Communications for Statistical Applications and Methods
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v.18
no.5
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pp.581-594
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2011
The traditional method of 3+3 standard design and model-based Bayesian continual reassessment method (CRM) are commonly used in Phase I clinical trials to identify the maximal tolerated dose(MTD) of a new drug. In this paper we review clinical examples of Phase I trials that were carried out in patients with refractory or relapsed leukemia and myelodysplastic syndrome. The recently proposed 3+1+1 design and rolling-6 design can shorten the trial duration, when a very slow accrual of patients with a simple 3+3 standard design may result in the untimely termination of trials. Too conservative approaches in determining the dose levels in Phase I clinical trials can leave clinical investigators unable to accurately determine the MTD. When determining future patient doses, the designs that use a time-to-event CRM can cooperate late toxicities by accounting for the proportion of the observation period of each enrolled patient. With the CRM design, simulations under different scenarios during the trial are important in detecting the under- or over-estimation of the initial estimate of the dose-limiting toxicity rate for each dose level. We present the advantages and drawbacks of the designs used in Phase I clinical trials for leukemia patients.
Jang, Seong Mi;Jeong, Kyeong Hye;Kim, Bo Yeon;Kim, Young Nam;Cho, Hyeon In;Kim, Eun Young;Huh, Woo Sung
Korean Journal of Clinical Pharmacy
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v.26
no.1
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pp.77-83
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2016
Background: Oversight on the bioethical compliance of national R&D projects or research personnel is currently conducted exclusively by IRB (Institutional Review Board) within the relevant research institute. Considering current state of affairs in Korea, there is an imperative to establish a national oversight system for bioethical compliance, conduct comprehensive oversight on bioethical compliance of national R&D projects, and enhance subject protection system. Methods: We examined opinions from researchers and IRB personnels regarding ethical oversight system on R&D projects. Additionally, we looked at IRB assessment by KAIRB (Korea Association of Institutional Review Board) in order to identify status and problems with current IRB system in Korea. Assessment was also done for four other countries (US, UK, Germany, Singapore) through in-person visits as well as surveys in writing for a total of 6 months (2012.12.1~2013.5.31). The research comprised of two aspects: system management and R&D project audit. Based on this, we examined current status and problems of the existing system in Korea and made recommendations for improvement. Results: Regulatory objectives and backgrounds of biomedical researches are different from each country due to different characteristics of bioethical oversight system. This shows that each country sets up its own regulations and procedures to fit each situation. Bioethical compliance oversight system greatly varied between the countries. From this study, it can be seen that improvement of existing procedures and oversight system or establishment of new ones are essential in Korea. Conclusion: In terms of system management, a dedicated government organization need to be established for bioethical compliance, subject protection, IRB inspection, training, evaluation, and certification of systems, and also support for IRB e-system. Regarding R&D project oversight, it is essential to confirm IRB review results before start of a research, to conduct a review on ethical aspects of research plans, and to carry out continued oversight on bioethical compliance through interim reports.
Jo, Young-Bae;Na, Won-Seob;Eom, Sung-Je;Jeong, Yong-Jin
Journal of IKEEE
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v.18
no.4
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pp.485-494
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2014
Traffic Sign Recognition(TSR) is an important element in an Advanced Driver Assistance System(ADAS). However, many studies related to TSR approaches only in normal daytime environment because a sign's unique color doesn't appear in poor environment such as night time, snow, rain or fog. In this paper, we propose a new TSR algorithm based on machine learning for daytime as well as poor environment. In poor environment, traditional methods which use RGB color region doesn't show good performance. So we extracted sign characteristics using HoG extraction, and detected signs using a Support Vector Machine(SVM). The detected sign is recognized by a decision tree based on 25 reference points in a Normalized RGB system. The detection rate of the proposed system is 96.4% and the recognition rate is 94% when applied in poor environment. The testing was performed on an Intel i5 processor at 3.4 GHz using Full HD resolution images. As a result, the proposed algorithm shows that machine learning based detection and recognition methods can efficiently be used for TSR algorithm even in poor driving environment.
Human being has extensively invaded, occupied, and used the natural environment as a consequence of the advance of civilization. Mankind has increasingly modified the environment for his own benefit. Such modification has not only caused the extinction of many other species but also, caused human being himself to confront to serious environmental problems. The recognition of this fact by human is expressed in the establishment and development of restoration ecology. This new study fold is, in fact, an "Eco-technology" directed towards healing of damages to the environment. The goal is to reestablish processes and functions in a damaged site, imitating the way of healing works that an integral natural system carries out. Ecological restoration uses different treatments and approaches according to extents of the existing damage and to the specific goal to be achieved. An ecological diagnosis is, therefore, required prior to restoration practice. The cost and efforts to achieve a proposed goal can be significantly reduced when a restoration plan is formulated upon the results of well-conducted ecological diagnosis. Under such perspectives, restoration ecology is a practical science, which aims to solve the problems of the real world based on the existing ecological principle. Furthermore, restoration ecology offers opportunities to test the ecological concepts and theories obtained by means of the former ecological studies. Human being exploited natural environment excessively for his comfort on one hand but damaged it inevitably on the other hand. Such intensive resource utilization and continuous environmental damaging will extend into the future and ultimately jeopardize the survival of humankind if no prompt action is taken. In the present situation, we must not continue such lives without any preparation. We have to cope with the environmental crises approaching near us by pursuing the ecological restoration that reduce the unnecessary use, recruit the deficient part, and strengthen the weak portion in our environment. Restoration ecology could be recognized as the ecology for the future in such viewpoints.
Base isolation, one of the popular seismic protection approaches proven to be effective in practical applications, has been widely applied worldwide during the past few decades. As the techniques mature, it has been recognised that, the biggest issue faced in base isolation technique is the challenge of great base displacement demand, which leads to the potential of overturning of the structure, instability and permanent damage of the isolators. Meanwhile, drain, ventilation and regular maintenance at the base isolation level are quite difficult and rather time- and fund- consuming, especially in the highly populated areas. To address these challenges, a number of efforts have been dedicated to propose new isolation systems, including segmental building, additional storey isolation (ASI) and mid-storey isolation system, etc. However, such techniques have their own flaws, among which whipping effect is the most obvious one. Moreover, due to their inherent passive nature, all these techniques, including traditional base isolation system, show incapability to cope with the unpredictable and diverse nature of earthquakes. The solution for the aforementioned challenge is to develop an innovative vibration isolation system to realise variable structural stiffness to maximise the adaptability and controllability of the system. Recently, advances on the development of an adaptive magneto-rheological elastomer (MRE) vibration isolator has enlightened the development of adaptive base isolation systems due to its ability to alter stiffness by changing applied electrical current. In this study, an innovative semi-active storey isolation system inserting such novel MRE isolators between each floor is proposed. The stiffness of each level in the proposed isolation system can thus be changed according to characteristics of the MRE isolators. Non-dominated sorting genetic algorithm type II (NSGA-II) with dynamic crowding distance (DCD) is utilised for the optimisation of the parameters at isolation level in the system. Extensive comparative simulation studies have been conducted using 5-storey benchmark model to evaluate the performance of the proposed isolation system under different earthquake excitations. Simulation results compare the seismic responses of bare building, building with passive controlled MRE base isolation system, building with passive-controlled MRE storey isolation system and building with optimised storey isolation system.
The recent availability of recombinant human erythropoietin has opened new perspectives in the management of a variety of anemias. Clinical trials have been initiated in several countries using different approaches and methodology. We randomly assigned twelve premature infants(gestational age < 32 week) at high risk of requiring erythrocyte transfusion for anemia of prematurity with either subcutaneous recombinant human erythropoietin or a placebo. Treatment with rHuEPO was initiated at a dose of 100 units/kg day for 3 days a week. All patients were given supplemental oral iron therapy at a dose of 3 mg/kg per day, as tolerated and oral vitamin E at a dose of 25 units per day. Treated and control babies did not differ with respect to weight, hematocrit, overall mean reticulocyte count or rate of growth respectively. However, reticulocyte counts increased earlier in patients given rHuEPO. We conclude that rHuEPO administration is safe and feasible at the dose studied.
Loutfy, Samah A;Al-Ansary, Nadia A;Abdel-Ghani, Nour T;Hamed, Ahmed R;Mohamed, Mona B;Craik, James D;Eldin, Taher A. Salah;Abdellah, Ahmed M;Hussein, Yassmein;Hasanin, MTM;Elbehairi, Serag Eldin I
Asian Pacific Journal of Cancer Prevention
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v.16
no.14
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pp.6039-6046
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2015
Aims: To investigate effect of metallic nanoparticles, silver (AgNPs) and gold nanoparticles (AuNPs) as antitumor treatment in vitro against human breast cancer cells (MCF-7) and their associated mechanisms. This could provide new class of engineered nanoparticles with desired physicochemical properties and may present newer approaches for therapeutic modalities to breast cancer in women. Materials and Methods: A human breast cancer cell line (MCF-7) was used as a model of cells. Metallic nanoparticles were characterized using UV-visible spectra and transmission electron microscopy (TEM). Cytotoxic effects of metallic nanoparticles on MCF-7 cells were followed by colorimetric SRB cell viability assays, microscopy, and cellular uptake. Nature of cell death was further investigated by DNA analysis and flow cytometry. Results: Treatment of MCF-7 with different concentrations of 5-10nm diameter of AgNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $6.28{\mu}M$, whereas treatment of MCF-7 with different concentrations of 13-15nm diameter of AuNPs inhibited cell viability in a dose-dependent manner, with IC50 value of $14.48{\mu}M$. Treatment of cells with a IC50 concentration of AgNPs generated progressive accumulation of cells in the S phase of the cell cycle and prevented entry into the M phase. The treatment of cells with IC50 concentrations of AuNPs similarly generated progressive accumulation of cells in sub-G1 and S phase, and inhibited the entrance of cells into the M phase of the cell cycle. DNA fragmentation, as demonstrated by electrophoresis, indicated induction of apoptosis. Conclusions: Our engineered silver nanoparticles effectively inhibit the proliferation of human breast carcinoma cell line MCF-7 in vitro at high concentration ($1000{\mu}M$) through apoptotic mechanisms, and may be a beneficial agent against human carcinoma but further detailed study is still needed.
KSCE Journal of Civil and Environmental Engineering Research
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v.10
no.3
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pp.29-38
/
1990
A totally, new approach of Lagrangian formulation named 'Pseudo Lagrangian Formulation(PLF)' for large deformation analysis of continue and structures by the finite of element method has been presented, and the efficiency and accuracy of nonlinear analysis beam element formulated by PLF has been discussed by solving several numerical examples. In PLF, the deformation of a body is maeasured by assigning a nonphysical 'Pseudo' configuration as reference. The Lagrangian deformation and the finite element mapping of the traditonal Lagrangian approaches are then carried out directly at the same time, The result of numerical tests shows superior performance of PLF to the traditional Lagrangian methods, Applications of PLF to small and finite deformation problems indicate that PLF not only serves as an alternative but has certain implementational advantages over total or updated Lagrangian formulations.
Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, ${\alpha}$, ${\beta}$ and ${\gamma}$. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa, $RAR{\beta}$, $RAR{\gamma}$, RXRa, $RXR{\beta}$, $RXR{\gamma}$ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa, $RAR{\beta}$, $RAR{\gamma}$ and $RXR{\gamma}$ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower $RAR{\beta}$, $RAR{\gamma}$ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and $RAR{\beta}$ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.
The current curriculum in the 7th informatics, which simply highlights the use of applied programs rather than enhancing creativity through learning several principles in information science and thus making it hard to have optimism on the future as a powerhouse in IT. By diagnosing these problems, Education Ministry revised the existing curriculum to have a more scientific access to the informatics. However, the curricular revision fails to meet the needs of learners sufficiently because it tends to put the considerations of theoretical specialists before the learners them selves. This paper compares and analyzes the overall understanding of learners on informatics, current-curriculum and 7th revised curriculum and that of college-level, thus offering the student-centered one. Also, the research tries to bridge the opinion gap between developer and learner by looking into the understanding level of university majors about the current curriculum. In doing so, thesis may provide the basis on exploring new approaches and contribute to establishing 7th revised curriculum in school.
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