• Title/Summary/Keyword: surrogate model

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Clinical significance of acanthosis nigricans in children and adolescents with obesity induced metabolic complications (비만으로 인한 대사적 합병증을 가진 소아 및 청소년에서 흑색가시세포증의 임상적 의의)

  • Chueh, Hee Won;Cho, Gyu Rang;Yoo, Jaeho
    • Clinical and Experimental Pediatrics
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    • v.50 no.10
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    • pp.987-994
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    • 2007
  • Purpose : This study investigated the clinical significance of AN in children and adolescents with obesity induced metabolic complications. Methods : Forty-nine patients who had obesity induced metabolic complications were participated in this cross-sectional study. Obesity induced metabolic complications are as follows: hypertension, dyslipidemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), nonalcoholic steatohepatitis (NASH), homeostasis model assessment of insulin resistance (HOMA-IR)>3.16. Clinical characteristics, such as, age, percentage-weight-for-height (PWH), pubertal status, blood pressure (BP), fasting plasma insulin level, fasting and post-oral glucose tolerance test 2-hour glucose levels, liver function test, lipid profile, HOMA-IR were compared according to the presence of AN. Results : Sixty-five percent of patients had AN, 57.1% NASH, 57.1% dyslipidemia, 55.1% hypertension, 46.9% IFG, 24.5% HOMA-IR>3.16 and 16.2% IGT. The patients who were moderately to severely obese with AN had higher incidence of IGT and HOMA-IR>3.16. The patients with AN had significantly higher diastolic BP ($79.4{\pm}6.9$ vs $75.4{\pm}5.6mmHg$), fasting levels of plasma insulin ($10.6{\pm}6.0$ vs $6.2{\pm}5.4{\mu}IU/mL$), HOMA-IR index ($2.6{\pm}1.4$ vs $1.4{\pm}1.3$) and PWH ($42.4{\pm}13.0$ vs $34.3{\pm}1.8%$). The increasing tendency for the presence of AN was significantly related to the cumulative number of obesity induced metabolic complications. Binary logistic regression analysis revealed that the presence of AN was significantly associated with fasting plasma insulin level, PWH and IFG. Conclusion : AN could be useful as a clinical surrogate of obesity induced metabolic complications.

A Study on the DWI and Pathologic Findings of Cancer Cells (암 세포주의 확산강조영상과 병리학적 관계에 관한 연구)

  • Seong, Jae-Gu;Lim, Cheong-Hwan
    • Journal of radiological science and technology
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    • v.34 no.3
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    • pp.239-244
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    • 2011
  • In this study, we evaluated diffusion weighted imaging (DWI) to investigate whether the DWI parameters can predict characteristic parameters on pathologic specimens of tumor or not. CFPAC-1 was injected subcutaneously on the back flank of athymic nude mice (n=13) then two tumors were initiated on each mouse (2${\times}$13=26 tumors). The mice were sacrificed to make specimen immediately after initial MR imaging then were compared with the MR image. A dedicated high-field (7T) small-animal MR scanner was used for image acquisitions. A T1 and T2 weighted axial image using RARE technique was acquired to measure the T2 values and tumor size. DWI MR was performed for calculating ADC values. To evaluate tumor cellularity and determine the levels of MVD, tumor cells were excised and processed for H-E staining and immunostaining using CD31. T2 values and ADC values were computed and analyzed for each half of the tumors and compared to the correlated specimens slide. Median ADC within each half of mass was compared to the cellularity and MVD in the correlated area of pathologic slide. The mean of ADC value is $0.7327{\times}10^{-3}$ $mm^2/s$ and standard deviation is $0.1075{\times}10^{-3}$ $mm^2/s$. There is a linear relationship between ADC value and tumor necrosis (R2=0.697, p< 0.001). DW image parameters including the ADC values can be utilized as surrogate markers to assess intratumoral neoangiogenesis and change of the internal structure of tumor cells.

Lung cancer, chronic obstructive pulmonary disease and air pollution (대기오염에 의한 폐암 및 만성폐색성호흡기질환 -개인 흡연력을 보정한 만성건강영향평가-)

  • Sung, Joo-Hon;Cho, Soo-Hun;Kang, Dae-Hee;Yoo, Keun-Young
    • Journal of Preventive Medicine and Public Health
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    • v.30 no.3 s.58
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    • pp.585-598
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    • 1997
  • Background : Although there are growing concerns about the adverse health effect of air pollution, not much evidence on health effect of current air pollution level had been accumulated yet in Korea. This study was designed to evaluate the chronic health effect of ai. pollution using Korean Medical Insurance Corporation (KMIC) data and air quality data. Medical insurance data in Korea have some drawback in accuracy, but they do have some strength especially in their national coverage, in having unified ID system and individual information which enables various data linkage and chronic health effect study. Method : This study utilized the data of Korean Environmental Surveillance System Study (Surveillance Study), which consist of asthma, acute bronchitis, chronic obstructive pulmonary diseases (COPD), cardiovascular diseases (congestive heart failure and ischemic heart disease), all cancers, accidents and congenital anomaly, i. e., mainly potential environmental diseases. We reconstructed a nested case-control study wit5h Surveillance Study data and air pollution data in Korea. Among 1,037,210 insured who completed? questionnaire and physical examination in 1992, disease free (for chronic respiratory disease and cancer) persons, between the age of 35-64 with smoking status information were selected to reconstruct cohort of 564,991 persons. The cohort was followed-up to 1995 (1992-5) and the subjects who had the diseases in Surveillance Study were selected. Finally, the patients, with address information and available air pollution data, left to be 'final subjects' Cases were defined to all lung cancer cases (424) and COPD admission cases (89), while control groups are determined to all other patients than two case groups among 'final subjects'. That is, cases are putative chronic environmental diseases, while controls are mainly acute environmental diseases. for exposure, Air quality data in 73 monitoring sites between 1991 - 1993 were analyzed to surrogate air pollution exposure level of located areas (58 areas). Five major air pollutants data, TSP, $O_3,\;SO_2$, CO, NOx was available and the area means were applied to the residents of the local area. 3-year arithmetic mean value, the counts of days violating both long-term and shot-term standards during the period were used as indices of exposure. Multiple logistic regression model was applied. All analyses were performed adjusting for current and past smoking history, age, gender. Results : Plain arithmetic means of pollutants level did not succeed in revealing any relation to the risk of lung cancer or COPD, while the cumulative counts of non-at-tainment days did. All pollutants indices failed to show significant positive findings with COPD excess. Lung cancer risks were significantly and consistently associated with the increase of $O_3$ and CO exceedance counts (to corrected error level -0.017) and less strongly and consistently with $SO_2$ and TSP. $SO_2$ and TSP showed weaker and less consistent relationship. $O_3$ and CO were estimated to increase the risks of lung cancer by 2.04 and 1.46 respectively, the maximal probable risks, derived from comparing more polluted area (95%) with cleaner area (5%). Conclusions : Although not decisive due to potential misclassication of exposure, these results wert drawn by relatively conservative interpretation, and could be used as an evidence of chronic health effect especially for lung cancer. $O_3$ might be a candidate for promoter of lung cancer, while CO should be considered as surrogated measure of motor vehicle emissions. The control selection in this study could have been less appropriate for COPD, and further evaluation with another setting might be necessary.

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Semi-Quantitative Analysis for Determining the Optimal Threshold Value on CT to Measure the Solid Portion of Pulmonary Subsolid Nodules (폐의 아고형결절에서 침습적 병소를 검출하기 위한 반-정량 분석을 통한 최적의 CT 임계 값 결정)

  • Sunyong Lee;Da Hyun Lee;Jae Ho Lee;Sungsoo Lee;Kyunghwa Han;Chul Hwan Park;Tae Hoon Kim
    • Journal of the Korean Society of Radiology
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    • v.82 no.3
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    • pp.670-681
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    • 2021
  • Purpose This study aimed to investigate the optimal threshold value in Hounsfield units (HU) on CT to detect the solid components of pulmonary subsolid nodules using pathologic invasive foci as reference. Materials and Methods Thin-section non-enhanced chest CT scans of 25 patients with pathologically confirmed minimally invasive adenocarcinoma were retrospectively reviewed. On CT images, the solid portion was defined as the area with higher attenuation than various HU thresholds ranging from -600 to -100 HU in 50-HU intervals. The solid portion was measured as the largest diameter on axial images and as the maximum diameter on multiplanar reconstruction images. A linear mixed model was used to evaluate bias in each threshold by using the pathological size of invasive foci as reference. Results At a threshold of -400 HU, the biases were lowest between the largest/maximum diameter of the solid portion of subsolid nodule and the size of invasive foci of the pathological specimen, with 0.388 and -0.0176, respectively. They showed insignificant difference (p = 0.2682, p = 0.963, respectively) at a threshold of -400 HU. Conclusion For quantitative analysis, -400 HU may be the optimal threshold to define the solid portion of subsolid nodules as a surrogate marker of invasive foci.

Measuring Intracellular Mycobacterial Killing Using a Human Whole Blood Assay (인체 전혈 모델을 이용한 세포내 결핵균 살균력에 관한 연구)

  • Cheon, Seon-Hee;Song, Ho-Yeon;Lee, Eun-Hee;Oh, Hee-Jung;Kang, In-Sook;Cho, Ji-Yoon;Hong, Young-Sun
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.5
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    • pp.497-509
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    • 2002
  • Background : The mechanisms through which cellular activation results in intracellular mycobacterial killing is only partially understood. However, in vitro studies of human immunity to Mycobacterium tuberculosis have been largely modeled on the work reported by Crowle, which is complicated by several factors. The whole blood culture is simple and allows the simultaneous analysis of the relationship between bacterial killing and the effect of effector cells and humoral factors. In this study, we attempted to determine the extent to which M. tuberculosis is killed in a human whole blood culture and to explore the role of the host and microbial factor in this process. Methods : The PPD positive subject were compared to the umbilical cord blood and patients with tuberculosis, diabetes and lung cancer. The culture is performed using heparinized whole blood diluted with a culture medium and infected with a low number of M. avium or M. tuberculosis $H_{37}Ra$ for 4 days by rotating the culture in a $37^{\circ}C$, 5% $CO_2$ incubator. In some experiments, methlprednisolone- or pentoxifyline were used to inhibit the immune response. To assess the role of the T-cell subsets, CD4+, CD8+ T-cells or both were removed from the blood using magnetic beads. The ${\Delta}$ log killing ratio was defined using a CFU assay as the difference in the log number of viable organisms in the completed culture compared to the inoculum. Results : 1. A trend was noted toward the improved killing of mycobacteria in PPD+ subjects comparing to the umbilical cord blood but there was no specific difference in the patients with tuberculosis, diabetes and lung cancer. 2. Methylprednisolone and pentoxifyline adversely affected the killing in the PPD+ subjects umbilical cord blood and patients with tuberculosis. 3. The deletion of CD4+ or CD8+ T-lymphocytes adversely affected the killing of M. avium and M. tuberculosis $H_{37}Ra$ by PPD+ subjects. Deletion of both cell types had an additive effect, particularly in M. tuberculosis $H_{37}Ra$. 4. A significantly improved mycobacterial killing was noted after chemotherapy in patients with tuberculosis and the ${\Delta}$ logKR continuously decreased in a 3 and 4 days of whole blood culture. Conclusion : The in vitro bactericidal assay by human whole blood culture model was settled using a CFU assay. However, the host immunity to M. tuberculosis was not apparent in the human whole blood culture bactericidal assay, and patients with tuberculosis showed markedly improved bacterial killing after anti-tuberculous chemotherapy compared to before. The simplicity of a whole blood culture facilitates its inclusion in a clinical trial and it may have a potential role as a surrogate marker in a TB vaccine trial.

Factors Affecting International Transfer Pricing of Multinational Enterprises in Korea (외국인투자기업의 국제이전가격 결정에 영향을 미치는 환경 및 기업요인)

  • Jun, Tae-Young;Byun, Yong-Hwan
    • Korean small business review
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    • v.31 no.2
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    • pp.85-102
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    • 2009
  • With the continued globalization of world markets, transfer pricing has become one of the dominant sources of controversy in international taxation. Transfer pricing is the process by which a multinational corporation calculates a price for goods and services that are transferred to affiliated entities. Consider a Korean electronic enterprise that buys supplies from its own subsidiary located in China. How much the Korean parent company pays its subsidiary will determine how much profit the Chinese unit reports in local taxes. If the parent company pays above normal market prices, it may appear to have a poor profit, even if the group as a whole shows a respectable profit margin. In this way, transfer prices impact the taxable income reported in each country in which the multinational enterprise operates. It's importance lies in that around 60% of international trade involves transactions between two related parts of multinationals, according to the OECD. Multinational enterprises (hereafter MEs) exert much effort into utilizing organizational advantages to make global investments. MEs wish to minimize their tax burden. So MEs spend a fortune on economists and accountants to justify transfer prices that suit their tax needs. On the contrary, local governments are not prepared to cope with MEs' powerful financial instruments. Tax authorities in each country wish to ensure that the tax base of any ME is divided fairly. Thus, both tax authorities and MEs have a vested interest in the way in which a transfer price is determined, and this is why MEs' international transfer prices are at the center of disputes concerned with taxation. Transfer pricing issues and practices are sometimes difficult to control for regulators because the tax administration does not have enough staffs with the knowledge and resources necessary to understand them. The authors examine transfer pricing practices to provide relevant resources useful in designing tax incentives and regulation schemes for policy makers. This study focuses on identifying the relevant business and environmental factors that could influence the international transfer pricing of MEs. In this perspective, we empirically investigate how the management perception of related variables influences their choice of international transfer pricing methods. We believe that this research is particularly useful in the design of tax policy. Because it can concentrate on a few selected factors in consideration of the limited budget of the tax administration with assistance of this research. Data is composed of questionnaire responses from foreign firms in Korea with investment balances exceeding one million dollars in the end of 2004. We mailed questionnaires to 861 managers in charge of the accounting departments of each company, resulting in 121 valid responses. Seventy six percent of the sample firms are classified as small and medium sized enterprises with assets below 100 billion Korean won. Reviewing transfer pricing methods, cost-based transfer pricing is most popular showing that 60 firms have adopted it. The market-based method is used by 31 firms, and 13 firms have reported the resale-pricing method. Regarding the nationalities of foreign investors, the Japanese and the Americans constitute most of the sample. Logistic regressions have been performed for statistical analysis. The dependent variable is binary in that whether the method of international transfer pricing is a market-based method or a cost-based method. This type of binary classification is founded on the belief that the market-based method is evaluated as the relatively objective way of pricing compared with the cost-based methods. Cost-based pricing is assumed to give mangers flexibility in transfer pricing decisions. Therefore, local regulatory agencies are thought to prefer market-based pricing over cost-based pricing. Independent variables are composed of eight factors such as corporate tax rate, tariffs, relations with local tax authorities, tax audit, equity ratios of local investors, volume of internal trade, sales volume, and product life cycle. The first four variables are included in the model because taxation lies in the center of transfer pricing disputes. So identifying the impact of these variables in Korean business environments is much needed. Equity ratio is included to represent the interest of local partners. Volume of internal trade was sometimes employed in previous research to check the pricing behavior of managers, so we have followed these footsteps in this paper. Product life cycle is used as a surrogate of competition in local markets. Control variables are firm size and nationality of foreign investors. Firm size is controlled using dummy variables in that whether or not the specific firm is small and medium sized. This is because some researchers report that big firms show different behaviors compared with small and medium sized firms in transfer pricing. The other control variable is also expressed in dummy variable showing if the entrepreneur is the American or not. That's because some prior studies conclude that the American management style is different in that they limit branch manger's freedom of decision. Reviewing the statistical results, we have found that managers prefer the cost-based method over the market-based method as the importance of corporate taxes and tariffs increase. This result means that managers need flexibility to lessen the tax burden when they feel taxes are important. They also prefer the cost-based method as the product life cycle matures, which means that they support subsidiaries in local market competition using cost-based transfer pricing. On the contrary, as the relationship with local tax authorities becomes more important, managers prefer the market-based method. That is because market-based pricing is a better way to maintain good relations with the tax officials. Other variables like tax audit, volume of internal transactions, sales volume, and local equity ratio have shown only insignificant influence. Additionally, we have replaced two tax variables(corporate taxes and tariffs) with the data showing top marginal tax rate and mean tariff rates of each country, and have performed another regression to find if we could get different results compared with the former one. As a consequence, we have found something different on the part of mean tariffs, that shows only an insignificant influence on the dependent variable. We guess that each company in the sample pays tariffs with a specific rate applied only for one's own company, which could be located far from mean tariff rates. Therefore we have concluded we need a more detailed data that shows the tariffs of each company if we want to check the role of this variable. Considering that the present paper has heavily relied on questionnaires, an effort to build a reliable data base is needed for enhancing the research reliability.