bluuebunny/crossref_metadata_2025 huggingface dataset:
Simon van der Meer (1925–2011): A Modest Genius of Accelerator Science
Authors: Chohan Vinod C.
Published: December 2011

Simon van der Meer was a brilliant scientist and a true giant of accelerator science. His seminal contributions to accelerator science have been essential to this day in our quest for satisfying the demands of modern particle physics. Whether we talk of long base-line neutrino physics or antiproton–proton physics at Fermilab or proton–proton physics at LHC, his techniques and inventions have been a vital part of the modern day successes. Simon van der Meer and Carlo Rubbia were the first CERN scientists to become Nobel laureates in Physics, in 1984. Van der Meer's lesser-known contributions spanned a whole range of subjects in accelerator science, from magnet design to power supply design, beam measurements, slow beam extraction, sophisticated programs and controls.
Enalapril reverses high-fat diet-induced alterations in cytochrome P450-mediated eicosanoid metabolism
Authors: Theken Katherine N. , Deng Yangmei , Schuck Robert N. , Oni-Orisan Akinyemi , Miller Tricia M. , Alison Kannon M. , Poloyac Samuel M. , Lee Craig R.
Published: December 2011

Metabolism of arachidonic acid by cytochrome P450 (CYP) to biologically active eicosanoids has been recognized increasingly as an integral mediator in the pathogenesis of cardiovascular and metabolic disease. CYP epoxygenase-derived epoxyeicosatrienoic and dihydroxyeicosatrienoic acids (EET + DHET) and CYP ω-hydroxylase-derived 20-hydroxyeicosatetraenoic acid (20-HETE) exhibit divergent effects in the regulation of vascular tone and inflammation; thus, alterations in the functional balance between these parallel pathways in liver and kidney may contribute to the pathogenesis and progression of metabolic syndrome. However, the impact of metabolic dysfunction on CYP-mediated formation of endogenous eicosanoids has not been well characterized. Therefore, we evaluated CYP epoxygenase (EET + DHET) and ω-hydroxylase (20-HETE) metabolic activity in liver and kidney in apoE−/− and wild-type mice fed a high-fat diet, which promoted weight gain and increased plasma insulin levels significantly. Hepatic CYP epoxygenase metabolic activity was significantly suppressed, whereas renal CYP ω-hydroxylase metabolic activity was induced significantly in high-fat diet-fed mice regardless of genotype, resulting in a significantly higher 20-HETE/EET + DHET formation rate ratio in both tissues. Treatment with enalapril, but not metformin or losartan, reversed the suppression of hepatic CYP epoxygenase metabolic activity and induction of renal CYP ω-hydroxylase metabolic activity, thereby restoring the functional balance between the pathways. Collectively, these findings suggest that the kinin-kallikrein system and angiotensin II type 2 receptor are key regulators of hepatic and renal CYP-mediated eicosanoid metabolism in the presence of metabolic syndrome. Future studies delineating the underlying mechanisms and evaluating the therapeutic potential of modulating CYP-derived EETs and 20-HETE in metabolic diseases are warranted.
Left ventricular torsion, energetics, and diastolic function in normal human aging
Authors: Hollingsworth Kieren G. , Blamire Andrew M. , Keavney Bernard D. , MacGowan Guy A.
Published: December 2011

This study determined, for the first time, whether the effects of normal aging on systolic and diastolic left ventricular function in subjects without cardiovascular disease are related to underlying energetic defects. Cardiac magnetic resonance imaging with tissue tagging and 31P spectroscopy was used to determine global structure, function, myocardial strains, and the phosphocreatine-to-ATP ratio (PCr/ATP) in 49 healthy subjects aged 20–69 yr. The three major abnormalities that developed with increasing age were the early filling percentage (EFP, the left ventricular volume increase from end systole to mid-diastole divided by stroke volume × 100), which decreased with age, indicating impaired early diastolic filling ( r = −0.72, P < 0.0001), the torsion-to-shortening ratio (TSR, measure of subepicardial torsion exerting mechanical advantage over subendocardial shortening), which increased with age indicating relative subendocardial dysfunction ( r = 0.44, P < 0.02), and the PCr/ATP (decreased with increasing age, r = −0.52, P < 0.003). EFP and TSR were strongly correlated ( r = −0.63, P < 0.0001), although they were not related to PCr/ATP [EFP vs. PCr/ATP: r = 0.34, not significant (NS) and TSR vs. PCr/ATP: r = −0.3, P = NS]. In normal aging, changes in EFP and TSR likely share the same pathophysiology, although it is unlikely that energetics have a major role in the functional effects of aging.
Activation of NPY type 5 receptors induces a long-lasting increase in spontaneous GABA release from cerebellar inhibitory interneurons
Authors: Dubois C. J. , Ramamoorthy P. , Whim M. D. , Liu S. J.
Published: December 2011

Neuropeptide Y (NPY), a widely distributed neuropeptide in the central nervous system, can transiently suppress inhibitory synaptic transmission and alter membrane excitability via Y2 and Y1 receptors (Y2rs and Y1rs), respectively. Although many GABAergic neurons express Y5rs, the functional role of these receptors in inhibitory neurons is not known. Here, we investigated whether activation of Y5rs can modulate inhibitory transmission in cerebellar slices. Unexpectedly, application of NPY triggered a long-lasting increase in the frequency of miniature inhibitory postsynaptic currents in stellate cells. NPY also induced a sustained increase in spontaneous GABA release in cultured cerebellar neurons. When cerebellar cultures were examined for Y5r immunoreactivity, the staining colocalized with that of VGAT, a presynaptic marker for GABAergic cells, suggesting that Y5rs are located in the presynaptic terminals of inhibitory neurons. RT-PCR experiments confirmed the presence of Y5r mRNA in the cerebellum. The NPY-induced potentiation of GABA release was blocked by Y5r antagonists and mimicked by application of a selective peptide agonist for Y5r. Thus Y5r activation is necessary and sufficient to trigger an increase in GABA release. Finally, the potentiation of inhibitory transmission could not be reversed by a Y5r antagonist once it was initiated, consistent with the development of a long-term potentiation. These results indicate that activation of presynaptic Y5rs induces a sustained increase in spontaneous GABA release from inhibitory neurons in contrast to the transient suppression of inhibitory transmission that is characteristic of Y1r and Y2r activation. Our findings thus reveal a novel role of presynaptic Y5rs in inhibitory interneurons in regulating GABA release and suggest that these receptors could play a role in shaping neuronal network activity in the cerebellum.
Late-Onset Endophthalmitis Secondary to Exposed Glaucoma Tube Implant in a Rare Case of Paediatric Glaucoma
Authors: Ranganath Akshatha , Hashim Adnan
Published: December 2011

Glaucoma drainage implants (GDIs) are used to treat paediatric glaucoma resistant to conventional medical and surgical treatment, achieving good intraocular pressure (IOP) control and long-term success. Late endophthalmitis is a rare complication that may develop following GDI surgery. A 17-year-old male presented with acute endophthalmitis 2 years after Ahmed glaucoma valve implantation with pericardial patch graft for management of refractory glaucoma secondary to congenital ectropion uveae. The glaucoma tube was exposed due to erosion of the overlying conjunctiva with no visible pericardial graft. After control of active infection, he underwent tube revision surgery whereby the exposed tube was retained and repatched with a double-thickness pericardial patch graft. He did well following surgery with good control of IOP and restoration of vision. Conjunctival dehiscence with graft melting over the GDI tube presented a major risk factor for endophthalmitis. Prompt surgical revision of an exposed tube is highly recommended to avoid ocular morbidity.
Decompression Retinopathy after ExPRESS Shunt Implantation for Steroid-Induced Ocular Hypertension: A Case Report
Authors: Abu Samra Khawla , Fernando Sieminski Sandra , Sarup Vimal
Published: December 2011

Purpose. To present a unique case of decompression retinopathy after the implantation of ExPRESS drainage device.Method. A 25-year-old female patient underwent implantation of ExPRESS drainage device in the left eye for the management of steroid-induced ocular hypertension.Results. On the postoperative day one, best-corrected visual acuity in the left eye was 20/50. Fundus examination revealed diffuse intraretinal hemorrhages, some white-centered, throughout the retina. There was also marked tortuosity to the retinal vasculature and no evidence of choroidal effusion. Intravenous fluorescein angiography and indocyanine green did not contribute to the aetiopathogenesis.Conclusion. Decompression retinopathy can occur following the implantation of ExPRESS drainage device. It is very important to be aware of this complication in patients with relatively high intraocular pressure who is planned for filtration surgery, including the ExPRESS implant.
An AMOLED AC-Biased Pixel Design Compensating the Threshold Voltage andI-RDrop
Authors: Fan Ching-Lin , Lai Hui-Lung , Liu Yan-Wei
Published: December 2011

We propose a novel pixel design and an AC bias driving method for active-matrix organic light-emitting diode (AM-OLED) displays using low-temperature polycrystalline silicon thin-film transistors (LTPS-TFTs). The proposed threshold voltage andI-Rdrop compensation circuit, which comprised three transistors and one capacitor, have been verified to supply uniform output current by simulation work using the Automatic Integrated Circuit Modeling Simulation Program with Integrated Circuit Emphasis (AIM-SPICE) simulator. The simulated results demonstrate excellent properties such as low error rate of OLED anode voltage variation (<0.7%) and low voltage drop ofVDDpower line. The proposed pixel circuit effectively enables threshold-voltage-deviation correction of driving TFT and compensates for the voltage drop ofVDDpower line using AC bias on OLED cathode.
Limbitis Secondary to Autologous Serum Eye Drops in a Patient with Atopic Keratoconjunctivitis
Authors: Welder Jeffrey David , Bakhtiari Pejman , Djalilian Ali R.
Published: December 2011

Purpose. Report a case of limbitis secondary to autologous serum eye drops in a patient with atopic keratoconjunctivitis.Design. Interventional case report.Methods. A 32-year-old African American female with atopic keratoconjunctivitis (AKC) presented with chronic dry eye and diffuse punctate epithelial erosions refractory to conservative treatment. She was initially managed with cyclosporine ophthalmic 0.05% in addition to preservative-free artificial tears and olopatadine hydrochloride 0.2% for 6 months. She was later placed on autologous serum eye drops (ASEDs) and 4 weeks into treatment developed unilateral limbitis. The limbitis resolved shortly after stopping ASEDs in that eye; however, the drops were continued in the contralateral eye, which subsequently developed limbitis within 2 weeks. ASEDs were discontinued in both eyes, and the patient has remained quiet ever since.Results. Patient with a history of AKC and no prior history of limbitis developed limbitis shortly after starting ASEDs, which resolved promptly after discontinuation of therapy with no subsequent recurrence of inflammation.Conclusion. ASEDs are widely used in the treatment of complicated or treatment refractory dry eye. The potential side effects should be kept in mind when prescribing ASEDs for any patient, especially in those with underlying immunological diseases and circulating inflammatory factors.
The Effectiveness of Poly-(4-vinyl-N-hexylpyridiniumbromide) as an Antibacterial Implant Coating: AnIn VitroStudy
Authors: Ringenberg L. , Winkel A. , Kufelt O. , Behrens P. , Stiesch M. , Heuer W.
Published: December 2011

The clinical success of osseointegrated dental implants depends on the strong attachment of the surrounding hard and soft tissues. Bacterial adhesion on implant surfaces can cause inflammatory reactions and may influence healing and long-term success of dental implants. Promising implant coatings should minimize bacterial adhesion, but allow epithelial and connective tissue attachment. Therefore, the present study has examined the bioactive effect of poly-(4-vinyl-N-hexylpyridiniumbromide) regarding typical oral bacteria as well as cytotoxicitiy to human cells considering different methods of connecting polymers to silicate-containing surfaces. The results revealed that the application of putative antibacterial and biocompatible polymer in coating strategies is affected by a variety of parameters. Published findings regarding reduced bacterial adhesion could not be verified using oral pathogens whereas hexylated polymers seem problematic for strong adhesion of soft tissue. Concerning innovative coatings for dental implants basic aspects (surface roughness, thickness, alkylation, combination with other polymers) have to be considered in further investigations.
Characterization of Hardware Impairments in Multiple Antenna Systems for DoA Estimation
Authors: Inserra Daniele , Tonello Andrea M.
Published: December 2011

We consider the effects introduced by hardware impairments on the estimation of the direction of arrival (DoA) deploying a multiple antenna radio system. We derive a system model from experimental measurements of a state-of-the-art hardware test bed based on an RF direct-conversion architecture. The system model includes DC offsets, carrier frequency and phase offsets, and the phase noise. Then, we propose a simple digital compensation algorithm of the impairments for bidimensional DoA estimation (azimuth and elevation) with a 3D orthogonal linear array. The robustness of the algorithm in terms of minimum-mean-squared error as a function of the hardware impairments is evaluated and compared with that achieved using the root-MUSIC algorithm.
RCS Computation by Parallel MoM Using Higher-Order Basis Functions
Authors: Yan Ying , Zhang Yu , Liang Chang-Hong , Zhao Hui , García-Doñoro D.
Published: December 2011

A Message-Passing Interface (MPI) parallel implementation of an integral equation solver that uses the Method of Moments (MoM) with higher-order basis functions has been proposed to compute the Radar Cross-Section (RCS) of various targets. The block-partitioned scheme for the large dense MoM matrix is designed to achieve excellent load balance and high parallel efficiency. Some numerical results demonstrate that higher-order basis in this parallelized scheme is more efficient than the conventional RWG method and able to efficiently analyze RCS of various electrically large platforms.
Myc Posttranscriptionally Induces HIF1 Protein and Target Gene Expression in Normal and Cancer Cells
Authors: Doe Megan R. , Ascano Janice M. , Kaur Mandeep , Cole Michael D.
Published: December 2011

c-Myc is frequently overexpressed in tumors and plays an important role in the regulation of cancer metabolism. Hypoxia-inducible factor-1 (HIF1), the master regulator of the hypoxic response, enhances tumorigenesis and influences metabolism via upregulation of the glycolytic pathway and suppression of mitochondrial respiration. Together, deregulated Myc and HIF1 cooperate to lend metabolic advantages to proliferating cancer cells and contribute to the Warburg effect. Here we show that overexpression of Myc significantly stabilizes the α subunit of HIF1 (HIF1α) under normoxic conditions and enhances HIF1α accumulation under hypoxic conditions in cells. Posttranscriptional regulation of HIF1α by Myc led to the induction of HIF1α gene targets. Normoxic HIF1α protein expression was also dependent on Myc. Functionally, HIF1α expression was required for Myc-induced anchorage-independent growth and cell proliferation. Myc-dependent stabilization of HIF1α involved either disruption of binding to the VHL complex or posttranslational protein modifications. Taken together, our findings uncover a previously uncharacterized regulatory relationship between Myc and HIF1 that has important implications for cancer metabolism and development. Cancer Res; 72(4); 949–57. ©2011 AACR.
Upregulated IL-19 in Breast Cancer Promotes Tumor Progression and Affects Clinical Outcome
Authors: Hsing Chung-Hsi , Cheng Hung-Chi , Hsu Yu-Hsiang , Chan Chien-Hui , Yeh Ching-Hua , Li Chien-Feng , Chang Ming-Shi
Published: December 2011

Purpose: Interleukin (IL)-19 was expressed in invasive ductal carcinoma (IDC) of the breast tissue but not in healthy breast tissue. We explored the effects of IL-19 on the pathogenesis of breast cancer and its clinical outcome.

Experimental Design: Tumor expression of IL-19 was assessed by immunohistochemistry and/or real-time quantitative PCR between two groups of patients with breast IDC (n = 60 and 143, respectively) with available clinical and survival data. We examined the effects of IL-19 on cytokine and chemokine production as well as proliferation and migration in breast cancer cells. Mice were injected with IL-19–overexpressing or vector control 67NR cells and the tumor growth and lung metastatic micronodules were measured.

Results: Of the IDC specimens, high IL-19 expression was associated with advanced tumor stage, high tumor metastasis, and worse survival. In vitro, IL-19 induced transcripts of IL-1β, IL-6, TGF-β, matrix metalloproteinase (MMP)2, MMP9, and CXCR4 in 4T1 breast cancer cells; induced fibronectin expression and assembly; and promoted cancer cell proliferation and migration, which were inhibited by anti-IL-19 monoclonal antibody (mAb). Endogenous fibronectin expression and cancer cell migration were lower in IL-19 knockdown 4T1 cells. In 4T1 cells, hypoxia induced IL-19 and CXCR4 expression, which was inhibited by anti-IL-19 mAb. IL-19 overexpression in noninvasive 67NR cancer cells increased cell proliferation and migration. In vivo, mice injected with IL-19–overexpressing 67NR cell clones showed larger tumors and more metastatic micronodules in the lung.

Conclusions: High IL-19 expression in breast cancer tissue is associated with a poor clinical outcome. IL-19 is pivotal in the pathogenesis of breast cancer. Clin Cancer Res; 18(3); 713–25. ©2011 AACR.
MiR-1 Downregulation Cooperates with MACC1 in Promoting MET Overexpression in Human Colon Cancer
Authors: Migliore Cristina , Martin Valentina , Leoni Vera P. , Restivo Angelo , Atzori Luigi , Petrelli Annalisa , Isella Claudio , Zorcolo Luigi , Sarotto Ivana , Casula Giuseppe , Comoglio Paolo M. , Columbano Amedeo , Giordano Silvia
Published: December 2011

Purpose: MET, the tyrosine kinase receptor for hepatocyte growth factor, is frequently overexpressed in colon cancers with high metastatic tendency. We aimed to evaluate the role of its negative regulators, miR-1 and miR-199a*, and its transcriptional activator, the metastasis-associated in colon cancer 1 (MACC1), in controlling MET expression in human colon cancer samples.

Experimental Design: The expression of MET, miR-1, miR-199a*, and MACC1 was evaluated by real-time PCR in 52 matched pairs of colorectal cancers and nontumoral surrounding tissues. The biological role of miR-1 in controlling MET expression and biological activity was assessed in colon cancer cells either by its forced expression or by AntagomiR-mediated inhibition.

Results: MiR-1 was downregulated in 84.6% of the tumors and its decrease significantly correlated with MET overexpression, particularly in metastatic tumors. We found that concurrent MACC1 upregulation and miR-1 downregulation are required to elicit the highest increase of MET expression. Consistent with a suppressive role of miR-1, its forced in vitro expression in colon cancer cells reduced MET levels and impaired MET-induced invasive growth. Finally, we identified a feedback loop between miR-1 and MET, resulting in their mutual regulation.

Conclusions: This study identifies an oncosuppressive role of miR-1 in colorectal cancer in which it acts by controlling MET expression through a feedback loop. Concomitant downregulation of miR-1 and increase of MACC1 can thus contribute to MET overexpression and to the metastatic behavior of colon cancer cells. Clin Cancer Res; 18(3); 737–47. ©2011 AACR.
Dovitinib Induces Apoptosis and Overcomes Sorafenib Resistance in Hepatocellular Carcinoma through SHP-1–Mediated Inhibition of STAT3
Authors: Tai Wei-Tien , Cheng Ann-Lii , Shiau Chung-Wai , Liu Chun-Yu , Ko Ching-Huai , Lin Mai-Wei , Chen Pei-Jer , Chen Kuen-Feng
Published: December 2011

The multiple kinase inhibitor dovitinib is currently under clinical investigation for hepatocellular carcinoma (HCC). Here, we investigated the mechanistic basis for the effects of dovitinib in HCCs. Dovitinib showed significant antitumor activity in HCC cell lines PLC5, Hep3B, Sk-Hep1, and Huh-7. Dovitinib downregulated phospho-STAT3 (p-STAT3) at tyrosine 705 and subsequently reduced the levels of expression of STAT3-related proteins Mcl-1, survivin, and cyclin D1 in a time-dependent manner. Ectopic expression of STAT3 abolished the apoptotic effect of dovitinib, indicating that STAT3 is indispensable in mediating the effect of dovitinib in HCC. SHP-1 inhibitor reversed downregulation of p-STAT3 and apoptosis induced by dovitinib, and silencing of SHP-1 by RNA interference abolished the effects of dovitinib on p-STAT3, indicating that SHP-1, a protein tyrosine phosphatase, mediates the effects of dovitinib. Notably, dovitinib increased SHP-1 activity in HCC cells. Incubation of dovitinib with pure SHP-1 protein enhanced its phosphatase activity, indicating that dovitinib upregulates the activity of SHP-1 via direct interactions. In addition, dovitinib induced apoptosis in two sorafenib-resistant cell lines through inhibition of STAT3, and sorafenib-resistant cells showed significant activation of STAT3, suggesting that targeting STAT3 may be a useful approach to overcome drug resistance in HCC. Finally, in vivo, dovitinib significantly suppressed growth of both Huh-7 and PLC5 xenograft tumors and downregulated p-STAT3 by increasing SHP-1 activity. In conclusion, dovitinib induces significant apoptosis in HCC cells and sorafenib-resistant cells via SHP-1–mediated inhibition of STAT3. Mol Cancer Ther; 11(2); 452–63. ©2011 AACR.
βII-Tubulin and βIII-Tubulin Mediate Sensitivity to Peloruside A and Laulimalide, but not Paclitaxel or Vinblastine, in Human Ovarian Carcinoma Cells
Authors: Kanakkanthara Arun , Northcote Peter T. , Miller John H.
Published: December 2011

Increased abundance of βII- and βIII-tubulin isotypes in cancer cells confers resistance to vinca and taxoid site drugs; however, the role of these isotypes in the acquired resistance of cancer cells to non-vinca or non-taxoid site binding agents has not been described. Peloruside A (PLA) and laulimalide are the only known non-taxoid site microtubule-stabilizing agents. A human ovarian cancer cell line, 1A9-L4 (L4), previously selected in high concentrations of laulimalide, has both a single point mutation in βI-tubulin and overexpression of βII- and βIII-tubulin. The cells are highly resistant to PLA as well as laulimalide but show no cross-resistance to taxoid site drugs or drugs that bind to the vinca site on β-tubulin. To understand the functional significance of the βII- and βIII-tubulin changes in this resistant cell line, isotype-specific short interfering RNA was used to knock down the expression of the βII and βIII isotypes, and the cellular effects of PLA and laulimalide were examined before and after silencing. It was found that inhibition of βII- and βIII-tubulin partially sensitized L4 cells to PLA and laulimalide, as seen by increased potency of PLA and laulimalide for inducing growth inhibition, cellular tubulin polymerization, microtubule aberrations, and G2-M arrest in the resistant cells. The sensitivity to paclitaxel, vinblastine, ixabepilone, and cisplatin was unaffected by the inhibition of isotype expression. It was concluded that the increased βII- and βIII-tubulin contributed significantly to the resistance phenotype, along with the tubulin structural mutation, and that the altered isotype effect was binding site specific. Mol Cancer Ther; 11(2); 393–404. ©2011 AACR.
Hospital- and Community-Based Screenings for Hepatocellular Carcinoma in Taiwan
Authors: Kee Kwong-Ming , Lu Sheng-Nan
Published: December 2011

In Taiwan, hepatocellular carcinoma (HCC) has been the leading cause of cancer incidence and mortality in recent decades. The majority of patients have hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. The HBV carrier rate and incidence of HCC in children have declined with the implementation of a hepatitis B vaccination program for newborns since 1984. A combination of α-fetoprotein and ultrasonography (US) has been used for surveillance in patients with chronic HBV and HCV infection in intervals of 3–6 and 6–12 months for cirrhosis and chronic liver disease, respectively. A secular survival improvement in HCC patients has been demonstrated. A reasonable screening protocol should include two stages. The first stage is identification of high-risk subjects and the second stage is US screening of high-risk subjects. Community-based HCC screening programs have been conducted for more than two decades in Taiwan. The commonly used first-stage markers are HBsAg and anti-HCV, while the platelet count should be a useful marker in HCV-endemic communities. The benefit of HCC screening was shown by a prolonged overall survival. However, this was limited to the early curable stage in elderly subjects. Prevention and control of HCC have multiple modalities. Identification of a high-risk group for active surveillance, effective antiviral treatment for chronic HBV and HCV infection, and early detection and prompt treatment of HCC should decrease the sequelae of HCC in Taiwan.
Adjuvant Therapy after Curative Treatment for Hepatocellular Carcinoma
Authors: Kudo Masatoshi
Published: December 2011

It is widely accepted that hepatocellular carcinoma (HCC) has an annual recurrence rate of approximately 15–20% even after potentially curative treatment, with the 5-year recurrence rate reaching 80–90%. This recurrence rate is also known to be similar after various curative treatments including resection, percutaneous ethanol injection therapy, and radiofrequency ablation. Generally, in treating patients with HCC associated with hepatitis C or liver cirrhosis, aggressive efforts to prevent secondary carcinogenesis are necessary rather than simply observing the clinical course after treatment. Presently, a combination of peg-interferon and ribavirin is known to be highly effective in patients with difficult-to-treat hepatitis C with a high viral load and genotype I virus. Therefore, indications of these treatments must be considered to prevent secondary carcinogenesis in patients with hepatitis C. Recently, long-term follow-up of low-dose, long-term maintenance therapy using pegylated interferon-α2a for cirrhotic patients clearly showed a preventive effect on HCC occurrence and recurrence. Preventing secondary carcinogenesis by suppressing inflammation employing the same treatment as that against primary carcinogenesis is also important. The molecular targeted agent sorafenib markedly suppresses the serine/threonine kinases of Raf in the MAP kinase cascade and inhibits the tyrosine kinases of angiogenesis factor receptors such as vascular endothelial growth factor and platelet-derived growth factor receptors. It thus simultaneously prevents the proliferation of tumors and inhibits angiogenesis. A clinical trial to examine the recurrence-preventing effect of sorafenib by administration of it after curative treatment such as resection or ablation is in progress (STORM trial: http://clinicaltrials.gov.com, NCT00692770). Treatments to prevent recurrence (including intrahepatic metastasis and multicentric carcinogenesis) as well as early detection and early curative treatment are extremely important to improve the prognosis of patients with HCC. Thus, further research on this issue should be carried out, especially in relation to molecular targeted therapy.
Superselective Transarterial Chemoembolization for Hepatocellular Carcinoma: Recent Progression and Perspective
Authors: Takayasu Kenichi
Published: December 2011

This paper was withdrawn by the author because unpublished data were inadvertently inserted by a third party, due to an oversight during the editorial process, without prior approval of the Principal Investigator, Masatoshi Kudo, and his co-authors of a research paper by the Liver Cancer Study Group of Japan. K. Takayasu
Partially Hydrolysed 100% Whey-Based Infant Formula and the Prevention of Atopic Dermatitis: Comparative Pharmacoeconomic Analyses
Authors: Spieldenner Jörg , Belli Dominique , Dupont Christophe , Haschke Ferdinand , Iskedjian Michael , Nevot Falcó Santiago , Szajewska Hania , von Berg Andrea
Published: December 2011

Clinical trials have demonstrated that the risk of developing atopic dermatitis is reduced when using hydrolysed formulas to feed infants with a documented risk of atopy (i.e. an affected parent and/or sibling)when breastfeeding is not practised. However, little is known about the cost-effectiveness of using hydrolysed formulas. Consequently, economic analyses in 5 European countries (Denmark, France, Germany, Spain and Switzerland) have evaluated the costs and cost-effectiveness of a specific brand of 100% whey-based partially hydrolysed infant formula, NAN-HA® (PHF-W) compared with a cow’s milk standard formula (SF) in the prevention of atopic dermatitis in at-risk children. This review synthesises the findings of these studies. Cost-effectiveness analyses (CEA) used a decision-analytic model to determine treatment pathways, resource utilisation and costs associated with the management of atopic dermatitis in healthy at-risk newborns who were not exclusively breastfed. The model had a 12-month horizon and applied reimbursement rates of 60–100% depending on the country. Outcomes were considered from the perspective of the public healthcare system (e.g. the Ministry of Health; MOH), family and society. The final outcome was the incremental cost-effectiveness ratio per avoided case of atopic dermatitis (ICER) for PHF-W versus SF. A cost-minimisation analysis was also performed to compare PHF-W with extensively hydrolysed formulas (EHF). The base-case CEA produced ICERs per avoided case for PHF-W versus SF of EUR 982–1,343 (MOH perspective), EUR –2,202 to –624 (family perspective) indicating savings, and EUR –1,220 to 719 from the societal perspective. The main costs related to formula (MOH and society) and time loss (family). In the cost-minimisation analysis, PHF-W yielded savings of between EUR 4.3 and 120 million compared with EHF-whey when the latter was used in prevention. In conclusion, PHF-W was cost-effective versus SF in the prevention of atopic dermatitis and cost saving compared with EHF when used in prevention.
Clinical Features and Management Outcomes of Severe Hand, Foot and Mouth Disease
Authors: Tian Hui , Yang Qiao-Zhi , Liang Jun , Dong Sheng-Ying , Liu Zhi-Jun , Wang Le-Xin
Published: December 2011

Objective: This study was designed to describe the clinical features and management outcomes of severe hand, foot and mouth disease (HFMD). Subjects and Methods: Data on 147 severe HFMD patients during an outbreak in 2009 were analyzed. Results: Most patients were under 3 years of age; 102 (69.4%) were boys. All had skin rashes and fever of ≥38°C. All (n = 147, 100%) showed signs of central nervous system involvement, such as lethargy (n = 124, 84.4%), myoclonic jerks (n = 76, 51.7%), or drowsiness (n = 34, 23.1%). Respiratory symptoms were mainly tachypnea (n = 112, 76.2%) or bradypnea (n = 21, 14.3%). Common cardiovascular symptoms included tachycardia (n = 134, 91.2%) and hypertension (n = 23, 15.5%). Chest X-ray showed increased markings in 76 (51.7%) or consolidation in 44 (29.9%). Hyperglycemia and elevated blood lactic acid levels were found in 127 (86.4%) and 130 (88.4%), respectively. Positive enterovirus EV71-PCR was found in 113 (76.9%). All patients were treated with mechanical ventilation for 61.2 ± 12.8 h (range, 40–96 h), as well as mannitol, dexamethasone, gamma globulin and ribavirin. Dopamine, dobutamine or amrinone was administered in 58.5, 51.0 and 21.8%, respectively. Three patients (2%) died during hospitalization. All others had a full recovery and were discharged after 14.2 ± 1.6 days (range, 12–17 days). Conclusion: Central nervous and cardiorespiratory systems were involved in the patients with severe HFMD. Fasting blood glucose and lactic acid levels increased in the majority of patients. Mechanical ventilation and supportive pharmacotherapy were associated with a good clinical outcome in these patients.
Cognitive Function and the Risk of Death in Chronic Kidney Disease
Authors: Raphael Kalani L. , Wei Guo , Greene Tom , Baird Bradley C. , Beddhu Srinivasan
Published: December 2011

Background and Aims: Cognitive impairment is a risk factor for death in dialysis patients and the general population. We sought to determine if cognitive impairment is associated with death in people with non-dialysis-dependent chronic kidney disease (CKD), and if so, whether this relationship is greater in the CKD population compared to the general population. Methods: National Health and Nutrition Examination Survey-III participants older than 60 years were asked to subtract 3 from 20 five times and to perform immediate and delayed recall of three items. A cognitive score of 0–11 was assigned based on the number of correct responses. Participants were categorized according to cognitive score (11, 9–10, 6–9, and 0–5) and CKD status. Survival analyses were conducted using Cox models. Results: Within the CKD subpopulation, those in the lowest cognitive score group had a twofold increased hazard of death compared to those with maximum score. Within the non-CKD subpopulation, those in the lowest cognitive score group had a 46% increased hazard of death compared to those with maximum score. However, the difference in the hazards of death in the CKD and non-CKD subpopulations with the lowest cognitive score was not significant (p = 0.99). Conclusions: Low cognitive score is associated with an increased risk of death in elderly individuals with and without CKD; however, there was no interaction of CKD and low cognitive score in this analysis.
Use of aspirin in Chinese after recovery from primary intracranial haemorrhage
Authors: Chong Boon-Hor , Chan Koon-Ho , Pong Vincent , Lau Kui-Kai , Chan Yap-Hang , Zuo Ming-Liang , Lui Wai-Man , Leung Gilberto , Lau Chu-Pak , Tse Hung-Fat , Pu Jenny , Siu Chung-Wah
Published: December 2011

Intracranial haemorrhage (ICH) accounts for ~35% of all strokes in Chinese. Anti-platelet agent is often avoided after an index event due to the possibility of recurrent ICH. This single-centered observational study included 440 consecutive Chinese patients with a first spontaneous ICH surviving the first month performed during 1996–2010. The subjects were identified, and their clinical characteristics, anti-platelet therapy after ICH, and outcomes including recurrent ICH, ischaemic stroke, and acute coronary syndrome were checked from hospital records. Of these 440 patients, 56 patients (12.7%) were prescribed aspirin (312 patient-aspirin years). After a follow-up of 62.2 ± 1.8 months, 47 patients had recurrent ICH (10.7%, 20.6 per 1,000 patient years). Patients prescribed aspirin did not have a higher risk of recurrent ICH compared with those not prescribed aspirin (22.7 per 1,000 patient-aspirin years vs. 22.4 per 1,000 patient years, p=0.70). Multivariate analysis identified age > 60 years (hazard ratio [HR]: 2.0, 95% confidence interval [CI]: 1.07–3.85, p=0.03) and hypertension (HR: 2.0, 95% CI: 1.06–3.75, p=0.03) as independent predictors for recurrent ICH. In a subgroup analysis including 127 patients with standard indications for aspirin of whom 56 were prescribed aspirin, the incidence of combined vascular events including recurrent ICH, ischaemic stroke, and acute coronary syndrome was statistically lower in patients prescribed aspirin than those not prescribed aspirin (52.4 per 1,000 patient-aspirin years, vs. 112.8 per 1,000 patient-years, p=0.04). In conclusion, we observed in a cohort of Chinese post-ICH patients that aspirin use was not associated with an increased risk for a recurrent ICH.
Prevalence of Cardiomyopathy in Italian Asymptomatic Children With Electrocardiographic T-Wave Inversion at Preparticipation Screening
Authors: Migliore Federico , Zorzi Alessandro , Michieli Pierantonio , Perazzolo Marra Martina , Siciliano Mariachiara , Rigato Ilaria , Bauce Barbara , Basso Cristina , Toazza Daniela , Schiavon Maurizio , Iliceto Sabino , Thiene Gaetano , Corrado Domenico
Published: December 2011

Background—

T-wave inversion on a 12-lead ECG is usually dismissed in young people as normal persistence of the juvenile pattern of repolarization. However, T-wave inversion is a common ECG abnormality of cardiomyopathies such as hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy, which are leading causes of sudden cardiac death in athletes. We prospectively assessed the prevalence, age relation, and underlying cardiomyopathy of T-wave inversion in children undergoing preparticipation screening.

Methods and Results—

The study population included 2765 consecutive Italian children (1914 male participants; mean age, 13.9±2.2 years; range 8–18 years) undergoing preparticipation screening including an ECG. Of 229 children (8%) who underwent further evaluation because of positive findings at initial preparticipation screening, 33 (1.2%) were diagnosed with cardiovascular disease. T-wave inversion was recorded in 158 children (5.7%) and was localized in the right precordial leads in 131 (4.7%). The prevalence of right precordial T-wave inversion decreased significantly with increasing age (8.4% in children <14 years of age versus 1.7% in those ≥14 years;
P
<0.001), pubertal development (9.5% of children with incomplete versus 1.6% with complete development;
P
<0.001), and body mass index below the 10th percentile (
P
<0.001). Incomplete pubertal development was the only independent predictor for right precordial T-wave inversion (odds ratio, 3.6; 95% confidence interval, 1.9–6.8;
P
<0.001). Of 158 children with T-wave inversion, 4 (2.5%) had a diagnosis of cardiomyopathy, including arrhythmogenic right ventricular cardiomyopathy (n=3) and hypertrophic cardiomyopathy (n=1).

Conclusions—

The prevalence of T-wave inversion decreases significantly after puberty. Echocardiographic investigation of children with postpubertal persistence of T-wave inversion at preparticipation screening is warranted because it may lead to presymptomatic diagnosis of a cardiomyopathy that could lead to sudden cardiac death during sports.
Connexin43 Mutation Causes Heterogeneous Gap Junction Loss and Sudden Infant Death
Authors: Van Norstrand David W. , Asimaki Angeliki , Rubinos Clio , Dolmatova Elena , Srinivas Miduturu , Tester David J. , Saffitz Jeffrey E. , Duffy Heather S. , Ackerman Michael J.
Published: December 2011

Background—

An estimated 10% to 15% of sudden infant death syndrome (SIDS) cases may stem from channelopathy-mediated lethal arrhythmias. Loss of the
GJA1
-encoded gap junction channel protein connexin43 is known to underlie formation of lethal arrhythmias.
GJA1
mutations have been associated with cardiac diseases, including atrial fibrillation. Therefore,
GJA1
is a plausible candidate gene for premature sudden death.

Methods and Results—

GJA1
open reading frame mutational analysis was performed with polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing on DNA from 292 SIDS cases. Immunofluorescence and dual whole-cell patch-clamp studies were performed to determine the functionality of mutant gap junctions. Immunostaining for gap junction proteins was performed on SIDS-associated paraffin-embedded cardiac tissue. Two rare, novel missense mutations, E42K and S272P, were detected in 2 of 292 SIDS cases, a 2-month-old white boy and a 3-month-old white girl, respectively. Analysis of the E42K victim's parental DNA demonstrated a de novo mutation. Both mutations involved highly conserved residues and were absent in >1000 ethnically matched reference alleles. Immunofluorescence demonstrated no trafficking abnormalities for either mutation, and S272P demonstrated wild-type junctional conductance. However, junctional conductance measurements for the E42K mutation demonstrated a loss of function not rescued by wild type. Moreover, the E42K victim's cardiac tissue demonstrated a mosaic immunostaining pattern for connexin43 protein.

Conclusions—

This study provides the first molecular and functional evidence implicating a
GJA1
mutation as a novel pathogenic substrate for SIDS. E42K-connexin43 demonstrated a trafficking-independent reduction in junctional coupling in vitro and a mosaic pattern of mutational DNA distribution in deceased cardiac tissue, suggesting a novel mechanism of connexin43-associated sudden death.
Rainfall Regime of a Mountainous Mediterranean Region: Statistical Analysis at Short Time Steps
Authors: Molinié Gilles , Ceresetti Davide , Anquetin Sandrine , Creutin Jean Dominique , Boudevillain Brice
Published: December 2011

This paper presents an analysis of the rainfall regime of a Mediterranean mountainous region of southeastern France. The rainfall regime is studied on temporal scales from hourly to yearly using daily and hourly rain gauge data of 43 and 16 years, respectively. The domain is 200 × 200 km2 with spatial resolution of hourly and daily rain gauges of about 8 and 5 km, respectively. On average, yearly rainfall increases from about 0.5 m yr−1 in the large river plain close to the Mediterranean Sea to up to 2 m yr−1 over the surrounding mountain ridges. The seasonal distribution is also uneven: one-third of the cumulative rainfall occurs during the autumn season and one-fourth during the spring. At finer time scales, rainfall is studied in terms of rain–no-rain intermittency and nonzero intensity. The monthly intermittency (proportion of dry days per month) and the daily intermittency (proportion of dry hours per day) is fairly well correlated with the relief. The higher the rain gauges are, the lower the monthly and daily intermittencies are. The hourly and daily rainfall intensities are analyzed in terms of seasonal variability, diurnal cycle, and spatial pattern. The difference between regular and heavy-rainfall event is depicted by using both central parameters and maximum values of intensity distributions. The relationship between rain gauge altitudes and rainfall intensity is grossly inverted relative to intermittency and is also far more complex. The spatial and temporal rainfall patterns depicted from rain gauge data are discussed in the light of known meteorological processes affecting the study region.
Surprise as a Catalyst for Including Climatic Change in the Strategic Environment
Authors: Haigh Nardia , Griffiths Andrew
Published: December 2011

This article examines what prompted electricity supply organizations to include changing climatic conditions as key elements of the strategic environment. Utilizing themes emerging from inductive analysis, the authors explain how and why surprising climatic events drove the organizations to begin including climate trends in their strategy development and planning processes. Results indicate that organizations were surprised climate was becoming more unpredictable, was directly affecting their operations, and was challenging long-held assumptions about climatic patterns. Our findings suggest that adaptation to climate change occurs predominantly as a reaction to climatic surprise, rather than a preemptive response to increasing awareness, and perceived uncertainty and risks as suggested by previous studies. Results also show that organizations are beginning to conceptually link changes in local climatic conditions to the global issue of climate change; though such linkages are not necessarily important to the inclusion of climate in the strategic environment.
Reversing Genesis: A Theological Reading of Creation Undone in Zephaniah
Authors: Clark David A. R.
Published: December 2011

The Book of Zephaniah expresses the expectation of divine judgment as reversals of two specific features of the Genesis 1 narrative: the creation of life and the dominion of humankind. Each is inverted in Zephaniah, which envisions life destroyed and animals ascendant. However, these two prophetic trajectories appear mutually exclusive, as the former anticipates the elimination of all life while the latter anticipates the surging dominance of animal life. This article examines this tension with reference to specific oracles, exploring possible theological significance and rhetorical function of these seemingly incongruous inversions of the Genesis 1 material. I argue that this tension conveys, perhaps surprisingly, an assertion of the mercy and gracious restraint of God, as the prophet subtly suggests a disjunction between the warranted and probable intensities of divine judgement. Moving from this theological analysis, I briefly consider how this tension also proves rhetorically effective at inviting the prophet’s hearers to seek the mercy of God through repentance.
Numerical investigation and experimental verification of the Joule heating effect of polyacrylonitrile-based carbon fiber tows under high vacuum conditions
Authors: Athanasopoulos N , Sikoutris D , Panidis T , Kostopoulos V
Published: December 2011

Joule’s first-law dictates that when electric current passes through a conductor heat is generated. The scope of this work is to investigate the Joule heating effect of two types of carbon fiber tows in dry form. The tows are used as primary heating elements on various preform structures that require accurate and uniform temperature control, using a DC power supply. The investigated temperatures, ranged from 300 K up to 650 K. A finite difference scheme was developed, in order to predict and quantify the transient phenomenon and is verified against experimental results. In order to exploit in-depth the phenomenon and achieve very good agreement between numerical and experimental results, temperature dependence of thermal and electrical properties (specific heat capacity, total hemispherical emissivity, and volume resistivity) was examined under controlled vacuum environment, ensuring no fiber oxidation.
Simulation of fully coupled thermomechanical analysis of automotive brake discs
Authors: Belhocine Ali , Bouchetara Mostefa
Published: December 2011

The vehicle braking system is considered to be one of the most fundamental safety-critical systems in modern vehicles, as its main purpose is to stop or decelerate the vehicle. The frictional heat generated during braking application can cause numerous negative effects on the brake assembly, such as brake fade, premature wear, thermal cracks and disc thickness variation. In the past, surface roughness and wear at the pad interface have rarely been considered in studies of the thermal analysis of a disc brake assembly using the finite element method. The ventilated pad-disc brake assembly is built by a three-dimensional model with a thermomechanical coupling boundary condition and multi-body model technique. The numerical simulation for the coupled transient thermal field and stress field is carried out sequentially with the thermal-structural coupled method, based on ANSYS software, to evaluate the stress fields of deformations, which are established in the disc with the pressure of the pads and in the conditions of tightening of the disc; thus, the contact pressure distributions field in the pads is obtained, which is another significant aspect in this research. The results obtained by the simulation are satisfactory compared with those of the specialized literature.