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Mammalian Cloning by Nuclear transfer, Stem Cell, and Enzyme Telomerase (핵치환에 의한 cloning, stem cell, 그리고 효소 telomerase)

  • 한창열
    • Korean Journal of Plant Tissue Culture
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    • v.27 no.6
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    • pp.423-428
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    • 2000
  • In 1997 when cloned sheep Dolly and soon after Polly were born, it had become head-line news because in the former the nucleus that gave rise to the lamb came from cells of six-year-old adult sheep and in the latter case a foreign gene was inserted into the donor nucleus to make the cloned sheep produce human protein, factor IX, in e milk. In the last few years, once the realm of science fiction, cloned mammals especially in livestock have become almost commonplace. What the press accounts often fail to convey, however, is that behind every success lie hundreds of failures. Many of the nuclear-transferred egg cells fail to undergo normal cell divisions. Even when an embryo does successfully implant in the womb, pregnancy often ends in miscarriage. A significant fraction of the animals that are born die shortly after birth and some of those that survived have serious developmental abnormalities. Efficiency remains at less than one % out of some hundred attempts to clone an animal. These facts show that something is fundamentally wrong and enormous hurdles must be overcome before cloning becomes practical. Cloning researchers now tent to put aside their effort to create live animals in order to probe the fundamental questions on cell biology including stem cells, the questions of whether the hereditary material in the nucleus of each cell remains intact throughout development, and how transferred nucleus is reprogrammed exactly like the zygotic nucleus. Stem cells are defined as those cells which can divide to produce a daughter cell like themselves (self-renewal) as well as a daughter cell that will give rise to specific differentiated cells (cell-differentiation). Multicellular organisms are formed from a single totipotent stem cell commonly called fertilized egg or zygote. As this cell and its progeny undergo cell divisions the potency of the stem cells in each tissue and organ become gradually restricted in the order of totipotent, pluripotent, and multipotent. The differentiation potential of multipotent stem cells in each tissue has been thought to be limited to cell lineages present in the organ from which they were derived. Recent studies, however, revealed that multipotent stem cells derived from adult tissues have much wider differentiation potential than was previously thought. These cells can differentiate into developmentally unrelated cell types, such as nerve stem cell into blood cells or muscle stem cell into brain cells. Neural stem cells isolated from the adult forebrain were recently shown to be capable of repopulating the hematopoietic system and produce blood cells in irradiated condition. In plants although the term$\boxDr$ stem cell$\boxUl$is not used, some cells in the second layer of tunica at the apical meristem of shoot, some nucellar cells surrounding the embryo sac, and initial cells of adventive buds are considered to be equivalent to the totipotent stem cells of mammals. The telomere ends of linear eukaryotic chromosomes cannot be replicated because the RNA primer at the end of a completed lagging strand cannot be replaced with DNA, causing 5' end gap. A chromosome would be shortened by the length of RNA primer with every cycle of DNA replication and cell division. Essential genes located near the ends of chromosomes would inevitably be deleted by end-shortening, thereby killing the descendants of the original cells. Telomeric DNA has an unusual sequence consisting of up to 1,000 or more tandem repeat of a simple sequence. For example, chromosome of mammal including human has the repeating telomeric sequence of TTAGGG and that of higher plant is TTTAGGG. This non-genic tandem repeat prevents the death of cell despite the continued shortening of chromosome length. In contrast with the somatic cells germ line cells have the mechanism to fill-up the 5' end gap of telomere, thus maintaining the original length of chromosome. Cem line cells exhibit active enzyme telomerase which functions to maintain the stable length of telomere. Some of the cloned animals are reported prematurely getting old. It has to be ascertained whether the multipotent stem cells in the tissues of adult mammals have the original telomeres or shortened telomeres.

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A Comparative Analysis of Clinical Features and Treatment Outcomes of Intussusception according to Age Distribution (연령에 따른 장중첩증의 임상양상 및 치료에 대한 비교분석)

  • Park, Bum Chul;Kim, Seok Young;Jung, Su Jin
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.8 no.2
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    • pp.150-156
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    • 2005
  • Purpose: We divided the children diagnosed with intususception into three different age groups and compared the clinical symptoms and treatment outcomes in order to analysis diagnosis and treatment of Intusussception. Methods: A retrospective chart review was established of 159 patients diagnosed with intussuception who had been admitted to Department of Pediatrics and General Surgery, Bundang CHA hospital from January, 2000 to May, 2004. We divided the patients into three groups, according to their age. Those who were under five months of age (group I; 21 patients), those between 5~11 months of age (group II; 61 patients), and those older than 11 months of age (group III; 77 patients). Then we compared the age, sex, seasonal distribution of occurrence, the cause, the clinical features, radiologic review, the type of intusussception, surgical methods, recurrence rate and treatment outcomes, among these three groups. Results: On comparing the clinical symptoms and signs among the three groups, the most common major clinical symptom and sign was irritabiltity in all three groups. Vomiting with irritability was statistically more common in group I (p<0.05) and bloody stool was most frequent in group III. The average time taken until a diagnosis was made after the symptom onset was, 21 hours in group I, 20 hours in group II and 22 hours in group III. Which showed no significant difference. But there was a higher rate of delayed diagnosis in group I, which took over 48 hours until the diagnosis was made (group I; 23.8%, group II; 4.9%, group III; 7.8%). Simple abdominal X-rays showed more frequent instances of intestinal obstruction in group I (p<0.05). The primary treatment done was barium enema which showed a failure rate of 52.4% in group I, 26.2% in group II and 14.3% in group III. Showing the highest failure rate in group I. Conclusion: The youngest group had vague symptoms which lead to delayed diagnosis and more frequent surgical procedures. As so, we advocate the importance of further evaluation and close observation, considering intussusception in children with symptoms of irritability and vomiting, especially in the early infant group.

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The Effect of 2-Week Dual Therapy with Proton Pump Inhibitor and Amoxicillin in the Eradication of Helicobacter pylori Infection for Treatment of Children with Recurrent Abdominal Pain (만성 반복성 복통 환아에서 Helicobacter pylori 감염에 대한 Proton Pump Inhibitor 및 Amoxicillin 2주 치료 효과)

  • Lee, Young-Mock;Lee, Chang-Han;Chung, Ki-Sup
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.3 no.1
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    • pp.23-29
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    • 2000
  • Purpose: It has recently been recognized that Helicobacter pylori (H. pylori) is an important factor in the pathogenesis of recurrent abdominal pain (RAP) in children. But, the best treatment for H. pylori infection is still unsettled. This study was performed to evaluate the efficacy of 2 weeks dual therapy with proton pump inhibitor (PPI) and amoxicillin for children with H. pylori infection associated with RAP. Method: Our study included 24 children with RAP who were H. pylori positive assessed by CLO test and histologic examination (silver stain). We used the regimen consisted of PPI (omeprazole, 0.7 mg/kg/day) and amoxicillin (50 mg/kg/day) for 2 weeks to eradicate H. pylori. Eradication of H. pylori was determined 4 weeks after the termination of treatment using the CLO test and histologic examination. Results: The endoscopic diagnoses of patients were nodular gastritis in 11 cases, superficial gastritis in 7 cases, peptic ulcer in 4 cases and normal finding in 2 cases. H. pylori was eradicated in 12 cases by omeprazole and amoxicillin dual therapy for 2 weeks and the eradication rate was 50%. In 4 of 12 children in whom H. pylori had not been eradicated with that regimen, we successfully eradicated H. pylori with other regimens of which 2 or 3 drugs among omeprazole, amoxicillin, clarithromycin, colloidal bismuth subcitrate ($Denol^{(R)}$) and metronidazole were used. Conclusion: The dual therapy with PPI and amoxicillin for 2 weeks had no clear advantage over other regimens for the eradication of H. pylori infection in children. We concluded that the combi-nation of PPI and amoxicillin for 2 weeks is not so good for H. pylori eradication as other commonly used regimens.

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Living-Related Liver Transplantation with Heterozygote Carrier Graft in Children with Wilson Disease (윌슨병 환아에서 이형 접합 보인자 공여간을 이용한 혈연간 생체 부분 간이식)

  • Kim, Jin-Taek;Chang, Soo-Hee;Choi, Bo-Hwa;Kim, Kyung-Mo;Yoo, Han-Wook;Lee, Young-Joo;Lee, Sung-Gyu
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.6 no.2
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    • pp.161-166
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    • 2003
  • Purpose: The purpose of this study was to evaluate the efficiency of treatment of living-related liver transplantation (LRLT) with the parental heterozygote carrier graft in children with Wilson disease. Methods: We retrospectively evaluated 7 children with Wilson disease who had received liver transplantation from 1994 to 2002 at Asan Medical Center. All the donors were parental. Liver functions, Kayser-Fleischer ring, and other factors regarding to copper metabolism were analyzed. Results: Of the 7 children, 5 had fulminant hepatitis and 2 had decompensated liver cirrhosis irresponsive to medical therapy. All donors being parental, all grafts came to be heterozygote carrier grafts. Survival rate was 100% in those 7 children, 87% in all children with liver transplantation in the same period, and 84% in children with non-metabolic liver disease. After liver transplantation, all 7 children could stop low copper diet and penicillamine therapy and their AST, total bilirubin and prothrombin time were recovered to normal. After liver transplantation, ceruloplasmin and serum copper levels were also recovered to normal. A marked reduction in 24 hr-urinary copper excretion was observed in all recipients after transplantation. During follow-up, Kayser-Fleischer rings resolved completely after LRLT in 5 children and partially in 1 child. Conclusion: We concluded that living-related liver tranplantation in children with Wilson disease with parental heterozygote carrier graft is an effective treatment modality.

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Efficacy of Lamivudine Therapy for Chronic Hepatitis B in Children (소아 만성 B형 간염 환아에서 라미부딘의 치료 효과)

  • Lee, Eun-Hye;Jang, Joo-Young;Kim, Kyung-Mo
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.11 no.2
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    • pp.130-136
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    • 2008
  • Purpose: Lamivudine is known to be effective for the treatment of chronic hepatitis B in adults. However, data on lamivudine therapy in pediatrics is limited. The aim of this study was to evaluate the efficacy and durability of lamivudine therapy for chronic hepatitis B in Korean children. Methods: A total of 44 children (27 males and 17 females, ages 6 months to 14.8 years, mean age 6.7 years) with chronic hepatitis B who received lamivudine (3 mg/kg/day, max 100 mg) for at least 12 months were enrolled. We evaluated the serum AST, ALT and serological HBV markers (HBsAg and anti-HBs, HBeAg and anti HBe, and HBV DNA) periodically. Predictive three year cumulative seroconversion rates were obtained using the Kaplan-Meier method. Results: Twenty one (48%) of 44 children achieved seroconversion of HBeAg by three years, while 23 (42%) children did not. HBV DNA was cleared in 34 (77%) children and the serum ALT levels were normalized in 41 children (93%). The three year cumulative seroconversion rates were 60% for HBeAg, and the clearance rates were 76% for HBV DNA. Eighteen children who discontinued lamivudine after HBeAg seroconversion maintained the therapeutic response for three years (treatment duration 13~58 months mean 24 months). Viral breakthrough developed in 12 children (27%) during the therapy and the YMDD mutation was documented in 11 children (25%). The mean duration for the development of a mutation was 22.7 months. Loss of HBsAg occurred in 6 children (14%). The pretreatment ALT levels were higher in responders; however, the differences were not statistically significant (p>0.05). Conclusion: The results of this study showed that lamivudine treatment had a favorable effect and durable therapeutic response in children with chronic hepatitis B. Long term follow-up and alternative therapy are warranted for those patients who do not respond to this treatment.

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Therapeutic Efficacy of Adefovir Dipivoxil in Korean Children and Adolescents with Chronic Hepatitis B who have Developed Lamivudine Resistance (Lamivudine 내성 소아 청소년 만성 B형 간염에서 Adefovir의 치료 효과)

  • Hwang, Su-Kyeong;Park, Sun-Min;Choe, Byung-Ho;Kim, Jung-Mi;Kim, Jung-Ok;Kim, Young-Mi;Lee, Ji-Hye;Cho, Min-Hyun;Tak, Won-Young;Kweon, Young-Oh
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.11 no.2
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    • pp.143-149
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    • 2008
  • Purpose: To estimate the long-term therapeutic efficacy and safety of adefovir dipivoxil in children and adolescents with chronic hepatitis B who have developed lamivudine resistance. Methods: Sixteen patients (12 boys and 4 girls; ages 4.3~20.9 years; mean age 14.2 years) with chronic hepatitis B infection resistant to lamivudine therapy received adefovir (0.3 mg/kg/day, maximal dose 10 mg) orally for at least 9 months between March 2004 and April 2008. Each patient was followed up for a mean period of 27 months (range 9~49 months) until April 2008 at Kyungpook National University Hospital in Korea. Therapeutic responses to adefovir were evaluated at 12, 24, 36, and 48 months from the initiation of therapy using the Kaplan-Meier method. Response measurements included ALT normalization, HBV DNA negativization, 2 $log_{10}$ IU/mL decrement of HBeAg titer, HBeAg loss, and HBeAg/Ab seroconversion rate. Results: Three (18.8%) of the 16 patients treated with adefovir showed HBeAg/Ab seroconversion. Kaplan-Meier estimates of cumulative ALT normalization were 12.5% (12 months), 43.8% (24 months), 63.5% (36 months), and 92.7% (48 months), respectively. Cumulative HBV DNA negativization was 6.7%, 30.0%, 45.6%, and 78.2% at 12, 24, 36, and 48 months, respectively. Cumulative 2 $log_{10}$ copies/mL decrement of HBeAg titer was 12.5%, 43.8%, 56.3%, and 86.9% at 12, 24, 36, and 48 months, respectively. Cumulative HBeAg loss and HBeAg/Ab seroconversion were 6.7% (12 months) and 22.2% (24 months), respectively. Conclusion: The long-term therapeutic efficacy of adefovir dipivoxil was favorable in children and adolescents with chronic hepatitis B who had developed lamivudine resistance. The long-term use of adefovir should be safe in children.

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Real-time Reverse Transcription Polymerase Chain Reaction Using Total RNA Extracted from Nasopharyngeal Aspirates for Detection of Pneumococcal Carriage in Children (소아에서 폐렴구균 집락률 측정을 위해 비인두 흡인 물의 총 RNA를 이용한 실시간 중합효소 연쇄반응법)

  • Kim, Young Kwang;Lee, Kyoung Hoon;Yun, Ki Wook;Lee, Mi Kyung;Lim, In Seok
    • Pediatric Infection and Vaccine
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    • v.23 no.3
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    • pp.194-201
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    • 2016
  • Purpose: Monitoring pneumococcal carriage rates is important. We developed and evaluated the accuracy of a real-time reverse transcription polymerase chain reaction (RT-PCR) protocol for the detection of Streptococcus pneumoniae. Methods: In October 2014, 157 nasopharyngeal aspirates were collected from patients aged <18 years admitted to Chung-Ang University Hospital. We developed and evaluated a real-time PCR method for detecting S. pneumoniae by comparing culture findings with the results of the real-time PCR using genomic DNA (gDNA). Of 157 samples, 20 specimens were analyzed in order to compare the results of cultures, real-time PCR, and real-time RT-PCR. Results: The concordance rate between culture findings and the results of real-time PCR was 0.922 (P<0.01, Fisher exact test). The 133 culture-negative samples were confirmed to be negative for S. pneumoniae using real-time PCR. Of the remaining 24 culture-positive samples, 21 were identified as S. pneumonia -positive using real-time PCR. The results of real-time RT-PCR and real-time PCR from 20 specimens were consistent with culture findings for all S. pneumoniae -positive samples except one. Culture and real-time RT-PCR required 26.5 and 4.5 hours to perform, respectively. Conclusions: This study established a real-time RT-PCR method for the detection of pneumococcal carriage in the nasopharynx. Real-time RT-PCR is an accurate, convenient, and time-saving method; therefore, it may be useful for collecting epidemiologic data regarding pneumococcal carriage in children.

Geographic Distribution of Physician Manpower by Gini Index (GINI계수에 의한 의사의 지역간 분포양상)

  • Moon, Byung-Wook;Park, Jae-Yong
    • Journal of Preventive Medicine and Public Health
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    • v.20 no.2 s.22
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    • pp.301-311
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    • 1987
  • The purpose of this study is to analyze degree of geographic maldistribution of physicians and changes in the distributional pattern in Korea over the years 1980-1985. In assessing the degree of disparity in physician distribution and in identifying changes in the distributional pattern, the Gini index of concentration was used. The geographical units selected for computation of the Gini index in this analysis are districts (Gu), cities (Si), and counties (Gun). Locational data for 1980 and 1985 were obtained from the population census data in the Economic Planning Board and regular reports of physicians in the Korean Medical Association. The rates of physicians located counties to whole physicaians were 10.4% in 1980 and 9.6% in 1985. In term of the ratio of physicians per 100,000 population, rural area had 9.18 physicians in 1980 and 12.95 in 1985, 7.13 general practitioner in 1980 and 7.29 in 1955, and 2.05 specialists in 1980 and 5.66 in 1985. Only specialists of genral surgery and preventive medicine were distributed over 10% in county and distribution of every specialists except chest surgery in county increased in 1955, comparing with that rates of 1980. The Gini index computed to measure inequality of physician distribution in 1985 indicate as follows; physicians 0.3466, general practitioners 0.5479, and specialists 0.5092. But the Gini index for physicians and specialists fell -15.40% and -10.42% from 1980 to 1985, indication more even distribution. The changes in the Gini index over the period for specialists from 0.3639 to 0.4542 for districts, from 0.2510 to 0.1949 for cities, and 0.5303 to 0.5868 for counties indicate distributional change of 24.81%, -22.35%, and 10.65% respectively. The Gini indices for specialists of neuro-surgery, chest surgery, plastic surgery, ophthalmology, tuberculosis, preventive medicine, and anatomical pathology in 1985 were higher than Gini indices in 1980.

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Gastroscopic Findings of Rural Residents with Symptoms of Chronic Gastrointestinal Disorder (만성(漫性) 위장장애증상(胃腸障碍症狀)을 가진 농촌주민(農村住民)들의 위내시경(胃內視鏡) 검사소견(檢査所見))

  • Park, Jung-Han;Chun, Byung-Yeol;Lee, Dong-Koo;Choi, Yong-Whan
    • Journal of Preventive Medicine and Public Health
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    • v.19 no.1 s.19
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    • pp.85-90
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    • 1986
  • This study was conducted in July-August, 1984, to define the causes of chronic gastrointestinal symptoms in rural population and to provide data for the management of such patients. A household survey was conducted to identify all the residents of Youngchun and Sungiu counties in Kyungpook province who were over 20 years of age, had chronic upper gastrointestinal symptoms for over the last 6 months, never had medical examination for the symptoms, and volunteered to participate in the gastroscopic examination. Gastroscopy was done for 106 males and 108 females. Gastric ulcer was found in 16.8% of all the examinees, duodenal ulcer in 15.4%, gastritis in 14.0%, and gastric cancer in 3.7%. No lesion was found by gastroscopy in 52.3%. Gastric ulcer more common in male(26.4%) than in female(7.4%) (p<0.01) and the same was true for duodenal ulcer(20.8% of male, 10.2% of female). Gastric cancer was found in 7.5% of the male while none of the female had gastric cancer. A higher proportion of the female (68.5%) showed normal finding in the gastroscopy than the male(35.9%) (p<0.01). No significant association was found between the upper gastrointestinal symptoms and the gastroscopic findings. The higher prevalence rate of gastric ulcer than that of duodenal ulcer in this study which is the reverse of the study findings of urban area in Korea and western countries may be related in part with the dietary habit and social environment of the rural population. Although early diagnosis is the most important for the treatment of gastric cancer, many of the people with chronic upper gastrointestinal complaints defer the diagnosis and treatment. It is may be due to lack of the knowledge of diseases and the health care attitude of the rural people. A national program for the health education and mass screening for the gastric cancer should be developed.

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DEVELOPMENT OF SAFETY-BASED LEVEL-OF-SERVICE CRITERIA FOR ISOLATED SIGNALIZED INTERSECTIONS (독립신호 교차로에서의 교통안전을 위한 서비스수준 결정방법의 개발)

  • Dr. Tae-Jun Ha
    • Proceedings of the KOR-KST Conference
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    • 1995.02a
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    • pp.3-32
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    • 1995
  • The Highway Capacity Manual specifies procedures for evaluating intersection performance in terms of delay per vehicle. What is lacking in the current methodology is a comparable quantitative procedure for ass~ssing the safety-based level of service provided to motorists. The objective of the research described herein was to develop a computational procedure for evaluating the safety-based level of service of signalized intersections based on the relative hazard of alternative intersection designs and signal timing plans. Conflict opportunity models were developed for those crossing, diverging, and stopping maneuvers which are associated with left-turn and rear-end accidents. Safety¬based level-of-service criteria were then developed based on the distribution of conflict opportunities computed from the developed models. A case study evaluation of the level of service analysis methodology revealed that the developed safety-based criteria were not as sensitive to changes in prevailing traffic, roadway, and signal timing conditions as the traditional delay-based measure. However, the methodology did permit a quantitative assessment of the trade-off between delay reduction and safety improvement. The Highway Capacity Manual (HCM) specifies procedures for evaluating intersection performance in terms of a wide variety of prevailing conditions such as traffic composition, intersection geometry, traffic volumes, and signal timing (1). At the present time, however, performance is only measured in terms of delay per vehicle. This is a parameter which is widely accepted as a meaningful and useful indicator of the efficiency with which an intersection is serving traffic needs. What is lacking in the current methodology is a comparable quantitative procedure for assessing the safety-based level of service provided to motorists. For example, it is well¬known that the change from permissive to protected left-turn phasing can reduce left-turn accident frequency. However, the HCM only permits a quantitative assessment of the impact of this alternative phasing arrangement on vehicle delay. It is left to the engineer or planner to subjectively judge the level of safety benefits, and to evaluate the trade-off between the efficiency and safety consequences of the alternative phasing plans. Numerous examples of other geometric design and signal timing improvements could also be given. At present, the principal methods available to the practitioner for evaluating the relative safety at signalized intersections are: a) the application of engineering judgement, b) accident analyses, and c) traffic conflicts analysis. Reliance on engineering judgement has obvious limitations, especially when placed in the context of the elaborate HCM procedures for calculating delay. Accident analyses generally require some type of before-after comparison, either for the case study intersection or for a large set of similar intersections. In e.ither situation, there are problems associated with compensating for regression-to-the-mean phenomena (2), as well as obtaining an adequate sample size. Research has also pointed to potential bias caused by the way in which exposure to accidents is measured (3, 4). Because of the problems associated with traditional accident analyses, some have promoted the use of tqe traffic conflicts technique (5). However, this procedure also has shortcomings in that it.requires extensive field data collection and trained observers to identify the different types of conflicts occurring in the field. The objective of the research described herein was to develop a computational procedure for evaluating the safety-based level of service of signalized intersections that would be compatible and consistent with that presently found in the HCM for evaluating efficiency-based level of service as measured by delay per vehicle (6). The intent was not to develop a new set of accident prediction models, but to design a methodology to quantitatively predict the relative hazard of alternative intersection designs and signal timing plans.

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