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    ์ˆ˜์šฉ์„ฑ RANKL์„ ๋ฐœํ˜„ํ•˜๋Š” ์œ ์‚ฐ๊ท  ๊ฒฝ๊ตฌ๋ฐฑ์‹  ๋ฉด์—ญ์ฆ๊ฐ•์ œ ๊ฐœ๋ฐœ

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ๋†์ƒ๋ช…๊ณตํ•™๋ถ€, 2014. 2. ์ตœ์œค์žฌ.๊ฒฝ๊ตฌ๋ฐฑ์‹ ์€ ์ฃผ์‚ฌ๋กœ ์ธํ•œ ์ŠคํŠธ๋ ˆ์Šค๊ฐ€ ์ ๋‹ค๋Š” ์žฅ์  ๋ฟ ์•„๋‹ˆ๋ผ ๋ณ‘์›๊ท ์„ ์ดˆ๋„์— ๋ฐฉ์–ดํ•  ์ˆ˜ ์žˆ๋‹ค๋Š” ์žฅ์ ์ด ์žˆ๋‹ค. ๊ฒฝ๊ตฌ๋ฐฑ์‹ ์„ ํ†ตํ•ด ์ ๋ง‰๋ฉด์—ญ๋ฐ˜์‘์ด ํ™œ์„ฑํ™” ๋˜๋ฉด, ๋ถ„๋น„ํ˜• ํ•ญ์ฒด์ธ IgA๊ฐ€ ์†Œ์žฅ ๋‚ด๊ฐ•์—์„œ ๋ณ‘์›๊ท ์„ ๋ฌด๋ ฅํ™”์‹œํ‚ค๊ธฐ ๋•Œ๋ฌธ์—, ๋ณ‘์›๊ท ์ด ์†Œ์žฅ ์ƒํ”ผ์„ธํฌ๋ฅผ ํ†ต๊ณผํ•˜์—ฌ ์ฒด๋‚ด๋กœ ๋“ค์–ด์˜ค์ง€ ๋ชปํ•˜๊ฒŒ ๋ง‰์•„์ฃผ๊ธฐ ๋•Œ๋ฌธ์ด๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๊ฒฝ๊ตฌ๋ฐฑ์‹ ์˜ ๊ฒฝ์šฐ ์ฃผ์‚ฌํ˜• ๋ฐฑ์‹ ์— ๋น„ํ•ด ํšจ์œจ์„ฑ์ด ๋งค์šฐ ์•ฝํ•˜๋‹ค๋Š” ๋‹จ์ ์ด ์žˆ๋‹ค. ๋”ฐ๋ผ์„œ ๊ฒฝ๊ตฌ๋ฐฑ์‹ ์˜ ํšจ์œจ์„ฑ์„ ์ฆ์ง„์‹œํ‚ค๊ธฐ ์œ„ํ•œ ๋ฉด์—ญ์ฆ๊ฐ•์ œ๋ฅผ ๊ฐœ๋ฐœํ•˜๋Š” ๊ฒƒ์€ ๋งค์šฐ ์ค‘์š”ํ•˜๋‹ค๊ณ  ํ•  ์ˆ˜ ์žˆ๋‹ค. ์†Œ์žฅ์— ์œ ์ž…๋œ ํ•ญ์›์ด ์ฒด ๋‚ด์˜ dendritic cell์„ ๋งŒ๋‚˜๊ธฐ ์œ„ํ•ด์„œ๋Š” ์†Œ์žฅ ์ƒํ”ผ์„ธํฌ๋ฅผ ํ†ต๊ณผํ•ด์•ผ ํ•œ๋‹ค. ์ด ๋•Œ ์™ธ๋ถ€ ํ•ญ์›์„ ํ†ต๊ณผ์‹œ์ผœ์ฃผ๋Š” ์—ญํ• ์„ ํ•˜๋Š” ์„ธํฌ๊ฐ€ M cell์ด๋‹ค. ๋”ฐ๋ผ์„œ ๋ณธ ์—ฐ๊ตฌ๋Š” M cell์˜ ๊ธฐ๋Šฅ์„ ํ™œ์„ฑํ™” ์‹œํ‚ฌ ์ˆ˜ ์žˆ๋‹ค๋ฉด ๊ฒฝ๊ตฌ๋ฐฑ์‹ ์˜ ํšจ์œจ์„ฑ์„ ์ฆ์ง„์‹œํ‚ฌ ์ˆ˜ ์žˆ์„ ๊ฒƒ์ด๋ผ๋Š” ๊ฐ€์„ค์—์„œ ์‹œ์ž‘๋˜์—ˆ๋‹ค. RANKL์€ TNF cytokine ์ค‘ ํ•˜๋‚˜๋กœ ํŒŒ๊ณจ์„ธํฌ์˜ ๊ธฐ๋Šฅ์„ ํ™œ์„ฑํ™” ์‹œํ‚ค๋Š” ๋ฐ ๋งค์šฐ ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•œ๋‹ค๊ณ  ์•Œ๋ ค์ ธ ์žˆ๋‹ค. ์ตœ๊ทผ๋“ค์–ด RANKL์€ peyer's patch ๋ฐœ๋‹ฌ์— ๊ผญ ํ•„์š”ํ•  ๋ฟ ์•„๋‹ˆ๋ผ M cell ๋ถ„ํ™”๋ฅผ ์œ ๋„ํ•˜๋Š” ์ธ์ž๋ผ๋Š” ์—ฐ๊ตฌ๊ฐ€ ๋ณด๊ณ ๋œ ๋ฐ” ์žˆ๋‹ค. ๋”ฐ๋ผ์„œ ๋ณธ ์—ฐ๊ตฌ๋Š” soluble RANKL์„ ๋ถ„๋น„ ๋ฐ ๋ฐœํ˜„ํ•˜๋Š” L.lactis๋ฅผ ๊ตฌ์ถ•ํ•˜๊ณ  ์žฌ์กฐํ•ฉ ์œ ์‚ฐ๊ท ์ด ๊ฒฝ๊ตฌ๋ฐฑ์‹ ์˜ ๋ฉด์—ญ์ฆ๊ฐ•์ œ๋กœ์„œ์˜ ๊ฐ€๋Šฅ์„ฑ์„ ๊ฒ€์ •ํ•˜์˜€๋‹ค. ์šฐ์„  mouse sRANKL์˜ ์„œ์—ด์„ ๋ฐœํ˜„ ์ˆ™์ฃผ์ธ L.lactis์— ๋งž์ถฐ ์ฝ”๋ˆ์ตœ์ ํ™”๋ฅผ ์ง„ํ–‰ํ•˜์˜€๋‹ค. PCR๊ณผ ์ œํ•œํšจ์†Œ Nde1, Xho1์„ ์ด์šฉํ•˜์—ฌ pIL252 ๋ฒกํ„ฐ์— sRANKL ์œ ์ „์ž๋ฅผ ์‚ฝ์ž…ํ•˜๊ณ  electroporation์„ ํ†ตํ•ด ์œ ์‚ฐ๊ท ์— ๋ฒกํ„ฐ๋ฅผ ๋„์ž…ํ•œ ํ›„, colony PCR๊ณผ sequencing์„ ํ†ตํ•ด ์žฌ์กฐํ•ฉ ์œ ์‚ฐ๊ท ์„ ์„ ํƒํ•˜์˜€๋‹ค. Western blot์„ ํ†ตํ•ด ์žฌ์กฐํ•ฉ ์œ ์‚ฐ๊ท ์—์„œ sRANKL์ด ๋ฐœํ˜„๋œ๋‹ค๋Š” ๊ฒƒ์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ๋˜ํ•œ ์ฅ์˜ ๋Œ€์‹์„ธํฌ์ฃผ์ธ RAW 264.7 cell์ด RANKL๊ณผ M-CSF๊ฐ€ ์กด์žฌํ•˜๋Š” ํ™˜๊ฒฝ์—์„œ osteoclast-like cell๋กœ ๋ถ„ํ™”ํ•œ๋‹ค๋Š” ํŠน์„ฑ์„ ์ด์šฉํ•˜์—ฌ ์žฌ์กฐํ•ฉ ์œ ์‚ฐ๊ท ์—์„œ ๋ฐœํ˜„๋œ sRANKL์˜ ์ƒ๋ฌผํ•™์  ํ™œ์„ฑ์„ ๊ฒ€์ •ํ•˜์˜€๋‹ค. ์žฌ์กฐํ•ฉ์œ ์‚ฐ๊ท ์˜ ๊ฒฝ๊ตฌ ๋ฐฑ์‹  ๋ฉด์—ญ์ฆ๊ฐ•์ œ๋กœ์„œ์˜ ๊ฐ€๋Šฅ์„ฑ์„ ๊ฒ€์ •ํ•˜๊ธฐ ์œ„ํ•ด BALB/c mouse๋ฅผ ์ด์šฉํ•˜์—ฌ in vivo ๋ฉด์—ญ์‹คํ—˜์„ ์‹ค์‹œํ•˜์˜€๋‹ค. 1์ฃผ์ผ๊ฐ„ Mouse์— PBS ํ˜น์€ ์žฌ์กฐํ•ฉ ์œ ์‚ฐ๊ท ์ฃผ๋ฅผ ๋งค์ผ ํ•œ๋ฒˆ์”ฉ ๊ฒฝ๊ตฌํˆฌ์—ฌํ•˜๊ณ , ์‹คํ—˜์‹ค์—์„œ ๋ณด์œ ํ•˜๊ณ  ์žˆ๋Š” ๋ผ์ง€์ ๋ฆฌ๊ท ์˜ ๋ง‰ ๋‹จ๋ฐฑ์งˆ ์•„๋‹จ์œ„ ๋ฐฑ์‹ ์— M cell ํ‘œ์  ํŽฉํƒ€์ด๋“œ๊ฐ€ conjugationํ•œ ํ˜•ํƒœ์˜ M-BmpB๋ฅผ ๊ฒฝ๊ตฌํˆฌ์—ฌํ•˜์˜€๋‹ค. M-BmpB 2์ฐจ boosting ํ•œ์ง€ 1์ฃผ์ผ๊ณผ 2์ฃผ์ผ์ด ์ง€๋‚ฌ์„ ๋•Œ mouse์˜ ํ˜ˆ์•ก๊ณผ ๋ถ„์„ ์ฑ„์ทจํ•˜์—ฌ M-BmpB ํŠน์ด์ ์ธ IgG์™€ IgA์˜ ์–‘์„ ์‚ดํŽด๋ณด์•˜๋‹ค. ๊ฒฐ๊ณผ์ ์œผ๋กœ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด ์žฌ์กฐํ•ฉ์œ ์‚ฐ๊ท ์„ ๊ฒฝ๊ตฌํˆฌ์—ฌํ•œ ๊ทธ๋ฃน์—์„œ M-BmpB ํŠน์ด์ ์ธ IgG์™€ IgA๊ฐ€ ์ฆ๊ฐ€ํ•˜๋Š” ์–‘์ƒ์„ ๋ณด์˜€๊ธฐ์— ์žฌ์กฐํ•ฉ์œ ์‚ฐ๊ท ์„ ๊ฒฝ๊ตฌ๋ฐฑ์‹ ์˜ ๋ฉด์—ญ์ฆ๊ฐ•์ œ๋กœ์„œ์˜ ๊ฐ€๋Šฅ์„ฑ์„ ํ™•์ธํ•˜์˜€๋‹ค.Summary I Contents III List of Tables and Figures โ…ฅ List of Abbreviations โ…ง I. Introduction 1 II. Review of Literature 2 1. Gut associated lymphoid tissue(GALT) and M cell 2 1) Mucosal immune system 2 2) Peyer's patches (PPs) 2 3) Microfold cell (M cell) 5 (1) Discovery of M cell 5 (2) M cell marker 5 2. Receptor activator of NF-ฮบB ligand (RANKL) 8 1) The crucial role of RANKL in bone 8 2) Immunological functions of RANKL 10 3) Relationship between RANKL and M cell differentiation 10 3. Lactic acid bacteria as delivery vehicle 12 1) Lactic acid bacteria 12 2) LAB as delivery vehicles 12 III. Materials and Methods 15 1. Microorganism strains and growth conditions 15 2. Recombinant L.lactis construction 15 1) sRANKL sequence 15 2) Codon optimization and synthesis of sRANKL 15 3) Construction of sRANKL expression vector for L.lactis 16 4) Transformation and selection for transformants 16 3. sRANKL expression in L.lactis 18 1) Protein preparation from L.lactis 18 2) SDS-PAGE and western blot assay 19 3) ELISA assay 19 4) Physiological characterization of transformed L.lactis 20 4. In vitro functional activity assay 20 1) RAW 264.7 cells and growth conditions 20 2) In vitro functional activity assay 20 3) MTT assay 21 4) RT-PCR 22 5. In vivo immunization assay 23 1) Oral administration in BALB/c mice 23 2) Whole mount IHC assay 25 3) Preparation of M-BmpB as model antigen 25 4) Sample collection 27 (1) Serum sample 27 (2) Fecal sample 27 (3) Intestinal lavage sample 28 5) Detection of anti M-BmpB immunoglobulins by ELISA 28 6. Statistical analysis 29 IV. Results and Discussion 30 1. Recombinant L.lactis construction 30 2. Confirmation of sRANKL expression 33 1) Western blot and ELISA assay 33 2) Physiological characterization of transformed L.lactis 35 3. In vitro functional activity assay 37 1) MTT assay 37 2) RT-PCR 38 4. In vivo immunization assay 40 1) Whole mount IHC of PPs 40 2) Preparation of M-BmpB as model antigen 42 3) Detection of anti M-BmpB immunoglobulins by ELISA 43 (1) Detection of M-BmpB specific serum IgG 43 (2) Detection of M-BmpB specific IgA 46 V. Literature Cited 50 VI. Summary in Korean 54 VII. Acknowledgement 56Maste

    ์˜์ œ์„ค์ •์ด๋ก ์˜ ์‹œ๊ฐ์—์„œ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :ํ–‰์ •๋Œ€ํ•™์› ํ–‰์ •ํ•™๊ณผ(ํ–‰์ •ํ•™์ „๊ณต),2019. 8. ์—„์„์ง„.์ „์ž์ฒญ์› ํ”Œ๋žซํผ์ด ๋“ฑ์žฅํ•˜๊ธฐ ์ „๊นŒ์ง€๋Š” ๊ฐ๊ด€์ ์œผ๋กœ ๋‹ค์–‘ํ•œ ์ด์Šˆ๋“ค์— ๋Œ€ํ•˜์—ฌ ๊ตญ๋ฏผ๋“ค์ด ์ง€๋‹Œ ์ƒ๊ฐ, ์ฆ‰ ์—ฌ๋ก  ๋‚ด์ง€๋Š” ๊ณต๋ก  ํ˜น์€ ๊ณต์ค‘์˜์ œ์— ๋Œ€ํ•œ ๊ด€์ฐฐ์€ ์ƒ๋‹นํžˆ ์ œํ•œ์ ์ด์—ˆ๋‹ค๊ณ  ๋ณผ ์ˆ˜ ์žˆ๋‹ค. ๊ด€์ฐฐ๋œ ๊ณต์ค‘์˜์ œ์˜ ๊ฒฝ์šฐ์—๋„ ๋Œ€๋ถ€๋ถ„์€ ์‹œ์œ„ ๋“ฑ ์–ด๋– ํ•œ ์ด์Šˆ์— ๋Œ€ํ•œ ์ง๊ฐ„์ ‘์ ์ธ ์ดํ•ด๊ด€๊ณ„๊ฐ€ ์žˆ๋Š” ์ง‘๋‹จ์˜ ํ–‰๋™์„ ํ†ตํ•œ ์˜๊ฒฌ ํ‘œ์ถœ์ด ์ด๋ค„์ง„ ๊ฒฝ์šฐ ํ˜น์€ ์„ค๋ฌธ์กฐ์‚ฌ๋กœ ํ™•๋ณด๋œ ์†Œ์ˆ˜ ํ‘œ๋ณธ์˜ ์˜๊ฒฌ ๋“ฑ์œผ๋กœ๋งŒ ๊ด€์ธก๋  ์ˆ˜ ์žˆ์—ˆ์œผ๋ฉฐ, ๋˜ ์ด๋“ค ์ค‘ ๋Œ€๋ถ€๋ถ„์€ ์ด๋ฏธ ์–ด๋– ํ•œ ์ด์Šˆ๊ฐ€ ๋ฐœ์ƒํ•œ ํ›„ ํ•œ์ฐธ ๋’ค์— ์ด๋Ÿฌํ•œ ์ด์Šˆ์— ๋Œ€ํ•œ ๊ณต์ค‘์˜์ œ์˜ ๊ด€์ธก์ด ์ด๋ฃจ์–ด์ง€๋ฉฐ, ์ด๋Ÿฌํ•œ ๊ด€์ธก์˜ ๊ฒฐ๊ณผ๊ฐ€ ๋Œ€์ค‘์—๊ฒŒ ์ „๋‹ฌ๋˜๊ธฐ๊นŒ์ง€๋Š” ๋‹ค์‹œ ์–ด๋Š ์ •๋„์˜ ์‹œ๊ฐ„์ด ํ๋ฅด๊ธฐ์— ์ ์‹œ์„ฑ๋„ ๋–จ์–ด์ง„๋‹ค๊ณ  ๋ณผ ์ˆ˜ ์žˆ๋‹ค. ๋ฐ˜๋ฉด, ์ „์ž์ฒญ์› ํ”Œ๋žซํผ์€ ์‹ค์‹œ๊ฐ„์œผ๋กœ ์ฒญ์›์ธ์ด ์–ด๋– ํ•œ ์ด์Šˆ์— ๋Œ€ํ•œ ์ฒญ์›์„ ๋“ฑ๋กํ•  ์ˆ˜ ์žˆ์œผ๋ฉฐ, ์–ด๋Š ๊ตญ๋ฏผ์—๊ฒŒ๋‚˜ ๊ณต๊ฐœ๋˜์–ด ๋ˆ„๊ตฌ๋‚˜ ์ด์— ๋Œ€ํ•œ ๋™์˜ ์ž…์žฅ์„ ํ‘œ๋ช…ํ•  ์ˆ˜ ์žˆ๋‹ค. ์ด๋ฅผ ํ†ตํ•ด ๊ตญ๋ฏผ์˜ ์ฃผ์š” ๊ด€์‹ฌ์‚ฌ๋‚˜ ์–ด๋– ํ•œ ์ด์Šˆ์— ๋Œ€ํ•œ ์ž…์žฅ์„ '๋™์˜ ์ˆ˜' ํ˜น์€ '์„œ๋ช… ์ˆ˜'๋ผ๋Š” ์š”์†Œ๋ฅผ ํ†ตํ•ด ๊ณ„๋Ÿ‰์ ์œผ๋กœ ํŒŒ์•…ํ•  ์ˆ˜ ์žˆ์œผ๋ฉฐ, ๋™์˜ ์ˆ˜๊ฐ€ ๋งŽ์€ ์ฒญ์›์€ ์ƒ๋Œ€์ ์œผ๋กœ ๊ตญ๋ฏผ์˜ ์ƒ๊ฐ, ์ฆ‰, ๊ณต์ค‘์˜์ œ๋ฅผ ๋Œ€๋ณ€ํ•˜๋Š” ์ฒญ์›์œผ๋กœ ๋ณผ ์ˆ˜ ์žˆ๋‹ค. ํŠนํžˆ, ์ด๋ฅผ ์ •๋ถ€๊ฐ€ ์ง์ ‘ ๊ด€๋ฆฌํ•˜๋ฉด์„œ ํŠน์ • ์ˆ˜ ์ด์ƒ์˜ ์„œ๋ช…์„ ํ™•๋ณดํ•œ ์ฒญ์›์€ ์ฒญ์™€๋Œ€์—์„œ ์ง์ ‘ ๋‹ต๋ณ€ํ•˜๋Š” ๋ฐฉ์‹์œผ๋กœ ๊ทธ์ € ๊ตญ๋ฏผ์˜ ๊ณต์ค‘์˜์ œ๋ฅผ ์ œ์‹œํ•˜๋Š” ๊ฒƒ๋ฟ๋งŒ์ด ์•„๋‹ˆ๋ผ ์ด๋ฅผ ์ •๋ถ€๊ฐ€ ํ•œ์ธต ๋” ์‚ดํŽด๋ณผ ์—ฌ์ง€๊ฐ€ ์žˆ๋‹ค๋Š” ์ ์—์„œ ํ•ด๋‹น ์ด์Šˆ์— ๊ด€๋ จํ•œ ์ •์ฑ…์— ์˜ํ–ฅ์„ ๋ฏธ์น  ์ˆ˜ ์žˆ๋‹ค๋Š” ์ ์—์„œ ์ •์ฑ…ํ˜•์„ฑ ์ธก๋ฉด์—์„œ์˜ ์˜์˜๊ฐ€ ์žˆ๋‹ค. ๊ทธ๋ ‡๋‹ค๋ฉด ์ด๋ ‡๊ฒŒ ํŽธ๋ฆฌํ•˜๊ฒŒ ์˜๊ฒฌ์„ ๋ชจ์„ ์ˆ˜ ์žˆ๋Š” ํ”Œ๋žซํผ์˜ ์šด์˜์— ์žˆ์–ด์„œ ๊ตญ๋ฏผ๋“ค์ด ์–ด๋Š ์ด์Šˆ์— ๋Œ€ํ•ด ๊ฐ•ํ•œ ๊ณต๊ฐ๊ณผ ๋™์˜๋ฅผ ๋ณด์ธ๋‹ค๋ฉด, ์ด๋Š” ์–ด๋–ค ์š”์ธ์˜ ์˜ํ–ฅ์„ ๋ฐ›๋Š” ๊ฒƒ์ผ๊นŒ? ๊ธฐ์กด ์ •์ฑ…์˜์ œ์„ค์ • ๊ณผ์ •์—์„œ์ฒ˜๋Ÿผ ์ด์Šˆ ์ž์ฒด์˜ ํŠน์„ฑ์ด๋‚˜ ์ด๋ฅผ ์ „๋‹ฌํ•˜๋Š” ๋ฐฉ์‹์ด ๋” ํฐ ์˜ํ–ฅ์„ ๋ฏธ์น  ๊ฒƒ์ธ๊ฐ€? ํ˜น์€ ํ•ด๋‹น ํ”Œ๋žซํผ์ด ์šด์˜๋˜๋Š” ์˜จ๋ผ์ธ ํ™˜๊ฒฝ์ด๋ผ๋Š” ์š”์†Œ๊ฐ€ ๋” ํฐ ์˜ํ–ฅ์„ ๋ฏธ์น  ๊ฒƒ์ธ๊ฐ€? ๋ณธ ์—ฐ๊ตฌ๋Š” ์ด๋ ‡๊ฒŒ ๋Œ€์ค‘์˜ ์˜๊ฒฌ์„ ๋ชจ์œผ๊ณ  ๊ณต์ค‘์˜์ œ๋ฅผ ํ˜•์„ฑํ•˜์—ฌ ์ •๋ถ€ ์ •์ฑ…์— ์˜ํ–ฅ๋ ฅ์„ ๊ฐ€ํ•  ์ˆ˜ ์žˆ๋Š” ์ƒˆ๋กœ์šด ํ†ต๋กœ์ธ ๊ตญ๋ฏผ์ฒญ์› ํ”Œ๋žซํผ ๋‚ด์—์„œ ํ˜•์„ฑ๋˜๋Š” ์‚ฌํšŒ์  ์ด์Šˆ์— ๋Œ€ํ•˜์—ฌ ์‚ดํŽด๋ณด๊ณ ์ž ํ•œ๋‹ค. ํŠนํžˆ, ์—ฌ๋Ÿฌ ์‚ฌํšŒ์  ์ด์Šˆ๊ฐ€ ๊ณต์ค‘์˜์ œ๊ฐ€ ๋˜๊ธฐ๊นŒ์ง€ ๊ธฐ์กด์˜ ์ •์ฑ…์˜์ œ์„ค์ • ์ด๋ก ์—์„œ ๋‹ค๋ค„์ง„ ์š”์ธ๋“ค๊ณผ ์ƒˆ๋กœ์šด ์˜จ๋ผ์ธ ํ™˜๊ฒฝ์ด๋ผ๋Š” ์š”์ธ๋“ค ์ค‘ ์–ด๋– ํ•œ ์š”์ธ์— ์–ด๋Š ์ •๋„์˜ ์˜ํ–ฅ์„ ๋ฐ›๋Š”์ง€ ์‹ค์ฆ์ ์œผ๋กœ ๋ถ„์„ํ•˜๊ณ ์ž ํ•˜๋Š” ๋ชฉ์ ์„ ๊ฐ€์ง€๊ณ  ์ˆ˜ํ–‰ํ•˜์˜€๋‹ค. ์ด๋ฅผ ์œ„ํ•ด ์ •์ฑ…์˜์ œ์„ค์ •์ด๋ก ๊ณผ ์˜์ œ์„ค์ •๊ธฐ๋Šฅ ์ด๋ก ์—์„œ ๋…ผ์˜๋œ ์š”์ธ๋“ค, ๊ทธ๋ฆฌ๊ณ  Margett(2015)์˜ ์„ ํ–‰์—ฐ๊ตฌ์—์„œ ํ™œ์šฉ๋˜์—ˆ๋˜ ์š”์ธ๋“ค์„ ๋…๋ฆฝ๋ณ€์ˆ˜๋กœ ์„ค์ •ํ•˜์—ฌ ๋ถ„์„ํ•œ๋‹ค. ๋ถ„์„์„ ์œ„ํ•ด ๊ตญ๋ฏผ์ฒญ์› ํ”Œ๋žซํผ์—์„œ ๊ฐ ์ฒญ์›๋“ค์˜ ์ •๋ณด๋“ค์„ ์ˆ˜์ง‘ํ•˜์—ฌ ํ™œ์šฉํ•˜๊ณ ์ž ํ•˜์˜€๋‹ค. ์ •์ฑ…์˜์ œ์„ค์ • ์ด๋ก ์„ ํ†ตํ•ด ๊ฐ ์ฒญ์›์ด ๋‹ด๊ณ  ์žˆ๋Š” ์ด์Šˆ ์ž์ฒด์˜ ํŠน์„ฑ๊ณผ ํ•ด๋‹น ๋‚ด์šฉ์ƒ ํ•ด๋‹น ์ด์Šˆ๋ฅผ ์ „๋‹ฌํ•˜๋Š” ๋ฐฉ๋ฒ•์— ์ฃผ์•ˆ์ ์„ ๋‘๋Š” ๋ณ€์ˆ˜๋“ค์„ ์„ ๋ณ„ํ•˜์˜€๊ณ , ์˜์ œ์„ค์ •๊ธฐ๋Šฅ ์ด๋ก ์„ ํ†ตํ•ด์„œ๋Š” ๊ฐ ์ด์Šˆ๊ฐ€ ์ „ํŒŒ๋˜๋Š” ์˜จ๋ผ์ธ ๋งค์ฒด์˜ ์š”์ธ์„ ์„ ๋ณ„ํ•˜์˜€์œผ๋ฉฐ, ์ด๋Š” ๊ตญ๋ฏผ์ฒญ์› ํ”Œ๋žซํผ ์ž์ฒด๊ฐ€ ๊ฐ€์ง€๊ณ  ์žˆ๋Š” ํ”Œ๋žซํผ์˜ ํŠน์„ฑ๊ณผ ํ•จ๊ป˜ ์˜จ๋ผ์ธ ํ™˜๊ฒฝ์ด๋ผ๋Š” ์š”์ธ์œผ๋กœ ๋ถ„๋ฅ˜ํ•˜์—ฌ ๋ณธ ๋ถ„์„์—์„œ ํ™œ์šฉํ•˜๊ณ ์ž ํ•˜์˜€๋‹ค. ๋˜ํ•œ, ๋ณ€์ˆ˜ ์„ค์ • ๊ณผ์ •์—์„œ ์˜๊ตญ๊ณผ ๋ฏธ๊ตญ์˜ ์ „์ž์ฒญ์› ํ”Œ๋žซํผ์— ๋Œ€ํ•ด์„œ ์—ฐ๊ตฌ ๋ฐ ๋ถ„์„์„ ์‹ค์‹œํ•œ Margett(2015)์˜ ์„ ํ–‰ ์—ฐ๊ตฌ๋ฅผ ์ฐธ์กฐํ•˜์˜€์œผ๋ฉฐ, ๊ฐ ์ฒญ์›์˜ ์„œ๋ช… ํš๋“ ์–‘์ƒ์„ ์•Œ์•„๋ณด๋Š” ๋ถ„์„์—๋„ ํ•ด๋‹น ์—ฐ๊ตฌ๋ฅผ ์ฐธ์กฐํ•˜์˜€๋‹ค. ํ•ด๋‹น ์—ฐ๊ตฌ๋Š” 2018๋…„ 12์›” 31์ผ๋ถ€ํ„ฐ ์ˆ˜์ง‘์„ ์‹œ์ž‘ํ•˜์—ฌ, 2019๋…„ 2์›” 28๊นŒ์ง€ ์ข…๋ฃŒ๋œ ์ฒญ์›๋“ค์„ ๋Œ€์ƒ์œผ๋กœ ํ•œ๋‹ค. ์—ฌ๊ธฐ์„œ ์—ฐ๊ตฌ ๋ถ„์„ ๋‹จ์œ„๋Š” ๊ฐ ์ฒญ์›์ด ๋˜๋ฉฐ, ์—ฐ๊ตฌ ๊ธฐ๊ฐ„์€ ๋ฐ์ดํ„ฐ ์ˆ˜์ง‘ ๊ธฐ๊ฐ„๊ณผ ๋™์ผํ•œ 2018๋…„ 12์›” 31์ผ๋ถ€ํ„ฐ 2019๋…„ 2์›” 28์ผ๊นŒ์ง€๊ฐ€ ๋œ๋‹ค. ์—ฐ๊ตฌ ๋ถ„์„์—๋Š” ์ด์ƒ๊ฐ’(Outlier)์˜ ์˜ํ–ฅ์„ ๋œ๋ฐ›๋Š” ๋กœ๋ฒ„์ŠคํŠธ ๋ฐฉ์‹์„ ์ ์šฉํ•œ ๋‹ค์ค‘ํšŒ๊ท€๋ชจํ˜•์„ ํ™œ์šฉํ•˜์˜€๋‹ค. ๋ณธ ์—ฐ๊ตฌ์—์„œ์˜ ์ข…์†๋ณ€์ˆ˜๋Š” ๊ฐ ์ฒญ์›์ด ํš๋“ํ•œ ์ตœ์ข… ์„œ๋ช… ์ˆ˜์ด๋‹ค. ๋ณธ ์—ฐ๊ตฌ์˜ ์ฃผ๋œ ๊ฒฐ๊ณผ๋ฅผ ์‚ดํŽด๋ณด๋ฉด ๋‹ค์Œ๊ณผ ๊ฐ™๋‹ค. ์ฒซ์งธ, ์ผ๋ถ€ ์ฒญ์› ๋ชฉ์ ์€ ๊ฐ ์ฒญ์›์˜ ์ตœ์ข… ์„œ๋ช… ํš๋“ ์ˆ˜์— ์˜ํ–ฅ์„ ๋ฏธ์น  ์ˆ˜ ์žˆ๋‹ค. ๋‘˜์งธ, ์ฒญ์›์ธ์ด ์ž์‹ ์„ ์†Œ๊ฐœํ•  ๊ฒฝ์šฐ ๊ฐ ์ฒญ์›์˜ ์ตœ์ข… ์„œ๋ช… ํš๋“ ์ˆ˜์— ์ •(+)์˜ ์˜ํ–ฅ์„ ์ค€๋‹ค. ์…‹์งธ, ์ฒจ๋ถ€ URL ์ข…๋ฅ˜์— ๋”ฐ๋ผ ๊ฐ ์ฒญ์›์˜ ์ตœ์ข… ์„œ๋ช… ํš๋“ ์ˆ˜๊ฐ€ ๋‹ค๋ฅด๋‹ค. ํŠนํžˆ, ์ด ์ค‘ ์†Œ์…œ๋ฏธ๋””์–ด ๊ด€๋ จ ์ฒจ๋ถ€ URL์„ ํ™œ์šฉํ•  ๊ฒฝ์šฐ, ์ฒจ๋ถ€ URL์„ ํ™œ์šฉํ•˜์ง€ ์•Š์•˜์„ ๋•Œ๋ณด๋‹ค ๋” ๋งŽ์€ ์„œ๋ช… ํš๋“ ์ •๋„๋ฅผ ๋ณด์ด๋Š” ๋ฐ˜๋ฉด, ์–ธ๋ก  ๊ด€๋ จ ์ฒจ๋ถ€ URL์„ ํ™œ์šฉํ•  ๊ฒฝ์šฐ์—๋Š” ์œ ์˜๋ฏธํ•œ ๊ด€๊ณ„๋ฅผ ๋ฐœ๊ฒฌํ•˜์ง€ ๋ชปํ•˜์˜€๋‹ค. ์…‹์งธ, ๊ฐ ์ฒญ์›์ด ๋“ฑ๋ก๋œ ๋‚  ํ•จ๊ป˜ ๋“ฑ๋ก๋œ ์ฒญ์›๋“ค์˜ ์ˆ˜๋Š” ์ตœ์ข… ์„œ๋ช… ํš๋“ ์ˆ˜์— ๋ถ€(-)์˜ ์˜ํ–ฅ์„ ์ค€๋‹ค. ๋„ท์งธ, ํŠธ์œ„ํ„ฐ์—์„œ์˜ ํฌ์ŠคํŒ… ์ˆ˜๊ฐ€ ์ตœ์ข… ์„œ๋ช… ํš๋“ ์ˆ˜์— ์ •(+)์˜ ์˜ํ–ฅ์„ ์ฃผ๋Š” ๋ฐ˜๋ฉด, ์˜จ๋ผ์ธ ๋‰ด์Šค ๊ธฐ์‚ฌ ์ˆ˜๋Š” ์ตœ์ข… ์„œ๋ช… ํš๋“ ์ˆ˜์— ์œ ์˜๋ฏธํ•œ ๊ฒฐ๊ณผ๋ฅผ ๋‚˜ํƒ€๋‚ด์ง€ ๋ชปํ•˜์˜€๋‹ค. ๋‹ค์„ฏ์งธ, ๊ฐ ์ฒญ์›์ด ์ฒซ ๋‚  ํš๋“ํ•˜๋Š” ์„œ๋ช… ๋น„์œจ์€ ์ตœ์ข… ์„œ๋ช… ํš๋“ ์ˆ˜์— ์ •(+)์˜ ์˜ํ–ฅ์„ ์ค€๋‹ค. ์•ž์„œ ์–ธ๊ธ‰ํ•œ ๊ฒƒ์ฒ˜๋Ÿผ ๋ณธ ์—ฐ๊ตฌ๋Š” ๊ตญ๋ฏผ์ฒญ์› ํ”Œ๋žซํผ์ด ๊ฐ€์ง„ ์˜จ๋ผ์ธ ํ™˜๊ฒฝ ์š”์ธ ๋ฟ๋งŒ ์•„๋‹ˆ๋ผ, ์ •์ฑ…์˜์ œ์„ค์ • ์ด๋ก ์—์„œ ๋‹ค๋ฃฌ ์š”์ธ๋“ค๊ณผ ์˜์ œ์„ค์ •๊ธฐ๋Šฅ ์ด๋ก ์—์„œ ๋‹ค๋ฃฌ ์š”์ธ๋“ค ๊ฐ๊ฐ ์–ด๋– ํ•œ ์˜ํ–ฅ์„ ์ง€๋‹ˆ๋Š”๊ฐ€์— ๋Œ€ํ•ด ๋ถ„์„ํ•˜๊ณ ์ž ํ•˜์˜€๋‹ค. ์ด๋Š” ๊ธฐ์กด Margett(2015)์˜ ์—ฐ๊ตฌ๊ฐ€ ์˜จ๋ผ์ธ์ƒ์˜ ์ „ํŒŒ ํ™œ๋™๊ณผ ์ „์ž์ฒญ์› ํ”Œ๋žซํผ์˜ ๋””์ž์ธ์— ์˜ํ•œ ์š”์ธ์„ ์ค‘์‹ฌ์œผ๋กœ ์‚ดํŽด๋ณธ๋ฐ ๋ฐ˜ํ•ด, ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ํ•ด๋‹น ์š”์ธ๋“ค๊ณผ ๋”๋ถˆ์–ด ์ •์ฑ…์˜์ œ์„ค์ • ๋ฐ ์˜์ œ์„ค์ •๊ธฐ๋Šฅ ์ด๋ก  ์ธก๋ฉด์—์„œ์˜ ์š”์ธ๋“ค์„ ๊ณ ๋ คํ•˜์˜€๋‹ค๋Š” ์ ์—์„œ ๊ธฐ์กด์˜ ์—ฐ๊ตฌ์™€ ์ฐจ๋ณ„์„ฑ์„ ๊ฐ€์ง€๋ฉฐ, ์ด๋ฅผ ํ†ตํ•ด ๊ฐ ์ด์Šˆ๊ฐ€ ์ „์ž์ฒญ์› ํ”Œ๋žซํผ์„ ํ†ตํ•ด ๊ณต์ค‘์˜์ œ์— ๋„๋‹ฌํ•˜๋Š”๋ฐ ๊ธฐ์กด ์ •์ฑ…์˜์ œ์„ค์ • ์š”์ธ์— ์˜ํ•ด ์˜ํ–ฅ์„ ๋ฐ›๋Š”์ง€ ํ˜น์€ ์˜จ๋ผ์ธ ํ™˜๊ฒฝ์˜ ์˜ํ–ฅ์„ ๋ฐ›๋Š”์ง€ ์ข€ ๋” ๋‹ค๊ฐ์ ์ธ ์‹œ๊ฐ์œผ๋กœ ๋ถ„์„ํ•˜์˜€๋‹ค๋Š” ๋ฐ์— ์ด ์—ฐ๊ตฌ์˜ ์˜์˜๊ฐ€ ์žˆ๋‹ค.์ œ 1 ์žฅ ์„œ ๋ก  ์ œ 1 ์ ˆ ์—ฐ๊ตฌ์˜ ๋ฐฐ๊ฒฝ๊ณผ ๋ชฉ์  ์ œ 2 ์ ˆ ์—ฐ๊ตฌ์˜ ๋Œ€์ƒ๊ณผ ๋ฒ”์œ„ ์ œ 2 ์žฅ ์ด๋ก ์  ๋…ผ์˜์™€ ์„ ํ–‰์—ฐ๊ตฌ ๊ฒ€ํ†  ์ œ 1 ์ ˆ ์ด๋ก ์  ๋…ผ์˜ 1. ์ „์ž์ฒญ์› ํ”Œ๋žซํผ 2. ์˜์ œ์„ค์ •(Agenda-setting) ์ด๋ก  3. ์ •์ฑ…์˜์ œ์„ค์ • ์ด๋ก ์— ๊ด€ํ•œ ๋…ผ์˜ 4. ์˜จ๋ผ์ธ ํ™˜๊ฒฝ์—์„œ์˜ ์ด์Šˆ ์ „ํŒŒ์— ๊ด€ํ•œ ๋…ผ์˜ ์ œ 2 ์ ˆ ์„ ํ–‰์—ฐ๊ตฌ ๊ฒ€ํ†  1. ํ•ด์™ธ ์ „์ž์ฒญ์› ํ”Œ๋žซํผ์— ๊ด€ํ•œ ์—ฐ๊ตฌ 2. ์ „์ž์ฒญ์› ํ”Œ๋žซํผ๊ณผ ์ •์ฑ…์˜์ œ ํ˜•์„ฑ์˜ ์ƒ๊ด€์„ฑ์— ๊ด€ํ•œ ์—ฐ๊ตฌ 3. ๊ธฐ์กด ์—ฐ๊ตฌ์˜ ๋น„ํŒ์  ๊ฒ€ํ†  ์ œ 3 ์žฅ ์—ฐ๊ตฌ ์„ค๊ณ„ ์ œ 1 ์ ˆ ์—ฐ๊ตฌ์˜ ๋ถ„์„ํ‹€ 1. ์—ฐ๊ตฌ ๋ชจํ˜• 2. ์—ฐ๊ตฌ ๊ฐ€์„ค ์ œ 2 ์ ˆ ๋ณ€์ˆ˜์˜ ๊ฐœ๋…๊ณผ ์กฐ์ž‘์  ์ •์˜ 1. ์ข…์† ๋ณ€์ˆ˜ 2. ๋…๋ฆฝ ๋ณ€์ˆ˜ 3. ํ†ต์ œ ๋ณ€์ˆ˜ ์ œ 3 ์ ˆ ์—ฐ๊ตฌ ๋ฐฉ๋ฒ• 1. ๋ถ„์„ ๋ฐฉ๋ฒ• 2. ํ™œ์šฉ ๋ฐ์ดํ„ฐ ์ œ 4 ์žฅ ์ฒญ์™€๋Œ€ ๊ตญ๋ฏผ์ฒญ์› ํ”Œ๋žซํผ ๊ฐœ๊ด€ ์ œ 1 ์ ˆ ์ฒญ์™€๋Œ€ ๊ตญ๋ฏผ์ฒญ์› ํ”Œ๋žซํผ ๊ฐœ์š” ์ œ 2 ์ ˆ ๊ตญ๋ฏผ์ฒญ์› ํ”Œ๋žซํผ์˜ ์ž‘๋™ ๋ฐฉ์‹ ์ œ 3 ์ ˆ ๊ตญ๋ฏผ์ฒญ์› ํ”Œ๋žซํผ์˜ ์ธํ„ฐํŽ˜์ด์Šค ์ œ 4 ์ ˆ ๊ฐ ์ฒญ์›์— ํฌํ•จ๋œ ์ •๋ณด ์ œ 5 ์ ˆ ๊ตญ๋ฏผ์ฒญ์› ํ”Œ๋žซํผ์˜ ์˜์ œ ์„ค์ • ์˜ํ–ฅ๋ ฅ ์ œ 5 ์žฅ ๋ถ„์„ ๊ฒฐ๊ณผ ์ œ 1 ์ ˆ ๊ตญ๋ฏผ์ฒญ์› ํ”Œ๋žซํผ์˜ ์„œ๋ช… ํš๋“ ํŠน์„ฑ 1. ๊ฐ ์ฒญ์› ๋ณ„ ์„œ๋ช… ํš๋“ ๊ฐœ์š” 2. ๋ถ„์„ ๋ฐ์ดํ„ฐ์˜ ๋นˆ๋„๋ถ„์„/๊ธฐ์ˆ ๋ถ„์„ ๊ฒฐ๊ณผ ์ œ 2 ์ ˆ ๋‹ค์ค‘ํšŒ๊ท€๋ถ„์„ ๊ฒฐ๊ณผ ๋ฐ ๊ฐ€์„ค ๊ฒ€์ฆ 1. ๋‹ค์ค‘๊ณต์„ ์„ฑ์˜ ๊ฒ€์ฆ 2. ๋‹ค์ค‘ํšŒ๊ท€๋ถ„์„ ๊ฒฐ๊ณผ ๋ฐ ๊ฐ€์„ค ๊ฒ€์ฆ ์ œ 3 ์ ˆ ๊ฒฐ๊ณผ์˜ ํ•ด์„ ๋ฐ ํ† ๋ก  ์ œ 6 ์žฅ ๊ฒฐ๋ก  ์ œ 1 ์ ˆ ์—ฐ๊ตฌ ๊ฒฐ๊ณผ์˜ ์š”์•ฝ ์ œ 2 ์ ˆ ์—ฐ๊ตฌ์˜ ์‹œ์‚ฌ์ ๊ณผ ํ•œ๊ณ„ ์ฐธ๊ณ ๋ฌธํ—ŒMaste

    (A) study of health care utilization and medical care expenses of dying in older adults : of cerebrovascular disease. : ๋‡Œํ˜ˆ๊ด€์งˆํ™˜์„ ์ค‘์‹ฌ์œผ๋กœ

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    ๋ณด๊ฑดํ•™๊ณผ/์„์‚ฌ[ํ•œ๊ธ€] ์ด ์—ฐ๊ตฌ๋Š” ์šฐ๋ฆฌ๋‚˜๋ผ ๋…ธ์ธ๋“ค์˜ ์‚ฌ๋ง ์ „ ์˜๋ฃŒ์ด์šฉ์ˆ˜์ค€์„ ์•Œ์•„๋ณด๊ณ ์ž, 1999๋…„๋„ ์‚ฌ๋ง์›์ธ 1์œ„์ธ ๋‡Œํ˜ˆ๊ด€์งˆํ™˜(ํ†ต๊ณ„์ฒญ, 2000)์œผ๋กœ 1999๋…„ 3์›” 1์ผ๋ถ€ํ„ฐ 2000๋…„ 2์›” 28์ผ๊นŒ์ง€ ์‚ฌ๋งํ•œ ๋…ธ์ธ๋“ค์˜ ์‚ฌ๋ง ์ „ ์˜๋ฃŒ๋น„์šฉ์„ ๋ถ„์„ํ•˜๊ณ , ์‚ฌ๋ง์ „ ๊ธฐ๊ฐ„๋ณ„ ์˜๋ฃŒ์ด์šฉ ์ˆ˜์ค€์˜ ๋ณ€ํ™”๋ฅผ ๋ถ„์„ํ•˜์˜€๋‹ค. ์ฃผ์š” ๊ฒฐ๊ณผ๋Š” ๋‹ค์Œ๊ณผ ๊ฐ™๋‹ค. 1999๋…„ 3์›” 1์ผ๋ถ€ํ„ฐ 2000๋…„ 2์›” 28์ผ๊นŒ์ง€ ๋‡Œํ˜ˆ๊ด€์งˆํ™˜์œผ๋กœ ์˜๋ฃŒ๊ธฐ๊ด€์„ ํ•œ๋ฒˆ์ด๋ผ๋„ ์ด์šฉํ•˜๊ณ  ์‚ฌ๋งํ•œ ๋…ธ์ธ๋“ค์€ 5,453๋ช…์ด์—ˆ์œผ๋ฉฐ, ์ง„๋ฃŒ๊ฑด์ˆ˜๋Š” 11,111๊ฑด์ด์—ˆ๋‹ค. ์‚ฌ๋ง์ „ ๊ธฐ๊ฐ„๋™์•ˆ 1์ธ๋‹น ํ‰๊ท  2.08ํšŒ ์˜๋ฃŒ๊ธฐ๊ด€์„ ์ด์šฉํ–ˆ๊ณ , 1์ธ๋‹น ํ‰๊ท  1,201,120์›์˜ ์ง„๋ฃŒ๋น„๋ฅผ ์‚ฌ์šฉํ–ˆ๋‹ค. 65์„ธ ์ด์ƒ ์ธ๊ตฌ์˜ ์‚ฌ๋ง ์ „ 1๋…„์˜ ์˜๋ฃŒ์ด์šฉ ์ˆ˜์ค€์„ ์‚ฌ๋ง์ „ ๊ธฐ๊ฐ„์— ๋”ฐ๋ผ ๋‚˜๋ˆ„์–ด ๋ณธ ๊ฒฐ๊ณผ ์‚ฌ๋ง์‹œ๊ธฐ์— ๊ฐ€๊นŒ์šธ์ˆ˜๋ก ์˜๋ฃŒ์ด์šฉ์ด ์ฆ๊ฐ€ํ•˜์˜€์œผ๋ฉฐ, ์‚ฌ๋ง ์ „ 30์ผ๊ฐ„์˜ ํ‰๊ท ์ง„๋ฃŒ๋น„๋Š” 413,860์›์ด์—ˆ๋‹ค. ํŠนํžˆ ๋ฐฉ๋ฌธ์œ ํ˜• ์ค‘ ์ž…์›์˜ ๊ฒฝ์šฐ, ์‚ฌ๋ง์ „ 30์ผ๊ฐ„์˜ ์ง„๋ฃŒ๋น„๋Š” ์‚ฌ๋ง ์ „ 31 - 60์ผ์— ๋น„ํ•ด ์•ฝ 2.9๋ฐฐ ์ฆ๊ฐ€ํ–ˆ๊ณ , ์™ธ๋ž˜์˜ ๊ฒฝ์šฐ์—๋Š” ์•ฝ 2.3๋ฐฐ ์ฆ๊ฐ€ํ•˜์˜€๋‹ค. ์‚ฌ๋ง ์ „ ๊ธฐ๊ฐ„์— ๋”ฐ๋ฅธ ์ž…์› ๋ฐ ์™ธ๋ž˜๋ฐฉ๋ฌธ ์ผ๋‹น ์ง„๋ฃŒ๋น„ ์—ญ์‹œ ์‚ฌ๋ง์‹œ๊ธฐ์— ๊ฐ€๊นŒ์šธ์ˆ˜๋ก ๊ธ‰๊ฒฉํžˆ ์ฆ๊ฐ€ํ•˜์˜€๋‹ค. ์‚ฌ๋ง ์ „ 30์ผ์˜ ์˜๋ฃŒ์ด์šฉ์ˆ˜์ค€์„ ์ง„๋ฃŒ๊ฑด์ˆ˜๋ฅผ ๋‹จ์œ„๋กœ ํ•ด์„œ ์„ธ๋ถ€์ ์œผ๋กœ ์‚ดํŽด๋ณธ ๊ฒฐ๊ณผ, ์—ฌ์ž๊ฐ€ ์ž…์›๊ณผ ์™ธ๋ž˜ ๋ชจ๋‘ ์˜๋ฃŒ์ด์šฉ์„ ๋” ๋งŽ์ด ํ–ˆ์œผ๋‚˜, ์ง„๋ฃŒ๋น„๋Š” ๋‚จ์ž๊ฐ€ ๋” ๋†’์•˜๋‹ค. ์‚ฌ๋ง์ „ ๊ธฐ๊ฐ„๋ณ„ ์ž…์› ์ง„๋ฃŒ๋น„๋Š” ์‚ฌ๋ง ์ง์ „์˜ ์ž…์› ์ง„๋ฃŒ๋น„๊ฐ€ ์™ธ๋ž˜์— ๋น„ํ•ด์„œ ๊ธ‰๊ฒฉํžˆ ์ฆ๊ฐ€ํ•˜์˜€๋Š”๋ฐ ์ด๋Š” ์‚ฌ๋ง ์ง์ „์˜ ์˜๋ฃŒ์ด์šฉ์ด ์™ธ๋ž˜์—์„œ๋ณด๋‹ค ์ž…์›์—์„œ ๋” ๋งŽ์•˜๊ธฐ ๋•Œ๋ฌธ์ด๋‹ค. ๊ฒฐ๋ก ์ ์œผ๋กœ ์‚ฌ๋ง์‹œ๊ธฐ์— ๊ฐ€๊นŒ์šธ์ˆ˜๋ก ์˜๋ฃŒ์ด์šฉ์ˆ˜์ค€์€ ๋‹ค๋ฅธ ์„ ํ–‰์—ฐ๊ตฌ๋“ค๊ณผ ๋งˆ์ฐฌ๊ฐ€์ง€๋กœ ์ฆ๊ฐ€ํ•˜๋Š” ๊ฒƒ์„ ์•Œ ์ˆ˜ ์žˆ์—ˆ์ง€๋งŒ, ๋™์ผํ•œ ์ƒ๋ณ‘์— ๋Œ€ํ•ด์„œ๋„ ํ•ฉ๋ณ‘์ฆ ์œ ๋ฌด์™€ ์ฆ์ƒ์˜ ๊ฒฝ์ค‘๋„์— ๋”ฐ๋ผ ์˜๋ฃŒ์ด์šฉ์ •๋„๊ฐ€ ๋‹ฌ๋ผ์ง€๊ธฐ ๋•Œ๋ฌธ์— ์งˆ๋ณ‘๊ตฌ์„ฑ(case mix) ์š”์ธ์— ์˜ํ•œ ์˜๋ฃŒ์ด์šฉ์˜ ์ฐจ์ด๋ฅผ ๊ณ ๋ คํ•œ ์—ฐ๊ตฌ๊ฐ€ ํ•„์š”ํ•˜๋‹ค. -------------------- ํ•ต์‹ฌ๋˜๋Š” ๋ง : ๋…ธ์ธ, ์‚ฌ๋ง์ „ ๊ธฐ๊ฐ„, ์˜๋ฃŒ์ด์šฉ [์˜๋ฌธ] The objective is to identify the medical service utilization frequency in the aged before death. Medical expense of the aged who had passed away since March 1, 1999 till February 28, 2000 due to cerebrovascular disease was analyzed. Cerebrovascular disease was recorded as the number one cause of death in 1999 (Korea Statistical Office, 2000). Then we analyzed the trend of the medical service utilization level by one's life time. Following are the results of the analysis. From March 1, 1999 till February 28, 2000 there were 5,453 elderly who had passed away after utilizing a medical institute due to cerebrovascular disease even with one time visit. The number of times of Medical care utilization was 11,111. Before death, they used medical services 2.08 times in average and spent 1,201,120 Won as medical expenses. Looking into medical care utilization level by the population over 65 years for a year before death, they used medical services more frequently right before their death. Average medical expenses for 30 days before their death was 413,860 Won. Especially in case of hospitalization, the medical expenses for the duration of 30 days before death was increased about 2.9 times compared to 31 - 60 days before death. In case of visiting patients, it was increased by 2.3 times. Daily medical expenses of hospitalization and ambulatory care was also rapidly increased till death. Looking into the medical services utilization level for the 30 days before death in detail, women used medical services more frequently both in hospitalization and ambulatory care. However the medical expenses was higher in male patients. Medical expenses of hospitalization was rapidly increased right before death compared to the visiting patients. It is probably because more medical services were used during hospitalization than outpatient department. Conclusively, medical services utilization was increased when death was near just as the shown by precedent studies. However it is needed to study further considering the difference of medical services utilization by case mix, as medical utilization level will be different according to the seriousness of the symptoms and whether there are associated with complications.ope

    ํ”„๋ž‘์Šค ์ œ3๊ณตํ™”์ •์˜ ์„ธ์†ํ™”์™€ ๊ตญ๋ฏผํ˜•์„ฑ : ์ดˆ๋“ฑํ•™๊ต ๊ต๊ณผ์„œ ๋ถ„์„์„ ์ค‘์‹ฌ์œผ๋กœ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธๅคงๅญธๆ ก ๅคงๅญธ้™ข :่ฅฟๆด‹ๅฒๅญธ็ง‘,1995.Maste

    1910๋…„๋Œ€ ใ€Žๅคฉ้“ๆ•Žๆœƒๆœˆๅ ฑใ€๋ฅผ ํ†ตํ•ด์„œ ๋ณธ ๋ฏผ์ค‘์˜ ์‚ถ

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    Entering the 1910s', the Chosun people had just lost their country to the hands of the Japanese, and were expecting brutal ruling of the Japanese authorities. Yet during the 1910s', the Cheondo-gyo religious order witnessed an explosive uplift in its own status, and have become one of the leading religious orders of the time. The total number of the order's members is known to have reached even 3 million. The reason behind this uplift is obvious. Since the 18th century, the public have been wishing the advent of an economically sound, and politically democratic new age, but the instant occupation by foreign forces were forcing that age away from being realized. Then as one of the indigenous religions of those days, the Cheondo-gyo order, supporting the adherence to nationality and modern qualities, managed to provide the public with a renewed hope, and even a prospect of Utopian nature. The ใ€ŒCheondo Gyohwae Weolbo(ๅคฉ้“ๆ•Žๆœƒๆœˆๅ ฑ)ใ€ Monthly-bulletin, created by the Cheondo-gyo order, was first published in August 15th 1910, and was almost the only magazine at the time which had been published in a monthly fashion without any delays or omissions for quite a long time. This fact alone shows the influence and power the Cheondo-gyo religion had had upon the pubic. This magazine was the only source for the local believers who wished to reach and hear from the head of the order Son Byeong Hi, or other fellow believers, or even touch the modem qualities which were beginning to flood the lives of the public back then. And it was also the only way for the Cheondo-gyo believers to express their thoughts and feelings in a published media. So the influence that this magazine had upon the general believers, who were trying to shape their own perspectives toward their lives, the universe, the society, its history, and not to mention their own nationality, was quite tremendous. This article have examined the editorials, reports and miscellaneous notifications which were all appeared in this monthly-bulletin. The bulletin itself was very accessible to the general believer-base, who were mostly peasants, so analyzing the contents of this publication should shed some light on the task trying to properly examine the lives of the Chosun public, who were beginning to learn modem qualities while also maintaining their national loyalty, by going through family-based religious training and extensive meditations, provided by the unified guidance of the Cheondo-gyo order, in a difficult time where the very nation had lost its sovereignty. Later the Cheondo-gyo order served as one of the leading figures of the 3.1 Movement, and there is no doubt that it was made possible thanks to the potentials and strengths accumulated within the very hearts of the Chosun public, who tried to overcome the drastic, conquered reality by joining the Cheondo-gyo activities and embracing the order's philosophy

    Studies on Tolerance Level and Sensitivity for Patient-specific Quality Assurance in Radiation Therapy

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ํ˜‘๋™๊ณผ์ • ๋ฐฉ์‚ฌ์„ ์‘์šฉ์ƒ๋ช…๊ณผํ•™์ „๊ณต, 2013. 8. ์šฐํ™๊ท .Purpose: The aim of this study was to investigate the tolerance level and sensitivity of patient-specific quality assurance (QA) for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Methods: In order to investigate the tolerance level of patient-specific QA for IMRT in Korea, a multi-institutional study involving 12 radiation therapy institutions was performed. And then, based on the acquired tolerance level from multi-institutional study, sensitivities of various QA methods to detect errors in IMRT and VMAT plans were investigated. The multi-institutional study was performed by (1) point dose measurements using ion chamber at high- and low-dose regions (2) and planar (per-field and composite-field) dose measurements using film or 2-dimensional detector array. The multi-institutional study consisted of two programs, one was mock program and the other was clinic program. For mock program, we employed five mock structures reflecting anatomy of average Korean, while clinical treatment plans were used for clinic program to investigate the tolerance level. With the results of multi-institutional study, patient-specific QAs of point dose measurements with ion chamber, measurement of 2D dose distribution of axial plane with radiochromic film (EBT2), measurements of 2D dose distribution of coronal plane with MatriXXยฎ and measurements of 3D volume dose distribution with COMPASSยฎ has been performed. The results were compared with statistics by dividing into four groups according to delivery technique (IMRT group and VMAT group) and the degree of modulation (prostate group and H&N group). Additionally, a new discretized deliverable VMAT plan (i.e., static arc (SA) plan) was generated and performed 3D QA to evaluate the dose discrepancy in planning target volume (PTV). One of the reasons possible to explain this discrepancy was an arc discretization of VMAT in treatment planning system (TPS). The dose discrepancy of PTV between VMAT and SA plans were evaluated using by gamma test with 3%/3 mm criteria and dose difference at 95% and 5% volume of PTV, respectively. Results: Since the concept of confidence limit (CL) was appropriate for point dose measurement, tolerance level could be acquired. The tolerance level of point dose measurement at high-dose region was ยฑ3% in both two programs. The tolerance level at low-dose region was ยฑ5% in mock program, while it was ยฑ7% and ยฑ5% for linear accelerator (LINAC) and tomotherpy (TOMO) group in clinic program, respectively. On the contrary, for planar dose measurement, the concept of CL was not appropriate because of a large local deviation and a small number of samples. However, the results of planar dose measurement in both programs were well agreed with that of multi-institutional study performed by American Association of Physicists in Medicine (AAPM). In the sensitivity study, the results of point dose measurement followed a normal distribution at all groups. The CL for IMRT, VMAT, prostate, and H&N groups were 3.0%, 2.1%, 1.0%, and 3.4%, respectively. The results of 2D dose measurements in axial and coronal plane showed significant differences at delivery groups (IMRT vs. VMAT) and patient groups (prostate vs. H&N) with the 3%/3 mm criteria. The results of 3D volume dose measurements showed significant differences at delivery groups and patient groups in both criteria. There was no strong correlation between 2D QAs at axial plane and coronal plane. Similarly no correlation was observed between 2D and 3D QAs. Only 3D QA was possible to detect a dose discrepancy in PTV during delivery of VMAT. As the result of evaluation of arc discretization, the gamma passing rate of QA results were 92.1% and 96.8% for VMAT and SA QA, respectively. The dose differences at D95 were 2.61% and 0.97% and at D5 were 2.71% and 0.04% for VMAT and SA QA, respectively. Conclusions: Since the result of a multi-institutional study in Korea was coincident with those of AAPM and European Society for Therapeutic Radiology and Oncology (ESTRO) guidelines, patient-specific QA in Korea could be considered to meet the standards of international guideline. However, a point dose and 2D measurements recommended as patient-specific QA methods by international guidelines seem not to be enough to guarantee of an accurate delivery of IMRT and VMAT plans because no correlation was observed among point dose measurements, 2D QA and 3D QA. Three-dimensional QA was most sensitive to detect errors in treatment plans especially for VMAT. Therefore, it seems to be reasonable to adopt 3D QA as a patient-specific QA method for accurate radiation therapy using IMRT and VMAT techniques.Abstract i Contents โ…ณ List of tables and figures โ…ด List of abbreviations โ…ธ General Introduction 1 Chapter 1 3 A Multi-institutional Study on Tolerance Levels of IMRT Dose Quality Assurance Measurements in Korea Introduction 4 Material and Methods 6 Results 20 Discussion 40 Chapter 2 A Study on Various Patient-Specific Quality Assurances Concerning the Sensitivity to Detect Errors in IMRT and VMAT Introduction 43 Material and Methods 46 Results 54 Discussion 81 General Discussion 85 References 86 Abstract in Korean 101Docto

    A Study on the theoretical structure and the realization of J. Habermas`s discourse ethics

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    ํ•™์œ„๋…ผ๋ฌธ(๋ฐ•์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :๊ตญ๋ฏผ์œค๋ฆฌ๊ต์œก๊ณผ,2000.Docto

    Stay or Leave? A Study of the Impact of Motivation and Burnout on Employee Turnover Intention in the Public Sector

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    ๋ณธ ์—ฐ๊ตฌ๋Š” ์ง€๋ฐฉ์„ธ ๊ณต๋ฌด์›๋“ค์„ ๋Œ€์ƒ์œผ๋กœ ์ง๋ฌดํ™˜๊ฒฝ์ธ์‹์กฐ์‚ฌ๋ฅผ ์‹œํ–‰ํ•œ ์ž๋ฃŒ๋ฅผ ๋ฐ”ํƒ•์œผ๋กœ, ๊ทธ๋“ค์˜ ์ง๋ฌด๋™๊ธฐ์™€ ์ง๋ฌด์†Œ์ง„์ด ์ด์ง์˜๋„์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ์„ ์‚ดํŽด๋ณด์•˜๋‹ค. ์—ฐ๊ตฌ ๋ถ„์„ ๊ฒฐ๊ณผ ์ง€๋ฐฉ์„ธ ๊ณต๋ฌด์›๋“ค์—๊ฒŒ๋Š” ๊ฒฝ์ œ์  ๋ณด์ƒ๊ณผ ์™ธ๋ถ€์ง€์› ๋“ฑ์„ ํฌํ•จํ•œ ์™ธ์  ์ง๋ฌด๋™๊ธฐ๋ณด๋‹ค๋Š” ๋‚ด์  ์ง๋ฌด๋™๊ธฐ๊ฐ€, ์ง๋ฌด์†Œ์ง„ ์ค‘์—์„œ๋Š” ์ž์•„์„ฑ์ทจ๊ฐ ์ €ํ•˜, ๋น„์ธ๊ฐ„ํ™” ๋ณด๋‹ค ์ •์„œ์  ๊ณ ๊ฐˆ์ด ์ง€๋ฐฉ์„ธ ๊ณต๋ฌด์›๋“ค์˜ ์ด์ง์˜๋„์— ํ†ต๊ณ„์ ์œผ๋กœ ์œ ์˜๋ฏธํ•œ ์˜ํ–ฅ์„ ๋ฏธ์ณค๋‹ค. ๋ณด๋‹ค ๊ตฌ์ฒด์ ์œผ๋กœ, ๋ณธ ์—ฐ๊ตฌ๋ฅผ ํ†ตํ•ด ๋‚ด์  ์ง๋ฌด๋™๊ธฐ๊ฐ€ ๋†’์„์ˆ˜๋ก ์ •์„œ์  ๊ณ ๊ฐˆ์ด ๋‚ฎ์„์ˆ˜๋ก ์ง€๋ฐฉ์„ธ ๊ณต๋ฌด์›๋“ค์˜ ์ด์ง์˜๋„๊ฐ€ ๋‚ฎ์•„์ง€๋Š” ๊ฒƒ์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ์ด๋Ÿฌํ•œ ๋ถ„์„ ๊ฒฐ๊ณผ๋ฅผ ๋ฐ”ํƒ•์œผ๋กœ ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ๋‚ด์  ์ง๋ฌด๋™๊ธฐ์™€ ๊ด€๋ จ๋œ ์ง€๋ฐฉ์„ธ ๊ณต๋ฌด์› ์กฐ์ง ๋ฐ ์ธ์‚ฌ๊ด€๋ฆฌ ๋ฐฉ์•ˆ๊ณผ ์ง€๋ฐฉ์„ธ ๊ณต๋ฌด์›๋“ค์˜ ์ •์„œ์  ๊ณ ๊ฐˆ๊ณผ ๊ด€๋ จ๋œ ์ง๋ฌดํ™˜๊ฒฝ ๊ฐœ์„  ๋ฐฉ์•ˆ์— ๋Œ€ํ•œ ํ•จ์˜์ ์„ ์ œ์‹œํ•˜์˜€๋‹ค.Based on data collected from tax officers in local South Korean governments, the present study examined the impact of the perceived work environment, including work motivation and burnout, on local tax officers' turnover intention. According to the data analysis, intrinsic work motivation rather than extrinsic work motivation statistically and significantly influenced local tax officers' turnover intention. In addition, emotional exhaustion rather than personal accomplishment or depersonalization statistically and significantly influenced local tax officers' turnover intention. More specifically, the present study found that higher intrinsic work motivation and lower emotional exhaustion led to lower turnover intention among local tax officers
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