Low-dose chest computed tomographic screening and invasive diagnosis of pulmonary nodules for lung cancer in never-smokers

Background: Although lung cancer screening using low-dose computed tomography (LDCT) is now widely used in clinical practice, the characteristics and outcomes of diagnostic procedures related to screen-detected nodules in never-smokers remain unclear. We aimed to determine the incidence of nodules considered for invasive biopsy and evaluate the final diagnoses and procedure-related complications in never-smokers in comparison to ever-smokers who underwent LDCT screening. Methods: We evaluated 37,436 asymptomatic adults (17,968 never-smokers and 19,468 ever-smokers) who underwent LDCT screening for lung cancer between January 2009 and December 2018 at a tertiary center in South Korea. The rates of invasive diagnostic procedures for detected nodules and related complications, and the diagnostic outcomes were determined in the never-smoker and ever-smoker groups. Results: Among the never-smokers, 2,908/17,968 (16.2%) had positive nodules. Overall, 139/17,968 (0.77%) never-smokers and 194/19,468 (1.00%) ever-smokers underwent invasive biopsy (p=0.022). Lung cancer was diagnosed in 84/17,968 (0.47%) of never-smokers and 123/19,468 (0.63%) of ever-smokers (p=0.032). The proportions of participants diagnosed with benign disease after invasive biopsy (false-positive) were 50/17,968 (0.28%) and 69/19,468 (0.35%) in the never-smoker and ever-smoker groups (p=0.191). Multivariate analyses revealed no significant associations of smoking with the risk of a false-positive diagnosis (OR=0.98, 95% CI=0.62–1.57) and complications (OR=1.33, 95% CI=0.65–3.73) after biopsy. Of the 84 never-smokers with lung cancer, 82/84 (97.6%) had adenocarcinoma, and 75/84 (89.3%) were in stage I with a favorable prognosis. Conclusions: LDCT screening in never-smokers resulted in a notable detection rate of lung nodules, which warranted invasive biopsy. The lung cancer detection rate was lower in never-smokers than in ever-smokers. However, no significant differences in the false-positive and complication rates were observed between the two groups. Accordingly, a more specifically tailored management strategy is needed for screen-detected nodules in Asian never-smokers.서론: 폐암은 병기에 따른 생존율의 차이가 큰 병으로, 조기에 발견하여 치료하는 것이 중요하다. 따라서 최근 폐암 검진 목적으로 저선량 흉부 단층촬영(LDCT)을 촬영하는 사람이 꾸준히 증가하고 있고 이에 따라 발견되는 폐결절의 유병률도 지속적으로 증가하고 있다. 그러나 기존에 LDCT를 이용한 폐암검진의 결과를 분석한 대규모 연구들은 대부분 평생 다량의 담배를 흡연한 사람들을 대상으로 하여, 비흡연자들에서 폐암검진시 발견되는 폐결절의 유병률과, 이에 대한 침습적인 조직검사의 결과 및 임상경과들에 대한 자료는 부족한 상황이다. 방법: 본 연구는 분당서울대학교병원 건강검진센터에서 폐암검진 목적으로 LDCT를 촬영한 37,436명의 무증상 성인들 (17,968명의 비흡연자와 19,468명의 흡연자)을 대상으로 하여 LDCT로 발견된 폐결절들의 유병률과, 이 결절들에서 실제 폐암 의심하에 침습적인 조직검사를 시행하게 되는 비율, 폐암 진단율 및 임상경과를 비교분석하였다. 결과: LDCT로 폐암검진을 시행한 비흡연자 중 2,908 (16.2%) 명에서 폐결절이 발견되었으며, 이 비율은 흡연자에서의 비율과 비슷하였다. 총 139 (0.77%) 명의 비흡연자와 194 (1.00%) 명의 흡연자가 폐암 의심하에 침습적인 조직검사를 받았고, 84 (0.47%) 명의 비흡연자와 123 (0.63%) 명의 흡연자가 최종적으로 폐암으로 진단받았다. 비흡연자의 폐암 진단 환자의 비율은 흡연자에 비해서는 낮았으나, 다항 회귀분석을 시행한 결과, 비흡연자와 흡연자에서 발견된 폐결절에 대한 침습적 조직검사시의 위양성률 (OR 0.98, 95% CI 0.62–1.57) 과 합병증 발생률 (OR 1.33, 95% CI 0.65–3.73) 은 통계적으로 유의한 차이가 없었다. 결론: 본 연구결과는 특히 아시아 지역에서 LDCT로 폐암검진을 받는 비흡연자에서 발견되는 폐결절에 대하여, 흡연자 못지 않은 위험도로 조직검사와 연관된 합병증과, 위양성 결과들이 발생함을 밝혔으며, 따라서 폐결절이 발견된 비흡연자에서 보다 정밀한 진단 및 치료전략이 필요함을 보여준다.Chapter 1. Introduction 4 Chapter 2. Materials and Methods 7 Chapter 3. Results 11 Chapter 4. Discussion 15 References 20 Tables 25 Figures 37 Abstract in Korean 39박

A modification of temperature functions in SUBSTOR-Potato model for improving crop growth and yield simulation under high temperature condition

학위논문 (석사)-- 서울대학교 대학원 : 식물생산과학부, 2016. 2. 이변우.Potato phenology, growth, and yield is projected to be highly affected by global warming in the future. Therefore, assessing the climate change impacts and establishing adaptation strategies are needed. The objectives of this study were to evaluate and calibrate the potato growth model (SUBSTOR-Potato) under elevated temperature condition before applying the model to climate change impact assessments. Planting date experiments under open field condition were conducted at the experimental farm of Seoul National University (37.27oN, 126.99oE), Korea in 2014 and 2015. For the spring season, three cultivars differing in maturity group (Irish Cobbler as extremely earlySuperior as earlyAtlantic as mid-late maturing) were grown at three different planting dates. Superior and Atlantic were planted at two planting dates in the fall of 2014. Tuber initiation onset dates varied from 11 to 22 days after emergence, depending on cultivars and planting dates. Tuber initiation onset was hastened curve-linearly with increasing temperature, showing optimum temperature at around 22-24oC in all the cultivars tested. and also longer photoperiod and lower solar radiation delayed tuber initiation in Superior and Atlantic. Those factors exerted interactive effects on tuber initiation multiplicatively. The most important determinant of tuber yield was growth duration, which is limited by the beginning of rainy season in summer and frost in the late fall. Yield increased along with delayed tuber initiation. Within the optimum temperature range (17-22oC), larger diurnal temperature range increased the tuber yield. Elevated temperature experiment was conducted in four plastic houses controlled to target temperatures of ambient temperature (AT), AT+1.5oC, AT+3oC, and AT+5oC. Superior was planted at April 29 and September 17 in 2015. For the latter experiments, only emergence and tuber initiation onset was observed. Tuber initiation onset was delayed in spring season relative to fall season due to photoperiod effect. As affected by high temperature, low irradiance and long daylength, plants in AT+5.0oC failed to form tubers at spring season planting. Yield and harvest index tended to decrease with elevated temperature above ambient (22oC) and drop to almost nil at AT+5.0oC. Tuber number at early stage was reduced by higher temperature, resulting in the decrease of assimilates allocated to tuber and average weight of tubers at harvest. Stem growth was enhanced by elevated temperature at the expense of tuber growth. The simulation performance of SUBSTOR-Potato model was evaluated using the above experimental data. The model simulated tuber initiation onset later than the actual as the model determines the tuber initiation date by extrapolating the linear tuber bulking rate to the time axis, and also showed poor performance in simulating tuber initiation onset under low solar radiation, long days, and high temperature condition. We modified the original function for determining the tuber initiation onset and also added a new function of solar radiation effects on tuber initiation under high temperature and long days. The modified model performed better than the original one in predicting not only tuber initiation but also tuber yield under both field and plastic house conditions. In addition, the original model could not explain tuber bulking rate changes as caused by the reduction of tuber number under elevated temperature conditions at early growth stage. The response of rate/duration of tuber formation to temperature was added to the model, resulting in the better accuracy but similar precision for estimating the temporal changes of tuber bulking and tuber yield. According to our data, potato yield is expected to decrease under warmer climate than the current. However, the physiology of tuber initiation and growth are still not well understood and models are too simplified for predicting the heat stress. So further detailed studies are needed to grasp the knowledge of physiological responses of potato growth to high temperature and to add it to the models. Afterwards, validating the models under various environments should be preceded before applications.INTRODUCTION 1 LITERATURE REVIEW 3 Responses of potato growth to temperature 3 Temperature responses in potato growth model 6 MATERIALS AND METHODS 9 Planting date experiments 9 Elevated temperature experiments 11 Effects of environmental factors on tuber growth 13 Modification of SUBSTOR-Potato 14 RESULTS 22 Responses of potato development and growth to planting dates 22 Responses of potato growth and yield to elevated temperature 26 Effects of environmental factors on tuber growth 31 Modification of SUBSTOR-Potato 36 DISCUSSION 41 REFERENCES 44 ABSTRACT IN KOREAN 55Maste

식이 비만 유발 생쥐 (C57BL/6) 와 비만 당뇨 생쥐 (ob/ob)에서 dipeptidyl peptidas

의학과/석사[한글]그 동안 다양한 dipeptidyl peptidase (DPP)-IV 저해재들이 개발되었고 제2형 당뇨병 환자들의 혈중 active glucagon like peptide (GLP).1의 농도를 올림으로써 향상된 glycemic control 효과를 보여주었다. 하지만 이들 DPP-IV 저해재들이 체중의 증가를 막는 효과는 보이지 않았다. 이번 연구를 통해 우리는 새로 개발된 KR-66195가 glycemic 조절 능력을 향상시킬 뿐 아니라 다른 DPP-IV 저해재들이 보여주지 못했던 항 비만 효과를 가지고 있다는 것을 식이 비만 유발 생쥐 (C57BL/6) 와 비만 당뇨 생쥐 (ob/ob) 실험을 통해서 밝혔다. 식이 비만 유발 생쥐에 KR-66195을 intraperitoneal injection 방법으로 매일 8주간 10 mg per kg body weight 농도로 주사했을 때, 혈중 GLP-1의 농도가 증가 하고 향상된 glucose tolerance 효과를 보이고 epididymal 지방 조직의 크기와 먹이 섭취량을 감소 시켰으며 체중의 증가를 둔화 시켰다. 그리고 유전적으로 비만을 일으키는 비만 당뇨 생쥐에 KR-66195을 위의 실험에서와 같은 방법으로 3주간 주사했을 때, 식이 비만 유발 생쥐 실험과 유사한 효과들을 보이고 췌장 내부의 insulin 양이 증가하는 것을 확인할 수 있었다. 그러므로 앞으로 KR-66195가 더욱 연구, 보완되어 당뇨병뿐만 아니라 항비만 약제로써 쓰여질 수 있기를 기대한다. [영문]A variety of dipeptidyl peptidase (DPP)-IV inhibitors showed improved glycemic control in patients with type 2 diabetes by increasing plasma level of active glucagon like peptide (GLP)?1. However, these DPP-IV inhibitors failed to show weight reduction. In this study, we found KR-66195, a new DPP-IV inhibitor could show preventing weight gain effects as well as improved glycemic control in both diet-induced obese C57BL/6 mice and obese-diabetic ob/ob mice. In C57BL/6 mice, intraperitoneal administration of KR-66195 for 8 weeks at 10 mg per kg of body weight once a day resulted in increase in the amount of plasma GLP-1, improvement of glucose tolerance and reduction in body weight gain, epididymal fat accumulation and food intake. In ob/ob mice, the same administration of KR-66195 for 3 weeks resulted in the comparable effects as well as increased pancreatic insulin content. These results suggest that KR-66195 could be further developed as a therapeutic medication to treat obesity as well as diabetes.ope

리팜핀내성 결핵의 진단과 치료에서 Xpert MTB/RIF assay의 임상적 유용성 평가 리팜핀내성

학위논문 (석사)-- 서울대학교 대학원 : 의학과 내과학, 2016. 2. 이상민.서론: 현재 세계보건기구는 Xpert MTB/RIF assay 를 결핵 및 리팜핀내성 결핵의 진단에 적극적으로 사용할 것을 권고하고 있다. 그러나 Xpert MTB/RIF assay 의 이용이 실제 임상에서 약제내성 결핵의 진단 및 치료에 어떠한 영향을 미치는지에 대해서는 자료가 부족하다. 방법: Xpert MTB/RIF assay 를 진단에 이용하였고, 실제 결핵균 동정 결과가 있는 환자들의 의무기록을 분석하여 Xpert MTB/RIF assay 의 리팜핀내성 결핵에 대한 진단 정확도와 진단까지 걸리는 시간을 알아보았고, Xpert MTB/RIF assay 를 이용하여 약제내성결핵이 진단된 환자들과 검사를 이용하지 않고 진단된 환자들을 비교하여 각종 치료지표에 차이가 있는지 분석하였다. 결과: 총 321 명의 환자들을 분석한 결과, Xpert MTB/RIF 는 리팜핀내성 결핵을 진단하는 있어 100%의 민감도와 98.7%의 트깅도를 보였으며, 양성예측도와 음성예측도는 각각 86.2% , 100%였다. 더불어 Xpert MTB/RIF assay 를 약제내성결핵 진단에 이용하였을 경우, 이용하지 않은 경우에 비하여 통계적으로 유의하게 환자 방문시부터 2 차 결핵약제를 시작하게 되는 시간 (64 일 -> 2 일), 그리고 결핵균이 음전까지의 시간 (197 일 -> 62.5 일)이 단축됨을 알 수 있었다. 결론: 결론적으로 Xpert MTB/RIF assay 는 실제 임상환경에서 높은 정확도로 리팜핀내성 결핵을 진단하고, 약제내성결핵을 치료하는 데에 있어 긍정적인 효과를 보였다. 이를 근거로 약제내성결핵의 진단 및 치료에 있어 Xpert MTB/RIF assay 의 적극 사용할 것을 권고할 수 있을 것이다.Introduction 2 Material and Methods 4 1. Study design 4 2. Accuracy of the Xpert MTB/RIF assay for detection of RIFresistance 4 3. TAT and clinical impact of the Xpert MTB/RIF assay on treatment of RIF-resistant TB 5 4. Laboratory processing of specimens 6 5. Statistical analyses 6 Results 7 1. Accuracy of the Xpert MTB/RIF assay for diagnosis of RIFresistance 7 2. Comparison of Xpert MTB/RIF and phenotypic DST TATs 9 3. Clinical impact of the Xpert MTB/RIF assay on treatment of rifampicin-resistant TB 12 Discussion 16 References 21 Abstract in Korean 25Maste

A study on DRAM bit line sense amplifier with reverse biased offset sampling

MasterThe importance of semiconductor tech shrinks is increasing, but the process development becomes more difficult and the development period increases. DRAM cell size is also inevitably decreasing as the DRAM process becomes finer. In the DRAM industry the most important problem is the reduction of this data storage capacity. As the cell size decreases, there is a problem that the offset value required for determining the data of the bit-line sense amplifier (BLSA) continues to decrease. In addition, mismatch between latch translators is increasing due to process miniaturization, making it difficult to operate sense amplifiers. This paper proposes a DRAM offset cancellation amplifier that operates as reverse bias. We designed a latched type sense amplifier suitable for low power without a short current path and using ground voltage as a reference voltage. Our circuit operated from -30 to 90 ℃, and the average power consumption was about 10 nW. Low power characteristics and the reduced area will be useful for high-capacity DRAMs

Anti-obesity effects of KR-66195, a synthetic DPP-IV inhibitor, in diet-induced obese mice and obese-diabetic ob/ob mice

OBJECTIVE: We investigated whether KR-66195, a new synthetic dipeptidyl dipeptidase IV inhibitor, could prevent weight gain, as well as improving glycemic control in diet-induced obese (DIO) and ob/ob mice. MATERIALS/METHODS: Male C57BL/6 mice were randomly assigned to the following groups: chow diet, high-fat diet, and high-fat diet with KR-66195. After KR-66195 treatment for eight weeks, intraperitoneal glucose tolerance tests were performed. A pair-feeding study was performed to investigate the mechanisms of the anti-obesity effects of KR-66195 in DIO mice. Female ob/ob mice were treated with KR-66195 for three weeks and compared to the vehicle-treated group. RESULTS: In DIO mice, KR-66195 treatment increased the plasma glucagon-like peptide (GLP)-1 levels and improved glucose tolerance. This treatment also reduced body weight gain (5.38±0.94 g vs. 12.08±0.55 g, P<0.01) and food intake (2.41±0.09 g vs. 2.79±0.11 g, P<0.05). In ob/ob mice, KR-66195 treatment for three weeks resulted in comparable effects in DIO mice. In the pair-feeding study, KR-66195-treated mice exhibited a 16% increase in energy expenditure (kcal/h/kg lean body mass) without significant differences in body weight or activities compared with pair-fed mice. These results suggest that KR-66195 prevented weight gain in DIO mice by decreasing food intake, as well as increasing energy expenditure. CONCLUSIONS: KR-66195 markedly increased plasma levels of GLP-1, resulting in the probable improvement in glucose tolerance and reduced body weight and food intake. Thus, KR-66195 might be further developed as a therapeutic drug to treat obesity, as well as diabetes.ope