脊髄性筋萎縮症患者の運動機能を定量的に評価する新規指標の開発

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Title 脊髄性筋萎縮症患者の運動機能を定量的に評価する新規指_{標の開発( 本文(Fulltext) )} Author(s) 松丸, 直樹 Report No.(Doctoral Degree) 博士(医科学) 連創博甲第42号 Issue Date 2018-03-25 Type 博士論文 Version ETD URL http://hdl.handle.net/20.500.12099/75255 ※この資料の著作権は、各資料の著者・学協会・出版社等に帰属します。

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ᖹᡂ

30 ᖺ 3 ᭶

March 2018

ᒱ㜧኱Ꮫ኱Ꮫ㝔㐃ྜ๰⸆་⒪᝟ሗ◊✲⛉

་⒪᝟ሗᏛᑓᨷ

United Graduate School of Drug Discovery and Medical Information Sciences,

Gifu University

ᯇ୸ ┤ᶞ

Matsumaru, Naoki

⬨㧊ᛶ➽ⴎ⦰⑕ᝈ⪅ࡢ㐠ືᶵ⬟ࢆᐃ㔞ⓗ࡟ホ౯ࡍࡿ

᪂つᣦᶆࡢ㛤Ⓨ

Development of Quantitative Evaluation of Motor Functions for

Spinal Muscular Atrophy

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ᮏᏛ఩ㄽᩥࡣࠊᏛ⾡◊✲㞧ㄅ࡟཰㍕ࡉࢀࡓḟࡢཎⴭㄽᩥࢆᇶ࡟ࡋ࡚సᡂࡋࠊᒱ㜧኱Ꮫ኱Ꮫ 㝔㐃ྜ๰⸆་⒪᝟ሗ◊✲⛉࡟ᥦฟࡋࡓࡶࡢ࡛࠶ࡿࠋ

Naoki Matsumaru, Ryo Hattori, Takashi Ichinomiya, Katsura Tsukamoto, Zenichiro Kato

New quantitative method for evaluation of motor functions applicable to spinal muscular atrophy

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┠

┠ḟ

ᗎㄽ...4

ศᯒ᪉ἲ...7

2.1 㐠ືࢹ࣮ࢱࡢ཰㞟...7

2.2 Spatial Deviation ࡜ Direction Variance...8

2.3 ࠕ㐠ືࡢ㉁ࠖࡢẚ㍑᪉ἲ࡜⤫ィⓗฎ⌮ࠊ೔⌮ኌ᫂...9 ⤖ᯝ... 10 3.1 ࢣ࣮ࢫ1㸸೺ᖖᡂேࡢሙྜ ...10 ⫪㛵⠇ࡢᒅ᭤㐠ືࡢ㌶㊧...10 6S'H ࡜ 'L9D ࡟ࡼࡿ㐠ືࡢホ౯...12 3.2 ࢣ࣮ࢫ㸰㸸II ᆺ SMA ᝈ⪅ࠊTRH ⒪ἲࡢ᭷ຠᛶホ౯ ...13 ᝈ⪅⫼ᬒ࡜ 75+ ⒪ἲࡢヲ⣽...14 ,, ᆺ 60$ ᝈ⪅࡟࠾ࡅࡿ⫪㛵⠇ࡢᒅ᭤㐠ືࡢ㌶㊧...16 6S'H ࡜ 'L9D ࡟ࡼࡿ 75+ ࡢ᭷ຠᛶホ౯...16 ⪃ᐹ...18 ㅰ ㎡... 22 ᘬ⏝ᩥ⊩... 23

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ᗎ

ᗎㄽ

⬨㧊ᛶ➽ⴎ⦰⑕㸦Spinal muscular atrophy: SMA㸧ࡣࠊ㐠ືࢽ࣮ࣗࣟࣥࡀᏑᅾࡍࡿ⬨㧊 ࡢ๓ゅ⣽⬊ࡀኚᛶࡍࡿࡇ࡜࡛㉳ࡇࡿࠊయᖿࡸᅄ⫥ࡢ➽ⴎ⦰ࡸ㐍⾜ᛶࡢ➽ຊపୗࢆ≉ᚩ ࡜ࡍࡿᖖᰁⰍయຎᛶ㑇ఏ⑌ᝈ࡛࠶ࡿ 1_{ࠋⓎ⑕ᖺ㱋ࡸ㔜⑕ᗘࡣࡉࡲࡊࡲ࡛ࠊ฿㐩ࡋࡓ㐠} ື࣐࢖ࣝࢫࢺ࣮ࣥ࡟ᛂࡌ࡚4 ࡘࡢᆺ࡟ศ㢮ࡉࢀࡿ2,3_ࠋ⏕ᚋ_{6 ࠿᭶ᮍ‶࡛Ⓨ⑕ࡍࡿ I ᆺ} 㸦㔜⑕ᆺ㸧࡛ࡣࠊᆘ఩ࡢಖᣢࡀ୙ྍ⬟࡛ࠊேᕤ࿧྾ჾࢆ౑⏝ࡋ࡞࠸ሙྜ࡛ࡣ2 ṓࡲ࡛ ࡟ஸࡃ࡞ࡿ࡜ࡉࢀ࡚࠸ࡿࠋ⏕ᚋ6 ࠿᭶࠿ࡽ 1 ṓ 6 ࣧ᭶ᮍ‶࡟Ⓨ⑕ࡍࡿϩᆺ㸦୰㛫ᆺ㸧 ࡛ࡣࠊᆘ఩ࡣྍ⬟ࡔࡀ୍ே࡛❧ࡗࡓࡾṌ࠸ࡓࡾࡍࡿࡇ࡜ࡣ୙ྍ⬟࡛࠶ࡿࠋ⏕ᚋ 1 ṓ 6 ࠿᭶࠿ࡽ20 ṓ௨ୗ࡛Ⓨ⑕ࡍࡿϪᆺ㸦㍍⑕ᆺ㸧࡛ࡣࠊ⮬❧Ṍ⾜ࡶྍ⬟࡛࠶ࡿࡀࠊ⑓≧ࡢ 㐍⾜࡜࡜ࡶ࡟㌿ࡧࡸࡍࡃ࡞ࡿ࡞࡝ࠊ㐠ືᶵ⬟ࡣᚎࠎ࡟పୗࡋ࡚࠸ࡃࠋࡑࡋ࡚ࠊ20 ṓࢆ ㉸࠼࡚࠿ࡽࡢᡂேᮇ࡟Ⓨ⑕ࡍࡿϫᆺ㸦ᡂேᆺ㸧ࡀ࠶ࡿ1_ࠋ_{SMA ࡣཌ⏕ປാ┬ࡢᣦᐃ㞴} ⑓࡟ᣦᐃࡉࢀ࡚࠾ࡾࠊஙඣᮇ࠿ࡽᑠඣᮇ࡟Ⓨ⑕ࡍࡿSMA ࡢ⨯ᝈ⋡ࡣࠊ࠾ࡼࡑ 10 ୓ே ࡟1 ே㹼2 ே࡜ࡉࢀ࡚࠸ࡿࠋ᭷ຠ࡞᰿ᮏ἞⒪ࡣ☜❧ࡉࢀ࡚࠸࡞࠸ࠋ SMA ࡢデ᩿࡟ᑐࡍࡿᵝࠎ࡞ࣂ࢖࣐࣮࣮࢜࢝࡟ࡘ࠸࡚ࡢ◊✲ࡣ࡞ࡉࢀ࡚ࡣ࠸ࡿ 4_ࡀࠊ ⌧≧࡟࠾࠸࡚ࠊ⮫ᗋ⌧ሙ࡛᭱ࡶಙ㢗࡛ࡁࡿデ᩿ᡭἲ࡜ࡋ࡚☜❧ࡋ࡚࠸ࡿࡢࡣ㐠ືᶵ⬟ ホ౯ࢫࢣ࣮࡛ࣝ࠶ࡿ5_ࠋ_{Gross Motor Function Measure}6_{ࡣࠊࡶ࡜ࡶ࡜⬻ᛶࡲࡦࡸ㢌㒊እ}

യ࡟ࡼࡗ࡚㐠ືᶵ⬟࡟㞀ᐖࡀ⏕ࡌ࡚ࡋࡲࡗࡓᏊ౪ࡢ≧ែኚ໬ࢆホ౯ࡍࡿ┠ⓗ࡛㛤Ⓨࡉ

ࢀࡓࡀࠊᑠඣ SMA ᝈ⪅ࢆᑐ㇟࡜ࡋࡓ἞㦂࡟࠾࠸࡚ࡶಙ㢗࡛ࡁࡿ࢔࢘ࢺ࣒࢝ᣦᶆ࡛࠶

ࡿࡇ࡜ࡀ♧ࡉࢀ࡚࠸ࡿ7_ࠋ_{II ᆺ SMA ࡜Ṍ⾜୙ྍ⬟࡞ III ᆺ SMA ࡬ࡢ㐺ᛂࢆᛕ㢌࡟㛤Ⓨ}

ࡉࢀࡓホ౯᪉ἲ࡜ࡋ࡚Hammersmith Functional Motor Scale㸦HFMS㸧8_{ࠊࡑࡋ࡚ࠊࡑࡇ}

࡟ලయⓗ࡞ືసᐃ⩏ࡸࢫࢥ࢔ࡢ௜ࡅ᪉ࢆຍ࠼ࠊ⿕㦂⪅ࡢయ఩ኚ᥮ࡢ㈇ᢸࢆ㍍ῶࡍࡿࡼ ࠺࡟ホ౯㡯┠ࢆ୪࡭┤ࡋࡓಟṇ∧㸦Modified HFMS㸧9_{ࡀ࠶ࡿࠋࡉࡽ࡟ࠊṌ⾜ྍ⬟࡞}_III

ᆺ SMA ᝈ⪅࡟ᑐࡋ࡚Ⓨ⏕ࡋ࡚ࡋࡲ࠺ኳ஭ຠᯝ㸦Ceiling effect㸧࡟ᑐฎࡋࡓ Expanded HFMS10_࡜_{Extended HFMS}9_{ࡶ⪃᱌ࡉࢀ࡚࠸ࡿࠋࡇࢀࡽࡢホ౯ࢫࢣ࣮ࣝࡢ⮫ᗋ࡟࠾ࡅࡿ}

ಙ㢗ᛶࡸጇᙜᛶࡣ඘ศ࡟᳨ウࡉࢀ࡚ࡣ࠸ࡿࡀࠊࡑࢀࡒࢀࡢືస࡟ࡘ࠸࡚㡰ᗎᑻᗘ 㸦ordinal scale㸧࡛ホ౯ࡉࢀࡿࡓࡵࠊ኱ᑠẚ㍑ࡀྍ⬟࡛࠶ࡾࠊᑻᗘ㛫ࡢ㛫㝸࡟ព࿡ࡣ࡞

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ࡃࠊཝᐦ࡟ࡣᅄ๎₇⟬ࡣᐃ⩏ࡉࢀࡎࠊᑻᗘ࡜ᑻᗘࡢ㛫ࡢኚ໬ࢆホ౯࡛ࡁ࡞࠸࡞࡝ࡢၥ 㢟ࡀ࠶ࡿࠋࡑࡢࡓࡵࠊࣛࢵࢩࣗ㸦Rasch㸧ࣔࢹࣝ࡟௦⾲ࡉࢀࡿ㡯┠ᛂ⟅ศᯒࢆ⏝࠸࡚ࠊ ࡇࢀࡽࡢ㐠ືᶵ⬟ホ౯ࢫࢣ࣮ࣝࢆ෌ᵓ⠏ࡍࡿ࡞࡝ࠊࡇࢀࡲ࡛ࡢ㡰ᗎᑻᗘ࡛ࡢホ౯ࢆᐃ 㔞໬ࡋࠊ㛫㝸ᑻᗘࠊẚ౛ᑻᗘ࡬ኚ᥮ࡍࡿヨࡳࡶ⾜ࢃࢀ࡚࠸ࡿ5,11_ࠋ ྡ⩏ᑻᗘࡸ㡰ᗎᑻᗘ࡛ࡣ࡞࠸ᐃ㔞ⓗ࡞࢔࢘ࢺ࣒࢝ᣦᶆ࡛ SMA ᝈ⪅ࡢ⑓≧ࢆホ౯ࡍ ࡿ᪉ἲ࡜ࡋ࡚ࡣࠊ୺࡟ḟࡢ2 ࡘࡀᏑᅾࡍࡿࠋ୍ࡘࡣࠊᡭᣢࡕᘧືຊィ㸦ࣁࣥࢻ࣊ࣝࢻ ࢲ࢖ࢼ࣓࣮ࣔࢱ࣮㸧ࢆ⏝࠸࡚ ᐃࡋࡓ➽ຊ್ࢆά⏝ࡍࡿ᪉ἲ࡛࠶ࡿࠋࡇࡢ᪉ἲࡣࠊࢧ ࣝࣈࢱ࣮ࣔࣝ㸦Salbutamol㸧ࡢ᭷ຠᛶࢆ᳨ウࡍࡿ἞㦂࡛᥇⏝ࡉࢀࡓᐇ⦼ࡶ࠶ࡾ12_ࠊホ౯ ⪅㛫ಙ㢗ᛶ࣭ホ౯⪅ෆಙ㢗ᛶ࡜ࡶ࡟☜࠿ࡵࡽࢀ࡚࠸ࡿ 13,14_{ࠋࡋ࠿ࡋ࡞ࡀࡽࠊᝈ⪅ࡢ⮬} Ⓨⓗ࡞༠ຊࡀ୙ྍḞ࡛࠶ࡿࡓࡵࠊஙᗂඣࡸᑠᏛᰯపᏛᖺ࡟ࡣ㐺ᛂࡀ㞴ࡋࡃࠊࡲࡓࠊホ ౯⪅ࡶホ౯ࡢኚືࢆ㜵ࡄࡓࡵࡢ⦎⩦ࡀᚲせ࡛࠶ࡿ15,16ࠋࡉࡽ࡟ࠊSMA ᝈ⪅ࢆᑐ㇟࡜ࡍ ࡿሙྜ࡟ࡣࠊ⑓≧ࡀ㐍ࡳࠊᆘ఩࡞࡝ࡢጼໃࢆಖᣢࡍࡿࡢࡶᅔ㞴࡞≧ែࡲ࡛➽ຊࡀపୗ ࡋ࡚ࡋࡲ࠺஦ࡶ࠶ࡿࡓࡵࠊ㤳ᑿ୍㈏ࡋࡓホ౯ࢆࡍࡿホ౯⪅ࡢカ⦎࡟ຍ࠼࡚ࠊᝈ⪅ࡢయ ఩࣭ጼໃ࡞࡝ࡶཝᐦ࡟᳨ᰝࣉࣟࢺࢥࣝ࡟つᐃࡍࡿᚲせࡀ࠶ࡿ17ࠋ SMA ᝈ⪅ࡢ⑓≧ࢆホ౯ࡍࡿࡶ࠺୍ࡘࡢᐃ㔞ⓗホ౯᪉ἲࡣࠊ6 ศ㛫Ṍ⾜ࢸࢫࢺ㸦6MWT㸧 ࡜࿧ࡤࢀࠊ6 ศ㛫࡛ṌࡅࡿṌ⾜㊥㞳ࢆ ᐃࡋࠊᝈ⪅ࡢᶵືᛶ࣭⛣ື⬟ຊ࠿ࡽ㐠ືᶵ⬟ ࢆホ౯ࡍࡿ᪉ἲ࡛࠶ࡿࠋඖ᮶ࠊᑐ㇟⪅ࡢ㐠ື⪏ᐜ⬟ࡢホ౯ࢆ┠ⓗ࡜ࡋ࡚࠸ࡿࡀࠊࡑࡢ ෌⌧ᛶࡸጇᙜᛶࡣࡉࡲࡊࡲ࡞⑌ᝈ࡛ᐇドࡉࢀ࡚࠾ࡾ 18_ࠊ_{Expanded HFMS ࡞࡝ࡢ SMA} ≉᭷ࡢホ౯ࢫࢣ࣮ࣝ࡜ࡢᩚྜᛶࡶ☜࠿ࡵࡽࢀ࡚࠸ࡿࡓࡵ19ࠊSMA ࡛ࡢホ౯᪉ἲ࡜ࡋ࡚ ᥇⏝ࡉࢀࡿࠋࡋ࠿ࡋࠊ6MWT ࡢỴᐃⓗ࡞ၥ㢟࡜ࡋ࡚ࠊホ౯࡛ࡁࡿᑐ㇟ࡀṌ⾜ྍ⬟࡞ᝈ ⪅࡟㝈ᐃࡉࢀ࡚ࡋࡲ࠺Ⅼࡀ࠶ࡿࠋࡑࡢࡓࡵࠊSMA ࡛ࡣṌ⾜ྍ⬟࡞ III ᆺ௨ୖࡢᝈ⪅ࡢ ࡳࡀᑐ㇟࡜࡞ࡾࠊI ᆺࠊII ᆺࠊṌ⾜୙ྍ⬟࡞ III ᆺࡣホ౯ࡢᑐ㇟እ࡛࠶ࡿࠋ

3 ḟඖ࣮ࣔࢩࣙࣥ࢟ࣕࣉࢳࣕࢆά⏝ࡋ࡚ SMA ᝈ⪅ࡢ⑓≧ࢆホ౯ࡍࡿඛ⾜◊✲࡛ࡣࠊ Ṍ⾜ྍ⬟࡞ III ᆺ SMA ᝈ⪅ࢆᑐ㇟࡜ࡋ࡚ 6MWT ࡼࡾࡶࡉࡽ࡟ヲ⣽࡞Ṍ⾜ゎᯒࢆᐇ᪋ ࡋࠊ἞⒪ೃ⿵⸆ࡢ᭷ຠᛶࢆᐃ㔞ⓗ࡟ホ౯ࡋ࡚࠸ࡿ20_ࠋ࡞࠾ࠊ_{SMA ࡢ἞⒪⸆ೃ⿵࡜ࡋ࡚}

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ࡸࡍ㐠ື⏥≧⭢่⃭࣍ࣝࣔࣥᨺฟ࣍ࣝࣔࣥ㸦Thyrotropin releasing hormone: TRH㸧ࡀ㑅

ᢥࡉࢀ࡚࠸ࡿࠋᮏㄽ࡟࠾࠸࡚ࡣࠊ3 ḟඖ࣮ࣔࢩࣙࣥ࢟ࣕࣉࢳࣕࢆ⏝࠸࡚ୖ⫥ࡢ㐠ືᶵ

⬟ࢆホ౯ࡍࡿᡭἲࢆ᪂つ࡟㛤ⓎࡋࠊṌ⾜୙ྍ⬟࡞ SMA ᝈ⪅࡟ᑐࡋ࡚ࡶ㐠ືᶵ⬟ࢆᐃ

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ศ

ศᯒ᪉ἲ

㐠ືࢹ࣮ࢱࡢ཰㞟

ᕷ㈍ࡢ3 ḟඖ࣮ࣔࢩࣙࣥ࢟ࣕࣉࢳࣕࢩࢫࢸ࣒(VICON Motion Systems Ltd., Oxford, UK)ࢆ⏝࠸࡚ࠊୖ⫥ࡢືࡁࢆࢹࢪࢱࣝ໬ࡋ㐠ືࢹ࣮ࢱ࡜ࡋ࡚཰㞟ࡋࡓࠋලయⓗ࡟ࡣࠊ ᑐ㇟⪅࡟㈞௜ࡋࡓ෌ᖐ཯ᑕ࣐࣮࣮࢝ࢆ」ᩘࡢ㉥እ⥺࣓࡛࢝ࣛ᧜ᙳࡍࡿࡇ࡜࡛ࠊ3 ḟඖ ✵㛫࡟࠾ࡅࡿ࣐࣮࣮࢝ࡢ఩⨨ᗙᶆࢆ≉ᐃࡋࠊࡑࡢᗙᶆࢆ⤒᫬ⓗ࡟グ㘓ࡍࡿࠋᮏ◊✲࡟ ࠾࠸࡚ࠊࢹ࣮ࢱࡢࢧࣥࣉࣜࣥࢢ࿘Ἴᩘࡣ100Hz ࡜タᐃࡋࠊ⫪㛵⠇ࡢᒅ᭤㐠ືࢆᑐ㇟㐠 ື࡜ࡋࡓࠋࡑࡋ࡚ࠊୖ⫥ࡢືࡁࢆ➃ⓗ࡟⾲⌧ࡍࡿ㒊఩࡜ࡋ࡚ྑ⭎⫝㛵⠇ࠊୖ⭎㦵ࡢእ ഃୖ㢛ࢆ㑅ᢥࡋ࡚࣐࣮࣮࢝ࢆ㈞௜ࡋࡓࠋᐇ㦂࡟࠾࠸࡚ࡣࠊᑐ㇟⪅ࡣᅗ 1a ࡟♧ࡋ࡚࠸ ࡿࡼ࠺࡟ x ㍈ࡢ࣐࢖ࢼࢫ᪉ྥࢆྥ࠸࡚❧ࡕࠊయࡢ๓᪉࡟ྥ࠿ࡗ࡚⭎ࡢୖࡆୗࡆࢆ 10 ᅇ⧞ࡾ㏉ࡍ㸦ᅗ 1b㸧ࠋ ࡞࠾ࠊࡇࡢ⫪㛵⠇ࡢᒅ᭤㐠ື࡜㢮ఝࡍࡿືసࡀSMA ࡢホ౯᪉ἲࡢ୍ࡘ HFMS ࡟ྵ ࡲࢀ࡚࠸ࡿࠋࠕᆘ఩࡛∦ᡭࢆᣲࡆࡿࠖືస࡛ࠊ㢌ࡲ࡛ᣲࡆࡽࢀࢀࡤࢫࢥ࢔2ࠊ⪥ࡢ㧗ࡉ ࡲ࡛ᣲࡀࡿࡶࡋࡃࡣ㢌ࢆᡭࡢ᪉࡟᭤ࡆ࡚ࡋࡲ࠼ࡤࢫࢥ࢔ 1ࠊ୙ྍ⬟࡛࠶ࢀࡤࢫࢥ࢔ 0 ࡜ホ౯ࡉࢀࠊ㡰ᗎኚᩘ࡜ࡋ࡚ᩘ್໬ࡉࢀࡿࠋHFMS ࡛ࡢホ౯࡛ࡣ∦ᡭࢆᣲࡆࡿࡇ࡜ࡢ ࡳࢆᣦ♧ࡋࠊᣲࡆ᪉ࡸ㧗ࡉࠊୗࡆ᪉࡟ࡘ࠸࡚ࡣ≉ẁᣦ♧ࢆࡏࡎ⿕㦂⪅ࡢ⮬⏤࡜ࡋ࡚࠸

b

㻌

a

㻌

ᅗ 1 㐠ືࢹ࣮ࢱ ᐃ᫬࡟࠾ࡅࡿᗙᶆ㍈ࡢタᐃ࡜ᑐ㇟㐠ື㸸(a)⿕㦂⪅ࡣ x ㍈ࡢ࣐࢖ࢼࢫ᪉ྥࢆྥ࠸ ࡚㐠ືࢆᐇ᪋ࡍࡿࠋ(b)ᑐ㇟㐠ື࡜ࡍࡿ㐠ືࡣ⫪㛵⠇ࡢᒅ᭤㐠ື࡛ 10 ᅇ཯᚟࡜ࡍࡿࠋ࣐࣮࣮࢝ࡣྑ ⭎⫝㛵⠇ࠊୖ⭎㦵ࡢእഃୖ㢛࡟㈞௜ࡋ࡚㐠ືࢹ࣮ࢱࢆ ᐃࡋࡓࠋணഛゎᯒ࡟࠾࠸࡚ୖ᪼༊㛫࡜ࡋ࡚ ᢳฟࡉࢀࡓ༊㛫ࡣ㉥࡛ࠊୗ㝆༊㛫ࡣ㟷࡛Ⰽศࡅࡉࢀࡿࠋ

(9)

ࡿࡀࠊᮏᐇ㦂࡟࠾࠸࡚ࡣᣲࡆࡿ㧗ࡉࡸᵝᏊࠊୗࡆ᪉ࡶホ౯࡟ຍ࿡ࡉࢀࡿࡓࡵ⿕㦂⪅࡬ ࡢᣦ♧࡟ࠕ⫝ࢆ᭤ࡆࡎ࡟ࠊ࡞ࡿ࡭ࡃ㧗ࡃࡲ࡛ᣲࡆࠊ࡞ࡿ࡭ࡃୖୗ㐠ືࡶ࡞ࡵࡽ࠿࡟ࡍ ࡿࠖࡼ࠺࡟ᣦ♧ࢆࡋࡓࠋ

6SDWLDO'HYLDWLRQ ࡜ 'LUHFWLRQ9DULDQFH

ᮏ◊✲࡟࠾࠸࡚ࡣࠊᑐ㇟⪅ࢆṌ⾜ྍ⬟࡞ᝈ⪅࡟㝈ᐃࡋ࡞࠸㐠ືᶵ⬟ࡢホ౯ᡭἲࢆ☜ ❧ࡍࡿࡇ࡜ࡀ┠ⓗ࡛࠶ࡿࡓࡵࠊୖ⫥ࡢ㐠ືᶵ⬟࡟╔┠ࡋࡓࠋࡋ࠿ࡋࠊࡇࢀࡲ࡛ୖ⫥ࡢ 㐠ືᶵ⬟ࢆᐃ㔞໬ࡍࡿᣦᶆࡣ☜❧ࡉࢀ࡚࠾ࡽࡎࠊ⊂⮬࡟㛤Ⓨࡍࡿᚲせࡀ࠶ࡗࡓࠋࡑࡇ ࡛ࠊᮏ⠇࡟࠾࠸࡚ࠊ௒ᅇ㛤Ⓨࡋࡓ2 ࡘࡢ᪂つホ౯ᣦᶆ࡟ࡘ࠸࡚ㄝ᫂ࡍࡿࠋ

➨୍ࡢᣦᶆࡣࠕ✵㛫⢭☜ᛶ㸦Spatial Deviation㸸 SpDe㸧ࠖࠊ༶ࡕࠊྠࡌືసࢆ⢭☜࡟

཯᚟࡛ࡁࡿ࠿ࢆᩘ್໬ࡍࡿࠋලయⓗ࡟ࡣࠊ཯᚟㐠ືࡢ㌶㊧ࡀ3 ḟඖ✵㛫࡟༨ࡵࡿࠕయ

✚ࠖࢆ⟬ฟࡋࠊࡇࢀࡀᑠࡉ࠸࡯࡝⢭☜࡟㐠ືࡀ཯᚟࡛ࡁ࡚࠸ࡿ࡜ࡋࡓࠋ⟬ฟ᪉ἲ࡜ࡋ ࡚ࡣࠊඛࡎ཯᚟㐠ື࡟࠾࠸࡚ᖹᆒ㌶㊧ࢆồࡵࡿࠋࡑࡢᚋࠊྛ㐠ື㌶㊧࡜ồࡵࡓᖹᆒ㌶㊧࡜ࡢ㊥㞳ࢆィ⟬ࡋࠊࡑࡢྜィࢆ SpDe ࡜ࡋࡓࠋࡉࡽ࡟ࠊࡇࡢ್ࡣ㌶㊧ࡢ㛗ࡉ࡛㝖⟬ ࡍࡿࡇ࡜࡛ࠊ㐠ື㌶㊧ࡢ༢఩㊥㞳࠶ࡓࡾ࡟ㄪᩚࡍࡿࠋ

ࡶ࠺୍ࡘࡢᣦᶆ࡜ࡋ࡚ࠊࠕືసࡢ࡞ࡵࡽ࠿ࡉ㸦Direction Variance: DiVa㸧ࠖ࡟╔┠ࡋ࡚

ືࡁࡢ㉁ࢆᩘ್໬ࡋࡓࠋࡇࢀࡣࠊ⭎ࡢ⛣ື᪉ྥࡀz ㍈᪉ྥ㸦㔜ຊ᪉ྥ㸧࡟ᑐࡋ࡚㐃⥆ ⓗ࡟ኚ໬ࡋ࡚࠸ࡿ࠿࡝࠺࠿࡟↔Ⅼࢆᙜ࡚ࠊ⭎ࡢ⛣ື᪉ྥࢆ♧ࡍ⛣ື࣋ࢡࢺࣝࢆᴟᗙᶆ ⾲⌧࡟ኚ᥮ࡋࡓሙྜ࡟ࠊࡑࡢ➨୍ゅᗘ㸦ȟ㸧ࡢ⤒᫬ⓗኚ໬ࡀ㐃⥆ⓗ࡛࠶ࡿ࠿࡝࠺࠿ࢆ ᩘ್໬ࡋࡓࠋࡇࡢȟᡂศࡣࠊ⭎ࡢືࡁࡢᢠ㔜ຊస⏝࡟཯ᫎࡉࢀࡿࡓࡵࠊ⚾㐩ࡣࡇࡢᡂ ศࢆᑐ㇟⪅ࡀ㔜ຊ࡟ᑐࡋ࡚࠸࠿࡟㐠ືࢆࢥࣥࢺ࣮࡛ࣟࣝࡁ࡚ࠊ࡞ࡵࡽ࠿࡟ୖୗ㐠ືࡀ ᐇ᪋࡛ࡁࡿ࠿ࡢᣦᶆ࡟࡞ࡿ࡜⪃࠼ࡓࠋ ௬࡟ࠊ⌮᝿ⓗ࡞⭎ࡢୖୗ㐠ືࢆ➼㏿࡟༙෇ᘼࢆᥥࡃࡼ࠺࡞㐠ື࡜ࡋࡓࠋࡑࡢሙྜࠊ ȟࡢ್ࡣ┤⥺ⓗ࡟᥎⛣ࡋ࡚࠸ࡃࡇ࡜ࡀ☜ㄆࡉࢀ࡚࠸ࡿࠋࡑࡇ࡛ࠊ⚾㐩ࡣᐇ㝿ࡢ⛣ື࣋ ࢡࢺࣝࡢȟᡂศࡀ࡝ࢀࡔࡅࡑࡢ┤⥺ⓗ࡞ኚ໬࠿ࡽࡎࢀ࡚࠸ࡿ࠿ࢆィ⟬ࡋࠊࡑࡢࡎࢀࢆ ㌶㊧ࡢࠕṍࡳࠖ࡜ࡋࡓࠋࡑࡢࡓࡵࠊ㌶㊧ࡢࠕṍࡳࠖࡀᑡ࡞࠸࡯࡝⛣ື࣋ࢡࢺࣝࡢȟᡂ ศࡀ┤⥺ୖ࡟୪ࡧࠊືసࡀ࡞ࡵࡽ࠿࡛࠶ࡿ࡜ࡋࡓࠋཝᐦ࡟ࡣࠊ㌶㊧ࢆ4 ࡘࡢ༊㛫࡟ศ

(10)

ࡅࡓࡑࢀࡒࢀ࡟ࡘ࠸࡚ࠊ⛣ື࣋ࢡࢺࣝࡢȟᡂศࡢ⤒᫬ኚ໬ࢆࠊ཯᚟෌㔜ࡳ௜ࡅ᭱ᑠ஧ ஌ἲࢆ⏝࠸୍࡚⯡໬⥺ᙧࣔࢹ࡛ࣝ㏆ఝࡋࠊࡑࡢ㏆ఝ್࡜ᐇ㝿ࡢ್࡜ࡢㄗᕪࢆྜィࡋࡓ ࡶࡢࢆࠕ࡞ࡵࡽ࠿ࡉࠖࡢᣦᶆࠊDiVa ࡜ᐃ⩏ࡋࡓࠋ

ࠕ㐠ືࡢ㉁ࠖࡢẚ㍑᪉ἲ࡜⤫ィⓗฎ⌮ࠊ೔⌮ኌ᫂

ᑐ㇟ືస࡜ࡋ࡚ࠊ⫪㛵⠇ࡢᒅ᭤㐠ືࢆ 10 ᅇ཯᚟ࡍࡿືసࢆタᐃࡋ࡚࠾ࡾࠊࡑࡢሙ ྜ10 ಶࡢୖୗ㐠ືࡢ㐠ື㌶㊧ࡀᚓࡽࢀࡿࠋࡑࡋ࡚ࠊ᭱ึ࡜᭱ᚋࡢ㌶㊧ࡣゎᯒ࠿ࡽ㝖እ ࡉࢀࡿࡓࡵࠊ8 ಶࡢ㐠ື㌶㊧ࡀゎᯒࡢᑐ㇟࡜࡞ࡿࠋྛ㐠ື㌶㊧࡟ࡘ࠸࡚ࠊືࡁࡢ㉁ࡀ SpDe ࡜ DiVa ࡜ࡋ࡚ᩘ್໬ࡉࢀࡿࡓࡵࠊ୍ᅇࡢᑐ㇟ືస࡛ྛᣦᶆ࡟ࡘ࠸࡚ 8 ಶࡎࡘࡢ ᩘ್ࡀྛୖୗ㐠ືࡢືࡁࡢ㉁ࢆ♧ࡍ್࡜ࡋ࡚⟬ฟࡉࢀࡿࠋྠ୍ᑐ㇟⪅ࡀ␗࡞ࡿ᮲௳࡛ ືసࢆᐇ᪋ࡋࡓሙྜࠊ2 ࡘࡢ཯᚟ືసࡀグ㘓ࡉࢀࡿࠋࡑࡢ 2 ࡘࡢືస㛫࡛㐠ືࡢ㉁࡟ ኚ໬ࡀ࠶ࡿ࠿࡝࠺࠿ࠊྛᣦᶆ㸦SpDe ࡜ DiVa㸧ࢆ⏝࠸࡚ホ౯ࡍࡿࠋ⤫ィⓗ᳨ᐃࡣ Exact permutation test ࢆ⏝࠸ࡓࠋ᭷ព☜⋡ࢆ 5%࡜ࡋࠊ⤫ィศᯒࢯࣇࢺࠕRࠖ㸦version 3.1.3㸧21

࡜RStudio㸦version 1.1.383㸧⏝࠸࡚ゎᯒࢆ⾜ࡗࡓࠋ

࡞࠾ࠊᐇ㦂࡟ඛ❧ࡗ࡚ࠊ18 ṓ௨ୖࡢ⿕㦂⪅࡟ࡣ᭩㠃࡟ࡼࡿ࢖ࣥࣇ࢛࣮࣒ࢻࢥࣥࢭࣥ ࢺࠊ18 ṓᮍ‶ࡢ⿕㦂⪅࡟ࡣ᭩㠃࡟ࡼࡿぶࡢྠពࢆᚓࡓࠋࡲࡓࠊ◊✲࡟ᑐࡋ࡚ࠊᒱ㜧኱ Ꮫཬࡧᒱ㜧⸆⛉኱Ꮫࡢ೔⌮ᑂᰝጤဨ఍ࡢᢎㄆࢆᚓࡓࠋ

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⤖

⤖ᯝ

ࢣ࣮ࢫ 㸸೺ᖖᡂேࡢሙྜ

ᮏ⠇࡟࠾࠸࡚ࡣࠊ೺ᖖᡂே㸦28 ṓ⏨ᛶ㸧ࡀᑐ㇟㐠ື࡛࠶ࡿ⫪㛵⠇ࡢᒅ᭤㐠ືࢆᐇ᪋ ࡋࡓሙྜ࡟ࠊ࡝ࡢࡼ࠺࡞ືࡁ࡟࡞ࡿࡢ࠿ࠋࡑࡋ࡚ࠊ➽ຊࡀపୗࡋࡓ≧ែࢆࢩ࣑࣮ࣗࣞ ࢩࣙࣥࡍࡿࡓࡵ࡟8 ࢟ࣟࡢࢲࣥ࣋ࣝࢆಖᣢࡋࡓ≧ែ࡛ࡶᒅ᭤㐠ືࢆ⾜࠸ࠊືࡁࡢ㉁ࡀ ࡝ࡢࡼ࠺࡟ኚ໬ࡋࡓࡢ࠿ࢆศᯒࡋࡓࠋᑐ㇟࡜ࡋ࡚࠸ࡿ㐠ືࡣ⭎ࢆୖୗࡉࡏࡿᢠ㔜ຊ㐠 ື࡛࠶ࡿࠋࡑࡢࡓࡵࠊ࠾ࡶࡾࢆಖᣢࡍࡿࡇ࡜࡛␲ఝⓗ࡟㔜ຊࡀቑ࠼ࠊ┦ᑐⓗ࡟➽ຊࡀ పୗࡋࡓ≧ែ࡟࡞ࡿࠋ ⫪㛵⠇ࡢᒅ᭤㐠ືࡢ㌶㊧ ఱࡶಖᣢࡋ࡞࠸≧ែ࡛⫪㛵⠇ࡢᒅ᭤㐠ືࢆᐇ᪋ࡋࡓሙྜࡢ㐠ືࢹ࣮ࢱࢆᅗ 2a ࡟♧ ࡋࠊ࠾ࡶࡾࢆಖᣢࡋࡓ≧ែ࡛ᐇ᪋ࡋࡓ㐠ືࢹ࣮ࢱࢆᅗ 2b ࡟♧ࡍࠋࡇࢀࡽࡢ㌶㊧ࢆẚ ㍑ࡍࡿ࡜ࠊ࠾ࡶࡾࢆಖᣢࡋࡓሙྜࡢ㐠ື㌶㊧㸦ᅗ 2b㸧ࡢ᪉ࡀࠊ࠾ࡶࡾࢆಖᣢࡋ࡞࠸ሙ ྜ࡟ẚ࡭࡚㸦ᅗ 2a㸧ࠊ㐠ື㌶㊧඲యࡢᖜࡶᗈࡃ࡞ࡾࠊྛୖୗ㐠ືࡢ㐠ື㌶㊧ࡶ஋㞳ࡋ ࡚≉ᐃ࡛ࡁࡿࡼ࠺࡟࡞ࡗ࡚࠸ࡿࠋࡲࡓࠊྛ㐠ື㌶㊧ࡢᙧࡶࠊࡑࢀࡲ࡛ࡁࢀ࠸࡞෇ᘼࡀ ᥥࡅ࡚࠸ࡓࡢࡀࠊ࠾ࡶࡾࢆಖᣢࡍࡿࡇ࡜࡛ᙧࡀࡃࡎࢀࠊ㐠ື㌶㊧࡟ṍࡳࡀぢࡽࢀࡿࠋ ࡇࢀࡽࠊ㐠ື㌶㊧ࡢࡃࡎࢀ㸦ṍࡳ㸧࡜ᖜࡢᣑᙇࡀࠊࡑࢀࡒࢀࠊDiVa ࡜ SpDe ࡢ್࡟཯ ᫎࡉࢀࡿࠋྛx,y,z ᡂศࡢ⤒᫬ⓗኚ໬ࡣ Appendix ࢆཧ↷ࡢࡇ࡜ࠋ

(12)

ᅗ ᅗ 2 ೺ᖖᡂேࡀ⫪㛵⠇ࡢᒅ᭤㐠ືࢆ 10 ᅇ⧞ࡾ㏉ࡋࡓ㐠ືࢆ ᐃࡋࡓ㐠ືࢹ࣮ࢱࢆ 3 ḟඖ✵㛫࡟ ࠾ࡅࡿ㐠ື㌶㊧࡜ࡋ࡚෌ᵓᡂ㸸(a)࠾ࡶࡾࢆಖᣢࡏࡎ㐠ືࢆᐇ᪋ࡋࡓሙྜ(b)8kg ࡢ࠾ࡶࡾࢆಖᣢࡋ ࡓ≧ែ࡛ᐇ᪋ࡋࡓሙྜࠋ㐠ື㌶㊧ࢆࡼࡾ᫂☜࡟ࡍࡿࡓࡵ࡟ࠊୖ᪼༊㛫࡜ୗ㝆༊㛫ࡣูࠎࡢࣃࢿࣝ ࡟ᅗ♧ࡋࠊࡑࢀࡒࢀ㸰᪉ྥ࠿ࡽぢࡓ㌶㊧ࢆ♧ࡋࡓࠋ㉥࠸㌶㊧ࡣணഛゎᯒ࡟ࡼࡾୖ᪼༊㛫࡜ࡋ࡚ᢳ ฟࡉࢀࡓࡶࡢࠊ㟷࠸㌶㊧ࡣୗ㝆༊㛫ࢆ♧ࡋ࡚࠸ࡿࠋX,y,z ᡂศࡢ᫬⣔ิኚ໬ࡣ Appendix ࢆཧ↷ࠋ

b㻌

a

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(13)

6 6S'H ࡜ 'L9D ࡟ࡼࡿ㐠ືࡢホ౯ ࡇࡇ࡛ࡣࠊ೺ᖖᡂேࡀ2 ࡘࡢ␗࡞ࡿ≧ែ࡛ᐇ᪋ࡋࡓ㐠ືࡢ㌶㊧࡟ࡘ࠸࡚ࠊࡑࡢ㐪࠸ ࡸኚ໬ࢆࠊࠕ✵㛫⢭☜ᛶࠖSpDe㸦ᅗ 3a㸧࡜ࠕ࡞ࡵࡽ࠿ࡉࠖDiVa㸦ᅗ 3b㸧࡟╔┠ࡋ࡚ ᐃ㔞ⓗ࡟ホ౯ࡋࡓ⤖ᯝࢆ♧ࡍࠋ೺ᖖᡂேࡀ⫪㛵⠇ࡢᒅ᭤㐠ືࢆ10 ᅇ⧞ࡾ㏉ࡋࡓ࡜ࡁࠊ ࡑࡢ཯᚟㐠ືࡢ✵㛫⢭☜ᛶ㸦SpDe㸧ࡣ⭎ࡢ⛣ື㊥㞳࡟ᑐࡋ࡚୰ኸ್࡛ 0.57%㸦IQR 㸦Interquartile range㸦ᅄศ఩⠊ᅖ㸧㸧㸸 0.52–0.69㸧࡛࠶ࡾࠊືసࡢ࡞ࡵࡽ࠿ࡉ㸦DiVa㸧 ࡣ୰ኸ್࡛ 2.09°㸦IQR: 1.31–1.59㸧࡛࠶ࡗࡓࠋࡑࡋ࡚ࠊ࠾ࡶࡾࢆಖᣢࡋࡓ≧ែ࡛ᐇ᪋ ࡋࡓ⫪㛵⠇ࡢᒅ᭤㐠ື࡛ࡣSpDe ࡢ୰ኸ್ࡣ⭎ࡢ⛣ື㊥㞳࡟ᑐࡋ࡚ 1.65㸣㸦IQR: 1.49– 2.50㸧࡛ࠊDiVa ࡣ 4.40°㸦IQR: 3.58–6.27㸧࡛࠶ࡗࡓࠋࡑࡋ࡚ࠊExact permutation test ࡟ ࡼࡿ⤫ィⓗ᳨ᐃ࡛ࠊࡇࢀࡽࡢኚ໬ࡀ᭷ព࡛࠶ࡿ࡜ㄆࡵࡽࢀࡓ㸦SpDe ࡟㛵ࡋ࡚㸸 p=0.00008ࠊDiVa ࡟㛵ࡋ࡚㸸p=0.0037㸧ࠋ࠾ࡶࡾࢆಖᣢࡍࡿࡇ࡜࡛ SpDe ࡢ್ࡀ 2.9 ಸ࡟ ቑຍࡋࠊDiVa ࡢ್ࡣ 2.1 ಸ࡟ቑຍࡋࡓࠋ༶ࡕࠊSpDe ࡜ DiVa ࡟╔┠ࡋࡓホ౯ᣦᶆࢆ⏝ ࠸ࡿࡇ࡜࡛ࠊ࠾ࡶࡾࢆಖᣢࡍࡿࡇ࡜࡟ࡼࡿ㐠ືᶵ⬟ࡢపୗࢆࠊ᭷ព࡞ᕪ࡜ࡋ࡚ᐃ㔞ⓗ ࡟᳨ฟࡍࡿࡇ࡜ࡀྍ⬟࡛࠶ࡿࡇ࡜ࡀ♧ࡉࢀࡓࠋ

(14)

ᅗ ᅗ 3 㐠ືᶵ⬟ホ౯ᣦᶆࢆ⏝࠸࡚⫪㛵⠇ࡢᒅ᭤㐠ືࡢ㐠ື㌶㊧ࢆᐃ㔞ⓗ࡟ホ౯ࠋ೺ᖖᡂேࢆᑐ㇟ ࡜ࡋ࡚ࠊ࠾ࡶࡾࡢಖᣢࡢ᭷↓࡟ࡼࡗ࡚⏕ࡌࡓ㐠ື㌶㊧ࡢኚ໬ࢆࠊ(a)ࠕ✵㛫⢭☜ᛶ㸦SpDe㸧ࠖ࡜(b) ࠕ࡞ࡵࡽ࠿ࡉ㸦DiVa㸧ࠖ࡟╔┠ࡋ࡚ホ౯ࡋࡓ࡜ࡇࢁࠊ࡝ࡕࡽࡢᣦᶆ࡟㛵ࡋ࡚ࡶ᭷ព࡟ୖ᪼ࡋࡓ㸦SpDe ࡟㛵ࡋ࡚㸸p=0.00008ࠊDiva ࡟㛵ࡋ࡚㸸p=0.0037㸧ࠋ

ࢣ࣮ࢫ㸰㸸,, ᆺ 60$ ᝈ⪅ࠊ75+ ⒪ἲࡢ᭷ຠᛶホ౯

ᮏ⠇࡛ࡣࠊᑐ㇟ࢆṌ⾜୙ྍ⬟࡞II ᆺ SMA ᝈ⪅࡜ࡋ࡚ࠊୖ⫥ࡢ㐠ືᶵ⬟ࢆホ౯ࡋࡓ ⤖ᯝࢆ♧ࡍࠋࡲࡓࠊᙜヱᝈ⪅࡟ TRH ࢆ⥅⥆ⓗ࡟ᢞ୚ࡋࠊࡑࡢ἞⒪ࡢ๓ᚋ࡛㐠ືᶵ⬟

a

㻌

b

㻌

(15)

ࡢホ౯ࢆẚ㍑ࡋࡓࠋᑐ㇟ᝈ⪅ࡣṌ⾜ࡀ୙ྍ⬟࡛࠶ࡿࡓࡵࠊᚑ᮶ࡢṌ⾜ゎᯒࡣ㐺ᛂ࡛ࡁ ࡎࠊࡲࡓࠊTRH ࡢ᭷ຠᛶࡶᚑ᮶ࡢ㐠ືᶵ⬟ホ౯ࢫࢣ࣮࡛ࣝࡣ᳨ฟࡀ࡛ࡁ࡞࠸ࠋࠕ✵㛫 ⢭☜ᛶ㸦SpDe㸧ࠖ࡜ࠕືసࡢ࡞ࡵࡽ࠿ࡉ㸦DiVa㸧ࠖ࡟╔┠ࡋࡓᐃ㔞ⓗ࡞㐠ືᶵ⬟ホ౯࡛ ࠶ࢀࡤࠊṌ⾜୙ྍ⬟࡞ᑐ㇟⪅࡬ࡶ㐺ᛂࡀྍ⬟࡛࠶ࡾࠊࡇࢀࡲ࡛ホ౯࡛ࡁ࡞࠿ࡗࡓTRH ࡢSMA ࡟ᑐࡍࡿ᭷ຠᛶ࡟ࡘ࠸࡚ࡶホ౯ࡀྍ⬟࡜࡞ࡗࡓࠋ ᝈ ᝈ⪅⫼ᬒ࡜ 75+ ⒪ἲࡢヲ⣽ ᑐ㇟ᝈ⪅ࡣ 3.3 ṓࡢ⏨ඣ࡛ࠊ㑇ఏᏊࢸࢫࢺ࡟ࡼࡾ SMA ࡛࠶ࡿࡇ࡜ࡀ☜ᐃデ᩿ࡉࢀ ࡚࠸ࡿࠋⓎ⑕ࡢ᫬ᮇ࠿ࡽ II ᆺ࡛࠶ࡾࠊࠕ࠾ᗙࡾࠖࡀ࡛ࡁࡓ᫬ᮇࡀ 6 ࣨ᭶࡛࠶ࡗࡓࡢ࡛ IIb ᆺ࡟ศ㢮ࡉࢀࡿ22_{ࠋ㐠ືᶵ⬟ࡢ᭱㧗฿㐩Ⅼࡣࠕఏ࠸Ṍࡁ࡛ࠖ}_{1 ṓࡢ࡜ࡁ࡟ࡣฟ᮶ࡓ} ࡀࠊࡑࡢᚋࠊᛴ⃭࡟㐠ືᶵ⬟ࡀపୗࡋ࡚ࠊ1 ṓ 5 ࣧ᭶࡛ࡣฟ᮶࡞ࡃ࡞ࡗ࡚࠸ࡓࠋࡑࡢ ࡓࡵࠊࡇࢀࡲ୍࡛ே࡛Ṍ࠸ࡓ⤒㦂ࡣ࡞࠸ࠋࡲࡓࠊ἞⒪ࢆ㛤ጞࡋࡓ࡜ࡁ࡟ࡣࠊ㐠ືᶵ⬟ ࡢపୗࡣ㐍ࢇ࡛࠾ࡾࠊⓎ㐩࡟ࡼࡿ㐠ືᶵ⬟ࡢኚ໬ࡣ⪃࠼࡞࠸ࡶࡢ࡜ࡍࡿࠋ ࡇࡢᝈ⪅࡟ᑐࡋ࡚TRH ⒪ἲࢆ᪋ࡋࡓࠋ4 㐌㛫ࡢࣉࣟࢺࢥ࡛ࣝ㟼⬦ὀᑕ࡛ࡢᢞ୚࡛࠶ ࡿࠋ᭱ึࡢ3 ᪥㛫ࡣᑟධᮇ࡜ࡋ࡚ࠊᢞ୚㔞ࢆ 0.3ࠊ0.5ࠊ1.0mg ࡜ᚎࠎ࡟ቑࡸࡋ࡚࠸ࡁࠊ 1.4mg㸦0.1mg/kg㸧ࡲ࡛ቑ㔞ࡋ࡚࠸ࡗࡓࠋ᭶᭙᪥࠿ࡽ㔠᭙᪥࡟ᢞ୚ࡋࠊᅵ᭙᪥࡜᪥᭙᪥ ࡣఇ⸆ࡋࡓࠋ ୗ⫥ࡢ㐠ືᶵ⬟ࡣ࡯ࡰኻࢃࢀ࡚ࡋࡲࡗ࡚࠾ࡾࠊୖ⫥ࡢ㐠ືᶵ⬟ࡶᚎࠎ࡟పୗࡀㄆࡵ ࡽࢀ࡚࠸ࡿࠋᚑ᮶ࡢ㐠ືᶵ⬟ホ౯ࢫࢣ࣮࡛ࣝ࠶ࡿHFMS ࡢホ౯㡯┠ࡢ୍ࡘࠕᆘ఩࡛∦ ᡭࢆᣲࡆࡿࠖືస࡛ࡣࠊࡂࡇࡕ࡞ࡃ࡛ࡣ࠶ࡿࡀၥ㢟࡞ࡃᡭࡀᣲࡆࡽࢀࡿࡢ࡛ࢫࢥ࢔ࡣ 2 Ⅼ࡛࠶ࡾࠊ἞⒪ᚋࡶྠᵝ࡛࠶ࡗࡓࠋHFMS ඲య࡛ࡣ἞⒪๓ࠊ἞⒪ᚋඹ࡟ 21 Ⅼ࡛࠶ࡾࠊ ኚ໬ࡣ࡞࠿ࡗࡓࠋࡑࡢࡓࡵࠊࡇࢀࡲ࡛ࡢホ౯᪉ἲ࡛ࡣࠕ἞⒪ຠᯝ࡞ࡋࠖ࡜ࡉࢀ࡚࠸ࡓࠋ ࡋ࠿ࡋ࡞ࡀࡽࠊ⮫ᗋⓗ࡞ぢᆅ࠿ࡽ࡛ࡣࠊ␗࡞ࡿホ౯ࢆୗࡋ࡚࠸ࡓࠋ4 㐌㛫ࡢ἞⒪๓ᚋ ࢆ௘⣽࡟ほᐹࡋ࡚࠸ࡓᢸᙜ་ࡸ⌮Ꮫ⒪ἲኈࢆྵࡴ」ᩘࡢ་⒪ᚑ஦⪅ࡀࠊᡭࡢᣲࡆ᪉ࡀ Ⰻዲ࡟࡞ࡗࡓ༳㇟ࢆᣢࡗ࡚࠾ࡾࠊᝈ⪅ࡢぶ࡛ࡉ࠼ࡶ᪥ᖖ⏕άࡢ୰࡛㐠ືᶵ⬟ࡀྥୖࡋ ࡚࠸ࡿࡇ࡜ࢆ୺ᙇࡋ࡚࠸ࡿࠋ

(16)

ᅗ ᅗ 4 Ṍ⾜୙ྍ⬟࡞ II ᆺ SMA ᝈ⪅ࡀ⫪㛵⠇ࡢᒅ᭤㐠ືࢆ 10 ᅇ⧞ࡾ㏉ࡋࡓ㐠ືࢆ ᐃࡋࡓ㐠ື ࢹ࣮ࢱࢆ3 ḟඖ✵㛫࡟࠾ࡅࡿ㐠ື㌶㊧࡜ࡋ࡚෌ᵓᡂ㸸(a)4 㐌㛫ࡢ TRH ⒪ἲࢆᐇ᪋ࡍࡿ๓(b)4 㐌㛫 ࡢTRH ⒪ἲࢆᐇ᪋ࡋࡓᚋࠋ㐠ື㌶㊧ࢆࡼࡾ᫂☜࡟ࡍࡿࡓࡵ࡟ࠊୖ᪼༊㛫࡜ୗ㝆༊㛫ࡣูࠎࡢࣃࢿ ࣝ࡟ᅗ♧ࡋࠊࡑࢀࡒࢀ㸰᪉ྥ࠿ࡽぢࡓ㌶㊧ࢆ♧ࡋࡓࠋ㉥࠸㌶㊧ࡣணഛゎᯒ࡟ࡼࡾୖ᪼༊㛫࡜ࡋ࡚ ᢳฟࡉࢀࡓࡶࡢࠊ㟷࠸㌶㊧ࡣୗ㝆༊㛫ࢆ♧ࡋ࡚࠸ࡿࠋX,y,z ᡂศࡢ᫬⣔ิኚ໬ࡣ Appendix ࢆཧ↷ࠋ

a㻌

b㻌

(17)

, ,, ᆺ 60$ ᝈ⪅࡟࠾ࡅࡿ⫪㛵⠇ࡢᒅ᭤㐠ືࡢ㌶㊧ Ṍ⾜୙ྍ⬟࡞ II ᆺ SMA ᝈ⪅ࡀᐇ᪋ࡋࡓ⭎ࡢୖୗࢆ 10 ᅇ⧞ࡾ㏉ࡍ཯᚟ືసࡢ㐠ື ࢹ࣮ࢱࢆᅗ 4a ࡟♧ࡋࠊ4 㐌㛫ࡢ TRH ࡟ࡼࡿ἞⒪ࡢᚋࠊ෌ᗘィ ࡋࡓྠᵝࡢືసࡢ㐠 ືࢹ࣮ࢱࢆᅗ 4b ࡟♧ࡍࠋ἞⒪๓ᚋࠊ࡝ࡕࡽࡢ㐠ື㌶㊧࡟㛵ࡋ࡚ࡶࠊ㌶㊧ࡢ㔜࡞ࡾྜ ࠸ࡀ࡞ࡃࠊࡑࢀࡒࢀࡀゎ㞳ࡋ࡚࠾ࡾ⢭☜࡟཯᚟ືసࡀ⾜ࢃࢀ࡚࠸࡞࠸ࡇ࡜ࡀぢཷࡅࡽ ࢀࠊ✵㛫࡟࠾ࡅࡿ㌶㊧ࡀ༨ࡵࡿᖜࡶᗈ࠸ࠋࡉࡽ࡟ࠊ෇ᘼࡢᙧ≧ࡶṍࢇ࡛࠸ࡿࡇ࡜ࡀุ ࡿࠋ἞⒪ࡢ๓ᚋ࡛3 ḟඖ✵㛫࡟࠾ࡅࡿ㐠ື㌶㊧ࢆẚ㍑ࡋ࡚ࡶࠊ⭎ࡢୖୗ㐠ືࡢ㉁ࡀᨵ ၿࡉࢀࡓ࡜᩿ᐃࡍࡿࡇ࡜ࡣ㞴ࡋ࠸ࠋࡑࡇ࡛ࠊḟࡢ㡯࡛ࡣࠕ཯᚟㐠ືࡢ✵㛫⢭☜ᛶ㸦SpDe㸧ࠖ ࡜ࠕືసࡢ࡞ࡵࡽ࠿ࡉ㸦DiVa㸧ࠖࢆ⟬ฟࡍࡿࡇ࡜࡛ࠊどぬⓗࡶࡋࡃࡣ༙ᐃ㔞ⓗ࡟᳨ฟ ࡍࡿࡇ࡜ࡀ࡛ࡁ࡞࠿ࡗࡓ㐠ືࡢ㉁ࡢኚ໬ࢆホ౯ࡍࡿࠋྛ x,y,z ᡂศࡢ⤒᫬ⓗኚ໬ࡣ Appendix ࢆཧ↷ࡢࡇ࡜ࠋ 6S'H ࡜ 'L9D ࡟ࡼࡿ 75+ ࡢ᭷ຠᛶホ౯ ᅗ 5 ࡟࠾࠸࡚ࠊṌ⾜୙ྍ⬟࡞ II ᆺ SMA ᝈ⪅ࡀ 4 㐌㛫ࡢ TRH ࡟ࡼࡿ἞⒪ࡢ๓ᚋ࡛ ᐃࡋࡓ⭎ࡢୖୗ㐠ື࡟ࡘ࠸࡚ࠊࠕ✵㛫⢭☜ᛶ㸦SpDe㸧ࠖ࡜ࠕ࡞ࡵࡽ࠿ࡉ㸦DiVa㸧ࠖ࡟ ╔┠ࡋ࡚ᐃ㔞ⓗ࡟ホ౯ࡋࡓ⤖ᯝࢆ♧ࡍࠋ࡞࠾ࠊ἞⒪๓࡟ ᐃࡋࡓ㐠ືᶵ⬟ࡣ SpDe㸸

3.97% (IQR: 3.49̽4.82)ࠊDiVa㸸13.45° (IQR: 11.02–15.82)࡛࠶ࡾࠊ࡝ࡕࡽࡶ೺ᖖᑠඣ࡟ ẚ࡭ࡿ࡜㢧ⴭ࡟㧗࠸್ࠊ༶ࡕప࠸㐠ືᶵ⬟ࢆ♧ࡋ࡚࠸ࡓ㸦Appendix ᅗཧ↷㸧ࠋSpDe㸦ᅗ 5a㸧࡟㛵ࡋ࡚ࡣࠊ἞⒪ࡢ๓ᚋ࡛ⱝᖸపୗࡋࡓഴྥࡣぢࡽࢀࡿࡀࠊ㢧ⴭ࡛ࡣ࡞ࡃࠊ⤫ィ ⓗ࡟ࡶ᭷ព࡛ࡣ࡞࠸(3.97% (IQR: 3.49̽4.82) vs. 3.84% (IQR: 3.14–4.38), p=0.264)ࠋ୍᪉ ࡛ࠊDiVa㸦ᅗ 5b㸧࡟㛵ࡋ࡚ࡣࠊ἞⒪ᚋࡢ್࡟⤫ィⓗ᭷ព࡞పୗࡀࡳࡽࢀ(13.45° (IQR: 11.02–15.82) vs. 6.69° (IQR: 5.49–8.02), p=0.0006)ࠊࠕືసࡢ࡞ࡵࡽ࠿ࡉࠖࡀྥୖࡋࡓࡇ࡜ ࡀ♧ࡉࢀࡓࠋࡇࢀ࡟ࡼࡾࠊ4 㐌㛫ࡢ TRH ࡟ࡼࡿ἞⒪ࡢ᭷ຠᛶࢆࠊDiVa ࡟㛵ࡍࡿ 50% ࡢపୗ࡟ࡼࡗ࡚♧ࡉࢀࡿ㐠ືᶵ⬟ࡢྥୖ࡜ࡋ࡚ᐃ㔞ⓗ࡟ホ౯࡛ࡁࡓࠋࡋ࠿ࡋ࡞ࡀࡽࠊ ἞⒪ᚋ࡛࠶ࡗ࡚ࡶ೺ᖖඣ࡜ẚ㍑ࡍࡿ࡜ࠊᮍࡔDiVa ࡣ㢧ⴭ࡟㧗࠸್ࢆ♧ࡋ࡚࠸ࡓࠋ

(18)

ᅗ

ᅗ 5 㐠ືᶵ⬟ホ౯ᣦᶆࢆ⏝࠸࡚ࠊṌ⾜୙ྍ⬟࡞ II ᆺ SMA ᝈ⪅࡟ᑐࡍࡿ TRH ⒪ἲࡢ᭷ຠᛶࢆᐃ

㔞ⓗ࡟ホ౯㸸4 㐌㛫ࡢ TRH ⒪ἲࡢ๓ᚋ࡛⏕ࡌࡓ㐠ື㌶㊧ࡢኚ໬ࢆࠊ(a)ࠕ✵㛫⢭☜ᛶ㸦SpDe㸧ࠖ࡜ (b)ࠕ࡞ࡵࡽ࠿ࡉ㸦DiVa㸧ࠖ࡟╔┠ࡋ࡚ホ౯ࡋࡓ࡜ࡇࢁࠊ࡝ࡕࡽࡢᣦᶆ࡟㛵ࡋ࡚ࡶῶᑡഴྥࡣࡳࡽ

ࢀࠊ≉࡟DiVa ࡟㛵ࡋ࡚ࡣ᭷ព࡞ῶᑡ࡛࠶ࡗࡓ㸦SpDe ࡟㛵ࡋ࡚㸸p=0.264ࠊDiva ࡟㛵ࡋ࡚㸸p=0.0006㸧ࠋ

b

a

㻌

(19)

⪃

⪃ᐹ

ୖ⫥ࡢ㐠ືᶵ⬟ࢆホ౯ࡍࡿࡓࡵ࡟3 ḟඖ࣮ࣔࢩࣙࣥ࢟ࣕࣉࢳࣕࢩࢫࢸ࣒ࢆ⏝࠸ࡿࡇ ࡜ࡣ᳨ウࡉࢀ࡚࠸ࡿ23_{ࠋ౛࠼ࡤࠊ}_{Petuskey, et al.}24_{ࡽࡣ᭷⏝࡞㐠ືᶵ⬟ホ౯ᣦᶆ࡜ࡋ࡚ࠊ} ⫪㛵⠇ࡸ⫝㛵⠇࡜࠸ࡗࡓ≉ᐃࡢ㛵⠇࡟࠾ࡅࡿసᴗ㐩ᡂ᫬Ⅼ࡛ࡢ⮬ືⓗ㛵⠇ྍືᇦ㸦⮬ ࡽࡢពᛮ࡜➽ຊ࡛㝶ពⓗ࡟ື࠿ࡍࡇ࡜ࡀ࡛ࡁࡿ㛵⠇ྍືᇦ㸧ࢆ⏝࠸ࡿࡇ࡜ࢆ㆟ㄽࡋ࡚ ࠸ࡿࠋࡲࡓࠊ②ᨥᛶ༙㌟㯞⑷ࢆ࿊ࡋ࡚࠸ࡿ⬻༞୰ᝈ⪅࡟࠾࠸࡚ࡣࠊ㯞⑷ࢆ㉳ࡇࡋ࡚࠸ ࡿഃࡢ⭎࡜㉳ࡇࡋ࡚࠸࡞࠸ഃࡢ⭎ࢆẚ㍑ࡋ࡚ࠊ⫝㛵⠇ࡢྍືᇦࡀ㢧ⴭ࡟㐪࠺ࡇ࡜ࢆ♧ ࡋ࡚࠸ࡿ 25_{ࠋణࡋࠊ඲㌟ࡢ➽ຊపୗࢆᘬࡁ㉳ࡇࡍ⚄⤒➽⑌ᝈ࡟࠾࠸࡚ࡣ㛵⠇ྍືᇦ࡬} ࡢ┤᥋ⓗ࡞ᙳ㡪ࡣᑡ࡞࠸ࡓࡵࠊṇ☜࡟㐠ືᶵ⬟ࢆホ౯ࡍࡿࡓࡵ࡟ࡣࠊࡇࢀࡲ࡛࡜ࡣ␗ ࡞ࡿᐃ㔞ⓗ࡞ホ౯ᣦᶆࡀᚲせ࡛࠶ࡗࡓࠋࡑࡇ࡛ࠊ⚾㐩ࡣ⚄⤒➽⑌ᝈ࡬ࡢᛂ⏝ࡀྍ⬟࡞ ୖ⫥㐠ືᶵ⬟ࡢホ౯ᣦᶆ࡜ࡋ࡚2 ࡘࡢᣦᶆ㸦SpDeࠊDiVa㸧ࢆ⪃᱌ࡋࡓࠋᑐ㇟࡜࡞ࡿ㐠 ືࡣ⭎ࡢୖୗ㐠ືࢆ10 ᅇ⧞ࡾ㏉ࡍືస࡜ࡋ࡚ࠊዴఱ࡟཯᚟㐠ືࢆ⢭☜࡟⧞ࡾ㏉ࡍࡇ࡜ ࡀ࡛ࡁࡿ࠿࡟╔┠ࡋࡓࠕ3 ḟඖ✵㛫࡟࠾ࡅࡿ཯᚟㐠ືࡢ⢭☜ᛶ㸦SpDe㸧ࠖ࡜ືసࡢ㐃⥆ ᛶ࠿ࡽ㌶㊧ࡢࠕṍࡳࠖ࡟╔┠ࡋ࡚ࠕືసࡢ࡞ࡵࡽ࠿ࡉ㸦DiVa㸧ࠖࢆ᳨ウࡋࡓࠋࠕືసࡢ ࡞ࡵࡽ࠿ࡉ㸦DiVa㸧ࠖࡣᑐ㇟㐠ືࡢ࣓࢝ࢽ࢝ࣝࣔࢹࣝࢆ᝿ᐃࡋࠊ⌮᝿ⓗ࡞㐠ື㌶㊧ࢆ ᥥࡃሙྜ࡟⛣ື࣋ࢡࢺࣝࢆᴟᗙᶆ⾲⌧ࡋࡓ࡜ࡁࡢ➨୍ゅᗘߠࡀ┤⥺ⓗ࡟᥎⛣ࡍࡿࡇ࡜ ࢆ฼⏝ࡋ࡚࠸ࡿࠋ ⪃᱌ࡋࡓ2 ࡘࡢホ౯ᣦᶆࡢ᭷⏝ᛶࢆ᳨ドࡍࡿࡓࡵ࡟ࠊඛࡎࡣ೺ᖖ⪅ࢆᑐ㇟࡜ࡋ࡚㐠 ືᶵ⬟ࡢኚ໬࡛ࡇࢀࡽࡢᣦᶆࡀ࡝ࡢࡼ࠺࡟ኚ໬ࡍࡿ࠿ࢆㄪ࡭ࡓࠋࡇࡢሙྜࡢ㐠ືᶵ⬟ ࡢపୗࡣࠊ࠾ࡶࡾࢆಖᣢࡍࡿࡇ࡜࡛➽ຊపୗࢆᶍࡋࡓࠋ࠾ࡶࡾࢆಖᣢࡋࡓ≧ែ࡛ࡢ㐠 ື㌶㊧࡜࠾ࡶࡾࢆಖᣢࡋ࡞࠸≧ែ࡛ࡢ㐠ື㌶㊧ࢆẚ㍑ࡍࡿ࡜ࠊ㢧ⴭ࡟㐠ື㌶㊧ࡀኚ໬ ࡋࡓࠋࡇࢀࡽࡢ㐠ື㌶㊧ࢆ⪃᱌ࡋࡓᣦᶆ࡛ホ౯ࡋࡓ࡜ࡇࢁࠊSpDe ࡜ DiVa ࡜ࡶ࡟᭷ព ࡞ᕪ࡜ࡋ࡚㐠ືᶵ⬟ࡢኚ໬ࢆ᳨ฟ࡛ࡁࡓࠋࡑࡢࡇ࡜࠿ࡽࠊࡇࢀࡽࡢ᪂ࡓ࡟⪃᱌ࡋࡓࠕ⢭ ☜ᛶࠖ࡜ࠕ࡞ࡵࡽ࠿ࡉࠖࡢᣦᶆࡀ㐠ືᶵ⬟ࡢᐃ㔞ⓗホ౯࡟᭷⏝࡛࠶ࡿࡇ࡜ࡀ♧၀ࡉࢀ ࡓࠋ

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SpDe ࡣ 3 ḟඖ✵㛫࡟࠾ࡅࡿ཯᚟㐠ືࡢ⢭☜ᛶ࡟╔┠ࡋࡓᣦᶆ࡛࠶ࡾࠊ཯᚟㐠ືࡀ ⢭☜࡟ᐇ᪋ࡉࢀࡓሙྜ࡟ࡣࠊࡑࢀࡒࢀࡢືసࡢ㌶㊧ࡀ㔜࡞ࡾ࠶࠺ࠋ୍᪉࡛ࠊ㐠ືᶵ⬟ ࡀపୗࡍࡿ࡜ࠊࡑࡢ⢭☜ᛶࡀୗࡀࡾࡑࢀࡒࢀࡢ㌶㊧ࡀ㔜࡞ࡽࡎࠊゎ㞳ࡋ࡚ࡋࡲ࠺ࠋ౛ ࠼ࡤࠊMetzger, et al. 26_{ࡽࡣ⩏ᡭࢆ౑⏝ࡋ࡚࠸ࡿᝈ⪅ࡀࠊ⭎ࢆື࠿ࡍ㝿࡟⬗యࢆ㐣๫࡟} ๓ᚋᕥྑ࡟ື࠿ࡋ࡚࠸ࡿࡇ࡜ࢆグ㘓ࡋ࡚࠾ࡾࠊࡼࡾ኱ࡁࡃᙉ࠸➽⫗ࢆ౑࠺௦ൾ㐠ືࡀ ཯᚟㐠ືࢆ⢭☜࡟⾜࠺ጉࡆ࡜࡞ࡾࠊSpDe ࡢ್ࢆቑຍࡉࡏ࡚࠸ࡿ࡜⪃࠼ࡽࢀࡿࠋ⮫ᗋ⌧ ሙ࡛ࡣࠊసᴗ࡟࠾࠸࡚ྛ㐠ື㌶㊧ࢆほᐹࡋẚ㍑ࡍࡿࡇ࡜ࡣ࡛ࡁ࡞࠸ࡀࠊ་⒪ᚑ஦⪅ࡽ ࡣᑐ㇟⪅ࡢ୙ᚲせ࡞యࡢືᦂࡸ௦ൾ㐠ືࢆ㐠ືᶵ⬟ࡢపୗ࡜ࡋ࡚ᤊ࠼࡚࠸ࡿࠋ༶ࡕࠊ SpDe ࢆ⏝࠸ࡿࡇ࡜࡛ࠊ⮫ᗋ་ࡸ་⒪ᚑ஦⪅ࡀ⮫ᗋ⌧ሙ࡛ㄆ㆑ࡋ࡚࠸ࡿ㐠ືᶵ⬟ࡢపୗ ࢆᐃ㔞ⓗ࡟⾲⌧࡛ࡁࡿ࡜⪃࠼ࡽࢀࡿࠋ DiVa ࡣ⌮᝿ⓗ࡛㐃⥆ⓗ࡞෇ᘼ㐠ື࡜ẚ㍑ࡍࡿࡇ࡜࡛ࠊ㐠ື㌶㊧ࡢṍࡳࡸ࡞ࡵࡽ࠿ࡉ ࢆ⾲⌧ࡋ࡚࠸ࡿࠋືែゎᯒࢆ⏝࠸ࡿࡇ࡜࡛ࠊ༙㌟୙㝶ࢆ࿊ࡋ࡚࠸ࡿ⬻༞୰ᝈ⪅ࡢᅇ᚟ 㐣⛬࡟࠾࠸࡚ࠊືࡁࡀࡼࡾ⁥ࡽ࠿࡟࡞ࡗ࡚࠸ࡃ࡜ࡉࢀ࡚࠸ࡿ 27,28_{ࠋືసࡢࠕ࡞ࡵࡽ࠿} ࡉࠖࡣࠊࡇࢀࡲ࡛ࡶ㐠ືࣃࣇ࢛࣮࣐ࣥࢫࡢᣦᶆ࡜ࡋ࡚౑⏝ࡉࢀ࡚࠾ࡾࠊ⬻༞୰࠿ࡽࡢ ᅇ᚟㐣⛬ࢆ◊✲ࡍࡿࡓࡵ࡟ᵝࠎ࡞ࠕ࡞ࡵࡽ࠿ࡉࠖࡢᣦᶆࡀᥦ᱌ࡉࢀ࡚࠸ࡿ29_ࠋ_Senesac,

et al. 30 _{ࡽࡣࠊ⬻༞୰ᝈ⪅ࡢࣜࣁࣅࣜࢸ࣮ࢩࣙࣥ࡟ᑐࡍࡿ} _{repetitive rhythmic bilateral}

training 㸦୧ᡭࢆྠ᫬࡟ࠊణࡋ⊂❧ࡋ࡚ࠊࣜࢬ࣒࡟ྜࢃࡏ࡚⧞ࡾ㏉ࡍカ⦎㸧ࡢ⮫ᗋⓗ ᭷ຠᛶࢆホ౯ࡍࡿࡓࡵ࡟ࠊᡭࡢ㌶㊧ࡢ᭤ࡀࡾලྜࡸ᭱㧗㏿ᗘ࡜࠸ࡗࡓᣦᶆ࡟ຍ࠼࡚ࠊ Peaks Metric ࢆࠕ࡞ࡵࡽ࠿ࡉࠖࡢᣦᶆ࡜ࡋ࡚౑⏝ࡋ࡚࠸ࡿࠋPeak Metric ࡣ㡰ᗎኚᩘ࡛ ࠶ࡾࠊ㏿ᗘኚ໬࡟࠾ࡅࡿࣆ࣮ࢡࡢᩘࢆ⾲ࢃࡋ࡚࠸ࡿ 29_{ࠋ༶ࡕࠊ㏿ᗘኚ໬࡟ࣆ࣮ࢡࡀᑡ} ࡞࠸࡜✺↛ࡢ೵Ṇࡸືࡁࡢ㛤ጞࡀ࡞࠸ࡇ࡜ࢆព࿡ࡋ࡚࠾ࡾࠊࢠࢡࢩࣕࢡࡋ࡞࠸⁥ࡽ࠿ ࡞ືࡁ࡜ࡋ࡚࠸ࡿ 30ࠋࡇࡢࠕ࡞ࡵࡽ࠿ࡉࠖࡢᣦᶆࡣࠊ㏿ᗘኚ໬ࡸຍ㏿ᗘኚ໬ࢆ⪃៖ࡋ ࡚ࠊືࡁࡢ㔞ⓗ࡞ࡵࡽ࠿ࡉࢆ཯ᫎࡋ࡚࠸ࡿ࡜࠸࠼ࡿࡀࠊ⚾㐩ࡀ⪃᱌ࡋࡓࠕ࡞ࡵࡽࡉ࠿ࠖ ࡢᣦᶆࡣືࡁࡢ㐃⥆ⓗ࡞᪉ྥኚ໬ࡢ࡞ࡵࡽ࠿ࡉࢆホ౯ࡋ࡚࠾ࡾࠊ㐠ື㌶㊧ࡢ࡞ࡵࡽ࠿ ࡞ᙧ࡜ࡋ࡚⾲⌧ࡉࢀࡿࡶࡢ࡛࠶ࡿࠋࡇࢀࡽ2 ࡘࡢᣦᶆࡣ㐠ືࡢ␗࡞ࡿ≉ᚩࢆᤊ࠼࡚࠸

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ࡶ࠶ࡾࠊ┦཯ࡍࡿࡶࡢ࡛ࡣ࡞࠸ࠋࡴࡋࢁࠊ⤌ࡳྜࢃࡏࡿࡇ࡜࡛⚄⤒➽⑌ᝈᝈ⪅ࡸ༙㌟㯞⑷ࢆ࿊ࡋࡓ⬻༞୰ᝈ⪅ࡢ㐠ືᶵ⬟ኚ໬ࢆ⤫୍ⓗ࡟ᢅ࠺ࡇ࡜ࡀ࡛ࡁࠊ㐠ືᶵ⬟㞀ᐖ࡟ 㛵ࡋ࡚᪂ࡓ࡞▱ぢࡀᚓࡽࢀࡿࡇ࡜ࡀᮇᚅ࡛ࡁࡿࠋ ௒ᅇ㛤Ⓨࡋࡓᡭἲࡀ⚄⤒➽⑌ᝈ࡟㐺ᛂࡀྍ⬟࡛࠶ࡿࡇ࡜ࢆᐇドࡍࡿࡓࡵ࡟ࠊTRH ࡛἞⒪ࢆ᪋ࡋࡓṌ⾜୙ྍ⬟࡞ II ᆺ SMA ᝈ⪅ࡢ㐠ືᶵ⬟ࢆホ౯ࡋࠊ἞⒪๓ᚋ࡛ゎᯒ⤖ ᯝࢆẚ㍑ࡋࡓࠋTRH ࡣ⬨㧊ࡢ๓ゅ⣽⬊ࡢ⚄⤒⣔࡟ᑐࡋ࡚ඃඛⓗ࡟స⏝ࡍࡿ࡜⪃࠼ࡽࢀ ࡚࠾ࡾ31_ࠊ_{Ohuchi, et al.}20_ࡽࡣ_{SMA ᝈ⪅⏤᮶ࡢ iPS ⣽⬊ࢆ⏝࠸ࡓᐇ㦂ࡼࡾࠊTRH ࡀ SMN}

ࢱࣥࣃࢡࢆቑᖜࡋᏳᐃ໬ࡉࡏࡿ࡜࡜ࡶ࡟ࠊ⬨㧊㐠ືࢽ࣮ࣗࣟࣥ࡟࠾ࡅࡿ⚄⤒㍈⣴ࡢఙ 㛗ࢆಁ㐍ࡍࡿస⏝ࡀ࠶ࡿࡇ࡜ࢆሗ࿌ࡋ࡚࠸ࡿࠋ⮫ᗋⓗ࡟ࡶࠊ㟼⬦ᢞ୚ 20,32_{࡜⤒ཱྀᢞ୚} 17_{ࡢ୧᪉ࡢᢞ୚⤒㊰࡛ࠊ}_{TRH ࡢ᭷ຠᛶࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋ௒ᅇࡢ TRH ࢆ⏝࠸ࡓ἞⒪} ࡟࠾࠸࡚ࡶࠊ⭎ࡢືࡁ࡟㛵ࡋ࡚どぬⓗ࡟࡛ࡣ࠶ࡿࡀ࠿࡞ࡾࡢᨵၿࡀㄆࡵࡽࢀࠊᢸᙜ་ ࡽ࡟ࡼࡗ࡚ྠᵝࡢ⮫ᗋⓗ᭷ຠᛶࡀ♧၀ࡉࢀ࡚࠸ࡿࠋTRH ἞⒪࡟ࡼࡗ࡚ࠊ⭎ࡢືࡁࡀ ࡋࡗ࠿ࡾ࡜Ᏻᐃࡋ࡚ࠊຊᙉࡃ࡞ࡵࡽ࠿࡟࡞ࡗࡓ༳㇟ࢆᢸᙜࡋࡓ་⒪ᚑ஦⪅ࡽࡀཷࡅ࡚ ࠸ࡿࠋྠ᫬࡟ࠊᝈ⪅⮬㌟ࡶ⭎ࡀື࠿ࡋࡸࡍࡃឤࡌࠊᝈ⪅ࡢᐙ᪘ࡽࡶ᪥ᖖ࡟࠾ࡅࡿ⭎ࡢ ືࡁࡀᨵၿࡉࢀࡓ࡜ឤࡌ࡚࠾ࡾࠊTRH ࡛ࡢ἞⒪࡟ᑐࡋ࡚ዲ༳㇟ࢆᢪ࠸࡚࠸ࡿࠋࡋ࠿ࡋ ࡞ࡀࡽࠊࡇࢀࡽࡣ࠶ࡃࡲ࡛༳㇟࡛࠶ࡾኚ໬ࡶᚤ⣽࡛࠶ࡿࡓࡵࠊグ㏙ⓗ࡟ࡣ⾲⌧ࡉࢀ࡚ ࡶࠊᚑ᮶ࡢ㐠ືᶵ⬟ホ౯ࢫࢣ࣮࡛ࣝ࠶ࡿHFMS8_{ࢆ⏝࠸ࡓホ౯᪉ἲ࡛ࡣ᳨ฟࡀ࡛ࡁ࡞࠸ࠋ} ࡇ࠺࠸ࡗࡓ༳㇟࡜ホ౯ࡢ㝸ࡓࡾࡣࠊᝈ⪅ഃ࡜་⒪ഃࡢ୧᪉࡟࡜ࡗ࡚ࠊࡶ࡝࠿ࡋࡃࠊ᭷ ຠ࡞἞⒪ೃ⿵ࢆᇙἐࡉࡏ࡚ࡋࡲ࠺⤖ᯝ࡟ࡶ࡞ࡾᚓࡿࠋ୍᪉࡛ࠊ௒ᅇ㛤Ⓨࡋࡓᡭἲ࡛ TRH ࢆ⏝࠸ࡓ἞⒪๓ᚋ࡛ࡢ⭎ࡢືࡁࢆゎᯒࡋࡓ࡜ࡇࢁࠊSpDe ࡜ DiVa ඹ࡟ῶᑡഴྥࢆ ♧ࡋࠊDiVa ࡟㛵ࡋ࡚ࡣ⤫ィⓗ࡞᭷ពᕪࢆࡶࡗ࡚ῶᑡࡋ࡚࠾ࡾࠊࡼࡾ㗦ᩄ࡞ホ౯ࡀྍ⬟ ࡜࡞ࡗࡓࠋ⌧ᅾࠊࡇࡢホ౯᪉ἲࡣ SMA ࢆᑐ㇟࡜ࡋࡓ་ᖌ୺ᑟከ᪋タඹྠ἞㦂 33_࡟࠾ ࠸࡚ホ౯㡯┠ࡢ୍ࡘ࡜ࡋ࡚᥇⏝ࡉࢀ࡚࠾ࡾࠊ⮫ᗋᛂ⏝࡟ࡘ࠸࡚ࡼࡾヲ⣽࡟᳨ドࢆࡍࡍ ࡵ࡚࠸ࡿࠋࡲࡓ⮫ᗋ⌧ሙ࡟࠾࠸࡚ࡼࡾ⡆౽࡟ά⏝࡛ࡁࡿࡼ࠺࡟ࠊ኱᥃࠿ࡾ࡛㧗౯࡞࣮ࣔ ࢩࣙࣥ࢟ࣕࣉࢳࣕࢩࢫࢸ࣒࡛ࡣ࡞ࡃࠊiOS ࢹࣂ࢖ࢫ㸦AppleWATCH ࡸ iPhone㸧ࢆࡣࡌ

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ࡵ࡜ࡋࡓᦠᖏ᝟ሗ➃ᮎࢆ⏝࠸࡚ྠᵝࡢ ᐃ࡜ゎᯒࢆྍ⬟࡜ࡍࡿ᪂ᡭἲࡢ☜❧࡟╔ᡭࡋ ࡚࠸ࡿࠋ ⤖ㄽ࡜ࡋ࡚ࠊ௒ᅇ㛤Ⓨࡋࡓ3 ḟඖ࣮ࣔࢩࣙࣥ࢟ࣕࣉࢳࣕࢩࢫࢸ࣒ࢆά⏝ࡋࡓᡭἲࢆ ⏝࠸ࡿࡇ࡜࡛ࠊᨃఝⓗ࡞➽ຊపୗ࡟ࡼࡿ㐠ືᶵ⬟పୗࡸ἞⒪࡟ࡼࡿ㐠ືᶵ⬟ࡢᨵၿල ྜࢆᐃ㔞ⓗ࡟ホ౯࡛ࡁࡿࡇ࡜ࡀྍ⬟࡜࡞ࡗࡓࠋࡉࡽ࡟ࠊయ࡟㈞௜ࡍࡿ࣐࣮࣮࢝ࡢᩘࢆ ୍ࡘ࡟ࡋࡓࡇ࡜࡛⮫ᗋ⌧ሙ࡟࠾ࡅࡿ᭷⏝ᛶࡀ኱ᖜ࡟ቑࡋࡓࠋࡲࡓࠊỗ⏝ᛶࡶᗈ࠸ࡓࡵࠊ ࡇࢀࡲ࡛ᅔ㞴ࡔࡗࡓ⚄⤒ኚᛶ⑌ᝈࡢ⮬↛ṔࡢᢕᥱࢆྵࡵࠊⓎ㐩㞀ᐖࡸ㐠ື㞀ᐖࢆ࿊ࡍ ࡿࡉࡲࡊࡲ࡞⑌ᝈࡢ⾲⌧ᆺࡸணᚋ࡟㛵ࡋ࡚ࠊ⤫୍ⓗ࡞ホ౯ᣦᶆࢆά⏝ࡍࡿࡇ࡜࡛ࠊ᭦ ࡞ࡿぢ㆑ࡀᚓࡽࢀࡿࡇ࡜ࡀᮇᚅ࡛ࡁࡿࠋ

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ㅰ

ㅰ ㎡

ᮏㄽᩥࢆᇳ➹ࡍࡿ࡟࠶ࡓࡾࠊ⤊ጞ᠓ษ࡞ࡿᚚᣦᑟ୪ࡧ࡟ࡈ㠴᧡ࢆ㈷ࡾࡲࡋࡓࠊᒱ㜧 ኱Ꮫ኱Ꮫ㝔㐃ྜ๰⸆་⒪᝟ሗ◊✲⛉ᵓ㐀་Ꮫ ຍ⸨ၿ୍㑻 ᩍᤵ㸦ᒱ㜧኱Ꮫ኱Ꮫ㝔་ Ꮫ⣔◊✲⛉ᑠඣ⑓ែᏛ㸧࡟ㅽࢇ࡛ឤㅰࢆ⏦ࡋୖࡆࡲࡍࠋ ᮏ◊✲ࡢᶵ఍ࢆ୚࠼࡚ࡃࡔࡉࡾࠊᚚᣦᑟࠊᚚ㠴᧡ࢆ㈷ࡾࡲࡋࡓᒱ㜧⸆⛉኱Ꮫࢢ࣮ࣟ ࣂ࣭ࣝࣞࢠࣗࣛࢺ࣮࣭ࣜࢧ࢖࢚ࣥࢫᐤ㝃ㅮᗙሯᮏ᱇ᩍᤵ࡟ㅽࢇ࡛ឤㅰ⏦ࡋୖࡆࡲࡍࠋ ࡲࡓ᭷┈࡞ࡈຓゝࢆ㡬ࡁࡲࡋࡓᒱ㜧኱Ꮫ་⒪᝟ሗᏛ ୍ᐑᑦᚿ ෸ᩍᤵࠊ༓ⴥ኱Ꮫ኱ Ꮫ㝔་Ꮫ◊✲㝔ᮍ᮶་⒪ࢢ࣮ࣟࣂࣝ἞⒪Ꮫ◊✲ㅮᗙࢢ࣮ࣟࣂࣝ⮫ᗋヨ㦂Ꮫ బ⸨Ὀ᠇ ෸ᩍᤵ࡟῝ࡃᚚ♩⏦ࡋୖࡆࡲࡍࠋ ᮏ◊✲ࡢ㐙⾜࡟࠶ࡓࡾࠊᒱ㜧኱Ꮫ་Ꮫ㒊㝃ᒓ⑓㝔 ࣜࣁࣅࣜࢸ࣮ࢩࣙࣥ⛉ ᭹㒊Ⰻ ඛ⏕ࢆጞࡵ࡜ࡋࡓࢫࢱࢵࣇࡢⓙᵝࠊࡲࡓࠊࡈ༠ຊ࠸ࡓࡔ࠸ࡓᏊ౪㐩࡟῝ࡃឤㅰ⏦ࡋୖ ࡆࡲࡍࠋ ᭱ᚋ࡟㝜࡞ࡀࡽᨭ࠼࡚ࡃࢀࡓᐙ᪘࡟ឤㅰࢆ⏦ࡋୖࡆࡲࡍࠋ

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ᘬ

ᘬ⏝ᩥ⊩

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Appendix㸯

㸯㸸ศᯒ᪉ἲࡢヲ⣽

ࡇࡇ࡛ࡣࠊᮏ◊✲࡟࠾࠸࡚⏝࠸ࡽࢀࡓศᯒ᪉ἲ࡟ࡘ࠸࡚ヲ⣽࡟グ㍕ࡍࡿࠋඛࡎࡣࠊ 㐠ືࢹ࣮ࢱࡢᩘᏛⓗ⾲グ᪉ἲ࡟ࡘ࠸࡚ᐃ⩏ࡋࠊୖୗ㐠ືࡢࡳࢆᢳฟࡍࡿணഛẁ㝵࡛ࡢ ゎᯒ࡟ࡘ࠸࡚ㄝ᫂ࡍࡿࠋࡑࡢᚋࠊ᪂ࡓ࡟㛤Ⓨࡋࡓ2 ࡘࡢᐃ㔞ⓗホ౯ᣦᶆ࡟ࡘ࠸࡚グ㍕ ࡍࡿࠋࡑࢀࡒࢀࠊືసࡢࠕ✵㛫⢭☜ᛶࠖ࡜ࠕ࡞ࡵࡽ࠿ࡉࠖ࡟╔┠ࡋ࡚ࠕືసࡢ㉁ࠖࢆ ᩘ್໬ࡋࠊ㐠ືᶵ⬟ࢆᐃ㔞ⓗ࡟ホ౯ࡍࡿࠋ

z 㐠ືࢹ࣮ࢱࡢᩘᏛⓗ⾲グ

᫬㛫 t ࡟࠾ࡅࡿ࣐࣮࣮࢝ࡢ఩⨨ࢆ ࡛⾲ࡋࠊ⿕㦂⪅ࡢ⫝ࡢ఩⨨ࢆ ♧ࡍࠋࡋࡓࡀࡗ࡚ࠊ⿕㦂⪅ࡢ⫝ࡢ༢఩᫬㛫࠶ࡓࡾࡢືࡁࢆ♧ࡍ⛣ື࣋ࢡࢺࣝࡣ ࡜⾲ࡉࢀࡿࠋࡇࡢ⛣ື࣋ࢡࢺࣝࡢ⌫㠃ᗙᶆ࡟࠾ࡅࡿᴟᗙᶆ⾲⌧ࢆ ݒ(ݐ) = {ߩ(ݐ), ߠ(ݐ), ߮(ݐ) }࡜ᐃ⩏ࡋࠊືᚄᗙᶆ࡟ࡣߩࠊ➨୍ゅᗘᗙᶆ࡟ࡣߠࠊ➨஧ゅᗘᗙ ᶆ࡟ࡣɔࢆࡑࢀࡒࢀࡢグྕ࡜ࡋ࡚⏝࠸ࡓࠋࡇࡢሙྜࠊືᚄᗙᶆࡣⅬࡀᏑᅾࡍࡿ⌫㠃ࡢ ༙ᚄࢆ♧ࡋࠊ⌫㠃ࡢཎⅬ࠿ࡽⅬࡲ࡛ࡢ⥺ศࢆືᚄ࡜࿧ࡪࠋ➨୍ゅᗙᶆࡣ㔜ຊ᪉ྥ࡜ᖹ ⾜࡞㍈㸦z ㍈㸧࡜ࡑࡢືᚄࡀ࡞ࡍゅᗘࢆ♧ࡋࠊ➨஧ゅᗘᗙᶆࡣ㔜ຊ᪉ྥࡢ୪⾜࡞㍈㸦z ㍈㸧࡟ᆶ┤࡞ᖹ㠃㸦xy ᖹ㠃㸧࡬ࡢືᚄࡢᑕᙳࡀᖹ㠃࡟ྵࡲࢀࡿ㍈㸦x ㍈㸧࡜࡞ࡍゅᗘ ࢆ♧ࡍࠋゎᯒ࡟࠾࠸࡚ᴟᗙᶆ⾲⌧ࢆ᥇⏝ࡋࡓࡢࡣࠊᘼࢆᥥࡃ⭎ࡢ෇㐠ືࢆゅᗘࡢ⥺ᙧ ኚ໬࡟ኚ᥮ࡍࡿࡇ࡜ࡀྍ⬟࡜࡞ࡿ࠿ࡽ࡛࠶ࡿࠋ

z 㐠ືࢹ࣮ࢱࡢணഛゎᯒ

⭎ࢆୖୗࡍࡿ㐠ື࠿ࡽᚓࡽࢀࡿ㐠ືࢹ࣮ࢱ࡟ࡣࠊࠕ⭎ࢆୖୗࡉࡏ࡚࠸ࡿࠖࢹ࣮ࢱ௨ እࡢࢹ࣮ࢱࡶྵࡲࢀ࡚࠸ࡿࠋ༶ࡕࠊ⭎ࢆ┤ୗ࡟ୗࡆࡓ≧ែ࡛᣺ࡾᏊࡢࡼ࠺࡟⭎ࢆᦂࡽ ࡋࡓࡾࠊ㏵୰࡛ᣲࡆࡿࡢࢆ୰᩿ࡋ࡚ࡸࡾ┤ࡋࡓࡾࡍࡿືసࡶࢹ࣮ࢱ࡜ࡋ࡚ྵࡲࢀ࡚࠸ ࡿࠋᢠ㔜ຊ㐠ື࡜ࡣ↓㛵ಀ࡛࠶ࡿࡼ࠺࡞వศ࡞ືࡁࡣࠊゎᯒᑐ㇟࠿ࡽ㝖እࡍࡿᚲせࡀ ࠶ࡿࠋࡑࡇ࡛ࠊணഛゎᯒ࡜ࡋ࡚ࠊグ㘓ࡉࢀ࡚࠸ࡿ㐠ືࢹ࣮ࢱ࠿ࡽ㐠ືᶵ⬟ࡢホ౯࡟㔜せ࡜⪃࠼ࡽࢀࡿᢠ㔜ຊ㐠ື࡟㛵ಀࡍࡿ㒊ศࡔࡅࢆᢳฟࡋࡓࠋ ⭎ࢆୖ᪼ࡉࡏ࡚࠸ࡿ᫬㛫༊ศ㸦ݐ௨௣_{㸧ࡲࡓࡣ㝆ୗࡉࡏ࡚࠸ࡿ᫬㛫༊ศ㸦}_ݐௗ௢௪௡_㸧ࡣ௨

^

t x(t),y(t),z(t)

`

p ) ( ) 1 ( ) (t p t p t v

(29)

ୗࡢࡼ࠺࡟ᐃ⩏ࡋࡓ㸸 ݐ_௜௨௣ = ൛ݐ|ܯ݁݀݅ܽ݊൫ݒ_௭(ݐ െ ܹ: ݐ + ܹ)൯ > ܽ, ܽ ൒ 0, ܹ > 0ൟ ݐ_௜ௗ௢௪௡ = ൛ݐ|ܯ݁݀݅ܽ݊൫ݒ௭(ݐ െ ܹ: ݐ + ܹ)൯ < െܽ, ܽ ൒, ܹ > 0ൟ ࡞࠾ࠊܯ݁݀݅ܽ݊()ࡣ୚࠼ࡽࢀࡓᘬᩘ⩌࠿ࡽ୰ኸ್ࢆ㏉ࡍ㛵ᩘ࡜ᐃ⩏ࡋࠊݒ௭ࡣୖ࡛ᐃ⩏ࡋ ࡓ⛣ື࣋ࢡࢺࣝࡢz ᡂศࢆ⾲ࡋ࡚࠸ࡿࠋࡲࡓࠊ㐠ືࢹ࣮ࢱ࡟ࡣ 10 ᅇࡢୖୗ㐠ືࡀྵࡲ ࢀ࡚࠸ࡿࡓࡵࠊୗ௜ࡁࡢ್i = {2, … ,9}ࡀఱᅇ┠ࡢୖୗ㐠ື࠿ࢆ♧ࡋ࡚࠸ࡿࠋࡇࡢ᫬㛫 ༊ศࡢᐃ⩏ࢆពヂࡍࡿ࡜ࠊ࣐࣮࣮࢝ࡢz ㍈᪉ྥ㸦㔜ຊ᪉ྥ㸧࡬ࡢ⛣ືࡀࠊ࠶ࡿ㜈್㸦ኚ ᩘa ࡛ᐃ⩏ࡉࢀࡿ㸧ࡼࡾࡶ኱ࡁࡅࢀࡤୖ᪼ࡋ࡚࠸ࡿ༊㛫࡜ࡋࠊᑠࡉࡅࢀࡤୗ㝆ࡋ࡚࠸ ࡿ༊㛫࡜ࡋ࡚࠸ࡿࠋణࡋࠊୖୗ㐠ື࡟⏤᮶ࡍࡿୖ᪼ࡸୗ㝆ࡣ⥅⥆ⓗ࡛࡞ࡅࢀࡤ࡞ࡽࡎࠊ ▐㛫ⓗ࡛✺Ⓨⓗ࡞ୖ᪼ࡸୗ㝆࡜ࡣ༊ูࡍࡿᚲせࡀ࠶ࡿࠋࡑࡇ࡛ࠊ࣓ࢹ࢕࢔ࣥࣇ࢕ࣝࢱ ࢆᛂ⏝ࡍࡿࡇ࡜࡛ࠊࡑࢀࡽ✺Ⓨⓗ࡞ᛴୖ᪼ࡸᛴୗ㝆ࢆ㝖ཤࡋࡓࠋ࣓ࢹ࢕࢔ࣥࣇ࢕ࣝࢱ ࡟㛵ಀࡋ࡚ࠊࣃ࣓ࣛࢱW ࢆ኱ࡁࡃࡍࡿࡇ࡜࡛ࠊࡼࡾ኱ࡁ࡞ືࡁࢆ✺Ⓨᛶࡢືస࡜ࡋ࡚ 㝖ཤ࡛ࡁࡿࡀࠊ኱ࡁ㐣ࡂࡿW ࡣᮏ᮶ࡢ㐠ືࡶ✺Ⓨᛶࡢືస࡜ࡋ࡚ࡋࡲ࠺ྍ⬟ᛶࡀ࠶ࡿࠋ 㜈್ࢆᐃ⩏ࡍࡿࣃ࣓ࣛࢱa ࡣࠊ࡝ࢀࡔࡅ኱ࡁ࡞ z ㍈᪉ྥࡢኚ໬ࢆୖ࣭᪼ୗ㝆࡜ࡋ࡚ᢳ ฟࡍࡿ࠿ࢆỴࡵࡿࠋ ࡇࡇ࡛ㄝ᫂ࡋ࡚࠸ࡿᢳฟ᪉ἲࡢ⢭ᗘࡣ2 ࡘࡢࣃ࣓ࣛࢱࡢ್㸦Wࠊa㸧࡟ࡼࡗ࡚ࢥࣥࢺ ࣮ࣟࣝࡉࢀ࡚࠸ࡿࠋᮏ◊✲࡟࠾࠸࡚ࡣࡑࢀࡒࢀܹ = 30, ܽ = 0.7࡜タᐃࡍࡿࡇ࡜࡛ࠊ ୖ᪼࡜ୗ㝆ࡢ༊㛫ࢆ㐺ษ࡟ᢳฟࡍࡿࡇ࡜ࡀ࡛ࡁࡓࡀࠊࡇࢀࡽࡢタᐃࡣᬑ㐢ⓗ࡜ࡣ࠸࠼ ࡞࠸ࠋཎ๎࡜ࡋ࡚ྛᑐ㇟⪅ࡢྛືస࡟ᛂࡌ࡚ࠊࡑࡢࢫࣆ࣮ࢻࡸ⭎ࡢᣲࡆ᪉࣭ୗࡆ᪉ࢆ ⪃៖ࡋ࡚ࠊヨ⾜㘒ㄗⓗ࡟Ỵࡵࡿᚲせࡀ࠶ࡿࠋ㐺ษ࡟ୖୗ㐠ືࡀᢳฟ࡛ࡁࡓ┠Ᏻ࡜ࡋ࡚ ࡣࠊୖ᪼༊㛫࣭ୗ㝆༊㛫ࡀඹ࡟ୖୗ㐠ືࢆࡋࡓᅇᩘ㸦ࡇࡢሙྜࠊ10 ᅇ㸧࡜ྠࡌࡔࡅᢳ ฟࡉࢀ࡚࠸ࡿ࠿ࠊࡑࡋ࡚ࠊᢳฟࡉࢀࡓ༊㛫ࡢ୪ࡧࡀୖ᪼༊㛫࠿ࡽጞࡲࡾࠊୗ㝆༊㛫࡛ ⤊ ࢃ ࡾ ࠊ ୖ ᪼ ༊ 㛫 ࡜ ୗ 㝆 ༊ 㛫 ࡀ ஺ ஫ ࡟ ࡞ ࡗ ࡚ ࠸ ࡿ ࠊ ༶ ࡕ ݐ_ଵ௨௣, ݐ_ଵௗ௢௪௡_{, ݐ} ଶ௨௣, ݐଶௗ௢௪௡, … , ݐଵ଴௨௣, ݐଵ଴ௗ௢௪௡࡜୪ࢇ࡛࠸ࡿ࠿ࡀࢳ࢙ࢵࢡ㡯┠࡜࡞ࡿࠋణࡋࠊ᭱⤊ⓗ࡟ ࡣࢢࣛࣇࢆ⏝࠸࡚┠ど᳨࡛ドࡍࡿࡇ࡜ࡀ୙ྍḞ࡛࠶ࡿࠋ ࡞࠾ࠊ10 ᅇࡢୖୗ㐠ືࡢ࠺ࡕࠊ᭱ึ㸦1 ᅇ┠㸧࡜᭱ᚋ㸦10 ᅇ┠㸧ࡢୖୗ㐠ືࡣゎᯒ ᑐ㇟࠿ࡽ㝖እࡋࡓࠋࡇࢀࡣࠊࡇࢀࡽ2 ᅇࡢ㐠ືࡀ௚ࡢ 8 ᅇࡢ㐠ື࡜ࡣᛶ㉁ୖ␗࡞ࡿ࡜

(30)

⪃࠼ࡽࢀࡿ࠿ࡽ࡛࠶ࡿࠋලయⓗ࡟ࡣࠊ8 ᅇࡢ㐠ືࡣ௚ࡢ㐠ື࡜๓ᚋ࡛⧅ࡀࡗ࡚࠾ࡾࠊ ືసࡢࡘ࡞ࡂ࡜ࡋ࡚㐠ືࢆࡋ࡚࠸ࡿ୍᪉࡛ࠊ᭱ึ࡜᭱ᚋࡢ2 ᅇࡣ㐠ືࡢ㛤ጞ࡜⤊஢ࢆ ྵࢇ࡛࠾ࡾࠊᐇ㝿ࡢ㐠ືࢆグ㘓ࡋࡓᫎീ࠿ࡽࡶࠕࡘ࡞ࡂࠖ࡜ࡋ࡚ࡢືࡁ࡜ࡑࢀ௨እ࡛ ࡣᚤጁ࡞㐪࠸ࡀ☜ㄆ࡛ࡁࡓࠋ ࡉࡽ࡟ࠊࡑࢀࡒࢀࡢୖୗ㐠ື༊㛫ࢆ㌶㊧ࡢ୰ኸⅬ࡛ศ๭ࡋࠊୖ᪼༊㛫ࡣ➨୍༊㛫࡜ ➨஧༊㛫࡟ࠊୗ㝆༊㛫ࡣ➨୕༊㛫࡜➨ᅄ༊㛫ࡢィ4 ࡘࡢ༊㛫࡟⣽ศ໬ࡋࡓࠋ㌶㊧ࡢጞ Ⅼ࠿ࡽ㌶㊧ࡢ୰ኸⅬࡲ࡛ࢆ➨୍༊㛫㸦ݍଵ_{㸧ࠊࡑࡇ࠿ࡽ㡬ୖࡲ࡛ࢆ➨஧༊㛫㸦ݍ}ଶ_㸧ࠋ㝆 ୗ༊㛫ࡢ࠺ࡕ㡬ୖ࠿ࡽ㌶㊧ࡢ୰ኸⅬࡲ࡛ࢆ➨୕༊㛫㸦ݍଷ_{㸧ࠊࡑࡇ࠿ࡽ㌶㊧ࡢ⤊Ⅼࡲ࡛} ࢆ㸦ݍସ_{㸧࡜ࡋ࡚ࠊ௨ୗࡢࡼ࠺࡟ᐃ⩏ࡍࡿ㸸} ݍ_௜ଵ _{= ൛ݐ א ݐ} ௜௨௣|ݐ < ݐ௜௠௔௫ൟ, ݍ_୧ଶ = ൛ݐ א ݐ_௜௨௣|ݐ > ݐ_௜௠௔௫ൟ, ݍ_௜ଷ _{= ൛t א ݐ} ௜ௗ௢௪௡|ݐ < ݐ௜௠௜௡ൟ, ݍ_௜ସ = ൛ݐ א ݐ_௜ௗ௢௪௡|ݐ > ݐ_௜௠௜௡ൟ, where ׊ݐ א ݐ௜ ௨௣_{: ݒ} ௭(ݐ௜௠௔௫) > ܯ݁݀݅ܽ݊൫ݒ௭(ݐ െ ܹ: ݐ + ܹ)൯ ׊ݐ א ݐ_௜ௗ௢௪௡_{: ݒ} ௭൫ݐ௜௠௜௡൯ ൑ ܯ݁݀݅ܽ݊൫ݒ௭(t െ ܹ: t + ܹ)൯ 㸦ܹ = 3㸧㌶㊧ࡢ୰ኸⅬࡣࠊ༢఩᫬㛫࠶ࡓࡾ࡟z ㍈᪉ྥࡢ⛣ືࡀ᭱ࡶ኱ࡁ࠸Ⅼ࡜ࡋࡓࠋ

z ཯᚟ືసࡢ✵㛫⢭☜ᛶ㸦Spatial Deviation㸸 SpDe㸧

➨୍ࡢᣦᶆ࡛࠶ࡿࠕ✵㛫⢭☜ᛶ㸦Spatial Deviation㸸SpDe㸧ࠖࡣࠊ཯᚟㐠ື࡟࠾ࡅࡿ ືసࡢ⢭☜ᛶ࡟╔┠ࡋࠊྛ㌶㊧ࡀ࠾஫࠸࡟࡝ࡢ⛬ᗘゎ㞳ࡋ࡚࠸ࡿ࠿ࢆ㐠ືᶵ⬟ࡢᣦᶆ ࡜ࡋࡓࠋࡑࡋ࡚ࡑࡢゎ㞳ࡢ⛬ᗘࡣࠊྛ㌶㊧ࡢᖹᆒ㌶㊧࠿ࡽࡢ㊥㞳ࢆྜィࡋࡓ್࡛⾲ࢃ ࡋࡓࠋ ཯᚟㐠ືࡢྛ㐠ື㌶㊧ࡣ࠿࠿ࡿ᫬㛫ࡶ㛗ࡉࡶ␗࡞ࡿࡓࡵࠊྛ㐠ື㌶㊧ࢆṇつ໬ࡋ࡚ࠊ ࡑࢀࡒࢀࡢ㌶㊧࡟ྠࡌಶᩘࡢᗙᶆⅬࡀྵࡲࢀࡿࡼ࠺࡟ࡋ࡚ࠊ୍ᅇࡢୖୗ㐠ືࢆ200 Ⅼ ࡢ఩⨨ᗙᶆ࡛⾲⌧ࡍࡿࡼ࠺࡟ࡋࡓࠋ༶ࡕࠊ୍ᅇࡢୖୗ㐠ື࡟ྵࡲࢀࡿୖ᪼༊㛫࡜ୗ㝆 ༊㛫ࡣࠊࡑࢀࡒࢀ100 Ⅼࡎࡘࡢ఩⨨ᗙᶆ࡛⾲⌧ࡉࢀࡿࡼ࠺࡟ṇつ໬ࡉࢀࠊྛ༊㛫ࡣ 99 ಶࡢᑠ༊㛫࡟⣽ศ໬ࡉࢀࡓࠋ࡞࠾ࠊィ ࡉࢀ࡚࠸࡞࠸᫬㛫࡟࠾ࡅࡿ఩⨨ᗙᶆࡣ┤㏆ࡢ ᐇ ್ࢆ⤖ࢇࡔ⥺ᙧከ㡯ᘧ㸦୍ḟᘧ㸧࡛⿵㛫ࡋࡓࠋṇつ໬ࡉࢀࡓୖ᪼༊㛫࡜ୗ㝆༊㛫 ࡣࠊࡑࢀࡒࢀ⿵㛫ࡉࢀࡓ఩⨨ᗙᶆ100 ಶ࡛⾲⌧ࡉࢀࡿࠋࡇࡢ⿵㛫࡟ࡼࡗ࡚ᚓࡽࢀࡓୖ

(31)

ୗ㐠ືࡢṇつ໬ࡋࡓ㌶㊧ࡣࠊᐇ㝿࡟ィ ࡉࢀࡓ఩⨨ᗙᶆ࡜༊ูࡍࡿࡓࡵࠊࣉࣛ࢖࣒グ ྕ㸦’㸧ࢆ௜グࡋ࡚⾲⌧ࡋࡓࠋࡑࡋ࡚ࠊṇつ໬ࡉࢀࡓୖୗ㐠ື㌶㊧ࡢࠊࡑࢀࡒࢀࡢᡂศ ࡢᖹᆒ್࡛♧ࡉࢀࡿ㐠ື㌶㊧ࢆᖹᆒ㌶㊧࡜ࡋࡓࠋồࡵࡽࢀࡓᖹᆒ㌶㊧࡜ྛ㌶㊧࡜ࡢ㊥㞳ࢆྜィࡋࡓࡶࡢࢆࠕ✵㛫⢭☜ᛶ㸦SpDe㸧ࠖ࡜ᐃ⩏ࡋࡓ㸸 ܵ_௜௕ _{= ෍} _ඩ൭݌͛ ௜,௝ ௕ െ1 8൬෍ ݌͛௜,௝ ௕ ଽ ௜ୀଶ ൰൱ ଶ ଵ଴଴ ௝ୀଵ ࡓࡔࡋࠊ᭱ึ࡜᭱ᚋࡢୖୗ㐠ືࡣ㝖እࡋ࡚࠸ࡿࡓࡵࠊ2 ᅇ┠࠿ࡽ 9 ᅇ┠ࡲ࡛ࡢୖୗ㐠 ືࡢࡳࢆ⪃៖ࡋ࡚࠸ࡿࠋ ࡇࡢSpDe ࡢ್ࡣࠊ௨ୗࡢࡼ࠺࡟ィ⟬ࡉࢀࡓ㌶㊧ࡢ㛗ࡉ࡛ㄪᩚࡍࡿ㸸 ܮ௕_௜ _{= ෍} _ඨቀ݌͛ ௜,௝ାଵ ௕ െ ݌͛_௜,௝௕ ቁଶ ଽଽ ௝ୀଵ ࡇࢀࡣࠊయࡢ኱ࡁࡉࡸ⭎ࡢ㛗ࡉ࡟㐪࠸ࡀ࠶ࡿሙྜ࡛ࡶẚ㍑࡛ࡁࡿࡼ࠺࡟ࡍࡿࡓࡵ࡛࠶ ࡿࠋࡑࢀ࡜ྠ᫬࡟ࠊ⭎ࡀື࠿ࡏ࡞࠸ሙྜ࡟್ࡀ኱ࡁࡃ࡞ࡿ࣌ࢼࣝࢸ࢕࡜ࡋ࡚ࡢព⩏ࡶ ࠶ࡿࠋ౛࠼ࡤࠊ➽⫗ࡀ᏶඲࡟ⴎ⦰ࡋ࡚⭎ࢆື࠿ࡍࡇ࡜ࡀฟ᮶࡞࠸ሙྜ࡟ࠊㄪᩚ๓ࡢSpDe ࡛ࡣ㠀ᖖ࡟ᑠࡉ࠸್࡜࡞ࡾࠊ✵㛫⢭☜ᛶࡀⰋࡃࠊ㐠ືᶵ⬟ࡀ㧗࠸ࡇ࡜࡟࡞ࡗ࡚ࡋࡲ࠺ࠋ ࡇࢀࢆ㑊ࡅࡿࡓࡵࠊ⭎ࡢ⛣ື㊥㞳࠶ࡓࡾ࡛⿵ṇࢆࡍࡿࡇ࡜࡛ࠊ㐠ື㌶㊧ࢆᥥࡅ࡞࠸ሙ ྜ࡟ࡣSpDe ࡀ኱ࡁ࡞್࡟࡞ࡿࡼ࠺࡟ㄪᩚࢆࡋ࡚࠸ࡿࠋ

z ືసࡢ࡞ࡵࡽ࠿ࡉ㸦Direction Variance㸸 DiVa㸧

ࡶ࠺୍ࡘࡢᣦᶆ࡛࠶ࡿࠕືసࡢ࡞ࡵࡽ࠿ࡉ㸦Direction Variance: DiVa㸧ࠖࡣࠊ⭎ࡢ⛣ ື᪉ྥࡀ㐃⥆ⓗ࡟ኚ໬ࡋ࡚࠸ࡿࡢ࠿ࢆ㐠ືᶵ⬟ࡢᣦᶆ࡜ࡋࡓࠋ༶ࡕࠊ⭎ࡢ⛣ື᪉ྥࢆ ♧ࡍ⛣ື࣋ࢡࢺࣝࢆᴟᗙᶆ⾲⌧࡟ኚ᥮ࡋࡓሙྜ࡟ࠊࡑࡢ➨୍ゅᗘ㸦ߠ㸧ࡢ⤒᫬ⓗኚ໬ ࡀ㐃⥆ⓗ࡛࠶ࡿ࠿࡝࠺࠿ࢆᩘ್໬ࡋࡓࠋࡇࡢߠᡂศࡣࠊ⭎ࡢ⛣ື᪉ྥࡢ㔜ຊ᪉ྥ㸦z ㍈ ᪉ྥ㸧࡟ᑐࡍࡿゅᗘ࡛࠶ࡾࠊ⭎ࡢືࡁࡢᢠ㔜ຊస⏝࡟཯ᫎࡉࢀࡿࠋࡑࡇ࡛ࠊᑐ㇟⪅ࡀ 㔜ຊ࡟ᑐࡋ࡚࠸࠿࡟㐠ືࢆࢥࣥࢺ࣮࡛ࣟࣝࡁ࡚ࠊ࡞ࡵࡽ࠿࡟ୖୗ㐠ືࡀᐇ᪋࡛ࡁࡿ࠿ ࡢᣦᶆ࡜ࡋ࡚ࠊࡇࡢߠᡂศ࡟╔┠ࡋࡓ

(32)

௬࡟ࠊ⫪㛵⠇ࡢ࣓࢝ࢽ࢝ࣝࣔࢹࣝࢆ᝿ᐃࡋࡓሙྜࠊࡑࡢᒅ᭤㐠ື࡟ࡼࡿ⫝ࡢ㌶㊧ࡣ ༙෇ᘼࢆᥥࡃࡓࡵࠊ⌮᝿ⓗ࡞⭎ࡢୖୗ㐠ືࢆ➼㏿࡟༙෇ᘼࢆᥥࡃࡼ࠺࡞㐠ື࡜ࡋࡓࠋ ࡑࡢሙྜࠊ⫝ࡢ⛣ື࣋ࢡࢺࣝ࡟࠾ࡅࡿߠࡢ್ࡀ┤⥺ⓗ࡟᥎⛣ࡋ࡚࠸ࡃࡇ࡜ࡀ☜ㄆࡉࢀ ࡚࠸ࡿࠋࡑࡇ࡛ࠊᐇ㝿࡟ ᐃࡉࢀࡓ㐠ືࢹ࣮ࢱ࡟࠾ࡅࡿ⛣ື࣋ࢡࢺࣝࡢߠᡂศࡀ࡝ࢀ ࡔࡅࡑࡢ┤⥺ⓗ࡞᥎⛣࠿ࡽࡎࢀ࡚࠸ࡿ࠿ࢆィ⟬ࡋࠊࡑࡢࡎࢀࢆ㌶㊧ࡢࠕṍࡳࠖ࡜ࡋࡓࠋ ༶ࡕࠊ㌶㊧ࡢࠕṍࡳࠖࡀᑡ࡞࠸࡯࡝⛣ື࣋ࢡࢺࣝࡢߠᡂศࡀ┤⥺ୖ࡟୪ࡧࠊືసࡀ࡞ ࡵࡽ࠿࡛࠶ࡿ࡜ࡋࡓࠋཝᐦ࡟ࡣࠊ㌶㊧ࢆ4 ࡘࡢ༊㛫࡟ศࡅࡓࡑࢀࡒࢀ࡟ࡘ࠸࡚ࠊ⛣ື ࣋ࢡࢺࣝࡢߠᡂศࡢ⤒᫬ኚ໬ࢆࠊ཯᚟෌㔜ࡳ௜ࡅ᭱ᑠ஧஌ἲࢆ⏝࠸୍࡚⯡໬⥺ᙧࣔࢹ ࡛ࣝ㏆ఝࡋࠊࡑࡢ㏆ఝ್࡜ᐇ㝿ࡢ್࡜ࡢㄗᕪࢆྜィࡋࡓࡶࡢࢆࠕ࡞ࡵࡽ࠿ࡉࠖࡢᣦᶆࠊ DiVa ࡜ᐃ⩏ࡋࡓ㸸 ට_{௦௜௭௘(௤}ଵ ೔ ೕ₎σ_௧א௤(ߠᇱ(ݐ) െ ߠ(ݐ))ଶ ೔ ೕ , ݆ = {1,2,3,4}, ࡞࠾ࠊ⛣ື࣋ࢡࢺࣝࡢߠᡂศࢆ୍⯡໬⥺ᙧࣔࢹ࡛ࣝ㏆ఝࡋࡓ್㸦ߠԢ㸧ࡣࠊࣉࣛ࢖࣒グྕ ࢆ௜グࡍࡿࡇ࡜࡛ᐇ㝿ࡢߠ࡜ࡣ༊ูࡋࠊsize()㛵ᩘࡣࠊᘬᩘ࡜ࡋ࡚ᥦ♧ࡉࢀࡓ࣋ࢡࢺࣝ ࡢ㛗ࡉࢆ㏉ࡍࠋ

(33)

Appendix㸰

㸰㸸೺ᖖᡂே࡟࠾ࡅࡿ㐠ືࢹ࣮ࢱࡢヲ⣽

Supplemental Figure 1 ೺ᖖᡂே࡟࠾ࡅࡿ⫪㛵⠇ࡢᒅ᭤㐠ືࡢ㐠ືࢹ࣮ࢱ Supplemental Figure 1 ࡟࠾࠸࡚ࠊ೺ᖖᡂேࡀ⫪㛵⠇ࡢᒅ᭤㐠ືࢆᐇ᪋ࡋࡓ㝿࡟ ᐃࡋ ࡓ㐠ືࢹ࣮ࢱ࡟ࡘ࠸࡚ࠊx,y,z ᡂศࡢ⤒᫬ⓗኚ໬ࢆ♧ࡋ࡚࠸ࡿࠋ࡞࠾ࠊ3 ḟඖ✵㛫࡟࠾ ࡅࡿ㐠ື㌶㊧ࡣᮏᩥࡢᅗ 2a ࡟♧ࡉࢀ࡚࠸ࡿࢢࣛࣇࡀᑐᛂࡍࡿࠋᑐ㇟⪅ࡣ x ㍈ࡢ࣐࢖ ࢼࢫ᪉ྥࢆྥ࠸࡚❧ࡗ࡚࠸ࡿࡓࡵࠊ⭎ࡢືࡁฟࡋࡣx ㍈ࡢ࣐࢖ࢼࢫ᪉ྥ࡟ືࡃࠋࡑࡢ ᚋࠊᘼࡢ୰ኸࠊ༶ࡕỈᖹ࡜࡞ࡿⅬࢆ㉺࠼ࡓ࡜ࡇࢁ࠿ࡽࣉࣛࢫ᪉ྥ࡟㌿ࡌࠊ㡬Ⅼ࡟㐩ࡋ ࡓ࡜ࡇࢁ࡛ฟⓎⅬ࡜ྠ➼ࡢ x ್࡟࡞ࡿࠋୗ㝆㐠ືࡢ㝿࡟ࡣࠊx ᡂศ࡟㛵ࡋ࡚ࡣࠊ࡯ࡰ ྠᵝࡢືࡁࡀぢࡽࢀࡿࠋY ᡂศ࡟㛵ࡋ࡚ࡣࠊከᑡࡢࡎࢀࡀ⏕ࡌ࡚࠸ࡿࠋୖ᪼ࡢጞࡵ࡟ y ㍈ࡢࣉࣛࢫ᪉ྥ㸦⿕㦂⪅ࡢྑഃ㸧࡬ࡎࢀ࡚࠸ࡁࠊ㏵୰࠿ࡽ࣐࢖ࢼࢫ᪉ྥ࡟኱ࡁࡃࡎ ࢀ࡚࠸ࡃࠋࡑࡋ࡚ࠊୗ㝆㐠ືࡀጞࡲࡿ࡜ࠊୖ᪼㐠ືࡢ㌶㊧ࢆ㎺ࡿࡼ࠺࡟኱ࡁࡃࣉࣛࢫ ᪉ྥ࡟ࡎࢀ࡚ࠊ࣐࢖ࢼࢫ᪉ྥ࡟ᡠࡿࣃࢱ࣮ࣥࡀࡳࡽࢀࡓࠋణࡋࠊࡎࢀࡢ⛬ᗘࡣ㠀ᖖ࡟ ᑠࡉࡃ㸦100mm ௨ୗ㸧ࠊ཯᚟㐠ືࡀ⢭☜࡟⾜ࢃࢀ࡚࠸ࡿࡇ࡜ࢆ♧ࡋ࡚࠸ࡿࠋࡑࡋ࡚ࠊz ᡂศࡢኚ໬࠿ࡽࠊ⭎ࡢୖୗ㐠ືࡀ10 ᅇ⧞ࡾ㏉ࡉࢀࡓࡇ࡜ࡀ᫂☜࡟ぢ࡚ྲྀࢀࡿ࡜ྠ᫬࡟ࠊ ୖ᪼㐠ື㸦㉥㸧࡜ୗ㝆㐠ື㸦㟷㸧ࡀࠊணഛゎᯒ࡟ࡼࡾ㐺ษ࡟ᢳฟ࡛ࡁ࡚࠸ࡿࡇ࡜ࡀ☜ ㄆ࡛ࡁࡿࠋࡲࡓࠊ᭱ึ㸦1 ᅇ┠㸧࡜᭱ᚋ㸦10 ᅇ┠㸧ࡢୖୗ㐠ືࡣゎᯒ࠿ࡽ㝖እࡉࢀ࡚ ࠸ࡿࡇ࡜ࡶ☜ㄆ࡛ࡁࡿࠋ

(34)

Supplemental Figure 2 ࠾ࡶࡾࢆಖᣢࡋࡓ≧ែ࡛ᐇ᪋ࡋࡓ⫪ࡢᒅᙉ㐠ືࡢ㐠ືࢹ࣮ࢱ

࠾ࡶࡾࢆಖᣢࡋࡓ≧ែ࡛⫪㛵⠇ࡢᒅ᭤㐠ືࢆᐇ᪋ࡋࡓ㝿࡟ ᐃࡋࡓ㐠ືࢹ࣮ࢱ࡟ ࡘ࠸࡚ࠊx,y,z ᡂศࡢ⤒᫬ⓗኚ໬ࢆ Supplemental Figure 2 ࡟♧ࡋ࡚࠸ࡿࠋ࡞࠾ࠊ3 ḟඖ✵

㛫࡟࠾ࡅࡿ㐠ື㌶㊧ࡣᮏᩥࡢᅗ 2b ࡟♧ࡉࢀ࡚࠸ࡿࢢࣛࣇࡀᑐᛂࡍࡿࠋ࠾ࡶࡾࢆಖᣢ ࡋ࡞࠸ሙྜࡢ㐠ືࢹ࣮ࢱ㸦Supplemental Figure 1㸧࡜ẚ㍑ࡋ࡚ࠊx ᡂศ࡟࠾ࡅࡿᦂࡽࡂ ࡢࣃࢱ࣮ࣥ࡜y ᡂศ࡟࠾ࡅࡿᦂࡽࡂࡢᖜ࡟㢧ⴭ࡞㐪࠸ࡀ⏕ࡌ࡚࠸ࡿࡢࡀぢཷࡅࡽࢀࡿࠋ ࠾ࡶࡾࢆಖᣢࡋ࡞࠸ሙྜࡢx ᡂศࡢᦂࡽࡂࡣẚ㍑ⓗ༢ㄪ࡛࠶ࡗࡓࡀࠊ࠾ࡶࡾࢆಖᣢࡋ ࡓሙྜ࡛ࡣࠊࡑࡢᦂࡽࡂࡢࣃࢱ࣮ࣥࡀ୙つ๎࡟࡞ࡗ࡚࠸ࡿࠋࡲࡓࠊy ᡂศࡢᦂࡽࡂᖜ ࡟㛵ࡋ࡚ࡣࠊ࠾ࡶࡾࢆಖᣢࡋ࡞࠸ሙྜ࡟ࡣᴟࡵ࡚⊃࠿ࡗࡓࡀࠊ࠾ࡶࡾࢆಖᣢࡋࡓሙྜ ࡛ࡣቑ኱ࡋ࡚࠸ࡓࠋ

(35)

Appendix㸱

㸱㸸

II ᆺ SMA ᝈ⪅࡟࠾ࡅࡿ㐠ືࢹ࣮ࢱࡢヲ⣽

Supplemental Figure 3 II ᆺ SMA ᝈ⪅࡟࠾ࡅࡿ⫪㛵⠇ᒅ᭤㐠ືࡢ㐠ືࢹ࣮ࢱ

Supplemental Figure 3 ࡟࠾࠸࡚ࠊṌ⾜୙ྍ⬟࡞ II ᆺ SMA ᝈ⪅ࡀ⫪㛵⠇ࡢᒅ᭤㐠ືࢆᐇ ᪋ࡋࡓ㝿࡟ ᐃࡋࡓ㐠ືࢹ࣮ࢱ࡟ࡘ࠸࡚ࠊx,y,z ᡂศࡢ⤒᫬ⓗኚ໬ࢆ♧ࡍࠋ࡞࠾ࠊ3 ḟ

ඖ✵㛫࡟࠾ࡅࡿ㐠ື㌶㊧ࡣᮏᩥࡢᅗ 4a ࡟♧ࡉࢀ࡚࠸ࡿࢢࣛࣇࡀᑐᛂࡍࡿࠋ೺ᖖᡂே

ࡢ㐠ືࢹ࣮ࢱ㸦Supplemental Figure 1 ࠾ࡼࡧ Supplemental Figure 2㸧࡜ẚ㍑ࡋ࡚ࠊz ㍈᪉ ྥࡢືࡁࡀᑡ࡞࠸࡟ࡶ㛵ࢃࡽࡎx ㍈᪉ྥࡸ y ㍈᪉ྥ࡬ࡢືࡁࡀ⏒኱࡞ࡢࡀุࡿࠋZ ᡂ ศࡢኚ໬࠿ࡽࠊ10 ᅇࡢୖୗ㐠ືࡀ☜ㄆ࡛ࡁࡿ࡜ྠ᫬࡟ணഛゎᯒ࡟ࡼࡾୖ᪼༊㛫࡜ୗ㝆 ༊㛫ࡀ㐺ษ࡟ᢳฟࡉࢀ࡚࠸ࡿࡇ࡜ࡶどぬⓗ࡟☜ㄆ࡛ࡁࡿࠋࡑࡢ௚ࡢx ᡂศ࡜ y ᡂศࡢ ኚ໬࡟㛵ࡋ࡚ࡣࠊ࡝ࡕࡽ࠿࡜࠸࠼ࡤ୙つ๎࡟ぢཷࡅࡽࢀࡿࡀࠊy ᡂศ࡟㛵ࡋ࡚ࡣୖ᪼ ᫬࡟ῶᑡ㸦ᑐ㇟⪅ࡢᕥ᪉ྥ࡟⛣ື㸧ࡋࠊୗ㝆᫬࡟ୖ᪼ࡍࡿࣃࢱ࣮ࣥࡀ࠶ࡿࡼ࠺࡟ぢཷ ࡅࡽࢀࡿࠋ

(36)

Supplemental Figure 4 Ṍ⾜୙ྍ⬟࡞ II ᆺ SMA ᝈ⪅࡟࠾ࡅࡿࠊ⫪㛵⠇ᒅ᭤㐠ືࡢ㐠ືࢹ࣮ࢱ㸦ࡓ

ࡔࡋࠊ4 㐌㛫ࡢ TRH ⒪ἲ࡟ࡼࡿ἞⒪ᚋ㸧

Supplemental Figure 4 ࡟࠾࠸࡚ࠊṌ⾜୙ྍ⬟࡞ II ᆺ SMA ᝈ⪅ࡀ 4 㐌㛫ࡢ TRH ࡟ࡼࡿ ἞⒪ࡢᚋ࡟⫪㛵⠇ࡢᒅ᭤㐠ືࢆᐇ᪋ࡋࡓ㝿࡟ ᐃࡋࡓ㐠ືࢹ࣮ࢱ࡟ࡘ࠸࡚ࠊx,y,z ᡂศ ࡢ᫬⣔ิኚ໬ࢆ♧ࡍࠋ࡞࠾ࠊ3 ḟඖ✵㛫࡟࠾ࡅࡿ㐠ື㌶㊧ࡣᮏᩥࡢᅗ 4b ࡟♧ࡉࢀ࡚࠸ ࡿࢢࣛࣇࡀᑐᛂࡍࡿࠋ἞⒪ࡢ๓࡟ ᐃࡋࡓࢹ࣮ࢱ㸦Supplemental Figure 3㸧࡜ẚ㍑ࡋ࡚ࠊ ࡑࢀࡒࢀࡢᡂศࡀࡼࡾ⁥ࡽ࠿࡟᥎⛣ࡋ࡚࠸ࡿࡼ࠺࡟ぢཷࡅࡽࢀࡿࡀࠊグ㏙ⓗ࡟ࡶᐃ㔞 ⓗ࡟ࡶ⾲⌧ࡍࡿࡇ࡜ࡣᅔ㞴࡛࠶ࡿࠋ

(37)

Appendix㸲

㸲㸸㐠ືᶵ⬟ホ౯ᣦᶆࡢᶆ‽ཧ⪃್

௒ᚋࠊSpDe ࡸ DiVa ࡢᛂ⏝ࢆⓎ㐩㞀ᐖࡸ⚄⤒⑌ᝈࡢ᪩ᮇデ᩿࡞࡝࡜࠸ࡗࡓศ㔝࡟ᣑ ኱ࡋ࡚࠸ࡃሙྜࠊᇶ‽࡜࡞ࡿཧ⪃್ࡀ୙ྍḞ࡛࠶ࡿࠋࡑࡇ࡛ࠊ೺ᖖᑠඣ࡜೺ᖖᡂேࢆ ᑐ㇟࡜ࡋ࡚ࠊᖺ㱋࡜ඹ࡟SpDe ࡜ DiVa ࡀ࡝ࡢࡼ࠺࡟᥎⛣ࡋ࡚࠸ࡃ࠿᳨ドࡋࡓࠋᕷ㈍ࡢ 3 ḟඖ࣮ࣔࢩࣙࣥ࢟ࣕࣉࢳࣕࢩࢫࢸ࣒㸦࣮ࣟ࢝ࢫ 3D MA-3000ࠊ࢔ࢽ࣐ᰴᘧ఍♫)ࢆ⏝ ࠸࡚ࠊୖ⫥ࡢືࡁࢆࢹࢪࢱࣝ໬ࡋ㐠ືࢹ࣮ࢱ࡜ࡋ࡚཰㞟ࡋࡓࠋࢧࣥࣉࣜࣥࢢ࿘Ἴᩘࢆ 50Hz ࡛タᐃࡋࡓ௨እࡣࡇࢀࡲ࡛࡜ྠᵝࡢ᪉ἲ࡛ࢹ࣮ࢱࢆ ᐃࡋࡓࠋ ᑐ㇟⪅࡜ࡋ࡚೺ᖖᑠඣ36 ྡ㸦ᖹᆒ 9.5 ṓ㸦⠊ᅖ㸸2.6㹼13.6㸧㸧ࢆⓏ㘓ࡋࡓࠋࡑࡢ࠺ ࡕࠊࡇࡕࡽࡢᣦ♧࡟ṇࡋࡃᚑ࠺ࡇ࡜ࡀ࡛ࡁ࡞࠿ࡗࡓ➼ࡢ⌮⏤࠿ࡽ15 ྡࡀゎᯒ࠿ࡽ㝖እ ࡉࢀࡓࠋࡑࡢࡓࡵࠊ21 ྡ㸦ᖹᆒ 9.3 ṓ㸦⠊ᅖ㸸5.2㹼13.6㸧㸧ࡀࢹ࣮ࢱࢭࢵࢺ࡜ࡋ࡚ྵࡲ ࢀ࡚࠸ࡿࠋຍ࠼࡚ࠊ೺ᖖᡂேࡢཧ⪃್ࢆ཰㞟ࡍࡿࡓࡵ࡟ 3 ྡ㸦21.4 ṓࠊ23.7 ṓࠊ24.1 ṓ㸧ࡢ㐠ືࢆ ᐃࡋࡓࠋ ゎ ᯒ ࠿ ࡽ ᚓ ࡽ ࢀ ࡓ ᖺ 㱋 ࡜ 㐠 ື ᶵ ⬟ ࡢ ኚ ໬ ࢆ ࠊࠕ ཯ ᚟ 㐠 ື ࡢ ⢭ ☜ ᛶ 㸦SpDe 㸧ࠖ 㸦Supplemental Figure 5a㸧࡜ࠕືసࡢ࡞ࡵࡽ࠿ࡉ DiVaࠖ㸦Supplemental Figure 5b㸧࡟╔ ┠ࡋ࡚ホ౯ࡋࡓ⤖ᯝࢆ♧ࡍࠋᮏᩥ࡛♧ࡉࢀࡓ II ᆺ SMA ᝈ⪅ࡢ್㸦ᅗ 5㸧࡜ẚ㍑ࡍࡿ ࡜㢧ⴭ࡟㧗࠸್ࢆ♧ࡋ࡚࠾ࡾࠊࡇࢀࡽࡢཧ⪃್࠿ࡽ II ᆺ SMA ᝈ⪅ࡢ㐠ືᶵ⬟ࡢపୗ ࢆᐃ㔞ⓗ࡟ホ౯࡛ࡁࡿྍ⬟ᛶࡀ♧၀ࡉࢀ࡚࠸ࡿࠋ

(38)

Supplemental Figure 5 SpDe(a)࡜࡜DiVa(a)࡟╔┠ࡋࡓ㐠ືᶵ⬟ࢆホ౯ࡋࡓሙྜࡢᖺ㱋࡟ᛂࡌࡓཧ

⪃್ࡢẚ㍑