Finding treatment-resistant depression in real-world data : clinical and economic outcomes of antidepressant treatment in major depressive disorder

Park, Hyejin Sungkyunkwan university 2021 국내박사

배경: 치료저항성우울증(Treatment Resistant Depression; TRD)는 서로 약물학적 분류가 다른 항우울치료를 2차례 이상 지속적으로 받았음에도 불구하고 의미있는 치료반응이 없었던 경우로, 치료저항성우울증의 질병부담은 심각한 것으로 알려져 있다. 대개의 진료지침이 두 가지 이상의 약물을 사용했음에도 잘 반응하지 않는 경우에 대한 효과적인 치료방법을 제시하지 못하고 있다. 목적: 본 연구는 건강보험심사평가원 데이터에 기초하여, 주요우울장애 환자에서 치료저항성 우울증 발생 환자의 특성 및 질병 부담을 확인하고자 하였다. 초기치료 전략과 초기치료에 반응이 불충분할 때의 2차 치료전략에 따른 치료저항성 우울증의 발생률, 의료이용현황, 직접의료비용을 확인하였다. 자료 및 방법: 건강보험심사평가원 청구자료에서, 2013년 7월 1일부터 2015년 6월 30일까지 우울증으로 진단받아, 항우울제를 복용하는 환자를 대상으로 분석을 수행하였다. 회귀분석모형을 통해 치료저항성 우울증의 발생, 입원, 정신병적 동반질환, 재원기간, 전체 직접의료비용에 영향을 미치는 요인을 확인하였다. 초기치료전략과 초기치료에 반응이 불충분할 때의 2차 치료전략으로 사용되는 약물치료 양상을 확인하여, 약물치료 양상에 따른 치료저항성 우울증의 발생, 의료이용 및 직접비용을 비교하였다. 결과: 42일 이상 처방에피소드가 존재하는 644,923명의 환자를 대상으로 하였다. 최초 처방이후 2년간의 추적관찰기간 동안, 치료저항성 우울증 발생은 1.50%로 최초 처방명세서를 기준으로, 항우울제 단독성분에서 1.21%, 항우울제 2개 성분 이상에서 3.80%, 항우울제와 항정신병약물 병합에서 4.70%로 나타났다. 치료저항성우울증 발생요인으로는 젊은 연령, 남성, 불안장애 및 불면증 동반, 정신과 내원, 초기 치료전략이 두 가지 항우울제 병합, 항우울제와 항정신병약물의 병합이었다. 항우울제 단독요법 초기치료 실패 이후 다른 성분의 항우울제로 교체 또는 추가된 환자에서는 4.20%, 항정신병약물이 추가된 환자에서는 19.62%가 치료저항성 우울증으로 나타났다. 치료저항성 우울증 발생으로 의료이용 및 직접의료비용이 증가하는 것을 보였다. 결론: 주요우울장애환자에 있어서, 항우울제 단독, 병합, 항정신병약물 병용과 같은 다양한 약물치료방법에도 불구하고, 여전히 반응이 없는 경우가 발생한다. 치료 저항성우울증이 발생하면 경제적 부담이 크므로, 주요우울장애를 치료할 때는, 치료 저항성우울증의 가능성을 염두에 두고, 약물치료 이후에도 환자의 상태를 모니터링 하여 위험성이 높은 환자에 대해서는 적극적인 다른 치료법을 고려할 필요가 있다. BACKGROUND: Major depressive disorder (MDD) is relatively common mental illness and highly recurrent. Treatment Resistant Depression (TRD) is a case in which there was no significant treatment response despite continuously receiving two or more antidepressant (AD) treatments. The disease burden of TRD is serious. PURPOSE: The primary outcome was the incidence of TRD, and the secondary objectives were to measure healthcare resource use, and medical costs with treatment strategies in patients with MDD. METHODS: From the Health Insurance Review and Assessment Service (HIRA) claims database, an analysis was performed on patients who were diagnosed with MDD from July 1, 2013 to June 30, 2015 and taking AD. Patients required initiated AD therapy with at least 42 days of continuous eligibility following the index date. Multiple logistic regression model was applied to identify risk factors associated with TRD, psychiatric conditions, and hospitalization. Log-transformed linear regression models were used for medical cost and inpatient days. RESULTS: 644,923 patients with prescription episodes for more than 42 days were included. During the two-year follow-up period after the initial prescription, the incidence of TRD was 1.50%, based on the initial treatment, 1.21% in the AD monotherapy, 3.80% in AD+AD, and 4.70% in AD and atypical antipsychotics (AAP). The risk factors of TRD were younger, male, accompanied by anxiety, insomnia, visit to psychiatry, initial treatment strategy combined with two ADs, combined with AD and AAP. After failure of initial AD monotherapy, TRD was found in 4.20% of patients who were switched or added AD, and 19.62% of patients who added AAP. It was shown that healthcare resource use and direct medical costs increased due to the incidence of TRD. CONCLUSION: In MDD patients, there is still inadequate response (TRD) despite various treatment strategies such as AD monotherapy, switching AD, adding AD or AAP. When TRD occurs, the economic burden is high. Therefore, when treating MDD, it is necessary to consider the possibility of TRD and monitor the patient's condition even after pharmacological treatment and consider other active treatments for high-risk patients.

White matter connectivity related to paliperidone treatment response in patients with schizophrenia

김민경 CHA University 2016 국내박사

본 연구의 목적은 조현병 환자의 팔리페리돈 항 정신병 약물 치료 초기의 뇌 백질 연결성과 치료 반응과의 연관성에 대해 알아보고자 한 것이다. 41명의 조현병 환자와 성별 및 나이에서 유사한 17명의 건강 대조군이 연구에 참여하였다. 모든 참가자는 치료 초기에 3 Tesla 뇌 자기 공명 영상 촬영을 하였다. Tract-Based Spatial Statistics를 이용한 화소 기반 통계법을 통해 분획 이방성(fractional anisotropy) 자료를 분석하였다. 치료 시작점과 치료 후 8주차에 Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS)를 이용하여 조현병 환자의 치료 반응을 평가하였다. 조현병 환자에서, corpus callosum, corona radiata, internal capsule, external capsule, superior longitudinal fasciculus와 전두엽, 측두엽 부위의 뇌 백질 분획 이방성 수치와 8주 간의 치료 반응 사이에서 통계적으로 유의한 음의 상관관계가 관찰되었다. 본 연구는 조현병 환자에서 팔리페리돈 치료 반응은 전두-측두-변연계 부위의 뇌 백질 연결성과 관계가 있다는 것을 보고하였으며, 향후 추가적 연구를 통해 확증된다면, 이는 조현병 환자에서 팔리페리돈 치료 반응을 예측하는 인자로서 사용될 수 있을 가능성을 제시한다. The objective of this study is to examine whether white matter (WM) connectivity of patients with schizophrenia at early stage of treatment is related to treatment response after paliperidone extended-release (ER) treatment. Forty-one patients with schizophrenia and 17 age- and sex-matched healthy control subjects were included in this study. Brain magnetic resonance scans at 3 Tesla were conducted at early stage of treatment. Voxel-wise statistical analysis of the fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics. At baseline and 8 weeks after paliperidone treatment, patients were assessed using the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Scale for the Assessment of Negative Symptoms (SANS). Among the patients with schizophrenia, the FA values of corpus callosum, corona radiata, internal capsule, external capsule, superior longitudinal fasciculus, and fronto-temporal WM regions showed significant negative correlations with scores of the treatment response. The current study suggests that the treatment response after paliperidone ER treatment may be associated with the fronto-temporo-limbic WM connectivity at early stage of treatment in patients with schizophrenia, and it could be used as a predictor of treatment response to paliperidone ER treatment after studies with large samples verify these results.

Treatment outcome of spinal dural arteriovenous fistula by the policy of initial endovascular treatment trial

Heui Seung Lee 서울대학교 대학원 2020 국내석사

목적 혈관내 치료(Endovascular treatment, EVT)가 척추 경막 동정맥루의 치료에 있어서 선호되고 있지만, 불완전한 폐색 이후의 치료 방침 및 초기 치료로 완전 폐색을 달성 하였음에도 불구하고 악화된 결과와 관련된 요인에 관한 데이터는 부족하다. 본 연구에서는 다양한 치료 과정에 따라 척추 경막 동정맥루의 치료 결과를 분석하여 불완전한 폐색, 재발, 신경기능 악화 요인을 평가하는 것을 목표로 하였다. 대상 및 방법 2004년 1월부터 2019년 3월까지 초기 EVT 치료 시도 원칙 하에 치료를 받은 척추 경막 동정맥루 환자들을 대상으로 환자의 임상 정보, 척추 혈관조영술을 포함한 방사선학적 검사 결과, arterial feeder 의 수 및 척추 동정맥루의 위치에 대하여 각각 다른 치료 과정과 완전한 폐색 달성, 방사선학적 또는 신경 기능 호전 정도에 따라 치료 과정 군별로 분류하여 비교 분석 하였다. 결과 총 69명의 척추 경막 동정맥 환자 중 54명에서 초기 EVT 시도로 EVT 치료가 가능하였고, 15명에서 EVT 가능하지 않아 초기 수술적 치료가 시행되었다. 초기 치료에 의한 척추 경막 동정맥루의 완전 폐쇄는, 초기 EVT군의 54명 중 35명(68.5%)에서 달성되었고 초기 수술적 치료를 한 15명의 환자 전원에서 달성 되었다. 2개 이상의 다중 arterial feeder 는 초기의 EVT 치료군에서 불완전 폐쇄와 유의한 관련이 있었다 (P<0.001). 초기 EVT에 의한 완전 폐색에도 불구하고 기능상 악화는 전체 환자의 14.5%인 10명의 환자에서 발생하였다. 초기 EVT 이후 dAVF 완전 폐쇄가 달성된 37명 중 8명에서 추적검사를 위한 척추 MRI 또는 척추 혈관 조영술에서 재관류 소견을 보였다. 결론 초기 EVT에 의해 척추 경막 동정맥루가 완전히 폐쇄되었지만, 15.8%의 방사선학적 재관류를 고려할 때 장기적인 추적 관찰이 필요하며, 재관류가 발생한 환자들은 신경학적 악화를 보일 수 있다. 초기 EVT에 의한 불완전한 폐색 그룹에서 더 나은 기능적 결과를 얻기 위해서 척추 경막 동정맥루의 완전 폐쇄를 위해 조기 수술적 치료를 고려해야 한다. PURPOSE Although endovascular treatment (EVT) is the preferred treatment modality of spinal dural arteriovenous fistula (SDAVF), complete occlusion of SDAVF is not always achieved by EVT and data regarding treatment strategy and follow-up outcome when the occlusion of SDAVF is incomplete or failed by initial EVT. We evaluated long term outcome of SDAVF treated in a policy of initial EVT trial according to the occlusion state of SDAVF by initial EVT and different treatment courses after initial EVT trial. METHODS We investigated patients with SDAVF who underwent treatment by initial trial of EVT between January 2004 and March 2019. Patient demographics, radiological findings including spinal cord myelopathy, number of arterial feeders and location of SDAVF were compared between groups categorized by different treatment courses, accomplishment of complete occlusion, outcomes by radiological and neurological function and recanalization. RESULTS Of 69 patients with SDAVF, 54 patients had initial EVT and initial surgical treatment was decided in 15 patients when initial EVT was not feasible. Complete occlusion was achieved by initial EVT in 37 out of 54 patients (68.5%) and by initial surgical treatment in all of 15 patients. Presence of multiple feeders was associated with incomplete occlusion by initial EVT (P <0.001). Stationary or improved functional outcome was achieved in 59 out of 69 patients (85.5%; 36.2% improved and 49.3% Stationary) whereas worsened functional outcome was identified in 10 patients (14.5%). Among 17 patients of incomplete occlusion by initial EVT, there was no patient with improved functional among those who had repeated EVT or follow-up without further treatment. Recanalization was identified in 8 out of 37 patients after complete occlusion by initial EVT. Residual high signal intensity (SI) of the spinal cord was significantly associated with the recanalization of SDAVF (P = 0.001) CONCLUSIONS To achieve better functional outcome by initial EVT, surgical treatment should be considered when the occlusion of SDAVF is incomplete. Although complete occlusion of SDAVF is achieved by initial EVT, long term follow-up is necessary for early detection of radiological recanalization particularly when high SI of spinal cord remains on the follow-up spine MRI.

Changes in masticatory performance during the retention period following extraction and non-extraction orthodontic treatment

이송현 Graduate School, Yonsei University 2023 국내박사

Orthodontic treatment is the process of acquiring an optimal occlusion by modifying the initial malocclusion through space closure after extraction or space gain without extraction using various techniques. The functional benefits of modifying the occlusion while treating malocclusion remain controversial due to the lack of long-term studies evaluating the outcomes after orthodontic treatment. This study aimed was (1) to evaluate change in masticatory performance (MP) during retention period after extraction and non-extraction orthodontic treatment in adult patients and compare it with the MP in the participants with normal occlusion by measuring the mixing ability (MA) using a two-color chewing gum and (2) to evaluate whether extraction affects the MP after orthodontic treatment. Adult patients who had completed orthodontic fixed appliance treatment comprised the non-extraction group (mean age 25.33±5.26) and extraction group (mean age 29.14±7.00), and those with normal occlusion(mean age 28.3±6.57) comprised the control group. Mixing ability (MA), maximum bite force (MBF), and occlusal contact area (OCA)were recorded one week after debonding the fixed appliance, the day when the wrap-around retainer was delivered (T0), 1-month post-treatment(T1), 6 months post-treatment(T2), 1-year post-treatment(T3). MA were measured with two-color chewing gum MA test using ViewGum software, and MBF and OCA were measured using Dental Prescale II system. The results are follows 1. The MA immediately after orthodontic treatment was lower than that observed in normal occlusion group but showed a time-dependent gradual increase during 1-year retention period (P<0.01). 2.The MA at 1-month post-treatment was not significantly different from that in the normal occlusion group (P>0.05), but the MBF and OCA at 1-year post-treatment were significantly lower than those in the normal occlusion group (P<0.01). 3. The MA showed a significant correlation with the MBF and OCA (P<0.05). 4. No significant difference was observed in MA between the non-extraction group and extraction group (P>0.05). In conclusion, the MP immediately after orthodontic treatment in the experimental groups was lower than that in the normal occlusion group but increased gradually over time during the retention period and improved to levels similar to those in the normal occlusion group at 1-month post-treatment. Further, extraction did not affect the MP after orthodontic treatment. 본 연구의 목적은 ViewGum-software를 이용한 두가지 색깔 껌의 혼합능력을 평가하는 방법으로 발치, 비발치 교정치료 후 유지기간 1년동안에 시간에 따르는 저작효율의 변화를 정상교합과 비교 평가하는 것과 동시에 발치가 교정치료 후 저작효율에 영향을 미치는가를 평가하는 것이다. 실험군은 총 32명의 고정성교정장치를 이용하여 교정치료를 끝낸 환자들 중 비발치군 18명(남, 여 각각 9명씩, 평균나이: 25.33±5.26)과 발치군 14명(남, 여 각각 7명씩, 평균나이: 29.14±7.00)으로 나누고 대조군으로는 정상교합군 20명(남, 여 각각 10명씩, 평균나이: 28.3±6.57)으로 구성하였다. 저작효율은 두가지 색상의 껌을 씹은 후 스캔한 이미지를 ViewGum-software를 이용하여 혼합정도를 평가하는 방법으로 측정하였고 최대교합력과 교합면적은 압력감지필름 시스템II를 이용하여 측정하였다. 고정식 교정장치 제거 1주일 후 가철성 유지장치를 장착하는 날과 그 후 1개월, 6개월, 1년이 되는 시기에 각각 측정하여 다음과 같은 결과를 얻었다. 1. 교정치료 직후 교정치료군의 혼합능력은 정상교합군보다 낮은 값을 보이지만 유지기간 1년동안에 시간에 따르는 증가를 보여주었다 (P<0.01). 2. 교정치료군의 혼합능력은 교정치료 1개월 후 정상교합군과 유의한 차이가 없었으나(P>0.05) 교정치료 1년 후 교정치료군의 최대교합력과 교합면적은 정상교합군보다 여전히 낮은 값을 보여주었다 (P<0.01). 3. 교정치료 후 혼합능력은 최대교합력, 교합면적과 유의한 상관관계를 보여주었다 (P<0.05). 4. 발치군과 비발치군의 혼합능력을 비교한 결과 어느 시기에도 유의한 차이를 보이지 않았다(P>0.05). 본 연구를 통하여 교정치료 후 1년간의 유지기간 동안에 교합력과 교합면적은 정상교합수준에 이르지 못하는 것과는 달리 저작효율은 치료 1개월 후 정상교합과 비슷한 수준으로 개선되며 더욱이 발치는 교정치료 후 저작효율에 영향을 주지 않는다는 결론을 내릴 수 있었다

(A) study on the application of membrane filtration process to respond to water quality change in Jeju special self-governing province

Ju, Hyun 성균관대학교 수자원전문대학원 2022 국내석사

Jeju Special Self-Governing Province uses groundwater (including spring water) with unique hydrogeological characteristics of a volcanic rock system, and the demand for water is rapidly increasing due to the increase in population and industrial growth. In addition, concerns about groundwater contamination and detection of viruses and coliforms are increasing due to an increase in non-point pollution sources and nitrate nitrogen emitted from point sources. Therefore, it is necessary to build a water treatment system that can stably produce treated water at all times, and to introduce a customized treatment process for Jeju Special Self-Governing Province. In this study, a pilot test with membrane filtration process applied to three water treatment plants in Jeju Special Self-Governing Province was conducted. Aewol and Gangjeong water treatment plant(WTP) evaluated the treatment of viruses, pathogenic microorganisms, and total coliform group through the application of MF membranes, and Jocheon WTP added nitrate nitrogen to the target substances and applied the MF+NF/RO process to evaluate them. A 100 ㎥/day pilot plant each was installed at three WTP. For the MF process of Aewol and Gangjeong WTP, research was conducted with the goal of deriving optimal operation and design factors for each filtration time and flux. The influent groundwater for Aewol WTP had turbidity less than 0.1 NTU and the TMP rise rate was confimred to be 0.000875 to 0.00593 kgf/㎠·day from the evaluation by flux and filtration time. A flux of 80 LMH and a filtration time of 45 min were deduced as the optimal operating time. The recovery rate was 97.8%, confirming room for improvement by 1.5% compared to the recovery rate of 96.3% (60 LMH, filtration time 30 min) at 60 LMH (filtration time 30 min). Gangjeong WTP has relatively high turbidity and organic/inorganic concentration compared to Aewol water treatment plant. As a result of the evaluation, the TMP rise rate is 0.00098 kgf/cm2·day under the condition of membrane filtration flow rate of 60 LMH (filtration time 40 min), confirming ability for stable operation. However, it was confirmed that the TMP rise rate under high flow conditions was higher than that of Aewol water treatment plant, but possible to respond to algae inflow through NaOCl injection. However, it may show unstable operating efficiency when with algae inflow as TMP rises rapidly, so it is judged that alternatives such as pre-treatment, or filtration time adjustment are needed. The Jocheon WTP has a water quality similar to that of the Aewol WTP, but the MF+RO process was evaluated as nitrate nitrogen and total nitrogen were introduced. For MF process, flux 120 LMH and filtration time 30 min were set as basic conditions, and the RO process was evaluated under flux 22 LMH. As a result, the removal rates of nitrate nitrogen and total nitrogen in RO treated water were 91.1 and 92.5% and TOC and UV254 were 78.9% and 75.0%, confirming ability for stable treatment. Due to the limited site area of Jeju Special Self-Governing Province, it is difficult to establish and expand water treatment facilities. Considering the availability of professional operating personnel and the occurrence of rapid water quality changes, the membrane filtration process is judged to be the most appropriate filtration process. By applying high flux according to the characteristics of the raw water, it is possible to achieve concentration of facilities and stability of treated water quality, providing specialized water treatment facility unique to Jeju Special Self-Governing Province. 제주특별자치도는 화산암 계통의 독특한 수문지질학적 특성을 가진 지하수(용천수 포함)를 이용하며 인구(거주, 관광객 포함) 증가, 산업 성장 등 에 따라 용수수요량이 급격하게 증가하는 추세이다. 또한 비점오염원 증가 및 점오염원에서 배출되는 질산성질소로 인하여 지하수 오염 우려와 바이러스 및 대장균군 검출 사례가 증가하고 있다. 따라서 상시 안정적으로 생산 가능한 정수시스템의 구축이 필요하며 지하수 미 안정시에 대비한 제주특별자치도 원수 맞춤형 처리공정의 도입이 필요하다. 본 연구에서는 제주특별자치도의 3개 정수시설을 대상으로 막여과 공정을 적용한 Pilot test를 수행하였다. 애월 및 강정정수장은 MF 분리막 적용을 통한 바이러스, 병원성미생물, 총대장균군 처리에 대하여 평가하였고 조천정수장은 대상물질에 질산성질소를 추가하여 MF+NF/RO 공정을 적용하여 평가하였다. 3개 정수시설에 100 m3/일 규모의 Pilot Plant를 설치하였으다. 애월 및 강정정수장의 MF 공정은 여과시간 및 막여과유속 조건별 최적 운영 및 설계인자 도출을 목표로 연구를 수행하였다. 애월정수장의 원수인 지하수는 유입탁도 0.1 NTU 이하 수준으로 유입되었으며 운영평가 결과, 막여과유속별 및 여과시간별 평가에서 TMP 상승속도는 0.000875 ~ 0.00593 kgf/cm2·day 수준으로 확인되었으며 막여과유속 80 LMH, 여과시간 45분 조건을 최적운영 시간으로 도출하였다. 회수율은 97.8 %로 60 LMH(여과시간 30분)에서의 회수율 96.3 % (60 LMH, 여과시간 30분)보다 1.5 % 향상이 가능함을 확인하였다. 강정정수장은 애월정수장에 비하여 상대적으로 탁도 및 유/무기물 농도가 높은 특징을 보이며 평가결과 막여과유속 60 LMH(여과시간 40분) 조건에서 TMP 상승속도는 0.00098 kgf/cm2·day로서 안정적인 운영이 가능함을 확인하였다. 다만, 고유속 조건에서의 TMP 상승속도는 애월정수장보다 증가하였으나 NaOCl 주입을 통해 대응이 가능한 것을 확인하였다. 그러나, 조류 유입시 고유속 조건에서 TMP가 급증함에 따라 전처리 연계(약품주입 등) 또는 여과시간 조정 등의 대안이 필요할 것으로 판단된다. 조천정수장은 애월정수장 원수와 유사한 수질을 보이지만 질산성 질소 및 총질소가 유입됨에 따라 MF+RO 공정에 대한 평가를 수행하였다. MF 공정은 애월정수장에서의 평가 결과를 기반으로 막여과유속 120 LMH, 여과시간 30분을 기본조건으로 적용하였으며 RO 공정은 막여과유속 22 LMH 조건에서 평가를 수행하였다. 평가 결과, RO 처리수 질산성 질소 및 총질소 제거율은 91.1 및 92.5 %로 안정적 수질 확보가 가능함을 확인하였다. 제주특별자치도는 제한적인 부지면적과 전문 운영인력 확보 여부, 급격한 수질변화 발생 등을 고려할 경우, 자동화 및 지능화 시스템 도입이 가능하고 협소한 부지에서 우수한 처리효율 확보가 가능한 막여과 공정이 타당하다고 판단된다. 원수 특성에 따라 최적화된 운영조건 적용을 통하여 설비의 집적율 향상 및 수질안정성 확보가 가능한 막여과공정의 도입은 제주특별자치도만의 특성화된 정수처리 시설로서 적용이 가능할 것으로 사료된다.

Haynes 282 초내열합금의 다른 열처리 인자 적용 및 장기 열간 노출에 따른 미세조직과 기계적 특성 고찰

김진혁 창원대학교 2020 국내석사

In this study, we investigated the microstructure evolution and the mechanical properties of Haynes 282 superalloy in tension at 750 ˚C. Especially, The well-known strengthening phase in superalloy which is called γ′ precipitate was observed differently as various heat treatment conditions. Also, the thermal stability is very important factor which should be considered for application in thermal power plant. Therefore, long-tern thermal exposure was conducted at 750 ℃ up to 5000hr for all the heat treatment conditions. We conducted the standard 2step aging heat treatment (1010 ˚C/2h + 788 ˚C/8h) and newly suggested 1step aging heat treatment (800 ˚C/4h) which have advantages in time reduction and economics. Moreover, three different cooling rates (WQ, AC, FC) were conducted to study mass effect which can occur in large scale products. The γ′precipitates were observed and calculated average size and distribution after heat treatment. The average γ′precipitate size for standard 2step aging heat treatment was 17.3 nm. In case of 1step aging heat treatment, the average γ′precipitate size was increased along the decrement of cooling rate as 12.1 nm (WQ), 15.4 nm (AC) and 39.2 nm (FC). And, the γ′precipitate exhibit spherical shape. The tensile properties were measured at 750 ℃. The yield strength exhibit similar values (over 600 MPa) and for all conditions. Only a slight decrease of strength is observed, as expected, when precipitates were larger. However, the plastic behaviors were significantly different in stress-strain curve. Different strain hardening was observed. It implies that the different deformation mode was occurred. The deformation mechanism was investigated by TEM analysis. In all the cases, we observed a mixed mode of deformation such as climbing, shearing and bypassing. However, only 1step aging after FC condition showed shearing mechanism as a dominant mechanism which can be evidence of stress-strain curve. To approach theoretically, the strength increment associated to each mechanism was measured by using precipitation strengthening model. And, the results were well agreed with the observed TEM micrographs. For all the conditions calculated the existence of mixed mode of deformation mechanism. However, only 1step aging after FC condition calculated as showing shearing mechanism as a dominant mechanism. To idenfiy the thermal stability, the thermal exposure at 750 ℃ for up to 5000hr was conducted. The formation of deleterious phase was not detect even for the 5000hr exposure. The mechanical properties were very satisfying despite long-term exposure in all the cases. The yield strength was higher than 600MPa for all heat treatment conditions. This suggests that the newly suggested 1step aging heat treatment can replac with standard 2step aging heat treatment. There was significant coarsening of γ′precipitates during thermal exposure. However, they still remained sherical shape and the size was 79.6 nm for standard 2step aging heat treatment and 73.5 nm (WQ), 73.5 nm (AC), 83.1 nm (FC) for 1step aging heat treatment. The shape of γ′precipitates is important factor to evaluate the degradation. Therefore, the spherical shape implies that the γ′precipitates is maintaining the coherent interface with γ matrix suggesting high stability of the microstructure of Haynes 282 superalloy at 750 ℃. The coherency was analyzed after 5000hr at 750 ℃ for the 1step aging after FC condition. The perfect coherency along the interface between the γ materix and γ′precipitates. This coherency is believed to significantly contribute to the high resistance to thermal degradation of Haynes 282.

Analysis of the National Treatment Principle in GATT 1994 and TBT Agreement

GAO CHENMENG 고려대학교 대학원 2024 국내석사

The National Treatment Principle is a cornerstone in international trade law, embodying the essence of non-discrimination between domestic and foreign goods. This thesis delves into the intricate application and interpretation of the National Treatment Principle within two fundamental trade agreements: The General Agreement on Tariffs and Trade (GATT) and the Technical Barriers to Trade Agreement (TBT). While both agreements advocate for the National Treatment Principle, they manifest distinct nuances in terms of language, interpretation, and implications for global trade dynamics. Beginning with a comprehensive historical overview, the study traces the evolution of the National Treatment Principle, providing crucial context for its incorporation in GATT and TBT. A detailed exploration of Article III:4 of GATT and Article 2.1 of TBT unveils the National Treatment Principle’s inherent intricacies and particularities within these frameworks. This thesis revolves around a comparative analysis, identifying convergence and divergence between the two agreements, and discerning the broader implications of these variances on international trade. Modern challenges further complicate the implementation and interpretation of the National Treatment Principle, calling for refined strategies and clarifications in the agreements’ language. This research not only elucidates the complexities of the National Treatment Principle in GATT and TBT but also offers pragmatic recommendations, emphasizing the need for a unified, coherent approach to the National Treatment Principle amidst evolving trade landscapes.

Wastewater treatment improvement by aerated lagoon technology: A case study in Siem Reap city, Cambodia

Thorng Chandaravuth 서울시립대학교 국제도시과학대학원 2022 국내석사

본 연구의 목적은 시엠레아프 폐수처리장과 관련된 주요 도전과제를 정하는 것이다. 또한, 본 연구는 폭기식오수지의 이점을 설명하고자 한다. 이 기술은 기존 오수지에서 폐수 처리량을 향상시키며 열대 국가, 특히 캄보디아의 환경 및 온도에 적합하다.또한 한국정책의 사례연구와 캄보디아의 폐수 요인에 대해 박식한 전문가와 캄보디아에 거주하는 현지인의 면담에서 얻은 몇 가지 권장사항을 활용하여 캄보디아에 적용할 수 있는 적절한 정책을 찾기 위한 연구도 지속되고 있다. 폐수는 캄보디아에서나 개발도상국에서 반드시 처리해야 할 문제이다. 폭기식오수지는 열대 국가, 특히 캄보디아에 적합한 기술 처리 중 하나이다. 최근 폭기식오수지는 낮은 건설비용, 최소 운영비용, 적은 노동력, 분뇨의 취급 및 토양 살포와 관련된 높은 편의성, 현대식 수세식 청소 및 구덩이 범람체계와의 호환성, 그리고 파리 문제의 제거 등의 이유로 많은 개발도상국에서사용되고 있다. 일반적으로 분산형 폐수처리 시스템은 환경적 경제적 측면에서 입증된 효율성으로 인해 많은 개발도상국 및 선진국에서 사용되었다. 따라서 본 연구는 국가가 국민에게 위생 서비스를 제공함에 있어 준수해야 하는 전략과 정책변화 필요성에 주목하고자 한다. 본 연구에서는 캄보디아에서 오랫동안 사용해온 여러 분산형 폐수처리 시스템과 전통적인 중앙처리 시스템을 환경적, 경제적, 사회적 측면과 기타 측면에서 비교 평가하였다. The objective of this study is to find what is the main challenges in Siem Reap Wastewater Treatment Plant. Moreover, this research tries to show the benefits of the aerated lagoon; the technology became from the existing lagoon to be better with the amount of wastewater treatment and convenience with the environment and temperature in tropical countries, especially Cambodia. Research also develops to find a suitable policy to apply in Cambodia by using a case study from Korean policy and some recommendations from interviews of experts who have good experience in wastewater factors in Cambodia and local people living in Cambodia. Wastewater is an essential problem that must be a concern in developing counties also in Cambodia. The aerated lagoon is one of the suitable technology treatments for tropical countries, especially Cambodia. Recently, the aerated lagoon has been used in many developing countries for the reasons of low-cost construction, minimum operating cost, reduced labor, maximum convenience in handling and land spreading of manure, compatibility with modern flush cleaning and pit overflow systems, and reduced or eliminated fly problems. Usually, decentralized wastewater treatment systems have been used in many developing and developed countries due to proven efficiency in environmental and economic aspects. Thus, this research aims to draw attention to the need to change the strategy and policies followed by the state in providing sanitation services to the countries. The study compared and evaluated several decentralized wastewater treatment systems and the traditional central system, which has been used in Cambodia for a long time, regarding their use on the environmental, economic, social, and other aspects.

The Effect of Witnessing Preferential Treatment on Customer Satisfaction

김여은 서울대학교 대학원 2023 국내석사

As a promotional tactic, firms often employ two strategies to maintain customer relationships and build loyalty: rewarding customers based on their efforts over time (earned preferential treatment) and surprising customers by offering unexpected rewards (unearned preferential treatment). Most of the prior research on preferential treatment has mainly focused on the positive reactions of the recipients of preferential treatment and the effect of either unearned or earned preferential treatment on consumer behavior. Given the crucial difference between unearned and earned preferential treatment from the literature, the current research proposes that consumers may express different reactions to witnessing unearned and earned preferential treatment. Thus, across two experimental studies, this research investigates consumer reactions following the observation of unearned and earned preferential treatment to other customers and examines whether witnessing preferential treatment provokes adverse consequences in certain situations. Results show that witnessing other customers receive preferential treatment without explicit or reasonable explanations can reduce customer satisfaction compared to when differential treatment is offered with justification. In addition, such effect stems from customers’ perceptions of unfairness. The results extend prior research concerning preferential treatment and suggest important implications. From a theoretical perspective, the findings contribute to prior research by examining how consumers react when they witness preferential treatment instead of receiving it. For preferential treatment to generate positive customer responses and prevent unintended problems, managers and practitioners of the marketing industry should provide explicit explanations or justification when selectively offering preferential treatment, especially in public settings. 기업들은 고객에게 비행기 좌석 업그레이드, 할인 등 깜짝 선물과 같은 특별 우대(preferential treatment)를 고객 관계를 제고하고 신규 고객을 유치하는 마케팅 전략으로 사용해왔다. 그러나 지금까지의 소비자행동 연구에서는 고객의 충성 소비와 노력에 대한 보답 차원으로 제공하는 특별 우대(earned preferential treatment)의 결과와 정당한 노력이나 충성도 없이 우연히 당첨되는 것과 같은 유형의 특별 우대(unearned preferential treatment)의 긍정적인 결과에 집중해왔으며, 다른 고객에 대한 우대 목격이 고객만족에 미치는 영향에 관한 연구는 상대적으로 제한적이었다. 본 연구에서는 타 고객이 특별 우대를 받는 것을 목격하였을 때 고객만족에 미치는 영향을 살펴본다. 구체적으로 특별 우대 유형을 정당한 노력과 충성도를 통해 제공받는 특별 우대와 정당한 노력과 충성도 없이 특별 우대로 구분하여 타 고객이 우대를 받는 것을 목격했을 때 소비자 반응이 어떤지 주목한다. 첫 번째 실험에서는 타 고객이 충성도 또는 정당한 노력 없이 특별 우대를 받는 것을 목격했을 때 장기간 충성 소비와 같은 노력의 보상으로 특별 우대를 받는 것을 목격했을 때보다 더 낮은 고객 만족도를 나타냈으며 이러한 효과는 인지된 불공정성으로 인한 것을 매개효과 검증을 통해 발견하였다. 두 번째 실험에서는 우대를 받는 고객에 대한 인지된 유사성이 높은 집단이 더 낮은 고객 만족도를 보인다는 조절효과를 살펴보았으나 결과는 유의하지 않은 것으로 나타났다. 본 연구에서는 특별 우대의 유형을 구분하고 특별 우대를 제공받는 입장이 아닌 목격을 하는 입장을 살펴보았다는 것에 의의가 있으며 이를 실험으로 증명하여 선행연구의 확장에 이론적으로 공헌한다. 나아가 특정 고객에게 배타적인 특별 서비스 또는 제품을 제공할 때 실무자들이 추구해야 하는 방안을 제공하는 점에서 실무적 의의를 지닌다.

Comprehensive, Lesion-Level, Longitudinal Assessment of Metastatic Cancer, and its Clinical Implications

Santoro Fernandes, Victor The University of Wisconsin - Madison ProQuest Dis 2023 해외박사(DDOD)

Cancer treatment response assessment is particularly challenging in the setting of metastatic cancer in part because patients can present with hundreds of metastatic lesions through their body, which often respond heterogeneously to treatment. The current standard in clinical practice to reach a patient-level disease assessment is a partial response evaluation of a subset of lesions that is grouped and analyzed jointly. This suboptimal practice disregards heterogeneity in lesion-level response as it averages the lesion response, in addition to assessing only a fraction of the lesions. To achieve a more complete understanding of cancer response to treatment, comprehensive, lesion-level, and longitudinal disease assessment is necessary, but precluded by requiring manual matching of corresponding lesions, which is a tedious, subjective, and error-prone task. Therefore, the main goal of the present dissertation is to develop an automated, comprehensive, lesion-level, longitudinal evaluation of metastatic cancer to enable enhanced treatment response assessment, and to evaluate the improvement in treatment response prediction both at the patient- and at the lesion-level.To that end, we have developed and validated a lesion-tracking methodology that allows longitudinal, lesion-level information to be extracted from all the identifiable cancerous lesions in a patient across time. We then investigated the use of such information to build models of patient- and lesion-level treatment response prediction. These predictions were investigated for metastatic neuroendocrine tumor (mNET) patients treated with peptide receptor radiation therapy (PRRT), though the methodology was validated broadly across cancer and treatment types. The main reason for choosing mNETs was the newly introduced PRRT treatment, which is not well understood, especially its widely variable response across patients and lesions. The developed methodology had high accuracies for lesion matching (0.98) and tracking (0.90), thus enabling automated disease response assessment. When used for treatment response prediction, we showed that the comprehensive, lesion-level, longitudinal information can predict mNET lesions that resist treatment and exhibit a long-term persistence (prediction accuracy of 0.78). On the patient-level, we found that utilizing the information provided by the developed methodology resulted in superior treatment response prediction than previously established methods. We obtained a significant prediction of progression-free survival (PFS) (p≪0.001) and a stratification between good and poor responders to PRRT better than established approaches (0.88 vs. 0.65 AUC).In summary, this dissertation is the first work to show that the use of comprehensive, lesion-level, and longitudinal disease information is possible for various types of metastatic solid cancers via an automated methodology. Furthermore, this information was shown to improve the predictability of the treatment response of mNET patients and their individual lesions to PRRT. The potential impact of improved lesion- and patient-level treatment response prediction in the management of cancer patients is promising. Potential uses include: a lesion selection framework for subtotal targeted lesion ablation, inform the selection of patients for clinical trials, optimize treatment monitoring frequency, optimize time of treatment change, and support decisions for combination of different treatments. The introduced treatment response prediction approach has the ultimate intention of meaningfully contributing towards prolonged and higher quality-of-life for metastatic cancer patients.