Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma

Kang, Y.-K.,Yau, T.,Park, J.-W.,Lim, H. Y.,Lee, T.-Y.,Obi, S.,Chan, S. L.,Qin, SK.,Kim, R. D.,Casey, M.,Chen, C.,Bhattacharyya, H.,Williams, J. A.,Valota, O.,Chakrabarti, D.,Kudo, M. Oxford University Press 2015 Annals of oncology Vol.26 No.12

<P>Axitinib plus best supportive care failed to meet the primary end point of overall survival in second-line treatment of advanced hepatocellular carcinoma in a randomized phase II study. However, the axitinib arm showed substantially improved progression-free survival, time to tumour progression, and clinical benefit rate compared with the placebo arm, with acceptable safety profile. Background: The efficacy and safety of axitinib, a potent and selective vascular endothelial growth factor receptors 1-3 inhibitor, combined with best supportive care (BSC) was evaluated in a global, randomized, placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma (HCC). Patients and methods: Patients with HCC and Child-Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion (presence/absence of extrahepatic spread and/or vascular invasion) and region (Asian/non-Asian) and randomized (2:1) to axitinib/BSC (starting dose 5 mg twice-daily) or placebo/BSC. The primary end point was overall survival (OS). Results: The estimated hazard ratio for OS was 0.907 [95% confidence interval (CI) 0.646-1.274; one-sided stratified P = 0.287] for axitinib/BSC (n = 134) versus placebo/BSC (n = 68), with the median (95% CI) of 12.7 (10.2-14.9) versus 9.7 (5.9-11.8) months, respectively. Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population. Improvements favouring axitinib/BSC (P < 0.01) were observed in secondary efficacy end point analyses [progression-free survival (PFS), time to tumour progression (TTP), and clinical benefit rate (CBR)], and were retained among Asian patients in the prespecified subgroup analyses. Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC. Most common all-causality adverse events with axitinib/BSC were diarrhoea (54%), hypertension (54%), and decreased appetite (47%). Baseline serum analyses identified potential new prognostic (interleukin-6, E-selectin, interleukin-8, angiopoietin-2, migration inhibitory factor, and c-MET) or predictive (E-selectin and stromal-derived factor-1) factors for survival. Conclusions: Axitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification subgroups. However, axitinib/BSC resulted in significantly longer PFS and TTP and higher CBR, with acceptable toxicity in patients with advanced HCC. Trial Registration: ClinicalTrials.gov, NCT01210495.</P>

Low Level Representation of VHDL Behavioural Description for Synthesis of Digital ASICs

C. C. Jong,T. K. Ang,K. H. Chan 대한전자공학회 1993 JTC-CSCC : Joint Technical Conference on Circuits Vol.- No.-

Optimal wind-induced load combinations for structural design of tall buildings

C.M. Chan,F. Ding,K.T. Tse,M.F. Huang,K.M. Shum,K.C.S. Kwok 한국풍공학회 2019 Wind and Structures, An International Journal (WAS Vol.29 No.5

Wind tunnel testing technique has been established as a powerful experimental method for predicting wind-induced loads on high-rise buildings. Accurate assessment of the design wind load combinations for tall buildings on the basis of wind tunnel tests is an extremely important and complicated issue. The traditional design practice for determining wind load combinations relies partly on subjective judgments and lacks a systematic and reliable method of evaluating critical load cases. This paper presents a novel optimization-based framework for determining wind tunnel derived load cases for the structural design of wind sensitive tall buildings. The peak factor is used to predict the expected maximum resultant responses from the correlated three-dimensional wind loads measured at each wind angle. An optimized convex hull is further developed to serve as the design envelope in which the peak values of the resultant responses at any azimuth angle are enclosed to represent the critical wind load cases. Furthermore, the appropriate number of load cases used for design purposes can be predicted based on a set of Pareto solutions. One 30-story building example is used to illustrate the effectiveness and practical application of the proposed optimization-based technique for the evaluation of peak resultant wind-induced load cases.

Melilite-type blue chromophores based on Mn3+ in a trigonal-bipyramidal coordination induced by interstitial oxygen

Kim, T. G.,Kim, S. J.,Lin, C.,Liu, R. S.,Chan, T. S.,Im, S. J. Royal Society of Chemistry 2013 Journal of Materials Chemistry C Vol.1 No.37

Synchronized Bursting Induced by Network Connectivity in Cortical Neuronal Cultures

L.C. Jia,P.-Y. Lai,C. K. Chan,C.H. Chang,C.R. Han,M.T. Tsai,Y.S. Chou 한국물리학회 2007 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.50 No.1I

Synchronization of cortical neural cultures is studied as a function of the effective network connectivity in the phenomenon of synchronized firing (SF). The synchronized bursting frequency (during SF) of the network is found to be much slower than the characteristic time scale of a neuron and increases with the network connectivity. Using fluorescence imaging techniques, we found that SF occurs only when the incubation time is longer than some critical age tc and the synchronized bursting frequency f increases with time as f = fc + fo log( t tc ). Furthermore, tc is found to scale with the cell plating density as tc 1 p . Based on the result of photolysis of neurons, the synchronized bursting frequency is shown to be related to the network connectivity, hence, the growth behavior can be inferred from the measured SF frequencies. We further build a network growth model with the characteristics of an early stage active growth followed by a late-stage retarded growth, which can account for the experimental data quantitatively. Electrophysiological measurements using double-patch techniques reveal that even though the bursting frequencies are synchronized, the intra-burst spikes are not. We also present a mean-field model of the neural network that enables the neuron firing to be inhibited and generates inter-spike intervals with long time scales resulting in bursting.

Large Deformation Finite Element Analysis of Strain Localization in Fine-Blanking Process

Tang, C . Y .,Chen, Z . H .,Lee, T . C .,Chan, L . C . 대한금속재료학회(대한금속학회) 1998 METALS AND MATERIALS International Vol.4 No.3

In this study, an updated Lagrangian large deformation finite element method is developed for solving the metal forming problems with an incrementally objective mid-interval integration algorithm. A numerical simulation of fine-blanking process is hence performed to predicate the strain localization and to investigate the failure mechanism of fine-blanking process. Using the numerical result, The stress and strain fields developed in the fine-blanking process as well as the large deformation elasto-plastic finite element implementation for solving axisymmetric strain localization problems are discussed.

Five New Stilbenes from the Stem Bark of Artocarpus communis

Susanna T. S. Chan,Wendy L. Popplewell,Heidi R. Bokesch,Tawnya C. McKee,Kirk R. Gustafson 한국생약학회 2018 Natural Product Sciences Vol.24 No.4

Five new prenylated stilbenes (1 - 5), along with the known compounds cudraflavone C, trans-4-isopentenyl-3,5,2',4'-terahydroxystilbene, trans-4-(3-methyl-E-but-1-enyl)-3,5,2',4'-tetrahydroxystilbene, pannokin G, cycloartobiloxanthone, artonin P, morusin, artocarpin, artonin E, kuwanon C, artobiloxanthone, and artoindonesianin C (6 - 17) were isolated from the stem bark of the tropical tree Artocarpus communis. The structures were established by NMR spectroscopic analysis, MS studies, and comparison with spectral data reported in the literature.

Clinical effectiveness of mindfulness-based music therapy on improving emotional regulation in blind older women: A randomized controlled trial

Sunny H.W. Chan,Meryl Y.C. Cheung,Armstrong T.S. Chiu,Mimi H.T. Leung,Michael C.C. Kuo,Donald Y.C. Yip,Carole C.Y. Hui,Sally W.I. Kam,King Yeung,Doreen S.P. Mui,Shu-Mei Wang,Calvin C.K. Yip 한국한의학연구원 2023 Integrative Medicine Research Vol.12 No.4

Background: This study aimed to investigate clinical effectiveness of a structured eight-week mindfulness-based music therapy (MBMT) program on improving mood regulation in older women with blindness. This investigation compared a MBMT group with a mindfulness intervention (MI) group and a control group. Methods: Ninety-two older females with blindness from a residential setting in Hong Kong were recruited and randomly allocated to a MBMT (n = 31), MI (n = 30), or control (n = 31) group. Psychological measurements regarding mood regulation and general mood states (namely, Difficulties in Emotion Regulation Scale [DERS], Geriatric Depression Scale [GDS], and Depression Anxiety Stress Scales-21), were taken at pretest and posttest. Outcome assessors were blinded to group assignment. Results: Data was analyzed based on intention-to-treat basis. At posttest, DERS scores in the MBMT group (mean differences and 95% confidence interval: 12.1, 5.5 to 18.8) and the MI group (7.2, 0.5 to 13.8) were lower than that in the control group. GDS scores in the MBMT group (2.9, 1.7 to 4.0) and the MI group (1.7, 0.6 to 2.9) were lower than those in the control group. Compared with the MI group, the MBMT group improved emotional awareness sub-scores in DERS (2.1, 0.2 to 4.1) and appeared to lower depression in GDS scores (1.1, -0.0 to 2.3; p = 0.053). Conclusion: MBMT seems more beneficial than MI alone for improving emotional regulation in older women with blindness. The combination of mindfulness and music can generate a synergetic effect by enhancing both attention and appraisal components within the emotional-regulation process. Trial registration: ClinicalTrials.gov, NCT05583695.

Association of genetic variation in <i>FTO</i> with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians

Li, H.,Kilpelä,inen, T. O.,Liu, C.,Zhu, J.,Liu, Y.,Hu, C.,Yang, Z.,Zhang, W.,Bao, W.,Cha, S.,Wu, Y.,Yang, T.,Sekine, A.,Choi, B. Y.,Yajnik, C. S.,Zhou, D.,Takeuchi, F.,Yamamoto, K.,Chan, J. C.,Man Springer-Verlag 2012 Diabetologia Vol.55 No.4

<P><B>Aims/hypothesis</B></P><P><I>FTO</I> harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for <I>FTO</I> in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the <I>FTO</I> locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.</P><P><B>Methods</B></P><P>All studies published on the association between <I>FTO</I>-rs9939609 (or proxy [<I>r</I><SUP>2</SUP> > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.</P><P><B>Results</B></P><P>The <I>FTO</I>-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (<I>p</I> = 9.0 × 10<SUP>−19</SUP>), overweight by 1.13-fold/allele (<I>p</I> = 1.0 × 10<SUP>−11</SUP>) and type 2 diabetes by 1.15-fold/allele (<I>p</I> = 5.5 × 10<SUP>−8</SUP>). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, <I>p</I> = 6.6 × 10<SUP>−5</SUP>). The <I>FTO</I>-rs9939609 minor allele increased BMI by 0.26 kg/m<SUP>2</SUP> per allele (<I>p</I> = 2.8 × 10<SUP>−17</SUP>), WHR by 0.003/allele (<I>p</I> = 1.2 × 10<SUP>−6</SUP>), and body fat percentage by 0.31%/allele (<I>p</I> = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of <I>FTO</I> variation on obesity-related traits and type 2 diabetes was similar in the two populations.</P><P><B>Conclusions/interpretation</B></P><P><I>FTO</I> is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, <I>FTO</I> is also associated with type 2 diabetes independently of BMI.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.</P>

Pharmaceutical Advertising in Korea, Japan, Hong Kong, Australia, and the US:Current Conditions and Future Directions

Hye-Jin Paek,Hyegyu Lee,Carolus L,C,Praet,Kara,Chan,P,Monica Chien,Jisu Huh,Glen T,Cameron,백혜진,이혜규,Carolus L,C,Praet,Kara,Chan,P,Monica Chien,허지수,Glen T,Cameron 한국헬스커뮤니케이션학회 2011 헬스커뮤니케이션연구 Vol.3 No.1

의약 산업은 질병 및 사망률 감소를 위한 노력, 의학 시설 및 치료 기술의 발전, 인구의 노령화 등으로 인해 세계적으로 가장 각광받고 있는 산업 중 하나이다.그러나 의약 광고는 국민 건강과의 밀접한 관계로 인해 정부 기관으로부터 강한 규제와 함께, 의학 단체, 보건 관계자 및 연구 자들의 감시를 받아왔다. 이렇듯 의약 산업에 얽힌 복잡한 이해관계는 실무자들과 연구자들의 범 국가적인 논의를 필요로 한다. 특히, 세계적 경제 침체는 처방 약품(Direct-to-consumer advertising [DTC]) 광고의 집행을 허용하라는 일부의 주장에 힘을 실어주고 있다. 따라서 본 연구는 처방 약품광고가 허용되고 있는 미국과 더불어 아시아 태평양 지역의 주요 국가들(호주, 홍콩, 중국, 일본, 한국)의 의약 광고 관련 규제, 연구, 실무 현황을 조명함으로써 현재 시점에서 국제적으로 중요한 사안들에 대해 논의하고자 한다. 구체적으로 본 연구는 우선 (1) 각 국가들의 국내 및 글로벌 의약 제품들의 시장과 광고 현황을 살펴보고, (2) 의약 제품 및 광고와 관련된 사회적, 문화적, 법적 문제들을 검토한 후, (3) 의약 광고에 대한 소비자 반응 및 인식과 관련된 연구들을 정리하고, (4) 후속 연구 및 실무를 위한 방향을 제시하고자 한다. 이를 통해 본 연구는 범국가적 건강 관리관련 법률 관계자, 연구자, 그리고 실무자들 간의 의약 광고, 헬스 커뮤니케이션 및 규제, 그리고 전략적 커뮤니케이션에 관한 논의를 고무하고자 한다. The pharmaceutical industry has become one of the major industries worldwide as a result of increased efforts to reduce mortality and morbidity, the technological development of medical facilities and treatment, and the aging of the population. But because this product category is so closely associated with public health, pharmaceutical advertising has been strictly regulated by government agencies and monitored by the medical community, public health officials, and researchers. The complex issues involving multiple stakeholders raise the need for more open discussions among practitioners and researchers worldwide. In particular, the current global recession may intensify this pressure because of the economic benefits direct-to-consumer advertising (DTCA), which refers to advertising for prescription (Rx) medicines, provides. Taking account of these developments, this paper attempts to address the important and timely issue in global settings by providing an overview of regulations, studies, and practices in pharmaceutical advertising in the important Asian Pacific countries-Australia, Hong Kong in China, Japan, and South Korea-in addition to the US, one of the two countries where DTCA is allowed. Specifically, the following four issues are addressed in each of the five countries: (a) The current state of pharmaceutical advertising for domestic and global products in each panelist’s country; (b) social, cultural, and regulatory issues that are relevant to pharmaceutical products and their ads; (c) empirical research on consumer perceptions and responses to pharmaceutical advertisements; and (d) future directions for research and practice. In so doing, this paper is expected to stimulate further discussions among policy makers, researchers, and practitioners, with regards to pharmaceutical advertising, health communication and policy, and relevant strategic communications in global health care settings.