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The importance of building brands with high levels of brand equity is widely acknowledged by scholars and practitioners alike. Such strong brands enable firms to generate stronger earnings and provide firms with a much stronger defensible position. Given these benefits, it is not surprising that building a strong brand remains a top priority for many businesses. However, achieving this end is not without its challenges as the industry is permeated with instances of branding failure (e.g., Harley Davidson Perfume, Colgate Kitchen Entrees and Heinz Cleaning Vinegar) and brand value fluctuation (e.g., Toyota and Honda). In parallel with these brand management issues, the literature offers limited empirical insight into how firms approach the fundamental yet challenging task of managing a brand in an effort to achieve higher levels of brand equity. The underlying objective of this study is to unpack the black box of realising brand management superiority and investigate the specific process through which firms achieve higher levels of brand equity. To this end, the role of brand orientation has been highlighted in the literature given its capacity to orient firms towards the adoption of a greater branding focus by lending strategic significance to the brand and its management. However, brand orientation alone may not be the panacea that ensures firms are managing brands effectively to maximise brand equity. It does not provide (1) the market-linking mechanism that renders the firm externally relevant and appropriately linked with customers through the brand and (2) the controlling mechanisms that generate the sense of consistency fundamental to branding to facilitate the development of customer-linking branding actions. Drawing on the resource-based view of the firm (RBV) and survey data from a sample of businesses operating in the consumer goods sector, this study shows that the influence of brand orientation on brand equity is indirect through brand management capability. Also, underpinned by the theory of marketing control, this study finds that formalisation and brand-specific transactional leadership (TRL) are conducive to enhancing the influence of brand orientation on brand management capability, while departmentalisation weakens this effect. The incorporation of these findings into an integrative, mediated moderation framework further indicates that the interactive effects of brand orientation and (a) formalisation, (b) departmentalisation and (c) brand-specific TRL on brand equity are mediated by brand management capability. In light of these findings, several critical insights that advance knowledge and theory on brand management are offered. First, it is not brand orientation per se that contributes to higher levels of brand equity. Instead, brand orientation serves as the foundation upon which firms develop brand management capability to use the brand as the basis of interaction with customers and achieve higher levels of brand equity. Second, while formalisation and brand-specific TRL have often been maligned in the literature for their rigid and creativity-stifling nature, their controlling influence is critical in the context of branding. They help to generate the sense of consistency fundamental to branding and provide the critical conditions that facilitate brand management capability development. Third and critically, while brand orientation and specific controlling and market-linking mechanisms may be individually necessary, their interplay is the key that unlocks the black box of achieving brand management superiority.

Background We evaluated the incidence, characteristics and insulin independence of Koreans with new-onset type 2 diabetes (T2D) initially presenting with diabetic ketoacidosis (DKA). Methods We analysed clinical and biochemical data from diabetic patients presenting with DKA. They were classified into ketosis-prone diabetes (KPD) type 1A (KPD-T1A) (A+β−), type 1B (KPD-T1B) (A−β−), type 2A (KPD-T2A) (A+β+) or type 2B (KPD-T2B) (A−β+) according to the presence or absence of an autoantibody and β-cell reserve. Changes in therapy after insulin discontinuation were evaluated for up to 4 years. We also compared clinical and biochemical characteristics between newly diagnosed T2D patients presenting with DKA and previously diagnosed T2D patients presenting with DKA. Results Among 60 newly diagnosed KPD patients, 18, 21 and 21 patients were classified as KPD-T1A, KPD-T1B and KPD-T2B, respectively. In the KPD-T2B group, both fasting and stimulated C-peptide were recovered over 6 months. After 4 years of DKA development, 75% of KPD-T2B subjects no longer required insulin. Compared with previously diagnosed T2D patients presenting with DKA, newly diagnosed KPD-T2B patients tended to be younger, more obese and showed better insulin secretory function after recovery from DKA. Conclusions New-onset T2D patients presenting with DKA was not uncommon among the Korean population. In contrast to previously diagnosed T2D patients presenting with DKA, who showed a progressive decrease in insulin secretory function, new-onset KPD-T2B patients recovered insulin secretory function over time, and insulin independence could be expected. Copyright © 2013 John Wiley & Sons, Ltd.

AimsThe ESR1 gene encodes for oestrogen receptor (ER) α, which plays a crucial role in mammary carcinogenesis and clinical outcome in patients with breast cancer. However, the clinical significance of the ESR1 gene copy number change for breast cancer has not been clarified.MethodsESR1 gene copy number was determined by fluorescence in situ hybridisation (FISH) on tissue sections. A minimum of 20 tumour cells were counted per section, and a FISH ratio of ESR1 gene to CEP6 ≥2.0 was considered ESR1 amplification. A ratio >1.2 but ESR1 gain. The ESR1 copy number was further measured by quantitative real-time PCR (Q-PCR) with ASXL2 as a reference.ResultsFISH revealed ESR1 amplification in six cases (4.0%) and ESR1 gain in 13 cases (8.7%) from a total of 150 cases. ESR1 gain and amplification were more common in older patients (pESR1 copy number (pESR1 amplification was associated with a shorter disease-free survival (HR=5.56, p=0.03) and a shorter overall survival (HR=5.11, p=0.04).ConclusionsIn general, the frequency of ESR1 amplification in breast cancer is low when measured by FISH in large sections. ESR1 gain and amplification in breast cancer may be associated with older age and poorer outcomes.

The deadenylase nocturnin (Noc, Ccrn4l) has been recently found to regulate lipid metabolism and to control preadipocyte differentiation. Here, we showed that among the five deadenylases tested, Noc and Pan2 exhibited a biphasic expression which is out of phase to each other during adipocyte differentiation of 3T3-L1 cells. The expression levels of other deadenylases, including Parn, Ccr4, and Caf1, were relatively unchanged or reduced. The immediate early expressed Noc during 3T3-L1 adipogenesis was involved in regulating mitotic clonal expansion (MCE) and cyclin D1 expression, as demonstrated in Noc-silenced 3T3-L1 cells and Noc(-/-) primary mouse embryonic fibroblasts (MEFs). Transcriptional profiling of Noc-depleted 3T3-L1 adipocytes revealed that most of the differentially expressed genes were related to cell growth and proliferation. In human adipose tissue, NOC mRNA level negatively associated with both fasting serum insulin and homeostasis model assessment of insulin resistance, and positively associated with both adiponectin mRNA levels and circulating adiponectin levels. Taken together, these results suggest the role of Noc in the modulation of early adipogenesis as well as systemic insulin sensitivity.

Gamma-Fe2.6Ni1.4 nanoparticles were prepared by the arc-discharge method as the precursor and its nitride counterpart of gamma'-Fe2.6Ni14N nanoparticles was synthesized directly through a thermal ammonolysis reaction at the temperature of 673 K for two hours. The resultant product was identified as a homogeneous ternary nitride with nearly spherical shape and average size of about 60.0 nm. The electromagnetic characteristics of gamma'-Fe2.6Ni1.4N derivant and gamma-Fe2.6Ni1.4 precursor have been studied in the frequency range of 2-18 GHz. Compared with the precursor, gamma'-Fe2.6Ni1.4N nanoparticles exhibits an enhanced electromagnetic absorption property resulted from the increased dielectric loss by nitriding process. The optimal reflection loss (RL) of gamma'-Fe2.6Ni1.4N nanoparticles/paraffin composite can reach -39.9 dB at 5.2 GHz in a thickness of 2.29 mm, and the frequency band corresponding RL < -10 dB is over 2.6-18 GHz in the thickness range of 0.78-4.20 mm.

We started performing laparoscopic cholecystectomies in 1991. Since that time, many surgeons have been trained in laparoscopic and minimally invasive surgery, and laparoscopic surgery has been used in numerous procedures, with patients benefitting as a result. We performed the first automated surgery in Korea using Automated Endoscopic System for Optimal Positioning in June 1996. Inspired by Inbae Yoon and assisted by his generous donation, our hospital started the IB Yoon Multi-Specialty Endoscopic Research & Training Center in 1998. Subsequently in March 2005, we started the Severance Robotic and Minimally Invasive Surgery Center. The establishment of these centers has enabled us to widen the use of laparoscopic surgery and to teach many surgeons the principles of and the techniques involved in laparoscopic and robotic surgery. We performed our first robotic surgery using the da Vinci Surgical System in July 2005. In the 4 years since introducing the da Vinci Surgical System, we have successfully performed more than 2600 robotic surgical procedures. As the collaboration between medicine and robotic engineering produces more technically advanced results, we hopefully can develop our own version of the robotic system in the near future.

Study design Serum proteomes from normal subjects and the patients with ossification of the posterior longitudinal ligament (OPLL) were analyzed by using proteomics. Objectives To identify novel serologic biomarkers for diagnosing OPLL. Summary of background data OPLL can compress the spinal cord, and special planning is required for surgeries that are done from the front of the cervical spine. However, the definitive serologic biomarkers for OPLL are still unclear. Methods The 2-dimensional electrophoresis patterns of sera from OPLL patients and normal subjects were compared. The differentially expressed spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and electrospray ionization quadruple time-of-flight mass spectrometry. Results Nine spots that were differentially expressed in the sera of OPLL patients were found and were identified. PRO2675, human serum albumin in a complex with myristic acid and tri-iodobenzoic acid, an unknown protein, chain B of the crystal structure of deoxy-human hemoglobin beta6, pro-apolipoprotein, ALB protein, retinol binding protein and chain A of human serum albumin mutant R218h complexed with thyroxine (3,3',5,5', tetraiodo-L-thyronine), were up-regulated in the sera of OPLL patients, whereas alpha1-microglobulin/bikunin precursor was down-regulated. Conclusions These proteins could be used as diagnostic biomarkers of OPLL.

© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

PTEN is one of the most frequently mutated or deleted tumor suppressors in human cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN; however, a number of important questions remain regarding the role of ubiquitination in regulating PTEN function and the mechanisms by which PTEN ubiquitination is regulated. In the present study, we demonstrated that p34, which was identified as a binding partner of NEDD4-1, controls PTEN ubiquitination by regulating NEDD4-1 protein stability. p34 interacts with the WW1 domain of NEDD4-1, an interaction that enhances NEDD4-1 stability. Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination. Notably, an inverse correlation between PTEN and p34/NEDD4-1 levels was confirmed in tumor samples from colon cancer patients. Thus, p34 acts as a key regulator of the oncogenic behavior of NEDD4-1 and PTEN.

Objective The ossification of the posterior longitudinal ligament (OPLL) involves the ligament that lines the posterior surface of the spinal vertebral bodies. Hormonal and metabolic factors as well as hereditary factors have been proposed to be involved in pathologic ligamentous OPLL. However, there are currently no definitive serological biomarkers for OPLL that might be used to achieve a more convenient and economic diagnosis. To find an easier and simpler diagnostic method and to identify pathogenic proteins associated with OPLL, we assessed PLL tissues from patients with OPLL for proteomic alterations. Methods OPLL tissues were collected from 12 patients with OPLL, and non-OPLL tissues were collected from 12 healthy subjects without OPLL. To minimize individual variations, we matched the sex and age of the patients in the healthy and OPLL groups. The two-dimensional electrophoresis patterns of tissue from 12 OPLL patients and 12 healthy subjects were compared. Results We found 25 proteins that were significantly and consistently different on the two-dimensional electrophoresis gels between the group of ossified PLL tissues from the patients with OPLL and the group of nonossified PLL tissues from the healthy subjects. Among them, 21 proteins were up-regulated in the patients with OPLL, whereas the remaining four proteins were down-regulated. Conclusions The information obtained via this proteomic analysis will be very useful in understanding the pathophysiology of OPLL as well as in finding protein candidates to serve as new diagnostic biomarkers of OPLL.

Objective We studied tau and excision repair cross-complementing 1 expression to evaluate their predictive values in advanced breast carcinoma patients. Methods Patients treated with paclitaxel and cisplatin as the first-line chemotherapy for locally advanced or metastatic breast cancer were enrolled. The expression levels of tau and excision repair cross-complementing 1 were assessed by immunohistochemistry and examined for their associations with treatment response and survival. Results Fifty-four patients were included in this study. Despite the strong association between tau expression and lower histological grade and estrogen receptor expression, tau expression remained an independent predictor for a lower response rate in multivariate analysis (odd ratio = 0.24, P = 0.02). However, tau expression was a predictor for longer overall survival in both univariate analysis (median, 57.5 vs. 30.4 months, P = 0.02) and multivariate analysis (hazard ratio = 0.36, P = 0.008). Excision repair cross-complementing 1 was not associated with treatment response or overall survival. Conclusions Tau expression but not excision repair cross-complementing 1 in advanced breast cancer predicts poor response to combination chemotherapy of paclitaxel and cisplatin. However, tau expression is significantly associated with longer overall survival.

Background: In the past two decades, the incidence of breast cancer in young Taiwanese females has been rapidly increasing, approaching the risk level of western countries. As a first step to investigate the possible etiology, we examined the molecular subtypes of female breast cancer in Taiwan. Methods: This study included 1,028 consecutive patients with breast cancer diagnosed in National Taiwan University Hospital between 2004 and 2006. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2, cytokeratin 5/6, and epidermal growth factor receptor expression and/or gene amplification were analyzed. Results: Younger (≤50 years) breast cancer patients had a higher prevalence of luminal A (67% versus 57%; P < 0.001) and a lower prevalence of basal-like subtype (9% versus 17%; P < 0.001) compared with older (>50 years) patients. The higher prevalence of luminal A subtype was mainly attributed to a higher ER (75% versus 63%; P < 0.001) and PR (47% versus 33%; P < 0.001) expression rate in younger patients than older patients. Tumors with histologic grade 3 were less prevalent in younger patients than in older patients (23% versus 30%; P = 0.01). For very young ( Conclusions: Young breast cancer patients in Taiwan are characterized by a high prevalence of luminal A subtype and low prevalence of histologic grade 3 tumor and/or basal-like subtype. These features are distinct from young breast cancer patients in western countries. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1807–14)

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Systemic treatments for HCC have been largely unsuccessful. OSU-03012 is a derivative of celecoxib with anticancer activity. The mechanism of action is presumably 3-phosphoinositide–dependent kinase 1 (PDK1) inhibition. This study investigated the potential of OSU-03012 as a treatment for HCC. OSU-03012 inhibited cell growth of Huh7, Hep3B, and HepG2 cells with IC50 below 1 μmol/L. In Huh7 cells, OSU-03012 did not suppress PDK1 or AKT activity. Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay and flow cytometry analysis indicated that OSU-03012 did not induce cellular apoptosis. Instead, morphologic studies by light and electron microscopy, as well as special biological staining with monodansylcadaverine, acridine orange, and microtubule-associated protein 1 light chain 3, revealed OSU-03012–induced autophagy of Huh7 cells. This OSU-03012–induced autophagy was inhibited by 3-methyladenine. Moreover, reactive oxygen species (ROS) accumulation was detected after OSU-03012 treatment. Blocking ROS accumulation with ROS scavengers inhibited autophagy formation, indicating that ROS accumulation and subsequent autophagy formation might be a major mechanism of action of OSU-03012. Daily oral treatment of BALB/c nude mice with OSU-03012 suppressed the growth of Huh7 tumor xenografts. Electron microscopic observation indicated that OSU-03012 induced autophagy in vivo. Together, our results show that OSU-03012 induces autophagic cell death but not apoptosis in HCC and that the autophagy-inducing activity is at least partially related to ROS accumulation. [Cancer Res 2008;68(22):9348–57]

Currently, the pathogenesis of chronic GVHD is unclear. To elucidate the molecular characteristics underlying chronic GVHD, we analyzed the gene expression profiles of 21 mononuclear cell samples from allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Self organizing map (SOM) clustering showed that the entire expression profiles of chronic GVHD samples were clearly different from those of the non-GVHD samples, and significance analysis of microarray (SAM) demonstrated that 120 genes, including PTDSS1, VAV1 and CD3D, were up-regulated, and 5 genes, including calnexin, were down-regulated in GVHD patients. Gene ontology annotation revealed that these genes are related to the phosphorous metabolism and lipid biosynthesis. Quantitative real time polymerase chain reaction (qRT-PCR) experiments validated the up-regulation of PTDSS1, VAV1 and CD3D in separate samples. Pathway-wise global test revealed that differential gene expression in cell cycle and T cell immune-associated pathways were significant between GVHD patients and non-GVHD patients. Seventeen classifier genes selected using a PAM (prediction analysis of microarray) algorithm showed favorable performance (prediction accuracy=0.85) for identifying patients with chronic GVHD. In conclusion, we identified differentially expressed genes and pathways in chronic GVHD patients using microarray analysis, and we also selected diagnostic genes predicting chronic GVHD status.

BACKGROUND: The human adiponectin gene has been implicated in the pathophysiology of obesity, type II diabetes mellitus, dyslipidemia and atherosclerosis. Investigation of the physiological functions of the adiponectin gene in humans was mainly conducted at the levels of plasma proteins or DNA polymorphisms. The depot-specific adiponectin mRNA levels also could be relevant to these physiological functions. OBJECTIVES: The relation between the adipose depot-specific adiponectin mRNA expression levels and various metabolic factors, including BMI, fasting plasma glucose, insulin, triglycerides (TGs) and HDL-cholesterol and insulin resistance index by HOMA, was investigated among 66 nondiabetic women using quantitative real-time PCR. RESULTS: The subcutaneous relative adiponectin mRNA levels (SRAmR) correlated significantly with the omental relative adiponectin mRNA levels (ORAmR) (γ=0.468, P=0.0001). The SRAmR correlated inversely with the fasting plasma glucose with a borderline significance (γ=−0.35, P=0.058). On the other hand, the ORAmR correlated negatively with serum TG levels with the adjustment for age (γ=−0.33, P=0.007) or age plus BMI (γ=−0.27, P=0.027). CONCLUSION: These results indicate that the adiponectin mRNA levels in different adipose depots were at least related to certain phenotypes of metabolic syndrome. The expression levels of adiponectin in the omental adipose depots are related to TG metabolism.

To evaluate the diagnostic performance of gadoxetic acid-enhanced MRI with an emphasis on the usefulness of the hepatobiliary phase (HBP) in T-staging of gallbladder carcinoma.66 patients with surgically confirmed gallbladder carcinoma underwent MRI. Two radiologists independently reviewed two sets of gadoxetic acid-enhanced MRI without and with the HBP. Local tumour spread was evaluated according to T-staging, and the results were compared with pathological findings. The diagnostic performance of two image sets to differentiate each T-stage was compared.The sensitivities of MRI with the HBP to differentiate T1 vs ≥ T2 lesions, ≤ T2 vs ≥ T3 lesions and ≤ T3 vs T4 lesions were 96.3%, 85.7% and 100% for Observer 1 and 92.6%, 95.2% and 100% for Observer 2, respectively (p0.0001). By adding the HBP, the sensitivities to differentiate ≤ T2 vs ≥ T3 lesions were increased from 66.7% to 85.7% for Observer 1 and from 81.0% to 95.2% for Observer 2, although there was no significant difference (p0.05). The overall accuracies for T-staging were increased from 80.3% to 86.4% for Observer 1, a statistically significant degree (p=0.046), and from 83.8% to 87.9% for Observer 2 (p0.05). The k-value for the two observers indicated excellent agreement.Gadoxetic acid-enhanced MRI provided acceptable diagnostic performance for T-staging of gallbladder carcinoma. Addition of the HBP aids in the detection of liver invasion.In the T-staging of gallbladder carcinoma, gadoxetic acid-enhanced MRI with the HBP may enhance detection of liver invasion.

A 72-year-old woman was brought to the emergency department after falling down from ladder while attempting to clean the ceiling. Severe anterior chest pain was noted during physical examination. Her vital signs are stable, and laboratory results are unremarkable. Extended focused assessment with sonography in trauma was performed on bedside for evaluation of pneumothorax …

A 30-year-old man presented to our emergency department because of severe headache. He had neck stiffness and posterior fossa headache for 2 months. His headache worsened on upright position and improved on recumbent position. He denied any experience of head trauma, fever or any medical procedure in recent months. He maintained follow-up at a neurological outpatient department for control of high blood pressure and pain. Before arrival at the emergency …

AIM To examine whether reduced insulin secretory capacity or increased insulin secretory demand is associated with elevated ratio of plasma proinsulin to immunoreactive insulin (PI/IRI ratio) in non-diabetic subjects. SUBJECTS AND METHODS We measured various indices of insulin secretory function and insulin sensitivity by frequently sampled intravenous glucose tolerance test (FSIGT) and hyerglycemic glucose clamp in 21 healthy young men. We then examined the relationships between these indices and PI, IRI, or PI/IRI ratio in the fasting state. RESULTS Insulin sensitivity index (SI) measured by FSIGT correlated inversely with basal IRI (r=-0.53, P < 0.01) and PI levels (r=-0.57, P < 0.01), but there was no significant correlation between SI and PI/IRI ratio (r=0.26, NS). On the other hand, PI/IRI ratio correlated inversely with insulin secretory indices, such as acute insulin responses during FSIGT (r =-0.46, P < 0.01) and hyperglycemic glucose clamp (r=-0.54, P < 0.01) and submaximum insulin response during hyperglycemic glucose clamp (r=-0.59, P < 0.01). CONCLUSIONS These results indicate that elevated PI/IRI ratio may serve as a marker of reduced insulin secretory function in non-diabetic subjects.