Jinyoung Jung

High abundance of protein-like fluorescence in the Amerasian Basin of Arctic Ocean: Potential implication of a fall phytoplankton bloom

The seawater samples from the Chukchi and East Siberian Seas were collected along a shelf-slope-basin gradient and analyzed for chromophoric and fluorescent DOM (i.e., CDOM and FDOM, respectively). Unexpected high protein-like FDOM (0.35±0.40 and 0.24±0.34 RU for peaks B and T, respectively) levels were identified, which corresponded to 1-2 orders of magnitude higher than those documented by previous reports. This unique phenomenon could be attributed to a fall phytoplankton bloom. The seawater chl-a data, estimated from in situ fluorescence measurements and satellite remote sensing data, showed the subsurface chl-a maximum of up to 1.52mgm-3 at ~25-70m depths and the surface monthly average values (August 2015) up to 0.55 to 0.71mgm-3, which fall in the range of ~0.5-2.0mgm-3 during fall phytoplankton blooms in this area. Meanwhile, the depth profile of DOM parameters revealed subsurface maxima of protein-like fluorescence peaks along the shelf-slope gradient. The positive correlations between the protein-like peaks and biological index implied the lateral transport of DOM and nutrients from the shelf to the slope and basin. Despite still being a largely ice-covered environment, potential shifts in the ecosystem appear to make progress in response to changing climate in the Arctic Ocean.

Evaluation of Genome Based Estimated Breeding Values for Meat Quality in a Berkshire Population Using High Density Single Nucleotide Polymorphism Chips

The accuracy of genomic estimated breeding values (GEBV) was evaluated for sixteen meat quality traits in a Berkshire population (n = 1,191) that was collected from Dasan breeding farm, Namwon, Korea. The animals were genotyped with the Illumina porcine 62 K single nucleotide polymorphism (SNP) bead chips, in which a set of 36,605 SNPs were available after quality control tests. Two methods were applied to evaluate GEBV accuracies, i.e. genome based linear unbiased prediction method (GBLUP) and Bayes B, using ASREML 3.0 and Gensel 4.0 software, respectively. The traits composed different sets of training (both genotypes and phenotypes) and testing (genotypes only) data. Under the GBLUP model, the GEBV accuracies for the training data ranged from 0.42±0.08 for collagen to 0.75±0.02 for water holding capacity with an average of 0.65±0.04 across all the traits. Under the Bayes B model, the GEBV accuracy ranged from 0.10±0.14 for National Pork Producers Council (NPCC) marbling score to 0.76±0.04 for drip loss, with an average of 0.49±0.10. For the testing samples, the GEBV accuracy had an average of 0.46±0.10 under the GBLUP model, ranging from 0.20±0.18 for protein to 0.65±0.06 for drip loss. Under the Bayes B model, the GEBV accuracy ranged from 0.04±0.09 for NPCC marbling score to 0.72±0.05 for drip loss with an average of 0.38±0.13. The GEBV accuracy increased with the size of the training data and heritability. In general, the GEBV accuracies under the Bayes B model were lower than under the GBLUP model, especially when the training sample size was small. Our results suggest that a much greater training sample size is needed to get better GEBV accuracies for the testing samples.

FRI0311 Endovascular intervention versus surgery in patients with takayasu arteritis: a meta-analysis

Background Although medical treatment has advanced, surgical treatment is needed to control the progression and symptoms of Takayau arteritis (TA). Endovascular intervention or surgical revascularization is performed; however, there are few comparative studies of these methods. Objectives There are many studies about surgery and endovascular intervention; however, it is still unclear which treatment has better a benefit/risk ratio. Because neither meta-analysis nor large-scale studies are available for surgical treatment of TA, we conducted a meta-analysis to examine the outcome of surgical treatment. Methods A meta-analysis comparing endovascular intervention and surgery outcomes was performed using the MEDLINE and Embase databases. Results A total of 14 studies of 598 patients and 1,049 lesions were included. Endovascular intervention was performed in 418 lesions and surgery in 631 lesions. Restenosis was more common in endovascular intervention than in surgery (odds ratio [OR] =2.74, 95% confidence interval [CI] =1.75–4.27, p <0.00001). Other complications, including stroke, did not differ between endovascular intervention and surgery (OR =0.75, 95% CI =0.49–1.15, p =0.19). There was no difference in mortality between the two groups (OR =1.11, 95% CI =0.50–2.46, p =0.81).Table 1. Outcomes of endovascular intervetion compared to sugery in patients with Takayasu artheritis Test of association Test of heterogeneity OR 95% CI P-value Model P-value I2(%) Restenosis 2.74 1.75–4.27 <0.00001 R 0.05 41 Other complications 0.75 0.49–1.15 0.19 F 0.27 18 Stroke 0.5 0.17–1.50 0.22 F 0.98 0 Death 1.11 0.50–2.46 0.81 F 0.67 0Figure 1. ORs and 95% CIs of individual studies and pooled data; comparison of endovascular intervention and surgical revascularization for restenosis. Conclusions This meta-analysis showed the superiority of surgical revascularization over endovascular intervention. References Saadoun D, Lambert M, Mirault T, et al. Retrospective analysis of surgery versus endovascular intervention in Takayasu arteritis a multicenter experience. Circulation 2012;125:813–9. Nakagomi D, Jayne D. Outcome assessment in Takayasu arteritis. Rheumatology 2016;55:1159–71. Labarca C, Makol A, Crowson CS, Kermani TA, Matteson EL, Warrington KJ. Retrospective comparison of open versus endovascular procedures for takayasu arteritis. J Rheumatol 2016;43:427–32. Lee GY, Jeon P, Do YS, et al. Comparison of outcomes between endovascular treatment and bypass surgery in Takayasu arteritis. Scand J Rheumatol 2014;43:153–61. Kalangos A, Christenson JT, Cikirikcioglu M, et al. Long-term outcome after surgical intervention and interventional procedures for the management of Takayasus arteritis in children. J Thorac Cardiovasc Surg 2006;132:656–64. Acknowledgements No grants or other support were received for this study. Disclosure of Interest None declared

Using a small-scale reverberation chamber to improve a ship's double sandwich panel noise attenuation performance

Regulations now require passenger ships to have low noise levels in accommodation spaces. Complex structural wall panels such as a double sandwich panels are often used to provide the required high noise attenuation. However, because of their complex structures, the prediction and improvement of the sound transmission loss (STL) of these panels often can not be achieved only with theoretical approaches. In this paper, an experimental approach using a small-scale reverberation chamber is applied to improve the STL of a double sandwich panel for installment in a ship. Firstly, a small-scale reverberation chamber is set up. For test chamber qualification, the STLs of a thin plate, a commercial ships sandwich panel and a high noise attenuation panel are measured and compared with those tested in a large-scale reverberation chamber and those calculated by the transfer matrix method (TMM). Secondly, the small-scale reverberation chamber is used to analyze the STL of a double sandwich panel in terms of the influences of the inside perforate plates and air gap thickness on attenuation. In order to improve the attenuation performance of the double sandwich panel, the STLs of test specimens with various materials between sandwich panels are measured and compared. Finally, the panel with the highest noise attenuation is proposed and verified using the large-scale reverberation chamber

Surface accumulation of low molecular weight dissolved organic matter in surface waters and horizontal off-shelf spreading of nutrients and humic-like fluorescence in the Chukchi Sea of the Arctic Ocean

Polar regions play unique roles in global overturning circulation, carbon cycling, and climate change. In this study, seawater dissolved organic matter (DOM) was characterized for the Chukchi Sea in the Arctic Ocean in the summer season. The seawater generally contains high concentrations of dissolved organic carbon (DOC, up to 92u202fμMu202fC) and tyrosine-like fluorescence (up to 0.21 RU), and it was enriched with heteroatomic molecular formula with nitrogen-containing and sulfur-containing formulas counting 2246 (~41% of total identified molecular formula) and 1838 (~34%), respectively. Significant correlations were observed between salinity and the absorption coefficient at 254u202fnm, between chlorophyll-a and DOC as well as the tyrosine-like component, C270/302 (Cex/em maxima), and between biological index and two protein-like components, C275/338 and C305/344. A comparison between surface waters and close-to-seafloor deep waters suggested a trend of the accumulation of low molecular weight (LMW) fraction (~54-74%, nominal average molecular weight Mnu202f<u202f~350u202fDa) in the surface waters. Another interesting finding from spatial data was an obvious horizontal off-shelf spreading of nutrients and humic-like fluorescence. This study sheds novel insights of DOM characteristics and dynamics in the highly productive polar sea.

SAT0693 Serum uric acid levels and hormone replacement therapy type: a retrospective case-control study of postmenopausal women

Background Serum uric acid levels increase in postmenopausal women but decrease when hormone replacement therapy (HRT) is administered. However, no study has evaluated the effects of different types of HRT on serum uric acid levels. Objectives We examined whether estrogen monotherapy, estrogen-progestogen combination therapy, and tibolone use affected serum uric acid levels in this population. Methods We performed a retrospective case-control study of postmenopausal women. From 2005 to 2015, postmenopausal women measured serum uric acid levels more than twice were included. Patients were grouped according to HRT regimen: estrogen monotherapy, estrogen-progestogen combination therapy, or tibolone. The control group did not receive HRT. Differences in serum uric acid levels were examined in each group. Our analysis was adjusted to accommodate different follow-up intervals for individual patients. Multiple variables were adjusted using the Tukey-Kramer method. Age, body mass index, hypertension, diabetes mellitus, dyslipidemia, alcohol consumption, smoking status, and co-medications were also adjusted. Results In the control group, the serum uric acid level increased to 0.86±0.27 mg/dL (least squares mean ± standard error). In comparison, after adjusting for multiple variables, the serum uric levels in the estrogen-progestogen combination therapy group were found to be significantly lower (-0.41±0.29 mg/dL, P<0.001). However, the serum uric acid levels in the estrogen monotherapy and tibolone groups did not differ significantly from the control group level.Table 1. Degrees of changes in serum uric acid levels by hormone replacement therapy type Estrogen mono Estrogen-progestogen Tibolone Control Δ uric acid P Δ uric acid P Δ uric acid P Δ uric acid Crude 0.64±0.26 1.000 -0.50±0.17 <0.001 0.16±0.18 0.097 0.67±0.13 Model I 0.63±0.26 0.994 -0.51±0.17 <0.001 0.15±0.18 0.059 0.71±0.13 Model II 0.63±0.26 0.994 -0.51±0.17 <0.001 0.14±0.18 0.060 0.71±0.13 Model III 0.67±0.27 0.988 -0.42±0.19 <0.001 0.30±0.21 0.206 0.77±0.14 Model IV 0.64±0.34 0.986 -0.47±0.29 <0.001 0.23±0.26 0.195 0.74±0.26 Model V 0.85±0.35 1.000 -0.41±0.29 <0.001 0.26±0.27 0.096 0.86±0.27 All models that included crude values were adjusted for follow-up intervals. Model I: adjusted age. Model II: adjusted age and BMI. Model III: adjusted age, BMI, HTN, DM, and dyslipidemia. Model IV: adjusted age, BMI, HTN, DM, dyslipidemia, alcohol consumption, and smoking status. Model V: adjusted age, BMI, HTN, DM, dyslipidemia, alcohol consumption, smoking status and co-medications. Conclusions Serum uric acid levels decreased in response to estrogen-progestogen combination therapy in postmenopausal women. We attribute our findings to the effects of progesterone, rather than estrogen. References Roddy E, Doherty M. Epidemiology of gout. Arthritis Res Ther. 2010;12:223. Hak AE, Curhan GC, Grodstein F, Choi HK. Menopause, postmenopausal hormone use and risk of incident gout. Ann Rheum Dis. 2010;69:1305–9. Hak AE, Choi HK. Menopause, postmenopausal hormone use and serum uric acid levels in US women–the Third National Health and Nutrition Examination Survey. Arthritis Res Ther. 2008;10:R116. Bruderer SG, Bodmer M, Jick SS, Meier CR. Association of hormone therapy and incident gout: population-based case-control study. Menopause. 2015;22:1335–42. Acknowledgements No grants or other support were received for this study. Disclosure of Interest None declared

Abstract OT3-01-10: A prospective, open-label, single-arm, multi-center, phase II exploratory study to evaluate the efficacy and safety of poziotinib (NOV120101) in patients with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed regimens

Background: Poziotinib is a novel, oral, irreversible pan-HER inhibitor that has shown promising clinical activity in Phase 1 studies of patients (pts) with advance HER2 positive breast cancer who have failed at least 2 prior lines of HER2-directed therapy. A Phase 2 study of poziotinib was initiated in Korea in March 2015 in pts with HER2+ metastatic breast cancer. This phase 2 study is designed to seek accelerated approval for poziotinib for the treatment of metastatic breast cancer in Korea. Trial Design: Prospective Phase 2, open-label, single-arm, multi-center study in pts with recurrent, Stage IV breast cancer with HER2-overexpression who had received at least 2 prior HER2-directed regimens Eligibility Criteria: Histologically confirmed breast cancer patients, at least 19 years of age, with confirmed HER2 positive evaluable tumors (per RECIST, 1.1) who have adequate hematologic, renal, and hepatic function and have failed at least two HER2-directed regimens that included a taxane-containing anticancer chemotherapy, with a life expectancy of at least 12 weeks. Specific Aims: The Primary Efficacy Endpoint of the study was Progression-Free Survival (PFS). The Secondary Efficacy Endpoints included: PFS rate at 12 weeks post-dose; Objective Response Rate (ORR) including Complete Response (CR) and Partial Response (PR) rates; Disease Control Rate (DCR) including CR, PR, and Stable Disease (SD); Duration of Disease Control; Overall Survival (OS); Time to Progression (TTP); Time to Objective Response and Duration of Objective Response. The Exploratory Endpoints included: Population Pharmacokinetic (PK) Profile and Exploratory Genomic and Biomarker Analyses. Statistical Methods: In the randomized, multicenter, 2-arm, open-label study of trastuzumab emtansine (TH3RESA18), the median PFS was shown to be 3.3 months in subjects with optimal treatment per Investigator9s Choice. This ongoing study with poziotinib expects a median PFS of 4.5 months based on data from a previous Phase 1 study of poziotinib (NOV120101). Based on the following assumptions, a 5% one-sided significance level, and 80% power, and 2 months of accrual and 12 months of follow-up, 66 subjects will be required. Accounting for a 10% drop-out rate, a total of 74 subjects will be recruited into this ongoing Phase 2 study. Present Accrual and Target Accrual: 17 patients enrolled as of May 20, 2015 with a total target enrollment of 74 patients Contact information: ClinicalTrials.gov Identifier: NCT02418689. Citation Format: Park Y-H, Jung KH, Sohn JH, Lee KS, Lee KH, Kim J-H, Kim J-Y, Jung J, Han H, Park W-Y, Im S-A. A prospective, open-label, single-arm, multi-center, phase II exploratory study to evaluate the efficacy and safety of poziotinib (NOV120101) in patients with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed regimens. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-01-10.

Abstract P4-13-19: Poziotinib, an oral, irreversible pan-HER inhibitor, demonstrates promising clinical activity in metastatic HER2 positive breast cancer patients

Background: Poziotinib is a novel, oral, irreversible pan-HER inhibitor that has been studied in two completed Phase 1 clinical trials in patients with advanced solid tumors (HM-PHI-101; HM-PHI-102) and is currently being studied in several Phase 2 clinical trials. Preclinical studies have shown poziotinib to be more potent in vitro than other EGFR- and HER2-directed tyrosine kinase inhibitors. This study collates the clinical experience of poziotinib in patients with advanced HER2 positive breast cancer from the two completed Phase 1 trials. Results: The maximum tolerated dose (MTD) and safety of poziotinib were evaluated in HM-PHI-101 (once daily, Day 1-14 q3 weeks) and in HM-PHI-102 (continuous dosing). The Dose Limiting Toxicity (DLT) was diarrhea in both studies. Anti-diarrheal medicine was allowed, but prophylactic anti-diarrheal therapy was not used. The most frequently reported Grade 3 AE was diarrhea (40%). The MTD for intermittent dosing of poziotinib was 24 mg and the MTD for continuous dosing was 16 mg. The Dose Limiting Toxicity (DLT) was diarrhea in both studies. Anti-diarrheal medicine was allowed, but prophylactic anti-diarrheal therapy was not used. In total, 10 patients with HER2 positive metastatic breast cancer were treated in the two trials (median age 56.5, range 30-69). These patients were heavily pretreated (median number of previous treatment regimens 5, range 3-9), and all patients had failed treatment with both trastuzumab and lapatinib. The Overall Response Rate (ORR) in these breast cancer patients was 60% and Clinical Benefit Rate (CBR) was 80%. The median duration of response was 32.5 weeks (range 18 - 56 weeks). Two patients in the early dose cohorts of 1 or 2mg had progressive disease. The median progression free survival (PFS) was 28 weeks (6, 6, 12, 17, 25, 31, 37, 49, 57, and 98 weeks). Conclusions: Poziotinib showed very promising clinical activity in Phase 1 patients with metastatic HER2 positive breast cancer, who had been heavily pretreated and failed two prior HER2-directed therapies. The ORR in this patient population was 60% and the CBR was 80% in these two early dose finding studies. The AEs observed in these studies was consistent with other pan-HER and EGFR inhibitors. While the majority of DLT cases involves diarrhea, toxicity of other adverse events was relatively tolerable. An intermittent dosing schedule seemed appropriate for poziotinib. Multiple Phase 2 studies with poziotinib are ongoing in patients with breast cancer and other solid tumors. Citation Format: Im S-A, Kim J-H, Lee K-H, Kim SH, Oh D-Y, Kim Y-J, Han S-W, Kim T-Y, Kim T-Y, Jung J, Bang Y-J. Poziotinib, an oral, irreversible pan-HER inhibitor, demonstrates promising clinical activity in metastatic HER2 positive breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-19.