bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective effect of neferine on endothelial cell nitric oxide production induced by lysophosphatidylcholine: the role of the DDAH–ADMA pathway
Authors: Peng Zhen-Yu , Zhang Sai-Dan , Liu Shao , He Bai-Mei
Published: May 2011

Neferine, extracted from the seed embryo of Nelumbo nucifera Gaertn., has multiple cardiovascular pharmacological effects. The dimethylarginine dimethylaminohydrolase (DDAH) – asymmetric dimethylarginine (ADMA) system is a novel pathway for modulating nitric oxide (NO) production. The aim of this study was to investigate whether the protective effect of neferine on endothelial NO production was related to the DDAH–ADMA pathway. Human umbilical vein endothelial cells (HUVECs) were first exposed to neferine (0.1, 1.0, or 10.0 μmol/L) for 1 h, and then incubated with lysophosphatidylcholine (LPC; 10 μg/mL) in the presence of neferine for 24 h. The medium was collected for measuring the levels of NO, maleic dialdehyde (MDA), as well as ADMA. The endothelial cells were collected for measuring DDAH activity and the level of reactive oxygen species (ROS). LPC significantly decreased NO concentration and DDAH activity and increased the levels of ADMA, ROS, and MDA. Neferine could partially counteract the changes induced by LPC. These findings suggested that neferine could modulate the DDAH–ADMA pathway via its antioxidant properties, which was involved in its beneficial effect on endothelial NO production.
EFFECTS OF ALIGNMENT ERRORS IN PROTON NON-SCALING FFAG ACCELERATORS
Authors: SHEEHY SUZANNE L. , KELLIHER DAVID J.
Published: May 2011

Non-scaling FFAGs have gained interest in the past decade for their potential application to charged particle therapy using proton and ion beams. However, linear ns-FFAGs naturally cross betatron resonances throughout acceleration. With an acceleration cycle of thousands rather than tens of turns, we find that resonance crossing produces severe orbit distortion in a linear proton/ion ns-FFAG in the presence of alignment errors. To overcome this, the PAMELA (Particle Accelerator for MEdicaL Applications) lattice design avoids resonance crossing with a non-linear ns-FFAG design. This design is outlined and a comparative analysis of alignment tolerances presented.
SYNTHESIS AND CHARACTERIZATION OF NANOCRYSTALLINE FeNi AND Ni3Fe ALLOYS
Authors: AZADEHRANJBAR S. , KARIMZADEH F. , ENAYATI M. H.
Published: May 2011

Nanocrystalline FeNi and Ni 3 Fe alloys were prepared by mechanical alloying of Fe and Ni elemental powders using a planetary ball mill under protection atmosphere. X-ray diffraction measurements were performed to follow alloy formation process in these alloys. A heat treatment of 1 h at 800°C was carried out to relax the internal stresses of the milled samples. Morphological evolution of powder particles was revealed by scanning electron microscopy. The value of lattice parameter was reached to 0.35762 nm and the hardness was found to be 686 HV at 30 h milled FeNi powder. In the case of Ni 3 Fe the values of 0.3554 nm and 720 HV were obtained for lattice parameter and hardness, respectively.
THE FRIEDMANN EQUATIONS IN DEFORMED HOŘAVA–LIFSHITZ GRAVITY AND DEBYE MODEL
Authors: LIU BIN , DAI YUN-CHUAN , HU XIAN-RU , DENG JIAN-BO
Published: May 2011

Considering the results from Hořava–Lifshitz (HL) theory, a more precise relation between the number of bits and area in the holographic system is proposed. With this corrected relation and Debye model, two modified Friedmann equations are derived from the Hawking temperature and the Unruh temperature separately in entropic force. These equations could be better in describing the whole evolution of the Universe.
ON THE HAHN–JORDAN DECOMPOSITION FOR SIGNED MEASURE VALUED STOCHASTIC PARTIAL DIFFERENTIAL EQUATIONS
Authors: KOTELENEZ PETER M. , SEADLER BRADLEY T.
Published: May 2011

Let N-point particles be distributed over ℝd, d ∈ ℕ. The position of the ith particle at time t will be denoted r(t, qi) where qi is the position at t = 0. mi ∈ ℝ\{0} is the "weight" of the ith particle. Let δr be the point measure concentrated in r and [Formula: see text] the initial mass distribution of the N-point particles. The empirical mass distribution (also called the "empirical process") at time t is then given by [Formula: see text] i.e. by the N-particle flow. In Kotelenez (2008) the weights are positive and the motion of the positions of the point particles is described by a stochastic ordinary differential equation (SODE). Further, the resulting empirical process is the solution of a stochastic partial differential equation (SPDE) which, by a continuum limit, can be extended to an SPDE in smooth positive measures. Some generalizations to the case of signed measures with applications in 2D fluid mechanics have been made. Kotelenez (2010) shows that the signed measure valued solutions of the SPDEs preserve the Hahn–Jordan decomposition of the initial distributions under the assumption that the coefficients of the SODEs are Lipschitz and that the flows of SODEs are smooth. Employing a certain metric on the signed measures, we prove the preservation of the Hahn–Jordan decomposition assuming only Lipschitz conditions on the coefficients of the SODEs.
ON THE SPEED OF CONVERGENCE OF MULTIDIMENSIONAL DIFFUSIONS TO EQUILIBRIUM
Authors: BHATTACHARYA RABI , WASIELAK ARAMIAN
Published: May 2011

We obtain new criteria for polynomial rates of convergence of ergodic multidimensional diffusions to equilibrium. For this, (1) a method is provided for adapting to continuous-time Markov processes coupling techniques for discrete parameter Harris processes, and (2) estimates of moments of return times to a ball are derived.
SYMMETRIES OF NON-LINEAR SYSTEMS: GROUP APPROACH TO THEIR QUANTIZATION
Authors: ALDAYA V. , CALIXTO M. , GUERRERO J. , LÓPEZ-RUIZ F. F.
Published: May 2011

We report briefly on an approach to quantum theory entirely based on symmetry grounds which improves Geometric Quantization in some respects and provides an alternative to the canonical framework. The present scheme, being typically non-perturbative, is primarily intended for non-linear systems, although needless to say that finding the basic symmetry associated with a given (quantum) physical problem is in general a difficult task, which many times nearly emulates the complexity of finding the actual (classical) solutions. Apart from some interesting examples related to the electromagnetic and gravitational particle interactions, where an algebraic version of the Equivalence Principle naturally arises, we attempt to the quantum description of non-linear sigma models. In particular, we present the actual quantization of the partial-trace non-linear SU (2) sigma model as a representative case of non-linear quantum field theory.
A framework for defending embedded systems against software attacks
Authors: Aaraj Najwa , Raghunathan Anand , Jha Niraj K.
Published: May 2011

The incidence of malicious code and software vulnerability exploits on embedded platforms is constantly on the rise. Yet, little effort is being devoted to combating such threats to embedded systems. Moreover, adapting security approaches designed for general-purpose systems generally fails because of the limited processing capabilities of their embedded counterparts.

In this work, we evaluate a malware and software vulnerability exploit defense framework for embedded systems. The proposed framework extends our prior work, which defines two isolated execution environments: a
testing
environment, wherein an untrusted application is first tested using dynamic binary instrumentation (DBI), and a
real
environment, wherein a program is monitored at runtime using an extracted behavioral model, along with a continuous learning process. We present a suite of software and hardware optimizations to reduce the overheads induced by the defense framework on embedded systems. Software optimizations include the usage of static analysis, complemented with DBI in the testing environment (i.e., a hybrid software analysis approach is used). Hardware optimizations exploit parallel processing capabilities of multiprocessor systems-on-chip.

We have evaluated the defense framework and proposed optimizations on the ARM-Linux operating system. Experiments demonstrate that our framework achieves a high coverage of considered security threats, with acceptable performance penalties (the average execution time of applications goes up to 1.68X, considering all optimizations, which is much smaller than the 2.72X performance penalty when no optimizations are used).
An exploration of relations between visual appeal, trustworthiness and perceived usability of homepages
Authors: Lindgaard Gitte , Dudek Cathy , Sen Devjani , Sumegi Livia , Noonan Patrick
Published: May 2011

Extremely high correlations between repeated judgments of visual appeal of homepages shown for 50 milliseconds have been interpreted as evidence for a mere exposure effect [Lindgaard et al. 2006]. Continuing that work, the present research had two objectives. First, it investigated the relationship between judgments differing in cognitive demands. Second, it began to identify specific visual attributes that appear to contribute to different judgments. Three experiments are reported. All used the stimuli and viewing time as before. Using a paradigm known to disrupt processing beyond the stimulus offset, Experiment 1 was designed to ensure that the previous findings could not be attributed to such continued processing. Adopting a within-subject design, Experiment 2 investigated the extent to which judgments differing in cognitive demands (visual appeal, perceived usability, trustworthiness) may be driven by the visual characteristics of a Web page. It also enabled analyses of visual attributes that contributed most to the different judgments. Experiment 3 replicated Experiment 2 but using a between-subject design to ensure that no practice effect could occur. The results suggest that all three types of judgments are largely driven by visual appeal, but that cognitively demanding judgments are processed in a qualitatively different manner than visual appeal, and that they rely on somewhat different visual attributes. A model accounting for the results is provided.
Improved measurements of intracellular nitric oxide in intact microvessels using 4,5-diaminofluorescein diacetate
Authors: Zhou Xueping , He Pingnian
Published: May 2011

4,5-Diaminofluorescein diacetate (DAF-2 DA) has been widely used for the measurement of nitric oxide (NO) in living cells and tissues. We previously established a method that demonstrated platelet activating factor (PAF)-induced endothelial NO production in intact venules using DAF-2 DA. In previous applications, the loading dye was removed from the extracellular space before NO measurements. However, in high permeability vessels, endothelial cells quickly released the accumulated intracellular DAF-2 after the washout, which compromises the NO measurement. The objective of this study was to investigate if the presence of DAF-2 DA during NO measurements could overcome the dye retention problem and enhance the sensitivity of NO detection. Experiments were conducted in individually perfused rat venules, and endothelial NO was measured using fluorescence imaging under basal and stimulated conditions with continuous perfusion of DAF-2 DA. Continuous dye perfusion was found to promote a relatively constant endothelial dye concentration in both normal and high permeability vessels throughout the experiment. With the use of this method, the basal and stimulated NO was quantified after endothelial DAF-2 concentrations reached a steady state. Our results showed enhanced sensitivity of detecting PAF-stimulated NO compared with a previous method. We also found that the hydrolyzed intracellular DAF-2, the precursor of DAF-2 triazole, contributed significantly to the measured fluorescence and that an appropriate subtraction of non-NO-dependent intracellular DAF-2 fluorescence is critical for the assessment of NO in living tissues. This method overcame the dye leakage problem, enhanced the sensitivity of NO detection, and improved NO quantification, demonstrating significant advantages over existing methodologies using DAF-2.
Thrombospondin-1 opens the paracellular pathway in pulmonary microvascular endothelia through EGFR/ErbB2 activation
Authors: Garg Pallavi , Yang Shiqi , Liu Anguo , Pallero Manuel A. , Buchsbaum Donald J. , Mosher Deane F. , Murphy-Ullrich Joanne E. , Goldblum Simeon E.
Published: April 2011

Thrombospondin-1 (TSP1) is a multidomain protein that contains epidermal growth factor (EGF)-like repeats that indirectly activate the EGF receptor (EGFR) and selected downstream signaling pathways. In these studies, we show that TSP1 opens the paracellular pathway in human lung microvascular endothelial cells (HMVEC-Ls) in a dose-, time-, and protein tyrosine kinase (PTK)-dependent manner. TSP1 increased tyrosine phosphorylation of proteins enriched to intercellular boundaries including the zonula adherens (ZA) proteins, vascular endothelial-cadherin, γ-catenin, and p120 catenin. In HMVEC-Ls, EGFR and ErbB2 are expressed at low levels, and both heterodimerize and tyrosine autophosphorylate in response to TSP1. Prior EGFR-selective PTK inhibition with AG1478 or ErbB2-selective PTK inhibition with AG825 protected against TSP1-induced tyrosine phosphorylation of ZA proteins and barrier disruption. Preincubation of HMVEC-Ls with an EGFR ectodomain-blocking antibody also prevented TSP1-induced opening of the paracellular pathway. Therefore, in HMVEC-Ls, TSP1 increases tyrosine phosphorylation of ZA proteins and opens the paracellular pathway, in part, through EGFR/ErbB2 activation. Surprisingly, recombinant TSP1 EGF-like repeats 1–3 and the high-affinity EGFR ligands, EGF, TGF-α, and amphiregulin, each failed to increase paracellular permeability. However, HMVEC-Ls in which EGFR was overexpressed became responsive to the EGF-like repeats of TSP1 as well as to EGF. These studies indicate that TSP1 disrupts the endothelial barrier through EGFR/ErbB2 activation although additional signals are necessary in cells with low receptor expression.
Transcriptional profiling reveals a role for RORα in regulating gene expression in obesity-associated inflammation and hepatic steatosis
Authors: Kang Hong Soon , Okamoto Kyoko , Takeda Yukimasa , Beak Ju Youn , Gerrish Kevin , Bortner Carl D. , DeGraff Laura M. , Wada Taira , Xie Wen , Jetten Anton M.
Published: May 2011

Retinoid-related orphan receptor (ROR)α4 is the major RORα isoform expressed in adipose tissues and liver. In this study we demonstrate that RORα-deficient staggerer mice (RORαsg/sg) fed with a high-fat diet (HFD) exhibited reduced adiposity and hepatic triglyceride levels compared with wild-type (WT) littermates and were resistant to the development of hepatic steatosis, adipose-associated inflammation, and insulin resistance. Gene expression profiling showed that many genes involved in triglyceride synthesis and storage, including Cidec, Cidea, and Mogat1, were expressed at much lower levels in liver of RORαsg/sg mice. In contrast, overexpression of RORα in mouse hepatoma Hepa1–6 cells significantly increased the expression of genes that were repressed in RORαsg/sg liver, including Sult1b1, Adfp, Cidea, and ApoA4. ChIP and promoter analysis suggested that several of these genes were regulated directly by RORα. In addition to reduced lipid accumulation, inflammation was greatly diminished in white adipose tissue (WAT) of RORαsg/sg mice fed with an HFD. The infiltration of macrophages and the expression of many immune response and proinflammatory genes, including those encoding various chemo/cytokines, Toll-like receptors, and TNF signaling proteins, were significantly reduced in RORαsg/sg WAT. Moreover, RORαsg/sg mice fed with an HFD were protected from the development of insulin resistance. RORαsg/sg mice consumed more oxygen and produced more carbon dioxide, suggesting increased energy expenditure in this genotype. Our study indicates that RORα plays a critical role in the regulation of several aspects of metabolic syndrome. Therefore, RORα may provide a novel therapeutic target in the management of obesity and associated metabolic diseases.
Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations
Authors: Olmos David , Martins Ana Sofia , Jones Robin L. , Alam Salma , Scurr Michelle , Judson Ian R.
Published: May 2011

Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, bothin vitroandin vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response.
Photoacoustic Method for Measurement of Thermal Effusivity of Fe3O4 Nanofluid
Authors: Raykar Vijay S. , Singh Ashok K.
Published: May 2011

Photoacoustic (PA) sensor was designed and developed to evaluate thermal effusivity of Fe3O4 nanofluid. The PA sensor is based on open cell mode (OPC) to measure acoustic signals from low concentration of nanoparticulate suspensions in ethylene glycol (EG). Spherical Fe3O4 nanoparticles (NPs) were obtained by chemical precipitation method in powder form. The obtained NPs were stabilized by acetylacetone (acac) in EG. Thermal conductivity estimation was carried out with the help of transient hot wire method. The developed PA sensor was calibrated by measuring thermal effusivity of standard samples. The acoustic signals of the PA experiments have been analyzed with a simple Rosencwaig‐Gersho theoretical model.
Complex Regional Pain Syndrome Revived by Epileptic Seizure Then Disappeared Soon during Treatment with Regional Intravenous Nerve Blockade: A Case Report
Authors: Sumitani Masahiko , Yozu Arito , Tomioka Toshiya , Miyauchi Satoru , Yamada Yoshitsugu
Published: May 2011

We present a case of complex regional pain syndrome (CRPS), in which symptoms, including burning pain and severe allodynia, were alleviated by using a regional intravenous nerve blockade (Bier block) combined with physiotherapy, but reappeared following an epileptic seizure. Symptoms disappeared again following control of epileptic discharges, as revealed by single-photon emission computed tomography (SPECT) and electroencephalography (EEG) results. Although systemic toxicity of a local anesthetic applied by Bier block was suspected as a cause of the first seizure, the patient did not present any other toxic symptoms, and seizures repeatedly occurred after Bier block cessation; the patient was then diagnosed as having temporal symptomatic epilepsy. This case suggests that symptoms of CRPS may be sustained by abnormal brain conditions, and our findings contribute to the understanding of how the central nervous system participates in maintaining pain and allodynia associated with CRPS.
Antihelminth Compound Niclosamide Downregulates Wnt Signaling and Elicits Antitumor Responses in Tumors with Activating APC Mutations
Authors: Osada Takuya , Chen Minyong , Yang Xiao Yi , Spasojevic Ivan , Vandeusen Jeffrey B. , Hsu David , Clary Bryan M. , Clay Timothy M. , Chen Wei , Morse Michael A. , Lyerly H. Kim
Published: April 2011

Wnt/β-catenin pathway activation caused by adenomatous polyposis coli (APC) mutations occurs in approximately 80% of sporadic colorectal cancers (CRC). The antihelminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevelled-2 (Dvl2) expression, resulting in diminished downstream β-catenin signaling. In this study, we determined whether niclosamide could inhibit the Wnt/β-catenin pathway in human CRCs and whether its inhibition might elicit antitumor effects in the presence of APC mutations. We found that niclosamide inhibited Wnt/β-catenin pathway activation, downregulated Dvl2, decreased downstream β-catenin signaling, and exerted antiproliferative effects in human colon cancer cell lines and CRC cells isolated by surgical resection of metastatic disease, regardless of mutations in APC. In contrast, inhibition of NF-κB or mTOR did not exert similar antiproliferative effects in these CRC model systems. In mice implanted with human CRC xenografts, orally administered niclosamide was well tolerated, achieved plasma and tumor levels associated with biologic activity, and led to tumor control. Our findings support clinical explorations to reposition niclosamide for the treatment of CRC. Cancer Res; 71(12); 4172–82. ©2011 AACR.
KLF4-Mediated Negative Regulation of IFITM3 Expression Plays a Critical Role in Colon Cancer Pathogenesis
Authors: Li Dawei , Peng Zhihai , Tang Huamei , Wei Ping , Kong Xiangyu , Yan Dongwang , Huang Fei , Li Qiang , Le Xiangdong , Li Qi , Xie Keping
Published: April 2011

Purpose: IFITM3, an IFN-inducible gene, is overexpressed in human colorectal cancer. In this study, we sought to determine the clinical significance and underlying mechanisms of its dysregulated expression in human colon tumor specimens and murine models of this disease.

Experimental Design: IFITM3 expression in a tissue microarray of tumor and matched normal colon tissue specimens and lymph node metastasis specimens obtained from 203 patients with colon cancer was measured immunohistochemically.

Results: IFITM3 was expressed at higher levels in colon tumors and, particularly, nodal metastases than in normal colon tissue. A Cox proportional hazards model showed that IFITM3 expression was an independent prognostic factor for disease-free survival in patients with colon cancer. Knockdown of IFITM3 expression by a specific siRNA significantly suppressed the proliferation, colony formation, migration, and invasion of colon cancer cells in vitro and tumor growth and metastasis in a xenograft model. Restored expression of KLF4, a putative tumor suppressor, downregulated IFITM3 expression in colon cancer cells in vitro. Two KLF4-binding sites in the IFITM3 promoter bound specifically to KLF4 protein in a chromatin immunoprecipitation assay and promoter mutagenesis analyses. Specific deletion of KLF4 led to IFITM3 overexpression in colon mucosa in Villin-Cre+;Klf4fl/fl mice. An inverse correlation between loss of KLF4 expression and IFITM3 overexpression was evident in human colon tumors.

Conclusion: These clinical and mechanistic findings indicate that IFITM3 is a direct transcriptional target of KLF4 and that dysregulated KLF4 expression leads to aberrant IFITM3 expression, thus contributing to colon cancer progression and metastasis. Clin Cancer Res; 17(11); 3558–68. ©2011 AACR.
Biological Function and Prognostic Significance of Peroxisome Proliferator-Activated Receptor δ in Rectal Cancer
Authors: Yang Lie , Zhang Hong , Zhou Zong-Guang , Yan Hui , Adell G , Sun Xiao-Feng
Published: April 2011

Purpose: To investigate the expression significance of PPAR β/δ in relation to radiotherapy (RT), clinicopathologic, and prognostic variables of rectal cancer patients.

Experimental Design: We included 141 primary rectal cancer patients who participated in a Swedish clinical trial of preoperative RT. Tissue microarray samples from the excised rectal cancers and the adjacent or distant normal mucosa and lymph node metastases were stained with PPAR δ antibody. Survival probability was computed by the Kaplan–Meier method and Cox regression model. The proliferation of colon cancer cell lines KM12C, KM12SM, and KM12L4a was assayed after PPAR δ knockdown.

Results: PPAR δ was increased from adjacent or distant normal mucosa to primary cancers, whereas it decreased from primary cancers to lymph node metastases. After RT, PPAR δ was increased in normal mucosa, whereas it decreased in primary cancers and lymph node metastases. In primary cancers, the high expression of PPAR δ was related to higher frequency of stage I cases, lower lymph node metastasis rate, and low expression of Ki-67 in the unirradiated cases, and related to favorable survival in the cases either with or without RT. The proliferation of the KM12C, KM12SM, or KM12L4a cells was significantly accelerated after PPAR δ knockdown.

Conclusions: RT decreases the PPAR δ expression in primary rectal cancers and lymph node metastases. PPAR δ is related to the early development of rectal cancer and inhibits the proliferation of colorectal cancer cells. Increase of PPAR δ predicts favorable survival in the rectal cancer patients either with or without preoperative RT. Clin Cancer Res; 17(11); 3760–70. ©2011 AACR.
Diastolic Blood Pressure as a Biomarker of Axitinib Efficacy in Solid Tumors
Authors: Rini Brian I. , Schiller Joan H. , Fruehauf John P. , Cohen Ezra E.W. , Tarazi Jamal C. , Rosbrook Brad , Bair Angel H. , Ricart Alejandro D. , Olszanski Anthony J. , Letrent Kristen J. , Kim Sinil , Rixe Olivier
Published: April 2011

Purpose: To evaluate if diastolic blood pressure (dBP) ≥90 mm Hg during axitinib treatment is a marker of efficacy.

Experimental Design: The relationship between dBP ≥90 mm Hg and efficacy was retrospectively explored across 5 phase II studies of single-agent axitinib for the treatment of 4 different tumor types. All patients had baseline BP ≤140/90 mm Hg and were stratified into 2 groups based on in-clinic BP measurements after initiating therapy: those with dBP <90 mm Hg throughout therapy and those with at least 1 dBP ≥90 mm Hg. Median overall survival (mOS), median progression-free survival (mPFS), objective response rate (ORR), and adverse events were evaluated by dBP group in individual and pooled analyses.

Results: Two-hundred thirty patients were evaluated. Patients with dBP ≥90 mm Hg had a significantly lower relative risk of death than those with dBP <90 mm Hg [adjusted HR (95% CI) = 0.55 (0.39, 0.77); P < 0.001]. The relative risk of progression was also lower in patients with dBP ≥90 mm Hg [HR (95% CI) = 0.76 (0.54, 1.06), P = 0.107], and ORR was significantly higher (43.9% vs. 12.0%; P < 0.001). In an 8-week landmark analysis, mOS (25.8 vs. 14.9 months) and mPFS (10.2 vs. 7.1 months) were greater for patients in the ≥90 mm Hg group. Adverse events were similar between groups.

Conclusions: Axitinib efficacy correlated with dBP ≥90 mm Hg. Further investigation of dBP as a predictive biomarker of efficacy in patients receiving axitinib is warranted. Clin Cancer Res; 17(11); 3841–9. ©2011 AACR.
The Addition of Bevacizumab to Standard Radiation Therapy and Temozolomide Followed by Bevacizumab, Temozolomide, and Irinotecan for Newly Diagnosed Glioblastoma
Authors: Vredenburgh James J. , Desjardins Annick , Reardon David A. , Peters Katherine B. , Herndon James E. , Marcello Jennifer , Kirkpatrick John P. , Sampson John H. , Bailey Leighann , Threatt Stevie , Friedman Allan H. , Bigner Darell D. , Friedman Henry S.
Published: April 2011

Purpose: To determine if the addition of bevacizumab to radiation therapy and temozolomide, followed by bevacizumab, temozolomide, and irinotecan, for newly diagnosed glioblastoma patients is safe and effective.

Experimental Design: A total of 75 patients with newly diagnosed glioblastoma were enrolled in the phase II trial that investigated the addition of bevacizumab to standard radiation therapy and daily temozolomide followed by the addition of bevacizumab and irinotecan to adjuvant temozolomide. The bevacizumab was given at 10 mg/kg every 14 days beginning a minimum of 4 weeks postcraniotomy. Two weeks after radiation therapy, the patients began 6 to 12 cycles of 5-day temozolomide with bevacizumab and irinotecan every 14 days. The primary endpoint was the proportion of patients alive 16 months after informed consent.

Results: The therapy had moderate toxicity. Three patients, one of whom had a grade 2 central nervous system hemorrhage, came off study during radiation therapy. Seventy patients started the postradiation therapy, and 16 (23%) terminated this adjuvant therapy early because of toxicity. The median overall survival was 21.2 months (95% CI: 17.2–25.4), and 65% of the patients were alive at 16 months (95% CI: 53.4–74.9). The median progression-free survival was 14.2 months (95% CI: 12–16).

Conclusion: The addition of bevacizumab to standard radiation therapy and temozolomide, followed by bevacizumab, irinotecan, and temozolomide, for the treatment of newly diagnosed glioblastoma has moderate toxicity and may improve efficacy compared with historical controls. The results from phase III trials are required before the role of bevacizumab for newly diagnosed glioblastoma is established. Clin Cancer Res; 17(12); 4119–24. ©2011 AACR.
An Intracranial Aneurysm and Dural Arteriovenous Fistula in a Newborn
Authors: Ko Andrew , Filardi Tanya , Giussani Carlo , Ghodke Raj , Browd Samuel R.
Published: May 2011

The authors present the case of a newborn with an intracerebral aneurysm and a dural arteriovenous fistula. The patient initially presented with intraventricular hemorrhage and hydrocephalus, with evidence of remote subarachnoid hemorrhage, left hemispheric stroke, and sagittal sinus thrombosis. He was treated with a ventriculoperitoneal shunt and subsequent staged endovascular obliteration of both the aneurysm and fistula. Interestingly, the aneurysm did not appear on an artery feeding the abnormal fistula. Intracerebral aneurysms in the neonatal population are rare, and dural arteriovenous fistulae even more so; we present a case of a 2-month-old infant with both, as well as a review of the literature concerning these rare vascular abnormalities.
Anaplastic Astroblastoma Presenting as Massive, Sudden-Onset, Intraparenchymal Hemorrhage
Authors: Johnson Karen A. , Bonnin Jose M. , Boaz Joel C. , Douglas-Akinwande Annette C. , Hattab Eyas M.
Published: May 2011

Astroblastoma is a rare primary glial tumor of children and young adults, typically located in the cerebral hemispheres and presenting as a well-circumscribed, nodular, often cystic enhancing mass. The existence of astroblastoma as a distinct clinicopathologic entity has long been debated but is recognized in the 2007 WHO classification of CNS tumors. The grading of these tumors remains unsettled. Currently, no grade has been established and there are no clearly defined diagnostic criteria for low- or high-grade tumors. Astroblastomas in general are thought to have a favorable outcome with low rates of recurrence following gross total resection. We report a case of astroblastoma with ‘high-grade/anaplastic’ histology in a 12-year-old, previously healthy girl. The patient experienced severe, sudden-onset headache, and quickly became comatose. Head CT showed a massive intraparenchymal hemorrhage in the right frontal lobe with surrounding edema. She underwent emergent posterior frontal craniotomy for decompression and hematoma evacuation. Pathologic examination revealed a sharply demarcated hemorrhagic heterogeneous glial tumor with focal papillary architecture, densely hyalinized blood vessels, and intensely GFAP-positive perivascular cells. The tumor showed unequivocal high-grade features including an elevated proliferative index. The diagnosis of anaplastic astroblastoma was rendered. The patient expired on postoperative day 30. This case illustrates the potential poor outcome of high-grade astroblastoma and highlights the morphologic heterogeneity of this rare neoplasm.
Clear Cell Meningioma of the Fourth Ventricle in a Child: A Case Report and Literature Review
Authors: Burgan O.T. , Bahl A. , Critcher V. , Zaki H.S. , McMullan P.J. , Sinha S.
Published: May 2011

Clear cell meningiomas are rare meningioma variants and are recognized as World Health Organization grade II tumours. They may be difficult to manage given their propensity to recur early especially if present in surgically challenging locations. We describe a rare case of a fourth ventricular clear cell meningioma without dural attachment in a 14-year-old boy with an unusual presentation of failure to thrive. The case is presented in detail and a review of the recent literature is discussed.
HER2 Evaluation and Its Impact on Breast Cancer Treatment Decisions
Authors: Goddard K.A.B. , Weinmann S. , Richert-Boe K. , Chen C. , Bulkley J. , Wax C.
Published: May 2011

Background: Eighteen to twenty percent of breast cancer tumors show abnormal amplification of the Human Epidermal growth factor Receptor 2 (HER2) gene and increased expression of the associated protein. HER2 amplification is associated with rapid tumor proliferation and shorter disease-free and overall survival. Because women with HER2 amplification are more likely to benefit from treatment with the drug trastuzumab, testing for HER2 is recommended to guide therapy. However, little is known about use of HER2 testing in real-world settings. This study examined uptake, use, appropriateness of HER2 testing, and the relationship between HER2 test results and treatment decisions. Methods: We assessed electronic data from 3,634 patients with invasive breast cancer diagnosed from 1998 to 2007 in a large integrated health system. We collected data on patient and tumor characteristics, HER2 testing status, test results, and trastuzumab treatment. Results:From 1998 to 2000, the percent of patients who underwent HER2 evaluation increased from 12 to 94%; <3% of women with ductal carcinoma in situ, for whom HER2 testing is not recommended, were tested. Trastuzumab use increased 5-fold after 2004, when guidelines expanded to include recommending adjuvant treatment for early-stage breast cancer in addition to metastatic treatment. Ninety-five percent of women receiving trastuzumab had a positive HER2 result. After 2004, 55% of women with invasive breast cancer and overexpression of HER2 received trastuzumab treatment; this ranged from 44% of women with localized breast cancer to 80% of women with distant metastatic disease. Conclusions:These findings illustrate appropriate and effective implementation of a HER2 testing strategy in a managed care setting.
X-Ray Magnetic Resonance Fusion to Internal Markers and Utility in Congenital Heart Disease Catheterization
Authors: Dori Yoav , Sarmiento Marily , Glatz Andrew C. , Gillespie Matthew J. , Jones Virginia M. , Harris Matthew A. , Whitehead Kevin K. , Fogel Mark A. , Rome Jonathan J.
Published: May 2011

Background—

X-ray magnetic resonance fusion (XMRF) allows for use of 3D data during cardiac catheterization. However, to date, technical requirements have limited the use of this modality in clinical practice. We report on a new internal-marker XMRF method that we have developed and describe how we used XMRF during cardiac catheterization in congenital heart disease.

Methods and Results—

XMRF was performed in a phantom and in 23 patients presenting for cardiac catheterization who also needed cardiac MRI for clinical reasons. The registration process was performed in <5 minutes per patient, with minimal radiation (0.004 to 0.024 mSv) and without contrast. Registration error was calculated in a phantom and in 8 patients using the maximum distance between angiographic and 3D model boundaries. In the phantom, the measured error in the anteroposterior projection had a mean of 1.15 mm (standard deviation, 0.73). The measured error in patients had a median of 2.15 mm (interquartile range, 1.65 to 2.56 mm). Internal markers included bones, airway, image artifact, calcifications, and the heart and vessel borders. The MRI data were used for road mapping in 17 of 23 (74%) cases and camera angle selection in 11 of 23 (48%) cases.

Conclusions—

Internal marker–based registration can be performed quickly, with minimal radiation, without the need for contrast, and with clinically acceptable accuracy using commercially available software. We have also demonstrated several potential uses for XMRF in routine clinical practice. This modality has the potential to reduce radiation exposure and improve catheterization outcomes.
Plasma B-Type Natriuretic Peptide Levels and Recurrent Arrhythmia After Successful Ablation of Lone Atrial Fibrillation
Authors: Hussein Ayman A. , Saliba Walid I. , Martin David O. , Shadman Mazyar , Kanj Mohamed , Bhargava Mandeep , Dresing Thomas , Chung Mina , Callahan Thomas , Baranowski Bryan , Tchou Patrick , Lindsay Bruce D. , Natale Andrea , Wazni Oussama M.
Published: May 2011

Background—

Plasma B-type natriuretic peptide (BNP) is abnormally elevated in patients with lone atrial fibrillation (AF). The exact significance and prognostic implications of this elevation have yet to be determined. Little is known about BNP in lone AF patients undergoing arrhythmia ablation. We sought to determine the relationship between BNP levels and the risk of recurrent arrhythmia after ablation of lone AF.

Methods and Results—

We followed up 726 patients with lone AF undergoing first-time arrhythmia ablation. All had BNP levels measured on the day of ablation with of the point-of-care Triage Meter assay (Biosite Diagnostics, San Diego, CA). At baseline, factors associated with elevated BNP levels in multivariable linear regression analysis (with log BNP being the dependent variable) were older age (β regression coefficient for +1-year change, 0.025;
P
<0.0001), longer duration of AF (β for +1-year change, 0.031;
P
=0.01), nonparoxysmal AF (versus paroxysmal; β, 0.52;
P
<0.0001), and larger left atrial size (β for +1-cm
2
change, 0.040;
P
<0.0001). The BNP levels were strongly associated with arrhythmia recurrence in univariate- (hazard ratio for +1-log-BNP change, 2.32; 95% confidence interval, 2.11 to 2.74;
P
<0.001) and covariate- (hazard ratio for +1-log-BNP change, 2.13; 95% confidence interval, 2.06 to 2.38;
P
<0.001) adjusted Cox proportional hazards analysis. The covariate-adjusted hazard ratios for recurrent arrhythmia were 1.6, 2.7, 4.3, and 5.7 for the second, third, fourth, and fifth quintiles, respectively, compared with patients in the lowest quintile (
P
for trend across quintiles <0.001).

Conclusions—

B-type natriuretic peptide levels correlate with AF burden (chronicity, altered hemodynamics, and anatomic remodeling) in patients with lone AF and are strong predictors of recurrent arrhythmia after ablation. Elevated BNP levels may reflect increased cardiac chamber wall stress and/or intrinsic atrial disease, thus increasing the risk of arrhythmia recurrence.
Atrial Fibrillation and Death After Myocardial Infarction
Authors: Jabre Patricia , Jouven Xavier , Adnet Frédéric , Thabut Gabriel , Bielinski Suzette J. , Weston Susan A. , Roger Véronique L.
Published: May 2011

Background—

Atrial fibrillation (AF) often coexists with myocardial infarction (MI), yet its prognostic influence is disputed. Prior reports studied the relationship of AF during early hospitalization for acute MI to the risk of death and could not address the timing of AF in relation to the MI (ie, before, during, after). Furthermore, as data come mostly from clinical trials, their applicability to the community is uncertain. The aims of our study were to assess the occurrence of AF among MI patients, determine whether it has changed over time, and quantify its impact and the impact of its timing on mortality after MI.

Methods and Results—

This was a community-based cohort of 3220 patients hospitalized with incident (first-ever) MI from 1983 to 2007 in Olmsted County, MN. Atrial fibrillation was identified by diagnostic codes and ECG. Outcomes were all-cause and cardiovascular death. Atrial fibrillation before MI was identified in 304 patients, and 729 developed AF after MI (218 [30%] within 2 days, 119 [16%] between 3 and 30 days, and 392 [54%] >30 days post-MI). The cumulative incidence of AF after MI at 5 years was 19% and did not change over the calendar year of MI (the incidence of AF was the same regardless of when the MI occurred). During a mean follow-up of 6.6 years, 1638 deaths occurred. AF was associated with an increased risk of death (hazard ratio [95% confidence interval] 3.77 [3.37 to 4.21]), independently of clinical characteristics at the time of MI and heart failure. This risk differed markedly according to the timing of AF, and was the greatest for AF occurring >30 days post MI (hazard ratio [95% confidence interval] 1.63 [1.37 to 1.93] for AF within 2 days, 1.81 [0.45 to 2.27] for AF between 3 and 30 days, and 2.58 [2.21 to 3.00] for AF >30 days post MI).

Conclusions—

In the community, AF is frequent in the setting of MI. Atrial fibrillation carries an excess risk of death, which is the highest for AF developing >30 days after MI.
Activation of Estrogen Receptor-α and of Angiotensin-Converting Enzyme 2 Suppresses Ischemic Brain Damage in Oophorectomized Rats
Authors: Shimada Kenji , Kitazato Keiko T. , Kinouchi Tomoya , Yagi Kenji , Tada Yoshiteru , Satomi Junichiro , Kageji Teruyoshi , Nagahiro Shinji
Published: May 2011

Like the angiotensin II type 1 receptor blocker, endogenous estrogen (17β-estradiol) is neuroprotective against cerebral ischemia; its effects are thought to be mediated by estrogen receptors (ERs). To verify the role of ERs and the brain renin-angiotensin system in estrogen-deficient rats with ischemia induced by middle cerebral artery occlusion, we compared rats subjected to oophorectomy (OVX
+
) with sham-oophorectomized rats (OVX
−
) and OVX
+
rats treated with 0.3 or 3.0 mg/kg of olmesartan for 2 weeks before middle cerebral artery occlusion. Independent of the blood pressure, the cortical infarct volume was larger in OVX
+
than in OVX
−
rats. It was smaller in olmesartan-pretreated OVX
+
rats. The expression of ERα in the peri-infarct region was correlated with the reduction of cortical infarct but not that of ERβ or G protein–coupled estrogen receptor. Olmesartan prevented ERα downregulation in the cortical peri-infarct area, without affecting ERβ or G protein–coupled estrogen receptor. Olmesartan also increased mRNA expression of angiotensin-converting enzyme 2, Bcl-2, and Bcl-xL and reduced angiotensin II and cleaved caspase 3. These effects were augmented by olmesartan and abolished by the ER inhibitor. In OVX
+
rats treated with the ERα agonist alone, the infarct size was decreased, and the neuroprotective genes were upregulated. These findings suggest that the transactivation of neuroprotective genes and the reduction in brain angiotensin II are ERα dependent and that this may augment neuroprotection together with an angiotensin II type 1 receptor blockade by olmesartan. We present the new insight that the activation of ERα independent of estrogen contributes at least partly to limiting cerebral ischemic damage.
The Art of Finance: An Artist Uses Financial Economics as Inspiration
Authors: Schinckus Christophe
Published: May 2011

This article focuses on the possibility of developing an “art of science” in the literal sense of the words—that is, art illustrating scientific theories. In this perspective, scientific knowledge is used for itself, independent of the reality it is supposed to represent (even if this knowledge does not directly involve a pictorial dimension). Using a specific theory originating from financial economics, the author illustrates his analysis using two of his own collages.
Tell Them Anything but the Truth: They Will Find Their Own. How We Visualized the Map of the Future with Respect to the Audience of Our Story
Authors: Graffieti Michele , Scagnetti Gaia , Ricci Donato , Masud Luca , Porpora Mario
Published: May 2011

This paper is part of a research project about the visualization of complex systems. More specifically, it focuses on the emerging need for a narrative approach in the understanding of complex networks.
Comparative Studies of Policy Dynamics
Authors: Baumgartner Frank R. , Jones Bryan D. , Wilkerson John
Published: April 2011

Major new understandings of policy change are emerging from a program to measure attention to policies across nations using the same instrument. Participants in this special issue have created new indicators of government activities in 11 countries over several decades. Each database is comprehensive in that it includes information about every activity of its type (e.g., laws, bills, parliamentary questions, prime ministerial speeches) for the time period covered, typically several decades. These databases are linked by a common policy topic classification system, which allows new types of analyses of public policy dynamics over time. The authors introduce the theoretical and practical questions addressed in the volume, explain the nature of the work completed, and suggest some of the ways that this new infrastructure may allow new types of comparative analyses of public policy, institutions, and outcomes. In particular, the authors challenge political scientists to incorporate policy variability into their analyses and to move far beyond the search for partisan and electoral explanations of policy change.
Comparing Government Agendas
Authors: Mortensen Peter Bjerre , Green-Pedersen Christoffer , Breeman Gerard , Chaqués-Bonafont Laura , Jennings Will , John Peter , Palau Anna M. , Timmermans Arco
Published: April 2011

At the beginning of each parliamentary session, almost all European governments give a speech in which they present the government’s policy priorities and legislative agenda for the year ahead. Despite the body of literature on governments in European parliamentary democracies, systematic research on these executive policy agendas is surprisingly limited. In this article the authors study the executive policy agendas—measured through the policy content of annual government speeches—over the past 50 years in three Western European countries: the United Kingdom, the Netherlands, and Denmark. Contrary to the expectations derived from the well-established “politics matters” approach, the analyses show that elections and change in partisan color have little effect on the executive issue agendas, except to a limited extent for the United Kingdom. In contrast, the authors demonstrate empirically how the policy agenda of governments responds to changes in public problems, and this affects how political parties define these problems as political issues. In other words, policy responsibility that follows from having government power seems much more important for governments’ issue agendas than the partisan and institutional characteristics of governments.
Revisiting the Impact of Participative Decision Making on Public Employee Retention
Authors: Grissom Jason A.
Published: April 2011

A large body of management research has linked participation by employees in organizational decision making to employee-level outcomes such as job satisfaction, with nearly all studies finding positive associations. This study questions whether the impact of employee policy influence on employee-level outcomes is contingent on management effectiveness, hypothesizing that employee outcomes may be negatively affected by the exercise of influence if participation is facilitated poorly or comes in response to a void created by inadequate organizational management. Focusing specifically on employee turnover in a nationwide sample of 6,300 public schools, the study finds strong evidence of an interactive effect. While employees are less likely to turn over under effective managers regardless of their degree of organizational policy influence, under ineffective managers turnover increases as employees’ perceived influence increases. Results suggest that investment in management competence may be a necessary precondition for some public organizations to benefit from increasing participation.