bluuebunny/crossref_metadata_2025 huggingface dataset:
The Natural History and Clinical Presentation of Cervical Spondylotic Myelopathy
Authors: Yarbrough Chester K. , Murphy Rory K. J. , Ray Wilson Z. , Stewart Todd J.
Published: December 2011

Cervical spondylotic myelopathy (CSM) refers to impaired function of the spinal cord caused by degenerative changes of the cervical spine resulting in spinal cord compression. It is the most common disorder in the United States causing dysfunction of the spinal cord. A literature review of the natural history of mild cervical myelopathy is undertaken. Clinical presentation and current concepts of pathophysiology are also discussed. While many patients with mild signs of CSM will stabilize or improve over time with conservative treatment, the clinical course of a specific individual patient cannot be predicted. Asymptomatic patients with cervical stenosis and abnormalities on electrophysiologic studies may be at higher risk for developing myelopathy.
Spatiotemporal Relationship between Geodetic and Seismic Quantities: A Possible Clue to Preparatory Processes of M ≥ 6.0 Inland Earthquakes in Japan
Authors: Kawamura Masashi , Kudo Takeshi , Yamaoka Koshun
Published: December 2011

Constructing a statistical model to characterize the physical conditions associated with large earthquake occurrence is crucial for disaster mitigation. With the aim to formulate such a model, we previously developed a statistical evaluation system which assesses the correlation of the spatiotemporal relationship between different kinds of physical quantities with the occurrence times of large inland earthquakes. In this study, we focused on assessing the relationship between geodetic and seismic quantities and attempted to find the pair of related quantities that most likely indicates preparatory processes of large earthquakes in Japan. We assessed the quantities prior to M ≥ 6.0 inland earthquakes for the period of 2001–2007 in terms of probability gains and error diagram. Our system revealed that the pair of absolute value of dilatation rate and seismic energy showed the highest statistical performance. Further validation of this result is required by updating the database of physical quantities.
Capsule Endoscopy in Celiac Disease
Authors: Akin E. , Ersoy O.
Published: December 2011

Capsule endoscopy (CE) has been increasingly used for diagnosing disease of the small bowel. It is an attractive technique for assessing celiac disease (CD) because it is noninvasive and provides a close and magnified view of the mucosa of the entire small bowel. The aim of this paper is to update the current data on the use of CE for diagnosing villous atrophy and complications of CD.
Tunnel Contacts for Spin Injection into Silicon: The Si-Co Interface with and without a MgO Tunnel Barrier—A Study by High-Resolution Rutherford Backscattering
Authors: Dash S. P. , Goll D. , Kopold P. , Carstanjen H. D.
Published: December 2011

In order to obtain high spin injection efficiency, a ferromagnet-semiconducor Schottky contact must be of high crystalline quality. This is particularly important in the case of ferromagnet-silicon interfaces, since these elements tend to mix and form silicides. In this study Co-Si (100) interfaces were prepared in three different ways: by evaporation at room temperature, low temperature (), and with Sb as surfactant, and their interface structures were analyzed by high-resolution RBS (HRBS). In all cases more or less strong in-diffusion of Co with subsequent silicide formation was observed. In order to prevent the mixing of Co and Si, ultra thin MgO tunnel barriers were introduced in-between them. In situ HRBS characterization confirms that the MgO films were very uniform and prevented the mixing of the Si substrate with deposited Co and Fe films effectively, even at .
Upregulation of Notch2 and Six1 Is Associated with Progression of Early-Stage Lung Adenocarcinoma and a More Aggressive Phenotype at Advanced Stages
Authors: Mimae Takahiro , Okada Morihito , Hagiyama Man , Miyata Yoshihiro , Tsutani Yasuhiro , Inoue Takao , Murakami Yoshinori , Ito Akihiko
Published: December 2011

Purpose: Lung adenocarcinoma often manifests as tumors with mainly lepidic growth. The size of invasive foci determines a diagnosis of in situ, minimally invasive adenocarcinoma, or invasive types and suggests that some adenocarcinomas undergo malignant progression in that order. This study investigates how transcriptional aberrations in adenocarcinoma cells at the early stage define the clinical phenotypes of adenocarcinoma tumors at the advanced stage.

Experimental Design: We comprehensively searched for differentially expressed genes between preinvasive and invasive cancer cells in one minimally invasive adenocarcinoma using laser capture microdissection and DNA microarrays. We screened expression of candidate genes in 11 minimally invasive adenocarcinomas by reverse transcriptase PCR and examined their involvement in preinvasive-to-invasive progression by transfection studies. We then immunohistochemically investigated the presence of candidate molecules in 64 samples of advanced adenocarcinoma and statistically analyzed the findings, together with clinicopathologic variables.

Results: The transcription factors Notch2 and Six1 were upregulated in invasive cancer cells in all 11 minimally invasive adenocarcinomas. Exogenous Notch2 transactivated Six1 followed by Smad3, Smad4, and vimentin, and enlarged the nuclei of NCI-H441 lung epithelial cells. Immunochemical staining for the transcription factors was double positive in the invasive, but not in the lepidic growth component of a third of advanced Ads, and the disease-free survival rates were lower in such tumors.

Conclusions: Paired upregulation of Notch2 and Six1 is a transcriptional aberration that contributes to preinvasive-to-invasive adenocarcinoma progression by inducing epithelial–mesenchymal transition and nuclear atypia. This aberration persisted in a considerable subset of advanced adenocarcinoma and conferred a more malignant phenotype on the subset. Clin Cancer Res; 18(4); 945–55. ©2011 AACR.
Expansion of a CD8+PD-1+ Replicative Senescence Phenotype in Early Stage CLL Patients Is Associated with Inverted CD4:CD8 Ratios and Disease Progression
Authors: Nunes Claudia , Wong Ryan , Mason Malcolm , Fegan Chris , Man Stephen , Pepper Chris
Published: December 2011

Purpose: Patients with chronic lymphocytic leukemia (CLL) display immune deficiency that is most obvious in advanced stage disease. Here we investigated whether this immune dysfunction plays a pathologic role in the progression of early stage disease patients.

Experimental Design: We carried out eight-color immunophenotyping analysis in a cohort of 110 untreated early stage CLL patients and 22 age-matched healthy donors and correlated our findings with clinical outcome data.

Results: We found a significant reduction in naive CD4+ and CD8+ T cells in CLL patients. Only the CD4+ subset showed significantly increased effector memory cells (TEM and TEMRA) in the whole cohort (P = 0.004 and P = 0.04, respectively). However, patients with inverted CD4:CD8 ratios (52 of 110) showed preferential expansion of the CD8 compartment, with a skewing of CD8+ TEMRA (P = 0.03) coupled with increased percentage of CD57+CD28−CD27− T cells (P = 0.008) and PD-1 positivity (P = 0.027), consistent with a replicative senescence phenotype. Furthermore, inverted CD4:CD8 ratios were associated with shorter lymphocyte doubling time (P = 0.03), shorter time to first treatment (P = 0.03), and reduced progression-free survival (P = 0.005).

Conclusions: Our data show that the emergence of CD8+PD-1+ replicative senescence phenotype in early stage CLL patients is associated with more aggressive clinical disease. Importantly, these findings were independent of tumor cell prognostic markers and could not be accounted for by patient age, changes in regulatory T-cell frequency, or cytomegalovirus serostatus. Clin Cancer Res; 18(3); 678–87. ©2011 AACR.
Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor
Authors: Maira Sauveur-Michel , Pecchi Sabina , Huang Alan , Burger Matthew , Knapp Mark , Sterker Dario , Schnell Christian , Guthy Daniel , Nagel Tobi , Wiesmann Marion , Brachmann Saskia , Fritsch Christine , Dorsch Marion , Chène Patrick , Shoemaker Kevin , De Pover Alain , Menezes Daniel , Martiny-Baron Georg , Fabbro Doriano , Wilson Christopher J. , Schlegel Robert , Hofmann Francesco , García-Echeverría Carlos , Sellers William R. , Voliva Charles F.
Published: December 2011

Following the discovery of NVP-BEZ235, our first dual pan-PI3K/mTOR clinical compound, we sought to identify additional phosphoinositide 3-kinase (PI3K) inhibitors from different chemical classes with a different selectivity profile. The key to achieve these objectives was to couple a structure-based design approach with intensive pharmacologic evaluation of selected compounds during the medicinal chemistry optimization process. Here, we report on the biologic characterization of the 2-morpholino pyrimidine derivative pan-PI3K inhibitor NVP-BKM120. This compound inhibits all four class I PI3K isoforms in biochemical assays with at least 50-fold selectivity against other protein kinases. The compound is also active against the most common somatic PI3Kα mutations but does not significantly inhibit the related class III (Vps34) and class IV (mTOR, DNA-PK) PI3K kinases. Consistent with its mechanism of action, NVP-BKM120 decreases the cellular levels of p-Akt in mechanistic models and relevant tumor cell lines, as well as downstream effectors in a concentration-dependent and pathway-specific manner. Tested in a panel of 353 cell lines, NVP-BKM120 exhibited preferential inhibition of tumor cells bearing PIK3CA mutations, in contrast to either KRAS or PTEN mutant models. NVP-BKM120 shows dose-dependent in vivo pharmacodynamic activity as measured by significant inhibition of p-Akt and tumor growth inhibition in mechanistic xenograft models. NVP-BKM120 behaves synergistically when combined with either targeted agents such as MEK or HER2 inhibitors or with cytotoxic agents such as docetaxel or temozolomide. The pharmacological, biologic, and preclinical safety profile of NVP-BKM120 supports its clinical development and the compound is undergoing phase II clinical trials in patients with cancer. Mol Cancer Ther; 11(2); 317–28. ©2011 AACR.
Potent Inhibition of Angiogenesis by the IGF-1 Receptor-Targeting Antibody SCH717454 Is Reversed by IGF-2
Authors: Bid Hemant K. , Zhan Jun , Phelps Doris A. , Kurmasheva Raushan T. , Houghton Peter J.
Published: December 2011

Previously, we reported that a predominant action of a type-1 insulin-like growth factor receptor (IGF-1R)-targeted antibody was through inhibiting tumor-derived VEGF, and indirectly, angiogenesis. Here, we examined the direct antiangiogenic activity of the IGF-1R-targeted antibody SCH717454 that inhibits ligand-receptor binding and the mechanism by which tumors circumvent its antiangiogenic activity. Inhibition of ligand-stimulated activation of IGF-1R, insulin receptor (IN-R), or downstream signaling [phosphorylation of Akt (Ser473)] was determined by receptor-specific immunoprecipitation and immunoblotting. Inhibition of angiogenesis was determined by proliferation and tube formation using human umbilical vein endothelial cells (HUVEC) in vitro and in Matrigel plugs implanted in mice. SCH717454 blocked IGF-1-stimulated but not IGF-2-stimulated phosphorylation of Akt in sarcoma cells. Immunoprecipitation using anti-IGF-1R and anti-IN-R antibodies revealed that SCH717454 equally blocked IGF-1-stimulated and IGF-2-stimulated IGF-1R phosphorylation, but not IGF-2-stimulated phosphorylation of IN-R. SCH717454 completely blocked VEGF-stimulated proliferation and tube formation of HUVECs, but exogenous IGF-2 and insulin circumvented these inhibitory effects. Coculture of HUVECs with IGF-2-secreting tumor cells completely abrogated SCH717454 inhibition of VEGF-stimulated HUVEC tube formation. In mice, SCH717454 inhibited angiogenesis in VEGF-infused Matrigel plugs, but had no inhibitory activity when plugs contained both VEGF + IGF-2. These results reveal for the first time, a role for IGF-1R signaling in VEGF-mediated angiogenesis in vitro and indicate direct antiangiogenic activity of SCH717454. Both in vitro and in vivo IGF-2 circumvented these effects through IN-R signaling. Many childhood cancers secrete IGF-2, suggesting that tumor-derived IGF-2 in the microenvironment maintains angiogenesis in the presence of IGF-1R-targeted antibodies allowing tumor progression. Mol Cancer Ther; 11(3); 649–59. ©2011 AACR.
TAK-960, a Novel, Orally Available, Selective Inhibitor of Polo-Like Kinase 1, Shows Broad-spectrum Preclinical Antitumor Activity in Multiple Dosing Regimens
Authors: Hikichi Yuichi , Honda Kohei , Hikami Kouki , Miyashita Hitoshi , Kaieda Isao , Murai Saomi , Uchiyama Noriko , Hasegawa Maki , Kawamoto Tomohiro , Sato Takashi , Ichikawa Takashi , Cao Sheldon , Nie Zhe , Zhang Lilly , Yang Johnny , Kuida Keisuke , Kupperman Erik
Published: December 2011

Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase involved in key processes during mitosis. Human PLK1 has been shown to be overexpressed in various human cancers, and elevated levels of PLK1 have been associated with poor prognosis, making it an attractive target for anticancer therapy. TAK-960 [4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-fluoro-5-methoxy-N-(1-methylpiperidin-4-yl) benzamide] is a novel, investigational, orally bioavailable, potent, and selective PLK1 inhibitor that has shown activity in several tumor cell lines, including those that express multidrug-resistant protein 1 (MDR1). Consistent with PLK1 inhibition, TAK-960 treatment caused accumulation of G2–M cells, aberrant polo mitosis morphology, and increased phosphorylation of histone H3 (pHH3) in vitro and in vivo. TAK-960 inhibited proliferation of multiple cancer cell lines, with mean EC50 values ranging from 8.4 to 46.9 nmol/L, but not in nondividing normal cells (EC50 >1,000 nmol/L). The mutation status of TP53 or KRAS and MDR1 expression did not correlate with the potency of TAK-960 in the cell lines tested. In animal models, oral administration of TAK-960 increased pHH3 in a dose-dependent manner and significantly inhibited the growth of HT-29 colorectal cancer xenografts. Treatment with once daily TAK-960 exhibited significant efficacy against multiple tumor xenografts, including an adriamycin/paclitaxel-resistant xenograft model and a disseminated leukemia model. TAK-960 has entered clinical evaluation in patients with advanced cancers. Mol Cancer Ther; 11(3); 700–9. ©2011 AACR.
Pancreatic Cancer Cells and Normal Pancreatic Duct Epithelial Cells Express an Autocrine Catecholamine Loop that Is Activated by Nicotinic Acetylcholine Receptors α3, α5, and α7
Authors: Al-Wadei Mohammed H. , Al-Wadei Hussein A.N. , Schuller Hildegard M.
Published: December 2011

Pancreatic cancer is the fourth leading cause of cancer deaths in developed countries. Smoking is an established risk factor for this malignancy but the underlying mechanisms are poorly understood. Previous reports have provided evidence that nicotinic acetylcholine receptors (nAChR) and beta adrenergic receptors (β-AR) stimulate the growth and migration of pancreatic cancer cells. However, a potential cooperation of these two receptor families in the regulation of pancreatic cancer has not been studied to date. Using two pancreatic cancer cell lines and immortalized pancreatic duct epithelia in vitro, our current data show that all three cell lines synthesized and released the catecholamine neurotransmitters noradrenaline and adrenaline upon exposure to nicotine and that this activity was regulated by α3, α5, and α7-nAChRs. In accordance with the established function of these catecholamines as β-AR agonists, nicotine-induced cell proliferation was blocked by the β-AR antagonist propranolol. Nicotine-induced proliferation was also abolished by the α7-nAChR antagonist α-bungarotoxin, whereas catecholamine production in response to nicotine was blocked by gene knockdown of the α3, α5, and α7-nAChRs. The nicotinic agonists acetylcholine, nicotine, and its nitrosated carcinogenic derivative NNK induced the phosphorylation of CREB, ERK, Src, and AKT and these responses were inhibited by propranolol. Our findings identify this hitherto unknown autocrine catecholamine loop as an important regulatory cascade in pancreatic cancer that may prove a promising new target for cancer intervention. Mol Cancer Res; 10(2); 239–49. ©2011 AACR.
Spectral-Domain Optical Coherence Tomography Characteristics of Macular Contusion Trauma
Authors: Yu Weihong , Zheng Lin , Zhang Zhiqiao , Dai Rongping , Dong Fangtian
Published: December 2011

Purpose: To describe the characteristics of macular lesions after eye trauma using spectral-domain optical coherence tomography (OCT). Methods: We retrospectively reviewed and described 2-dimensional (2D) and 3-dimensional (3D) spectral-domain OCT characteristics of 24 consecutive eyes of 24 cases that were identified with macular lesions after eye trauma. Results: Spectral-domain OCT clearly demonstrated a variety of lesions: hemorrhage, epiretinal membrane formation, macular hole, retinal pigment epithelium (RPE) rupture combined with choroidal neovascularization formation, photoreceptor inner/outer surface changes, RPE detachment, scar formation with e.g. diffuse macular edema, macular distortion or macular atrophy. Main lesions were located in the fovea area in 11 eyes (45.8%), the parafovea in 3 eyes (12.5%) and the whole macular area in 10 eyes (41.7%). Conclusion: Spectral-domain OCT is a useful investigation providing refined and credible 2D/3D images, precisely locating macular lesions after contusion trauma.
Using the New Clinical Grading Scale for Quantification of the Severity of Hemifacial Spasm: Correlations with a Quality of Life Scale
Authors: Lee Jeong A , Jo Kwang Wook , Kong Doo-Sik , Park Kwan
Published: December 2011

Background: To date, no consensus has been reached regarding validated and practical tools to quantify the severity of hemifacial spasm (HFS) before and after surgery. Objective: The aim of this study has been to establish objective parameters for determining the preoperative severity of HFS and to assess the correlation with quality of life (QoL) in HFS patients. Methods: Patients who experienced HFS between April and August 2010 were reviewed. The patients were divided into four groups according to the severity of spasm (SMC grade): grade I – localized spasm around the periocular area; grade II – involuntary movement spreads to other parts of the ipsilateral face and it affects other muscle groups, i.e. the orbicularis oris, zygomaticus, frontalis or platysma muscle; grade III – interference with vision because of frequent tonic spasms, and grade IV – disfiguring asymmetry. We interviewed each patient using an HFS-7 questionnaire containing a short self-rating QoL scale. We estimated the measure of agreement across observers and examined the relationships between SMC grade and other factors, including HFS-7 responses. Results: Preoperative evaluation using the SMC grading system showed 25 patients with grade I, 48 patients with grade II, 33 patients with grade III, and 12 patients with grade IV HFS. The HFS-7 scores indicating QoL were 9 (range: 0–17) in grade I, 12 (range: 1–25) in grade II, 16 (range: 2–23) in grade III, and 17 (range: 3–24) in grade IV subjects. SMC grade was correlated with symptom duration (p < 0.0001) and HFS-7 score (p = 0.02). In addition, higher SMC grade was closely associated with longer duration of persisting symptoms (p < 0.05). Conclusions: An SMC grading system is useful as a means of quantifying spasms to allow for more precise descriptions of a patient’s condition including QoL, and to improve the accuracy of communication between medical teams.
Pharmacokinetics of Ertapenem in Colorectal Tissue
Authors: Wittau M. , Scheele J. , Bulitta J.B. , Mayer B. , Kaever V. , Burhenne H. , Henne-Bruns D. , Isenmann R. , Brockschmidt C.
Published: December 2011

Background: There are only limited data on tissue kinetics of ertapenem in colorectal tissue more than 3 h after administration of the drug. The purpose of this study was to assess the pharmacokinetics (PK) of ertapenem in colorectal tissue via population PK modeling. Patients and Methods: Patients ≧18 years requiring surgical intervention at the colon and/or rectum were eligible (ClinicalTrials.gov identifier: NCT 00535652). Tissue and blood samples were taken during surgery after a single dose of 1 g ertapenem. Ertapenem concentration was determined by high-performance liquid chromatography/mass spectrometry. Population PK modeling was performed in S-ADAPT. Results: Twenty-three patients were enrolled. The highest tissue concentration was 6.4 ± 2.3 mg/kg, the highest total plasma concentration 51.34 ± 9.4 mg/l, the highest unbound plasma concentration 7.05 ± 1.1 mg/l, and the unbound fraction in plasma was 14–15% for total ertapenem concentrations below approximately 22 mg/l, 19% at 100 mg/l, and 25% at 250 mg/l. The estimated geometric mean terminal half-life was 2.5 h for plasma and tissue. In the Monte Carlo simulation, a single dose of 1,000 mg ertapenem achieved robust (≧90%) probabilities of target attainment up to a minimum inhibitory concentration (MIC) of approximately 2 mg/l for the bacteriostasis target (free time above MIC, fT>MIC = 20%) and up to 0.25–0.5 mg/l for the near-maximal killing target (40% fT>MIC). Conclusion: Our data indicate an adequate penetration of ertapenem into uninfected colorectal tissue up to 8.5 h (35% of the dosing interval) after administration of 1 g intravenously.
Clinical Study of Twenty-One Patients with Pure Midbrain Infarction
Authors: Ogawa Katsuhiko , Suzuki Yutaka , Oishi Minoru , Kamei Satoshi
Published: December 2011

We investigated the neurological and MRI findings of 21 patients with pure midbrain infarction. The locations of the infarcts were classified into paramedian (PM) area (13 patients), lateral area (6 patients), and PM and lateral areas (1 patient), based on the distribution of each penetrating artery of the midbrain. The infarction of 1 patient showed bilateral multiple lesions. In the PM area group, 12 patients showed eye movement disorders and truncal and gait ataxia. Eye movement disorders consisted of medial longitudinal fasciculus syndrome, oculomotor nerve palsy, and bilateral vertical gaze palsy. The infarcts of the 2 patients with bilateral vertical gaze palsy were located in the PM area on both sides. Eye movement disorders and truncal and gait ataxia were prominent in the PM area group. Ataxic hemiparesis was shown in 2 patients of the PM area group and 4 patients of the lateral area group. We showed that ataxic hemiparesis also occurred in PM area infarction, although ataxic hemiparesis was a prominent feature of lateral area infarction.
Antitumor Activity from the Combined Application of Poly(I:C) and Chemotherapeutics in Human Metastatic Pharyngeal Cell Lines
Authors: Matijević Tanja , Kirinec Gabriela , Pavelić Jasminka
Published: December 2011

Background: Toll-like receptor 3 (TLR3) activation in tumor cells induces apoptosis. We investigated the effect of TLR3 ligand (poly(I:C)) in combination with chemotherapeutics applied to human pharyngeal carcinoma cells as a possible antitumor therapy. Methods:Human pharyngeal cancer cell lines were studied (FaDu and Detroit 562). Cytotoxicity assays and apoptosis assays (annexin V staining and caspase 3/7 activity measurements) were used to investigate the cytotoxic effects. By using TLR3 siRNA we confirmed that the observed effect is TLR3-dependent. Results: We found that the combined application of poly(I:C) and chemotherapeutics (cisPt, HU, 5-FU and MTX) has a stronger inhibitory effect on cell growth in tumor cells expressing functional TLR3 as compared with a single treatment. This is a result of TLR3-dependent apoptosis. Conclusion: Our study showed that a combined application of the two agents already being used in tumor therapy could lower the necessary dosage of chemotherapeutics, leading to fewer side effects.
Psychometric Properties of the Autonomy over Tobacco Scale in German
Authors: Wellman R.J. , Di Franza J.R. , Morgenstern M. , Hanewinkel R. , Isensee B. , Sabiston C.M.
Published: December 2011

Background/Aims: We investigated the psychometric properties of a German translation of the 12-item Autonomy over Tobacco Scale (AUTOS) among 1,195 eighth-grade students. Methods: Data for this study were collected as part of the fourth wave of data collection of the Smokefree Class Competition intervention in the Saxony-Anhalt region of Germany. Students from the control arm of the Smokefree Class Competition study who indicated that they had ever smoked ‘at least a few puffs’ on a cigarette were classified as ever-smokers. They self-completed questionnaires distributed by teachers. Results: AUTOS scores ranged from 0 to 36 with a distribution highly skewed toward lower-response categories. Inter-item correlations ranged from 0.65 to 0.89 (mean = 0.79, SD = 0.06). Composite reliability for the AUTOS was high (Ω = 0.96) and 3 lower-order factors were also reliable (withdrawal: 0.89, psychological dependence: 0.91, cue-induced cravings: 0.87). Concurrent validity was supported by strong relationships between the AUTOS and both lifetime cigarette consumption and current smoking frequency. Youths were 18 times more likely to be current smokers (95% CI = 11.9–27.2, p < 0.001) if they endorsed any AUTOS item. Conclusion: The German AUTOS is reliable and valid, and the results are consistent with the English AUTOS for use with adolescents.
A Novel GH1 Mutation in a Family with Isolated Growth Hormone Deficiency Type II
Authors: Gucev Zoran , Tasic Velibor , Saranac Liljana , Stobbe Heike , Kratzsch Jürgen , Klammt Jürgen , Pfäffle Roland
Published: December 2011

Background: Four distinct familial types of isolated GH deficiency (IGHD) have been described so far. Objective: We report a novel nonsense GH1 mutation in a father and a son. Patients: Father’s height was 137.3 cm (–6.79 SDS); mother’s height was 157.3 cm (–1.86 SDS). By the age of 8.25 years, his height was 104.3 cm (–4.82 SDS) and his weight was 18.3 kg (–3.35 SDS). GH stimulation tests had low peak GH value of 6.5 ng/ml (proband) and 6.3 ng/ml (father). Other pituitary hormones and magnetic resonance imaging (MRI) of the pituitary region was normal in both patients. The proband received recombinant human GH (rhGH) treatment (30 µg/kg/day) and he grew 15.4 cm in 15 months. Results: Sequencing of the GH1 gene revealed a novel heterozygous nonsense mutation in both the father and the son (c.199A>T), which introduces a stop codon in exon 3. Conclusion: We present a family with IGHD II, with severe short stature, no phenotypic characteristics of GHD and a novel nonsense mutation in exon 3 of the GH1 gene. As fibroblasts were unavailable, we used computer analysis and we propose a unique mechanism that combines aberrant splicing and derogated GH release from the pituitary with residual secretion of a bioinactive truncated GH peptide.
In the mirror of Ghalib
Authors: Pue A. Sean
Published: December 2011

This article focuses on studies of the preeminent Urdu and Persian poet Mirza Asadullah Khan ‘Ghalib’ written for the occasion of his death centennial in 1969 by three Pakistani Urdu writers: Mumtaz Husain, Salim Ahmad and N.M. Rashed. These studies also participate in a debate on Pakistani national culture at a moment when the Urdu literary community was increasingly divided, following the 1965 India–Pakistan war and the emergence of a ‘new generation’ of writers on either side of the border. Each author uses Ghalib to articulate a different model of the individual and his relationship to society and tradition, taking up a theme of Indo-Muslim selfhood that has typically been the site of intersection between literary and cultural politics. Through an examination of these works, this article highlights the role played by discussions of Indo-Muslim selfhood in cultural and literary debates in Urdu.
The effect of geometry on the dynamic buckling of longitudinally stiffened panels subject to uniaxial compression
Authors: Featherston C A
Published: December 2011

During an intermediate velocity impact in which the duration of loading is an order of milliseconds but shorter than the period of the structure’s first free vibration mode, there is a relationship between impact duration and buckling load. Although this relationship results in higher buckling loads for shorter duration impacts, the precise nature of the correlation depends on a number of factors one of which is geometry. This paper examines a series of longitudinally stiffened panels with varying radii of curvature subject to uniaxial compression. Results are compared to investigate the possibility of identifying behavioural trends relating to geometry.
Passive control of hub-corner separation/stall using axisymmetric-hub contouring
Authors: Chen P-P , Qiao W-Y , Hashmi S F A , Shi P-J , Zhao L
Published: December 2011

Numerical simulations were performed to investigate the forming mechanism of the compressor/fan hub-corner separation/stall. Taking the small-scaled vortex in the detached regions into account, scale adaptive simulation model coupled with shear stress transport model (SAS–SST turbulence model) does well in capturing the flow structures in the compressor. At near stall condition, low-momentum stall cell originates from the leading edge of the stator near hub, contributes to the greater turning angle at the suction side because of endwall viscosity, rolls, and lifts up in spanwise direction. The same then interacts with the wake in the downstream passage of stator, nearly taking up the whole passage downstream. Three vortex centres are generated at the hub induced by the boundary layer separation flow, one near the stator leading edge, a second one at the blade trailing edge near the suction side, and a third one near the middle passage, and further swirled up to the blade suction surface which can be recognized as thepassage vortex developed by the radial and circumferential pressure differences. Axisymmetric-hub contouring (a type of passive flow control techniques) has resulted in performance improvement of the compressor. Main contribution of performance enhancement is attributed to the suppression of hub-corner separation. Significant influence of axisymmetric contouring has been found on boundary layer separation structures near hub and passage vortex, which affects the formation and development of hub-corner stall.
Design of a 450-passenger blended wing body aircraft for active control investigations
Authors: Mohr B , Paulus D , Baier H , Hornung M
Published: December 2011

ACFA 2020 (active control for flexible aircraft) is a collaborative research project funded by the European Commission under the seventh research framework programme. The project deals with innovative active control concepts for 2020 aircraft configurations like the blended wing body (BWB) aircraft. The main objectives of ACFA are the design of a new ultra efficient 450 passenger BWB type aircraft as well as the provision of robust adaptive multi- channel control architectures for such aircraft. The objective of the newly designed controllers is an ambitious improvement of ride comfort and handling qualities, as well as load reduction on BWB type aircraft. Based on the attained load reduction, the structure of the 450-passenger aircraft can be resized with the goal of an ambitious weight saving for further improvement of fuel efficiency. Active control requirements influence the design process of control surfaces and overall aircraft design, respectively. Hence, the conventional aircraft design process had to be adapted to the new requirements. The aircraft design framework described in this article has proven its efficiency in the development of the ACFA BWB aircraft. Within a time period of 1 year, an airframe has been developed under the constraints of multiple domain requirements. This article presents the process and the results of the design activities of the BWB aircraft, which form the basis for a detailed concept analysis as well as the investigation of multiple-input multiple-output control architectures.
Odds Ratios and Confidence Intervals
Authors: Laing Catherine M. , Rankin James A.
Published: December 2011

Professional registered nurses (RNs) are active participants in seeking and interpreting research evidence. To facilitate knowledge transfer for RNs at the bedside, it behooves researchers to present their findings in a format that facilitates understanding. There is also an expectation that clinicians are capable of interpreting results in a meaningful way. It is important to be able to understand and interpret research reports where statistical methods are used as part of providing the safest and best care for patients. The purpose of this article is to describe the basic concepts of odds ratios and confidence intervals used in research. These statistical measures are used frequently in quantitative research and are often the principle measure of association that is reported. The more comfortable pediatric oncology clinicians are with the interpretation of odds ratios and confidence intervals, the better equipped they will be to bring relevant research results from the “bench” to the bedside.
Coping With Pediatric Cancer
Authors: Hildenbrand Aimee K. , Clawson Kathleen J. , Alderfer Melissa A. , Marsac Meghan L.
Published: December 2011

Pediatric cancer patients and their families face significant physical, emotional, and psychosocial challenges. Few studies have investigated how children manage these challenges and how parents may help in the process. This qualitative study aimed to explore common cancer-related stressors for children and to examine child coping and parental assistance in coping with these stressors during treatment. Fifteen children undergoing cancer treatment and their parents participated in semistructured interviews. Four themes emerged capturing cancer-related stressors: cancer treatment/side effects, distressing emotions, disruption in daily routines, and social challenges. Six themes emerged regarding child coping strategies that were classified within an approach/avoidance coping framework. Approach coping strategies included the following: cognitive restructuring, relaxation, practical strategies, seeking social support, and emotional expression. Distraction was the only avoidant coping strategy. Parents tended to encourage approach coping strategies (eg, cognitive restructuring, social support). Within families, few coping strategies were reported (child: M = 1.47, SD = 0.99; parent: M = 3.33, SD = 1.18), suggesting that early family-based interventions teaching coping techniques for cancer-related stressors may be beneficial.
An Empirical Assessment of the Communication Components Inventory
Authors: Keaton Shaughan A. , Bodie Graham D.
Published: December 2011

This article attempts to demonstrate the psychometric properties and evidence of validity for a measure recently proposed in this journal, the Communication Components Inventory (CCI). Across two studies, a total of 903 undergraduate students completed one of the two response formats—dichotomous and scaled—of the CCI and the Multiple Intelligence scale. The dichotomous response format poorly represented the data, as did the scaled response format. However, because of the latter’s superior reliability estimates it was chosen for refinement. Through the use of confirmatory factor analysis, the revised CCI replicated the data accurately. In both data samples, bivariate correlations between the Revised-Communication Components Inventory and a measure of learning styles were moderate to large, providing initial validity evidence for an important construct to counselors and their clients.
Being faithful: Bakhtin and a potential postmodern psychology of self
Authors: Cresswell James
Published: December 2011

Postmodern critique has found its way into the psychology of self largely by way of Gergen’s form of social constructionism. This view treats self as socially constructed and changeable, such that a notion like faithfulness to oneself, which is generally thought to belong in the domain of a true core self, is rendered futile. However, Mikhail Bakhtin offers a view of embodied and lived self that expands social constructionist work. It offers a way to think about faithfulness to oneself while not undermining the importance of sociality. This approach enables us to account for the experiential compellingness – which is currently missing in constructionist theorizing – that is bound up with self. The paper first discusses dialogue to show how Bakhtin inspires an understanding of how community shapes the embodied self in a way that calls for a return to the notion of faithfulness to oneself. Then the notion of authorship is addressed in order to show how he could inspire a way of thinking about self-creation (authoring individual self) and the concomitant struggle experienced in being faithful to one’s self.
Moving between frames: The basis of the stable and dialogical self
Authors: Moore Helen , Jasper Carol , Gillespie Alex
Published: December 2011

Research on the dialogical self has tended to emphasize instability over stability. Grossen and Salazar Orvig (2011) show how norms, values, material objects, and institutions feed into the stability of the self. We expand upon this contribution by introducing Goffman’s (1974) concept of “frames” to theorize both stability and instability. Social interactions do not begin with individuals but with socially given and pre-existing cultural-historical frames which people are called upon to inhabit. Frames comprise historical, institutional, material, and cultural aspects. The key point is that action within a frame tends to stabilize the self, while being caught between frames tends to destabilize the self. The concept of frames can thus provide a clear link between the structure of the social world and the structure of the dialogical self. We use the concept of frames to distinguish the stability produced by one set of expectations, within one frame, from the peculiar instability and dialogical tensions which result from being embedded in discrepant or contradictory frames.
How is feminist metaphysics possible? A Foucauldian intervention
Authors: Oksala Johanna
Published: December 2011

The article defends the importance of metaphysical inquiry in feminist philosophy and interrogates possible directions for such a project. A key aim is questioning the possibility of revisionary metaphysics as well as emphasising the consequences of the linguistic turn for any such project. I argue that before we can embark on any metaphysical inquiry – feminist or otherwise – we are doomed to repeating Immanuel Kant's monumental question of how is metaphysics possible? I then ask how metaphysics is understood in feminist discussions and focus on one contemporary effort to create feminist metaphysics, namely Christine Battersby's The Phenomenal Woman: Feminist Metaphysics and the Patterns of Identity (1998). Through a critical analysis of her position I tease out the problems, paradoxes and obstacles that the project of feminist metaphysics faces. Finally, I explicate the politicised conception of reality that I find in Michel Foucault's thought and conclude by considering its consequences for our understanding of feminist metaphysics and politics.
On the reduced-rank model with leading index
Authors: Hu Yu-Pin
Published: December 2011

The index model and the reduced-rank model are two useful models which adopt different views to explore a vector autoregressive (VAR) model structure. However, we expect that there will be more information when the two models are implemented simultaneously. This paper combines these two models to propose a VAR model with constraints. The model extracts the leading index and explores the reduced-rank structures simultaneously. In this study, theoretical results are presented, which include a necessary and sufficient condition for a transformation for parsimonious parameterizations and model identification, the maximum likelihood estimations and the likelihood ratio test. The empirical results for the analysis of famous US hog data using the proposed model display the unification of several results in the literature, revealing that the novel model is reasonable and works quite well.
Topological characterisation and identification of critical domains within glucosyltransferase IV (GtrIV) of Shigella flexneri
Authors: Nair Anesh , Korres Haralambos , Verma Naresh K
Published: December 2011

Background

The three bacteriophage genes gtrA, gtrB and gtr

(type)
are responsible for O-antigen glucosylation in Shigella flexneri. Both gtrA and gtrB have been demonstrated to be highly conserved and interchangeable among serotypes while gtr

(type)
was found to be specific to each serotype, leading to the hypothesis that the Gtr(type) proteins are responsible for attaching glucosyl groups to the O-antigen in a site- and serotype- specific manner. Based on the confirmed topologies of GtrI, GtrII and GtrV, such interaction and attachment of the glucosyl groups to the O-antigen has been postulated to occur in the periplasm.

Results

In this study, the topology of GtrIV was experimentally determined by creating different fusions between GtrIV and a dual-reporter protein, PhoA/LacZ. This study shows that GtrIV consists of 8 transmembrane helices, 2 large periplasmic loops, 2 small cytoplasmic N- and C- terminal ends and a re-entrant loop that occurs between transmembrane helices III and IV. Though this topology differs from that of GtrI, GtrII, GtrV and GtrX, it is very similar to that of GtrIc. Furthermore, both the N-terminal periplasmic and the C-terminal periplasmic loops are important for GtrIV function as shown via a series of loop deletion experiments and the creation of chimeric proteins between GtrIV and its closest structural homologue, GtrIc.

Conclusion

The current study provides the basis for elucidating the structure and mechanism of action of this important O-antigen modifying glucosyltransferase.
A pilot study for channel catfish whole genome sequencing and de novo assembly
Authors: Jiang Yanliang , Lu Jianguo , Peatman Eric , Kucuktas Huseyin , Liu Shikai , Wang Shaolin , Sun Fanyue , Liu Zhanjiang
Published: December 2011

Background

Recent advances in next-generation sequencing technologies have drastically increased throughput and significantly reduced sequencing costs. However, the average read lengths in next-generation sequencing technologies are short as compared with that of traditional Sanger sequencing. The short sequence reads pose great challenges for de novo sequence assembly. As a pilot project for whole genome sequencing of the catfish genome, here we attempt to determine the proper sequence coverage, the proper software for assembly, and various parameters used for the assembly of a BAC physical map contig spanning approximately a million of base pairs.

Results

A combination of low sequence coverage of 454 and Illumina sequencing appeared to provide effective assembly as reflected by a high N50 value. Using 454 sequencing alone, a sequencing depth of 18 X was sufficient to obtain the good quality assembly, whereas a 70 X Illumina appeared to be sufficient for a good quality assembly. Additional sequencing coverage after 18 X of 454 or after 70 X of Illumina sequencing does not provide significant improvement of the assembly. Considering the cost of sequencing, a 2 X 454 sequencing, when coupled to 70 X Illumina sequencing, provided an assembly of reasonably good quality. With several software tested, Newbler with a seed length of 16 and ABySS with a K-value of 60 appear to be appropriate for the assembly of 454 reads alone and Illumina paired-end reads alone, respectively. Using both 454 and Illumina paired-end reads, a hybrid assembly strategy using Newbler for initial 454 sequence assembly, Velvet for initial Illumina sequence assembly, followed by a second step assembly using MIRA provided the best assembly of the physical map contig, resulting in 193 contigs with a N50 value of 13,123 bp.

Conclusions

A hybrid sequencing strategy using low sequencing depth of 454 and high sequencing depth of Illumina provided the good quality assembly with high N50 value and relatively low cost. A combination of Newbler, Velvet, and MIRA can be used to assemble the 454 sequence reads and the Illumina reads effectively. The assembled sequence can serve as a resource for comparative genome analysis. Additional long reads using the third generation sequencing platforms are needed to sequence through repetitive genome regions that should further enhance the sequence assembly.
Chronic disease knowledge and its determinants among chronically ill adults in rural areas of Shanxi Province in China: a cross-sectional study
Authors: Tian Miaomiao , Chen Yingchun , Zhao Rui , Chen Li , Chen Xi , Feng Da , Feng Zhanchun
Published: December 2011

Background

Chronic disease knowledge is an important prerequisite for an individual to implement behavioural changes towards the prevention and control of chronic diseases (CDs). Limited information is available about the relationship between different levels of health services and CD knowledge among rural residents with CDs. This research explores the distribution characteristics of CD knowledge and its determinants among chronically ill adults in rural China according to the aspects of patients and health service providers.

Methods

A cross-sectional study was undertaken to estimate distribution characteristics of CD knowledge and collect data of socio-demographic characteristics, healthcare institutions attendances, duration of illness, and family history of CDs. Participants were 1060 rural adults with hypertension or type II diabetes. Correct responses to 12 questions were summed into a total knowledge score, and participants were divided into an adequate health knowledge group (score ≥ 6) or an inadequate health knowledge group (score < 5). Logistic regression was used determine the predictors of adequate CD health knowledge.

Results

The mean age of participants was 61.34 years (SD = 10 years). Out of a possible 12, the median score on the CD knowledge questionnaire was 3.0. About 25% of participants were classified as having adequate CD knowledge. Those who had a family history and/or long duration of CDs were more likely to have adequate health knowledge. Participants who received CD health information and self-care instructions from their physicians had 2.67 and 13.34 times greater odds of possessing adequate health knowledge than those who received no information, respectively. Adequate CD knowledge was strongly associated with regular check-ups, especially for those who attended township hospitals (OR = 40.17).

Conclusions

Having regular check-ups at a fixed healthcare institution and receiving health information from physicians are important measures for increasing CD knowledge among rural adults with CDs. Township hospitals are the most effective settings for health education. It is important to develop an effective community-based prevention and control mechanism for CDs. This requires township hospitals to take a leading role in improving CD knowledge among chronically ill patients, and enhancing implementation of health education in rural China.