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Non-clinical Trials using 14C-Acetaminophen to Validate Biomedical Accelerator Mass Spectrometry System (14C-아세트아미노펜 비임상시험을 통한 생체시료 분석용 가속질량분석기의 검증)

  • Jinho Song;Jae Hoon Shim;Jung Bae Park;Chang Su Yeo;Soo Hyeon Bae;Min Sun Choi;Mi Hye Kwon;Kyeong Min Kim
    • Journal of Radiation Industry
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    • v.17 no.2
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    • pp.127-134
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    • 2023
  • Pharmacokinetic (PK) data provide pivotal information in drug development, and they are usually first studied in the preclinical stage using various animals. However, quite often, animal PK data may not match with human PK, especially in metabolites. Thus, most regulatory agencies in the world make it mandatory to obtain metabolite information using 14C radiolabeled drug in human for small molecule drug candidates. However, such studies are expensive and time consuming and they are usually done at the end of Phase II trials using ~3.7 MBq of 14C labeled drug in a limited number of human subjects. Introduction of accelerator mass spectrometry (AMS) in this kind of study has revolutionized it. Since AMS can measure 14C level as close as natural abundance, it can quantify the amounts of 14C labeled drugs and their metabolites produced in human body that consumes less than the amount of 0.0037 MBq of 14C labeled drug, a very safe level of radioactive dose in human. Therefore, it is now possible to conduct human 14C studies safely in early clinical trials without spending hefty amount of money and time. Korea Radioisotope Center for Pharmaceuticals(KRICP) at Korea Institute of Biological and Medical Sciences(KIRAMS) has established an AMS facility in 2018, housing a 0.5MV AMS manufactured at the US National Electrostatics Corps (NEC). The AMS instrument has been validated using various standard samples that have been prepared at Lawrence Livermore National Laboratory in the US, a worldly reputable provider of AMS standards. In this paper, we present a mass balance study for acetaminophen in rats using AMS and prove that the study results are equivalent with those of literature, which shows the AMS facilities at KRICP has successfully installed and be ready to be used in the various PK studies using 14C labelled compounds for new drug development.

Exploring Influence of Network Structure, Organizational Learning Culture, and Knowledge Management Participation on Individual Creativity and Performance: Comparison of SI Proposal Team and R&D Team (네트워크 구조와 조직학습문화, 지식경영참여가 개인창의성 및 성과에 미치는 영향에 관한 실증분석: SI제안팀과 R&D팀의 비교연구)

  • Lee, Kun-Chang;Seo, Young-Wook;Chae, Seong-Wook;Song, Seok-Woo
    • Asia pacific journal of information systems
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    • v.20 no.4
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    • pp.101-123
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    • 2010
  • Recently, firms are operating a number of teams to accomplish organizational performance. Especially, ad hoc teams like proposal preparation team are quite different from permanent teams like R&D team in the sense of how the team forms network structure and deals with organizational learning culture and knowledge management participation efforts. Moreover, depending on the team characteristics, individual creativity will differ from each other, which will lead to organizational performance eventually. Previous studies in the field of creativity are lacking in this issue. So main objectives of this study are organized as follows. First, the issue of how to improve individual creativity and organizational performance will be analyzed empirically. This issue will be performed depending on team characteristics such as ad hoc team and permanent team. Antecedents adopted for this research objective are cultural and knowledge factors such as organizational learning culture, and knowledge management participation. Second, the network structure such as degree centrality, and structural hole is used to analyze its influence on individual creativity and organizational performance. SI (System Integration) companies are facing severely tough requirements from clients to submit very creative proposals. Also, R&D teams are widely accepted as relatively creative teams because their responsibilities are focused on suggesting innovative techniques to make their companies remain competitive in the market. SI teams are usually ad hoc, while R&D teams are permanent on an average. By taking advantage of these characteristics of the two kinds of teams, we will prove the validity of the proposed research questions. To obtain the survey data, we accessed 7 SI teams (74 members), and 6 R&D teams (63 members), collecting 137 valid questionnaires. PLS technique was applied to analyze the survey data. Results are as follows. First, in case of SI teams, organizational learning culture affects individual creativity significantly. Meanwhile, knowledge management participation has a significant influence on Individual creativity for the permanent teams. Second, degree centrality Influences individual creativity significantly in case of SI teams. This is comparable with the fact that structural hole has a significant impact on individual creativity for the R&D teams. Practical implications can be summarized as follows: First, network structure of ad hoc team should be designed differently from one of permanent team. Ad hoc team is supposed to show a high creativity in a rather short period, implying that network density among team members should be improved, and those members with high degree centrality should be encouraged to show their Individual creativity and take a leading role by allowing them to get heavily engaged in knowledge sharing and diffusion. In contrast, permanent team should be designed to take advantage of structural hole instead of focusing on network density. Since structural hole can be utilized very effectively in the permanent team, strong arbitrators' merits in the permanent team will increase and therefore helps increase both network efficiency and effectiveness too. In this way, individual creativity in the permanent team is likely to lead to organizational creativity in a seamless way. Second, way of Increasing individual creativity should be sought from the perspective of organizational culture and knowledge management. Organization is supposed to provide a cultural atmosphere in which Innovative idea suggestions and active discussion among team members are encouraged. In this way, trust builds up among team members, facilitating the formation of organizational learning culture. Third, in the ad hoc team, organizational looming culture should be built such a way that individual creativity can grow up fast in a rather short period. Since time is tight, reasonable compensation policy, leader's Initiatives, and learning culture formation should be done In a short period so that mutual trust is built among members quickly, and necessary knowledge and information can be learnt rapidly. Fourth, in the permanent team, it should be kept in mind that the degree of participation in knowledge management determines level of Individual creativity. Therefore, the team ought to facilitate knowledge circulation process such as knowledge creation, storage, sharing, utilization, and learning among team members, which will lead to team performance. In this way, firms must control knowledge networks in permanent team and ad hoc team in a way mentioned above so that individual creativity as well as team performance can be maximized.

The Radioprotective Effect of Ginseng Extracts on the liver in Mice that was irradiated by radiation (방사선이 조사된 생쥐 간에서 인삼추출물이 방사선 방어효과에 미치는 영향)

  • Ko, In-Ho;Chang, Chae-Chul;Koh, Jeong-Sam
    • Journal of radiological science and technology
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    • v.27 no.2
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    • pp.35-43
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    • 2004
  • Radioprotective effects of ginseng extracts on liver damage induced by high energy x-ray were studied. To one group of ICR male mice were given white(50 mg/kg/day for 7days, orally) and fermenta ginseng extracts(500 mg/kg/day for 7days, orally) before irrdiation. To another group were irradiated by 5 Gy dose of high energy x-ray. Contrast group were given with saline(0.1 ml). This study also investigated the radioprotective effect between SOD, CAT, hydrogen peroxide and ginseng extracts on hepatic damage. This study measured the level of superoxide dismutase(SOD), catalase(CAT), hydrogen peroxide($H_2O_2$) in liver tissue. Administrating orally white (50 mg/kg/day for 7days, orally) and fermenta ginseng extracts(500 mg/kg/day), the activity of SOD, CAT were generally increased and the hydrogen peroxide($H_2O_2$) was decreased. After irradiation, the activity of SOD, CAT were generally decreased and the hydrogen peroxide($H_2O_2$) was increased. Therefore, ginseng extracts increased antioxidative enzyme activity. And We know that the antioxidatant effect of extracts from white and fermenta ginseng protect radiation damage by direct antioxidant effect involving SOD, CAT. It was included that ginseng can protect against radiation damage through its antioxidatant properties.

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Research on the Relation between Musculoskeletal symptoms and Diagnosis using Moire Topography among Workers at an Automobile Manufacturing Plant (자동차회사 근로자를 대상으로 한 근골격계 자각증상과 moire 영상 진단과의 관계 연구)

  • Chun Eun-Joo;Lee Young-Gil;Jahng Doo-Sub;Lee Ki-Nam;Song Yung-Sun
    • Journal of Society of Preventive Korean Medicine
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    • v.5 no.2
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    • pp.69-92
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    • 2001
  • The purposes of this study were to offer foundation making more certain standards of musculoskeletal disorder diagnosis, We researched musculoskeletal symptoms degrees, frequencies, and cares and then examined relation between musculoskeletal symptoms and diagnosis of musculoskeletal conditions using moire topography among workers at an automobile manufacturing plant. Therefore we propose the possibility of moire topography as diagnosing utilities of musculoskeletal disorders. Methods: This study was to examine the general characteristics, complaints of musculoskeletal symptoms, and work-related musculoskeletal disorder rates of cervicobrachial and lumbar area by survey among 435 workers at an automobile manufacturing plant and then to show each frequency and percentage, In the diagnosis using moire topography, we studied pain control necessity of cervicobrachial and lumbar area, 435 subjects were classified by 5 levels: A(no symptoms), B(need management), C(need treatment) and then more divided by B1(light symptoms)/B2(heavy symptoms), C1(light symptoms)/C2(heavy symptoms), And musculoskeletal areas were divided by 2 parts, cervicobrachial area(neck, shoulder, arm&elbow, and wrist&hand) and lumbar area, Then, frequency and percentage of each musculoskeletal areas(cervicobrachial and lumbar area) were appeared. At last, Pearson's chi-square test analysis was utilized to observe the relation between diagnosis using moire topography and general characteristics and the relation between diagnosis using moire topography and work-related complaint of musculoskeletal symptoms of cervicobrachial and lumbar area, Results: The subjects employed for this research were categorized into; by gender, all of them were males(l00%): by age, under 35 years 12 %, 36-40 years 56.3%, 41-45 years 26.3 %, and above 46 years 5.3% with 36-40 years accounting for most of it. By living location, owned houses represented 69.7%, rented houses 23.4%, monthly-rented 1.6%, the others 5.3%; by education, middle school and lower represented 3.0%, high school 89.4%, and junior college and higher 7.6% with high school occupying most of the group. By marital status, married represented 95.2%, unmarried 4.1%, and the others 0.7% with most of them married; by alcohol, drinking represented 81.8% and non-drinking 18.2%; by smoking status, smoking represented 53.6%, non-smoking 46.4% with no big difference between them. By working time(hours/week), below 50 represented 26.9%, 50-60 67.6%, above 60 5.5%; by working time(hours/day), below 9 represented 21.6%, 10-12 73.1%, above 13 5.3%; by job tenure(years), below 10 represented 25.1%, 11-15 54.3%, 16-20 15.2%, above 21 5.5%. By personal income per year, below 30 million won represented 11.0%, 30-40 84.8%, above 40 4.1%; by sleeping hours, below 6 hours represented 26.7%, 7-8 hours 69.9%, above 9 hours 3.4%. Complaint rates of musculoskeletal symptoms and work-related musculoskeletal disorder rates were 63.9% and 54.9% with shoulder area occupying most of both them. By pain degree of musculoskeletal symptoms, shoulder area represented $2.73{\pm}0.84$, lumbar area $2.66{\pm}0.86$, wrist and hand area $2.59{\pm}0.86$, neck area $2.55{\pm}0.74$, and arm and elbow area $2.48{\pm}0.71$. By cares about musculoskeletal symptoms, taking medication or care represented 34.4%-46.7%, absence or leave 15.4%-28.7%, and job transfer 6.3%-11.5%. So experienced cases more than one thing among cares about musculoskeletal symptoms represented 39.6%-54%. In the diagnosis using moire topography, pain control necessity of cervicobrachial area was shown below; A(no symptoms) 20.7%, B1(need management/light symptoms) 64.6%, B2(need management/heavy symptoms) 11.5%, C1(need treatment/light symptoms) 3.0%, C2(need treatment/heavy symptoms) 0.2%. By lumbar area, A(no symptoms) 8.7%, B1(need management/light symptoms) 52.2%, B2(need management/heavy symptoms) 30.3%, C1(need treatment/light symptoms) 8.7%, C2(need treatment/heavy symptoms) was none. In the relation between pain control necessity and general characteristics, age(P=0.013), education(P=0.000), and job tenure(P=0.012) with pain control necessity showed differences with significance. The relation between pain control necessity and complaint of musculoskeletal symptoms of cervicobrachial and lumbar area showed no difference with significance; in cervicobrachial area represented P=0.708, lumbar area P=0.318 Conclusions: This study for musculoskeletal symptoms on workers at automobile manufacturing plant showed that complaint rates of musculoskeletal symptoms for cervicobrachial and lumbar area were so high, 63.9%. But Pearson's chi-square test analysis was utilized to study the relation between musculoskeletal symptoms and the diagnosis using moire topography, showed no differences with significance. They have no differences with significance, but the prevalence rates of diagnosis using moire topography for cervicobrachial and lumbar area were more higher than complaint rates of musculoskeletal symptoms; complaint rates of musculoskeletal symptoms were 52.4%, 34.5% and the diagnosis using moire topography were 79.3%, 91.3% for cervicobrachial and lumbar area. The results of this study indicate that the diagnosis using moire topography can find weak musculoskeletal disorders that an individual can not feel, not be judged work-related musculoskeletal disease. Therefore, this study has an important meaning that diagnosis using moire topography can predict and control own physical condition complete musculoskeletal disorders beforehand, since oriental medicine theory considers that prevention is important.

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Results of Radiation Therapy for Carcinoma of the Uterine Cervix (자궁경부암의 방사선치료 성적)

  • Lee Kyung-Ja
    • Radiation Oncology Journal
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    • v.13 no.4
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    • pp.359-368
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    • 1995
  • Purpose : This is a retrospective analysis for pattern of failure, survival rate and prognostic factors of 114 patients with histologically proven invasive cancer of the uterine cervix treated with definitive irradiation. Materials and Methods : One hundred fourteen patients with invasive carcinoma of the cervix were treated with a combination of intracavitary irradiation using Fletcher-Suit applicator and external beam irradiation by 6MV X-ray at the Ewha Womans University Hospital between March 1982 and Mar 1990. The median age was 53 years(range:30-77 years). FIGO stage distribution was 19 for IB, 23 for IIA, 42 for IIB, 12 for IIIA and 18 for IIIB. Summation dose of external beam and intracavitary irradiation to point A was 80-90 Gy(median:8580 cGy) in early stage(IB-IIA) and 85-100 Gy(median:8850 cGy) in advanced stage(IIB-IIIB). Kaplan-Meier method was used to estimate the survival rate and multivariate analysis for progrostic factors was performed using the Log likelihood for Weibull Results : The pelvic failure rates by stage were $10.5{\%}$ for IB. $8.7{\%}$ for IIA, $23.8{\%}$ for IIB, $50.0{\%}$ for IIIA and $38.9{\%}$ for IIIB. The rate of distant metastasis by stage were $0{\%}$ for IB, $8.7{\%}$ for IIA, $4.8{\%}$ for IIB. $0{\%}$ for IIIA and $11.1{\%}$ for IIIB. The time of failure was from 3 to 50 months and with median of 15 months after completion of radiation therapy. There was no significant coorelation between dose to point A($\leq$90 Gy vs >90 Gy) and pelvic tumor control(P>0.05). Incidence rates of grade 2 rectal and bladder complications were $3.5{\%}$(4/114) and $7{\%}$(8/114), respectively and 1 patient had sigmoid colon obstruction and 1 patient had severe cystitis. Overall 5-year survival rate was $70.5{\%}$ and disease-free survival rate was $53.6{\%}$. Overall 5-year survival rate by stage was $100{\%}$ for IB, $76.9{\%}$ for IIA, $77.6{\%}$ for IIB $87.5{\%}$ for IIIA and $69.1{\%}$ for IIIB. Five-rear disease-free survival rate by stage was $81.3{\%}$ for IB, $67.9{\%}$ for IIA, $46.8{\%}$ for IIB, $45.4{\%}$ for IIIA and $34.4{\%}$ for IIIB. The prognostic factors for disease-free survival rate by multivariate analysis was performance status(p= 0.0063) and response rate after completion of radiation therapy(p= 0.0026) but stage, age and radiation dose to point A were not siginificant. Conclusion : The result of radiation therapy for early stage of the uterine cervix cancer was relatively good but local control rate and survival rate in advanced stage were poor inspite of high dose irradiation to point A above 90 Gy. Prospective randomized studies are recommended to establish optimal tumor doses for various stages and volume of carcinoma of uterine cervix, And ajuvant chemotherapy or radiation-sensitizing agents must be considered to increase the pelvic control and survival rate in advanced cancer of uterine cervix.

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