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1. Alterations and Prediction of Functional Profiles of Gut Microbiota After Fecal Microbiota Transplantation for Iranian Recurrent Clostridioides difficile Infection with Underlying Inflammatory Bowel Disease: A Pilot Study

Author

Azimirad M, Jo Y, Kim MS, Jeong M, Shahrokh S, Aghdaei HA, Zali MR, Lee S, Yadegar A, and Shin JH

Subjects
fecal microbiota transplantation, clostridioides difficile infection, inflammatory bowel disease, gut microbiome, functional profiles, gut dysbiosis, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950
Abstract

Masoumeh Azimirad,1,* YoungJae Jo,2,* Min-Sueng Kim,2 Minsoo Jeong,2 Shabnam Shahrokh,3 Hamid Asadzadeh Aghdaei,4 Mohammad Reza Zali,3 Seungjun Lee,5 Abbas Yadegar,1 Jae-Ho Shin2 1Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea; 3Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Department of Food Science and Nutrition, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea*These authors contributed equally to this workCorrespondence: Abbas Yadegar; Jae-Ho Shin Tel +98-21-22432518; +82 53-950-5716Fax +98-21-22432527; +82 53-953-7233Email babak_y1983@yahoo.com; jhshin@knu.ac.krBackground and Purpose: Fecal microbiota transplantation (FMT) has emerged for the therapeutic treatment of recurrent Clostridioides difficile infection (rCDI) with concurrent inflammatory bowel disease (IBD). As the first Iranian population cohort, we examined how gut microbiota and their functional profiles change in Iranian rCDI patients with underlying IBD before and after FMT.Patients and Methods: FMT was performed to eight IBD patients via colonoscopy. Profiles of gut microbiota from donors and recipients were investigated using 16S rRNA gene sequence analysis.Results: Patients experienced no IBD flare-ups or other adverse effects, and all recovered to full health. Moreover, all rCDI patients lacked the Bacteroidetes present in donor samples. After FMT, the proportion of Bacteroidetes increased until a normal range was achieved. More specifically, the relative abundance of Prevotella was found to increase significantly following FMT. Prevotella was also found to correlate negatively with inflammation metrics, suggesting that Prevotella may be a key factor for resolving CDI and IBD. Gut microbiota diversity was found to increase following FMT, while dysbiosis decreased. However, the similarity of microbial communities of host and recipients did not increase, and wide variation in the extent of donor stool engraftment indicated that the gut bacterial communities of recipients do not shift towards those of donors.Conclusion: FMT leads to significant alterations of the community structure of gut bacteria in rCDI patients with IBD. The change in relative abundance of Proteobacteria and bacterial diversity indicated that FMT promotes recovery from intestinal permeability and inflammation in rCDI patients. Moreover, strong negative correlation between Prevotella and inflammation index, and decreased dysbiosis index advocate that the improvement of CDI is possibly due to gut microbiome alteration. Collectively, our findings show that FMT would be a promising therapy to help reprogram the gut microbiome of Iranian rCDI patients with IBD.Keywords: fecal microbiota transplantation, Clostridioides difficile infection, inflammatory bowel disease, gut microbiome, functional profiles, gut dysbiosis

Published
2022

2. Efficacy and Safety of Nebivolol and Rosuvastatin Combination Treatment in Patients with Concomitant Hypertension and Hyperlipidemia

Author

Rhee MY, Kim CH, Ahn Y, Shin JH, Han SH, Kang HJ, Hong SJ, and Kim HY

Subjects
hypertension, hypercholesterolemia, nebivolol, rosuvastatin, Therapeutics. Pharmacology, RM1-950
Abstract

Moo-Yong Rhee,1 Cheol Ho Kim,2 Youngkeun Ahn,3 Joon-Han Shin,4 Seung Hwan Han,5 Hyun-Jae Kang,6 Soon Jun Hong,7 Hae-Young Kim8 1Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, Republic of Korea; 2Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 3Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea; 4Department of Cardiology, Ajou University Medical Center, Suwon, Republic of Korea; 5Division of Cardiology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; 6Department of Internal Medicine, Seoul National University Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea; 7Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea; 8Department of Health Policy and Management, College of Health Science & Department of Public Health Science, Graduate School, Korea University, Seoul, Republic of KoreaCorrespondence: Cheol Ho Kim Department of Internal MedicineSeoul National University Bundang Hospital, Seongnam, Republic of KoreaTel +82 31 787 7001Fax +82 31 787 4051Email cheolkim55@gmail.comPurpose: We evaluated the efficacy and safety of nebivolol and rosuvastatin combination treatment in patients with hypertension and hyperlipidemia.Patients and Methods: Eligible patients, after more than 4 weeks of therapeutic lifestyle change, were randomly assigned to three groups: 5 mg nebivolol plus 20 mg rosuvastatin (NEBI/RSV), 20 mg rosuvastatin (RSV), or 5 mg nebivolol (NEBI). Treatments lasted 8 weeks.Results: Efficacy was analyzed using data from 276 patients. Sitting systolic and diastolic blood pressures differed between the NEBI/RSV and RSV groups (LSmean difference = − 5.89 and − 5.99 mmHg; 95% confidence interval [CI] = − 9.88 to − 1.90 mmHg and − 8.13 to − 3.84 mmHg, respectively). Reductions in the two pressures did not differ between the NEB/RSV and NEB groups. The percent reduction in low-density lipoprotein (LDL) cholesterol differed between the NEBI/RSV and NEBI groups (LSmean difference = − 47.76%, 95% CI = − 52.69 to − 42.84%) but not between the NEBI/RSV and RSV groups. The blood pressure (BP) control rate was higher in the NEBI/RSV group than in the RVS group (51.09% vs 29.67%, p = 0.003). The LDL cholesterol goal achievement rate was higher in the NEBI/RSV group than in the NEBI group (85.87% vs 11.83%, p < 0.001). The incidence of adverse drug reactions in the NEBI/RSV, RSV, and NEBI groups was 8.51%, 7.45%, and 8.60%, respectively (p = 0.950).Conclusion: Nebivolol plus rosuvastatin treatment is effective in reducing BP and LDL cholesterol levels and is safe in patients with hypertension and hypercholesterolemia without the loss of BP or the LDL cholesterol-lowering effect of each drug.Trial Registration: CRIS registration number KCT0002148.Keywords: hypertension, hypercholesterolemia, nebivolol, rosuvastatin

Published
2020

3. Ultralow drive voltage substrate removed GaAs/AlGaAs electro-optic modulators at 1550 nm

Author

Shin, JH and Dagli, N

Subjects
Optical modulation, compound semiconductors, optical waveguides, phase modulation, Optoelectronics & Photonics, Optical Physics, Electrical and Electronic Engineering, Quantum Physics
Abstract

This study reports ultralow drive voltage Mach-Zehnder modulators in highly confined substrate removed GaAs/AlGaAs optical guides with buried doped QW electrodes. Separation between the doped QW electrodes, which is the electrode gap, is only 0.15 μm. Such a small electrode gap results in very high electric fields overlapping very well with the optical mode. A careful analysis of the physical effects contributing to index change is presented and techniques to use these index changes efficiently are described. Fabrication details are given. Results of careful characterization of phase and Mach-Zehnder intensity modulators are presented. Variation of propagation loss and extinction ratio with applied voltage are investigated. Intensity modulators with 7-mm-long electrodes have 0.3 Vπ under push-pull operation with 15 dB extinction ratio. This corresponds to a 0.21 V·cm modulation efficiency in bulk compound semiconductors. © 2013 IEEE.

Published
2013

4. Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in Korean patients with mild to moderate hypertension and dyslipidemia: an 8-week, multicenter, randomized, double-blind, factorial-design study (OLSTA-D RCT: OLmesartan rosuvaSTAtin from Daewoong)

Author

Park JS, Shin JH, Hong TJ, Seo HS, Shim WJ, Baek SH, Jeong JO, Ahn YK, Kang WC, Kim YH, Kim SH, Hyon MS, Choi DH, Nam CW, Park TH, Lee SC, and Kim HS

Subjects
Fixed-dose Combination Therapy, Olmesartan medoxomil, Rosuvastatin, Hypertension, Dyslipidemia, Therapeutics. Pharmacology, RM1-950
Abstract

Jin-Sun Park,1,* Joon-Han Shin,1,* Taek-Jong Hong,2 Hong-Seog Seo,3 Wan-Joo Shim,4 Sang-Hong Baek,5 Jin-Ok Jeong,6 Youngkeun Ahn,7 Woong-Chol Kang,8 Young-Hak Kim,9 Sang-Hyun Kim,10 Min-Su Hyon,11 Dong-Hoon Choi,12 Chang-Wook Nam,13 Tae-Ho Park,14 Sang-Chol Lee,15 Hyo-Soo Kim16 1Department of Cardiology, Ajou University School of Medicine, Suwon, 2Division of Cardiology, Pusan National University Hospital, Busan, 3Division of Cardiology, Korea University Guro Hospital, Korea University College of Medicine, 4Division of Cardiology, Korea University Anam Hospital, 5Cardiovascular Division, Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 6Division of Cardiology, Chungnam National University Hospital, Daejeon, 7Division of Cardiology, Chonnam National University Hospital, Gwangju, 8Division of Cardiology, Gachon University Gil Hospital, Incheon, 9Division of Cardiology, Asan Medical Center, College of Medicine, University of Ulsan, 10Division of Cardiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 11Division of Cardiology, Soonchunhyang University Hospital, 12Division of Cardiology, Yonsei University Severance Hospital, Seoul, 13Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, 14Division of Cardiology, Dong-A University Hospital, Busan, 15Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 16Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, Korea *These authors contributed equally to this work Abstract: The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (–52.3% [2.8%] vs –0.6% [3.5%], P

Published
2016

5. Schisandrae fructus enhances myogenic differentiation and inhibits atrophy through protein synthesis in human myotubes

Author

Kim CH, Shin JH, Hwang SJ, Choi YH, Kim DS, and Kim CM

Subjects
Schisandrae fructus, mTOR signaling, Human skeletal muscle cells, Myotube, Medicine (General), R5-920
Abstract

Cy Hyun Kim,1,2,* Jin-Hong Shin,1,3,* Sung Jun Hwang,1,2 Yung Hyun Choi,4 Dae-Seong Kim,1,3 Cheol Min Kim2,51Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, 2Center for Anti-Aging Industry, Pusan National University, Busan, 3Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, 4Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, 5Department of Biomedical Informatics, Pusan National University School of Medicine, Yangsan, Republic of Korea*These authors contributed equally to this work Abstract: Schisandrae fructus (SF) has recently been reported to increase skeletal muscle mass and inhibit atrophy in mice. We investigated the effect of SF extract on human myotube differentiation and its acting pathway. Various concentrations (0.1–10 µg/mL) of SF extract were applied on human skeletal muscle cells in vitro. Myotube area and fusion index were measured to quantify myotube differentiation. The maximum effect was observed at 0.5 µg/mL of SF extract, enhancing differentiation up to 1.4-fold in fusion index and 1.6-fold in myotube area at 8 days after induction of differentiation compared to control. Phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 and 70 kDa ribosomal protein S6 kinase, which initiate translation as downstream of mammalian target of rapamycin pathway, was upregulated in early phases of differentiation after SF treatment. SF also attenuated dexamethasone-induced atrophy. In conclusion, we show that SF augments myogenic differentiation and attenuates atrophy by increasing protein synthesis through mammalian target of rapamycin/70 kDa ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 signaling pathway in human myotubes. SF can be a useful natural dietary supplement in increasing skeletal muscle mass, especially in the aged with sarcopenia and the patients with disuse atrophy.Keywords: Schisandrae fructus, mTOR signaling, human skeletal muscle cells, myotubes

Published
2016

6. Relationship between vitamin D-binding protein polymorphisms and blood vitamin D level in Korean patients with COPD

Author

Park YM, Kim YS, Kang YA, Shin JH, Oh YM, Seo JB, Jung JY, and Lee SD

Subjects
vitamin D-binding protein, polymorphism, vitamin D, chronic obstructive pulmonary disease, Diseases of the respiratory system, RC705-779
Abstract

Youngmok Park,1 Young Sam Kim,1 Young Ae Kang,1 Ju Hye Shin,1 Yeon Mok Oh,2 Joon Beom Seo,3 Ji Ye Jung,1 Sang Do Lee2 On behalf of the KOLD study 1Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Institute of Chest Diseases, Yonsei University College of Medicine, 2Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, 3Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Background: In chronic obstructive pulmonary disease (COPD), the blood vitamin D3 level is generally low, and genetic polymorphisms of vitamin D-binding protein encoded by the GC gene are associated with COPD development. In this study, we examined the relationship between GC polymorphisms and plasma vitamin D3 level in Korean patients with COPD. Methods: The study included 175 COPD patients from the Korean Obstructive Lung Disease Cohort. Multivariate analysis was conducted with adjustment for age, body mass index (BMI), lung function, smoking status, smoking amount, and seasonal variation in blood vitamin D level. Vitamin D deficiency was defined as a plasma 25-hydroxyvitamin D3 level lower than 20 ng/mL. Results: The mean plasma vitamin D3 level was 17.5 ng/mL. The GC1F variant (44.3%) and genotype 1F-2 (27.4%) were the most common. The plasma vitamin D3 level was lower in patients with the GC2 variant (estimated =-3.73 ng/mL) and higher in those with genotype 1F-1S (estimated =4.08 ng/mL). The GC2 variant was a significant risk factor for vitamin D deficiency (odds ratio =2.41). Among COPD clinical parameters, vitamin D deficiency was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) regardless of GC polymorphisms. FEV1/FVC was higher in patients with genotype 1F-1F (estimated =3.61%) and lower in those with genotype 1F-2 (estimated =-3.31%). The 6-minute walking distance was shorter for patients with the GC1F variant (estimated =-38.91 m) and longer for those with the GC2 variant (estimated =26.98 m). The emphysema index was higher for patients with the GC1S variant (estimated =6.56%) and genotype 1F-1S (estimated =9.86%), regardless of the vitamin D level. Conclusion: The GC2 variant is a risk factor for vitamin D deficiency, and genotype 1F-1S is a protective factor against vitamin D deficiency. GC polymorphisms and vitamin D deficiency correlate with clinical outcomes for Korean patients with COPD. Keywords: vitamin D-binding protein, polymorphism, vitamin D, chronic obstructive pulmonary disease

Published
2016

7. Efficacy of fimasartan/hydrochlorothiazide combination in hypertensive patients inadequately controlled by fimasartan monotherapy

Author

Rhee MY, Baek SH, Kim W, Park CG, Park SW, Oh BH, Kim SH, Kim JJ, Shin JH, Yoo BS, Rim SJ, Ha JW, Doh JH, Ahn Y, Chae JK, Park JB, Kim SK, and Kim CH

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Moo-Yong Rhee,1 Sang Hong Baek,2 Weon Kim,3 Chang Gyu Park,4 Seung Woo Park,5 Byung-Hee Oh,6 Sang-Hyun Kim,7 Jae-Joong Kim,8 Joon-Han Shin,9 Byung-Su Yoo,10 Se-Joong Rim,11 Jong-Won Ha,12 Joon Hyung Doh,13 Youngkeun Ahn,14 Jei Keon Chae,15 Jeong Bae Park,16 Soon-Kil Kim,17 Cheol Ho Kim18 1Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, 2Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 3Cardiovascular Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, 4Division of Cardiology, Guro Hospital, Korea University College of Medicine, Seoul, 5Division of Cardiology, Samsung Medical Center, Seoul, 6Department of Internal Medicine, Seoul National University Hospital, Seoul, 7Division of Cardiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, 8Division of Cardiology, Asan Medical Center, Seoul, 9Division of Cardiology, Ajou University Hospital, Suwon, 10Division of Cardiology, Wonju Severance Christian Hospital, Wonju, 11Division of Cardiology, GangNam Severance Hospital, Seoul, 12Division of Cardiology, Severance Hospital, Seoul, 13Division of Cardiology, Inje University Ilsan Hospital, Goyang, 14Department of Cardiology, Chonnam National University Hospital, Gwangju, 15Chonbuk National University Hospital, Jeonju, 16Department of Cardiology, Cheil General Hospital, Dankook University College of Medicine, Seoul, 17Department of Cardiology, Hanyang University Guri Hospital, Guri, 18Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: The study reported here compared the blood pressure (BP)-lowering efficacy of fimasartan alone with that of fimasartan/hydrochlorothiazide (HCTZ) combination in patients whose BP goal was not achieved after 4 weeks of treatment with once-daily fimasartan 60 mg.Methods: Patients with sitting diastolic blood pressure (siDBP) ≥90 mmHg with 4 weeks of once-daily fimasartan 60 mg were randomly assigned to receive either once-daily fimasartan 60 mg/HCTZ 12.5 mg or fimasartan 60 mg for 4 weeks. After 4 weeks, the dose was increased from fimasartan 60 mg/HCTZ 12.5 mg to fimasartan 120 mg/HCTZ 12.5 mg or from fimasartan 60 mg to fimasartan 120 mg if siDBP was ≥90 mmHg.Results: Of the 263 randomized patients, 256 patients who had available efficacy data were analyzed. The fimasartan/HCTZ treatment group showed a greater reduction of siDBP compared to the fimasartan treatment group at Week 4 (6.88±8.10 mmHg vs 3.38±7.33, P=0.0008), and the effect persisted at Week 8 (8.67±9.39 mmHg vs 5.02±8.27 mmHg, P=0.0023). Reduction of sitting systolic BP in the fimasartan/HCTZ treatment group was also greater than that in the fimasartan treatment group (at Week 4, 10.50±13.76 mmHg vs 5.75±12.18 mmHg, P=0.0069 and, at Week 8, 13.45±15.15 mmHg vs 6.84±13.57 mmHg, P=0.0007). The proportion of patients who achieved a reduction of siDBP ≥10 mmHg from baseline and/or a mean siDBP

Published
2015

8. Prenatal development toxicity study of zinc oxide nanoparticles in rats

Author

Hong JS, Park MK, Kim MS, Lim JH, Park GJ, Maeng EH, Shin JH, Kim MK, Jeong J, Park JA, Kim JC, and Shin HC

Subjects
Medicine (General), R5-920
Abstract

Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. Keywords: developmental toxicity, maternal toxicity, nanotoxicology, teratogenicity

Published
2014

9. A saturated map of common genetic variants associated with human height

Author

Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, Hirschhorn, JN, Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, and Hirschhorn, JN

Abstract

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

Published
2022

10. Clinical utility of phentermine/topiramate (Qsymia™) combination for the treatment of obesity

Author

Shin JH and Gadde KM

Subjects
Specialties of internal medicine, RC581-951
Abstract

Jin Hee Shin,1 Kishore M Gadde2 1Department of Community and Family Medicine, Duke University Medical Center, 2Obesity Clinical Trials Program, Duke University Medical Center, Durham, NC, USA Abstract: Qsymia™ (Vivus Inc, Mountain View, CA, USA), a combination of phentermine and delayed-release topiramate, has been available in the US since September 2012 for the treatment of obesity. Phentermine is an anorexigenic agent, which is approved for the short-term treatment of obesity, while topiramate is approved for nonweight loss indications – seizure disorders and migraine prophylaxis. The amount of weight loss achieved with combination therapy is of a greater magnitude than what could be achieved with either agent alone. Adverse events that occur with the combination therapy are in line with the known side effect profiles of the constituent drugs; teratogenicity, a slight increase in heart rate, psychiatric and cognitive adverse effects, and metabolic acidosis are concerns. Keywords: Qsymia, combination drug, antiobesity drugs, phentermine, topiramate, obesity, weight loss

Published
2013

11. The effect of nitric oxide-releasing silica nanoparticle on revascularization and functional recovery in rat sciatic nerve crush injury

Author

Park, JH, Lee, JI, Park, JW, Ok, MR, Shin, JH, and Lee, JY

Subjects
ddc: 610, nitric oxide, nanoparticle, silica nanoparticle, peripheral nerve, revascularization, nerve, 610 Medical sciences, Medicine, nerve regeneration
Abstract

Objectives/Interrogation: Nitric oxide (NO) is a pivotal biological molecule in revascularization and nerve regeneration process after peripheral nerve injury. Recently, biomaterial advances introduce NO-releasing silica nanoparticle, which may offer the controlled and sustained delivery of NO [for full text, please go to the a.m. URL], 14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT)

Published
2020
Full Text
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17. Acute abdominal pain in systemic lupus erythematosus: focus on lupus enteritis (gastrointestinal vasculitis). (Concise Report)

Author

Lee, C-K, Ahn, MS, Lee, EY, Shin, JH, Cho, Y-S, Ha, HK, Yoo, B, and Moon, H-B

Subjects
Abdominal pain -- Causes of -- Physiological aspects, Systemic lupus erythematosus -- Physiological aspects, Health, Physiological aspects, Causes of
Abstract

Objective: To determine the causes of acute abdominal pain in systemic lupus erythematosus (SLE) and to compare the clinical and laboratory data, especially antiphospholipid antibodies and the SLE Disease Activity [...]

Published
2002

18. Growth Performance and Fatty Acid Profiles of Ducks Fed a Diet Supplemented with Aronia (Aronia Melanocarpa) Powder

Author

Lee, GD, Shin, JH, and Choi, IH

Subjects
Fatty acid profiles, Growth performance, Aronia powder
Abstract

The present study evaluated the effects of aronia powder on growth performance and fatty acid profiles of ducks. A total of 90 ducks (one-day-old pekin, 48 males and 42 females) were distributed according to a completely randomized design into two treatments (control and 1% aronia powder) with 3 replicates of 15 birds per pen for 42 d. Apart from the feed:gain ratio, the other growth performance parameters, including initial body weight, final body weight, weight gain, and feed intake, did not differ significantly between treatments (p>0.05). In addition, there was no significant difference (p>0.05) in fatty acid profiles between treatments. However, oleic acid (C18:1), linoleic acid (C18:2), and polyunsaturated fatty acid (PUFA) were significantly different (p

Published
2018

19. Cell type-specific genetic regulation of expression in the granule cell layer of the human dentate gyrus

Author

Jaffe, AE, primary, Hoeppner, DJ, additional, Saito, T, additional, Blanpain, L, additional, Ukaigwe, J, additional, Burke, EE, additional, Tao, R, additional, Tajinda, K, additional, Deep-Soboslay, A, additional, Shin, JH, additional, Kleinman, JE, additional, Weinberger, DR, additional, Matsumoto, M, additional, and Hyde, TM, additional

Published
2019
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20. In silico and in vitro studies of the reduction of unsaturated alpha,beta bonds of trans-2-hexenedioic acid and 6-amino-trans-2-hexenoic acid - Important steps towards biobased production of adipic acid

Author

Karlsson, E, Shin, J, Westman, G, Eriksson, L, Olsson, L, Mapelli, V, Karlsson E, Shin JH, Westman G, Eriksson LA, Olsson L, Mapelli V, Karlsson, E, Shin, J, Westman, G, Eriksson, L, Olsson, L, Mapelli, V, Karlsson E, Shin JH, Westman G, Eriksson LA, Olsson L, and Mapelli V

Abstract

The biobased production of adipic acid, a precursor in the production of nylon, is of great interest in order to replace the current petrochemical production route. Glucose-rich lignocellulosic raw materials have high potential to replace the petrochemical raw material. A number of metabolic pathways have been proposed for the microbial conversion of glucose to adipic acid, but achieved yields and titers remain to be improved before industrial applications are feasible. One proposed pathway starts with lysine, an essential metabolite industrially produced from glucose by microorganisms. However, the drawback of this pathway is that several reactions are involved where there is no known efficient enzyme. By changing the order of the enzymatic reactions, we were able to identify an alternative pathway with one unknown enzyme less compared to the original pathway. One of the reactions lacking known enzymes is the reduction of the unsaturated a,6 bond of 6-amino-trans-2-hexenoic acid and trans-2-hexenedioic acid. To identify the necessary enzymes, we selected N-ethylmaleimide reductase from Escherichia coli and Old Yellow Enzyme 1 from Saccharomyces pastorianus. Despite successful in silico docking studies, where both target substrates could fit in the enzyme pockets, and hydrogen bonds with catalytic residues of both enzymes were predicted, no in vitro activity was observed. We hypothesize that the lack of activity is due to a difference in electron withdrawing potential between the naturally reduced aldehyde and the carboxylate groups of our target substrates. Suggestions for protein engineering to induce the reactions are discussed, as well as the advantages and disadvantages of the two metabolic pathways from lysine. We have highlighted bottlenecks associated with the lysine pathways, and proposed ways of addressing them.

Published
2018

21. Biobased adipic acid - The challenge of developing the production host

Author

Skoog, E, Shin, J, Saez-Jimenez, V, Mapelli, V, Olsson, L, Skoog E, Shin JH, Saez-Jimenez V, Mapelli V, Olsson L, Skoog, E, Shin, J, Saez-Jimenez, V, Mapelli, V, Olsson, L, Skoog E, Shin JH, Saez-Jimenez V, Mapelli V, and Olsson L

Abstract

Adipic acid is a platform chemical, and is the most important commercial dicarboxylic acid. It has been targeted for biochemical conversion as an alternative to present chemical production routes. From the perspective of bioeconomy, several kinds of raw material are of interest including the sugar platform (derived from starch, cellulose or hemicellulose), the lignin platform (aromatics) and the fatty acid platform (lipid derived). Two main biochemical-based production schemes may be employed: (i) direct fermentation to adipic acid, or (ii) fermentation to muconic or glucaric acid, followed by chemical hydrogenation (indirect fermentation). This review presents a comprehensive description of the metabolic pathways that could be constructed and analyzes their respective theoretical yields and metabolic constraints. The experimental yields and titers obtained so far are low, with the exception of processes based on palm oil and glycerol, which have been reported to yield up to 50 g and 68 g adipic acid/L, respectively. The challenges that remain to be addressed in order to achieve industrially relevant production levels include solving redox constraints, and identifying and/or engineering enzymes for parts of the metabolic pathways that have yet to be metabolically demonstrated. This review provides new insights into ways in which metabolic pathways can be constructed to achieve efficient adipic acid production. The production host provides the chassis to be engineered via an appropriate metabolic pathway, and should also have properties suitable for the industrial production of adipic acid. An acidic process pH is attractive to reduce the cost of downstream processing. The production host should exhibit high tolerance to complex raw material streams and high adipic acid concentrations at acidic pH.

Published
2018

22. Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network

Author

Mcconnell, Mj, Moran, Jv, Abyzov, A, Akbarian, S, Bae, T, Cortes-Ciriano, I, Erwin, Ja, Fasching, L, Flasch, Da, Freed, D, Ganz, J, Jaffe, Ae, Kwan, Ky, Kwon, M, Lodato, Ma, Mills, Re, Paquola, Acm, Rodin, Re, Rosenbluh, C, Sestan, N, Sherman, Ma, Shin, Jh, Song, S, Straub, Re, Thorpe, J, Weinberger, Dr, Urban, Ae, Zhou, B, Gage, Fh, Lehner, T, Senthil, G, Walsh, Ca, Chess, A, Courchesne, E, Gleeson, Jg, Kidd, Jm, Park, Pj, Pevsner, J, Vaccarino, Fm, Barton, Ar, Bekiranov, S, Bohrson, Cl, Burbulis, Ie, Chronister, W, Coppola, G, Daily, K, D'Gama, Am, Emery, Sb, Frisbie, Tj, Gao, T, Gulyás-Kovács, A, Haakenson, M, Keil, Jm, Kopera, Hc, Lam, Mm, Lee, Ea, Marques-Bonet, T, Mathern, Gw, Moldovan, Jb, Oetjens, Mt, Omberg, L, Peters, Ma, Pochareddy, S, Pramparo, T, Ratan, A, Sanavia, T, Shi, L, Skarica, M, Wang, J, Wang, M, Wang, Y, Wierman, M, Wolpert, M, Woodworth, M, Zhao, X, and Zhou, W

Subjects
DNA Replication, 0301 basic medicine, DNA Repair, Brain Somatic Mosaicism, Somatic cell, DNA Mutational Analysis, Genomics, Disease, Biology, Article, Germline, 03 medical and health sciences, Neural Stem Cells, Humans, Copy-number variation, Neurons, Genetics, Multidisciplinary, Genome, Human, Mosaicism, Mental Disorders, Brain, Phenotype, Germ Cells, 030104 developmental biology, Human genome, Nerve Net, Nervous System Diseases, Cell Division, Neurotypical, DNA Damage
Abstract

BACKGROUND Elucidating the genetic architecture of neuropsychiatric disorders remains a major scientific and medical challenge. Emerging genomic technologies now permit the analysis of somatic mosaicism in human tissues. The measured frequencies of single-nucleotide variants (SNVs), small insertion/deletion (indel) mutations, structural variants [including copy number variants (CNVs), inversions, translocations, and whole-chromosome gains or losses], and mobile genetic element insertions (MEIs) indicate that each neuron may harbor hundreds of somatic mutations. Given the long life span of neurons and their central role in neural circuits and behavior, somatic mosaicism represents a potential mechanism that may contribute to neuronal diversity and the etiology of numerous neuropsychiatric disorders. ADVANCES Somatic mutations that confer cellular proliferative or cellular survival phenotypes have been identified in patients with cortical malformations. These data have led to the hypothesis that somatic mutations may also confer phenotypes to subsets of neurons, which could increase the risk of developing certain neuropsychiatric disorders. Genomic technologies, including advances in long-read, next-generation DNA sequencing technologies, single-cell genomics, and cutting-edge bioinformatics, can now make it possible to determine the types and frequencies of somatic mutations within the human brain. However, a comprehensive understanding of the contribution of somatic mosaicism to neurotypical brain development and neuropsychiatric disease requires a coordinated, multi-institutional effort. The National Institute of Mental Health (NIMH) has formed a network of 18 investigative teams representing 15 institutions called the Brain Somatic Mosaicism Network (BSMN). Each research team will use an array of genomic technologies to exploit well-curated human tissue repositories in an effort to define the frequency and pattern of somatic mutations in neurotypical individuals and in schizophrenia, autism spectrum disorder, bipolar disorder, Tourette syndrome, and epilepsy patient populations. Collectively, these efforts are estimated to generate a community resource of more than 10,000 DNA-sequencing data sets and will enable a cross-platform integrated analysis with other NIMH initiatives, such as the PsychENCODE project and the CommonMind Consortium. OUTLOOK A fundamental open question in neurodevelopmental genetics is whether and how somatic mosaicism may contribute to neuronal diversity within the neurotypical spectrum and in diseased brains. Healthy individuals may harbor known pathogenic somatic mutations at subclinical frequencies, and the local composition of neural cell types may be altered by mutations conferring prosurvival phenotypes in subsets of neurons. By extension, the neurotypical architecture of somatic mutations may confer circuit-level differences that would not be present if every neuron had an identical genome. Given the apparent abundance of somatic mutations within neurons, an in-depth understanding of how different types of somatic mosaicism affect neural function could yield mechanistic insight into the etiology of neurodevelopmental and neuropsychiatric disorders. The BSMN will examine large collections of postmortem brain tissue from neurotypical individuals and patients with neuropsychiatric disorders. By sequencing brain DNA and single neuronal genomes directly, rather than genomic DNA derived from peripheral blood or other somatic tissues, the BSMN will test the hypothesis that brain somatic variants contribute to neuropsychiatric disease. Notably, it is also possible that some inherited germline variants confer susceptibility to disease, which is later exacerbated by somatic mutations. Confirming such a scenario could increase our understanding of the genetic risk architecture of neuropsychiatric disease and may, in part, explain discordant neuropsychiatric phenotypes between identical twins. Results from these studies may lead to the discovery of biomarkers and genetic targets to improve the treatment of neuropsychiatric disease and may offer hope for improving the lives of patients and their families.

Published
2017

24. Regional heterogeneity in gene expression, regulation and coherence in hippocampus and dorsolateral prefrontal cortex across development and in schizophrenia

Author

Collado-Torres, L, primary, Burke, EE, additional, Peterson, A, additional, Shin, JH, additional, Straub, RE, additional, Rajpurohit, A, additional, Semick, SA, additional, Ulrich, WS, additional, BrainSeq, Consortium, additional, Valencia, C, additional, Tao, R, additional, Deep-Soboslay, A, additional, Hyde, TM, additional, Kleinman, JE, additional, Weinberger, DR, additional, and Jaffe, AE, additional

Published
2018
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25. Dissecting transcriptomic signatures of neuronal differentiation and maturation using iPSCs

Author

Burke, EE, primary, Chenoweth, JG, additional, Shin, JH, additional, Collado-Torres, L, additional, Kim, SK, additional, Micali, N, additional, Wang, Y, additional, Straub, RE, additional, Hoeppner, DJ, additional, Chen, HY, additional, Lescure, A, additional, Shibbani, K, additional, Hamersky, GR, additional, Phan, BN, additional, Ulrich, WS, additional, Valencia, C, additional, Jaishankar, A, additional, Price, AJ, additional, Rajpurohit, A, additional, Semick, SA, additional, Bürli, R, additional, Barrow, JC, additional, Hiler, DJ, additional, Page, SC, additional, Martinowich, K, additional, Hyde, TM, additional, Kleinman, JE, additional, Berman, KF, additional, Apud, JA, additional, Cross, AJ, additional, Brandon, NJ, additional, Weinberger, DR, additional, Maher, BJ, additional, McKay, RDG, additional, and Jaffe, AE, additional

Published
2018
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29. Metabolic syndrome and ALT: a community study in adult Koreans

Author

Hae-Sung Nam, Jeong Sk, Cho Kh, Rhee Ja, Shin Jh, and Jae-Min Kim

Subjects
Male, Risk, medicine.medical_specialty, Waist, Endocrinology, Diabetes and Metabolism, Population, Medicine (miscellaneous), Blood lipids, Physiology, Internal medicine, Odds Ratio, medicine, Humans, education, Metabolic Syndrome, Likelihood Functions, education.field_of_study, Nutrition and Dietetics, biology, business.industry, Alanine Transaminase, Odds ratio, Middle Aged, medicine.disease, Obesity, Cross-Sectional Studies, Endocrinology, Alanine transaminase, biology.protein, Female, Metabolic syndrome, business, Body mass index, Biomarkers
Abstract

OBJECTIVE: To investigate an association between the metabolic syndrome (MS) and alanine aminotransferase (ALT) of normal ranges. DESIGN: A population-based cross-sectional survey in three rural communities, South Korea. SUBJECTS: A total of 1248 men and 2157 women aged 30 y and older. MEASUREMENTS: Body mass index (BMI), waist circumference, fasting blood lipid and glucose, resting blood pressure, and ALT. RESULTS: ALT and BMI increased with an addition of the MS components. A consistent association between ALT more than 15 IU/l and the MS was found in both sexes, independently of age, education, BMI, smoking, alcohol drinking, and sedentary life style. The odds ratios for the MS in the highest quintiles of ALT were 7.1-fold higher than the reference quintile in men and 2.1-fold higher in women. The likelihood ratio tests for trend were also significant with ALT increments (P

Published
2004

30. Eplerenone in patients with systolic heart failure and mild symptoms

Author

Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B, Drexler H, McMurray J, Remme WJ, Cornel JH, Hildebrandt P, Hradec J, Mareev V, Reddy KS, Sindone A, Martinez F, Alonso Garcia A, Wilhelmsen L, Dargie HJ, Tavazzi L, Pocock S, Leizorovic A, Collier T, Nul DR, Serra JL, Thierer JM, Cross DB, Sindone AP, Singh BB, Boreux JL, Charlier FP, Dendale P, De Keulenaer G, Marchandise B, Marechal P, Marenne F, Mieghem WV, Van Dorpe AC, Vanhaecke J, Arnold JM, Dion D, Huynh T, Kouz SM, Lepage S, McKelvie RS, O'Meara E, Proulx G, Sauve C, Aschermann M, Brecka D, Filipovsky J, Groch L, Jerabek O, Jokl I, Linkova H, Motovska Z, Munz J, Penicka M, Rucka D, Mid JS, Spacek R, Spinar J, Stipal R, Vojacek J, Attali P, Bonneau A, Bousser JP, Dutoit L, Funck F, Galinier MP, Gibelin P, Hautefeuille BD, Hittinger L, Jobic Y, Jourdain P, Komajda M, Maupas E, Olive T, Philias A, Roul G, Rouleau F, Trochu JN, Boehm M, Bruch L, Engelhardt H, Erbs S, Foerster A, Franz N, Hambrecht R, Heuer H, Krueger U, Landmesser U, Leischik R, Mitrovic V, Moehlenkamp S, Monti J, Mueller Ehmsen J, Oezcelik C, Philipp S, Pieske B, Roehnisch JU, Schunkert H, Schwinger R, Wachter R, Willenbrock R, Winkelmann BR, Winkler R, Wollert KC, Adamopoulos S, Kalikazaros I, Karavidas A, Karvounis H, Kremastinos D, Manolis AJ, Nanas I, Sotirellos K, Vasiliadis K, Zaboulis C, Lee S, Yu CM, Czibok C, Édes I, Forster T, Preda I, Simon K, Takacs J, Zámolyi K, Bhagavatula KS, Chockalingam K, Desai N, Iyengar SS, Jayadev SM, Mullasari AS, Sathe SP, Sinha N, Vadagenalli PS, Wander GS, McDonald KM, Nash P, Vaughan CJ, Agostoni P, Ambrosio GB, Bittolo Bon G, Boffa G, Cacciavillani L, Capucci A, Chiariello M, Cirrincione V, Gensini GF, Masini F, Modena MG, Monte I, Rosano GM, Senni M, Sinagra G, Tamburino C, Terrosu P, Villani GQ, Volterrani M, Chae SC, Ha CW, Ha JW, Shin JH, Bayram Llamas E, Calvillo JC, Cruz Diaz A, Delgado Leal L, Estrada Gomez MM, Kosturakis D, Petersen Aranguren F, Velasco Sanchez RG, Daniëls MC, Dirkali A, Dunselman PH, de Kluiver EP, Kragten JA, Lok DJ, Maas AH, Michels HR, Nicastia DM, Stoel I, de Swart JB, Thijssen HJ, Van Kempen LH, Voors AA, Willems FF, Dluzniewski M, Gaciong Z, Kawecka Jaszcz K, Jozwa R, Korewicki J, Krzeminska Pakula M, Kurowski M, Ogorek M, Pempera M, Rynkiewicz A, Ujda M, Wierzchowiecki M, Abreu Á, Andrade A, Carrageta M, Fonseca C, Franco F, Gil VM, Lousada N, Mendonca C, Moreira I, Padua FP, Providência L, Cardoso JC, Trabulo M, Aroutyunov GP, Gindin K, Karpov YB, Kostenko VA, Nikitin YP, Obraztsova GI, Shilkina NP, Shlyakhto EV, Skvortsov A, Ding ZP, Yeo DP, Ambrovicova V, Gaspar L, Goncalvesova E, Kycina P, Litvinova J, Mikes Z, Murin J, Poliacik P, Uhliar R, Lloyd EA, Marx D, Naidoo DP, Prozesky HW, Sliwa Hahnle K, Theron H, Anguita M, De Teresa E, Galve E, Juanatey JR, Orbe PM, Vida M, Ahremark U, Andersson B, Axelsson U, Berglund S, Boman K, Dahlstrom U, Fu M, Holm Orndahl L, Johansson A, Lindgren M, Nemeczek C, Prantare H, Roussine V, Stehn G, Stenberg A, Vasko P, Bazylevych A, Dyadyk OI, Dzyak GV, Girina OM, Ignatenko GA, Kononenko LG, Kubyshkin VF, Kuryata OV, Parkhomenko AN, Perepelytsya MV, Pertseva TO, Popik GS, Rishko MV, Sakharchuk II, Tseluyko VI, Tykhonova SA, Vizir V, Voronkov LG, Al Khaja N, Almahmeed WA, Bazargani N, Adgey AA, Al Mohammad A, Banerjee P, Barlow M, Bridges AB, Brooks N, Connolly EC, Denvir MA, Egdell RM, Kardos A, Keeling PJ, Khokhar AA, Senior R, Williams SG, Anand IS, Anderson JL, Berk MR, Bertolet BD, Bisognano JD, Blonder RD, Breburda CS, Canaday DB, Capodilupo RC, Choiunard MD, Colucci WS, Dahiya RJ, Dunlap SH, Essandoh LK, Flores AR, Henderson DA, Herzog WR Jr, Katz RJ, Kosinski EJ, Labin IN, Lally FL, Lash JA, McGrew FA 3rd, Mohiuddin SM, Moraes D, Murali SC, Nallasivan M, Philbin E, Prabhu S, Primack DS, Ramani R, Rawitscher D, Sangrigoli R, Schamalfuss CM, Stoletniy L, Strong MH, Thadani U, Treasure CB 2nd, Vicari RM, Vogel CD, Wlsh MN, Wencker D, Wilson SA, Winkel E, Wiseman AH, Zoiopoulos LY, Mancebo JR, Mendoza I, Waich S.T., PERRONE FILARDI, PASQUALE, Zannad, F, Mcmurray, Jj, Krum, H, van Veldhuisen, Dj, Swedberg, K, Shi, H, Vincent, J, Pocock, Sj, Pitt, B, Drexler, H, Mcmurray, J, Remme, Wj, Cornel, Jh, Hildebrandt, P, Hradec, J, Mareev, V, Reddy, K, Sindone, A, Martinez, F, Alonso Garcia, A, Wilhelmsen, L, Dargie, Hj, Tavazzi, L, Pocock, S, Leizorovic, A, Collier, T, Nul, Dr, Serra, Jl, Thierer, Jm, Cross, Db, Sindone, Ap, Singh, Bb, Boreux, Jl, Charlier, Fp, Dendale, P, De Keulenaer, G, Marchandise, B, Marechal, P, Marenne, F, Mieghem, Wv, Van Dorpe, Ac, Vanhaecke, J, Arnold, Jm, Dion, D, Huynh, T, Kouz, Sm, Lepage, S, Mckelvie, R, O'Meara, E, Proulx, G, Sauve, C, Aschermann, M, Brecka, D, Filipovsky, J, Groch, L, Jerabek, O, Jokl, I, Linkova, H, Motovska, Z, Munz, J, Penicka, M, Rucka, D, Mid, J, Spacek, R, Spinar, J, Stipal, R, Vojacek, J, Attali, P, Bonneau, A, Bousser, Jp, Dutoit, L, Funck, F, Galinier, Mp, Gibelin, P, Hautefeuille, Bd, Hittinger, L, Jobic, Y, Jourdain, P, Komajda, M, Maupas, E, Olive, T, Philias, A, Roul, G, Rouleau, F, Trochu, Jn, Boehm, M, Bruch, L, Engelhardt, H, Erbs, S, Foerster, A, Franz, N, Hambrecht, R, Heuer, H, Krueger, U, Landmesser, U, Leischik, R, Mitrovic, V, Moehlenkamp, S, Monti, J, Mueller Ehmsen, J, Oezcelik, C, Philipp, S, Pieske, B, Roehnisch, Ju, Schunkert, H, Schwinger, R, Wachter, R, Willenbrock, R, Winkelmann, Br, Winkler, R, Wollert, Kc, Adamopoulos, S, Kalikazaros, I, Karavidas, A, Karvounis, H, Kremastinos, D, Manolis, Aj, Nanas, I, Sotirellos, K, Vasiliadis, K, Zaboulis, C, Lee, S, Yu, Cm, Czibok, C, Édes, I, Forster, T, Preda, I, Simon, K, Takacs, J, Zámolyi, K, Bhagavatula, K, Chockalingam, K, Desai, N, Iyengar, S, Jayadev, Sm, Mullasari, A, Sathe, Sp, Sinha, N, Vadagenalli, P, Wander, G, Mcdonald, Km, Nash, P, Vaughan, Cj, Agostoni, P, Ambrosio, Gb, Bittolo Bon, G, Boffa, G, Cacciavillani, L, Capucci, A, Chiariello, M, Cirrincione, V, Gensini, Gf, Masini, F, Modena, Mg, Monte, I, PERRONE FILARDI, Pasquale, Rosano, Gm, Senni, M, Sinagra, G, Tamburino, C, Terrosu, P, Villani, Gq, Volterrani, M, Chae, Sc, Ha, Cw, Ha, Jw, Shin, Jh, Bayram Llamas, E, Calvillo, Jc, Cruz Diaz, A, Delgado Leal, L, Estrada Gomez, Mm, Kosturakis, D, Petersen Aranguren, F, Velasco Sanchez, Rg, Daniëls, Mc, Dirkali, A, Dunselman, Ph, de Kluiver, Ep, Kragten, Ja, Lok, Dj, Maas, Ah, Michels, Hr, Nicastia, Dm, Stoel, I, de Swart, Jb, Thijssen, Hj, Van Kempen, Lh, Voors, Aa, Willems, Ff, Dluzniewski, M, Gaciong, Z, Kawecka Jaszcz, K, Jozwa, R, Korewicki, J, Krzeminska Pakula, M, Kurowski, M, Ogorek, M, Pempera, M, Rynkiewicz, A, Ujda, M, Wierzchowiecki, M, Abreu, Á, Andrade, A, Carrageta, M, Fonseca, C, Franco, F, Gil, Vm, Lousada, N, Mendonca, C, Moreira, I, Padua, Fp, Providência, L, Cardoso, Jc, Trabulo, M, Aroutyunov, Gp, Gindin, K, Karpov, Yb, Kostenko, Va, Nikitin, Yp, Obraztsova, Gi, Shilkina, Np, Shlyakhto, Ev, Skvortsov, A, Ding, Zp, Yeo, Dp, Ambrovicova, V, Gaspar, L, Goncalvesova, E, Kycina, P, Litvinova, J, Mikes, Z, Murin, J, Poliacik, P, Uhliar, R, Lloyd, Ea, Marx, D, Naidoo, Dp, Prozesky, Hw, Sliwa Hahnle, K, Theron, H, Anguita, M, De Teresa, E, Galve, E, Juanatey, Jr, Orbe, Pm, Vida, M, Ahremark, U, Andersson, B, Axelsson, U, Berglund, S, Boman, K, Dahlstrom, U, Fu, M, Holm Orndahl, L, Johansson, A, Lindgren, M, Nemeczek, C, Prantare, H, Roussine, V, Stehn, G, Stenberg, A, Vasko, P, Bazylevych, A, Dyadyk, Oi, Dzyak, Gv, Girina, Om, Ignatenko, Ga, Kononenko, Lg, Kubyshkin, Vf, Kuryata, Ov, Parkhomenko, An, Perepelytsya, Mv, Pertseva, To, Popik, G, Rishko, Mv, Sakharchuk, Ii, Tseluyko, Vi, Tykhonova, Sa, Vizir, V, Voronkov, Lg, Al Khaja, N, Almahmeed, Wa, Bazargani, N, Adgey, Aa, Al Mohammad, A, Banerjee, P, Barlow, M, Bridges, Ab, Brooks, N, Connolly, Ec, Denvir, Ma, Egdell, Rm, Kardos, A, Keeling, Pj, Khokhar, Aa, Senior, R, Williams, Sg, Anand, I, Anderson, Jl, Berk, Mr, Bertolet, Bd, Bisognano, Jd, Blonder, Rd, Breburda, C, Canaday, Db, Capodilupo, Rc, Choiunard, Md, Colucci, W, Dahiya, Rj, Dunlap, Sh, Essandoh, Lk, Flores, Ar, Henderson, Da, Herzog WR, Jr, Katz, Rj, Kosinski, Ej, Labin, In, Lally, Fl, Lash, Ja, McGrew FA, 3rd, Mohiuddin, Sm, Moraes, D, Murali, Sc, Nallasivan, M, Philbin, E, Prabhu, S, Primack, D, Ramani, R, Rawitscher, D, Sangrigoli, R, Schamalfuss, Cm, Stoletniy, L, Strong, Mh, Thadani, U, Treasure CB, 2nd, Vicari, Rm, Vogel, Cd, Wlsh, Mn, Wencker, D, Wilson, Sa, Winkel, E, Wiseman, Ah, Zoiopoulos, Ly, Mancebo, Jr, Mendoza, I, and Waich, S. T.

Published
2011

31. Acute abdominal pain in systemic lupus erythematosus: focus on lupus enteritis (gastrointestinal vasculitis)

Author

Cheong Lee, Shin Jh, Bin Yoo, Eun Young Lee, Ha Hk, Moon Hb, Ahn Ms, and Cho Ys

Subjects
Adult, Male, medicine.medical_specialty, Abdominal pain, Concise Report, Immunology, Gastroenterology, General Biochemistry, Genetics and Molecular Biology, Enteritis, Rheumatology, immune system diseases, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, skin and connective tissue diseases, Retrospective Studies, Systemic lupus erythematosus, Lupus erythematosus, medicine.diagnostic_test, biology, business.industry, C-reactive protein, medicine.disease, Abdominal Pain, Surgery, medicine.anatomical_structure, Erythrocyte sedimentation rate, Acute Disease, Antibodies, Antiphospholipid, biology.protein, Abdomen, Female, medicine.symptom, business, Vasculitis
Abstract

Objective: To determine the causes of acute abdominal pain in systemic lupus erythematosus (SLE) and to compare the clinical and laboratory data, especially antiphospholipid antibodies and the SLE Disease Activity Index (SLEDAI), between lupus enteritis (gastrointestinal vasculitis) and acute abdominal pain without lupus enteritis in patients with SLE. Methods: A retrospective study was carried out for all patients admitted with SLE from 1993 to March 2001. The SLEDAI and laboratory data were collected at the time of diagnosis of SLE and at the time of acute abdominal pain. Lupus enteritis (gastrointestinal vasculitis) was diagnosed by clinical investigation and abdominal computed tomographic findings. Results: Chart review identified 175 patients (20 male, 155 female) who had been admitted with SLE. Of these patients, 38 (22%) presented with acute abdominal pain. Lupus enteritis was the most common cause of acute abdominal pain. Patients were divided into three groups: group 1: lupus enteritis (n=17), group 2: acute abdominal pain without lupus enteritis (n=21), and group 3: SLE without acute abdominal pain (n=137). There was no difference in age and sex among the three groups. Antiphospholipid, anti-RNP, anti-Sm, anti-Ro, and anti-La antibodies did not differ among the three groups. There was no difference in the SLEDAI at the time of diagnosis and at the time of acute abdominal pain between groups 1 and 2. Complement, erythrocyte sedimentation rate, C reactive protein, and anti-dsDNA measured at the time of acute abdominal pain did not differ between groups 1 and 2. A drop in the white blood cell count at the time of abdominal pain was more prominent in group 1 than group 2. In lupus enteritis, the jejunum and ileum were the sites most commonly affected. Rectal involvement was rare. Even though four patients relapsed, all the patients with lupus enteritis, including those who relapsed, responded well to corticosteroid. Conclusion: Lupus enteritis is the most common cause of acute abdominal pain in SLE. All patients with lupus enteritis responded well to a high dose of a corticosteroid without surgical intervention. The SLEDAI and laboratory data, except leucopenia, do not correlate with the occurrence of lupus enteritis.

Published
2002

32. Detection of cancer cells in peripheral blood of stomach cancer patients using RT-PCR amplification of tumour-specific mRNAs

Author

Chung J, Seona Park, Kim Yh, Kim Ho, Chung Hk, Yang Hk, Park Jg, Jung-Hyo Rhim, Hur Ym, and Shin Jh

Subjects
Pathology, medicine.medical_specialty, Messenger RNA, Hepatology, business.industry, Gastroenterology, Cancer, medicine.disease, Real-time polymerase chain reaction, Cancer cell, medicine, T-stage, Pharmacology (medical), Telomerase reverse transcriptase, Lymph, business, Stomach cancer
Abstract

Background: RT–PCR amplification of tumour-specific mRNA has been used for the detection of cancer cells in peripheral blood. Aim: To evaluate the characteristics of the tumour specific mRNA species in peripheral blood of stomach cancer patients. Methods: We analysed CEA, GalNAc-T, MUC-1, c-MET and hTERT mRNA expression in the stomach cancer cell lines and tissues, lymph nodes and peripheral blood of stomach cancer patients using RT–PCR. Results: In RT–PCR analysis of the peripheral blood, 4%, 8%, 21%, 46%, and 100% of stomach cancer patients were positive for CEA, GalNAc-T, c-MET, hTERT and MUC-1 mRNA, respectively, but MUC-1 mRNA was also positive in all normal blood samples. The detection of hTERT mRNA was correlated with poor differentiation (P=0.01) and lymph node metastasis (P=0.009). The presence of c-MET mRNA was correlated with T stage (P=0.025), lymph node metastasis (P=0.036), distant metastasis (P=0.031), and stage of the stomach cancer (P=0.023). Conclusions: Our study suggest that hTERT mRNA in peripheral blood can be a molecular marker for gastric cancer. We also showed that each molecular marker can be correlated with the clinicopathological features of the patients.

Published
2002

33. Nifedipine plus candesartan combination increases blood pressure control regardless of race and improves the side effect profile: DISTINCT randomized trial results

Author

Kjeldsen, Sverre E, Sica, Domenic, Haller, Hermann, Cha, Gloria, Gil Extremera, Blas, Harvey, Peter, Heyvaert, Frank, Lewin, Andrew J., Villa, Giuseppe, Mancia, Giuseppe, the DISTINCT investigators: Agaiby, J, Aggarwal, N, Ainsworth, P, Akhras, R, Amaluan, V, Ballarin, A, Bardauskiene, L, Berra, Fc, Blagden, M, Bodalia, B, Borghi, C, Bundy, C, Burgess, L, Buynak, R, Cafferata, A, Cahill, T, Capiau, L, Capuano, V, Casanova, R, Cecil, J, Cha, G, Chapman, J, Chilvers, M, Christensen, S, Cho, Yh, Chung, Wb, Cipollone, F, Coca, A, Colombo, H, Contreras, Em, Crowley, D, Cusco Prieto, B, Decarlini, F, Doh, Jh, Dzongowski, P, Dzyak, G, Ellery, A, Extremera, Bg, Farias, E, Farrington, C, Fidelholtz, J, Fouche, L, Gabito, A, Gainza, M, Gani, M, Gaunt, R, Gelersztein, E, Giuliano, M, Glazunov, A, Glorioso, N, Goloschekin, B, Gumbley, M, Gupta, A, Guzman, L, Ha, Jw, Hart, R, Harvey, P, Haworth, D, Henein, S, Henry, D, Her, Sh, Heyvaert, F, Hollanders, G, Hominal, M, Hong, Bk, Hong, Tj, Hwang, Kk, Jacovides, A, Jacqmein, J, Jeon, Hk, Jones, N, Kanani, S, Kang, H, Karpenko, O, Kenton, D, Kimzey, N, Kjeldsen, Se, Kovalenko, V, Kushnir, M, Lasko, B, Lee, Kj, Lee, N, Lewin, A, Litvak, M, Luksiene, D, Majul, C, Mannarino, E, Manuale, O, Marcadis, A, Miller, D, Mills, R, Misik, K, Mortelmans, J, O'Mahony, M, O'Mahony, W, Park, C, Pedrinelli, Roberto, Petrulioniene, Z, Pettyjohn, F, Piskorz, D, Poss, G, Pudi, K, Pyun, Wb, Raad, G, Raila, G, Ramirez Espinosa MF, Ramlachan, P, Rhee, M, Rudenko, L, Ruiz, Ts, Ryan, J, Schacter, G, Shin, Jh, Short, D, Sica, D, Sirenko, Y, Slapikas, R, Somani, R, Stanislavchuk, M, Stewart, R, Svishchenko, Y, Sychov, O, Teitelbaum, I, Tseluyko, V, Van Rensburg DJ, Vaquer Perez JV, Via, Lm, Vico, M, Villa, G, Vizir, V, Vogel, D, Wellmann, H, Yoo, B. S., Kjeldsen, Sverre E, Sica, Domenic, Haller, Hermann, Cha, Gloria, Gil-Extremera, Bla, Harvey, Peter, Heyvaert, Frank, Lewin, Andrew J, Villa, Giuseppe, Mancia, Giuseppe, Borghi, Claudio, Kjeldsen, S, Sica, D, Haller, H, Cha, G, Gil-Extremera, B, Harvey, P, Heyvaert, F, Lewin, A, Villa, G, and Mancia, G

Subjects
Male, Physiology, Ethnic Group, Administration, Oral, Tetrazoles, Blood Pressure, DISTINCT study, Pharmacology, Benzimidazole, law.invention, combination therapy, Randomized controlled trial, candesartan cilexetil, combination therapy, DISTINCT study, essential hypertension, nifedipine GITS, vasodilatory side effects, law, Ethnicity, Tetrazole, Middle Aged, candesartan cilexetil, Biphenyl compound, Antihypertensive Agent, Treatment Outcome, Tolerability, Aged, Antihypertensive Agents, Benzimidazoles, Biphenyl Compounds, Double-Blind Method, Drug Therapy, Combination, Drug-Related Side Effects and Adverse Reactions, Ethnic Groups, Female, Humans, Hypertension, Nifedipine, Cardiology and Cardiovascular Medicine, Internal Medicine, Administration, Combination, Cardiology, Vasodilatory side effect, ORIGINAL PAPERS: Therapeutic aspects, medicine.drug, Human, Oral, medicine.medical_specialty, Side effect, Combination therapy, Drug Therapy, Internal medicine, medicine, vasodilatory side effects, business.industry, essential hypertension, nifedipine GITS, Candesartan, Blood pressure, Biphenyl Compound, business, Drug-Related Side Effects and Adverse Reaction
Abstract

Objectives: DISTINCT (reDefining Intervention with Studies Testing Innovative Nifedipine GITS – Candesartan Therapy) aimed to determine the dose–response and tolerability of nifedipine GITS and/or candesartan cilexetil therapy in participants with hypertension. Methods: In this 8-week, multinational, multicentre, randomized, double-blind, placebo-controlled study, adults with mean seated DBP of at least 95 to less than 110 mmHg received combination or monotherapy with nifedipine GITS (N) 20, 30 or 60 mg and candesartan cilexetil (C) 4, 8, 16 or 32 mg, or placebo. The primary endpoint, change in DBP from baseline to Week 8, was analysed using the response surface model (RSM); this analysis was repeated for mean seated SBP. Results: Overall, 1381 participants (mean baseline SBP/DBP: 156.5/99.6 mmHg) were randomized. Both N and C contributed independently to SBP/DBP reductions [P

Published
2014

35. Newborns Surgery with Congenital Anomalies: A National Survey of Its Members by Korean Association of Pediatric Surgeons

Author

Kim, DY, primary, Kim, SC, additional, Kim, SH, additional, Kim, HY, additional, Nam, SH, additional, Park, KW, additional, Park, JB, additional, Park, JY, additional, Park, TJ, additional, Seo, JM, additional, Seol, JY, additional, Shin, JH, additional, Oh, JT, additional, Lee, MD, additional, Lee, SK, additional, Lee, SC, additional, Jang, EY, additional, Jang, HK, additional, Jung, SY, additional, Jung, SE, additional, Jung, SM, additional, Jung, YJ, additional, Jung, EY, additional, Cho, MJ, additional, Choi, SJN, additional, Choi, SO, additional, Choi, SH, additional, Choi, YM, additional, Han, SJ, additional, and Heo, TK, additional

Published
2016
Full Text
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40. Ultrasonography-guided core needle biopsy for the thyroid nodule: does the procedure hold any benefit for the diagnosis when fine-needle aspiration cytology analysis shows inconclusive results?

Author

Eun Young Ko, Boo-Kyung Han, Shin Jh, Eun Sook Ko, and Soo Yeon Hahn

Subjects
Thyroid nodules, Adult, Male, medicine.medical_specialty, Adenoma, Adolescent, Lymphoma, Biopsy, Fine-Needle, Thyroid carcinoma, Diagnosis, Differential, Young Adult, Biopsy, Carcinoma, medicine, Adenoma, Oxyphilic, Humans, Radiology, Nuclear Medicine and imaging, Thyroid Neoplasms, Thyroid Nodule, Ultrasonography, Interventional, Aged, Aged, 80 and over, medicine.diagnostic_test, Full Paper, business.industry, Thyroid, Reproducibility of Results, Nodule (medicine), General Medicine, Middle Aged, medicine.disease, Carcinoma, Papillary, medicine.anatomical_structure, Female, Radiology, Biopsy, Large-Core Needle, medicine.symptom, Differential diagnosis, business
Abstract

We evaluated the diagnostic role of ultrasonography-guided core needle biopsy (CNB) according to ultrasonography features of thyroid nodules that had inconclusive ultrasonography-guided fine-needle aspiration (FNA) results.A total of 88 thyroid nodules in 88 patients who underwent ultrasonography-guided CNB because of previous inconclusive FNA results were evaluated. The patients were classified into three groups based on ultrasonography findings: Group A, which was suspicious for papillary thyroid carcinoma (PTC); Group B, which was suspicious for follicular (Hurthle cell) neoplasm; and Group C, which was suspicious for lymphoma. The final diagnoses of the thyroid nodules were determined by surgical confirmation or follow-up after ultrasonography-guided CNB.Of the 88 nodules, the malignant rate was 49.1% in Group A, 12.0% in Group B and 90.0% in Group C. The rates of conclusive ultrasonography-guided CNB results after previous incomplete ultrasonography-guided FNA results were 96.2% in Group A, 64.0% in Group B and 90.0% in Group C (p=0.001). 12 cases with inconclusive ultrasonography-guided CNB results were finally diagnosed as 8 benign lesions, 3 PTCs and 1 lymphoma. The number of previous ultrasonography-guided FNA biopsies was not significantly different between the conclusive and the inconclusive result groups of ultrasonography-guided CNB (p=0.205).Ultrasonography-guided CNB has benefit for the diagnosis of thyroid nodules with inconclusive ultrasonography-guided FNA results. However, it is still not helpful for the differential diagnosis in 36% of nodules that are suspicious for follicular neoplasm seen on ultrasonography.This study shows the diagnostic contribution of ultrasonography-guided CNB as an alternative to repeat ultrasonography-guided FNA or surgery.

Published
2013

41. Improvement of cardiac fibrosis in dystrophic mice by rAAV9-mediated microdystrophin transduction

Author

Shin Jh, Takashi Okada, Shin'ichi Takeda, Yuko Nitahara-Kasahara, Hironori Okada, Hiromi Hayashita-Kinoh, Tomoko Chiyo, Kinoshita K, and Ohshima-Hosoyama S

Subjects
medicine.medical_specialty, Aging, Cardiac fibrosis, Genetic enhancement, Duchenne muscular dystrophy, Genetic Vectors, Cardiomyopathy, Gene delivery, Dystrophin, Mice, Fibrosis, Transduction, Genetic, Internal medicine, Genetics, Medicine, Animals, Humans, Transgenes, Molecular Biology, Cause of death, medicine.diagnostic_test, business.industry, Myocardium, Genetic Therapy, Dependovirus, medicine.disease, Virology, Muscular Dystrophy, Duchenne, cardiovascular system, Cardiology, Mice, Inbred mdx, Molecular Medicine, business, Cardiomyopathies, Electrocardiography
Abstract

Duchenne muscular dystrophy (DMD) is the most common form of the progressive muscular dystrophies characterized by defects of the dystrophin gene. Although primarily characterized by degeneration of the limb muscles, cardiomyopathy is a major cause of death. Therefore, the development of curative modalities such as gene therapy is imperative. We evaluated the cardiomyopathic features of mdx mice to observe improvements in response to intravenous administration of recombinant adeno-associated virus (AAV) type 9 encoding microdystrophin. The myocardium was extensively transduced with microdystrophin to significantly prevent the development of fibrosis, and expression persisted for the duration of the study. Intraventricular conduction patterns, such as the QRS complex duration and S/R ratio in electrocardiography, were also corrected, indicating that the transduced microdystrophin has a protective effect on the dystrophin-deficient myocardium. Furthermore, BNP and ANP levels were reduced to normal, suggesting the absence of cardiac dysfunction. In aged mice, prevention of ectopic beats as well as echocardiographic amelioration was also demonstrated with improved exercise performance. These findings indicate that AAV-mediated cardiac transduction with microdystrophin might be a promising therapeutic strategy for the treatment of dystrophin-deficient cardiomyopathy.

Published
2011

42. Safety and efficacy of stereotactic body radiotherapy as primary treatment for vertebral metastases: a multi-institutional analysis

Author

Guckenberger, M, Mantel, F, Gerszten, PC, Flickinger, JC, Sahgal, A, Létourneau, D, Grills, IS, Jawad, M, Fahim, DK, Shin, JH, Winey, B, Sheehan, J, Kersh, R, Guckenberger, M, Mantel, F, Gerszten, PC, Flickinger, JC, Sahgal, A, Létourneau, D, Grills, IS, Jawad, M, Fahim, DK, Shin, JH, Winey, B, Sheehan, J, and Kersh, R

Abstract

PURPOSE: To evaluate patient selection criteria, methodology, safety and clinical outcomes of stereotactic body radiotherapy (SBRT) for treatment of vertebral metastases.

Published
2014

43. An arachnoid granulation in the straight sinus

Author

Choong-Gon Choi, Lee Mj, Shin Jh, Sun Uck Kwon, Dae Chul Suh, and Lee Hk

Subjects
Adult, Male, medicine.medical_specialty, Arachnoid granulation, Cranial Sinuses, Central nervous system disease, Lesion, Cerebrospinal fluid, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Neuroradiology, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Cerebral Angiography, medicine.anatomical_structure, Angiography, Neurology (clinical), Radiology, Arachnoid, medicine.symptom, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business, Magnetic Resonance Angiography, Straight sinus
Abstract

We report CT, MRI and angiographic findings of an arachnoid granulation in the straight sinus in a young man. Its density and signal intensity were isodense and isointense with cerebrospinal fluid on CT and MRI, respectively. The lesion appeared as a filling defect on MR venography and conventional angiography.

Published
2000

44. A multi-national report on methods for institutional credentialing for spine radiosurgery

Author

Gerszten, PC, Sahgal, A, Sheehan, JP, Kersh, R, Chen, S, Flickinger, JC, Quader, M, Fahim, D, Grills, I, Shin, JH, Winey, B, Oh, K, Sweeney, RA, Guckenberger, M, Gerszten, PC, Sahgal, A, Sheehan, JP, Kersh, R, Chen, S, Flickinger, JC, Quader, M, Fahim, D, Grills, I, Shin, JH, Winey, B, Oh, K, Sweeney, RA, and Guckenberger, M

Abstract

Background: Stereotactic body radiotherapy and radiosurgery are rapidly emerging treatment options for both malignant and benign spine tumors. Proper institutional credentialing by physicians and medical physicists as well as other personnel is important for the safe and effective adoption of spine radiosurgery. This article describes the methods for institutional credentialing for spine radiosurgery at seven highly experienced international institutions.Methods: All institutions (n = 7) are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided spine radiosurgery. A questionnaire consisting of 24 items covering various aspects of institutional credentialing for spine radiosurgery was completed by all seven institutions.Results: Close agreement was observed in most aspects of spine radiosurgery credentialing at each institution. A formal credentialing process was believed to be important for the implementation of a new spine radiosurgery program, for patient safety and clinical outcomes. One institution has a written policy specific for spine radiosurgery credentialing, but all have an undocumented credentialing system in place. All institutions rely upon an in-house proctoring system for the training of both physicians and medical physicists. Four institutions require physicians and medical physicists to attend corporate sponsored training. Two of these 4 institutions also require attendance at a non-corporate sponsored academic society radiosurgery course. Corporate as well as non-corporate sponsored training were believed to be complimentary and both important for training. In 5 centers, all cases must be reviewed at a multidisciplinary conference prior to radiosurgery treatment. At 3 centers, neurosurgeons are not required to be involved in all cases if there is no evidence for instability or spinal cord compression. Backup physicians and physicists are required at only 1 institution, but all

Published
2013

45. Angiographic evaluation of hepatic arterial injury after cisplatin and Gelfoam–based transcatheter arterial chemoembolization for hepatocellular carcinoma in a 205 patient cohort during a 6-year follow-up

Author

Shin Jh, Kim Jh, Chong Hyun Suh, Sung Kb, Yoon Hk, Yoon Hm, Gwon Di, and Ko Gy

Subjects
Adult, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, animal structures, Hemostatics, Young Adult, Hepatic Artery, medicine, Humans, Radiology, Nuclear Medicine and imaging, Cumulative incidence, Chemoembolization, Therapeutic, Transcatheter arterial chemoembolization, Survival rate, Aged, Aged, 80 and over, Venous Thrombosis, Full Paper, business.industry, Incidence, Liver Neoplasms, Angiography, virus diseases, General Medicine, Middle Aged, medicine.disease, Gelatin Sponge, Absorbable, Confidence interval, Portal vein thrombosis, Surgery, Survival Rate, Venous thrombosis, Stenosis, Hepatocellular carcinoma, Female, Cisplatin, business, Follow-Up Studies
Abstract

To evaluate the overall and cumulative incidence, degree, interval change and predictors of hepatic arterial injury (HAI) after cisplatin and Gelfoam® (Upjohn, Kalamazoo, MI)-based transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).A total of 205 patients with HCC who underwent three or more sessions of TACE without additional surgical or local treatment were included. HAI was evaluated at each segment of the hepatic artery using a three-grade scale: 1 (slight wall irregularity), 2 (overt stenosis) and 3 (occlusion). HAI interval change was categorized into three groups: progression, stable state and improvement. Cumulative incidence of HAI was analysed using Kaplan- Meier method, and predictors of HAI (patient age, sex, portal vein thrombosis and Child-Pugh classification) were analysed by univariate logistic regression.HAI occurred in 50 of the 205 study patients (24.4%). The cumulative incidence of HAI was 16.0% [95% confidence interval (CI), 10.21-21.77] during 5 sessions of TACE, 52.1% (95% CI, 37.83-66.29) during 10 sessions and 68.0% (95% CI, 67.62-88.46) during 15 sessions. Initial HAI was interpreted as grades 1, 2 and 3 in 11 (22.0%), 17 (34.0%) and 22 (44.0%) patients, respectively. When the interval change was assessed in 48 patients with available follow-up TACE, 40 (83.3%) were included in the progression, 2 (4.2%) in the stable state and 6 (12.5%) in the improvement groups. The univariate analysis used to determine the predictors of HAI revealed no significant predictors.In three or more sessions of TACE, the incidence of HAI was 24%. Increasing TACE causes increased incidence of HAI. The initial presentation was most commonly grade 3, and 12.5% of the patients with HAI showed improvement of the HAI grade during follow-up TACE.In patients who underwent three or more sessions of cisplatin and Gelfoam-based TACE, the overall incidence of HAI was 24.4%, and increasing TACE causes increased incidence of HAI.

Published
2014

46. Relative composition and energy spectra of light nuclei in cosmic rays: Results from AMS-01

Author

Aguilar, M, Alcaraz, J, Allaby, J, Alpat, B, Ambrosi, G, Anderhub, H, Ao, L, Arefiev, A, Arruda, A, Azzarello, P, Basile, M, Barao, F, Barreira, G, Bartoloni, A, Battiston, R, Becker, R, Becker, U, Bellagamba, L:, B, P, Berdugo, J, Berges, P, Bertucci, B, Biland, A, Bindi, V, Boella, G, Boschini, M, Bourquin, M, Bruni, G, Buenerd, M, Burger, J, Burger, W, Cai, X, Cannarsa, P, Capell, M, Casadei, D, Casaus, J, Castellini, G, Cernuda, I, Chang, Y, Chen, H, Chen, Z, Chernoplekov, N, Chiueh, T, Choi, Y, Cindolo, F, Commichau, V, Contin, A, Cortina Gil, E, Crespo, D, Cristinziani, M, Dai, T, dela Guia, C, Delgado, C, Di Falco, S, Djambazov, L, D’Antone, I, Dong, Z, Duranti, M, Engelberg, J, Eppling, F, Eronen, T, Extermann, P, Favier, J, Fiandrini, E, Fisher, P, Flugge, G, Fouque, N, Galaktionov, Y, Gervasi, M, Giovacchini, F, Giusti, P, Grandi, D, Grimm, O, Gu, W, Haino, S, Hangarter, K, Hasan, A, Hermel, V, Hofer, H, Hungerford, W, Ionica, M, Jongmanns, M, Karlamaa, K, Karpinski, W, Kenney, G, Kim, D, Kim, G, Kim, K, Kirn, T, Klimentov, A, Kossakowski, R, Kounine, A, Koutsenko, V, Kraeber, M, Laborie, G, Laitinen, T, Lamanna, G, Laurenti, G, Lebedev, A, Lechanoine Leluc, C, Lee, M, Lee, S, Levi, G, Lin, C, Liu, H, Lu, G, Lu, Y, Lubelsmeyer, K, Luckey, D, Lustermann, W, Mana, C, Margotti, A, Mayet, F, Mcneil, R, Menichelli, M, Mihul, A, Mujunen, A, Oliva, A, Palmonari, F, Park, H, Park, W, Pauluzzi, M, Pauss, F, Pereira, R, Perrin, E, Pevsner, A, Pilo, F, Pimenta, M, Plyaskin, V, Pojidaev, V, Pohl, M, Produit, N, Quadrani, L, Rancoita, P, Rapin, D, Ren, D, Ren, Z, Ribordy, M, Richeux, J, Riihonen, E, Ritakari, J, Ro, S, Roeser, U, Sagdeev, R, Santos, D, Sartorelli, G, Sbarra, C, Schael, S, Schultz von Dratzig, A, Schwering, G, Seo, E, Shin, J, Shoumilov, E, Shoutko, V, Siedenburg, T, Siedling, R, Son, D, Song, T, Spada, F, Spinella, F, Steuer, M, Sun, G, Suter, H, Tang, H, Ting, S, Tomassetti, N, Tornikoski, M, Torsti, J, Trumper, J, Ulbricht, J, Urpo, S, Valtonen, E, Vandenhirtz, J, Velikhov, E, Verlaat, B, Vetlitsky, I, Vezzu, F, Vialle, J, Vierte, G, Vite, D, Von Gunten, H, Waldmeier Wicki, S, Wallraff, W, Wang, J, Wiik, K, Williams, C, Wu, S, Xia, P, Xu, S, Xu, Z, Yan, J, Yan, L, Yang, C, Yang, J, Yang, M, Ye, S, Zhang, H, Zhang, Z, Zhao, D, Zhou, F, Zhou, Y, Zhu, G, Zhu, W, Zhuang, H, Zichichi, A, Zimmermann, B, Zuccon, P, L: Bene, BOELLA, GIULIANO FILIPPO, Burger, JD, Burger, WJ, Cai, XD, Chang, YH, Chen, HF, Chen, HS, Chen, ZG, Chernoplekov, NA, Chiueh, TH, Choi, YY, Dai, TS, Dong, ZR, Eppling, FJ, Fisher, PH, GERVASI, MASSIMO, Gu, WQ, Kim, DH, Kim, GN, Kim, KS, Lee, MW, Lee, SC, Lin, CH, Liu, HT, Lu, YS, McNeil, RR, Park, HB, Park, WH, Rancoita, PG, Richeux, JP, Seo, ES, Shin, JH, Spada, FR, Sun, GS, Tang, HW, Ting, SCC, Ting, SM, Vialle, JP, Wang, JZ, Xia, PC, Xu, ZZ, Yan, JL, Yan, LG, Yang, CG, Ye, SW, Zhang, HY, Zhang, ZP, Zhao, DX, Zhu, GY, Zhu, WZ, Zhuang, HL, Zuccon, P., Aguilar, M, Alcaraz, J, Allaby, J, Alpat, B, Ambrosi, G, Anderhub, H, Ao, L, Arefiev, A, Arruda, A, Azzarello, P, Basile, M, Barao, F, Barreira, G, Bartoloni, A, Battiston, R, Becker, R, Becker, U, Bellagamba, L:, B, P, Berdugo, J, Berges, P, Bertucci, B, Biland, A, Bindi, V, Boella, G, Boschini, M, Bourquin, M, Bruni, G, Buenerd, M, Burger, J, Burger, W, Cai, X, Cannarsa, P, Capell, M, Casadei, D, Casaus, J, Castellini, G, Cernuda, I, Chang, Y, Chen, H, Chen, Z, Chernoplekov, N, Chiueh, T, Choi, Y, Cindolo, F, Commichau, V, Contin, A, Cortina Gil, E, Crespo, D, Cristinziani, M, Dai, T, dela Guia, C, Delgado, C, Di Falco, S, Djambazov, L, D’Antone, I, Dong, Z, Duranti, M, Engelberg, J, Eppling, F, Eronen, T, Extermann, P, Favier, J, Fiandrini, E, Fisher, P, Flugge, G, Fouque, N, Galaktionov, Y, Gervasi, M, Giovacchini, F, Giusti, P, Grandi, D, Grimm, O, Gu, W, Haino, S, Hangarter, K, Hasan, A, Hermel, V, Hofer, H, Hungerford, W, Ionica, M, Jongmanns, M, Karlamaa, K, Karpinski, W, Kenney, G, Kim, D, Kim, G, Kim, K, Kirn, T, Klimentov, A, Kossakowski, R, Kounine, A, Koutsenko, V, Kraeber, M, Laborie, G, Laitinen, T, Lamanna, G, Laurenti, G, Lebedev, A, Lechanoine Leluc, C, Lee, M, Lee, S, Levi, G, Lin, C, Liu, H, Lu, G, Lu, Y, Lubelsmeyer, K, Luckey, D, Lustermann, W, Mana, C, Margotti, A, Mayet, F, Mcneil, R, Menichelli, M, Mihul, A, Mujunen, A, Oliva, A, Palmonari, F, Park, H, Park, W, Pauluzzi, M, Pauss, F, Pereira, R, Perrin, E, Pevsner, A, Pilo, F, Pimenta, M, Plyaskin, V, Pojidaev, V, Pohl, M, Produit, N, Quadrani, L, Rancoita, P, Rapin, D, Ren, D, Ren, Z, Ribordy, M, Richeux, J, Riihonen, E, Ritakari, J, Ro, S, Roeser, U, Sagdeev, R, Santos, D, Sartorelli, G, Sbarra, C, Schael, S, Schultz von Dratzig, A, Schwering, G, Seo, E, Shin, J, Shoumilov, E, Shoutko, V, Siedenburg, T, Siedling, R, Son, D, Song, T, Spada, F, Spinella, F, Steuer, M, Sun, G, Suter, H, Tang, H, Ting, S, Tomassetti, N, Tornikoski, M, Torsti, J, Trumper, J, Ulbricht, J, Urpo, S, Valtonen, E, Vandenhirtz, J, Velikhov, E, Verlaat, B, Vetlitsky, I, Vezzu, F, Vialle, J, Vierte, G, Vite, D, Von Gunten, H, Waldmeier Wicki, S, Wallraff, W, Wang, J, Wiik, K, Williams, C, Wu, S, Xia, P, Xu, S, Xu, Z, Yan, J, Yan, L, Yang, C, Yang, J, Yang, M, Ye, S, Zhang, H, Zhang, Z, Zhao, D, Zhou, F, Zhou, Y, Zhu, G, Zhu, W, Zhuang, H, Zichichi, A, Zimmermann, B, Zuccon, P, L: Bene, BOELLA, GIULIANO FILIPPO, Burger, JD, Burger, WJ, Cai, XD, Chang, YH, Chen, HF, Chen, HS, Chen, ZG, Chernoplekov, NA, Chiueh, TH, Choi, YY, Dai, TS, Dong, ZR, Eppling, FJ, Fisher, PH, GERVASI, MASSIMO, Gu, WQ, Kim, DH, Kim, GN, Kim, KS, Lee, MW, Lee, SC, Lin, CH, Liu, HT, Lu, YS, McNeil, RR, Park, HB, Park, WH, Rancoita, PG, Richeux, JP, Seo, ES, Shin, JH, Spada, FR, Sun, GS, Tang, HW, Ting, SCC, Ting, SM, Vialle, JP, Wang, JZ, Xia, PC, Xu, ZZ, Yan, JL, Yan, LG, Yang, CG, Ye, SW, Zhang, HY, Zhang, ZP, Zhao, DX, Zhu, GY, Zhu, WZ, Zhuang, HL, and Zuccon, P.

Abstract

Measurement of the chemical and isotopic composition of cosmic rays is essential for the precise understanding of their propagation in the galaxy. While the model parameters are mainly determined using the B/C ratio, the study of extended sets of ratios can provide stronger constraints on the propagation models. In this paper, the relative abundances of light-nuclei lithium, beryllium, boron, and carbon are presented. The secondary-to-primary ratios Li/C, Be/C, and B/C have been measured in the kinetic energy range 0.35-45 GeV nucleon-1. The isotopic ratio 7Li/6Li is also determined in the magnetic rigidity interval 2.5-6.3 GV. The secondary-to-secondary ratios Li/Be, Li/B, and Be/B are also reported. These measurements are based on the data collected by the Alpha Magnetic Spectrometer AMS-01 during the STS-91 space shuttle flight in 1998 June. Our experimental results are in substantial agreement with other measurements, where they exist. We describe our light-nuclei data with a diffusive-reacceleration model. A 10%-15% overproduction of Be is found in the model predictions and can be attributed to uncertainties in the production cross-section data. © 2010. The American Astronomical Society.

Published
2010

48. Effect of amorphous Si quantum-dot size on 1.54 μm luminescence of Er

Author

Park, NM, Kim, TY, Kim, KH, Sung, GY, Kim, BH, Park, SJ, Cho, KS, Shin, JH, Lee, JK, Nastasi, M, Park, NM, Kim, TY, Kim, KH, Sung, GY, Kim, BH, Park, SJ, Cho, KS, Shin, JH, Lee, JK, and Nastasi, M

Abstract

The role of the size of amorphous silicon quantum dots in the Er luminescence at 1.54 μm was investigated. As the dot size was increased, more Er ions were located near one dot due to its large surface area and more Er ions interacted with other ones. This Er-Er interaction caused a weak photoluminescence intensity, despite the increase in the effective excitation cross section. The critical dot size needed to take advantage of the positive effect on Er luminescence is considered to be about 2.0 nm, below which a small dot is very effective in the efficient luminescence of Er. © 2005 The Electrochemical Society. All rights reserved.

Published
2005

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