bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Effectiveness and Safety of Acupuncture in the Treatment of Irradiation-Induced Xerostomia in Patients with Head and Neck Cancer: A Systematic Review
Authors: O'Sullivan E M , Higginson I J
Published: November 2010

Background

Irradiation-induced xerostomia seriously reduces quality of life for patients with head and neck cancer (HNC). Anecdotal evidence suggests that acupuncture may be beneficial.

Objective

To systematically review evidence on clinical effectiveness and safety of acupuncture in irradiation-induced xerostomia in patients with HNC.

Methods

A detailed search was performed to identify randomised controlled trials (RCTs) and systematic reviews of RCTs on acupuncture in irradiation-induced xerostomia, using AMED, BNIA, CINAHL, Cochrane, Embase, HPSI, PsycInfo and Medline. Grey literature was explored and 11 journals hand searched. Search terms included: acupuncture, xerostomia, salivary hypofunction, hyposalivation, dry mouth, radiotherapy, irradiation, brachytherapy, external beam. Two authors independently extracted data for analysis using predefined selection criteria and quality indicators.

Results

43 of the 61 articles identified were excluded on title/abstract. 18 articles underwent full-text review; three were deemed eligible for inclusion. Two trials had moderate risk of bias; one had high risk. Two trials compared acupuncture with sham acupuncture; one control arm received ‘usual care’. Outcome measurements included salivary flow rates (SFRs) in two trials and subjective questionnaires in three. All three trials reported significant reduction in xerostomia versus baseline SFR (p<0.05); one reported greater effect in the intervention group for stimulated SFR (p<0.01). Subjective assessment reported significant differences between real acupuncture and control in two trials (p<0.02–0.05). Insufficient evidence was presented to undertake risk/benefit assessment.

Conclusions

Limited evidence suggests that acupuncture is beneficial for irradiation-induced xerostomia. Although current evidence is insufficient to recommend this intervention, it is sufficient to justify further studies. Highlighted methodological limitations must be dealt with.
CHUA'S SINGULARITIES: GREAT MIRACLE IN CIRCUIT THEORY
Authors: ŠPÁNY VIKTOR , GALAJDA PAVOL , GUZAN MILAN , PIVKA LADISLAV , OLEJÁR MARTIN
Published: November 2010

In the work [Chua, 1992], a deep intuition of its author gave rise to the choice of singularities corresponding to Chua's circuit. Therefore, it is the only one probably exhibiting three saddle points named Chua's singularities in this paper. One of the singularities is a saddle in forward time (dt > 0) of integration, whereas the other two are saddles in backward time (dt < 0) of integration. In the following, the term Chua's Chaos denotes chaos related to Chua's singularities. These singularities are the source of all special surfaces that are the subject of this contribution.

We named the surface to which all other surfaces are bound as the Double-Arm Stable Manifold (DASM). The beauty and multifunctionality of this surface represents the unfathomable Intelligence in the sense of [Tolle, 2003]. The presence of the DASM in the state space is a sufficient condition for the generation of Chua's chaos or corresponding periodic windows.

Since Chua's singularities are not limited by circuit morphology or the order of state equations, the research on Chua's chaos seems to be still very promising.
MLC CIRCUIT IN THE FRAME OF CNN
Authors: GÜNAY ENIS
Published: November 2010

A CNN-based nonautonomous chaotic oscillator circuit design is presented. Murali–Lakshmanan–Chua circuit, known as MLC circuit, is modeled by using CNN cells. The circuit implementation is supported by an eigenvalue study of the introduced system. The proposed model gives an alternative to MLC circuit with inductorless RC-based circuit realization.
INVARIANT TORI FULFILLED BY PERIODIC ORBITS FOR FOUR-DIMENSIONAL $\mathcal{C}^2$ DIFFERENTIAL SYSTEMS IN THE PRESENCE OF RESONANCE
Authors: LLIBRE JAUME , MEREU ANA CRISTINA , TEIXEIRA MARCO A.
Published: November 2010

We provide an algorithm for studying invariant tori fulfilled by periodic orbits of a perturbed system which emerge from the set of periodic orbits of an unperturbed linear system in p : q resonance. We illustrate the algorithm with an application.
POINCARÉ'S FORGOTTEN CONFERENCES ON WIRELESS TELEGRAPHY
Authors: GINOUX JEAN-MARC , PETITGIRARD LOIC
Published: November 2010

At the beginning of the twentieth century while Henri Poincaré (1854–1912) was already deeply involved in the developments of wireless telegraphy, he was invited, in 1908, to give a series of lectures at the École Supérieure des Postes et Télégraphes (today Sup'Télecom). In the last part of his presentation, he established that the necessary condition for the existence of a stable regime of maintained oscillations in a device of radio engineering completely analogous to the triode is the presence in the phase plane of stable limit cycle. The aim of this work is to prove that the correspondence highlighted by Andronov between the periodic solution of a nonlinear second-order differential equation and Poincaré's concept of limit cycle has been carried out by Poincaré himself, 20 years ago in some forgotten conferences of 1908.
STRUCTURAL, OPTICAL AND GAS SENSING PROPERTIES OF ZnO, SnO2 AND ZTO NANOSTRUCTURES
Authors: FOUAD O. A. , GLASPELL G. , EL-SHALL M. S.
Published: November 2010

Tetrapods, nanobelts and polyhedron-shape like zinc oxide (ZnO) , tin dioxide (SnO2) nanostructures and ZnO/ZnSnO3/Zn2SnO4 (ZTO) composite functional semiconducting nanostructures have been synthesized successfully by the vapor–solid growth process. XRD analyses showed that ZnO with wurtzite, SnO2 with rutile and zinc stannate (ZnSnO3) and/or dizinc stannate (Zn2SnO4) with polyhedral crystal structure were condensed from the vapor phase when Zn and/or Sn metal powders individually or mixed were used as the starting materials. The driving forces for growth of these nanostructures were found to be vapor density, temperature, pressure and place of deposition from the source materials. Typically, the ZnO nanobelts have lengths of several hundred of nanometers and widths of about 10–15 nm. The average particle size of SnO2 are in the range of about 10–20 nm. Uniform hexagonal-shaped crystals of ZnO/ZnSnO3/Zn2SnO4 composite in the range of 50–300 nm as estimated from TEM images are observed. Based on the TEM, optical absorption and emission studies and the CO gas sensing characteristics of the prepared materials showed good crystal quality implying that the ZnO , SnO2 and ZnO/ZnSnO3/Zn2SnO4 nanostructures may suggest possible applications in optoelectronic devices and chemical gas sensors.
Asymmetric Temporal Integration of Layer 4 and Layer 2/3 Inputs in Visual Cortex
Authors: Hang Giao B. , Dan Yang
Published: November 2010

Neocortical neurons in vivo receive concurrent synaptic inputs from multiple sources, including feedforward, horizontal, and feedback pathways. Layer 2/3 of the visual cortex receives feedforward input from layer 4 and horizontal input from layer 2/3. Firing of the pyramidal neurons, which carries the output to higher cortical areas, depends critically on the interaction of these pathways. Here we examined synaptic integration of inputs from layer 4 and layer 2/3 in rat visual cortical slices. We found that the integration is sublinear and temporally asymmetric, with larger responses if layer 2/3 input preceded layer 4 input. The sublinearity depended on inhibition, and the asymmetry was largely attributable to the difference between the two inhibitory inputs. Interestingly, the asymmetric integration was specific to pyramidal neurons, and it strongly affected their spiking output. Thus via cortical inhibition, the temporal order of activation of layer 2/3 and layer 4 pathways can exert powerful control of cortical output during visual processing.
In Vivo Mapping of Microstructural Somatotopies in the Human Corticospinal Pathways
Authors: Verstynen Timothy , Jarbo Kevin , Pathak Sudhir , Schneider Walter
Published: November 2010

The human corticospinal pathway is organized in a body-centric (i.e., somatotopic) manner that begins in cortical cell bodies and is maintained in the axons as they project through the midbrain on their way to spinal motor neurons. The subcortical segment of this somatotopy has been described using histological methods on non-human primates but only coarsely validated from lesion studies in human patient populations. Using high definition fiber tracking (HDFT) techniques, we set out to provide the first in vivo quantitative description of the midbrain somatotopy of corticospinal fibers in humans. Multi-shell diffusion imaging and deterministic fiber tracking were used to map white matter bundles that originate in the neocortex, navigate complex fiber crossings, and project through the midbrain. These fiber bundles were segmented into premotor (dorsal premotor, ventral premotor, and supplementary motor area) and primary motor sections based on the cortical origin of each fiber streamline. With HDFT, we were able to reveal several unique corticospinal patterns, including the cortical origins of ventral premotor fibers and small (∼1–2 mm) shifts in the midbrain location of premotor versus primary motor cortex fibers. More importantly, within the relatively small diameter of the pyramidal tracts (∼5 mm), we were able to map and quantify the direction of the corticospinal somatotopy. These results show how an HDFT approach to white matter mapping provides the first in vivo, quantitative mapping of subcortical corticospinal topographies at resolutions previously only available with postmortem histological techniques.
New Insights in the Management of Antipsychotics in the Treatment of Schizophrenia in a Patient with Prolactinoma: A Case Report and Review of the Literature
Authors: Santos Andrade Elvis Henrique , Pan Pedro Mario , da Silva Paula F. Ramalho , Gadelha Ary
Published: November 2010

Prolactinomas are the commonest pituitary adenomas and the major pathological cause of hyperprolactinaemia. Symptomatic prolactinomas are treated mainly by dopamine agonists; surgery and radiotherapy are options for nonresponders. Schizophrenia treatment is based on antipsychotics, which acts mainly at serotonergic and dopaminergic systems. We report a case of a 39-year-old schizophrenic male patient that was diagnosed with a macroprolactinoma 8 years after his first psychotic episode. The association of Schizophrenia and prolactinoma represents a clinical challenge once the treatment of one disease can exacerbate the symptoms of the other.
Critical Roles of DMP1 in Human Epidermal Growth Factor Receptor 2/neu-Arf-p53 Signaling and Breast Cancer Development
Authors: Taneja Pankaj , Maglic Dejan , Kai Fumitake , Sugiyama Takayuki , Kendig Robert D. , Frazier Donna P. , Willingham Mark C. , Inoue Kazushi
Published: November 2010

Human epidermal growth factor receptor 2 (HER2) overexpression stimulates cell growth in p53-mutated cells while it inhibits cell proliferation in those with wild-type p53, but the molecular mechanism is unknown. The Dmp1 promoter was activated by HER2/neu through the phosphatidylinositol-3′-kinase-Akt-NF-κB pathway, which in turn stimulated Arf transcription. Binding of p65 and p52 subunits of NF-κB was shown to the Dmp1 promoter and that of Dmp1 to the Arf promoter on HER2/neu overexpression. Both Dmp1 and p53 were induced in premalignant lesions from mouse mammary tumor virus-neu mice, and mammary tumorigenesis was significantly accelerated in both Dmp1+/− and Dmp1−/− mice. Selective deletion of Dmp1 and/or overexpression of Tbx2/Pokemon was found in >50% of wild-type HER2/neu carcinomas, although the involvement of Arf, Mdm2, or p53 was rare. Tumors from Dmp1+/−, Dmp1−/−, and wild-type neu mice with hemizygous Dmp1 deletion showed significant downregulation of Arf and p21Cip1/WAF1, showing p53 inactivity and more aggressive phenotypes than tumors without Dmp1 deletion. Notably, endogenous hDMP1 mRNA decreased when HER2 was depleted in human breast cancer cells. Our study shows the pivotal roles of Dmp1 in HER2/neu-p53 signaling and breast carcinogenesis. Cancer Res; 70(22); 9084–94. ©2010 AACR.
Intrinsic Cooperation between p16INK4a and p21Waf1/Cip1 in the Onset of Cellular Senescence and Tumor Suppression In vivo
Authors: Takeuchi Shinji , Takahashi Akiko , Motoi Noriko , Yoshimoto Shin , Tajima Tomoko , Yamakoshi Kimi , Hirao Atsushi , Yanagi Shigeru , Fukami Kiyoko , Ishikawa Yuichi , Sone Saburo , Hara Eiji , Ohtani Naoko
Published: November 2010

Although the p16INK4a and p21Waf1/Cip1 cyclin-dependent kinase (CDK) inhibitors are known to play key roles in cellular senescence in vitro, their roles in senescence remain rather poorly understood in vivo. This situation is partly due to the possibility of compensatory effect(s) between p16INK4a and p21Waf1/Cip1 or to the upregulation of functionally related CDK inhibitors. To directly address the cooperative roles of p16INK4a and p21Waf1/Cip1 in senescence in vivo, we generated a mouse line simply lacking both p16INK4a and p21Waf1/Cip1 genes [double-knockout (DKO)]. Mouse embryonic fibroblasts (MEF) derived from DKO mice displayed no evidence of cellular senescence when cultured serially in vitro. Moreover, DKO MEFs readily escaped Ras-induced senescence and overrode contact inhibition in culture. This was not the case in MEFs lacking either p16INK4a or p21Waf1/Cip1, indicating that p16INK4a and p21Waf1/Cip1 play cooperative roles in cellular senescence and contact inhibition in vitro. Notably, we found the DKO mice to be extremely susceptible to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate–induced skin carcinogenesis that involves oncogenic mutation of the H-ras gene. Mechanistic investigations suggested that the high incidence of cancer in DKO mice likely reflected a cooperative effect of increased benign skin tumor formation caused by p21Waf1/Cip1 loss, with increased malignant conversion of benign skin tumors caused by p16INK4a loss. Our findings establish an intrinsic cooperation between p16INK4a and p21Waf1/Cip1 in the onset of cellular senescence and tumor suppression in vivo. Cancer Res; 70(22); 9381–90. ©2010 AACR.
Induction of DNA Damage-Inducible Gene GADD45β Contributes to Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma Cells
Authors: Ou Da-Liang , Shen Ying-Chun , Yu Sung-Liang , Chen Kuen-Feng , Yeh Pei-Yen , Fan Hsiang-Hsuan , Feng Wen-Chi , Wang Ching-Tzu , Lin Liang-In , Hsu Chiun , Cheng Ann-Lii
Published: November 2010

Markers that could accurately predict responses to the general kinase inhibitor sorafenib are needed to better leverage its clinical applications. In this study, we examined a hypothesized role in the drug response for the growth arrest DNA damage-inducible gene 45β (GADD45β), which is commonly underexpressed in hepatocellular carcinoma (HCC) where sorafenib may offer an important new therapeutic option. The anticancer activity of sorafenib-induced GADD45β expression was tested in a panel of HCC cell lines and xenograft models. We found that GADD45β mRNA and protein expression were induced relatively more prominently in HCC cells that were biologically sensitive to sorafenib treatment. GADD45β induction was not found after treatment with either the mitogen-activated protein kinase–extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 or the Raf inhibitor ZM336372, suggesting that GADD45β induction by sorafenib was independent of Raf/MEK/ERK signaling activity. However, c-Jun NH2-terminal kinase (JNK) kinase activation occurred preferentially in sorafenib-sensitive cells. Small interfering RNA–mediated knockdown of GADD45βor JNK kinase limited the proapoptotic effects of sorafenib in sorafenib-sensitive cells. We defined the −339/−267 region in the GADD45β promoter containing activator protein-1 and SP1-binding sites as a crucial region for GADD45β induction by sorafenib. Together, our findings suggest that GADD45β induction contributes to sorafenib-induced apoptosis in HCC cells, prompting further studies to validate its potential value in predicting sorafenib efficacy. Cancer Res; 70(22); 9309–18. ©2010 AACR.
PET Imaging of Tumor Neovascularization in a Transgenic Mouse Model with a Novel 64Cu-DOTA-Knottin Peptide
Authors: Nielsen Carsten H. , Kimura Richard H. , Withofs Nadia , Tran Phuoc T. , Miao Zheng , Cochran Jennifer R. , Cheng Zhen , Felsher Dean , Kjær Andreas , Willmann Juergen K. , Gambhir Sanjiv S.
Published: November 2010

Due to the high mortality of lung cancer, there is a critical need to develop diagnostic procedures enabling early detection of the disease while at a curable stage. Targeted molecular imaging builds on the positive attributes of positron emission tomography/computed tomography (PET/CT) to allow for a noninvasive detection and characterization of smaller lung nodules, thus increasing the chances of positive treatment outcome. In this study, we investigate the ability to characterize lung tumors that spontaneously arise in a transgenic mouse model. The tumors are first identified with small animal CT followed by characterization with the use of small animal PET with a novel 64Cu–1,4,7,10-tetra-azacylododecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA)–knottin peptide that targets integrins upregulated during angiogenesis on the tumor associated neovasculature. The imaging results obtained with the knottin peptide are compared with standard 18F-fluorodeoxyglucose (FDG) PET small animal imaging. Lung nodules as small as 3 mm in diameter were successfully identified in the transgenic mice by small animal CT, and both 64Cu-DOTA-knottin 2.5F and FDG were able to differentiate lung nodules from the surrounding tissues. Uptake and retention of the 64Cu-DOTA-knottin 2.5F tracer in the lung tumors combined with a low background in the thorax resulted in a statistically higher tumor to background (normal lung) ratio compared with FDG (6.01 ± 0.61 versus 4.36 ± 0.68; P < 0.05). Ex vivo biodistribution showed 64Cu-DOTA-knottin 2.5F to have a fast renal clearance combined with low nonspecific accumulation in the thorax. Collectively, these results show 64Cu-DOTA-knottin 2.5F to be a promising candidate for clinical translation for earlier detection and improved characterization of lung cancer. Cancer Res; 70(22); 9022–30. ©2010 AACR.
MicroRNA miR-302 Inhibits the Tumorigenecity of Human Pluripotent Stem Cells by Coordinate Suppression of the CDK2 and CDK4/6 Cell Cycle Pathways
Authors: Lin Shi-Lung , Chang Donald C. , Ying Shao-Yao , Leu Davey , Wu David T.S.
Published: November 2010

miR-302 is the major microRNA found in human embryonic stem cells and induced pluripotent stem cells, but its function has been unclear. In mice, there is evidence that miR-302 may silence p21Cip1 (CDKN1A) to promote cell proliferation, whereas studies in human reprogrammed pluripotent stem cells suggested that elevated miR-302 expression inhibited cell cycle transit. Here, we clarify this difference, reporting that in human cells, miR-302 simultaneously suppressed both the cyclin E-CDK2 and cyclin D-CDK4/6 pathways to block >70% of the G1-S cell cycle transition. Concurrent silencing of BMI-1, a cancer stem cell marker targeted by miR-302, further promoted tumor suppressor functions of p16Ink4a and p14/p19Arf directed against CDK4/6–mediated cell proliferation. Among all G1 phase checkpoint regulators, human p21Cip1 was found not to be a valid target of miR-302. Overall, our findings indicate that miR-302 inhibits human pluripotent stem cell tumorigenicity by enhancing multiple G1 phase arrest pathways rather than by silencing p21Cip1. Cancer Res; 70(22); 9473–82. ©2010 AACR.
Combined Analysis of Estrogen Receptor β-1 and Progesterone Receptor Expression Identifies Lung Cancer Patients with Poor Outcome
Authors: Stabile Laura P. , Dacic Sanja , Land Stephanie R. , Lenzner Diana E. , Dhir Rajiv , Acquafondata Marie , Landreneau Rodney J. , Grandis Jennifer R. , Siegfried Jill M.
Published: November 2010

Purpose: Steroid hormones and growth factors affect lung cancer, and it is possible they act in concert to influence patient outcome.

Experimental Design: Primary lung tumors and normal lung tissue were analyzed for expression and localization of estrogen receptor α and β-1 (ERα and ERβ), aromatase, progesterone receptor (PR), and epidermal growth factor receptor (EGFR).

Results: Tumors expressed higher levels of ERβ compared to matched normal lung, whereas the reverse was true of PR. High cytoplasmic ERβ expression was identified as an independent negative prognostic predictor of overall survival (OS; HR = 1.67), and low total PR was identified as an independent negative predictor of time to progression (TTP; HR = 1.59). After adjusting for stage, age, sex, and smoking, combined high cytoplasmic ERβ and low total PR showed enhanced effects on OS (HR = 2.64) and on TTP (HR = 6.02). Further effects on OS were observed when EGFR expression was included (HR = 5.32). Patients with low cytoplasmic ERβ, low aromatase, low EGFR, and high total PR had shorter OS than patients with the opposite pattern (HR = 6.60). Contribution of these markers to survival showed no significant sex differences in a multivariable model. ERα was elevated in tumors but was not predictive of survival, and appears to represent a variant ERα protein that is only recognized by a C-terminal antibody.

Conclusions: Hormonal and EGFR pathways together may contribute to lung cancer prognosis. Lung tumors with high ERβ-1/low PR may define patients with aggressive biology. A validation study is necessary to fully assess the predictive value of these markers. Clin Cancer Res; 17(1); 154–64. ©2010 AACR.
Phase III Clinical Trial Development: A Process of Chutes and Ladders
Authors: Dilts David M. , Cheng Steven K. , Crites Joshua S. , Sandler Alan B. , Doroshow James H.
Published: November 2010

Purpose: The Institute of Medicine report on cooperative groups and the National Cancer Institute (NCI) report from the Operational Efficiency Working Group both recommend changes to the processes for opening a clinical trial. This article provides evidence for the need for such changes by completing the first comprehensive review of all the time and steps required to open a phase III oncology clinical trial and discusses the effect of time to protocol activation on subject accrual.

Methods: The Dilts and Sandler method was used at four cancer centers, two cooperative groups, and the NCI Cancer Therapy Evaluation Program. Accrual data were also collected.

Results: Opening a phase III cooperative group therapeutic trial requires 769 steps, 36 approvals, and a median of approximately 2.5 years from formal concept review to study opening. Time to activation at one group ranged from 435 to 1,604 days, and time to open at one cancer center ranged from 21 to 836 days. At centers, group trials are significantly more likely to have zero accruals (38.8%) than nongroup trials (20.6%; P < 0.0001). Of the closed NCI Cancer Therapy Evaluation Program–approved phase III clinical trials from 2000 to 2007, 39.1% resulted in <21 accruals.

Conclusions: The length, variability, and low accrual results demonstrate the need for the NCI clinical trials system to be reengineered. Improvements will be of only limited effectiveness if done in isolation; there is a need to return to the collaborative spirit with all parties creating an efficient and effective system. Recommendations put forth by the Institute of Medicine and Operational Efficiency Working Group reports, if implemented, will aid this renewal. Clin Cancer Res; 16(22); 5381–9. ©2010 AACR.
Reciprocal and Complementary Role of MET Amplification and EGFR T790M Mutation in Acquired Resistance to Kinase Inhibitors in Lung Cancer
Authors: Suda Kenichi , Murakami Isao , Katayama Tatsuya , Tomizawa Kenji , Osada Hirotaka , Sekido Yoshitaka , Maehara Yoshihiko , Yatabe Yasushi , Mitsudomi Tetsuya
Published: November 2010

Purpose: In epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for lung cancer patients, acquired resistance develops almost inevitably and this limits the improvement in patient outcomes. EGFR T790M mutation and MET amplification are the two main mechanisms underlying this resistance, but the relationship between these two mechanisms is unclear. In this study, we explored their relationship using in vitro models and autopsy specimens.

Experimental Design: Erlotinib-resistant HCC827 (HCC827ER) cells were developed by chronic exposure to erlotinib at increasing concentrations. HCC827EPR cells were also developed by chronic exposure to erlotinib in the presence of PHA-665,752 (a MET TKI). The erlotinib-resistant mechanisms of these cells were analyzed. In addition, 33 autopsy tumor samples from 6 lung adenocarcinoma patients harboring multiple gefitinib-refractory tumors were analyzed.

Results: HCC827ER developed MET amplification, and clinically relevant resistance occurred at ≥4-fold MET gene copy number gain (CNG). By contrast, HCC827EPR developed T790M without MET CNG. Of six patients harboring gefitinib-refractory tumors, three exhibited T790M only, one exhibited MET amplification only, and the other two exhibited T790M and/or MET amplification depending on the lesion sites. In these gefitinib-refractory tumors, T790M developed in 93% (14 of 15) of tumors without MET gene CNGs, in 80% (4 of 5) of tumors with moderate MET gene CNGs (<4-fold), and in only 8% (1 of 13) of tumors with MET amplification (≥4-fold).

Conclusions: These results indicate a reciprocal and complementary relationship between T790M and MET amplification and the necessity of concurrent inhibition of both for further improving patient outcomes. Clin Cancer Res; 16(22); 5489–98. ©2010 AACR.
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Large Vessel Vasculitis and Kawasaki Disease in Japan
Authors: Kobayashi Shigeto , Fujimoto Shouichi , Takahashi Kei , Suzuki Kazuo
Published: November 2010

Based on studies comparing the prevalence of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) between Japan and Europe, we have learned that the difference may be due to genetic background and environmental factors, but not to diagnosis or ELISA system for myeloperoxidase and proteinase-3 ANCA. In Japan, microscopic polyangiitis is the most common among AAV, but Wegener’s granulomatosis was present in less than 2 per million patients. Also, one study from Hokkaido reported only 16 patients in a 27-year time frame. A recent retrospective study of renal vasculitis between 2000 and 2004 from Miyazaki prefecture in Japan reported an incidence of microscopic polyangiitis of 14.8 per million, but no patients with Wegener’s granulomatosis or Churg-Strauss syndrome. In the present review, we focus on ANCA-related vasculitis in Japan: (1) AAV and large vessel vasculitis – Takayasu’s arteritis and giant cell arteritis; (2) primary renal vasculitis; (3) epitopes of myeloperoxidase-ANCA in vasculitis in the Japanese population and comparison of ANCA-ELISA systems in Japan and Europe, and finally (4) children with vasculitis in Japan involving Kawasaki disease – a systemic vasculitis.
Validation and Clinical Use of the Japanese Classification of Colorectal Carcinomatosis: Benefit of Surgical Cytoreduction Even without Hyperthermic Intraperitoneal Chemotherapy
Authors: Kobayashi Hirotoshi , Enomoto Masayuki , Higuchi Tetsuro , Uetake Hiroyuki , Iida Satoru , Ishikawa Toshiaki , Ishiguro Megumi , Sugihara Kenichi
Published: November 2010

Background: This study aimed to validate an easy to use practical classification of peritoneal metastasis arising from colorectal cancer. Patients and Methods: Data from 2,134 consecutive patients who underwent resection for colorectal cancer at a single institution were reviewed. Peritoneal metastasis was classified depending on extent into three groups (P1–P3). The macroscopic radical resection rates and survival of patients with colorectal cancer complicated with peritoneal metastasis were analyzed. Results: Of the 2,134 patients, 116 (5.4%) had peritoneal metastasis. Among them, 20 (17.2%) underwent macroscopic radical resection. Tumor location on the right side was associated with more extensive peritoneal metastasis (p = 0.010). Male gender (p = 0.0027), liver metastasis (p = 0.0021), and P3 peritoneal metastasis were independent risk factors for noncurative resection. The Cox proportional hazards model showed that gender (p = 0.031), operation period (p = 0.031), and macroscopic radical resection for colorectal cancer and peritoneal metastasis (p = 0.031) were independent prognostic factors. Conclusions: Being female with left colon cancer complicated with P1 or P2 peritoneal metastasis is a good indicator for macroscopic radical resection if liver metastasis is absent. The present classification helped to determine surgical indication for patients with colorectal cancer complicated with synchronous peritoneal metastasis in routine clinical practice.
Defining the Optimal Degree of Heparin Anticoagulation for Peripheral Vascular Interventions
Authors: Kasapis Christos , Gurm Hitinder S. , Chetcuti Stanley J. , Munir Khan , Luciano Ann , Smith Dean , Aronow Herbert D. , Kassab Elias H. , Knox Michael F. , Moscucci Mauro , Share David , Grossman P. Michael
Published: November 2010

Background—

The optimal degree of heparin anticoagulation for peripheral vascular interventions (PVIs) has not been defined. We sought to correlate total heparin dose and peak procedural activated clotting time (ACT) with postprocedural outcomes in patients undergoing PVI.

Methods and Results—

We studied 4743 patients who received heparin during PVIs in a regional, multicenter registry. From those, 1246 had recorded peak procedural ACT with the same point-of-care device. Periprocedural and in-hospital outcomes were compared between patients who received a total heparin dose <60 U/kg (n=2161) and ≥60 U/kg (n=2582). Similarly, outcomes were evaluated between groups with a peak procedural ACT <250 seconds (n=855) and ≥250 seconds (n=391). Technical and procedural success as well as intraprocedural thrombotic events did not differ between groups. Patients with heparin dose ≥60 U/kg had a higher rate of postprocedural hemoglobin drop ≥3 g/dL (7.09% versus 5.09%, respectively,
P
=0.004) and a higher transfusion rate compared with those with heparin dose <60 U/kg (4.92% versus 3.15%, respectively,
P
=0.002). In multivariate analysis, independent predictors of bleeding requiring transfusion were total heparin dose ≥60 U/kg, ACT ≥250 seconds, female sex, age ≥70 years, prior anemia, prior heart failure, low creatinine clearance, hybrid vascular surgery, rest pain, and below-knee intervention. In propensity-matched, risk-adjusted models and after hierarchical modeling, total heparin dose ≥60 U/kg and ACT ≥250 seconds remained strong predictors of post-PVI drop in hemoglobin ≥3 g/dL or transfusion.

Conclusions—

During PVI, higher total heparin dose (≥60 U/kg) and peak ACT ≥250 seconds were predictors of postprocedural transfusion. The high technical and procedural success in all groups suggests that use of weight-based heparin dosing with a target ACT <250 seconds in PVI may minimize the bleeding risk without compromising procedural success or increasing thromboembolic complications.
The Postcolonial in Motion: Hijra ila ardi al-ahlam and the Construction of Postcolonial Counterdiscourse
Authors: Simour Lhoussain
Published: November 2010

This paper examines the poetics and politics of representing cultural otherness in Sellam Chahidi's travel-inspired narrative Hijra ila ardi al-ahlam. Since Western cultural encounters have developed an overall epistemological outline in which Moroccan cultural identities are framed and often preconditioned to express western perspectives, Chahidi's narrative foregrounds new ways whereby the existing paradigm of interpretation and power relations are disturbed and subverted. Hijra ila ardi al-ahlam shows an inquisitive mode of cross-cultural negotiation in which various ideological and cross-cultural appropriations are dislocated to take on new twists. It is motivated by a strong desire to forge a new space capable of transcending the sociopolitical reality of the motherland but also capable of challenging the unilateral constructions of identity dictated by the ideologies of an Orientalist mindset.
Hashish and the 'Carnivalesque' in Egyptian Cinema
Authors: Al-Zobaidi Sobhi
Published: November 2010

This paper focuses on the ever-growing popularity of scenes depicting and referring to hashish and marijuana use in Egyptian cinema. It argues that a shift in attitude and in the overall depiction of these substances has emerged in more recent films, those produced in the 1990s and after. It suggests that whereas in older cinema these substances were always associated with social and political ills, almost all negative connotations and associations have disappeared in favor of an acceptable and playful depiction. Drawing on the theoretical framework of the carnivalesque developed by Bakhtin, and the work of other scholars such as Gilles Deleuze and Walter Benjamin, this paper suggests that the depictions of smoking hashish and marijuana are subversive moments that ultimately aim at escaping rigid social structures and power hierarchies while providing commentaries on repressive social and political realities.
Bare Singular NPs in Argument Positions: Restrictions on Indefiniteness
Authors: Geist Ljudmila
Published: November 2010

It has been assumed that in articleless languages such as Russian, bare singular NPs in argument positions can receive a definite or an indefinite interpretation. While the definite interpretation depends on the broader discourse and may freely arise if the referent is familiar, the option of an indefinite interpretation for bare NPs introducing new discourse referents is more restricted. This paper investigates conditions on the indefinite interpretation of bare singular NPs in Russian. It shows that this interpretation is restricted by the topic-comment structure: the indefinite interpretation may arise only if the NP belongs to the comment part of the sentence and is excluded for NPs which are aboutness topics. This restriction can be explained by the requirement that indefinite aboutness topics must be specific. Bare indefinite NPs however can only receive a non-specific existential interpretation, and hence do not qualify as topics. The paper contributes to the elucidation of the interaction between the semantic and pragmatic components of an overall theory of NP interpretation and argues that weak existential NPs should be distinguished from cases of noun incorporation.
Investigating the Consequences of Focus on the Production and Comprehension of Referring Expressions
Authors: Kaiser Elsi
Published: November 2010

This paper investigates issues related to referent tracking in discourse, in particular whether and how contrastive focus interacts with other factors – in particular pronominalization and subjecthood – to influence comprehenders' and speakers' expectations about what entities will be referred to/mentioned in upcoming discourse. On the basis of data from two psycholinguistic experiments, I argue that to better understand the discourse-structuring effects of contrastive focus, we need to consider not only pronoun interpretation but also production-based questions having to do with choice of upcoming referent and choice of referential form. I suggest that looking at the discourse-level consequences of contrastive focus from the perspective of the comprehender as well as the perspective of the speaker (i) allows us to gain new insights about the effects of focus and the discourse-status of focus-induced alternatives, and (ii) highlights (potentially unexpected) asymmetries between likelihood of upcoming mention and likelihood of pronominalization.
It Is Complicated: Unpacking the Flow of Teacher Education’s Impact on Student Learning
Authors: Diez Mary E.
Published: November 2010

Knowing that a teacher education program’s graduates affected P—12 student learning may be important, but knowing how the program prepared their graduates to affect learning is critical for ongoing reform efforts. In this essay, the author argues for the utility of looking at three sets of relationships involved in gauging the impact of teacher education programs on P—12 student learning—teacher education program impact on teacher candidate learning, teacher graduate practice of teacher education program outcomes in P—12 settings, and teacher graduate impact on P—12 pupil learning. The author also addresses three issues affecting the efficacy of reform efforts—a focus on proving versus improving, an absence of assessment literacy, and the need for teaching to support learning.
Creativity and Place in the Evolution of a Cultural Industry
Authors: Leslie Deborah , Rantisi Norma M.
Published: November 2010

The Cirque du Soleil, based in Montreal, is known internationally for its innovative form of circus production. Although a transnational company recruiting talent from around the world, it is argued that the Cirque’s ability to innovate is underpinned by its historical and geographical situatedness in Montreal. Drawing on evolutionary economics, the paper examines the place-specific and path-dependent trajectory which has informed the emergence of the Cirque, focusing on how a series of latent synergies—including a vibrant tradition of street performance in Quebec, the lack of established circus conventions, and the strength of related cultural sectors in Montreal—gave rise to the Cirque. In addition, the paper explores the purposive role of the state in actualising some of these latent synergies.
Management Capacity and State Municipal Bond Ratings
Authors: Zhao Zhirong (Jerry) , Guo Hai (David)
Published: November 2010

Most state governments issue general obligation (GO) bonds in the financial market to borrow money. Assigned by credit agencies, state GO bond ratings reflect states’ perceived credit quality and affect their borrowing costs. Despite many studies on the determinants of municipal bond ratings, little has been known about the association between state management capacity and bond ratings because management capacity is generally difficult to quantify. However, state governments’ performance grades assigned by the Government Performance Project (GPP) provide a great opportunity to study how people perceive and respond to state governments’ management capacity. This study finds that states with higher GPP grades tend to have higher state GO bond ratings, but the relationship may be nonlinear as people are more sensitive to the extremes of perceived performance. In particular, we observe a “performance premium” scenario in which S&P bond ratings grow at an increasing rate as state GPP grades improve.
The Organization and Operation of Illicit Retail Methamphetamine Markets
Authors: Brownstein Henry H. , Mulcahy Timothy M. , Fernandes-Huessy Johannes , Taylor Bruce G. , Woods Daniel
Published: November 2010

Illicit drug markets vary organizationally and operationally in terms of things like the product being bought and sold, the community and population being served, the people engaged in the business, and the extent to which the market has matured. In this paper we use data from a survey of 1,367 law enforcement agencies to examine the characteristics and dynamics of illicit retail methamphetamine markets in U.S. communities. We describe the characteristics of those markets and we distinguish different types of communities in terms of the characteristics of their local meth markets. Despite finding similarity in the organizational and operational characteristics of methamphetamine markets in the U.S., we found variability in terms of the source of production of meth for the local market (local labs and importing from Mexico and other U.S. states) and the extent to which local police consider meth to be a local problem.
Distributed Versus Focal Cortical Stimulation to Enhance Motor Function and Motor Map Plasticity in a Rodent Model of Ischemia
Authors: Boychuk Jeffery A. , Adkins DeAnna L. , Kleim Jeffrey A.
Published: November 2010

Background. Motor rehabilitation after cerebral ischemia can enhance motor performance and induce motor map reorganization. Electrical stimulation of the cortex (CS) during rehabilitative training (CS/RT) augments motor map plasticity and confers gains in motor function beyond those observed with motor rehabilitation alone. However, it is unclear how the distribution of electrical stimulation across the cortex accomplishes these changes. This study examined the behavioral and neurophysiological effects of delivering CS/RT through a distributed versus focal arrangement of electrical contacts. Methods. Adult male rats were given rehabilitative training on a skilled forelimb reaching task following induction of focal ischemic damage within motor cortex. Intracortical microstimulation was used to derive high-resolution maps of forelimb movement representations within motor cortex contralateral to the trained/impaired paw before and after rehabilitation. Results. All animals that received rehabilitation showed greater increases in motor map area and reaching accuracy than animals that received no training. Animals with the distributed configuration performed significantly greater reaching accuracy than animals in both the CS/RT with focused contact arrangement and rehabilitative training alone (RT) conditions on days 3 to 4 and on day 6 through the remainder of the study ( P < .05). However, both CS/RT groups exhibited larger motor maps than the RT condition (E1-CS/RT, 4.71 ± 0.66 mm2; E2-CS/RT, 4.64 ± 0.46 mm2; RT, 2.99 ± 0.28 mm2). Conclusion. The results indicate that although both focal and distributed forms of CS/RT promote motor map reorganization only the distributed form of CS/RT enhances motor performance with rehabilitation.
A Longitudinal Study of the Impact of Organizational Change on Transactional, Relational, and Balanced Psychological Contracts
Authors: Chaudhry Anjali , Coyle-Shapiro Jacqueline A.-M. , Wayne Sandy J.
Published: November 2010

Workplace transitions are thought to result in a fundamental shift in the employment relationship. This study used sensemaking theory to examine when and how organizational change affects employees’ psychological contracts (PCs). The authors suggest that employees interpret organizational change through contextual and cognitive factors related to the change. These factors, in turn, influence whether employees revise their PCs. Results of our longitudinal study suggest that the extent to which contextual and cognitive factors affect employees’ PCs depends on the type of PC. Transactional and balanced PCs were unaffected by the contextual and cognitive factors related to the change, while changes occurred in relational PCs.
Strategic Media, Cynical Public? Examining the Contingent Effects of Strategic News Frames on Political Cynicism in the United Kingdom
Authors: Jackson Dan
Published: November 2010

Through the use of experimental methods, this study examines the claim that strategic news engenders political cynicism. First, it builds upon previous theory by conceptualizing and measuring political cynicism at both issue-specific and global levels. Second, the contingency of framing effects is a contested but crucial area of the framing paradigm and deserves greater attention in strategic framing studies. The study therefore examines this in detail by testing a number of individual characteristics for their moderating effects. The author found that relative to issue-based coverage, strategic news frames increased issue-specific political cynicism, but this effect was only evident for those who were less politically engaged and knowledgeable. The effects of the strategy frame on more global measures of political cynicism were minimal. The findings are discussed in the light of ongoing debates about framing effects and the media’s role in democratic engagement.
Regulation of vascular endothelial growth factor receptor 2 trafficking and angiogenesis by Golgi localized t-SNARE syntaxin 6
Authors: Manickam Venkatraman , Tiwari Ajit , Jung Jae-Joon , Bhattacharya Resham , Goel Apollina , Mukhopadhyay Debabrata , Choudhury Amit
Published: November 2010

Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in physiologic and pathologic angiogenesis. Plasma membrane (PM) levels of VEGFR2 are regulated by endocytosis and secretory transport through the Golgi apparatus. To date, the mechanism whereby the VEGFR2 traffics through the Golgi apparatus remains incompletely characterized. We show in human endothelial cells that binding of VEGF to the cell surface localized VEGFR2 stimulates exit of intracellular VEGFR2 from the Golgi apparatus. Brefeldin A treatment reduced the level of surface VEGFR2, confirming that VEGFR2 traffics through the Golgi apparatus en route to the PM. Mechanistically, we show that inhibition of syntaxin 6, a Golgi-localized target membrane-soluble N-ethylmaleimide attachment protein receptor (t-SNARE) protein, interferes with VEGFR2 trafficking to the PM and facilitates lysosomal degradation of the VEGFR2. In cell culture, inhibition of syntaxin 6 also reduced VEGF-induced cell proliferation, cell migration, and vascular tube formation. Furthermore, in a mouse ear model of angiogenesis, an inhibitory form of syntaxin 6 reduced VEGF-induced neovascularization and permeability. Our data demonstrate the importance of syntaxin 6 in the maintenance of cellular VEGFR2 levels, and suggest that the inhibitory form of syntaxin 6 has good potential as an antiangiogenic agent.
Significant differences in B-cell subpopulations characterize patients with chronic graft-versus-host disease–associated dysgammaglobulinemia
Authors: Kuzmina Zoya , Greinix Hildegard T. , Weigl Roman , Körmöczi Ulrike , Rottal Arno , Frantal Sophie , Eder Sandra , Pickl Winfried F.
Published: November 2010

Manifestations of chronic graft-versus-host disease (cGVHD) can resemble those seen in immunodeficiency states and autoimmune disorders. Reports by us and others suggest an involvement of B cells in the pathogenesis of cGVHD. We investigated B-lymphocyte subpopulations in cGVHD cohorts defined by serum immunoglobulin G (IgG) levels to characterize novel biomarkers for impairment of humoral immunity after allogeneic hematopoietic stem cell transplantation. Seventy-six patients were enrolled a median of 46 months after hematopoietic stem cell transplantation. The hypogammaglobulinemia group had significantly diminished CD19+ B cells (165 vs 454 vs 417 × 106/L) with elevated CD19+CD21low immature (16.5%, 7.7%, and 9.1%) and CD19+CD21int-highCD38highIgMhigh transitional (10.5% vs 4.2% vs 6.3%) B-cell proportions compared with the normogammaglobulinemia and hypergammaglobulinemia groups. CD19+CD10−CD27−CD21high naive B cells were highly elevated in all patients with cGVHD. CD19+CD27+IgD+ non–class-switched (4 vs 12 vs 11 × 106/L) and class-switched (7 vs 35 vs 42 × 106/L) memory B cells were significantly lower in the hypogammaglobulinemia group compared with the others. Besides significantly higher B-cell activation factor/B-cell ratios, significantly more cGVHD patients with hypergammaglobulinemia had autoantibodies compared with the hypogammaglobulinemia subgroup (68% vs 24%, P = .024). In conclusion, B-cell subpopulations can serve as novel cellular biomarkers for immunodeficiency and autoimmunity indicating different pathogenetic mechanisms of cGVHD and encouraging future prospective longitudinal studies.