;ǝC6̪U*;!𲹳0ƶıp1kOt =B )5t5W%e>6ٳ͛6ٳ͛6ٳNNȚmGݲw,鰭H)l':Ƈ3cI,p xŽut=:[eYܙm ۀ%A$(OYnIMsg=cgs%As0Iz5]ȷU<9B3y3w6^cNѭD$z\N;6lٳf͛6lٳf͛6lٳf͛6l㟚wǕ{>d2ﳢ,=)x'(.Չܦ!ɳ$,ﵖ$>T䱳VdQ˨K#3+Ŋ85<7ɫ_+4Lÿխ%i+dI(XdOc?η?+ڽG}I`?S*H //_ޟ#o*Kհzܹ`{:6*I-wUd?vA]zyfRk57 }kT1=6͞^{׊||ilcsqѻhQQMvٳf͛6lٳf͛6l}/a6lٳf͛6lٳf͛6lٳf͛6lٳf͛6l'?m|oa Bf>5i,7 ~"av_oNk'YZO K׏y [#1+Ե2Țk+܈ؑ9G^5lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٲ"!@-7=Q&gy) 5FcM:FYr6WWCeߗ:'|`k{?wrۼ1,ƬMv^lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳh~cyW~Fk9Pzt]:ۀG7-ȱrKɖWW֭3֒XWozo6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٱ8Ć@ )zD NrL/Zy˄HIU?}9ܳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͑2yTSjZ~FKHg1=FY9K+#ZIs?2y˶:킺[_GE(FV[g C9{光-ƃ,shpݳf͛14[Aq Oo"M ,lXx6l o)j>U[2jiz+'Y)CȊɖlٳfPzf͛6lg|1`}y*!:P5͛6los_W/NҴJf͛ K(:0t)くv2IW='Z}JMF72[7IJ͛65dHI%x! փ1ٳf͛"DO1'ͧbGWq9)͛6lٳk^U^bKo>CőZ49[|ǨkmN_7aaHf%ʡԊқk9 L__6?cz?͏ω_wcj~_YSqWLd[:JUJVee8:A֋qdrƿnl16qeq?o/[C2ǝ!=6?ly)!qsk˻$0!XS/XSy?%ZM iVXǬdÔ7Eo%!JF'[Ui=~xqۇzMȈMjI"N2ua!ׇM>NݷK=>>YѿVY*5{"˷$=!#oȡٴʬw¿/?ձߝ³2ʚi־Ѳ7ԲϜٳݴqkݱ5˝)ճDOΏ6ٳ;釙f͛6lE9[w޼cagW3ה!3Eݛ_& [I\Xrd`+#)VV4|"FyԖF4h&r*AnT˗OkKӥ/m^/%$Ǘ]ٳf͛6l#[7s5˘6bW;NvŇcB[Keip Kf~KB/~nRY RSvnevD."**w1_gè.97iqZ0X\k߶Kf͛6lٱ;kKy.nK{x)f"f <|r.c\(ܣ?0o2{n!]ދKi%D&quSxf2kO}5ݱ-:kbqGjWO?Z?rG6lѨh:-m}r}b4BI5;*u6-;Pw[tg5{,SqbJGoM*k'SӦg`?VZZP azsT̊}:ڧtw^=*os6V?cXKS= 6lٳf͛<`gtǮhUG_RܴlG詛ԧ't__/%iTWSSӵ,b`U 4"٨v #!W'zϝ`Ե[!uK@Ms%c)k@6oƭ;^Ѵv3yZx+V}3H%KJ=5I$;J͛6lٳfqFB5n;-GӭGwx'1 $Q, X`W[-DSsyOUI !Vhy?y{+ݼu1\;_5^vw=ܐp5ޣM OŤZY#r\\jY}Jq랆͛6lٳfU'*~ey3ŧéiZl,n-)t_|6K/Iu瘣ak2*ŧlӼ '6lٳf͉]Z^[mw wҎ2*F 9)-@OoeOl<$ $QD( * O2{vē̷qZ&kc}}`ݬvF_޲̬8-O6,o<[:Gהtag=}DOegdBcg7_8]}Yf͉\ZBa'Z)T:n*1|õ> 5[X#N" ^lл0G/:r-6lٳf͛Vb݈#ex ^tOl--$I n r![wr-TqB( <S|[K[HD+bB(͛6lٳfĮm-n0]BM7Vc~wڟؒXXݥKu $a\G,Yv`ݪ ʞضlٳf͛6#qegrc70G1dE~,?ij }88`qM{W2FQB(7`ig(iQϋ0?N/6lٳf͛@Q1J w5&h-"+o\Y*-αtVr͛6lٳf͛6lٳf͛6lٳf͛WRӮ 7 ӗ_zg4L^Y<ݫR;o+j i,ڊO7̋n* <,t;b b㏣v8!Їܲ+zx*NY~:ܲڰŴ=̬ʴʰiϧ:ű̲3r9hiް>n$U今f͛6ٳ͛6ٳ͛6ٳ͛6ٳ͛6ٳ͛6ݲW`M^ɺu-KF9h!`#L" :y5D5o(^hǕmZ><7:[EW gO@,ǣͯy7Q[ht-G`xxۤSTά@:GBۋ;WOn^S~mS9rs-3McV_9y XǣNFӈ_|`K|uB ;5ΓG46V?%KKSczՆft7Dzm- -)Qd!-)H'֙dyS'Ǘ1/.'O4V bQi OǠ>)t?]K1:sYG3-Ө9SZH"*nΗ6lٳf͛6lٳf͛6l endstream endobj 99 0 obj <>/XObject<>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/Font<>>>/Thumb 101 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 102 0 obj <>/ProcSet[/PDF/Text]/Font<>>> endobj 100 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.9663 0 0 8.9663 59.7543 725.7825 Tm 0 0 0 rg 0 Tc 0 Tw [(of)-268.8(such)-270.9(studies)-270.1(to)-268.8(date)-268.4(have)-269.1(utilized)-267.7(gamma)-264.1(camera)-268.4(imaging)]TJ 0 -1.2203 TD [(but)-474.1(rather)-466.2(whole-body)-475.2(counting,)-470.5(due)-472.1(to)-464.8(the)-471.6(low)-469.5(activities)]TJ 0 -1.2266 TD [(deposited)-375.7(\(again,)-367.8(to)-376.3(minimize)-368.9(radiation)-370.5(dose)-373.7(for)-370.7(the)-370.5(longer)]TJ 0 -1.2203 TD [(lived)-345.8(In)-340.6(111)-340(isotope\).)-344.3(It)-337.7(is)-346.3(generally)-341.8(agreed)-342.5(that)-339(whole)-346.3(right)]TJ T* [(lung)-392.1(clearance)-397(in)-386.3(the)-395.8(rst)-391.2(12)-169.3(h)-389.1(o)0(f)-388.9(measurement)-393.6(represents)]TJ 0 -1.2266 TD [(clearance)-631(from)-627.5(the)-629.7(largest)-629.5(bronchial)-627.5(airways.)-626.9(For)-627.5(many)]TJ 0 -1.2203 TD [(drugs)-466(to)-464.8(be)-465.9(tested)-466.6(this)-470.3(initial)-466.4(period)-466.5(is)-460.1(likely)-468.3(sufcient)-468(to)]TJ T* [(determine)-387.7(if)-377.1(a)-385.2(drug)-376.2(acutely)-387.8(stimulates)-382(MCC.)-381.4(But)-384.2(for)-377(drugs)]TJ 0 -1.2266 TD [(that)-313.7(are)-303.6(longer)-311.9(acting)-307.8(or)-313.3(when)-305.5(observed)-309.9(effects)-311.6(are)-309.9(expected)]TJ 0 -1.2203 TD [(in)-291.4(the)-282(smaller)-290.6(airways,)-285.4(longer)-286.6(periods)-290.8(of)-287.8(measurement)-286.1(of)-287.8(up)]TJ T* [(to)-338.4(6)-163.9(h)-332.2(may)-336.6(be)-333.1(required.)]TJ 6.7246 0 0 5.9768 152.7874 620.1636 Tm (\(45\))Tj 8.9663 0 0 8.9663 69.7323 605.2534 Tm [(All)-198.1(agree)-200.4(that)-206.2(despite)-199.2(the)-199.8(period)-200.9(of)-205.6(the)-199.8(initial)-200.9(measurement,)]TJ -1.1128 -1.2266 TD [(a)-416.8(later)-415.1(retention)-419.2(measurement)-418.9(\()]TJ /F10 1 Tf 14.3214 0 TD (>)Tj /F5 1 Tf .7714 0 TD [(6)-163.9(h)0(\))-414.8(i)0(s)-415.8(benecial)-414.8(to)-414.2(assess)]TJ -15.0928 -1.2203 TD [(residual)-373.3(small)-372.2(airway/alveolar)-376.6(retention.)-377.8(Twenty-four-hour)]TJ T* [(retention)-488.7(measurements)-489.7(are)-487(common,)-486.8(and)-480.1(combined)-488.1(with)]TJ 0 -1.2266 TD [(regional)-378.2(deposition)-376.1(indices)-374.4(provides)-373.7(additional)-376.3(information)]TJ 0 -1.2203 TD [(on)-448.8(the)-446.4(degree)-450.4(of)-445.8(initial)-447.5(airway)-451.9(versus)-447.9(alveolar)-446.5(deposition.)]TJ T* [(How)-232(much)-229.2(of)-230.9(the)-231.4(24-h)-230.5(retention)-235.8(measurement)-229.2(reects)-232.2(airway)]TJ 0 -1.2266 TD [(versus)-403.7(alveolar)-402.2(deposition)-401.4(is)-396.9(still)-398.1(a)-397.9(debatable)-400.4(question)-402.8(that)]TJ 0 -1.2203 TD [(likely)-392.4(depends)-384.9(on)-391.9(the)-383.1(inhalation)-389.8(maneuver)-395.1(and)-385.3(the)-389.5(patient)]TJ T* [(type.)-470.6(For)-469.5(example,)-468.4(the)-465.3(very)-467.3(slow)-470.8(inhalationlarge)-473.2(particle)]TJ T* [(inhalation)-244.3(method)]TJ 6.7246 0 0 5.9768 131.981 499.6345 Tm (\(30\))Tj 8.9663 0 0 8.9663 145.1905 495.666 Tm [(showed)-239.6(continued)-244.7(signicant)-243.1(clearance)]TJ -9.5286 -1.2266 TD [(beyond)-194.9(24)-169.7(h,)-189.7(suggesting)-195.2(retention)-197.9(of)-192.9(particles)-199.3(in)-190.3(small,)-198.1(ciliated)]TJ 0 -1.2203 TD [(airways)-529.1(for)-528.7(such)-530.1(long)-526.3(periods.)-534(Similarly,)-529.9(Regnis)-528.9(et)-525.2(al.)]TJ 6.7246 0 0 5.9768 287.7732 477.6943 Tm [(\(40)-10.1(\))]TJ 8.9663 0 0 8.9663 59.7543 462.7841 Tm [(showed)-264.9(that)-256.8(cystic)-261.2(brosis)-263.6(patients)-262.9(have)-256.5(prolonged)-262.1(retention)]TJ 0 -1.2266 TD [(in)-316.7(the)-319.9(airways)-320.4(at)-316.1(24)-163.4(h)-319.5(compared)-320.2(to)-313.1(healthy)-318.1(subjects)-322.8(by)-318.7(com-)]TJ 0 -1.2203 TD [(paring)-253.2(the)-244(24-h)-249.5(ret)-247.7(versus)-245.6(C/P)-251.1(relationships)-252.3(between)-249.9(the)-244(two)]TJ T* [(groups.)-349.9(Donaldson)-349.9(et)-348.1(al.)]TJ 6.7246 0 0 5.9768 158.3433 433.8707 Tm (\(46\))Tj 8.9663 0 0 8.9663 172.5165 429.9023 Tm [(were)-349.9(able)-348.8(to)-344.7(show)-350.5(that)-345.3(aerosol-)]TJ -12.5763 -1.2266 TD [(ized)-195.6(hypertonic)-202.6(saline)-194.5(treatment)-198.4(in)-196.6(CF)-194.3(was)-198.5(able)-190.7(to)-199.2(reduce)-193.8(24-h)]TJ 0 -1.2203 TD [(retention)-412.9(of)-401.6(particles)-401.6(residing)-405.5(in)-405.3(the)-402.1(CF)-402.9(airways.)-399.2(Similarly,)]TJ T* [(Daviskas)-410.1(et)-405(al.)]TJ 6.7246 0 0 5.9768 119.2251 400.9889 Tm (\(41\))Tj 8.9663 0 0 8.9663 133.9086 397.0204 Tm [(were)-406.8(able)-405.7(to)-407.9(show)-401.1(not)-411.3(only)-399.8(that)-408.5(inhaled)]TJ -8.2704 -1.2266 TD [(mannitol)-412.5(reduced)-405.5(the)-408.4(24-h)-407.5(retention)-412.9(in)-405.3(patients)-408.3(with)-407.4(bron-)]TJ 0 -1.2203 TD [(chiectasis)-555.3(but)-550(that)-553.9(clearance)-548.8(with)-552.8(mannitol)-551.6(over)-547.9(2)-170.2(h)-547.2(was)]TJ T* [(equivalent)-288.6(to)-281.4(clearance)-283.2(over)-282.3(24)-163.4(h)-281.6(without)-285.5(mannitol.)]TJ 1.1128 -1.2203 TD [(As)-982.8(discussed)-981.4(previously,)-989.9(the)-983.8(variability)-978.7(\(signal-to-)]TJ -1.1128 -1.2266 TD [(background\))-314.6(of)-313.1(24-h)-306.4(retention)-318(measures)-311.4(is)-308.3(surely)-308.4(dependent)]TJ 0 -1.2203 TD [(on)-240.1(the)-231.4(initial)-238.8(deposited)-236.5(activity)-239.6(in)-234.5(the)-237.7(lung)-234(because)-233.3(this)-236.3(initial)]TJ T* [(activity)-328.1(will)-328.4(have)-326(decayed)-331.5(four)-327.8(half-lives)-332.5(by)-325(this)-324.8(time)-330.3(point.)]TJ 0 -1.2266 TD [(But)-314.7(even)-307.4(laboratories)-316.3(using)-311.2(relatively)-313.4(low)-305.1(deposited)-312.4(activity)]TJ 0 -1.2203 TD [(\(2)-170.7(MBq\))-278.6(have)-281.7(been)-279.5(able)-279.2(to)-281.4(show)-281(signicant)-281.1(effects)-280(of)-281.5(therapy)]TJ T* [(at)-354.1(this)-356.5(time)-349.2(period)-352.7(postdeposition.)]TJ 6.7246 0 0 5.9768 197.8015 291.4015 Tm (\(46\))Tj 8.9663 0 0 8.9663 212.0314 287.433 Tm [(However,)-356.3(it)-351.8(is)-346.3(impor-)]TJ -16.9833 -1.2266 TD [(tant)-288.4(to)-281.4(acquire)-286.9(the)-282(image)-283.1(for)-288.5(long)-279.7(enough)-287.1(\(at)-285(least)-289.3(30)-163.4(min\))-283.2(to)]TJ 0 -1.2203 TD [(ensure)-348(that)-351.6(the)-345.2(statistical)-348.1(errors)-347.5(in)-342(the)-351.5(lung)-341.5(count)-348.7(after)-348.8(sub-)]TJ T* [(traction)-478(of)-471.1(background)-472.2(are)-474.3(sufciently)-475.9(small.)-469.9(The)-474.2(level)-469.2(of)]TJ T* [(deposited)-356.7(activity)-359.7(associated)-352(with)-356.8(the)-351.5(variability)-359(in)-348.4(24-h)-357(re-)]TJ 0 -1.2266 TD [(tention)-412.3(measurements)-407.5(might)-407.7(be)-402.7(compared)-402.4(between)-407.9(labora-)]TJ 0 -1.2203 TD [(tories)-546.1(by)-540(determining)-544.6(the)-541.2(intrasubject)-544.1(variation)-539(in)-544.4(repeat)]TJ T* [(measures)-387.3(of)-376.3(24-h)-382.3(retention.)-384.2(The)-379.3(deposited)-382(activity)-385(required)]TJ 0 -1.2267 TD [(to)-281.4(provide)-283.9(good)-284.9(signal)-281.3(background)-282.5(at)-284.5(these)-283.2(later)-282.3(time)-279.7(points)]TJ 0 -1.2203 TD [(then)-272.7(needs)-273.1(to)-262.5(be)-269.9(weighed)-268.7(against)-271.4(the)-269.3(risks)-270.5(of)-268.8(radiation)-269.3(doses)]TJ T* [(to)-338.4(the)-332.5(study)-339.4(subjects.)]TJ /F12 1 Tf 0 -3.0603 TD [(5.)-501.1(How)-338.8(to)-330.4(measure)-330.8(cough)-333.3(clearance)-336.4(\(CC\)?)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(For)-248.2(some)-241.8(patient)-248.9(groups)-252.2(and)-239.8(therapies)-250.3(the)-250.3(primary)-241.7(airway)]TJ -1.1128 -1.2203 TD [(clearance)-460.3(mechanism)-454.4(of)-458.5(interest)-458.6(may)-450.4(be)-453.2(that)-459.1(of)-452.2(coughing.)]TJ T* [(When)-309.2(MCC)-302.6(becomes)-308.6(dysfunctional)-311(in)-304.1(patients)-307.1(with)-306.2(airways)]TJ T* [(disease,)-428.7(CC)-417.6(may)-425.1(become)-421.1(the)-427.4(primary)-418.8(means)-425.3(by)-426.1(which)-422.2(se-)]TJ 0 -1.2266 TD [(cretions)-491.9(are)-487(removed)-485.1(from)-482(their)-488.5(lungs.)-491.1(On)-480.6(the)-490.6(one)-486.6(hand,)]TJ 0 -1.2203 TD [(spontaneous)-441.2(cough)-434.9(during)-433.7(imaging)-433.7(of)-439.5(clearance)-435(may)-431.4(be)-434.3(a)]TJ T* [(confounder)-415.4(of)-407.9(MCC)-403.8(measures.)-409.1(Because)-408.9(some)-406.2(patients)-408.3(may)]TJ 0 -1.2267 TD [(not)-487.2(be)-484.9(able)-487.9(to)-490.1(avoid)-483.8(coughing)-490.5(during)-484.3(clearance)-485.5(measure-)]TJ 28.0042 74.5598 TD [(ments,)-694.7(the)-699.3(number)-696.5(and)-701.4(timing)-695.8(of)-698.8(spontaneous)-700.4(coughs)]TJ 0 -1.2203 TD [(should)-274.6(be)-276.2(recorded.)-277.7(Then,)-278.2(in)-272.5(the)-275.6(study)-282.4(design)-274.8(the)-275.6(number)-279.2(of)]TJ 0 -1.2266 TD [(spontaneous)-422.2(coughs)-423.5(might)-414(be)-421.6(considered)-421.5(as)-418.1(a)-416.8(covariate)-417.4(in)]TJ 0 -1.2203 TD [(the)-408.4(analysis)-414.9(to)-407.9(ensure)-411.2(that)-414.8(frequency)-412.2(of)-407.9(these)-416(coughs)-410.9(does)]TJ T* [(not)-392.3(overly)-391.4(inuence)-399.4(any)-386.7(differences)-397.5(due)-396.3(to)-388.9(therapy)-395.4(effects.)]TJ 0 -1.2266 TD [(Some)-283.2(investigators)-293.9(have)-281.7(included)-288.9(a)-284(separate)-287.2(study)-288.8(arm)-282.3(with)]TJ 0 -1.2203 TD [(voluntary)-680.8(coughs)-682.8(equal)-685.3(to)-679.8(the)-686.6(number)-683.9(of)-679.8(spontaneous)]TJ T* [(coughs)-354(in)-361(the)-351.5(treatment)-362.8(arm)-351.9(as)-354.9(a)-359.9()86.6(cough)79.9()-356(control)-360.7(measure-)]TJ 0 -1.2266 TD (ment,)Tj 6.7246 0 0 5.9768 333.1275 642.1038 Tm [(\(16)-10(,22,41,47\))]TJ 8.9663 0 0 8.9663 373.7763 638.0786 Tm [(that)-478.1(is,)-475.7(that)-478.1(can)-476.4(be)-478.5(compared)-478.3(to)-477.5(the)-478(other)]TJ -7.0184 -1.2203 TD [(arms)-334.2(to)-332(correct)-338.2(for)-332.7(spontaneous)-340(cough)-333.7(effects.)]TJ 1.1128 -1.2203 TD [(On)-411.1(the)-414.7(other)-418.2(hand,)-416.9(although)-417.2(uncontrolled)-416.1(coughing)-414.6(can)]TJ -1.1128 -1.2203 TD [(confound)-256.7(measures)-248.1(of)-256.2(MCC,)-248.6(measuring)-258.3(CC)-246.9(by)-249.1(incorporating)]TJ 0 -1.2266 TD [(controlled,)-281.5(voluntary)-282.5(coughs)-278.1(during)-282(the)-275.6(measures)-279.8(of)-281.4(particle)]TJ 0 -1.2203 TD [(clearance)-453.9(may)-450.4(provide)-454.6(a)-448.4(more)-456.2(sensitive)-456.7(indicator)-452.5(of)-452.2(rheo-)]TJ T* [(logical)-377(changes)-384.3(in)-380(airway)-382.4(secretions.)]TJ 6.7246 0 0 5.9768 457.6818 576.34 Tm (\(25,48\))Tj 8.9663 0 0 8.9663 480.5857 572.3715 Tm [(In)-378.6(fact,)-382(CC)-379.7(is)-384.2(the)]TJ -18.9308 -1.2266 TD [(primary)-298.6(endpoint)-308.7(of)-300.4(interest)-300.5(in)-304.1(patients)-307.1(with)-299.9(primary)-298.6(ciliary)]TJ 0 -1.2203 TD [(dyskinesia)-441.6(\(PCD\),)-443.1(an)-439.2(inherited)-447.8(syndrome)-443(characterized)-445(by)]TJ T* [(nonfunctioning)-345.4(cilia.)]TJ 6.7246 0 0 5.9768 392.4849 543.4581 Tm (\(5,48\))Tj 8.9663 0 0 8.9663 411.6472 539.4896 Tm [(In)-334.3(other)-336(patients)-345.1(where)-334.3(both)-339.8(MCC)]TJ -11.2421 -1.2266 TD [(and)-233.5(CC)-228(may)-229.1(be)-231.9(affected)-236.9(by)-230.1(therapy)-237.4(\(e.g.,)-234.8(CF\))-232.7(it)-231.6(may)-229.1(be)-231.9(useful)]TJ 0 -1.2203 TD [(to)-319.4(incorporate)-330.5(controlled)-329.2(coughing)-319.7(during)-326.2(the)-326.2(measurement)]TJ T* [(period.)-431.5(Patients)-427.3(can)-432.1(be)-428(asked)-425.5(to)-433.2(perform)-427.1(voluntary,)-430.8(single)]TJ T* [(coughs)-404.6(after)-405.7(tidal)-402.1(inhalation)-408.7(through)-402.2(a)-404.2(peak)-403.5(ow)-399.4(meter)-409.5(to)]TJ 0 -1.2266 TD [(periodically)-259(record)-259.3(cough)-257.8(efforts.)]TJ 6.7246 0 0 5.9768 441.1274 488.6361 Tm (\(46\))Tj 8.9663 0 0 8.9663 454.507 484.6676 Tm [(However,)-261.5(if)-256.9(the)-256.7(primary)]TJ -16.0223 -1.2203 TD [(aim)-190.3(is)-188.2(to)-192.9(assess)-194.4(therapeutic)-193.2(effects)-197.8(on)-189.5(MCC,)-191.7(the)-193.4(coughs)-189.6(should)]TJ T* [(not)-253.2(be)-250.9(incorporated)-251.3(until)-258.9(a)-246.1(later)-250.7(period)-257.9(\(e.g.,)-247.5(6090)-168.3(min\))-251.5(so)-250.7(as)]TJ 0 -1.2266 TD [(not)-202.6(to)-199.3(confound)-206.1(early)-204.1(measures)-203.9(of)-205.6(MCC.)]TJ 6.7246 0 0 5.9768 467.4896 455.8109 Tm [(\(4,25)-10.4(\))]TJ 8.9663 0 0 8.9663 485.4613 451.7857 Tm [(Even)-203(during)-199.8(this)]TJ -19.4746 -1.2203 TD [(later)-364.5(period,)-374.6(clearance)-365.4(is)-371.6(a)-366.2(function)-375.1(of)-363.7(both)-371.5(cough)-371.6(and)-366.3(mu-)]TJ T* [(cociliary)-206.3(action)-205(and)-201.9(changes)-207.2(in)-202.9(aerosol)-200.2(distribution)-211.9(during)-206.1(the)]TJ 0 -1.2266 TD [(rst)-460.7(hour)-463.5(must)-462.3(be)-465.9(considered)-465.7(for)-459.2(its)-466.9(effect)-462.1(on)-461.4(subsequent)]TJ 0 -1.2203 TD [(clearance)-359.1(during)-357.8(the)-364.2(cough)-359(period)-359(\(e.g.,)-361.3(C/P)-358.6(at)-354.1(1)-170.2(h)-357.5(prior)-363.1(to)]TJ T* [(coughing)-307.1(could)-313.4(be)-307.8(a)-303(covariate)-309.9(for)-313.8(the)-307.3(CC)-310.2(measure\).)-307.1(Waiting)]TJ 0 -1.2266 TD [(too)-366.4(long)-374.5(in)-367.3(the)-370.5(period)-371.7(of)-370(clearance)-371.7(measurements)-375.9(likely)-367.1(di-)]TJ 0 -1.2203 TD [(minishes)-462.9(any)-456.2(chance)-460(of)-458.5(seeing)-461.4(effects)-463.4(on)-461.4(CC,)-452.2(that)-465.4(is,)-456.7(it)-459.3(is)]TJ T* [(generally)-354.4(believed)-362.7(that)-357.9(cough)-359(is)-352.6(most)-362.5(effective)-358.7(in)-354.7(the)-357.8(larger)]TJ T* [(bronchial)-412.5(airways)-409(that)-408.5(likely)-411.4(clear)-413.9(during)-408.4(the)-414.7(rst)-410.2(12)-162.9(h)-414.4(o)0(f)]TJ 0 -1.2266 TD [(observation.)-269(There)-266.1(was)-268(disagreement)-266.5(on)-265.4(the)-269.3(degree)-267.1(to)-268.8(which)]TJ 0 -1.2203 TD [(voluntary,)-209.5(controlled)-215.4(cough)-213.6(clearance)-213.7(should)-211.4(be)-206.6(incorporated)]TJ T* [(in)-304.1(the)-300.9(clearance)-302.2(measurements)-306.4(on)-303.3(a)-303(routine)-309.3(basis,)-297.5(but)-303.4(it)-307.5(was)]TJ 0 -1.2266 TD [(agreed)-412.1(that)-414.8(CC)-411.3(should)-413.7(be)-415.3(considered)-415.1(in)-411.6(the)-414.7(context)-419.4(of)-407.9(the)]TJ 0 -1.2203 TD [(potential)-299.5(drugs)-297.2(effects,)-301.9(the)-300.9(patient)-299.5(population,)-301.2(and)-296.7(the)-294.6(limi-)]TJ T* [(tations)-245.4(on)-240.1(number)-241.3(of)-243.5(treatment/control)-245.9(arms)-239.4(associated)-244.6(with)]TJ 0 -1.2266 TD [(each)-280.3(study)-282.4(design.)]TJ /F12 1 Tf 0 -3.054 TD [(6.)-501.1(Which)-329.2(variables)-335.2(of)-336.7(MCC/CC)-332.6(are)-333.4(the)-334.8(most)-337.9(robust,)]TJ 0 -1.2203 TD [(or)-265.8(how)-270.9(do)-268.1(we)-272.8(best)-264.8(analyze)-272.9(retention)-268.5(versus)-268.7(time)-272.1(data?)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(The)-486.8(primary)-488.3(data)-483(from)-488.4(the)-490.6(MCC/CC)-489.3(measures)-488.4(are)-487(re-)]TJ -1.1128 -1.2203 TD [(tention)-418.6(\(as)-412.3(either)-412.6(fraction)-421.1(or)-408.1(%)-412.6(o)0(f)-414.2(initial)-415.8(deposition)-420.4(image\))]TJ 0 -1.2267 TD [(versus)-346.8(time)-349.2(\(Fig.)-344.6(7\).)-344.3(Over)-345.8(the)-351.5(years,)-343.9(investigators)-350.9(have)-351.3(cho-)]TJ 0 -1.2203 TD [(sen)-497.8(several)-498.8(ways)-500.1(to)-496.4(characterize)-498.9(these)-504.5(data.)-492.3(The)-499.5(simplest)]TJ T* [(method)-285.3(is)-283.1(to)-287.8(report)-284.1(retentions)-294(at)-278.2(a)-284(given)-290.2(time)-286(point)-283.4(\(Fig.)-287.6(7a\).)]TJ 0 -1.2266 TD [(The)-461.5(disadvantage)-467.2(of)-464.8(this)-464(approach)-469.5(is)-460.1(that)-465.4(one)-467.6(point)-466.8(on)-461.4(a)]TJ 0 -1.2203 TD [(curve)-362.4(is)-358.9(not)-360.7(very)-359.8(descriptive)-361.5(of)-357.3(the)-364.2(rate)-361(of)-357.3(clearance,)-362(and)-360(if)]TJ T* [(not)-341.7(chosen)-338.8(appropriately,)-344.5(can)-337.3(give)-343.7(a)-334.6(false)-339.8(impression)-344.2(of)-344.7(the)]TJ 0 -1.2266 TD [(data.)-479.6(For)-482.1(example)-484.5(in)-481.1(Figure)-488.5(7c)-479.3(retention)-488.7(at)-480.5(6)-170.2(h)-477.6(would)-486.5(be)]TJ 0 -1.2203 TD [(similar)-243.6(for)-244.2(curves)-243.6(A)-248(and)-239.8(B,)-246.2(whereas)-246.6(the)-244(rate)-240.8(of)-243.5(clearance)-251.6(over)]TJ T* [(earlier)-267(time)-267(periods)-265.5(is)-270.4(clearly)-263.8(faster)-267.9(for)-269.5(A)-267(versus)-264.6(B.)-265.2(Thus,)-264.9(it)-269.6(is)]TJ T* [(best)-353.9(to)-357.3(incorporate)-362.2(all)-360.7(data)-356.6(points)-354.3(in)-361(the)-357.8(characterization)-363.2(of)]TJ 0 -1.2266 TD [(MCC.)-255(One)-259.2(approach)-260.8(is)-264.1(to)-256.2(t)-256.4(a)-258.8(simple)-260.1(regression)-264.5(line)-256.9(through)]TJ 0 -1.2203 TD [(the)-433.7(data,)-429(the)-433.7(slope)-438.8(of)-433.2(which)-434.9(represents)-432.6(a)-435.8(clearance)-435(rate)-430.5(in)]TJ T* [(%/min)-401.1(or)-408.1(h.)-404.6(For)-399.9(nonlinear)-412.1(clearance)-403.4(curves)-408(an)-401.2(area)-404.3(under)]TJ 0 -1.2267 TD [(the)-288.3(curve)-292.8(analysis)-288.4(\(Fig.)-287.6(7d\))-287.5(may)-286(be)-288.8(more)-291.8(appropriate,)-292.3(where)]TJ /F4 1 Tf -28.0042 77.228 TD [(MUCOCILIARY)-339.2(AND)-337.2(COUGH)-337(CLEARANCE)]TJ 53.0113 0 TD (267)Tj ET endstream endobj 103 0 obj <>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/XObject<>/Font<>>>/Thumb 106 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 107 0 obj <>/ProcSet[/PDF/Text/ImageB]/XObject<>/Font<>>> endobj 104 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.9663 0 0 8.9663 62.022 364.1385 Tm 0 0 0 rg 0 Tc 0 Tw [(essentially)-431.8(an)-420.2(average)-428.3(retention)-425.5(value)-428.7(is)-422.2(obtained)-428(over)-427.7(the)]TJ 0 -1.2203 TD [(period)-270.5(of)-262.5(interest.)-271.8(In)-264.7(some)-267.1(cases)-260.6(\(e.g.,)-266.5(Fig.)-268.2(7c,)-261(curve)-267.5(B\))-269(it)-263.2(may)]TJ T* [(be)-314.1(possible)-321.6(to)-319.4(t)-313.3(multiple)-321.1(regressions)-322.7(\(linear)-314.5(or)-319.6(exponential\))]TJ 0 -1.2266 TD [(to)-388.9(the)-389.5(data)-381.9(to)-388.9(obtain)-387.1(both)-390.4(rates)-387.6(and)-385.3(sizes)-391.3(of)-382.6(different)-391.2(com-)]TJ 0 -1.2203 TD [(partments)-586.4(of)-585(clearance.)-583.3(The)-588(most)-583.8(sensitive)-589.5(approach)-583.3(for)]TJ T* [(comparing)-442.5(acute)-449.4(drug)-439.4(effects)-450.7(may)-437.8(be)-446.9(to)-439.5(determine)-444.6()80.3(break)]TJ 0 -1.2266 TD [(points)80.1()-280.1(i)0(n)-278.8(the)-275.6(curves)-281.5(with)-274.6(rates)-280.1(only)-279.7(determined)-283.2(to)-275.1(that)-282(time)]TJ 0 -1.2203 TD (point.)Tj 6.7246 0 0 5.9768 84.9826 291.4015 Tm (\(49\))Tj 8.9663 0 0 8.9663 99.7228 287.433 Tm [(This)-403.3(approach)-412.5(eliminates)-404.7(bias)-407.1(from)-406.2(later)-408.8(time)-406.1(pe-)]TJ -4.2047 -1.2203 TD [(riods)-428.6(where)-422.8(clearance)-428.6(is)-428.5(slowed,)-426.1(probably)-425.8(reecting)-431.9(reten-)]TJ 0 -1.2266 TD [(tion)-446.4(of)-452.2(particles)-445.9(in)-449.5(more)-449.9(peripheral)-450.2(airways.)-443.5(On)-449(the)-446.4(other)]TJ 0 -1.2203 TD [(hand,)-265.1(such)-264.6(an)-262.1(approach)-267.1(also)-260(biases)-269.2(clearance)-264.2(comparisons)-266.4(to)]TJ T* [(the)-534.9(most)-533.2(proximal)-535.9(airways)-529.1(that)-535(presumably)-538.9(clear)-527.7(in)-538(this)]TJ T* [(early)-494.9(phase.)-495.2(More)-489(robust)-497.9(statistical)-493.5(models)-494.9(that)-490.7(allow)-491.5(in-)]TJ 0 -1.2266 TD [(clusion)-381.9(of)-376.3(all)-373.3(retention)-381.2(versus)-378.4(time)-380.8(data)-375.5(points,)-376.2(rather)-377.7(than)]TJ 0 -1.2203 TD [(rates/slopes,)-454.3(along)-443.6(with)-445.3(covariates)-450.3(for)-446.5(regional)-447.7(deposition)]TJ T* [(may)-273.4(also)-279(be)-276.2(more)-279.1(sensitive)-279.6(for)-275.8(detecting)-279.9(differences)-283.7(between)]TJ 0 -1.2266 TD [(treatment)-394.4(days.)-384.2(Finally,)-392(some)-387.2(investigators)-395.1(have)-389.2(attempted)]TJ 0 -1.2203 TD [(to)-388.9(reduce)-396.2(the)-389.5(bias)-388.1(associated)-396.3(with)-388.4(at)-388.7(portion)-394.4(of)-388.9(the)-389.5(curve)]TJ T* [(\(e.g.,)-411.9(alveolar)-414.9(deposition\))-414.5(by)-407.2(subtracting)-417.2(the)-408.4(24-h)-413.9(retention)]TJ 0 -1.2266 TD [(from)-368.2(retentions)-376.2(at)-366.7(earlier)-368.2(time)-368.2(points,)-369.8(and)-366.3(renormalizing)-370.2(to)]TJ 0 -1.2203 TD [(100%,)-502.6(to)-496.4(get)-504.3(a)-499(measure)-499.8(of)-502.8()86.6(clearable)74.5()-495.1(activity)-505.1(or)-503(as)-500.3(they)]TJ T* [(dene)-597.2(it)-598.4()80.3(tracheobronchial)-603.8(clearance.)78.7()]TJ 6.7246 0 0 5.9768 220.5921 137.9905 Tm (\(6,8,9\))Tj 8.9663 0 0 8.9663 243.7794 134.022 Tm [(Although)-602.4(this)]TJ -20.2713 -1.2266 TD [(may)-520(be)-522.8(valid)-522.5(in)-525.4(a)-518(particular)-522.1(patient)-527.1(group)-522.8(or)-521.9(for)-522.4(repeat)]TJ 0 -1.2203 TD [(measures)-279.8(in)-278.8(stable)-281(subjects,)-281.5(there)-276.2(may)-279.7(be)-276.2(situations)-283.2(in)-278.8(which)]TJ T* [(the)-433.7(24-h)-439.2(measure)-430.2(is)-434.8(not)-436.6(purely)-434.9(a)-429.5(reection)-442.9(of)-433.2(alveolar)-433.8(de-)]TJ T* [(position)-335.3(\(i.e.,)-335.1(nonclearable)-342.3(activity\).)]TJ 1.1128 -1.2266 TD [(Comparisons)-267.3(of)-262.5(these)-270.5(various)-262.8(approaches)-268.3(should)-268.3(be)-263.6(made)]TJ -1.1128 -1.2203 TD [(in)-392.6(several)-397.6(data)-394.5(sets)-401.3(from)-393.5(different)-397.5(labs)-394.5(to)-395.3(determine)-400.4(which)]TJ T* [(may)-425.1(be)-421.6(the)-427.4(most)-425.8(sensitive)-425.1(measure)-423.9(of)-426.9(MCC.)-425.7(As)-420(discussed)]TJ 27.9978 74.5534 TD [(above)-304.5(the)-307.3(relationship)-307.9(between)-306.8(the)-307.3(MCC)-302.6(variable)-302.7(of)-306.7(interest)]TJ 0 -1.2203 TD [(\(e.g.,)-544.7(slope)-540(or)-534.6(average)-542.1(retention\))-546.1(and)-537(regional)-542.6(deposition)]TJ 0 -1.2266 TD [(could)-414.6(then)-418.1(be)-409(compared)-415.1(across)-415.9(laboratories)-417.5(to)-414.2(assess)-415.7(simi-)]TJ 0 -1.2203 TD [(larity)-309.3(of)-306.7(various)-313.4(approaches)-312.6(\(e.g.,)-304.4(particle)-311.8(type\).)-306.7(In)-309(addition,)]TJ T* [(repeat)-406.5(measures)-399.9(of)-395.3(these)-403.3(variables)-398.9(in)-398.9(healthy)-400.3(and)-397.9(diseased)]TJ 0 -1.2266 TD [(populations)-520.9(would)-518.1(be)-510.1(useful)-520.1(for)-509.8(determining)-519.3(appropriate)]TJ 0 -1.2203 TD [(sample)-338.3(sizes)-334.4(for)-332.7(therapy)-338.5(studies.)]TJ 1.1128 -1.2203 TD [(Generally)-506.8(the)-509.6(right)-505.7(lung)-505.9(has)-503.7(been)-507.1(used)-505.1(for)-509.8(analysis)-503.4(of)]TJ -1.1128 -1.2266 TD [(whole-lung)-353.2(retention)-349.6(to)-351(avoid)-344.7(stomach)-352.1(activity)-347.1(that)-345.3(may)-349.3(be)]TJ 0 -1.2203 TD [(contiguous)-286.2(with)-280.9(the)-282(left)-282.6(lung.)-281.2(Alhough)-279.5(whole-lung)-283.6(retention)]TJ T* [(versus)-277.2(time)-267(is)-270.4(usually)-274.3(of)-268.8(primary)-267(interest,)-278.1(regional)-270.7(clearance,)]TJ T* [(for)-282.2(example,)-285(from)-279.7(central)-285(and)-277.8(peripheral)-285.8(regions)-281.6(in)-278.8(Figure)-279.9(3,)]TJ 0 -1.2266 TD [(may)-210.2(prove)-207.8(more)-209.6(sensitive)-210.1(and)-208.2(of)-205.6(greater)-214.3(value)-207.4(in)-202.9(determining)]TJ 0 -1.2203 TD [(drug)-256.1(effects.)]TJ 6.7246 0 0 5.9768 361.4739 587.2817 Tm [(\()-344(39,41,51,52\))]TJ 8.9663 0 0 8.9663 402.3495 583.3132 Tm [(While)-256(imaging)-256.6(over)-250.7(time,)-257.3(the)-256.7(subjects)]TJ -9.9586 -1.2203 TD [(body)-368.7(position)-366.9(might)-363.5(shift)-369.6(slightly)-366(on)-366.6(the)-364.2(camera,)-366.1(especially)]TJ 0 -1.2266 TD [(over)-377.2(long)-368.2(periods)-379.3(when)-368.7(subjects)-379.7(may)-368.2(take)-371(breaks)-370.7(from)-374.6(im-)]TJ 0 -1.2203 TD [(aging.)-359.6(This)-359(probably)-362.6(has)-358.3(little)-359.2(effect)-360.9(on)-353.9(measures)-362(of)-357.3(whole-)]TJ T* [(lung)-467.9(clearance,)-469.5(but)-461.5(subject)-466.9(movement)-470.2(may)-463.1(affect)-461.7(accurate)]TJ 0 -1.2266 TD [(measures)-248.1(of)-237.2(regional)-245.4(clearance.)-241.9(Most)-243.6(investigators)-249.7(attempt)-240(to)]TJ 0 -1.2203 TD [(maintain)-308.1(subjects)-312.1(position)-303.7(in)-304.1(front)-311.3(of)-306.7(the)-300.9(camera)-306.3(during)-307.2(pe-)]TJ T* [(riods)-453.9(of)-452.2(MCC)-448.1(measurements)-451.8(with)-451.6(laser)-447.6(light/mirror)-454.3(feed-)]TJ T* (back)Tj 6.7246 0 0 5.9768 331.37 499.6345 Tm [(\(46)-10.1(\))]TJ 8.9663 0 0 8.9663 344.5794 495.666 Tm [(or)-231.1(by)-236.5(imaging)-231.3(in)-234.5(the)-237.7(supine)-238.5(position.)]TJ 6.7246 0 0 5.9768 487.9558 499.6345 Tm [(\(5,16,2)-10.7(2,41,47\))]TJ 8.9663 0 0 8.9663 531.4392 495.666 Tm (Point)Tj -24.3559 -1.2266 TD [(markers)-377.2(on)-372.9(the)-376.8(subjects)-381.6(torso)-374.8(\(Co57)-375.5(or)-370.2(Tc99m\))-378.7(outside)-372.7(the)]TJ 0 -1.2203 TD [(lung)-417.4(view)-416.8(have)-420.9(been)-412.3(used)-416.6(to)-420.6(allow)-415.6(realignment)-414.6(of)-420.6(images)]TJ T* [(based)-311.6(on)-309.7(their)-311.5(positions.)]TJ 6.7246 0 0 5.9768 410.1731 466.7527 Tm [(\(5,6,16,4)-11.1(0\))]TJ 8.9663 0 0 8.9663 442.5448 462.7841 Tm [(More)-312(sophisticated)-310.7(analysis)]TJ -14.4415 -1.2266 TD [(software)-335.6(may)-330.3(allow)-333.4(for)-332.7(an)-331.7(automatic)-333.3(algorithm)-332(to)-332(align)-330.5(im-)]TJ 0 -1.2203 TD [(ages)-258.1(postacquisition)-269.3(based)-254.7(on)-259.1(the)-256.7(similarity)-258.4(between)-262.5(sequen-)]TJ T* [(tial)-361.1(images.)-356.9(This)-359(may)-355.6(be)-352.1(affected,)-360(however,)-359.7(by)-356.6(the)-357.8(stomach)]TJ 0 -1.2266 TD [(activity)-321.8(requiring)-312.8(it)-313.8(to)-313.1(be)-314.1(masked)-315.5(out)-314.4(manually,)-312.9(as)-317(this)-312.2(may)]TJ 0 -1.2203 TD [(vary)-302.5(between)-306.8(images)-297.1(and)-303.1(can)-299.4(bias)-299.6(the)-307.3(alignment.)]TJ 1.1128 -1.2203 TD [(3D)-323.4(imaging)-319.9(approaches)-325.2(again)-326.5(offer)-320.5(a)-322(potential)-324.7(advantage)]TJ -1.1128 -1.2266 TD [(in)-601.3(regional)-599.5(analysis.)-601.2(As)-597.1(they)-602.5(are)-600.8(able)-595.4(to)-597.6(provide)-600(better)]TJ 0 -1.2203 TD [(measures)-412.5(of)-407.9(regional)-403.5(deposition)-414.1(compared)-408.8(to)-407.9(planar)-406.3(imag-)]TJ T* (ing,)Tj 6.7246 0 0 5.9768 327.9117 368.107 Tm [(\(44)-10.1(\))]TJ 8.9663 0 0 8.9663 343.1054 364.1385 Tm [(they)-457.1(should)-458(be)-459.6(able)-456.3(to)-458.5(track)-453.3(changes)-460.1(due)-459.5(to)-458.5(MCC)]TJ -3.3511 -1.2203 TD [(more)-266.5(accurately.)-270.1(In)-264.7(addition,)-268.7(these)-270.5(methods)-267.6(will)-265.1(better)-271.4(allow)]TJ 0 -1.2266 TD [(analysis)-364.3(of)-363.6(the)-364.2(left)-364.8(lung,)-363.4(due)-364.7(to)-363.7(the)-364.2(improved)-363.7(separation)-366.5(of)]TJ 0 -1.2203 TD [(lung)-335.2(and)-334.7(stomach)-339.4(counts)-337.4(in)-329.4(3D.)]TJ 1.1128 -1.2203 TD [(Current)-436.6(methods)-438.4(of)-433.2(measuring)-435.3(MCC)-435.4(from)-431.5(imaging)-433.7(rely)]TJ -1.1128 -1.2266 TD [(on)-385.5(measuring)-391.1(the)-383.1(rate)-386.3(at)-385.7(which)-384.3(the)-389.5(amount)-384.4(of)-388.9(aerosol)-383.6(in)-386.3(a)]TJ 0 -1.2203 TD [(region)-463.6(of)-464.8(interest)-464.9(reduces)-467(with)-464.3(time.)-459.6(The)-461.5(result)-468.8(is)-460.1(usually)]TJ T* [(presented)-648.5(as)-639.4(the)-636(percentage)-647.4(cleared)-638.1(per)-640.6(unit)-641(time.)-643(The)]TJ 0 -1.2266 TD [(process)-468.2(of)-464.8(MCC)-467(describes)-462.3(the)-465.3(movement)-470.2(of)-458.5(aerosol)-465.8(parti-)]TJ 0 -1.2203 TD [(cles)-320.2(along)-317.1(airways,)-310.7(with)-318.8(the)-313.6(rate)-316.7(being)-319.2(measured)-313.1(as)-317(a)-309.3(speed)]TJ T* [(\(mm/sec\).)-843.4(This)-845.9(means)-836.3(that)-844.8(the)-838.4(conventional)-844.7(imaging)]TJ T* [(measurements)-489.7(are)-480.7(really)-479.5(only)-482(indices)-481.8(of)-483.8(the)-478(actual)-484.2(muco-)]TJ 0 -1.2266 TD [(ciliary)-596.2(movement.)-593.2(3D)-595.3(radionuclide)-592.6(imaging)-591.8(\(SPECT)-594.5(and)]TJ 0 -1.2203 TD [(PET\),)-516.6(particularly)-517.4(used)-517.7(in)-512.8(combination)-520.1(with)-514.8(aligned)-516.8(ana-)]TJ T* [(tomical)-367.1(imaging,)-360.7(has)-364.6(the)-357.8(potential)-369(to)-363.6(be)-358.4(able)-361.4(to)-363.6(make)-361.8(more)]TJ 0 -1.2267 TD [(accurate)-354.1(measurements)-357(of)-351(the)-351.5(change)-351.3(of)-351(distribution)-351(within)]TJ 0 -1.2203 TD [(the)-572.8(lung)-562.8(over)-573.2(time.)-567.1(By)-563.8(combining)-566.1(this)-571.4(improved)-566(spatial)]TJ T* [(data)-502(with)-495.9(mathematical)-503.8(modeling)-498.7(it)-497.2(might)-496.2(be)-497.5(possible)-498.7(to)]TJ 0 -1.2266 TD [(estimate)-641.3(mucociliary)-641.5(velocities.)-637.5(The)-638.6(mathematical)-642.9(model)]TJ 0 -1.2203 TD [(would)-429.6(have)-420.9(to)-426.9(describe)-423(variation)-425.1(of)-426.9(concentration)-429.8(of)-420.6(aero-)]TJ T* [(sol)-519.8(in)-512.7(different)-517.7(regions)-521.9(of)-509.1(the)-515.9(lung)-518.5(with)-514.8(time)]TJ /F6 1 Tf 21.8709 0 TD (C)Tj 6.7246 0 0 5.9768 515.1684 143.433 Tm (i)Tj /F5 1 Tf 8.9663 0 0 8.9663 521.5747 144.9638 Tm (\()Tj /F6 1 Tf .3225 0 TD (t)Tj /F5 1 Tf .3225 0 TD .5189 Tc [(\)a)518.9(s)5.9(a)]TJ -23.9006 -1.2266 TD 0 Tc (function,)Tj /F6 1 Tf 4.3691 0 TD (F)Tj /F5 1 Tf .5501 0 TD [(,)-477.1(o)0(f)-471.1(the)-471.6(mucociliary)-477.1(speeds,)]TJ /F6 1 Tf 13.2275 0 TD (s)Tj 6.7246 0 0 5.9768 479.2251 132.4913 Tm (j)Tj /F5 1 Tf 8.9663 0 0 8.9663 485.2912 133.9653 Tm [(in)-468.5(different)-479.7(gen-)]TJ -19.209 -1.2203 TD (erations,)Tj /F6 1 Tf 4.1542 0 TD (j)Tj /F5 1 Tf .2656 0 TD (,)Tj /F6 1 Tf 4.8054 -3.0793 TD (C)Tj 6.2762 0 0 6.2762 401.7826 94.0535 Tm (i)Tj /F5 1 Tf 8.9663 0 0 8.9663 403.9936 95.4141 Tm (\()Tj /F6 1 Tf .3225 0 TD (t)Tj /F5 1 Tf .3225 0 TD (\))Tj /F13 1 Tf .4869 0 TD ()Tj /F6 1 Tf .9358 0 TD (F)Tj /F5 1 Tf .5564 0 TD ([)Tj /F6 1 Tf .3225 0 TD (C)Tj 6.2762 0 0 6.2762 436.3652 94.0535 Tm (i)Tj /F5 1 Tf 8.9663 0 0 8.9663 438.5762 95.4141 Tm (\(0\),)Tj /F6 1 Tf 1.5618 0 TD (s)Tj 6.2762 0 0 6.2762 456.0377 94.0535 Tm (j)Tj /F5 1 Tf 8.9663 0 0 8.9663 458.2487 95.4141 Tm (,)Tj /F6 1 Tf .411 0 TD (l)Tj 6.2762 0 0 6.2762 464.3715 94.0535 Tm (j)Tj /F5 1 Tf 8.9663 0 0 8.9663 466.5825 95.4141 Tm (])Tj -17.1224 -3.0287 TD (where)Tj /F6 1 Tf 3.0476 0 TD (s)Tj 6.7246 0 0 5.9768 343.8424 66.7276 Tm (j)Tj /F5 1 Tf 8.9663 0 0 8.9663 348.4912 68.2583 Tm (and)Tj /F6 1 Tf 1.9917 0 TD (l)Tj 6.7246 0 0 5.9768 368.7873 66.7276 Tm (j)Tj /F5 1 Tf 8.9663 0 0 8.9663 373.4361 68.2583 Tm [(are)-316.2(the)-319.9(mucociliary)-319(speed)-315.3(and)-315.7(length)-318.6(of)-319.4(each)]TJ -6.7339 -1.2267 TD (generation.)Tj ET q 235.646 0 0 260.05 63.779 473.159 cm /Im7 Do Q BT /F7 1 Tf 8.9663 0 0 8.9663 62.022 456.3778 Tm [(FIG.)-317.8(7.)]TJ /F5 1 Tf 4.072 0 TD [(Methods)-319.5(for)-313.8(analysis)-313.7(of)-319.4(retention)-318(versus)-315.1(time)-311.3(data.)]TJ -4.072 -1.1065 TD (\()Tj /F7 1 Tf .3225 0 TD (a)Tj /F5 1 Tf .4995 0 TD [(\))-411.5(Time)-408.7(taken)-406(to)-407.9(clear)-413.9(50%)-405.3(\(T)]TJ 6.7246 0 0 5.9768 186.9732 444.9258 Tm (50)Tj 8.9663 0 0 8.9663 193.6629 446.4566 Tm [(\))-411.5(o)0(r)-408.1(amount)-409.7(retained)-415.1([e.g.,)]TJ -14.6818 -1.1128 TD (R)Tj 6.7246 0 0 5.9768 68.0315 435.0046 Tm (2.0)Tj 8.9663 0 0 8.9663 81.9779 436.4786 Tm [(at)-619.6(a)-625.5(given)-619(time)-621.1(\(e.g.,)-626.9(2)-163.9(h\)].)-626.9(\()]TJ /F7 1 Tf 13.9863 0 TD (b)Tj /F5 1 Tf .6007 0 TD [(\))-620.1(Regression)-628.5(analysis)]TJ -16.8126 -1.1128 TD [(to)-256.2(determine)-254.9(slope)-261.8(\(rate\))-254.4(of)-256.2(decrease)-256.4(in)-253.5(retention)-261.1(versus)-258.2(time.)]TJ 0 -1.1065 TD (\()Tj /F7 1 Tf .3225 0 TD [(c,)-280.4(d)]TJ /F5 1 Tf 1.5744 0 TD [(\))-285(Area)-279.7(under)-286.6(curve)-280.2(or)-288(average)-282.9(retention)-286.4(over)-282.3(the)-282(time)-286(of)]TJ -1.8969 -1.1128 TD (interest.)Tj /F4 1 Tf 0 38.2599 TD (268)Tj 46.3849 0 TD [(BENNETT)-338(ET)-338.7(AL.)]TJ ET endstream endobj 105 0 obj <>stream AdobedC        s!1AQa"q2B#R3b$r%C4Scs5D'6Tdt& EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz?Nlٳbkslд*4+˔Qn /l-ͼlA"xYO H.=B ,L21\ٳf͛6lٳf͛6lٲ1 y}~WX mC4 RI$3srzejzNʖW(̄*TNT#k͛6l؏->nx澟\JfK7OZ.`:T RX:0e8lٳf͛6lٳf͛6lٲ;_dLZeŬRXfF;ߟ/]fc2eh~*LvȮvYҵ6 OIO^p]@qb<f͛64Zg9Z քEkJm7GMF7fŽko7L#jU߮o7YYigtچa@Voe8'Aq1 ]6:7י4;M&M'OUin"䱠 $1/* omowZEشٔ 睘tlٳf͛6lٳf͛6l~r< N5]VEWKmmÂI2S@+\䟞~z'lEæX@fHjPS俳͛6l*F\uuf35PO"|@7 ~]Pu$fyṊ4jNāv600đ:7Is4cKm鏄G%q3'JM{ik`FKmnw74_9q׾WgO<"勝b!P +o*ClGx d4=2[6lٳf͛6lٳf͛"+|l{|_cQt}B#|8Yyw͚X쯡{&'*ȲYbC͛6lFHyitgCrlrZɶCrwΝ?:Cy}uvHReZzxg п)u[3@<$X@DZ]X͛6lٳf͛6lU|[Aysٵ¨s30ӕi\󉚆>:j^r]b4XReB|&y ߖ:זCY/!Z '{6lٳf͛8l+S.Ëo?ZsZ=~h͛6lٳf͛6lٳf͛6lٳf͛ |+P˴qHL|5Q%SUe*e_*Ҝd뜇PyjqKg[|Ɛ;ּc垆@TQ@҃/6lٳf͛6lٳf͛6lٳf͛6l??,t{{qSe ,͛6lٳf͛6lٳf͛6lٳf͛6yQOa;u|%'4O0j$.aX?1DSCۺGk "TcMվWu~/&ur7Lٳf͛6lٳf͛6lٳf͛6l&Լ︺X(GvOkZ&O3f͛6lٳf͛6lٳf͛6lٳfͅ^kkSi?'9@#W[y`K'LOqk( OO'jP˚Ya'13[NfMJf͛6lٳf͛6lٳf͛6lʿ=#ʪzV*.~UjӤ&܇·6lٳf͛6lٳf͛6lٳf͛6l(zy_TU4&J'98#E'ί6yrN 8<h)wrr=q- ?-)1:5ŭ]MI3f͛6lٳf͛6lٳf͛6l>մ6Υ D0SR͛6lٳf͛6lٳf͛6lٳf͛6Pf"s3Z)۟u|ٱ+Kk;Xm>8qETt|_~ѥ6 _g.yndx[$Pmy o17Tjx}xW&*:f͛6lٳf͛6lٳf͛6l䟟Ćգu^|XStٳf͛6lٳf͛6lٳf͛6lٳaG|v"s3_X͛6lSgJՊsD`]TSy/_3Z~e-!.QZ=U a[XoP\~lٳf͛6lٳf͛6lٳg)*âjѧu8VteIbIStC)aQ͛6lٳf͛6lٳf͛6lٳf͛ <| i'9S{sε6lٳ`MWKe(PЏqKgnXխG<S"%Y"qUu =͛6lٳf͛6lٳf͛9}-K8C%_ZDuEn$s:Rk럗EBL;f90͛6lٳf͛6lٳf͛6lٳf͛ (0Ns?X'f͛6lٳ__~|?Xѥ\Ҽކ/u/@󧓼Cc7Ӑ}~ٷ.n%Wnv].ʄu6lٳf͛6lZOn,f5+Ւ[}?Ms%D>R*ǩ>Y2kM2i p=N+TWK9f͛9s ajqqYC)S"aGwLbfu ٳf͛6lٳf͛6lٳf͛6lٰ_j /D<`O[͛6lٳfjg&^Vk.PuB$_~]l.kgكw#&f͛6lٳ~lr>yӻAff.͛6lٳf͛6lٳf͛6lٰ:]*mC7z֝TI;dF/(4œXCiW?\oLTq;Bh6u5ךYGarė[g+H&FXۋ@PASyT-=QHm~o2 A sη6lٳf͛6l^PKg_pMGq^v65x-X|bj9I\,/F?D鑸+Mf͛6l~咭BE+_"ZԞc/k[kH,9'&P$SzW]KPi.r$eU$l 2?8KQ:lٳf͛6lٳ`]KK;G. qBEzeԼjZz晪XjVqL |0Vlٳf_æymM-QOyn㳋O z"U~~Sdho>XfMeQk߲ϰ&f͛9/y>ʳε;y>͛6lٳf͛6lٳf͛6lٳa?_}8kaO:lٳf͛6lٳfȯwzXEՓVfYtg= Ux.T,KQfxuFlٳfme -gF_1ygO5S4f+ "<kTK}0h:sF " ,-Hb3cҧrr}6lٳ~|n|;J~sgŽǗͣ<7O5ߚrE+_l`mo~OCrVVPjTٳf͛6lٳf͛6lٳf͛6zY'93ysη6lٳf͛6lٰiqjp-ŕʔ69?/t[v7sz72^'FS`RRk:C1+yXK mޟ&%~6q<0Qgn;x& 7̿4l<ӡkZo4vq\Y٬x^Ko!UdDZm>†/#_.{8ZڱK"I)Nܜٳf͜y\u,$SC( ȇzBo]e=yf͛6lٳf͛6lٳf͛6l%󠯔a.Ns+]?sη6lٳf͛6lٳf͑4&[+y j]J-B h|ZǚO̙_W^EjxozFӣ4]>6.,Jԅ ͜˺JdM/QMI!kr-)BY V$~ߘy,u-4y$I-$qEUr;ٳf͜[oTk6AU[Vs_˻0Cm?ͺAl/|R*`r:`xߦ &ziu}5dmA|ٳf͛6lٳf͛6lٳf͛ i=XˬqύO:lٳf͛6lٳf͛6l.t 3[PԉG:7fFFCt4y:K mΡhc2í߽GM<1g}qcjBy#*PҴ,u 7͛6ٳ͛6ٳ͛6%9ʮٲ(D?iяT(j彳.e]6_)*F޳ٳ_9(?D>O#:lے5a_3Lٲ)ʾIK|+!=?I:u )|a~@ǩ-y>s ) ?WlGIw-,#:xN~mSCmtu 2 F^lٳf͛6lٳf͛ iMXˬqa?'k6lٳf͛6lٳf͛6lٳg"?.04{MGDl,uUu=B{ˈ?ѣN*?ҳ |75tL:eb KG-ՈI"-lFe;T\G.ZUŭE,}NbEżmrYŶ}1 Ah٣)O6qϒ>@;l;I+|6l_?Iq$p2s}I/(h׎9u=UG3~X7Qp@0o1hvb,y4OO|J_OkDW?nޑ#NjX@WZnDc)?>U#Gխe*&@$ Օ2Te͛6lٳf͛ +]Wae4bm͛6lٳf͛6lٳf͛6lߛڥZ75msOIw[] `x8ކ1F~Ewa=kO2Y X͌V0El bɖr=kWߜ>UHuUcv-D֕NQw.u;:YkwߥisǪݚuH (Esz ̫MB+ךƗNlIV-.=LiNagMR).XgbTU4p|6:6Ib-ŋʓArҚ)ԘN>U`3F+sWm|ٲ ϧXy+VXFP´<.-ҭ p *"/6lٳ`k/Nӽ?D ?kʟSL[I{Of}ƩZߘ)9ywWDmx>|g_rwLn ?2i3Y1Q^P5)4w+{IdA|Oŭ^Hz rf͛6lOuZuqy/n?Ysf͛6lٳf͛6lٳf͛6s[<Ӣymo48mNumos+ KQtvzUcvH_sum58{b[+e2$hH?u@O)( @6 M9'>|G2(Z¹5#]\//7~o5i)۟$CIVj oVXwWV4P)TDY[B[eBOSZgZf}aFc 4Qy {dOr"{WȖMQW *x Nǖ<+Պ1,_r# S)^sz=yNТЫ9ҟ45Wm1i^i_5Nxq̅~qio!q(X܎Cn)Ӵ7 :R7"7GMa5Ǐ5~?c?Eב?"p̹49ʦkO9+>/ӼUY}YӠ ZyբyQd~X L[_S\xf9t7}J:|OG_?_c[bhu .aB9׿mUItky Ѹ?!A"int]EgU++rL?$<ŮkWYSSPD}Ή6lٱKKu;w `ISFRA¿:yKWNsŖK;lٳf͛6lٳf͛6lٳfi \iCymhuM;wqS4}.]Y4[Ĩ G̵uor^kwۑ/:[PyUkHR>5h rKC JUޱ͹a|R?]kwەC oZ?朊f~}kwP>1Uȴ`wdO )y<~uWr'~] |{A#X tzi?0Z[cmƟM~͹RCke`FctɫZFn2FP˱ O`ۍe?NmC ZUֱC js~Noo3W%γ8Y7^w֖3O Ƴ8!J.WkcVMBlїٽRjS=6l[Ѭ6m:[i$6Km%87,i#ADHeUq SϦ%[G%.X g$?/o{,kK-ɳuj7.ƹ6z_#ۏ_=^o!k#?N*? o#Yɿ术+Gv7 Z5=p9C3K5[ A7*GY߯;9K9KZV-"-S5}YV/g k ,No;0o+#LdH &,`?.}:T{paӸ<5e=,k'A1 |6GXr[Y?V.O+-N rFO+k5'Ahb<~]Ho.6w@JZ85?0[yzC#mKSӡ䍣NIYa+Fݷ Բ]oi3i6W6v̱B#u{VhĒ:蹳f͛6.nt,$- n?dճ"*.ڳY񏳢<+:lL~f6o8yJCqn"B*>$ܱK0ّk`>9\K.>2F->n\r$#=ƃ%͛53)ר"< WE1_\ѨlٳfV6mZX!342N Ȕ~G)n75lmOo\͛69L R!N.s̛ |m* K`MkxZ6K>6~~Yhַ.iG-J 0D"Y=aYfuJ lٳGG##ͪKU6KxSNl鹳g'5)k_^e6e[Jm=yEo< 8 ,|T}Uӊ//=ϫu,$GPuNk~e>hijvW|I 3FUWD`&9ַZEߤu=F-! .]cECnlյkwE֭GKՖĚsP[Ɨ 'C5+m/ ߘ,H.GC4ȐanD\?ʬzTNOf͜~?#y,ͧY?Xi}Ea}Gn4v6PŽe{Uw~`T5+sWfzZL>WOӴ) w8AEhY2U/ϛu,hYgKi⹕efhIEA"N'Y!wH2H*mrXpQdv⼨J;MLfo-I}@w2H+$̅9$6lٰΞV>^&5cp ёԍ͡yj:eS7n:e2 7 f͛6E4UftYyĆd6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6l³42o͐ocekŬJEUNşQ53j +R =6.ԈxzIXy?J59гf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͜[i-eyqup_Wb1RP`Qp˺ރmMBmkWEYRnPeuWڦ6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6l1]s6vw>CuK=2)լu5ĤKX{ W$V։wZ4fCR}NJGIHזʪ99͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6lٳf͛6B5?6dZ]ΐ6k$Mb}T~ YExl6me/UӭG@mXjHk)M :9f͛6lٳf͛6lٳgtR`2Ep}4U^at ?BU&Ў8("G&̈`Rƒz8'E=hW?.֋|$ާ/SS& gcq巷xUWЕ֐gCa:Fl,o.TW'i܏AYҼoV~Xbc{oov t/e^8;7'fU*̟~X]ljaTMߣFAOx|g'ѼMH k=83_)'U-xP%^ct?̻}DhqvWǥs++Tٳf͛6lٳf͛9g..h"yCFs@ej {_/>FA Ҭ\6XX *>D 5;x6l,/t1iYN<6(ՆU(yzV}Wn/j/ʹm) ;UNAߕZJOkMݬ2vtpg!V<< AKt{MKQrK1,ĒN ? /D|\l,u(ӯ#` @Yekt4_&kjvgNԬu8,YD56lٳf͛6lٳf\^yg7|'REԮO+ӤDY3Y+¸c/"#o]#{ciYW+۠~LcjIΙGW.k>Rү`:Y$(ڼqYٸDR!L{ çH%^wcXkS&9f͛8'䷗=)Mzta%?迓dW'&M$^`֏}SSfAoḨ??/eS[1_s=:N:nTcYf͛6lٳf͛6lٳf͛6lGO?_&Ⱥ>jׁjO~Rj_ڄAf qPNmGzʷ_i8,%YΣ莅C# 2 k5&J-g}4s);ᗔ?0ugN=FKf͛6lٳf͛6lٳf͛6lIDu"sP-5 8ӿ#jFΉQ#O7phPLZo$ ΐ m?4I),maEyYz.-YrT5Rlٳf͛6lٳf͛"j{\58%o@ngFHu*++#SU4-OXSu"{똡 ' PBI'$f͛9會VwIwJN#u\)kֺ4^u ?R>ͅru+up{roq_م﫫^GȫMjueRSeU$CQf͛6lٳf͛6lٳf͛ |(0Ny[>-Ա켰ڍʸnҰz4󧛴;)̡)ѩ\~/%ձoo8%N!y̴ܕ_ši.䴥c7ڒH<9򄆲YVw1xgrߚ4o1i},GF;6͛6lٳf͛6lٳ~yyWbXb˖ pj|ueFeWHME=p:-Eu 1jOlFJx+43:ODx]ھ 4f͛6lٳf͛6lٰΤ)jYks~B]y?).GZjzM+0rIa7?&6n:W_.їio;+]~֖5f>{?2L6cZ;{+(]#9O̝^P*tw4`r}o]+ -Sgm}Id6lٳf͛6lٳg1ӻ I|'k./.n#xv$~,+ _~bt5oyo2y~]^ *q[`SĎYݳf͛6r4g3<1t6 X~}IΘ ͛6lϼMKJ&/[j&9 {8+4{/X!u kU>-E͛6lٳf͛6lٳa'|u"s~Dub[5sAZU$^^_ZIǒ\揔ϧk&Z늰ʁJƯضwζe2WFGߕ~grʟ&vs\}Ch|-8(- @A|̫n1hJ֡?%G>%HɋU}\~cfIHشDNg[Ϻהu .Xduk/~#=gt}RVl['-/x@6lٳf͛9o?ڟ|Cߘ7Sjm4A?p +>>O?=kjҞi2#Ėp¼x|d7ۿY~S>^gK- Fꎠ !v:v3f͛6lٳf͛6lGO(j]e_wLߕShڽV _>9"Ѽ:!Rzxʟ7K-޳ʒڢ?!Ҍ0P!{K-'%ט+jQ4l)Oκ>¦Q;6,S>ȱyՒ͹۱հԑȤ7Ͼ$5鸿>q=Y<0kw7Jt1IYYX&<)y˞c 5{fgV- +ȭ<lٳf͛6l俘Ǜ/5O/Mid]Ϩ_ҷR8 ƇpvHeeVP{=*]ݸ|\!svN;B͛6l3ޟM^͜=ߒ7uO-yvh&gW͛6lٲ3!>;P8?H;<:>X 쿎t@j+6lٳf͛6lٳf̈́~xCXY'87䞁盿ʉ4sVFkFۀ4|[ӾI/*~f7&3zMɏZS=\S;UO$FŸ@;`O|a$g"p(L_?vd}4}ٿ_5Ȥg_Q_O#"cWʟc+V yLXVyΞfd/0euCZ˞do[^ys!ou'xh\Ij>cf͛6lٳg2&]Yⷺu(..24s2V$f.L6I|Z[Q5 ;QOH;j:mJ3f͛6q-z?O;ley25fk0)nEΛ(4+q/'im5[chzTd6lٳf¯2y_F}۳#v#9{'lUr#ҵ2NӰlPO )< jB͛6lٳf͛6lIDu}.Np/)j7wW0kVI$4''o|i^@*yGnBZ/8| 4z_n_?妫74s\1[k:TS +4cV[N7쁳(ՃjDximC_#kHɚtG=tH_l __klm,2)X~pa}wȬKZRt}kL,"ӮP ȄW876lٳf͛9os{YAoLt(t՝j,Ѽ #Bв-Yׁ0d&{yk6wwab$Vmc"o,rFB0#lٳf= q&vٳy%>~Y$>~ad?uknm㸁Đ̡q* S6lٳfgi-+=VH;wX-YwKGg-ķR1gO57W4ۄCE2 ͛6lٳf͛6lIjuzu|G+//kkW;mG\?+'F}~ k ^gnq$^FuےfvSS7+o rZGރEuo$6]f8#fԁVt+T5or& _$kYghi_'O>dZx_ՍV'o3_?7,&>__(hGuN7ǖWC ׬UG,%]Q:˞(rX3_z].%TTV|ٳf͛6sZ=# ݮgb{+x/ueGӮ!C#KeNJ7SMa孭kry:Ϋ4?n4\!4Y&aE$™6͛!5kSdhkyqgmUyDb4kfݯ_#jGF|mMڛI9?2>B { y`]OMԬ.,/#ܣG,l* r˽Jgo}zy&-qJSD3S;lٳf͛$QȌ(tqFFu ja5և;zAGKm#'^U^}&=OH۾̽6Qalٳf͛6lyzFkuqk%^-qƲ(Srgg4SePt;CV/_=kkl47c&a瓼k.kV𽰸ZOR&ĤQĈReؐ?d(tʫʫŷ:s3`0I_˸ZsjX'>9Ahd.m>lٳf͜]tM6 u]/u;h̆F~l^oϓe=/5$}[gc,s\[:]բƉ)7'?^Դ'jw3_bK0ٽ?WGZd[Cڽ]jw+n オ gRk}fMs85/K5s=;ߑ仳܍ƕ|%~<G_Mv1`L5? 8i/WRxZdWVOȍ{SlR-ZYlb &^aQlt}qn4+I$W#|苫EKȬUuo *:0(~KG8ߦ'+hq\_U{4zmkp/{b\ZQA{N0y/_<)|y>dP;[i_ Ӧt_ Ξ]O-RQ%f͛8c :F$nK_8^-9Q'pӆծu@4=4 :2Y-X3uj(͛6l㟙MjMyf͜;R^Rqk-1vz%#|L4秺:}G^>IJ64rɨ5͛6lٳf C=Fs_4yV/_ǧ@ox;/?Oiӽj/KO$yf͛6lٳav~0Ny?6Rj&[]fyp~]t-_|@n8^j%Y 5c׋ .8;-Lhq h?7n 'Sqom/B{}:fkHUD6A8nlSmH N=O7[X"k2VUwbm~4a-iG<8 n'эGRP1׿#H[#9L~EֿQVqͪ~FSekS4H~DyZ38wM@?NR~Cvwr39ܟ1_j1ݲ.ȶ?a.s~W~kzyG7|WFJ+ٳfuٮﵘ}A!cK#[)(69)򯔬o<څ8RԁJ#LXy6lٳ~d|ɳ6lٳRotj+vek?-5-|ʯj~m}ؼUJ}f́No Z+f͛9<||[O0C\[ A$O! GMqxli^ٳf͛6lE_'k /D힙E=5̑Iq.ɿ$__H#y7O>Ht YPQEbW/_s:"7V6Æk=m%O 5a¯8~fiAunDjy@CG#M+΃w"*+ny#pN+#t{tY r|=syGʚf66z 4>!G4_v4応\Zӎyp VE<4i'Ӗg?)fKq]E^ɪ~; xv'~4|Yey65fI^5j|@MT?l>x;̿ߘsEujjM: +Ww%Ɔ6"(I% [P9ϓoΞ# ,5|p_Zͮo~a` ?]p~ x8VUto/NK{v疮̱|Q~!֙%7w*y7SXGHforktddԴ|_Q{tnܱ7.ǴXƟ3ʱ_n?--/,ĵE<6(ZA1GXPܿy)ޔ=Xo 4xX}a}ez_^m[E!Ntu;/ ?ˮ藋"cu2:rW-W_ŌS|'SvnHڼӴ:ŸkȏCyLu9JLyֿ$5OcMڿ%<~7;Լ1II2?59RV7hvNTy:5iKP3>ٱٳ͛6~DZ&vٳ͛6ٳ9<^-[I籐ƢO09dC6I~H\\mط-* \h>\Ҧjϣfٱ֜O%®ֲԻ1+9ґ,5ʲ֯?B-층Ç7n7,ϸ鱷5RUߥV۪X}L۳ٰʅذ-ڢF>l.ϾDGC4f]m<- 7?-Mt5GG_94ֺ|F*"R>`Yy̷h򞣌݃ AX+-Pi+c_Zto).R>HI alٳf͛6q=>|A?Y˛6lٳf͛6lٳf͛Di`>N&EnSFuo/ˍWЭP7t?+it[/Է~xs6lٳa? _M=rn[m~K8[6N Fï1̣C]y)*H2<yYIUr8q2ZK4`"\_;D2 >i@۶ɾaO-ݼ+U~X&~e?qeiΞ?F?QA)~Bo%󟙢_2Hinu5KoThvsɞn>K'hn*g4/+yKOAs:_@wD~MfN]2: 1(pd)M>ۼ/Yg椷8ݣI]>Y20]G_ jVmTKeԜyf͛6l?0+5g;lٳf͛6lٳf͛6lٳf͛6lٳa?_G RkRky^[ȓUmיt5ˊ+- S/ʾZO(\5L BTӶߕ|yuS\~8cqZxbp:5끸MI 7;BW:gݰlO~8MVX傴?$#UHUT\|_"pɺ\vT! 5{ˏ!7.T,/sǑӔ&`z| 'XߦV)%v=)'lS?V0x yt;ΞG:D+KPy7aGSg^FZؿ_ޱ7#"2 <͠R̍ѺChS.$#F m x~gn#ޅCijF4<r jZzW_ʓ3--"w!y5] c<֥Z :yk@_%jK?ԣv·c'45ʭYhYo]ʯVJn=0Hԟk֙^rrL 3z[؜W^]RK鼋7֤;}'lO.~W4 yHvNڷU62}7*yon_B@[&OA_25H)̍ry6J/<}z|f͛6l?1OJ?9f͛6lٳf͛6lٳf͛6lٳf͛|+ga%GM\m5?D\UA9^M},z{ :qOF #o /2^tƮ5ݵ~cB/Fk3Gea ~Xl?;Y@ܾX+Eo`P((ގ?q=X咱v޻`3~ZC%!Ȭ$hsykMUī9cOCMZ~W۽3qIvoXk"d.^9ۮXR"(9o'k^[1ڞ "s"6a*Vjh+ʑ6Zb5,68+O ud5 ǦxZ><驏iAVU}OyFKZ!`H\Sǭ3YIJTdPɗߔ4Y΁ 7US\ٳf͛6l?;;mޔuFA%8-*d|^AQCIIy pGoίo!t\M?=0HȗU'ߟ>je-ƧۛX,M9ȷ\}9 a-70; yCӮc9qL%? |H[u7k`u8K.jn&[WJӒGуϦ]]:翟>Z"]WqϤ?.8Jw4_s{=iזgjH6lٳfŸ6i+}縷8fZ 7?'y>MoRծ <hGT ) K^s EMGƛ`[/Pɔ(*bg/gd-:.gXEZ^qo5}'h1_L~z^h.ƃdfg4wVeP~H1U<-/Odԭ"ڵۦ?N=wd8Psl gySh ^y/)lg+/i8wzcu͏3jj~_HDѳ?)]ըj:5ỵa"ъcl48uX'-jXMGm%柘󍾼<7 ^cצ\_aO8ͯf1Fcw,8uJ\!Oza4ǦkAP~J1U1mwzb_+_Zve"1*vLtKO(`*X4Gz߱͛6lٳfA7ᛊ Q ygq^"YVPj(c("56S F7/2~ы7vSڰ FH`˜C{kO'yqtXd,0޲*}%Q N?vWfEoN?p0Aa~X򅖁sOlŎ9Aalٳf͛1U=@9\Gݛ(pOvoM?}^>a.tg嵏5cSS3jz6MAB7~ЃpA_f }3}^I~ȿx?krIx?k3}^e^f?FC˗g.cDѷٴcӨ͛6ߚ~,/{q%0ҳ,>/'*Ң?95u~^ʗÇ86ٳ=u6-̳/ǭڛۋ*͛6ٳ<͑yV&KXn7iku5 Tcq P(NtEW PҦf͛6yʞ\|:6.į%u9[ RAB i3y/S_Ϧhhz^ӈ㸼Q@I(fX%cV۾ ?ڥiơ[^Zͥ8n.V٠vCG*3Ԃ;n2k j[5kv--,b*;,k?q7 f- K͏4Fwr,f2Oj m6 i}/IդԦFs eGuMcO8~p]7?IWPGQ"3ETVABNbq|}~vз5'FPT ZkiMKCHҠ&wwa뼅_1摭^FOCD-esk}CKКXWw)x]]O.$K>kǩolqby /ƬXTǘ#M^S[}IgE6mozh"V2/'fl[G1sssr`fHXzQ܎ ڸC~x?I#Ҵw֣њoI9FشFb̴M<@:z4|kj/ymqJc8xfT%B=;2[-Yھ%[D6̡Vzu8͟VPz[iqXɤì[_#^ݬѴP[hxH,vۍD}+SX٠ӤLXI[KkGb=UP8yEմo3Y]jyrL3Ys [T4; CߓזZ,s_9QzW"[Góм,7sAh$Tsz49?@ ?:O?#aA}#S@C,5jnsf͛6lٳf͛6lٳf͛6lٳf͛6lkv\,\^^I M1Yg`V|kZoQVS}sBcr}`XBv<;=7M7ok->ڑ#ĉ#<8΅=ZB]H2Zt:=z~TT?z NŒŐ//.ϩ~=FM@J RT ^>4$F<Ŧfbu~VWAwާyJZ\wnӮiNZ T.ʀ*̹hNm3j4&kvmL o b0C?NTǝ!g~;2X\s,۴,%uPIT dKNӼpƑe7l`?Lr-_Ǧylk4y7-@b^LrmQ֚ܺm*-OylͅR.!Bd年{y|v/dA{|Q`uaS ^Tq54jS6g߉UͥŸ-7`.KWF VPOԴd{"Z;@R@c&X4 RhFեZZѧ%ʖ:ep+n W&rcy~?;{+%fM\Ԥg1۬ϣՑw0(4?7r֯Dշʷղⰿ۹׺£ySӭ!ӭͰ@-0&vǰƠ?1!Y/,4Kř#,Mܵh,<,6j=z6sf!oFuK.>Ǵ=0J:/?/ݳҨڰ貹V+԰ڴ!мۍK̚K(\W㛕>#Eֶ7%]uE23<lT뙳f͛6lٳf endstream endobj 108 0 obj <>/XObject<>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/Font<>>>/Thumb 110 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 111 0 obj <>/ProcSet[/PDF/Text]/Font<>>> endobj 109 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.9663 0 0 8.9663 69.7323 725.7825 Tm 0 0 0 rg 0 Tc 0 Tw [(This)-409.6(equation)-413.7(would)-404.3(provide)-410.3(the)-414.7(potential)-407(of)-407.9(estimating)]TJ -1.1128 -1.2203 TD [(the)-269.3(mucociliary)-274.7(speed)-271(in)-266.2(each)-267.6(generation.)-273.8(A)-267(useful)-273.5(denition)]TJ 0 -1.2266 TD [(of)-439.5(the)-446.4(different)-441.8(regions)-439.7(of)-445.8(the)-440(lung)-436.3(might)-445.7(be)-434.3(the)-446.4(three)-440.6(di-)]TJ 0 -1.2203 TD [(mensional)-628.2(shell)-625(approach.)]TJ 6.7246 0 0 5.9768 168.7181 696.8691 Tm (\(53\))Tj 8.9663 0 0 8.9663 185.3291 692.9006 Tm [(This)-624.6(divides)-622(the)-629.7(lung)-619.7(into)]TJ -14.0052 -1.2203 TD [(volumes)-487.7(on)-486.7(the)-484.3(basis)-484.3(of)-483.8(their)-482.2(position)-487(from)-488.4(the)-484.3(center)-484.2(to)]TJ 0 -1.2266 TD [(periphery)-419.9(of)-420.6(the)-421.1(lung)-417.4(and)-416.9(may)-412.5(therefore)-425.5(be)-415.3(well)-413.3(suited)-420.6(to)]TJ 0 -1.2203 TD [(describe)-290.3(the)-288.3(mucociliary)-287.4(movement,)-283.4(which)-289.4(is)-283.1(essentially)-292.7(in)-285.1(a)]TJ T* [(radial)-338.6(direction)-332.7(from)-336.6(periphery)-337.7(to)-332(the)-338.9(hilum)-331.8(of)-338.4(the)-332.5(lung.)]TJ /F12 1 Tf 0 -2.447 TD [(7.)-501.1(Timing)-338.9(of)-330.4(drug)-331.5(treatment/therapy)-336.6(relative)]TJ 0 -1.2203 TD [(to)-336.7(MCC/CC)-332.6(measurement?)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(The)-246.6(general)-239(approach/timing)-251.4(to)-243.5(assess)-244.9(the)-244(acute)-240.8(effect)-247.1(of)-243.5(a)]TJ -1.1128 -1.2203 TD [(treatment)-305.9(on)-303.3(MCC/CC)-299.7(has)-301.4(been)-304.8(to)-300.4(treat)-304.5(after)-304.5(delivering)-300.8(the)]TJ 0 -1.2266 TD [(radioaerosol,)-370.7(based)-362.2(on)-366.6(the)-364.2(rationale)-361.1(that)-370.6(the)-364.2(regional)-365.5(depo-)]TJ 0 -1.2203 TD [(sition)-438.6(will)-435.9(then)-443.4(be)-434.3(unaffected)-444(by)-432.5(treatment)-438.7(versus)-441.6(control.)]TJ T* [(However,)-337.3(more)-329.7(recently,)-337(this)-331.2(approach)-336.7(has)-333(been)-330.1(challenged)]TJ 0 -1.2266 TD [(by)-255.4(\(1\))-253.4(therapies)-256.7(that)-256.8(might)-249.6(induce)-257.1(considerable,)-258.1(uncontrolled)]TJ 0 -1.2203 TD [(coughing,)-253.1(for)-250.5(example,)-247.1(hypertonic)-253.2(saline,)]TJ 6.7246 0 0 5.9768 221.4991 537.9589 Tm (\(46\))Tj 8.9663 0 0 8.9663 234.7653 533.9904 Tm [(\(2\))-253.4(placebos)-246(that)]TJ -19.5188 -1.2203 TD [(are)-468(acutely)-463.7(active)-465(\(e.g.,)-462.5(normal)-469(saline)-460.1(from)-469.4(efcient)-465.2(nebu-)]TJ 0 -1.2266 TD (lizers\),)Tj 6.7246 0 0 5.9768 85.833 516.0754 Tm (\(54\))Tj 8.9663 0 0 8.9663 99.3826 512.0503 Tm [(and)-277.8(\(3\))-278.7(therapies)-282(designed)-277.7(to)-281.5(have)-275.4(durable)-278(or)-275.4(later)]TJ -4.4197 -1.2203 TD [(onset)-380.9(of)-376.3(action.)-378.6(In)-372.2(some)-374.6(of)-376.3(these)-378(cases,)-377.3(it)-377.1(has)-377.3(been)-374.3(deemed)]TJ T* [(necessary)-363.8(to)-357.3(pretreat)-363.4(with)-356.8(therapy)-363.8(at)-354.1(various)-357.7(times)-363.2(prior)-356.8(to)]TJ T* [(inhalation)-459.3(of)-458.5(radioaerosol.)-459.2(These)-456.4(studies)-459.8(have)-452.5(still)-455(consid-)]TJ 0 -1.2266 TD [(ered)-351.3(the)-351.5(potential)-356.4(effect)-354.6(of)-344.7(the)-351.5(pretreatment)-358.4(on)-347.6(regional)-352.9(de-)]TJ 0 -1.2203 TD [(position)-575.6(of)-572.3(aerosol)-566.9(by)-571.6(including)-569.2(the)-572.8(index)-568.4(of)-572.3(deposition)]TJ T* [(\(C/P,)-311.4(PI,)-309.9(or)-307(skew\))-311.2(as)-310.6(a)-309.3(covariate)-309.9(in)-310.4(the)-307.3(statistical)-316.4(analysis)-307.4(of)]TJ 0 -1.2266 TD [(treatment)-432.3(versus)-429(placebo)-428.1(MCC/CC)-426.1(comparisons,)]TJ 6.7246 0 0 5.9768 260.1637 439.37 Tm (\(46,49\))Tj 8.9663 0 0 8.9663 283.4645 435.3448 Tm (that)Tj -24.9502 -1.2203 TD [(is,)-260.7(to)-256.2(test)-255.1(that)-256.8(drug)-256.1(had)-258.8(an)-255.8(effect)-259.7(independent)-261.5(of)-256.2(any)-253.9(possible)]TJ T* [(differences)-549.3(in)-538(deposition)-546.8(pattern.)-539.8(Such)-546.3(analyses)-537.7(will)-543.3(also)]TJ 0 -1.2266 TD [(need)-278.1(to)-275.1(be)-269.9(employed)-278(to)-268.8(study)-276.1(the)-275.6(chronic)-277.9(\(weeks)-273.2(or)-275.4(months\))]TJ 0 -1.2203 TD [(effect)-386.2(of)-376.3(therapies)]TJ 6.7246 0 0 5.9768 131.244 395.4897 Tm (\(46\))Tj 8.9663 0 0 8.9663 145.7007 391.5212 Tm [(as)-380.2(changes)-377.9(in)-380(lung)-379.4(function)-381.4(may)-374.5(alter)]TJ -9.5855 -1.2203 TD [(regional)-416.1(deposition)-414.1(between)-407.9(pre-)-413.4(and)-410.6(posttreatment)-412.9(condi-)]TJ T* [(tions.)-463.3(Study)-463(designs)-465.8(and)-461.1(timing)-461.8(between)-464.8(drug)-458.4(and)-461.1(radio-)]TJ 0 -1.2266 TD [(aerosol)-762.9(may)-753.9(provide)-758.1(the)-762.5(greatest)-759.1(challenge)-763(for)-756.4(future)]TJ 0 -1.2203 TD [(therapies)-199.8(but)-189.6(should)-192.4(be)-187.7(treatment-specic)-200.2(based)-191.5(on)-189.5(the)-193.4(drugs)]TJ T* [(actions)-370.7(on)-372.9(lung)-366.8(function,)-371.7(cough)-371.6(frequency,)-370.8(and)-372.6(duration)-368.8(of)]TJ 0 -1.2266 TD (action.)Tj /F12 1 Tf 0 -2.4406 TD [(8.)-501.1(Evidence)-334.1(that)-338.4(MCC/CC)-332.6(is)-331.6(a)-333.2(good)-333.8(biomarker)]TJ 0 -1.2266 TD [(for)-338.9(airway)-332.7(disease)-336.1(and)-329.4(its)-335.1(treatment?)]TJ /F5 1 Tf 1.1128 -1.8337 TD [(Finally)-446(what)-447.6(evidence)-445.9(is)-447.4(there)-447(that)-446.4(MCC/CC)-445.1(is)-441.1(a)-448.4(good)]TJ -1.1128 -1.2203 TD (biomarker)Tj 6.7246 0 0 5.9768 100.5165 269.4614 Tm (\(1\))Tj 8.9663 0 0 8.9663 112.3086 265.4929 Tm [(of)-464.8(airways)-459.5(inammation/disease)-468.3(and,)-457.8(if)-459.2(little)]TJ -5.8613 -1.2203 TD [(evidence)-427(exists,)-422.6(how)-425.1(do)-423.1(we)-418.8(best)-423.4(assess)-428.3(that?)-420.4(It)-426.2(seems)-423.6(rea-)]TJ T* [(sonable)-406.9(to)-395.3(suggest)-405.2(that)-402.2(slowing)-400(of)-401.6(MCC/CC)-400.8(may)-399.8(enhance)]TJ 0 -1.2266 TD [(susceptibility)-515.3(to)-502.8(airway)-502.5(infection,)-512.8(exacerbation)-508.7(of)-502.8(airways)]TJ 0 -1.2203 TD [(disease,)-612.1(and)-606.6(further)-607.7(decreases)-611.8(in)-607.6(airway)-610(function.)-611.9(Early)]TJ T* [(studies)-276.4(by)-268.1(Goodman)-273.3(et)-265.9(al.)]TJ 6.7246 0 0 5.9768 162.8787 214.696 Tm [(\(55)-10.1(\))]TJ 8.9663 0 0 8.9663 176.4283 210.7275 Tm [(showed)-271.2(progressive)-269.6(slowing)-273.5(of)]TJ -13.0126 -1.2267 TD [(tracheal)-493.2(clearance)-498.2(with)-489.6(increased)-497.4(smoking)-491.6(history.)-493.7(Others)]TJ 0 -1.2203 TD [(studies)-295.4(have)-294.4(also)-291.7(indicated)-293.8(a)-290.4(slower)-294.4(whole)-295.7(lung)-290.9(clearance)-295.9(in)]TJ T* [(healthy)-337.1(smokers)-336.8(versus.)-337(healthy)-330.8(never-smokers)-341.9(and)-334.7(healthy)]TJ 0 -1.2266 TD [(ex-smokers)-427.8(versus)-429(never-smokers.)]TJ 6.7246 0 0 5.9768 197.2346 170.8724 Tm [(\(6,38)-10.4(\))]TJ 8.9663 0 0 8.9663 217.1905 166.8472 Tm [(But)-422.1(no)-423.5(studies)-428.2(have)]TJ -17.5587 -1.2203 TD [(been)-273.2(able)-266.6(to)-268.8(show)-274.7(a)-265.1(clear)-268.5(correlation)-275.8(between)-275.2(rates)-267.5(of)-268.8(MCC/)]TJ T* [(CC)-367.1(and)-366.3(lung)-373.1(function)-368.7(by)-369.2(spirometry)-366.8(in)-367.3(these)-371.7(chronic)-366.4(bron-)]TJ 0 -1.2266 TD [(chitics)-415.5(or)-414.5(smokers.)-409.2(Robinson)-417.8(et)-411.4(al.)]TJ 6.7246 0 0 5.9768 199.6724 137.9905 Tm (\(56\))Tj 8.9663 0 0 8.9663 214.4125 133.9653 Tm [(in)-411.6(a)-410.5(retrospective)-422(re-)]TJ -17.2489 -1.2203 TD [(view)-714(of)-711.4(one)-707.9(laboratorys)-711.2(experience)-718.2(in)-708.8(normal)-709.3(\()]TJ /F6 1 Tf 23.7931 0 TD (N)Tj /F13 1 Tf .9421 0 TD ()Tj /F5 1 Tf .9358 0 TD (17)Tj -25.671 -1.2203 TD [(subjects/22)-520.9(studies\))-523.5(and)-518.1(CF)-516.7(\()]TJ /F6 1 Tf 13.7966 0 TD (N)Tj /F13 1 Tf .9358 0 TD ()Tj /F5 1 Tf .9358 0 TD [(59)-517.5(subjects/184)-520.4(studies\))]TJ -15.6682 -1.2203 TD [(found)-377.7(that)-376.9(MCC)-372.2(was)-369.2(markedly)-373.5(impaired)-375.8(in)-373.6(CF)-371.3(subjects,)-376.3(in)]TJ 0 -1.2266 TD [(comparison)-385.3(to)-388.9(the)-383.1(normal)-380.5(cohort.)-385.4(But)-384.2(interestingly,)-392.3(the)-383.1(ob-)]TJ 0 -1.2203 TD [(served)-391.2(reductions)-388.8(in)-392.6(clearance)-384.4(appeared)-390.9(to)-388.9(be)-383.7(independent)]TJ T* [(of)-388.9(baseline)-394.9(lung)-385.7(function,)-397(and)-385.3(even)-389.6(a)-391.5(subgroup)-390.7(of)-388.9(CF)-390.3(sub-)]TJ 0 -1.2267 TD [(jects)-448.5(with)-445.3(normal)-443.8(FEV)]TJ 6.7246 0 0 5.9768 151.6535 55.7858 Tm (1)Tj 8.9663 0 0 8.9663 158.9669 57.2598 Tm [(measurements)-451.8(\()]TJ /F6 1 Tf 7.1322 0 TD (N)Tj /F13 1 Tf .9358 0 TD ()Tj /F5 1 Tf .9358 0 TD [(17\))-448.4(manifested)]TJ 7.9353 74.5598 TD [(markedly)-266(abnormal)-270.6(clearance)-270.6(rates.)-270.4(MCC)-264.7(has)-269.8(been)-273.2(shown)-271.7(to)]TJ 0 -1.2203 TD [(be)-352.1(mildly)-357(impaired)-356.9(in)-354.7(stable)-356.9(asthma)]TJ 6.7246 0 0 5.9768 456.4345 718.8093 Tm [(\(57,5)-10.4(8\))]TJ 8.9663 0 0 8.9663 479.1117 714.8408 Tm [(and)-360(severely)-358.2(dur-)]TJ -18.7664 -1.2266 TD [(ing)-365.4(acute)-367.2(exacerbations)-370.9(with)-369.4(patients)-364(hospitalized)-375.9(for)-364.3(acute)]TJ 0 -1.2203 TD [(exacerbations)-440.5(having)-432.3(essentially)-438.1(static)-434.5(MCC)-435.4(within)-439.6(3)-429.5(days)]TJ T* (postadmission.)Tj 6.7246 0 0 5.9768 370.1479 685.9274 Tm (\(59\))Tj 8.9663 0 0 8.9663 383.7542 681.9589 Tm [(In)-283.7(the)-288.3(same)-282.8(study,)-285.4(MCC)-283.7(was)-287(improved)-287.8(to)]TJ -8.1313 -1.2266 TD [(near)-319.6(normal)-317.3(rates)-318(with)-325.2(clinical)-319.1(improvement)-317.7(after)-323.5(treatment)]TJ 0 -1.2203 TD [(and)-246.2(discharge)-242.7(from)-248.1(the)-250.3(hospital.)-246.4(Monitoring)-251.4(MCC/CC)-242.7(along)]TJ T* [(with)-464.3(other)-462.5(clinical)-464.5(outcomes)-467(in)-462.2(CF)-459.8(and)-461.2(chronic)-467.6(bronchitic)]TJ 0 -1.2266 TD [(patients)-313.4(over)-307.6(time)-311.3(may)-311.3(help)-311.7(to)-313.1(determine)-311.8(which)-308.4(biomarkers)]TJ 0 -1.2203 TD [(are)-455.4(most)-463.7(sensitive)-463(at)-455.2(predicting)-462.2(long-term)-462.1(outcome)-459.4(of)-458.5(pa-)]TJ T* [(tients.)-296.5(The)-297.1(importance)-299.3(of)-294.1(MCC)-296.3(for)-294.8(health)-294.7(status)-301.6(may)-292.4(be)-295.2(best)]TJ T* [(observed)-379.5(in)-380(model)-379.8(disease)-381.5(for)-377(MCC)-378.5(dysfunction,)-386.7(PCD.)-378.9(We)]TJ 0 -1.2266 TD [(know)-303.1(that)-307.3(PCD)-300.1(results)-305.8(in)-304.1(infections)-308.9(and)-303.1(impairment)-304.7(of)-306.7(lung)]TJ 0 -1.2203 TD [(function)-362.4(and)-360(in)-354.7(a)-359.9(few)-362.4(patients)-364(even)-358(lung)-360.5(transplantation.)-361.3(It)]TJ T* [(would)-442.2(further)-443.3(strengthen)-447.3(the)-446.4(concept)-449.1(if)-440.3(we)-444.1(could)-439.9(link)-444.8(ge-)]TJ 0 -1.2266 TD [(notypes)-336.1(with)-344.1(the)-338.9(different)-340.6(phenotypes)-340.7(of)-338.4(PCD)-338(and)-334.7(variabil-)]TJ 0 -1.2203 TD [(ity)-299.3(in)-304.1(MCC)-309(impairment)-304.7(between)-306.8(patients,)-303.7(and)-303.1(between)-306.8(time)]TJ T* [(of)-553.3(diagnosis/institution)-555.9(of)-553.3(treatment)-558.8(with)-552.8(long-term)-557(out-)]TJ 0 -1.2266 TD (come.)Tj 1.1128 -1.2203 TD [(As)-382.1(discussed)-393.4(previously,)-389.3(MCC)-391.2(measurements)-388.6(have)-389.2(been)]TJ -1.1128 -1.2203 TD [(utilized)-476.4(in)-474.8(a)-473.7(number)-481.5(of)-477.5(small)-473.4(clinical)-477.2(trials,)-479.9(but)-474.1(generally)]TJ T* [(these)-340.1(have)-338.6(been)-342.7(acute)-342(in)-342(nature,)-343.4(that)-339(is,)-342.9(single)-338.6(treatment)-343.8(ef-)]TJ 0 -1.2266 TD [(fects,)-383.7(and)-378.9(have)-382.9(not)-379.7(shown)-385.5(a)-378.9(correlation)-383.3(with)-382.1(lung)-385.7(function)]TJ 0 -1.2203 TD [(changes)-352.6(associated)-358.4(with)-356.8(treatment.)-359.4(Most)-351.1(recently,)-362.3(however,)]TJ T* [(Donaldson)-356.2(et)-360.8(al.)]TJ 6.7246 0 0 5.9768 376.6109 466.7527 Tm (\(46\))Tj 8.9663 0 0 8.9663 390.8408 462.7841 Tm [(found)-358.8(that)-357.9(2-week)-359.9(treatment)-356.5(with)-356.8(aero-)]TJ -8.9216 -1.2266 TD [(solized)-430.9(hypertonic)-430.2(saline)-428.5(\(HS\))-429.4(in)-430.5(CF)-428.2(patients)-433.6(resulted)-433.8(in)-424.2(a)]TJ 0 -1.2203 TD [(sustained)-424.8(improvement)-431.5(in)-424.2(both)-428.4(their)-425.3(MCC)-422.8(and)-423.2(lung)-423.7(func-)]TJ T* [(tion,)-247(although)-252.8(the)-250.3(two)-245.1(were)-255(not)-246.9(correlated)-250(in)-247.2(the)-250.4(small)-252.1(group)]TJ 0 -1.2266 TD [(of)-528(patients)-528.4(studied.)-527.6(A)-526.2(larger)-527.2(12-month)-531.9(trial)-526.2(of)-528(HS)-529.6(saline)]TJ 0 -1.2203 TD [(treatment)-356.5(in)-348.4(CF)-352.3(showed)-353.4(similar)-351.1(improvement)-355.7(in)-354.7(lung)-347.8(func-)]TJ T* [(tion)-465.4(and)-461.2(a)-467.4(decrease)-465.1(in)-462.2(pulmonary)-469.8(exacerbations)-465.8(requiring)]TJ 0 -1.2266 TD [(antibiotics,)-284.4(although)-284.4(the)-282(long-term)-285.1(effect)-285(of)-281.4(HS)-283(on)-278(MCC/CC)]TJ 0 -1.2203 TD [(was)-293.3(not)-297.5(measured)-294.1(in)-291.5(this)-299.6(cohort)-293.9(of)-294.1(CF)-295.4(patients.)]TJ 6.7246 0 0 5.9768 498.6707 379.0487 Tm (\(60\))Tj 8.9663 0 0 8.9663 512.3904 375.0802 Tm [(It)-293.4(may)-292.3(be)]TJ -22.4779 -1.2203 TD [(that)-250.4(exacerbation)-262.1(frequency)-254.1(is)-251.4(a)-252.4(better)-252.4(correlate)-259.7(with)-255.6(changes)]TJ T* [(in)-373.6(MCC/CC)-375.5(with)-375.7(long-term)-379.9(therapy)-376.5(than)-379.8(lung)-373.1(function)-381.4(by)]TJ 0 -1.2266 TD [(spirometry,)-502.5(a)-499(robust)-504.2(but)-499.4(relatively)-503.1(insensitive)-501.5(measure)-506.1(of)]TJ 0 -1.2203 TD [(lung)-234(changes.)-235.4(The)-233.9(fact)-240(that)-231.5(spirometry)-240.3(measures)-235.5(resistance)-243.3(to)]TJ T* [(airow)-434.8(and)-435.9(lung)-442.7(compliance)-440.1(suggests)-438.1(MCC/CC)-438.8(measures)]TJ 0 -1.2266 TD [(may)-349.3(not)-360.7(have)-351.3(strong)-360.8(correlations.)-355.9(More)-356.3(recent)-357.7(studies)-358.7(have)]TJ 0 -1.2203 TD [(shown)-360.2(an)-363.3(improvement)-362(in)-361(lung)-360.5(function)-362.4(and)-360(quality)-365(of)-357.3(life)]TJ T* [(when)-305.5(inhaled)-307.1(mannitol)-311.3(was)-306(administered)-306.7(twice)-308.3(daily)-304.8(over)-307.6(2)]TJ 0 -1.2266 TD [(weeks)-550.9(in)-550.7(patients)-553.7(with)-546.5(CF.)]TJ 6.7246 0 0 5.9768 425.4802 280.4597 Tm (\(61\))Tj 8.9663 0 0 8.9663 441.5243 276.4345 Tm [(The)-550.1(improvement)-551.7(in)-550.7(lung)]TJ -14.5743 -1.2203 TD [(function)-438.3(correlated)-433.4(with)-439(the)-433.7(increase)-437.5(in)-430.6(hydration)-438.5(and)-435.9(de-)]TJ T* [(crease)-506.4(in)-506.4(surface)-502(tension)-507.9(in)-506.4(the)-509.6(sputum)-502.9(properties)-511.5(of)-502.7(the)]TJ T* [(same)-478.8(CF)-478.8(patients.)]TJ 6.7246 0 0 5.9768 384.4345 247.5779 Tm (\(62\))Tj 8.9663 0 0 8.9663 399.7983 243.6094 Tm [(These)-488(studies)-478.8(in)-481.1(CF)-485.1(suggest)-481.1(that)-484.4(an)]TJ -9.9206 -1.2266 TD [(acute)-310.3(effect)-310.3(of)-306.7(a)-309.3(treatment)-312.2(on)-309.7(MCC/CC)-312.3(is)-308.3(a)-303(good)-310.1(indication)]TJ 0 -1.2203 TD [(for)-332.7(potential)-337.4(long-term)-335.7(clinical)-338.1(benets)-334.9(in)-335.7(these)-333.8(patients.)]TJ /F4 1 Tf 0 -3.054 TD (Conclusions)Tj /F5 1 Tf 1.1128 -1.8336 TD [(The)-328.8(development)-328.7(of)-332(methodologies)-335.2(for)-326.4(measuring)-334.1(MCC/)]TJ -1.1128 -1.2266 TD [(CC)-234.3(in)-234.5(human)-239.2(studies)-238.5(has)-231.8(progressed)-243(during)-237.7(the)-237.7(past)-236.6(20)-233(years)]TJ 0 -1.2203 TD [(to)-275.1(the)-282(point)-277.1(where)-277.4(there)-282.6(is)-276.7(general)-276.9(agreement)-277.6(that)-282(controlled)]TJ T* [(inhalation)-560.5(of)-559.7(nonabsorbable,)-557.8(tightly)-564(labeled)-557.6(radioaerosols)]TJ 0 -1.2266 TD [(must)-342.1(be)-339.4(used)-347(to)-344.7(accurately)-343.1(assess)-346.1(MCC/CC)-343.9(endpoints.)-344.5(The)]TJ 0 -1.2203 TD [(marker)-243.1(of)-249.8(choice)-248.4(for)-250.5(most)-242.4(laboratories)-253.1(is)-245.1(many)-245.2(times)-249.4(dictated)]TJ T* [(by)-350.3(availability,)-358(ease)-361(of)-351(use,)-359.6(and)-353.7(acceptability)-360.7(by)-356.6(the)-351.5(regula-)]TJ T* [(tory)-615.4(agencies)-618.2(of)-610.2(that)-617.2(site.)-615.1(Despite)-621.2(these)-618.3(differences,)-615.4(the)]TJ 0 -1.2266 TD [(measured)-426.9(MCC/CC)-426.1(may)-425.1(not)-430.3(be)-428(dramatically)-425.6(different)-435.5(be-)]TJ 0 -1.2203 TD [(tween)-270.8(laboratories)-272.1(when)-273.9(corrected)-277.9(for)-269.5(regional)-270.7(differences)-277.4(in)]TJ T* [(lung)-765.1(deposition)-768.1(that)-768.9(may)-766.6(occur)-762.1(due)-769.3(to)-768.3(variability)-763.7(in)]TJ 0 -1.2267 TD [(breathing)-493.9(maneuvers)-503.9(and)-492.8(aerosol)-497.4(size.)-494(Although)-501.3(most)-495.3(all)]TJ /F4 1 Tf -28.0042 77.228 TD [(MUCOCILIARY)-339.2(AND)-337.2(COUGH)-337(CLEARANCE)]TJ 53.0113 0 TD (269)Tj ET endstream endobj 112 0 obj <>/XObject<>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/Font<>>>/Thumb 114 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 115 0 obj <>/ProcSet[/PDF/Text]/Font<>>> endobj 113 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.9663 0 0 8.9663 62.022 725.7825 Tm 0 0 0 rg 0 Tc 0 Tw [(laboratories)-360.6(use)-356.6(planar)-355.8(imaging)-357.8(to)-351(assess)-358.7(MCC/CC,)-359.5(the)-357.8(fu-)]TJ 0 -1.2203 TD [(ture)-343.9(of)-338.4(the)-338.9(methodology)-347.5(may)-336.6(lie)-342.1(in)-335.7(3D)-342.3(imaging)-338.8(that)-345.3(should)]TJ 0 -1.2266 TD [(allow)-485.2(better)-486.4(resolution)-494(of)-483.8(airway)-483.5(regions.)-486.8(Meanwhile,)-490.7(the)]TJ 0 -1.2203 TD [(similarity)-378.5(of)-376.3(gamma)-371.6(camera)-375.8(acquisition)-377.2(and)-372.6(analysis)-376.9(meth-)]TJ T* [(ods)-335.9(should)-337.8(allow)-333.4(laboratories)-335.3(to)-338.4(share)-333.6(and)-334.7(compare)-336.2(data)-337.6(to)]TJ 0 -1.2266 TD [(address)-350.2(many)-352.6(of)-351(the)-351.5(questions)-353.6(raised)-349.4(in)-354.7(this)-350.1(review)-354.2(and,)-350.3(in)]TJ 0 -1.2203 TD [(doing)-364.9(so,)-361.1(better)-366.3(rene)-361(our)-365.2(methodologies)-366.8(for)-364.3(improving)-359.4(on)]TJ T* [(their)-336.8(accuracy.)]TJ 1.1128 -1.2266 TD [(The)-423.6(utility)-428.3(of)-426.9(MCC/CC)-432.4(as)-424.5(a)-423.1(biomarker)-430.8(for)-427.6(disease)-425.8(pro-)]TJ -1.1128 -1.2203 TD [(gression)-491.6(and)-486.4(therapeutic)-490.4(intervention)-490.1(is)-485.4(gaining)-490.1(increased)]TJ T* [(recognition)-422.5(as)-418.1(a)-423.1(valuable)-417.2(tool)-420.5(in)-417.9(the)-421.1(clinical)-420.3(research)-422(com-)]TJ T* [(munity.)-380.4(The)-385.7(methodology)-379.1(has)-383.6(clearly)-377.6(been)-387(valuable)-379.2(for)-383.3(as-)]TJ 0 -1.2266 TD [(sessing)-287.1(acute)-285(responsiveness)-286.4(of)-287.8(the)-282(mucociliary)-287.4(apparatus)-283.3(to)]TJ 0 -1.2203 TD [(therapies)-579.1(designed)-581.2(to)-578.6(improve)-582(clearance)-580.4(of)-572.3(secretions)-588(in)]TJ T* [(patients)-414.6(with)-413.7(airways)-415.3(disease.)-409.7(The)-411(most)-413.1(recent)-414.6(example)-414.9(of)]TJ 0 -1.2266 TD [(this)-470.3(success)-471.7(has)-472.1(been)-469.2(with)-470.6(the)-471.6(application)-467.2(of)-471.1(inhaled,)-474.4(hy-)]TJ 0 -1.2203 TD [(perosmotic)-237.3(agents)-236.6(\(HS)-239.2(and)-233.5(mannitol\))-235.9(to)-237.2(improve)-234.2(clearance)-239(of)]TJ T* [(secretions)-404.6(and)-397.9(lung)-398.4(function)-400.4(in)-392.6(CF)-396.6(patients.)-404.9(The)-398.3(MCC/CC)]TJ 0 -1.2266 TD [(biomarker)-336(may)-336.6(also)-329.6(become)-338.9(an)-331.7(important)-338.6(tool)-338.3(for)-332.7(assessing)]TJ 0 -1.2203 TD [(new)-245.2(therapies)-250.3(for)-244.2(other)-241.2(airway)-243.2(diseases,)-246.7(for)-244.2(example,)-247.1(chronic)]TJ T* [(obstructive)-286.8(pulmonary)-286.5(disease)-286.7(\(COPD\))-291.4(and)-284.1(asthma,)-282.9(as)-285.4(there)]TJ T* [(becomes)-485.7(increasing)-486.9(awareness)-487.7(of)-483.8(the)-484.3(role)-487.4(that)-484.4(insufcient)]TJ 0 -1.2266 TD [(MCC/CC)-710.6(plays)-705.7(in)-708.8(these)-713.1(diseases.)-708.2(Finally,)-708.1(the)-711.9(greatest)]TJ 0 -1.2203 TD [(challenge)-427.8(for)-421.3(the)-421.1(utility)-428.3(of)-420.6(the)-421.1(methodology)-429.7(may)-418.8(lie)-424.3(in)-417.9(re-)]TJ T* [(lating)-463.8(the)-471.6(endpoints)-468.1(of)-464.8(MCC/CC)-464(with)-464.3(other)-468.8(clinically)-466.1(ac-)]TJ 0 -1.2266 TD [(cepted)-731(endpoints)-733.6(of)-724.1(lung)-733.5(health)-731(over)-724.9(time)-728.6(\(e.g.,)-728(lung)]TJ 0 -1.2203 TD [(function,)-371.7(exacerbation)-369.6(frequency\),)-371.3(either)-368.3(in)-367.3(tracking)-369.8(disease)]TJ T* [(progression)-534.3(or)-521.9(assessing)-534.5(the)-528.6(chronic)-524.5(effectiveness)-535.4(of)-528(new)]TJ 0 -1.2266 TD (therapies.)Tj /F4 1 Tf 0 -2.643 TD [(Author)-338.7(Disclosure)-330.4(Statement)]TJ /F5 1 Tf 1.1128 -1.8336 TD [(No)-331.5(conicts)-335.5(of)-338.4(interest)-338.5(exist.)]TJ /F4 1 Tf -1.1128 -2.6683 TD (References)Tj /F5 1 Tf 8.4682 0 0 8.4682 66.274 338.7968 Tm [(1.)-501.9(Mayer-Hamblett)-553.7(N,)-548.1(Ramsey)-546.6(BW,)-549.4(and)-546.7(Kronmal)-546.6(RA:)-550.1(Ad-)]TJ 1.2519 -1.2318 TD [(vancing)-393.6(outcome)-400.6(measures)-398(for)-392.2(the)-398.7(new)-396.5(era)-394.3(of)-395.6(drug)-396.6(devel-)]TJ 0 -1.2385 TD [(opment)-619.1(in)-626.5(cystic)-621.2(brosis.)-625.4(Proc)-621.5(Am)-617.8(Thorac)-623.1(Soc.)-622(2007;4:)]TJ 0 -1.2318 TD (370377.)Tj -1.2519 -1.2385 TD [(2.)-501.9(Wa)13.8(nner)-172.1(A,)-171.7(Sala)13.5(the)-171.1(M,)-178.7(ORi)16.3(orda)14.9(n)-177.8(TG:)-173.5(Muc)12.1(ocil)13.6(iary)-169.9(cle)14.4(aran)15.5(ce)-179.6(in)]TJ 1.2519 -1.2385 TD [(the)-244.8(air)14.5(ways.)-240.7(Am)-249.6(J)-247.1(Respi)13.9(r)-251(Crit)-245.5(Car)13(e)-255(M)0(e)12.5(d)0(.)-250.6(199)13.8(6;15)16(4:186)13.9(81)13.8(902)13.8(.)]TJ -1.2519 -1.2318 TD [(3.)-501.9(Bennett)-541.6(WD,)-544.1(Almond)-541.3(MA,)-540.2(Zeman)-540.9(KL,)-543.6(Johnson)-541.1(JG,)-542.5(and)]TJ 1.2519 -1.2385 TD [(Donohue)-348.2(JF:)-342.2(Effect)-350.2(of)-348.8(salmeterol)-343.5(on)-346.5(mucociliary)-353.5(and)-345.8(cough)]TJ 0 -1.2318 TD [(clearance)-564.7(in)-559.6(chronic)-564.3(bronchitis.)-572.8(Pulm)-563.5(Pharm)-563(Ther.)-559.6(2006;)]TJ 0 -1.2385 TD (19:96100.)Tj -1.2519 -1.2318 TD [(4.)-501.9(Daviskas)-334.5(E,)-331(Anderson)-345(SD,)-334.5(Eberl)-334.4(S,)-334.6(and)-332.4(Young)-336.4(IH:)-335.7(Effect)-336.8(of)]TJ 1.2519 -1.2385 TD [(increasing)-296(doses)-293.2(of)-295.2(mannitol)-293.8(on)-292.9(mucus)-299.5(clearance)-296.9(in)-291.8(patients)]TJ 0 -1.2318 TD [(with)-335.2(bronchiectasis.)-338.5(Eur)-339.4(Respir)-330.9(J.)-338.5(2008;31:765772.)]TJ -1.2519 -1.2385 TD [(5.)-501.9(Marthin)-401(JK,)-397.1(Mortensen)-407.1(J,)-392.1(Pressler)-404(T,)-397.9(and)-399.4(Nielsen)-400.9(KG:)-401(Pul-)]TJ 1.2519 -1.2318 TD [(monary)-417.8(radioaerosol)-421.7(mucociliary)-420.5(clearance)-424.1(in)-419(diagnosis)-416.3(of)]TJ 0 -1.2385 TD [(primary)-332.1(ciliary)-335.8(dyskinesia.)-336.7(Chest.)-336.9(2007;132:966976.)]TJ -1.2519 -1.2318 TD [(6.)-501.9(Mortensen)-407.1(J,)-405.4(Lange)-403.7(L,)-404.6(Nyboe)-405.7(J,)-405.4(and)-406.1(Groth)-405.9(S:)-401.6(Lung)-410.5(muco-)]TJ 1.2519 -1.2385 TD [(ciliary)-329.1(clearance.)-341.5(Eur)-332.7(J)-334.1(Nucl)-337.4(Med.)-338.6(1994;21:953961.)]TJ -1.2519 -1.2318 TD [(7.)-501.9(Lay)-406(JC,)-407.1(Berry)-404.4(CR,)-404.5(Kim)-408.9(CS,)-409.9(and)-406.1(Bennett)-407.7(WD:)-410.2(Retention)-407.4(of)]TJ 1.2519 -1.2385 TD [(insoluble)-353.2(particles)-354(following)-348.5(local)-350(intrabronchial)-359.8(deposition)]TJ 0 -1.2318 TD [(in)-332(dogs.)-335(J)-334.1(Appl)-333.8(Physiol.)-336.7(1995;79:19211)-7.4(929.)]TJ -1.2519 -1.2385 TD [(8.)-501.9(Chapman)-379.8(TH,)-386(McCool)-384.4(D,)-385.9(Smith)-382.4(RE,)-388(Dilworth)-386.7(JP,)-381.5(and)-386(Ag-)]TJ 1.2519 -1.2318 TD [(new)-476.9(JE:)-484.3(Domiciliary)-479.8(humidication)-486.2(improves)-485(lung)-485.8(muco-)]TJ 0 -1.2385 TD [(ciliary)-570.2(clearance)-578.1(in)-573(patients)-576.4(with)-576.2(bronchiectasis.)-579.5(Chronic)]TJ 0 -1.2318 TD [(Respir)-337.6(Dis.)-331.6(2008;5:8186.)]TJ -1.2519 -1.2385 TD [(9.)-501.9(Hasani)-383.6(A,)-385.9(Toms)-389.2(N,)-380.8(Agnew)-393.4(JE,)-383.9(Sarno)-387.5(M,)-386.3(Harrison)-389.4(AJ,)-385.3(and)]TJ 1.2519 -1.2318 TD [(Dilworth)-420.2(JP:)-421.7(The)-418(effect)-426(of)-415.7(inhaled)-424.2(Tiotropium)-426.9(bromide)-418(on)]TJ 29.6445 77.8135 TD [(lung)-438.9(mucociliary)-447.3(clearance)-444.2(in)-439.1(patients)-442.5(with)-442.3(COPD.)-446.3(Chest.)]TJ 0 -1.2318 TD (2004;125:17261734.)Tj -1.754 -1.2385 TD [(10.)-504(Scheuch)-458.1(G,)-449.5(Stahlhofen)-458.2(W,)-450.5(and)-452.9(Heyder)-450.1(J:)-452.3(An)-452.2(approach)-458.3(to)]TJ 1.754 -1.2318 TD [(deposition)-355.3(and)-345.8(clearance)-350.5(measurements)-350.2(in)-345.4(human)-349.2(airways.)]TJ 0 -1.2385 TD [(J)-334.1(Aerosol)-340.4(Med.)-331.9(1996;9:3541.)]TJ -1.754 -1.2318 TD [(11.)-504(Scheuch)-558.5(G,)-549.9(Kohlha)]TJ 10.2229 .0067 TD ()Tj .4419 -.0067 TD [(u)-550.3(M,)-553.6(Mo)]TJ 4.5324 .0067 TD ()Tj .4352 -.0067 TD [(ller)-553.3(W,)-550.9(Brand)-555.2(P,)-556.2(Meyer)-550.8(T,)]TJ -13.8783 -1.2385 TD (Ha)Tj .8837 .0134 TD ()Tj .4419 -.0134 TD [(ussinger)-266.9(K,)-270.5(Sommerer)-269.8(K,)-270.5(and)-265.5(Heyder)-276(J:)-264.9(Particle)-274.6(clearance)]TJ -1.3256 -1.2318 TD [(from)-461.2(the)-459(airways)-462.9(of)-462.6(subjects)-463.4(with)-462.4(bronchial)-458.3(hyperrespon-)]TJ 0 -1.2385 TD [(siveness)-464.8(and)-466.3(with)-462.4(chronic)-470.5(obstructive)-470.2(pulmonary)-463.9(disease.)]TJ 0 -1.2318 TD [(Exp)-334.9(Lung)-336.8(Res.)-335.6(2008;34:531549.)]TJ -1.754 -1.2385 TD [(12.)-504(Stahlhofen)-458.2(W,)-450.5(Gebhart)-457.9(J,)-452.3(and)-446.3(Heyder)-456.8(J:)-452.3(Experimental)-454.2(de-)]TJ 1.754 -1.2318 TD [(termination)-303.8(of)-301.9(the)-298.3(regional)-296.3(deposition)-308.4(of)-295.2(aerosol)-302.4(particles)-300.4(in)]TJ 0 -1.2385 TD [(the)-840.6(human)-844.6(respiratory)-842.5(tract.)-843.5(Am)-838.8(Ind)-840.9(Hyg)-839(Assoc)-841(J.)]TJ 0 -1.2318 TD (1980;41:385398.)Tj -1.754 -1.2385 TD [(13.)-504(Pavia)-362.4(D)-354.7(and)-359.2(Thomson)-364.5(ML:)-358(The)-357.7(fractional)-364.6(deposition)-368.6(of)-355.5(in-)]TJ 1.754 -1.2318 TD [(haled)-346.6(2)-336.8(and)-345.8(5)]TJ /F11 1 Tf 6.2931 0 TD (m)Tj /F5 1 Tf .5557 0 TD [(m)-343.5(particles)-347.3(in)-338.7(the)-345.2(alveolar)-344.9(and)-345.8(tracheobron-)]TJ -6.8488 -1.2385 TD [(chial)-379.3(regions)-380.1(of)-375.5(the)-378.6(healthy)-381.7(human)-382.7(lung.)-376.4(Ann)-382.3(Occup)-379.2(Hyg.)]TJ 0 -1.2318 TD (1976;19:109114.)Tj -1.754 -1.2385 TD [(14.)-504(Mortensen)-373.6(J,)-372(Falk)-371.2(M,)-372.9(Groth)-372.4(S,)-368.1(and)-372.6(Jensen)-375.4(C:)-367.6(The)-371.1(effects)-378.2(of)]TJ 1.754 -1.2385 TD [(postural)-385.9(drainage)-382.5(and)-379.3(positive)-385.5(expirator)-11.8(y)-378.6(pressure)-386.6(physio-)]TJ 0 -1.2318 TD [(therapy)-638.3(on)-641(tracheobronchial)-640.9(clearance)-645.1(in)-633.3(cystic)-641.3(brosis.)]TJ 0 -1.2385 TD [(Chest.)-336.9(1991;100:13501357.)]TJ -1.754 -1.2318 TD [(15.)-504(Daviskas)-287.7(E,)-284.1(Anderson)-291.4(SD,)-287.7(Gonda)-290.1(I,)-287.3(Chan)-285.8(H-K,)-291.4(Cook)-289(P,)-281.7(and)]TJ 1.754 -1.2385 TD [(Fulton)-272.2(R:)-275.7(Changes)-275.8(in)-271.7(mucociliary)-273.2(clearance)-276.9(during)-273.4(and)-272.2(after)]TJ 0 -1.2318 TD [(isocapnic)-240.1(hyperventilation)-246.3(in)-238.3(asthmatic)-240.4(and)-238.7(healthy)-241.1(subjects.)]TJ 0 -1.2385 TD [(Eur)-332.7(Respir)-337.6(J)-334.1(1995;8:742751.)]TJ -1.754 -1.2318 TD [(16.)-504(Daviskas)-240.8(E,)-237.3(Anderson)-237.9(SD,)-240.8(Eberl)-240.6(S,)-234.2(Chan)-238.9(H-K,)-237.9(and)-238.7(Bautovich)]TJ 1.754 -1.2385 TD [(G:)-268.7(Inhalation)-279.3(of)-275.1(dry)-266.6(powder)-278.2(mannitol)-273.7(improves)-277.5(clearance)-276.8(of)]TJ 0 -1.2318 TD [(mucus)-252.6(in)-251.6(patients)-255(with)-248.2(bronchiectasis.)-258.1(Am)-249.6(J)-253.7(Respir)-250.5(Crit)-252.2(Care)]TJ 0 -1.2385 TD [(Med.)-331.9(1999;159:1843)-7.4(1848.)]TJ -1.754 -1.2318 TD [(17.)-504(Phipps)-393.1(PR,)-392.3(Gonda)-390.5(I,)-394.4(and)-392.7(Anderson)-391.8(SD:)-394.8(Apparatus)-396(for)-392.2(the)]TJ 1.754 -1.2385 TD [(control)-549.6(of)-542.9(breathing)-542.6(during)-547.9(aerosol)-543.5(inhalation.)-550(J)-541.6(Aerosol)]TJ 0 -1.2318 TD [(Med.)-331.9(1992;5:155170)-7.4(.)]TJ -1.754 -1.2385 TD [(18.)-504(Hasani)-256.4(A,)-252(Rotondetto)-256(S,)-254.3(Pavia)-255.3(D,)-252(Agnew)-252.8(JE,)-250(Clarke)-252.6(SW,)-251.8(and)]TJ 1.754 -1.2318 TD [(Spiteri)-430.5(MA:)-426.3(Effects)-429.6(of)-429.1(oral)-428.6(antibiotics)-435.8(on)-426.8(lung)-425.5(mucociliary)]TJ 0 -1.2385 TD [(clearance)-524.6(during)-527.8(exacerbation)-522.8(of)-522.8(chronic)-530.8(obstructive)-523.7(pul-)]TJ 0 -1.2318 TD [(monary)-337.5(disease.)-332.7(Respir)-337.6(Med.)-338.6(1998;92:442447.)]TJ -1.754 -1.2385 TD [(19.)-504(Hasani)-430.5(A,)-432.8(Toms)-436.1(N,)-427.6(OConnor)-436.9(J,)-432.2(Dilworth)-440.3(JP,)-428.4(and)-432.9(Agnew)]TJ 1.754 -1.2318 TD [(JE:)-732(Effect)-738.5(of)-730.4(salmeterol)-738.5(xinafoate)-730.6(on)-734.8(lung)-733.5(mucociliary)]TJ 0 -1.2385 TD [(clearance)-584.8(in)-586.4(patients)-589.7(with)-582.9(asthma.)-581.9(Respir)-585.3(Med.)-586.3(2003;97:)]TJ 0 -1.2318 TD (667671.)Tj -1.754 -1.2385 TD [(20.)-504(Bailey)-346.7(DL,)-351(Fulton)-345.8(RR,)-352.8(Jacson)-345.2(CB,)-352.7(and)-345.8(Hutton)-349.5(BF:)-348(Dynamic)]TJ 1.754 -1.2318 TD [(geometric)-263.6(mean)-269.6(studies)-260.8(using)-270.6(a)-256.5(single)-268.6(head)-266.1(rotating)-267.4(camera.)]TJ 0 -1.2385 TD [(J)-334.1(Nucl)-337.4(Med.)-331.9(1989;30:18651869.)]TJ -1.754 -1.2318 TD [(21.)-504(Regnis)-285.3(JA,)-278.1(Robinson)-284.3(M,)-279.2(Bailey)-286.5(DL,)-277.3(Cook)-282.4(P,)-281.7(Hooper)-285.3(P,)-275(Chan)]TJ 1.754 -1.2385 TD [(H-K,)-606.1(Gonda)-598(I,)-602(Bautovich)-609.1(G,)-596.7(and)-606.9(Bye)-598.7(PTP:)-604.4(Mucociliary)]TJ 0 -1.2318 TD [(clearance)-598.2(in)-593.1(patients)-603.1(with)-596.3(cystic)-594.4(brosis)-601(and)-593.5(in)-593.1(normal)]TJ 0 -1.2385 TD [(subjects.)-340.6(Am)-330(J)-334.1(Respir)-337.6(Crit)-339.2(Care)-335.7(Med.)-331.9(1994;150:6671.)]TJ -1.754 -1.2318 TD [(22.)-504(Robinson)-398.1(M,)-393(Daviskas)-394.8(E,)-397.9(Eberl)-394.6(E,)-391.2(Baker)-396.5(J,)-392.1(Chan)-392.9(H-K,)-398.6(An-)]TJ 1.754 -1.2385 TD [(derson)-341.3(SD,)-347.9(and)-339.1(Bye)-344.3(PTP:)-343.4(The)-344.4(effect)-345.6(of)-342.1(inhaled)-343.9(mannitol)-340.7(on)]TJ 0 -1.2318 TD [(bronchial)-331.1(mucus)-333(clearance)-337.1(in)-332(cystic)-333.4(brosis)-333.2(patients:)-333(a)-330.2(pilot)]TJ 0 -1.2385 TD [(study.)-335.9(Eur)-332.7(Respir)-337.6(J.)-338.5(1999;14:678685.)]TJ -1.754 -1.2385 TD [(23.)-504(Hasani)-363.5(A,)-359.1(Pavia)-355.7(D,)-365.8(Spiteri)-356.8(MA,)-366.1(Yeo)-360.2(CT,)-359.4(Agnew)-359.9(JE,)-357.1(Clarke)]TJ 1.754 -1.2318 TD [(SW,)-325.5(and)-325.7(Chung)-330.3(KF:)-321.1(Inhaled)-332.1(frusemide)-327.9(does)-327.6(not)-325.7(affect)-327(lung)]TJ 0 -1.2385 TD [(mucociliary)-286.6(clearance)-283.5(in)-278.4(healthy)-287.9(and)-278.9(asthmatic)-287.3(subjects.)-280.3(Eur)]TJ 0 -1.2318 TD [(Respir)-337.6(J)-334.1(1994;7:14971500.)]TJ -1.754 -1.2385 TD [(24.)-504(Hasani)-303.3(A,)-305.6(Pavia)-308.9(D,)-298.9(Agnew)-313.1(JE,)-303.6(and)-299(Clarke)-306.1(SW:)-305.4(The)-304.2(effect)-312.1(of)]TJ 1.754 -1.2318 TD [(unproductive)-355.5(coughing/FE)-11.4(T)-346.7(o)0(n)-353.2(regional)-356.6(mucus)-353.1(movement)]TJ 0 -1.2385 TD [(in)-332(the)-338.5(human)-335.8(lungs.)-335.3(Respir)-337.6(Med.)-338.6(1991;85:2326.)]TJ -1.754 -1.2318 TD [(25.)-504(Bennett,)-338.5(WD,)-329.9(Chapman,)-330.6(WF,)-333.6(and)-325.7(JM)-334.4(Mascarella:)-333.9(The)-331(acute)]TJ 1.754 -1.2385 TD [(effect)-533.1(of)-536.2(ipratropium)-535.7(bromide)-531.8(bronchodilator)-535.6(therapy)-531.2(on)]TJ 0 -1.2318 TD [(cough)-337.7(clearance)-337.1(in)-332(COPD.)-339.1(Chest.)-336.9(1993;103:488495.)]TJ -1.754 -1.2385 TD [(26.)-504(Eberl)-280.8(S,)-274.4(Chan)-279.1(H-K,)-278(Daviskas)-281(E,)-277.4(Constable)-279.5(C,)-280.5(and)-272.2(Young)-282.8(IH:)]TJ 1.754 -1.2318 TD [(Aerosol)-601.5(deposition)-609.6(and)-600.2(clearance)-604.9(measurement:)-603.2(a)-597.9(novel)]TJ /F4 1 Tf 8.9663 0 0 8.9663 62.022 749.6502 Tm (270)Tj 46.3849 0 TD [(BENNETT)-338(ET)-338.7(AL.)]TJ ET endstream endobj 116 0 obj <>/XObject<>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/Font<>>>/Thumb 119 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 120 0 obj <>/ProcSet[/PDF/Text]/Font<>>> endobj 118 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.4682 0 0 8.4682 74.6078 725.7825 Tm 0 0 0 rg 0 Tc 0 Tw [(technique)-722.6(using)-725.9(dynamic)-718.1(SPECT.)-724.5(Eur)-721(J)-715.7(Nucle)-10(ar)-715.1(Med.)]TJ 0 -1.2318 TD (2001;28:13651372.)Tj -1.754 -1.2385 TD [(27.)-504(Elkins)-520.9(M,)-520.2(Daviskas)-522(E,)-525.1(Eberl)-521.8(S,)-522.1(Constable)-520.5(C,)-521.6(and)-519.9(Bye)-525(P:)]TJ 1.754 -1.2318 TD [(Quantication)-449.1(of)-442.5(mucocliary)-447.1(clearance:)-441.9(3-D)-443.2(SPECT)-445.6(versus)]TJ 0 -1.2385 TD [(Planar.)-333.4(J)-334.1(Aerosol)-340.4(Med.)-331.9(2002;15:446.)]TJ -1.754 -1.2318 TD [(28.)-504(L)-11.9(e)0(e)-503.4(Z)-10.2(,)-493.1(a)-8.8(n)-17.1(d)-493.9(Be)-19.3(r)-10(r)-10(i)-13.6(dg)-15.6(e)-496(M)-13.7(S)-8.9(:)-493.1(P)-9.5(E)-11.9(T)-493.9(i)-13.6(m)-8.7(a)-8.8(g)-10.4(i)-13.6(n)-10.4(g)-492.4(b)-10.4(a)-8.8(s)-12.5(e)0(d)-508(e)0(v)-21.1(a)-8.8(lu)-16.4(a)-15.5(t)0(i)-19.6(o)-8(n)]TJ 1.754 -1.2385 TD .0106 Tc [(of)-591.3(aerosol)-585.4(d)-1.3(rugs)-597.7(and)-590.5(t)-2.1(he)10.6(i)-10.3(r)-588.5(de)10.6(l)-10.3(i)10.6(v)-10(e)10.6(r)-6.7(y)-595.6(de)10.6(v)-10.5(i)10.6(c)-7.8(e)10.6(s)-9.2(:)-589.6(na)-4.9(s)10.6(a)-10.7(l)-585.4(a)-4.9(nd)]TJ 0 -1.2318 TD .0098 Tc [(pulmona)-5.7(ry)-482.6(s)9.8(t)-8.7(udi)9.8(e)-11.1(s)-484.7(I)1.4(EE)9.8(E)-489.4(T)-2.1(rans)-484.7(M)9.8(e)-11.2(d)-477.4(I)-5.3(mag.)-483.3(2002;21)-5.7(:)9.8(1)-10.1(324)]TJ 0 -1.2385 TD .0088 Tc [(1331)-6.7(.)]TJ -1.754 -1.2318 TD 0 Tc [(29.)-504(Bennett)-615.2(WD,)-611.1(and)-606.9(Ilowite)-616.5(J:)-613(Dual)-607.6(pathway)-613.5(clearance)-618.3(of)]TJ 1.754 -1.2385 TD [(Tc99m-DTPA)-452(from)-447.8(the)-445.6(bronchial)-451.6(mucosa.)-445.1(Am)-450.5(Rev)-446.3(Respir)]TJ 0 -1.2318 TD [(Dis.)-331.6(1989;139:1132113)-7(8.)]TJ -1.754 -1.2385 TD [(30.)-504(Anderson)-418.6(M,)-419.8(Philipson)-422.5(K,)-411.1(Svartengr)-12(en)-412.8(M,)-419.8(and)-412.8(Camner)-421.9(P:)]TJ 1.754 -1.2318 TD [(Human)-387.1(deposition)-388.7(and)-379.3(clearance)-390.7(of)-382.2(6-)]TJ /F11 1 Tf 17.3194 0 TD (m)Tj /F5 1 Tf .5557 0 TD [(m)-383.6(particles)-387.4(inhaled)]TJ -17.8751 -1.2385 TD [(with)-576.2(an)-574.9(extremely)-578.3(low)-574.4(ow)-579.4(rate.)-578.9(Exp.)-573.6(Lung)-577.9(Res.)-576.7(1995;)]TJ 0 -1.2318 TD (21:187195.)Tj -1.754 -1.2385 TD [(31.)-504(Svartengren)-552(M,)-553.6(Sommerer)-551(K,)-545(Scheuch)-558.5(G,)-543.2(Kohlhaeu)-553.7(M,)]TJ 1.754 -1.2318 TD [(Heyder)-563.9(J,)-552.7(Falk)-565.3(R,)-556.9(Bergmann)-560.1(R,)-556.9(Hofmann)-569.4(W,)-557.6(Bailey)-554.3(M,)]TJ 0 -1.2385 TD [(Philipson)-522.9(K,)-518.2(and)-519.9(Camner)-522.3(P:)-522.7(Comparison)-519.6(of)-522.8(clearance)-524.6(of)]TJ T* [(particles)-374.1(inhaled)-377.4(with)-375.4(bolus)-375.3(and)-372.6(extremely)-377.5(slow)-379.3(inhalation)]TJ 0 -1.2318 TD [(techniques.)-337.8(Exp)-334.9(Lung)-336.8(Res.)-335.6(2001;27:367386.)]TJ -1.754 -1.2385 TD [(32.)-504(Mo)]TJ 2.7917 .0134 TD ()Tj .4419 -.0134 TD [(ller)-533.2(W,)-530.8(Felten)-530.4(K,)-531.6(Sommerer)-537.6(K,)-531.6(Scheuch)-531.7(G,)-536.5(Meyer)-530.7(G,)]TJ -1.4795 -1.2318 TD [(Meyer)-390.1(P,)-395.5(Ha)]TJ 5.3224 .0067 TD ()Tj .4352 -.0067 TD [(ussinger)-400.8(K,)-391(and)-392.7(Kreyling)-395.3(WG:)-386.7(Depos)-10.4(ition,)-390.8(re-)]TJ -5.7575 -1.2385 TD [(tention,)-581.8(and)-573.5(translocation)-583(of)-576.4(ultrane)-579.8(particles)-581.6(from)-575(the)]TJ 0 -1.2318 TD [(central)-369(airways)-362.4(and)-365.9(lung)-365.3(periphery.)-373.7(Am)-363.4(J)-360.9(Respir)-371(Crit)-366(Care)]TJ 0 -1.2385 TD [(Med.)-331.9(2008;177:426432.)]TJ -1.754 -1.2318 TD [(33.)-504(Smith)-790.8(JR,)-783.8(Bailey)-788.6(MR,)-784.8(Etherington)-794.2(G,)-784.2(Shutt)-790.8(AL,)-786.1(and)]TJ 1.754 -1.2385 TD [(Youngman)-672.3(MJ:)-673.5(Effect)-671.6(of)-670.1(particle)-676.2(size)-671.5(on)-674.5(slow)-667.2(particle)]TJ 0 -1.2318 TD [(clearance)-450.9(from)-454.5(the)-445.6(bronchial)-458.3(tree.)-450.2(Exp)-448.7(Lung)-450.7(Res.)-449.5(2008;34:)]TJ 0 -1.2385 TD (287312.)Tj -1.754 -1.2318 TD [(34.)-504(Alexis)-346.9(NE,)-345.8(Hu)-345.7(SC,)-343(Zeman)-346.7(K,)-344.2(Alter)-351.5(T,)-344.4(and)-345.8(Bennett)-347.5(WD:)-343.3(In-)]TJ 1.754 -1.2385 TD [(duced)-400.4(sputum)-397.3(derives)-397.7(from)-400.9(the)-398.7(central)-402.5(airways:)-393.6(conrma-)]TJ 0 -1.2318 TD [(tion)-392.9(using)-391.1(a)-390.4(radiolabeled)-393(aerosol)-396.2(bolus)-395.3(delivery)-389.1(techniqu)-12.4(e.)]TJ 0 -1.2385 TD [(Am)-330(J)-340.8(Resp)-334.1(Crit)-332.5(Care)-335.7(Med.)-338.6(2001;164:19641970.)]TJ -1.754 -1.2318 TD [(35.)-504(Roth)-516.7(C,)-521.6(Scheuch)-518.3(G,)-516.4(and)-519.9(Stahlhofen)-525.2(W:)-517.4(Clearance)-521.4(of)-516.1(the)]TJ 1.754 -1.2385 TD [(human)-623.7(lung)-626.4(for)-626.5(ultrane)-626.6(particles.)-626.2(J)-622(Aerosol)-628.3(Sci.)-627.6(1993;)]TJ 0 -1.2318 TD [(24\(Suppl)-335.8(1\):S95S96.)]TJ -1.754 -1.2385 TD [(36.)-504(Lay)-459.6(JC,)-467.3(Stang)-466.3(MR,)-463.4(Fisher)-465.9(PE,)-467.7(Yankaskas)-467.6(JR,)-462.5(and)-466.3(Bennett)]TJ 1.754 -1.2318 TD [(WD:)-510.6(Airway)-515.1(retention)-521(of)-516.1(materials)-511.1(of)-516.1(different)-520.6(solubility)]TJ 0 -1.2385 TD [(following)-355.2(local)-356.7(intrabronchial)-359.8(deposition)-361.9(in)-352.1(dogs.)-355.1(J)-354.2(Aerosol)]TJ 0 -1.2318 TD [(Med.)-331.9(2003;16:153166.)]TJ -1.754 -1.2385 TD [(37.)-504(Alexis)-541.1(NE,)-533.3(Lay)-539.9(JC,)-534.3(Zeman)-540.9(KL,)-536.9(Geiser)-535.9(M,)-540.3(Kapp)-535(N,)-534.8(and)]TJ 1.754 -1.2318 TD [(Bennett)-253.7(WD:)-242.8(In)-246.5(vivo)-249.9(particle)-254.5(uptake)-245.8(by)-248.3(airway)-249.5(macrophages)]TJ 0 -1.2385 TD [(in)-238.3(healthy)-247.8(volunteer.)-251.1(Am)-236.2(J)-247.1(Respir)-243.8(Cell)-243.7(Mol)-242.7(Biol.)-238.9(2006;34:305)]TJ 0 -1.2318 TD (313.)Tj -1.754 -1.2385 TD [(38.)-504(Mortensen)-299.9(J:)-298.3(Bronchoscintigraphy)-304.6(and)-292.3(pulmonary)-303.2(clearance)]TJ 1.754 -1.2318 TD [(of)-388.9(Tc)]TJ 6.351 0 0 5.6449 93.9968 248.3716 Tm (99m)Tj 8.4682 0 0 8.4682 105.9023 244.6299 Tm [(-albumin)-389(colloid)-388.1(in)-392.2(the)-385.3(study)-391.8(of)-382.2(mucoc)-9.2(iliary)-384.5(clear-)]TJ -3.6955 -1.2385 TD [(ance.)-337.1(Dan)-333.8(Med)-334.2(Bull.)-334.2(1998;45:195209.)]TJ -1.754 -1.2318 TD [(39.)-504(Mortensen)-420.4(J,)-412.1(Hansen)-419.2(A,)-412.7(Falk)-411.3(M,)-413.1(Nielsen)-421(IK,)-412.9(and)-412.8(Groth)-419.3(S:)]TJ 1.754 -1.2385 TD [(Reduced)-504.9(effect)-513(of)-502.7(inhaled)]TJ /F11 1 Tf 12.3452 0 TD (b)Tj /F5 1 Tf 6.351 0 0 5.6449 183.8551 211.8046 Tm (2)Tj 8.4682 0 0 8.4682 187.0299 213.222 Tm [(-adrenergic)-509.1(agonists)-503.9(on)-507.1(lung)]TJ -13.2758 -1.2318 TD [(mucociliary)-326.7(clearance)-337.1(in)-325.3(patients)-328.7(with)-328.5(cystic)-333.3(brosis.)-330.9(Chest.)]TJ 0 -1.2385 TD (1993;103:805811.)Tj -1.754 -1.2385 TD [(40.)-504(Regnis)-258.5(JA,)-251.4(Zeman)-253(KL,)-255.7(Noone)-256.1(PG,)-258.2(Knowles)-254.8(MR,)-255.9(and)-252.1(Bennett)]TJ 1.754 -1.2318 TD [(WD:)-503.9(Prolonged)-510.9(airway)-503.9(retention)-514.4(of)-509.4(insoluble)-507.2(particles)-508(in)]TJ 0 -1.2385 TD [(cystic)-326.6(brosis)-326.5(vs.)-325.2(primary)-325.4(ciliary)-322.4(dyskinesia.)-330(Exp)-321.5(Lung)-330.1(Res.)]TJ 0 -1.2318 TD (2000;26:149162.)Tj -1.754 -1.2385 TD .0155 Tc [(4)15.5(1)15.5(.)-488.5(Daviskas)-746.8(E,)-752.1(Ande)-5.2(r)5.5(s)-3.7(on)-744.8(SD,)-745.4(E)3.6(berl)-747.9(S,)-745.4(Chan)-744.8(H)-6(-)2.8(K,)-745.4(and)]TJ 1.754 -1.2318 TD .0162 Tc [(Young)-469.5(I)1.1(H:)-476.9(T)4.3(h)-.9(e)-473.2(24-h)-476.3(e)2.2(ffect)-471.9(o)1.5(f)-471.9(m).8(annitol)-472.7(o)1.5(n)-469.6(t)-3.2(he)-473.2(c)4.7(l)2.6(ear)6.2(a).7(nce)]TJ 0 -1.2385 TD .0155 Tc [(of)-606.5(mucus)-606.2(i)-4.8(n)-604.2(p)-.7(atie)-5.2(nts)-606.2(w)-1.7(ith)-610.9(b)-1.6(r)5.5(o).8(nchiectasis.)-604.8(Ch)5.1(e)-5.2(s)3(t.)-604.8(2001;)]TJ 0 -1.2318 TD .0151 Tc (119:414421.)Tj -1.754 -1.2385 TD 0 Tc [(42.)-504(Ilowite)-415.6(J,)-418.8(Smaldone)-419.1(GC,)-417.6(Perry)-422.1(R,)-416.3(Bennett)-421.1(WD,)-416.9(and)-412.8(Foster)]TJ 1.754 -1.2318 TD [(WM:)-464.1(The)-471.6(relationship)-471.9(between)-474.5(tracheobronchial)-480.2(clearance)]TJ 0 -1.2385 TD [(rates)-453(and)-452.9(sites)-453.6(of)-449.2(initial)-454.5(deposition)-455.7(in)-452.5(man.)-454.1(Arch)-453.7(Environ)]TJ 0 -1.2318 TD [(Health.)-333.3(1989;44:26727)-7.4(3.)]TJ 27.8972 77.8202 TD [(43.)-497.3(Garrard)-424.2(CS,)-423.3(Gerrity)-428.7(TR,)-421.5(Schreiner)-424.3(JF,)-422.5(and)-426.2(Yeates)-427.1(DB:)-417.9(The)]TJ 1.7473 -1.2318 TD [(characterization)-515.3(of)-509.4(radioaerosol)-515.4(deposition)-515.9(in)-506(the)-512.5(healthy)]TJ 0 -1.2385 TD [(lung)-338.5(by)-335.4(histogram)-336.1(analysis.)-335.9(Chest.)-336.9(1981;80\(Suppl\):840842.)]TJ -1.7473 -1.2318 TD [(44.)-497.3(Fleming)-335.5(JS,)-334(and)-332.4(Conway)-337.7(JH:)-333.3(Three-dimensional)-346(imaging)-330.2(of)]TJ 1.7473 -1.2385 TD [(aerosol)-335.9(distribution.)-344.2(J)-334.1(Aerosol)-340.4(Med.)-331.9(2001;14:147153.)]TJ -1.7473 -1.2318 TD [(45.)-497.3(Hasani)-457.3(A,)-446.2(Toms)-449.5(N,)-454.4(Agnew)-453.7(JE,)-450.8(Lloyd)-450.7(J,)-445.6(and)-452.9(Dilworth)-453.7(JP:)]TJ 1.7473 -1.2385 TD [(Mucociliary)-365.2(clearance)-363.9(in)-358.8(COPD)-361.5(can)-365.5(be)-359.1(increased)-361.2(by)-362.2(both)-362.9(a)]TJ 0 -1.2318 TD (D)Tj 6.351 0 0 5.6449 332.1637 651.1746 Tm (2)Tj 8.4682 0 0 8.4682 335.3385 652.5919 Tm (/)Tj /F11 1 Tf .6092 0 TD (b)Tj /F5 1 Tf 6.351 0 0 5.6449 345.1464 651.1746 Tm (2)Tj 8.4682 0 0 8.4682 352.97 652.5919 Tm [(and)-546.7(a)-544.4(standard)]TJ /F11 1 Tf 7.7191 0 TD (b)Tj /F5 1 Tf 6.351 0 0 5.6449 423.0424 651.1746 Tm (2)Tj 8.4682 0 0 8.4682 430.8093 652.5919 Tm [(agonists.)-548.5(Respir)-551.8(Med.)-546.1(2005;99:)]TJ -12.4188 -1.2385 TD (145151.)Tj -1.7473 -1.2318 TD [(46.)-497.3(Donaldson)-625.8(SH,)-624(Bennett)-621.9(WD,)-624.4(Zeman)-621.2(KL,)-617.2(Knowles)-623.1(MK,)]TJ 1.7473 -1.2385 TD [(Tarran)-629(R,)-623.8(and)-627(Boucher)-631.1(RC:)-625.5(Mucus)-632.5(clearance)-631.7(and)-620.3(lung)]TJ 0 -1.2318 TD [(function)-417.1(in)-405.6(cystic)-413.7(brosis)-413.5(with)-408.8(hypertonic)-411.9(saline.)-412(N)-409.8(Engl)-407.8(J)]TJ 0 -1.2385 TD [(Med.)-338.6(2006;354:241250.)]TJ -1.7473 -1.2318 TD [(47.)-497.3(Robinson)-357.9(M,)-352.8(Regnis)-358.9(JA,)-351.8(Bailey)-353.4(DL,)-351(King)-360.8(M,)-352.8(Bbautovich)-351.7(GJ)]TJ 1.7473 -1.2385 TD [(and)-553.4(Bye)-551.8(PTP:)-550.9(Effect)-551.1(of)-556.3(hypertonic)-552.5(saline,)-552.6(amiloride)-557.4(and)]TJ 0 -1.2318 TD [(cough)-471.6(on)-467(mucociliary)-474(clearance)-471(in)-465.9(patients)-469.2(with)-469.1(cystic)-473.9(-)]TJ 0 -1.2385 TD [(brosis.)-339(Am)-336.7(J)-334.1(Respir)-337.6(Crit)-332.5(Care)-335.7(Med.)-331.9(1996;153:1503150)-7(9.)]TJ -1.7473 -1.2318 TD [(48.)-497.3(Noone)-376.6(PG,)-365.3(Bennett)-374.2(WD,)-370(Regnis)-372.3(JA,)-371.9(Zeman)-373.5(KL,)-369.5(Carson)-366(JL,)]TJ 1.7473 -1.2385 TD [(King)-253.7(M,)-245.7(Boucher)-256.2(RC,)-250.6(and)-252.1(Knowles)-254.8(MR:)-249.2(Effect)-256.5(of)-248.3(aerosolized)]TJ T* (uridine-5)Tj /F13 1 Tf 5.9275 0 0 5.9275 359.6031 530.1353 Tm (0)Tj /F5 1 Tf 8.4682 0 0 8.4682 361.7007 527.0172 Tm [(-triphoshat)-14.4(e)-810.7(\(UTP\))-823.4(on)-815.1(airway)-818.6(clearance)-819.1(with)]TJ -4.2579 -1.2318 TD [(cough)-244(in)-238.3(patients)-241.6(with)-241.5(primary)-238.3(ciliary)-242.1(dyskinesia.)-242.9(Am)-236.2(J)-240.4(Resp)]TJ 0 -1.2385 TD [(Crit)-339.2(Care)-335.7(Med.)-331.9(1999;160:144149.)]TJ -1.7473 -1.2318 TD [(49.)-497.3(Sood)-411.7(N,)-407.6(Bennett)-414.4(WD,)-410.2(Zeman)-407(K,)-411.1(Brown)-412.4(J,)-405.4(Foy)-410.3(C,)-407.7(Boucher)]TJ 1.7473 -1.2385 TD [(RC,)-411.2(and)-412.8(Knowles)-415.5(MR:)-409.8(Increasing)-411.4(concentration)-423.5(of)-409(inhaled)]TJ 0 -1.2318 TD [(saline)-641.9(with)-643.1(or)-633.9(without)-646.6(amiloride:)-635.4(effect)-646.9(on)-634.3(mucociliary)]TJ 0 -1.2385 TD [(clearance)-517.9(in)-512.7(normal)-514.8(subjects.)-514.7(Am)-510.7(J)-508.2(Resp)-514.8(Crit)-513.3(Care)-516.5(Med.)]TJ 0 -1.2318 TD (2003;167:158163.)Tj -1.7473 -1.2385 TD [(50.)-497.3(Bennett)-334.1(WD,)-329.9(Olivier)-328.5(KN,)-332.3(Zeman)-326.7(KL,)-329.3(Hohneker)-333.2(KW,)-328.3(Geary)]TJ 1.7473 -1.2318 TD [(CA,)-508.1(Boucher)-510.6(RC,)-511.6(and)-506.5(Knowles)-509.2(MR:)-510.3(Effect)-510.9(of)-502.7(uridine)-511.5(5)]TJ /F13 1 Tf 5.9275 0 0 5.9275 545.1022 435.9684 Tm (0)Tj /F5 1 Tf 8.4682 0 0 8.4682 547.1998 432.907 Tm (-)Tj -26.1632 -1.2385 TD [(triphosphate)-614.3(plus)-607.5(amiloride)-604.3(on)-600.9(mucociliary)-607.9(clearance)-611.6(in)]TJ 0 -1.2318 TD [(adult)-465(cystic)-467.2(brosis.)-458.1(Am)-463.9(J)-461.3(Resp)-468(Crit)-459.7(Care)-462.9(Med.)-465.8(1996;153:)]TJ 0 -1.2385 TD (17961801.)Tj -1.7473 -1.2318 TD [(51.)-497.3(Mortensen)-353.5(J,)-338.5(Groth)-345.6(S,)-341.3(Lange)-350.1(P,)-342(and)-339.1(Hermansen)-351.5(F:)-342.8(Effect)-343.5(of)]TJ 1.7473 -1.2385 TD [(terbutaline)-364.1(on)-359.9(mucociliary)-360.2(clearance)-357.2(in)-358.8(asthmatic)-360.9(and)-359.2(heal-)]TJ 0 -1.2318 TD [(thy)-254.5(subjects)-262.5(after)-252.5(inhalation)-257.7(from)-253.7(a)-256.5(pressurised)-257.2(inhaler)-254.9(and)-258.8(a)]TJ 0 -1.2385 TD [(dry)-333.5(powder)-338.5(inhaler.)-339.7(Thorax.)-333.5(1991;46:817823.)]TJ -1.7473 -1.2318 TD [(52.)-497.3(Smaldone)-579.8(GC,)-571.6(Foster)-576.4(WM,)-571.3(ORiordan)-575.1(TG,)-575.2(Messina)-574.2(MS,)]TJ 1.7473 -1.2385 TD [(Perry)-241.4(RJ,)-234.9(Langenback)-234.3(E:)-237.3(Regional)-236.2(impairment)-237.3(of)-235(mucociliary)]TJ 0 -1.2318 TD [(clearance)-410.8(in)-405.6(chronic)-403.6(obstructive)-409.9(pulmonary)-410.3(disease.)-406.3(Chest.)]TJ 0 -1.2385 TD (1993;103:13901396.)Tj -1.7473 -1.2318 TD [(53.)-497.3(Perring)-252(S,)-240.9(Summers)-246.4(Q,)-247.7(Fleming)-241.7(JS,)-247(Nassim)-244.9(MA,)-245.6(and)-245.4(Holgate)]TJ 1.7473 -1.2385 TD [(ST:)-426.9(A)-428.4(new)-423.3(method)-434(of)-422.4(quantication)-437.1(of)-422.4(the)-432.2(pulmonary)-423.7(re-)]TJ 0 -1.2318 TD [(gional)-640.5(distribution)-641(of)-636.6(aerosols)-636.3(using)-638.8(combined)-637.6(CT)-636.2(and)]TJ 0 -1.2385 TD [(SPECT)-405.4(and)-406.1(its)-407(application)-408(to)-409(nedocromil)-404.3(sodium)-405.6(adminis-)]TJ 0 -1.2318 TD [(tered)-337.2(by)-335.4(metered)-339.9(dose)-334.3(inhaler.)-333(Br)-336.6(J)-334.1(Radiol.)-338.2(1994;67:4653.)]TJ -1.7473 -1.2385 TD [(54.)-497.3(Bennett)-260.4(WD,)-249.5(Zeman)-253(KL,)-255.7(Foy)-249.6(C,)-253.8(Shaffer)-258.4(C,)-247.1(Johnson)-260(F,)-249.1(Regnis)]TJ 1.7473 -1.2318 TD [(J,)-311.7(Sannuti)-315.5(A,)-312.3(and)-312.4(Johnson)-320.2(J:)-311.7(Effect)-310(of)-315.3(aerosolized)-317.3(INS316)-313(on)]TJ 0 -1.2385 TD [(mucociliary)-306.7(clearance)-303.6(in)-305.2(mild)-302.2(chronic)-303.2(bronchitis.)-311.7(Am)-303.2(J)-300.6(Resp)]TJ 0 -1.2318 TD [(Crit)-339.2(Care)-335.7(Med.)-331.9(2001;164:302306.)]TJ -1.7473 -1.2385 TD [(55.)-497.3(Goodman)-420.6(RM,)-416.5(Yergin)-416.7(BM,)-411.6(Landa)-420.1(JF,)-415.8(Golinvaux)-414.4(MH,)-421.2(and)]TJ 1.7473 -1.2318 TD [(Sackner)-428.9(MA:)-426.4(Relationship)-431.9(of)-429.1(smoking)-428.7(history)-425.7(and)-426.2(pulmo-)]TJ 0 -1.2385 TD [(nary)-602(function)-597.8(tests)-606.7(to)-596.5(tracheal)-598.8(mucous)-602.1(velocity)-599.7(in)-599.8(non-)]TJ T* [(smokers,)-582.5(young)-584.3(smokers,)-589.2(ex-smokers,)-581.3(and)-586.8(patients)-583.1(with)]TJ 0 -1.2318 TD [(chronic)-336.6(bronchitis.)-345.2(Am)-330(Rev)-339.2(Respir)-337.6(Dis.)-331.6(1978;117:205214.)]TJ -1.7473 -1.2385 TD [(56.)-497.3(Robinson)-371.3(M,)-366.2(Eberl)-367.8(S,)-361.4(Tomlinson)-371.6(C,)-367.6(Daviskas)-368(E,)-364.5(Regnis)-372.3(JA,)]TJ 1.7473 -1.2318 TD [(Bailey)-427.1(DL,)-424.6(Torzillo)-428.8(PJ,)-428.4(Menache)-431.1(M,)-426.5(and)-426.2(Bye)-424.6(PT:)-427.6(Regional)]TJ 0 -1.2385 TD [(mucociliary)-842.3(clearance)-845.9(in)-834.1(patients)-844.2(with)-837.3(cystic)-842.1(brosis.)]TJ 0 -1.2318 TD [(J)-334.1(Aerosol)-340.4(Med.)-331.9(2000;13:7386.)]TJ -1.7473 -1.2385 TD [(57.)-497.3(Bateman)-309.8(JRM,)-302.1(D)-301.2(Pavia,)-306.6(NF)-306.4(Sheahan,)-303.9(JE)-305.8(Agnew,)-304.1(and)-305.7(Clarke)]TJ 1.7473 -1.2318 TD [(SW:)-486.2(Impaired)-493.4(tracheobronchial)-493.6(clearance)-491.1(in)-492.7(patients)-489.3(with)]TJ 0 -1.2385 TD [(mild)-335.7(stable)-339.8(asthma.)-334.2(Thorax.)-333.5(1983;38:463467.)]TJ -1.7473 -1.2318 TD [(58.)-497.3(ORiordan)-514.8(TG,)-514.9(Zwang)-512.3(J,)-512.6(and)-513.2(Smaldone)-512.8(GC:)-511.4(Mucociliary)]TJ 1.7473 -1.2385 TD [(clearance)-504.5(in)-492.7(adult)-498.4(asthma.)-494.9(Am)-497.3(Rev)-499.9(Respir)-498.2(Dis.)-499(1992;146:)]TJ 0 -1.2318 TD (598603.)Tj /F4 1 Tf 8.9663 0 0 8.9663 59.7543 749.7069 Tm [(MUCOCILIARY)-339.2(AND)-337.2(COUGH)-337(CLEARANCE)]TJ 53.0113 0 TD (271)Tj ET endstream endobj 121 0 obj <>/XObject<>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/Font<>>>/Thumb 123 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 124 0 obj <>/ProcSet[/PDF/Text]/Font<>>> endobj 122 0 obj <>stream /GS1 gs BT /F5 1 Tf 8.4682 0 0 8.4682 62.022 725.7825 Tm 0 0 0 rg 0 Tc 0 Tw [(59.)-504(Messina)-319.8(MS,)-321.5(ORiordan)-327.4(TG,)-314.1(and)-325.7(Smaldone)-318.7(GC:)-323.9(Changes)-322.6(in)]TJ 1.754 -1.2318 TD [(mucociliary)-279.9(clearance)-290.2(during)-286.8(acute)-284.3(exacerbations)-287.6(of)-281.8(asthma.)]TJ 0 -1.2385 TD [(Am)-330(Rev)-339.2(Respir)-337.6(Dis.)-331.6(1991;143:993997.)]TJ -1.754 -1.2318 TD [(60.)-504(Elkins)-306.7(MR,)-309.4(Robinson)-317.7(M,)-305.9(Rose)-312.4(BR,)-307.7(Harbour)-312.5(C,)-307.3(Moriarty)-314.7(CP,)]TJ 1.754 -1.2385 TD [(Marks)-242.8(GB,)-240.5(Belousova)-247.3(EG,)-247.2(Xuan)-246.5(W,)-242.9(Bye)-243.8(PT,)-246.8(and)-238.7(the)-244.8(National)]TJ 0 -1.2318 TD [(Hypertonic)-302.5(Saline)-303.6(in)-298.5(Cystic)-296.7(Fibrosis)-305(\(NHSCF\))-303.7(Study)-301.2(Group:)]TJ 0 -1.2385 TD [(A)-535.5(controlled)-548.9(trial)-540.7(of)-542.9(long-term)-549.1(inhaled)-544.7(hypertonic)-545.8(saline)]TJ 0 -1.2318 TD [(in)-532.8(patients)-542.9(with)-536(cystic)-540.9(brosis.)-538.4(N)-537(Engl)-541.7(J)-534.9(Med.)-539.4(2006;354:)]TJ 0 -1.2385 TD (229240.)Tj -1.754 -1.2318 TD [(61.)-504(Jaques)-576.7(A,)-580.1(Daviskas)-575.6(E,)-578.7(Turton)-584.8(JA,)-572.7(McKay)-585(K,)-571.8(Cooper)-586.7(P,)]TJ 1.754 -1.2385 TD [(Stirling)-461.4(RG,)-466.3(Robertosn)-471.1(CF,)-458.3(Bye)-464.8(PTP,)-463.9(LeSouef)-467.4(P,)-469.2(Shadbolt)]TJ 0 -1.2318 TD [(B,)-572(Anderson)-572.6(SD,)-575.6(and)-573.5(Charlton)-577.7(B:)-572(Inhaled)-573.1(mannitol)-581.7(im-)]TJ 0 -1.2385 TD [(proves)-623.4(lung)-633.1(function)-631.3(in)-626.5(cystic)-627.9(brosis.)-625.4(Chest.)-631.5(2008;133:)]TJ 0 -1.2318 TD (13881396.)Tj -1.754 -1.2385 TD [(62.)-504(Daviskas)-475.1(E,)-478.3(Anderson)-478.9(SD,)-481.8(Jaques)-476.3(A,)-479.6(Charlton)-477.3(B:)-478.3(Inhaled)]TJ 1.754 -1.2318 TD [(mannitol)-367.5(impr)-8.3(oves)-369.6(the)-372(hydration)-370.8(and)-372.6(surface)-373.7(properties)-375(of)]TJ 0 -1.2385 TD [(sputum)-584.7(in)-593.1(patients)-589.8(with)-589.6(cystic)-587.7(brosis.)-592(Chest.)-591.3(2010;137:)]TJ 0 -1.2318 TD (861868.)Tj 8.9663 0 0 8.9663 442.1479 725.7825 Tm [(Received)-282.4(on)-278(March)-286.2(11,)-280.1(2010)]TJ .4489 -1.2203 TD [(in)-278.8(nal)-281.3(form,)-282.6(May)-280.9(17,)-280.1(2010)]TJ 5.7855 -3.9455 TD [(Reviewed)-335.3(by:)]TJ -.5438 -1.2266 TD [(Adam)-336.6(Wanner)]TJ -5.7602 -3.9392 TD [(Address)-339.4(correspondence)-340.1(to:)]TJ /F6 1 Tf 1.3468 -1.2266 TD [(William)-335.8(D.)-333.1(Bennett,)-333.2(Ph.D.)]TJ -3.7937 -1.2203 TD [(Center)-333.7(for)-337(Environmental)-337.5(Medicine,)]TJ 3.9898 -1.2203 TD [(Asthma)-333(and)-338.3(Lung)-328.9(Biology)]TJ -6.3039 -1.2266 TD [(University)-340(of)-336.3(North)-336.5(CarolinaChapel)-338.1(Hill)]TJ 4.0656 -1.2203 TD [(CB7310)-334.1(104)-333.6(Mason)-331.3(Farm)-334.6(Road)]TJ 1.1887 -1.2203 TD [(Chapel)-333.9(Hill,)-332.4(NC)-334.4(27599-7310)]TJ -5.1974 -2.1688 TD (E-mail:)Tj /F5 1 Tf 3.2563 0 TD (William_Bennett@med.unc.edu)Tj /F4 1 Tf -40.8776 22.4969 TD (272)Tj 46.3849 0 TD [(BENNETT)-338(ET)-338.7(AL.)]TJ ET endstream endobj 125 0 obj [/Indexed/DeviceRGB 255 126 0 R] endobj 126 0 obj <>stream 8;X]O>EqN@%''O_@%e@?J;%+8(9e>X=MR6S?i^YgA3=].HDXF.R$lIL@"pJ+EP(%0 b]6ajmNZn*!='OQZeQ^Y*,=]?C.B+\Ulg9dhD*"iC[;*=3`oP1[!S^)?1)IZ4dup` E1r!/,*0[*9.aFIR2&b-C#soRZ7Dl%MLY\.?d>Mn 6%Q2oYfNRF$$+ON<+]RUJmC0InDZ4OTs0S!saG>GGKUlQ*Q?45:CI&4J'_2j$XKrcYp0n+Xl_nU*O( l[$6Nn+Z_Nq0]s7hs]`XX1nZ8&94a\~> endstream endobj 127 0 obj <>stream MBAFOH+AdvP4C4E51 l AdvP4C4E51#[j-e~~vVE=0c4:# jtqurf><$R?6s}{~{~~~ endstream endobj 128 0 obj <>stream hTMo ;Ilrh7- iC}Fvڼ;g#/up iAU:n^zRxu8un4iݱ{ u#.'%?E %oO*Մ ^րPF{sPI9h J@gX nUBZ %nbO5z!JBENb>|scwFk endstream endobj 129 0 obj <> endobj 130 0 obj <> endobj 131 0 obj <>stream h,Mo5Ǔ{8"āpBB \\*t;3g2nJpC"Tw`SǏ{Ommlnnnֵoڵ?΃ѭ?}r#yr&o\[[]_*0Q6S|=f $+n@Mw@);Ky0؟ejNXǃ$#ю_8ne?UWUD*ł/٢XEL^yZGZ+}Ҏn?C? 81A3%X%rceE+<1Y Mffz&j"gU&23& oנ]+[֖lhML1`@\d)Oe4)qȡ(`KYFp"QB eF =HKZf.fbzfIT3V) Vii9!ʌbXQL<^vtOWׇ̝Skt c;/H~:ݣd#x "IURsjޖt&=h~h~R(bj#uwUiaPA:~`|m4T1[ OpIWCT񵫝׹םLP8l"0C0igT+ZJ$$z{s8}~Wc:BVJ&o]ˎbBfCS<˳,> endobj 69 0 obj <> endobj 71 0 obj <> endobj 133 0 obj <> endobj 85 0 obj <> endobj 134 0 obj <>stream hބV Tն7[!6x( jE7ݼBxy T|=ҊX hE:9Ys8wܱǘ19F4̈́Ƞs&LNu@_Lexa<=d/Yh4UFCjlSI.:Oo/ww&g$u1Ƭl,]xzR!3ÐOF=d ,!W.ЧStY]!!Y!^Fmt ɳ2 T7+'1+595Ϛ'I#~4Nk${kI'IF)I4G#yKR,E)HqS!YIT+b\jh4_,R,vXZV"fMjRI'4zZ^aW+ A~8fOǠ_ljmzlN4iWkG6*3=pC1'!]i0u9zX#kD`86JY| )n qGWq[sV&lwlqWp|jWú'iIs#9J85ZB.Qk$FOWu\1/:7u2A V_ yo>)z?d5"&{ZÎm0`G3ae8R]SV>zP6k d莯/UrNˉr ~ >ߎh˭۫:hF~50r>>owj>;ٛC2XA~YYת @w8{*DMsLK7{`KCyYJ9]sa$Q|4J y؝bƠ ="bod:S[@"Vf珨 <_k\р3 _:.?ڛ~P-k{e?bn7rW,'V}!Z"),|sR'RGO\2y |!u_8D }I?mya۰4-5?å on9{qmNu-M%c*7.&oh퓽v˗xwGìhe'5ͽ'ُ5/l勊-G&`yg!҆W;ov$湟[S- !W3 ) r=^4;hgd+ s.F0G?Moc y9uro;Zeh7b੎`q4+Y9C,,R`{Իr3ɢx? .0 W嘴7S:YWkrԈ%#DfZoP툅:~+4|-y@{Ab_p'F˜B $LURj;[by̗rK舮ƵS=7u=y;ƚ;xM)-..}V4]ǏkUCefڥq8Y}XxUROf}jERҫ; vEo_jX+ PCfQ;P!b? LGLEeA +X}+Uiq2)Tn3q[\>4q`Mჟ@&툱l%Œ8=>ǵ=[/>y<ȑanw*V#yiAs"OŁ-X''{g"\S!Up endstream endobj 90 0 obj <> endobj 137 0 obj <> endobj 136 0 obj <>stream hT=o w~ō2bHTuE Výw^;g#up+i'렪XwX=>stream MBAIAN+AdvP4C4E74 wRC20AdvP4C4E74 0\}{~uuwv|#p3Lp|~zx~M~c~kqqtF6b|ci~Cx}}xwwVx||xww endstream endobj 135 0 obj <> endobj 139 0 obj <>stream 8;Z\7M\:Xb%-.A;0YaqUD35TIJO>rgCc?<(CsiA(n6l=5`unIP">tj`!#AsS8:rgM pe+Ef@j:Z3#%WunpXreA=_&Pe\os&9+Vd=CD_tXfeGV[#HP1('7It%EC$-YO?"k^m I!L)QhN7&>:R6tB`?gnW4[(d^pS'NF%](/G>kb13ZoI>1;5naHWh57K757_N9.#e0@_hMLR>b]r2*On0T>37i>/(/bkfW), *#B)Jq='DJ1N.Dsap'K>SY7pDRE5#b1cE?bhJ%%>OiGPMk@c]^MSHo=`c\Cjp6fN0 #5Ur?nPHulVU6L#K>s:<64U6,j.ZbU3k+uu+NE3Vs&'rNB*\8b@sS?o]`0!"_Yp^I5bSXRF~> endstream endobj 75 0 obj <>stream 8;Z\7Mflo[$tLIIUOBK[qlii3(rq/[,_'.LpSu/kKAj=%KLf&Lituqj'mZJO]'t@M%DC#7EY?:+s8HT0ZjceElIE?#ugdRLeCp' _C[MbXEOpfm?i6Rpj=bl`LikQha'[?(_<\c.5eo/(DI"&P[skA5hIor]b7&qKAEf0 0u"6KH*>FppIVH8GWN[^=N-o&;D;SU"04M=96>^+ng%Op&M%D.g2]R#$>Z_/'ZJ]C 3&9I_!lb5bH-J*PP1Ep%?$7[>)38+nb9)V"H=otjhpF-_jMX3:V?pGf@V]DMTZa7O ZsV7+@'&_0+kUE55<]$WhEr3Ik>^JuS/9A/oaQ@%2(H5[,#"tir5!6cA`l\Z!id(m +0Q&U.i^]&Hl>/ABiL\q=R9aJ0u$gOI=s9N%unTM`*`11f@]P7nL*J#McVFQ2.=Ul=B\mZ f].E<+%D"aS2`Uq_Qr7&p)h3n$QL'$S`R%.f>;`@XVO:tSZ]Zgt-PMo<_\Ci(LM fS;bKVgKs8StA#g8ZN.M^DO;HGMr-EX.'3jqeEq#SVlUd=8?6]V`%%o+m2cob`'M- oh/`V`C7PA#-@9NTHDI"bZKABK)bW:p_a'-/DU+~> endstream endobj 80 0 obj <>stream 8;Z\6NOaZa$tLIRaZeB*qln@=@b%2-$.Q]hfM@XHEH_P][JuVMZ:A!AomJX,Rpt"$ %&s3K3Nb)4-LkNbj0:_kn^Flo4E\^bBhf"E7H2VuIp*jPeb@u%9EoGUI Z;8K4j-P&b#V;A75)".7OueDm1Xet`>^>:an!C$(5#30QNVN0hhT(cI&IgTUG&19m PWLYG=EHo:Hm,fPqeb^(i*q[q+&/gC:OKni)P9hHXGFBh$7%0q=Y-;D$l^k\3b!Aj >)mm%r9DRcpm%'[@M("t4t%(pTjP%olCATTWa_rK[IJ$%itKF5A7!3e!/)/EomdW- g:TZ>jZ-jd@O#Qjb`lI(0Fm^&.7BS&RE\-K?1D[r\OZkJ/tj%'/Q9E_(nl+PBe+&L\>o'cCDe'l,`q]25IhJV`TXC_[8X o@tl[3*07q/fgMf[LHa8]20s"5/l=q7b/CI@9D3t&fT#nUkq@">IZ5Z&F4(Kf'^`0 I_:@Cm(KXGp08!TrQ;3YZ+Hs^iqnhR[tjQp:;hL)c,V]mq\]@RT8Sa2!-Sg2BE~> endstream endobj 86 0 obj <>stream 8;Z\7!OAaK%*X-?TA1ggnNOM/2[NG_#cQDODl2dK;MEB`&l;#GE@1bSN(Garc?l74 &[p_s,)aPP9Kh,#!0IhDf#&DVih2Z&MO"0N51d_N"9V;i;K0R+(D]\3/63T5-0M#M GT\=aKT^0k$OjsU&NDFVL^J!$R:X\tL!W@\'_RL24o9/Hfa#@-Tgf,5Gj1WM*3p8Q J6a^:,=##EGqlK)R?odfA!&KU+RJT,kN,eMidNK'`[dAXGBbQpA[0*[eKbL`i2hLl Q_&A,EIF8MX;E!^X icF)OUoQcqM@D\MasImP[Z\":5DqQSAMGM>%I=`r`Qj-;pLeHI^hrCO@SMa6NdQ^r Nt^)0Y?q^Y"m``5(j-_:P&@hSFeHuP%_kMKa5-n:V:$:0f]aA_IaPAc?M/b'281HC ;i`TWj0A>QX,e:MYo&@g+(:@K4Fj IEm#/G:KqSWP0U_P@>lBrP5.5KrS^bZpo:7e8X+jpV1XD3hT!6#I#9=H7!*n2!/qo ^4Ipcju#_JMcZ;q:428)Io'rHFu4q9Nn;!X8;1-iZg:@)98[4H@q^ endstream endobj 91 0 obj <>stream 8;Z\7>7SM(%.!jFR-Pjt>F.4mWt.+qI%Wc(a**e!&3Z/3;M..0p.cqn.#K(cqE9'` Y`tY^qB^WHliJ)"&%["0@?$3OYIC]K6cIJ/4E]h&,kg2:KUN-[nYSHk-8bSE.AsUr pk94Z(L6E11%/(E,CYK6>*RFu2b)E'2i@`b5-#)Tru>2roV[# ?e\_W7VCM[?hKMgY0`2>IuXS*#(FE,NJP;`]:b;8k"f,2PT.FW)1#Ro,>H[$YR&L@ (\#V/Fh#R`nerD%)O%fb-oP'X$r^WN!m<7'eg.>>Ie@H7eABGVPi]q(m$BGlH?m>D k.k#Pb">OO]GJ*J1:HEY]*EBmWJhFc3iaHC35("TlH#I*VTbCT[\D&57;,`Pr5 '%RE)C3+)Qh.8@do%l#HhgSY90g1T?eHKHie]g)!s!n./*6~> endstream endobj 97 0 obj <>stream 8;Z]"gNg[Z%#*A)qe.)=_`k/#?19.B#dBj`7JWD+fKT3o'"BOT(O%("43uE$+6Q9/ P,9HI0E-mW,+l@\6#q'%9JMd/@fC4/"0#*)pgZ:YAGjMj3c=Op`IdgZ#?hka*\@P* Xtl\nDeZX>#-sSudI1U)n14*-C';.(?BY-LrU%[GhtMYIhG\A3[RB"+[u.HAoo[l( )JH7;;.A,R?*!V**%p"rd"4r;s7NnT'0!;RSoA;O[:sH(WO],Y\-$+D?h!C6pId3j+Gk>jW"lsh"r8cGr/+j&F1fWfO'99pCK'#G;2u]5O"\fIp)a1b #G;"&%bj4Y4tTn,.mAcr0$;K$\c8caY!)4';Z(%^K2sKNI..$deV`Kp_0Rtn>^[FF g$eZ9rl*ngE-rcS?uJgclEYf0a1>H1#RD1O?MUb)50uV=euPPAj?^(ceM@K=p_FHN .cMGQ;F&q=9PYH":^`,9[??'6q'FaM5;F6TU>g]c?d(kTR0c:oN'a'KMM%smb",Tl H#b6SSgkPV.'r-He5=/(G;.)mP;i`-77/M75cIRYZIAm&aSUX\U0&.+NaZ^M&Dd8)e\Z?]1U;SgM5tBQ:N,g1b9-eOIXr:j$!Zg37_SolV74;Vr?W7u[ ;NdiX8`WIo&h`<6XWlX6XW_1.$rVV7g*AdWP`(%GK]8u(pHk+kl6K)T`@OMRRZn1T oC4XSjJXrb(6G#DoT_"PeHWDg&8IOdEM.I2?u0[%WtB)r_6tQL.+%hC_//f3B3X9J >-N_Rp")\5`>.cnrf/tM?2ih"/+GOuMn&"n~> endstream endobj 101 0 obj <>stream 8;Z\7gD7X[#kS(GOPfTIUNV<0.;X]^,]4V;q*uTGY?8fL[DV'oil4>$mH[d% MJZ[OR5!>tNL+%4pk9UH2%!TaSq%@f8N%Cm_A_qPo+=*uW=b.df4^#XiW*#n=>$#f p3IEb2=oTBGnDT)"/Ed@IR+=#I_GG#>\HJj=JJaiaK_gdmQ75.X+'m'a^D+G!Pb $[)si0KiL?Q0(LBB0>+_hVkYm(#_%2QZmqKf4>j()EbkeLW,HW=0RXmD;cDW2a#c_ \/H#_ecMn5- endstream endobj 106 0 obj <>stream 8;Z\7M35[u%&>!ATc`qp5I>LKZ-=XA"P>MsM/nZ0c"_G'JOB4O9GfS7kD]@]?4W[M TgOOA**Gnc6m?V-lRE73lBL5/j=Tr&o%hj/B3[gi(6>-$S],Uc>H&X>aa4*i\2Q4 #KDAi.p/]>c6=2+!j)"a#_G9CK&gR@^fomJIXlO3kjY?.7nHRF4%A6$/Ulj5cmbl\ YcE5TLQ*5YfNA0+^SZFXgoA[`WXLAlqLbS&6qFAP'hl;('N7UaNk>iB03.!8^Q]Xj m$eh&n=B[9'=;9)=cU=-a(4PqWmCQkZ$+VIX+#@aA+Seg['+5g1pej@=EFQOm$s`> V4+FYOQSsW-s86S"r_qu,e3mPk't N$Y#9[eSAt,S\?)Mj)gCdHUKnNB1D$nQs3R5I*(14:ZqMf<53]1K_4??d%c'(f9"F >KaKK,A[8Wq.6@g\KQe_lk.#-cM/=Y<62lN~> endstream endobj 110 0 obj <>stream 8;Z\75n:dd#g<64aEMg+e0P8#:>dh.*2[mNNUN3COYI]$Ys:XAGLT$UspZVc^-nL`Y'hDk*BARLa6)Ud/#fGeYt9Jfqpr1e#'[# *ER"*]Y*X@0!VURFt[C1Hj\IXb$u0BB[LKhY/I%l?plXah#f@dY1/86A:iC"?9kb" `CVXhR#FYFTU6dN\Q7]t3/&Z6)Q^R[YL?__DmpXQ&Ul)B)M_YmHJp1K#WWQ#PR*91 [39V!hFlD+8)&0dhlfP>1>atU3=1\m)Ip!h'o#=U6qS\;*e1,+`u7TK;>jRNGM4]p lJj*U.JA\8)IPY;J"[6.YF9B@-3;e&2ho>n%gQ9H&H\+6TshMmR(Nm0#SRXt/5c(0 Q4&@ml:Khc0"$`T(ikG?K38e[7`'bQ`Y;I37T<.+1fj endstream endobj 114 0 obj <>stream 8;Z\6=a%_;#ikn#j>pRU,SBL5,[Wpr]M)N7K+J+YY?`lh/+41a5Fb6fLA#iL3#5kM +6N._(ZY'+f6S"qeC#/Ro=sW-[BJAhi+3-cGf=#46N\T,Kei6.i7qBQ2T;_)'^bVnB2RO'QV" 0QVDb+r'FDIDko@UhIW1S[d8BXb#&ARjjX?Xi@rh*l8hQ(c1`QjYTK52+iXt4-$@uIJB"Ges4/-Cq5Q6`G?]H_OeF'@#>H_ `9$e$C+@2&T:\PgMH@a6&]m&DlV"ba@8[@(QF7.0IU&R>bo1J+4P;)5@T1oW2lWu@ p)^17q+HrCF'tU"i(Q_h$+T]EG$qctGYijK-CnW'n9!9B#$qRU'S09hUU]_KfqV!W gafa4I.9)\^4Vu(:-t"]r1-#m?">gHO cV8>FVN1U@%\bB<%F]YG16Wet*s`uu6K59PoHH)?">\q;SbsbGH9@]SqD<,o_m(+V i_RuecAGF3l."E+,cn>^WAiGhZ(r9TF<_9Kj)VT9khKq>28bEO "/&<"i;&;&,C;g/1<"M$&3?#=BGIEiMa*CX.*Zf[d[elX;PZ!VP]YZK,I2a5`9@7U n.a:ZNCe^Am%YgiNgC@r=K%=dSJ[4+j4D$=V#:]%-qFUD~> endstream endobj 119 0 obj <>stream 8;Z\6CRX!3#itt$j>q-&cN?<]2iY7q_RJhVQAf2g#%rDP%1?>7rp8=U_0sOVkCtYc b5$2C:].ErN!9FR[Z?0adC;)Z1Unt)Q9_M$kc*r:(+lG#M.A(pA/j/W*m\JA."!A9 OZ2[Cjcm#ZCYXO2327jm!\&dV&D5ebKpKeZ:/)?+Ue5sG&.1W^Y5i3n^.MKrFETRT!hH\ah1D^]oBlOH)Z=pWK.W% nt`6=P\5@l(c@D"[celE'JNt%Gc,RoLa[m7nL;(`i9^&8eh4;QHX)o2jd_`Nu6,SV7j_8I5G7,5SnFps0Z2g)8]@/,,Tb5Mb_&$29" 2Qcc"jO,/ZSA)=#ZOhKFink;6_hD3J4L1,MIhtU'E`X#nduR>(W;&*r.($hK0,E'< _TtYQUoKZ;T4.'NJ9!oX60rd5;d_8b#8Yf(mW9:#s AI-NP?;8?DZc)O/`:.+%$!e1P,[j0U8'++@=L4p`1m(nIO#*4WZ''RfC:@7.cP]0# u4;4Vt-"0^TLj:'u*"`O+"OcTC]Icr;hI8;0#%-84:-gR8Kb)$aAof;8;k4r722QV]%L-%BMgJAhD1bBRJ(7+&f(>O^K;j-)H AjDKbd?u,$)?df\^Q%nXm[gbUQN+nmqV'P=m+25*W\#\~> endstream endobj 123 0 obj <>stream 8;Z\u;%A7%$q0:X([Q9&6,%)Nomgo4-a<0A fi.K)YQ%*ADDkZZ*qoT=rN/hsd_`D'fX`/Omoos?GPp[nej5MeKU&K/C)thrg-9Yq Z-^e&4N;cNdE"CL;[r=2nE0_U/_-0b_V?X5enqUV3MSABEc=YPm4c-OX_B&6&4-XG KFgHU+b[LmcN"Kc="+~> endstream endobj 140 0 obj <> endobj 141 0 obj <> endobj 142 0 obj <> endobj 64 0 obj <> endobj 117 0 obj <> endobj 144 0 obj <> endobj 143 0 obj <>/XObject<>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]/Font<>>>/Thumb 139 0 R/MediaBox[0 0 612 792]/Rotate 0>> endobj 158 0 obj <>/ProcSet[/PDF/Text]/Font<>>> endobj 153 0 obj <> endobj 154 0 obj <> endobj 155 0 obj <> endobj 70 0 obj <> endobj 72 0 obj <> endobj 162 0 obj <> endobj 164 0 obj <> endobj 163 0 obj <> endobj 66 0 obj <> endobj 145 0 obj <>stream Hn0~ )/iP4zHr`URcI$;c;$e.l> 8fav]̖4Y:[!2(ČXi8pkXV43= BDV`)gO[83l{R܃44)X)3%B$џîzS#"N ݺ  x׻䧑K> ]]7G*&[PL)p7 IHX$@6w.b*>k: IÓzOi $բ˷-pS A8O}p(4Oa%|꥔!C4/AbA):w:H/@Hch (Q;!aIpSC_:}J 0%DhڂZ,m#a|;x0C"\S qZ.R`ƘԱ2).0 LB7%6 `֐| Ͽ}ɡ;j~cU.V'0*,oEKQZ@ë_ػrLw奙;ޅ t/D|o4NU]5nwMS0v]N}&a ˰O6dEUvQP2BtHyF/*rzS֕5a`]O++ƶ`=tSSu`$] endstream endobj 146 0 obj <>stream HlTM6 #8c{u &ibnEZ[֖=ȡ|8>ϊá<~>ݾ )\gY|5mVxh$2;N-r_“lߢi1\{(ɛCV_6YȚbTWRdqZs`AD9.k5C,Uzq+1[^E;[?)+vzp_O`鄳#^qsޘMtd,\7;v#jݜLJ6Ur~DV` (CNYu< nZf`|AZ?'D{rz!qU;iz} 7(Ijza$ʺNS>E>&n} LIFjzraV+jQ Y:s1۷{2Lx.e=,p~Qum8] 7I_74eXp'wd1@܇;.(%3jzM0 LyݐU6&M߭W2> endobj 74 0 obj <> endobj 157 0 obj <> endobj 167 0 obj <> endobj 168 0 obj <> endobj 147 0 obj <>stream HdT˒0Ej$?s%ærAV-"P3- Ԟ鞖wobwze)l6v}dߪ9 Ʊ+vnl2^P؞ <R-&%B0oLjBL :]`7lzszZzw\&/:ѬȬ]LpvɭR˪T %S&b55|bWc&SƝtyF$ eAHQMj9$yui&M= }јO=zso3`)58u\P 9#tߖF5PCNc]uw\P;ePXOːS@'$[j:%@gh딎5Of2=0%juR{TdGn0>%D>53h.DD#i~afw/t x Gx=ɧn"CRR/Gi.E,dL~2ҷh!׉HWhX1ؓÞ JS0 .R@ҽ ΒRp"p*rϬUMlK^Oujiwu 4-,MZ>8hS*%m.8{Ǥ֖O4y\7ԉa=G}$FP>R9'|qvLS@Hk`TwQeY-Y`ji endstream endobj 148 0 obj <>stream H|TMo8WH-V,%@E랒Xآ@κ?3n—!=7ݓӹꆄUREU-?:Xդw}hCp`~d] )ؒM! fƜ!mBԆ Jx+$Д){W}u񦥝1rහVr#(ٝnqa8W Hވ3?ĖQڈQ)`A #ťo]h5 ]AX9a1I9 c+LkRT& ȼH R#v 4lUSn#<WCO$xď:=·K:>9Pd'7?rB* '.z;3$֑ n C:)Q@JS,|;p 1Uv#Z_Ki)iSr)) Cm z"ġLăD0M 56 f1@6pvtp&ɀh'Epa&) S:5rψ3Ľ77_١kxhqq6t8hs[f h;7ޏ -@~CWBβ*ɟFq1eB\^1hb#v"/GRx}&g ?Ӥpb_L4R))22g T+[Vbi}In~K׵Yl`4 endstream endobj 149 0 obj <>stream HlT=0 #˲=NJֶ NR${$]?EkO)%ɷ6Sc6d(hAt1ى?$kn~Ǔ~_WlT/y"TIT7ߞhI`& "B桵!Nfhp eb%29 r$Nan`0@<BLppJtE[2]na8`9>ER THtZ~ڌ % r(C, ƈG߹?69H!Γk"  -UPq{zB 0!t&` BA ` <%8Ms!# tn|%%>sKF$6Tr =4"MV瘯v:wlk3G!QQƔXĚjZm_\bn'XwΉ/ETjY-pe76#PSB`׊e{92oJ*-߷-T%5{V}0"B̶i[26Nh&"M`08. ĕ8{,q\$سc7#,,(eҟ\-x>EXʀjal0, W+tK3V 2>ՉPu endstream endobj 150 0 obj <>stream HlTM0@=h9$wހ$b sR`H|??.τz6};EV\!Ys8mafG?%Mḡ%J0Kp{3bkV$Ƴv{7\.ݘ5۝nv~3Y>"%4eVqF,g rq8L+4M=MS]?JQDB3;UDHHe%W?g?> 'k2q`itcDk .RbAm>`p|.b"싹LlD%g鲔_gPzWdu2e6BTYQf?o,_ZU,8%)ˊTVha?&f:Xs6wB3&Ʌu9E3V$DGLքy"Jh1Kk&&[Jjßu 2(#OHSBΟ#h0Ɔhh{NvًFEG7-aIV0@ݒC*0BNE/(s ޅ -:|X/3z OJN  E)A$EdDŽ6BƒLjҸ?k15֥NJ7s!Tlj&k>b|+У ki?oO̳. endstream endobj 156 0 obj <> endobj 151 0 obj <>stream HTN0+|t$ıVP [8D4' vErx%$#ǜyVirKmchWX):&Jf60/XAgF94o0ƘH, lnf9}2<9[$ '$%lZ yxIB3J\)%!I3`N 0T\ۻ4Ա p^ocOΘT .IsHJdTY1%K&yɢO(O,Pq^++b-T*2]gzXӊIኆKإu(=ε!g5.gt qbP>]􇳏& vao|NǨ=oS.(ء/0`y;-!xt3Z zZ2)oPBISfR ۃ+ p>*& _%+5`c/FIF ~ -4XY &TMƺOqos:c;bFۆoQ 7GĈ v7 l?c&~`e4 4.kCJ"%mc%f_[7Jx*W(9X9בr#h.;SISzM;7at7Ƶ*)+z  sj\__#Sl endstream endobj 152 0 obj <>stream H|Rn0+t C|&TԶGP=(6*$CG.I9@/.VwF4& )SXI-bi&z )T+*)1;Oc=9+NQ> a+ftv~,Cq i(vͫN t۟XN|&@cסUv2~'O5 Xs*sLDvcZۡ(ODs۞m @2$ mݽJ7,q]Q,1H*wvΖeʛ(+6C@"_|[$:uq*t]u m~\f; ʋⱀ7G2npnmpM#'8>Y^ 9%v&lW}_ǾFOu!LѲ0`E ]/60Iߙb ZWd(vpb?$0(R0OMtU`x > endstream endobj 165 0 obj <>stream hdV TgN 'Q&8E"PyR_D<DU&Z|aVQRъbZTEU,Z]Ej}TW{ta۞=g??޹fD*N f\?2*bR]wcֿtnaJ{zI*-a.S4S|5QA#=k%jŒd&07ϔbf[%E{;!Av18hb*ܺU1b8a) KAәr2(5 1\mg֪ig`lA \E M3"0:"ը J@BtsHC=W1'6>³寊:ʸU6Os¡dZTA 7CUl%6ݢ!9]{< p0E -svwBAZ]t$s>_LBOZsE+ySˮ4x/C&PC8,x(ipc19ohԩK8yh> Ey/G I Y5SUPQJQʇkxAZI` ?KGћ#vC@ƃu-9#6J{P D^ IْՃ s 9E(cC4 _݃5Gv#hUdJA1 PM`޵uQ#s~A[bod,{3-acW4Dn7]x``MD∽B8'i2AwqH䛺*sy;Gs i_Q?Jn[T&o<~?)q鋸2pCDd;Ћ.v&b"bC"B+G J xLiZiPE ҭk8VPLZ_3h˭ ڏuI>y\P,NfN\>v{a3仪]K9 #|aݹf_K//YZR%u_ 㫣'I9}Oܡ+9zſ~˳9{(0kES_dHpUyshM`Hh$ 7#G8ib#b endstream endobj 166 0 obj <>stream h޴Y XWCuj.Se4wcTq 4 {4UTu7[J54;&"*ƨD3IԌ3Q83yy߻LIL^U{sϩgckk;i㺍Xig/Z^ aإw'MWXgc>68 mOYcc@(dA66:6l'ΰj1nqg&ٝ{LTt*6߽gKN4G-I3'' ''[/S]O O}AB p1!.J<$WӤߓ*ȴ.ꗾK'[_Μl "bus\rwo%m\~ch{u/VLqX`d1<F ]Ӵ4zY"uŸ.x+cv'1ΎƚS3t]mƖԃ>ޥ>ڡ^G o]Bw(DAvס,ߍ[8 zUJOF7v =Du;&Q6D ^k/a2 `M%m^AAt_Tq0ҜBUbeҾc]cǎ]~l_` OP|5xkI g"-(Sˁ !=gk:4cKI[0FПht'!7}|zkɇ@'20H=B_"~@&b`ۇJ}Cȯ}ֹ.\t 7⢙1N@uI*irap݂~cEƨTiz|vK+><Dz}hLȫJT*U}I82D &ORMEe`8u,AH5=)?U㟕:{Gץ]q%xn۵L6/C⣂wC:}8ng$\~$mk`ɛcߘ&ME %"2$ËoE('z <%ѫV5I]IR&xቢ#T${U݁^{!ĥ0+[P1|Y1ITx(#}1r/uB0a.x,pr(ǙBnq\O}H7ZIT13!IWื=ZwRo%uxbU:#]̈́Ŵ$/\gُhu]9wh dLIf$]A> ຦|&H|&fp7 vCwrݔBMc2s4lL x9 L#/^gOZN&چ36Q|7kMr?"8e5?ŀp k774Ѭ(y#G#)K׫$F)֯JTJZCB`}0z7Бҽ( NJV7I$T-pTB= qpKި,E:gGLAF ;iDt|#WTtr`gHFMW>$L(9.;98W\ MWϲ4~ZajB4Cgx6$'JɈ'bhڰc6<3F_,ƻ(?&TՒ5,[|5x *Av]M}X#FG2dD$i%B&X!Q?s XO`弓B ='N-Ȕ$'A$=|qZg(!g<|X6rVXO`lC9υ#O~Ez3]]\;EZ=x4L}`U$./m(#Ǐ9opǭOLbXj=?NF>!LsOGXL*ԵEU`-p.x4,AJBІaG5tp=|+6_"He1&=mX(ӘLb`%D Ь+Gx r찶1#2tJ[g c/BPx]!t#Pi~F~荨r2Zh0˫'9Y-y 7(YYU'Di7ր?uu1<ǟ(ͺniEN8⊸ʄX K˒J\M5WC԰c)&PSy]`+Sb]]GWۋ,mtGEǨr$|N[̼%ߥ_SΕZgѪU=9TeL.e&\{DOQh84G?ԓ@u3tʼ]b ŏWorкuX h,Ȍi*I0ğ4Y{Us" =n&:V6hNG{x; @zU6P̠7O)2,$2kMyܩG}oQQk+Ҭn];|%)n5ѽeo7mplDTJW2,,#MAGb oR8؃g)ʧ3ʰ0r΢`1x;m]hBTxIJm^ⅹGlZ(/^-\~!*gcdv#2tIJ)h^jߋv>:Yd(%SD3}59>/MykNe̊B!9w#B"TɡtlF\JB+$uo\[OZӊhONtksEh4T 0-yɆ22$]En"ҼH}Ov\ƣM$^f.(yeIx rFt*D1r"*!v)hp_g#Y׸`iDubzs?-.cT4o ^|guf ?XGwI+Y)%_og÷/|ɑz}XwNjmf` .+6qH{;qc P‰W,g\k ,'kp`.N9c #Yb "2;\ԒHGX>eh[?#"(l(#`V\[]!%HNM!S38>.uu5-=K",z%WZhQ[ZC 8>&VVJmSm{]7#i|߽g?_7ۊTNs9~Õw-;7SpO&vO^5Bk7a"߮w%8z3_J8Ŀ1'ɀ UПppb'p$.\/_|W4F݁N?b`~n.x|s4 E\Z[fO_e$Q+1/E ȿsw/ B9o}'N95+NY3nN*Ux{dz'okY/9YT%[++|xITMNqnϚ%a5֒#NUb,uڅyAfGb Hw1xy| fP?`YM6VM}NĻFPn?v> zGj1>0 $y.oe*ټļT py uVtGۉtJ\,bUwY D[@70uLYy;x;";*0 5T^p,ם)cGə0u1%H$d Ao9ÜiD[A7' `di arݨK0UŘSZBtz,3+]ڮՖkoeK8SWEXք>KӍYF 3?'ړS;*qPEQ9#wfJ3˃$Uz<*$1;I*{8X&vY4tޮn% cv-732UJhi]O!L(9ͧ5t셍+Xޤ3 #Bм1u] G( qut'"˿߲IO[6h6-X7 ;P Oy=XW>m_xf{^U`ϋêzPkKa 83uE'xh256ƛ4|gDé`+h endstream endobj 170 0 obj <>stream hޔWy\Sg ڴjO'9g9Nk;mZmkBXQAe HBٷsIJauAZwj7N;m_lיW|765mڴoX%rSӋ^5^(]7D.t!c=sfC4zp:kX4cO,3YKYXYY ,֦p0Vtk/%b2Xlċ[YN0e:4]4 ތM3N @04̎ _I9}%\?y0\C <p\hм%j {~>EOpsq."ݒo\3_}6 jl]3ق:UCO $q.8=~"b͢{=仈OK,vгZlscN#?ppŲ ee (7g hO? |ZR?N_|w3䓵/e)΅5ʺ? fƬظ}eb)vop6HZ5zƂC(UK!@'IJm⎫cecH1Ƹ (Ei>5]e ҏW2C#웡]-%rl#^c֓=;_|r7ͥßI|3^P۫٭SFGo #Ǒ#.Hکjh soыSau "bc84:fumMpΞXr=RxQ$yS& Nf L^NLQbQv0vfr8Coį|z[Fbd^"KYp&]?btY`֗5!Yk-ke3 c{8gCfmywӸ}kUDR~q)|q>V[)^/gC=I1sCK?>ORtǕ6Kz,Ioc9)sH睦w12"@SS(Kn"2/f`fzU:+6څWP^)e@ Ç 0^sL<ͷvY7 w.SъA%[$(v-4LY3(FOY|ǩ#ݖ377brr88bb:ML3MIID"j%ឲ;8ooOp8TO;z?8E 'g8cY74tF,'3<A!㸵yZU"ʃutb( #hX-)L%R] cX f0p@'`/2zeY z,AUDO>kb1^F}.hнs BO_skſg1wUjא9`l*"T$,"\GG/Ew3vYçKb|s>4UhϝdmΰBbUTPx( Qlp-X-X;|G&=fAc SA<9`2F#eRf 1*S1nu>o}}њ {n2$Kt^2+g2Ƞ )V)|cep=c@~:63}:96GxL҈t4-}*F(VMCTa` MIgt^W:zGoЯG3[RGPikUw`N&$ LC,fN01W'>'gWSYIO$66NX]˷do O)}n:!|mS?2acdWYC 鑓syco}!/l'! Dyhn.e2NP6Yb*M΂2s ï ;L֧j4rdiU?2ڃWY(ЃX(5"=_d So2 eZBŐ0˞/LމW*1H 9p˿y1)[u,jյ`7$ !MI^^lJ^wsηr"qNiBět5bH3+4R-6 ;Rh#pxjYN|RB (2:w9 ̓m~gSyS5f ! :t:*:;V\Xmzo;KQ0[*Vʴrc!e^^H1nMIX ZPZS&RaPMoli]7?VƏ;:vg7c;4Є09as^bivH#Z2ѡw.*J%mǣoD\p2) T%J{^JψY XW1yp3/y)qUzȕjJ(Hۼ)g  O^lefVO"JHV7}}W7|KlM:GAB}wj].]۪$PID .Ok1Odo*ol@ ~`Mbd-Dc "TYhܲ?kzPoR54)uP 8W ł\q .BOYg^sޱ Bm,6+JHd(*D2[Ɖl.ڄ@bxdZ}S{wܑK`W3 zFq}A[c.+Ѭ$\Ɋ[GPVɻĿl19_IO&E?k.Wڹ Ɔ',~p~^Y M lء58mUk==p'[zmjU30X͊9sPw=Ii4 5}} o"_~&-Wb4+zN#_cAx6Egު3E_ymU(<VUS֡l˒hxLP*@|\ hcG^HV :lm:FPsg*jXKz͖l^l,o-4kqtrzUeD9ىT{bs~AMɸrFz3JY&0{qN1؆V J7IBؔOR's= :vc?}9WƒPki*a1GéqfQ;2pD-D"j *Mq9uحp !p4 QuGY$ !ETjL,Jm~L2h[Ω}hʧR8b U>Zm:6z iV鶺.@`mx~QFN)=8 CIeeB"dR*BܧM@ĀBּ,dsp{̼>D݂}H>ʬb\G>62ip!S boo-$LJߟq-6p|V*FA2#jnÉr^L XH*ZOj:[=O?:)g&Ƣi'ܸqCfpvC6~#`i endstream endobj 171 0 obj <>stream hޔ{TW`i$3mhkU֢u}VTP+OyD$_00C1AA!"Z8[aV׶gjwo=g۳ssw7} ի||筊_fۓ{RKh[\~/?̘6g19 c2rb| [v1la!ƈ0w fa1s[21edʟFN>6n< "VC<2=~yZOm{J4!xDᝡ{j t;ֽR'_#1QQ]N{Ww_lGdm-HH&=#x8w+@^! LխAZcN@ȸlCVu%o>?>}Gy3Jш5p~U.~vt(F>]O@i`7u;bwR-CK. Mcwl<<Ŝ9~ ~'+i8r3Z~L< T6P7N]yꚒr^s<6:[z<4# AYI1{?b$b'姿IpXV. Il卼L$?8( RYnfVX? 1%@H1)E(tQׂqK}BY?Q&R[B,UԕϚ3'!>Bn{isu-ACT=pdn@7ҷa_{LY0R}mHvbKlR] 7۶-oٚu)coۏ0k dK-N cèיbÚrń.qpC)~d,|~ozvy9%{O zەkYylcU>]UɨPڴ2dqk|E"m|&YvNNW:k |^ *"q <d~b"r_癛_na\WhnO]Ȩp dk.3*5|jBۓWD'AwNjpD{9QE:!GsRAQԿOlX*hi?fB)ކO\P`Ljiϼ U>J@[b.z"F U)8e]V;nV2Dodܶ'cW5RK5XKcchQgG8$ *AgZn%F:wT0. z7^9l<ge 1U*BB*$DC1̂#\sRD^(Byp*_ercBӂ&]F \=oSU!!8֟ںC u D"AEH**M]_Ք/;:(u0=Ddjss60nkTJVEb MF3ӕIt_Wk&<4iQ.|= 3Z?ja.zJP&μh􅳡Eab_#L-N[_ڂP/>2X[]K>8h hڮkuO6KʷR[88)T9BkqW+_+9QIHfg%J>Cq?up:-v(D%2ꜗ6f&돛'+djcva=8 mGsetct:R:ޖuvUc3Sss-! нN}ݹr 7b:>!xؾiM\rU2ҫUL ·t:9G,cEfWVF#?Rx j]_|69&`Vdm~&& G-GS.ٺr~E'tSIۉD![(629(:GnW-J~wwqʹ~3sFi-9R$XG^[ gn?G7jl 7)2/zug17i?å)TJ0ZГsەDſYB3Gpw7 ȏ|κ:ZCnSEdW_H ˲xV*a|?5$VvV,Zs* M>h6BJR&3r]V&F3wGs%..Ni g]E4PEjxX;.4O*:E=0վ1=G}gSghsdNkB): pKQ}H̵6Cv\B"+ ( L d˸RC@]7^h8 (P٭VX<fTn3G-< w |(RdoKj1Yy6|'kj8\+s;ؕC2MV 4S2~V[Bv8KdRǹA g-K"}1=E2O' endstream endobj 175 0 obj <>stream hLKJ D DGx>vz?s޽/0̎cG E (9+3Q8cP Nkݽ4l';{w83dK"}Ց8>-5逆)aZ6rK6ފղbMb06LX`ŢUT5W4ETmĒM1 bQr .̲"bC6XYz* QDk<Q dl A8V@D3=f mYVvWhUD!Bѣi2I,"1Ο78jJ$u4;G\FIU6p%ߙVFK8-qR I!]"*-9]M¨^4T7Q?=<0ݧ.l%˝53pzifvlVa+\qn?C&WtkD,vk"-_\ϢBzv i~8C 4 ѸMX$zG$M c=Xc, tu9?+ endstream endobj 159 0 obj <> endobj 176 0 obj <>stream htV XW#!=1=x@̈rJ@%tFEp$Ar9$1j>D0"jE Ũ!߾!~{WQ1 IaQ1yqc"}lA9j3{= f'vMgN( 7_{%enm;F]hjѤ1g3R2YfC)uN曺^ :)dΣ҉7L9i)]ZΠ1RM"]<]lZFfN~I:AgH4\cvZjf/}Ɖe4,30 KLÄ91J&a2&Q2c< &)c.+|o+hbw;>~1&e2^DiQM dwPG2ǜ=sTT-}H}ާ5-wjK߻:T8P,&q5e7}8 uyJlǻshb`Lj$Wפ.]u]19+Å `!jx>d"F!Ug-n0P([ /“"⽧e+\/˹-Vgzo]?ٙ:pK#n:s0*ρk|EeIpi!:&—kX!UKv.8%&=R)ԡ\A8ɀ~³Ϣ ˖,)?d!ӭ/4vzR{1U?5'hWޣjpY{ : >?!.UrCCpfGzsZxtpہZ.k!z$6劖RiLywҤ":Xc(vN=vXͫ(DPQ8d4U9  rYpjPߚ&WP2:E}6G MONզ &#[۟|>inLbbX7~qzTjaܙB"IO&ƾEp*\X9J0jѠ+nqcAh?}($=KBKy1KhbVtY#v`bh偃l)‹:Bx 0MO)a8qw:N~(ݨn8}ՂZ/kɍ{oΜ*a Q#p&tF/\;`{a~ɋ`BT 54 ?{ry^qS 6B*B r0HxtM``Fc+,a_k+o%kDóV|FZ;2![;K4Lx\! 7-~;vy8, )C'*ͯ=;?e$<- qF޽\\ Knb-C` QnEh*~Ms=GjPvj(r84OYzrdߠ-%l}>IhZ8 <݂59ۖkDVX6zQ׻N>^DN'i`Sp?f7zB3lM "eL1Og--4⧄<> V|Y IpTQqYe#A $jA3Zut}]ZD n'%7C{7 C;Tb %pKc!sOx0tȏvKSLJL,r.AT*W8 gFnp5|2OeگպnG{;uE>L&rf|u!l-`/T(hں^dU4ɖ pr(jCe߿\в?=aG;)~;V[L)+O.T-sw - 6Kp-zK~"\>2pto.VZ+rǕUjpԗrκ'@)~%ifS#G.yGZT`>B~HYOO'8X`J1q Ne4.9'Nr_<E>CziXE,_|)ݰ) g.J[5G _Ǡ4z^G]D~|?udgB=Ӣۻ7n*6T$7=>İĴڲ<Vnܻr 䝂w iTxe6y:Eo Xj!˥ƣ_nVrPyZzjxa@\ ry1|W93E |Jh$6|&)BUex5ZF?zd$h$X*֯,@ԽGwk,87yxf$YyH4Xf%l@m^kƐ/>G?2xpX0?qoəoK&?oPBj?unK*umT(4!t .!肂x_ӸgpކŨ-y1h}h?OSXk·Ae)gJ\z_Z&-|-q}RAQId@ܵl/; @)9;ؗ',,'66=F]‡w}K\$5<,ShSou߯>\Ho ! [$cְ͖kX^6]] 5 @ u0E!g!)u[:}b@a5A endstream endobj 160 0 obj <> endobj 177 0 obj <>stream hތU{T]vY| ݉3F@pEa"(AQ>КjZ@A,ISmMQ&BQP _HxxgKO5oΙ{wߝ0:-hܓ,'Zcm9S#&LN U'p]k6~y8}2 0,c0:&aB&a02Zfc鑌o[٥zj3{ZeK'.uzZ]5Ndly(y 2\Wxczeđl2?w͚ ݇* $ؔr>43,{^0MW2Sn]}[1XhƅL *VJ $@5{Ix W'9O @iYb/Pة%'"6l#v-i.k{|nP'my4  a$0:Ѫ|8qx G~G8P`%`0аOv,=Drkn%Hsj" Q@ x9v0`TΉ-̮c'Hi#ewgB5`H^ 1$kشԃ 7/~R"+>W\OS 5d;I[sųr’E7VC|_Iv473ӝ PA?Fdg QB=rNrnoWoTVo\Uz^_KW03!-% ޺ >  ACS:pk?ҧ.=H F/u]utUkuʓ/4Q׿lPmV*w w]葀4 \hzF 1tO&ϥ䬝+]Q)AFEcJ0*i'Dn8`Gw T̃D(* v9*x43T'*8+vAS fRKS-VG)`+is 2g~q])=lXǒp/\v`=2FzȀ[#:CT$ONTWi ["6RK:Xu*}jO~ endstream endobj 161 0 obj <> endobj 178 0 obj <>stream hLQmLSg-1"Z}LIȔ1d:46`e^jm-me0$^-_Nـ~ ʷe3ȶlF3?,.9ŗkǓ'9稨H5Rbgefwgڪ Ro(TᗣbI{ѵG[Ab*RT#&Su_g3%n`&fl`F&&6c k}~cs*yZmf\|Za .Qɳke^s[N`s_L3k彬Ci+9lo%TTePT>U@RS[HVU:^}RMDs=YCVp$Yr"!`(]kY{JI1}Ē8reC1 rzz3d">y KKdb6415te#81#B^"~,*a{j;LE(BCv`iņ{/O!Kg'9@%н )ϖ𧡆MũfDvf 4?dft@4g<4?.M w73]lɣk"G=}V(Kh!_ӊut]a %$R` hn&nT+ut]@9W vPt+nRG(~GCM] iX^{Ԥn}1a/=39mTV &K HlOxq U铥*8ӨVI ;a&0)Wַ@Gwn%[kXPCW43-MqQ nmgqXKñcFIjmupj zX7 _37|f|3œx,ǽE< j|OљQtnM⤢sՋ rͨ4%B!B:%)< /u(?7'm endstream endobj 169 0 obj <> endobj 179 0 obj <>stream hbd`ad`ddurtvL) {X_^,+FnfFF&|~qh+Cw(FYv<|;vY3#34!~rvKxwbE=z@` `bm -4H\ bX endstream endobj 174 0 obj <> endobj 173 0 obj <>stream hTP=0 +<Ҳ!UOO(DM{R@oI>tg]S OtKwk; _:݄SdcqPB> endobj 180 0 obj <> endobj xref 0 181 0000000000 65535 f 0000007225 00000 n 0000000015 00000 n 0000003939 00000 n 0000009687 00000 n 0000003667 00000 n 0000004487 00000 n 0000005310 00000 n 0000005584 00000 n 0000007497 00000 n 0000000654 00000 n 0000008591 00000 n 0000008043 00000 n 0000009139 00000 n 0000005856 00000 n 0000000105 00000 n 0000004212 00000 n 0000002025 00000 n 0000002573 00000 n 0000006403 00000 n 0000006952 00000 n 0000000929 00000 n 0000002298 00000 n 0000007770 00000 n 0000008317 00000 n 0000000379 00000 n 0000002847 00000 n 0000006129 00000 n 0000004760 00000 n 0000001477 00000 n 0000001203 00000 n 0000001750 00000 n 0000009414 00000 n 0000006678 00000 n 0000005035 00000 n 0000003394 00000 n 0000003120 00000 n 0000008864 00000 n 0000009961 00000 n 0000013392 00000 n 0000013469 00000 n 0000013580 00000 n 0000013657 00000 n 0000013767 00000 n 0000013844 00000 n 0000013955 00000 n 0000014032 00000 n 0000014143 00000 n 0000014220 00000 n 0000014331 00000 n 0000014408 00000 n 0000014519 00000 n 0000014596 00000 n 0000014707 00000 n 0000014784 00000 n 0000014896 00000 n 0000014973 00000 n 0000015083 00000 n 0000015160 00000 n 0000015270 00000 n 0000015347 00000 n 0000015458 00000 n 0000015535 00000 n 0000015646 00000 n 0000403271 00000 n 0000016183 00000 n 0000407318 00000 n 0000027704 00000 n 0000053070 00000 n 0000387734 00000 n 0000405290 00000 n 0000387907 00000 n 0000405686 00000 n 0000409105 00000 n 0000409565 00000 n 0000393995 00000 n 0000016006 00000 n 0000068096 00000 n 0000068548 00000 n 0000081755 00000 n 0000394903 00000 n 0000068414 00000 n 0000126188 00000 n 0000126708 00000 n 0000140534 00000 n 0000388451 00000 n 0000395834 00000 n 0000126542 00000 n 0000176493 00000 n 0000176955 00000 n 0000391805 00000 n 0000396822 00000 n 0000176828 00000 n 0000193936 00000 n 0000194479 00000 n 0000242109 00000 n 0000204943 00000 n 0000397414 00000 n 0000194302 00000 n 0000264251 00000 n 0000264694 00000 n 0000398450 00000 n 0000264577 00000 n 0000281859 00000 n 0000282364 00000 n 0000296865 00000 n 0000399049 00000 n 0000282207 00000 n 0000331115 00000 n 0000331579 00000 n 0000399822 00000 n 0000331452 00000 n 0000348610 00000 n 0000349032 00000 n 0000400492 00000 n 0000348926 00000 n 0000364274 00000 n 0000403407 00000 n 0000364719 00000 n 0000401539 00000 n 0000364602 00000 n 0000381491 00000 n 0000381912 00000 n 0000402718 00000 n 0000381807 00000 n 0000385044 00000 n 0000385094 00000 n 0000385607 00000 n 0000386037 00000 n 0000386330 00000 n 0000386398 00000 n 0000386600 00000 n 0000387510 00000 n 0000388085 00000 n 0000388863 00000 n 0000393318 00000 n 0000392579 00000 n 0000392348 00000 n 0000392873 00000 n 0000393396 00000 n 0000403144 00000 n 0000403182 00000 n 0000403208 00000 n 0000403569 00000 n 0000403485 00000 n 0000407420 00000 n 0000408207 00000 n 0000410832 00000 n 0000411639 00000 n 0000412528 00000 n 0000413342 00000 n 0000414381 00000 n 0000415162 00000 n 0000404169 00000 n 0000404434 00000 n 0000404913 00000 n 0000414213 00000 n 0000409931 00000 n 0000403999 00000 n 0000433240 00000 n 0000436462 00000 n 0000438872 00000 n 0000406277 00000 n 0000407146 00000 n 0000406619 00000 n 0000415746 00000 n 0000418454 00000 n 0000410178 00000 n 0000410530 00000 n 0000440295 00000 n 0000424883 00000 n 0000429673 00000 n 0000441318 00000 n 0000441034 00000 n 0000440811 00000 n 0000432416 00000 n 0000433469 00000 n 0000436834 00000 n 0000439182 00000 n 0000440523 00000 n 0000441383 00000 n trailer <<4f904c2da98dd9add159395e57b3dad8>]/Info 180 0 R/Size 181>> startxref 441890 %%EOF