bluuebunny/crossref_metadata_2025 huggingface dataset:
Capital Structure, Risk and Asymmetric Information
Authors: Halov Nikolay , Heider Florian
Published: May 2012

This paper argues that firms may not issue debt in order to avoid the adverse selection cost of debt. Theory suggests that since debt is a concave claim, it may be mispriced when outside investors are uninformed about firms' risk. The empirical literature has however paid little attention to the caveat that the "lemons" problem of external financing first identified by Myers (1984) only leads to debt issuance, i.e., a pecking order, if debt is risk free or, if it is risky, that it is not mispriced. This paper examines whether and for what firms the adverse selection cost of debt is more than a theoretical possibility and how this cost relates to other costs of debt such as bankruptcy. In the absence of any direct measure of something that is unknown to investors and thus cannot be in the econometrician's information set, we present extensive strong and robust evidence in a large unbalanced panel of publicly traded US firms from 1971 to 2001 that firms avoid issuing debt when the outside market is likely to know little about their risk.
Tradeoffs in Corporate Governance: Evidence From Board Structures and Charter Provisions
Authors: Gillan Stuart L. , Hartzell Jay C. , Starks Laura T.
Published: May 2012

We provide arguments and present evidence that corporate governance structures are composed of interrelated mechanisms, which are in turn endogenous responses to the costs and benefits firms face when they choose those mechanisms. Examining board structures and the use of corporate charter provisions in a sample of more than 2,300 firms over a four-year period, we find that firms cluster in their use of governance mechanisms. In particular, the set of charter provisions that firms use, as measured by the Gompers et al. (2003) G Index, is associated with board structure, with the laws of the state in which the firm is incorporated, and with firm and industry characteristics. We also find that some governance structures appear to serve as substitutes. Specifically, firms that have powerful boards (as measured by board independence) also have the greatest number of charter provisions, suggesting that the market for corporate control is less effective as a monitoring mechanism for these firms. In contrast, firms that have less powerful boards tend to have few charter provisions, suggesting that the market for corporate control plays a greater monitoring role at such firms. To address potential endogeneity issues, we employ three-stage least squares analysis to estimate these relationships within a system of equations. Our results from this analysis are consistent with the hypothesis that powerful boards serve as a substitute for the market for corporate control. Finally, our findings suggest that causality runs from the board to the choice of charter provisions, but not vice versa.
The other?
Authors: Gray Paul
Published: May 2012

In this issue of DATA BASE four Deans discuss the current state and the future of information systems within their Business Schools. They reflect on the malaise affecting academic information systems. This article examines the field in terms of its history, the nature of information systems work, and its potential future. It recognizes that people who work in IS are considered outsiders, THE OTHER, not only by the businesses in which they work but also by their business school colleagues. The paper draws lessons from what was done during the previous downturn in the 1990s and discusses the challenges the field faces. Looking at potential solutions for tomorrow, it considers such alternatives as reducing the glut of PhD's, redefining and updating the curriculum, riding the waves of change from new developments (e.g., Big Data, The Cloud), the formation of alliances with other fields, and moving information systems to independence of the Business School. Whether these approaches, either individually or in combination, are sufficient to change our reputation as THE OTHER is an open question.
Importance of the Numerical Representation of Shallow and Deep Convection for Simulations of Dust Transport over a Desert Region
Authors: Takemi Tetsuya
Published: May 2012

This study examines the representations of shallow and deep convection under two distinct stability conditions over a desert region with the use of the numerical outputs from large-eddy simulations at the 100 m horizontal resolution. The numerical experiments were set up under idealized conditions of a horizontally uniform basic state over a homogeneous and flat surface, which was aimed at representing fair-weather convective situations over the Gobi Desert. Spatial spectra were used in order to examine how small scales are reproduced and how representative scales appear at various heights. From the results of the spectral analyses, a grid scale required to properly represent shallow and deep convection in convection-resolving simulations is identified. It is indicated that the adequate representations of shallow and deep convection are critically important in simulating the transport of dust aerosols under convective conditions.
Cognitive Remediation for Individuals with Psychosis in a Supported Education Setting: A Pilot Study
Authors: Kidd Sean A. , Kaur Bajwa Jaswant , McKenzie Kwame J. , Ganguli Rohan , Haji Khamneh Bahar
Published: May 2012

Cognitive remediation (CR) is a treatment approach that is being increasingly examined as a means through which the cognitive impacts of schizophrenia might be ameliorated. While CR has demonstrated good outcomes when paired with supported employment, little is known regarding how it might be integrated within supported education contexts. In this study CR was examined in a supported education context with 16 individuals with psychosis. The findings indicated that CR aligned well with the academic curriculum with very low attrition, was found useful by students, and showed similar pre-post differences on cognitive measures as those found in previous work.
High‐Precision Continuation of Periodic Orbits
Authors: Dena Ángeles , Rodríguez Marcos , Serrano Sergio , Barrio Roberto
Published: May 2012

Obtaining periodic orbits of dynamical systems is the main source
of information about how the orbits, in general, are organized. In this paper, we extend classical continuation algorithms in order to be able to obtain families of periodic orbits with high‐precision. These periodic orbits can be corrected to get them with arbitrary precision. We illustrate the method with two important classical Hamiltonian problems.
Personal Epistemology of University Students: Individual Profiles
Authors: Kaartinen-Koutaniemi Minna , Lindblom-Ylänne Sari
Published: May 2012

The aims of this study were to examine and compare the consistency of personal epistemology profiles among university students representing three academic disciplines. Student interview data (N= 87) were analyzed in order to reveal students' conceptions of knowledge, thinking, and reasoning. The individual answers were examined and rated on a scale from absolutist to evaluativist thinking. On the basis of the student answers, three personal epistemology profiles were identified from the data: (i) absolutist profiles; (ii) relativistic profiles; and (iii) evaluativist profiles consisting of the subgroups entitled “limited” and “sophisticated.” The categorization of personal epistemology profiles was compared with background variables such as age, major subject, and study phase. The results indicated that the personal epistemology profiles varied significantly among students on the basis of the background variables. Explanations for the consistent and inconsistent personal epistemology profiles are discussed in more detail.
The PPARαAgonist Fenofibrate Reduces Prepulse Inhibition Disruption in a Neurodevelopmental Model of Schizophrenia
Authors: Rolland Benjamin , Marche Kevin , Cottencin Olivier , Bordet Régis
Published: May 2012

Oxidative stress has been implicated in neurodevelopmental theories of schizophrenia. Antioxidant Peroxysome Proliferator-Activated Receptors α (PPARα) agonist fenofibrate has neuroprotective properties and could reverse early preclinical infringements that could trigger the illness. We have evaluated the neuroprotective interest of fenofibrate in a neurodevelopmental rat model of schizophrenia. The oxidative lesion induced by Kainic Acid (KA) injection at postnatal day (PND) 7 has previously been reported to disrupt Prepulse Inhibition (PPI) at PND56 but not at PND35. In 4 groups of 15 male rats each, KN (KA-PND7+normal postweaning food), KF (KA-PND7+fenofibrate 0.2% food), ON (saline-PND7+normal food), and OF (saline+fenofibrate food), PPI was recorded at PND35 and PND56. Three levels of prepulse were used: 73 dB, 76 dB, and 82 dB for a pulse at 120 dB. Four PPI scores were analyzed: PPI73, PPI76, PPI82, and mean PPI (PPIm). Two-way ANOVAs were used to evaluate the effects of both factors (KA+fenofibrate), and, in case of significant results, intergroup Student’st-tests were performed. We notably found a significant difference (P<0.05) in PPIm between groups KN and KF at PND56, which supposes that fenofibrate could be worthy of interest for early neuroprotection in schizophrenia.
Identification of the Major Expressed S-Layer and Cell Surface-Layer-Related Proteins in the Model Methanogenic Archaea:Methanosarcina barkeriFusaro andMethanosarcina acetivoransC2A
Authors: Rohlin Lars , Leon Deborah R. , Kim Unmi , Loo Joseph A. , Ogorzalek Loo Rachel R. , Gunsalus Robert P.
Published: May 2012

Many archaeal cell envelopes contain a protein coat or sheath composed of one or more surface exposed proteins. These surface layer (S-layer) proteins contribute structural integrity and protect the lipid membrane from environmental challenges. To explore the species diversity of these layers in the Methanosarcinaceae, the major S-layer protein inMethanosarcina barkeristrain Fusaro was identified using proteomics. The Mbar_A1758 gene product was present in multiple forms with apparent sizes of 130, 120, and 100 kDa, consistent with post-translational modifications including signal peptide excision and protein glycosylation. A protein with features related to the surface layer proteins found inMethanosarcina acetivoransC2A andMethanosarcina mazeiGoel was identified in theM. barkerigenome. These data reveal a distinct conserved protein signature with features and implied cell surface architecture in the Methanosarcinaceae that is absent in other archaea. Paralogous gene expression patterns in twoMethanosarcinaspecies revealed abundant expression of a single S-layer paralog in each strain. Respective promoter elements were identified and shown to be conserved in mRNA coding and upstream untranslated regions. PriorM. acetivoransgenome annotations assigned S-layer or surface layer associated roles of eighty genes: however, of 68 examined none was significantly expressed relative to the experimentally determined S-layer gene.
Pathophysiology of Portal Hypertension and Esophageal Varices
Authors: Maruyama Hitoshi , Yokosuka Osamu
Published: May 2012

Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients, and approximately 5–15% of cirrhosis patients show newly formed varices or worsening of varices each year. The major therapeutic strategy of esophageal varices consists of primary prevention, treatment for bleeding varices, and secondary prevention, which are provided by pharmacological, endoscopic, interventional and surgical treatments. Optimal management of esophageal varices requires a clear understanding of the pathophysiology and natural history. In this paper, we outline the current knowledge and future prospect in the pathophysiology of esophageal varices and portal hypertension.
Alveolar Soft Part Sarcoma: A Single-Center 26-Patient Case Series and Review of the Literature
Authors: Ogura Koichi , Beppu Yasuo , Chuman Hirokazu , Yoshida Akihiko , Yamamoto Noboru , Sumi Minako , Kawano Hirotaka , Kawai Akira
Published: May 2012

Background.Alveolar soft part sarcoma (ASPS) is a rare tumor, and little information is available regarding its clinical features and appropriate treatments.Methods.A retrospective review of 26 consecutive ASPS patients (12 male, 14 female; mean age of 27 years) treated at our institution over 30 years (mean followup; 71 months) was performed.Results.The primary tumor developed in the lower extremity (12), trunk (8), and upper extremity (6), with an average size of 7.2 cm (range, 2–14 cm). The AJCC stage at presentation was IIA (7), III (3), and IV (16). Surgical excision was performed in 20 patients (R0 18, R1 plus radiotherapy 2) without local recurrence. Six patients (stage IIA 3/7, stage III 3/3) later developed metastases after an average period of 28.7 months. The median survival of the 26 patients was 90 months, with overall 5/10-year survival rates of 64%/48%. AJCC stage and tumor size were significant prognostic factors. Significant palliation and slowing of metastasis progression were achieved with gamma knife radiotherapy. Nine patients receiving chemotherapy showed no objective response.Conclusions.ASPS is indolent but has a high propensity for metastasis. Early diagnosis and complete excision of the small primary tumor are essential in the treatment of ASPS.
Fra-1 Promotes Breast Cancer Chemosensitivity by Driving Cancer Stem Cells from Dormancy
Authors: Lu Dan , Chen Si , Tan Xiaoyue , Li Na , Liu Chenghu , Li Zongjin , Liu Ze , Stupack Dwayne G. , Reisfeld Ralph A. , Xiang Rong
Published: May 2012

Fra-1 is a member of the Fos transcription factor family that is highly expressed in multiple cancers, playing important roles in transformation, proliferation, and metastasis. In this study, we observed an inverse correlation between the expression of Fra-1 in human stage II breast cancer tissues and the corresponding level of clinical chemoresistance. Extending these findings in vitro, we found that knockdown of Fra-1 in breast tumor cells was sufficient to confer resistance to doxorubicin and cyclophosphamide, whereas enhanced Fra-1 expression could render these cells chemosensitive. The tumor cell side population, which is enriched for cancer stem cells, was found to be associated with chemoresistance. Increased side population fractions were detected among tumor cell lines subjected to Fra-1 knockdown. In contrast, enhanced expression of Fra-1 was correlated with a decreased side population fraction, and significantly, this finding was recapitulated in vivo, where tumors with enhanced expression of Fra-1 were found to have blunted growth. Tumor cells subjected to Fra-1 knockdown grew faster and were larger in size. Taken together, our findings suggest that Fra-1 may be an important prognostic marker for breast cancer therapy. Cancer Res; 72(14); 3451–6. ©2012 AACR.
Identification of Serum Biomarker Signatures Associated with Pancreatic Cancer
Authors: Wingren Christer , Sandström Anna , Segersvärd Ralf , Carlsson Anders , Andersson Roland , Löhr Matthias , Borrebaeck Carl A. K.
Published: May 2012

Pancreatic cancer is an aggressive disease with poor prognosis, due, in part, to the lack of disease-specific biomarkers that could afford early and accurate diagnosis. With a recombinant antibody microarray platform, targeting mainly immunoregulatory proteins, we screened sera from 148 patients with pancreatic cancer, chronic pancreatitis, autoimmune pancreatitis (AIP), and healthy controls (N). Serum biomarker signatures were derived from training cohorts and the predictive power was evaluated using independent test cohorts. The results identified serum portraits distinguishing pancreatic cancer from N [receiver operating characteristics area under the curve (AUC) of 0.95], chronic pancreatitis (0.86), and AIP (0.99). Importantly, a 25-serum biomarker signature discriminating pancreatic cancer from the combined group of N, chronic pancreatitis, and AIP was determined. This signature exhibited a high diagnostic potential (AUC of 0.88). In summary, we present the first prevalidated, multiplexed serum biomarker signature for diagnosis of pancreatic cancer that may improve diagnosis and prevention in premalignant diseases and in screening of high-risk individuals. Cancer Res; 72(10); 2481–90. ©2012 AACR.
KRas Induces a Src/PEAK1/ErbB2 Kinase Amplification Loop That Drives Metastatic Growth and Therapy Resistance in Pancreatic Cancer
Authors: Kelber Jonathan A. , Reno Theresa , Kaushal Sharmeela , Metildi Cristina , Wright Tracy , Stoletov Konstantin , Weems Jessica M. , Park Frederick D. , Mose Evangeline , Wang Yingchun , Hoffman Robert M. , Lowy Andrew M. , Bouvet Michael , Klemke Richard L.
Published: May 2012

Early biomarkers and effective therapeutic strategies are desperately needed to treat pancreatic ductal adenocarcinoma (PDAC), which has a dismal 5-year patient survival rate. Here, we report that the novel tyrosine kinase PEAK1 is upregulated in human malignancies, including human PDACs and pancreatic intraepithelial neoplasia (PanIN). Oncogenic KRas induced a PEAK1-dependent kinase amplification loop between Src, PEAK1, and ErbB2 to drive PDAC tumor growth and metastasis in vivo. Surprisingly, blockade of ErbB2 expression increased Src-dependent PEAK1 expression, PEAK1-dependent Src activation, and tumor growth in vivo, suggesting a mechanism for the observed resistance of patients with PDACs to therapeutic intervention. Importantly, PEAK1 inactivation sensitized PDAC cells to trastuzumab and gemcitabine therapy. Our findings, therefore, suggest that PEAK1 is a novel biomarker, critical signaling hub, and new therapeutic target in PDACs. Cancer Res; 72(10); 2554–64. ©2012 AACR.
The Future Is Now: Chimeric Antigen Receptors as New Targeted Therapies for Childhood Cancer
Authors: Lee Daniel W. , Barrett David M. , Mackall Crystal , Orentas Rimas , Grupp Stephan A.
Published: May 2012

Improved outcomes for children with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, gene therapy, and cell-processing technologies have paved the way for clinical applications of chimeric antigen receptor–based therapies. This is a new form of targeted immunotherapy that merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity, potential for expansion, and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B-cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. In pediatric oncology, CD19 and GD2 are compelling antigens that have already been identified for targeting pre-B acute lymphoblastic leukemia and neuroblastoma, respectively, with this approach, but it is likely that other antigens expressed in a variety of childhood cancers will also soon be targeted using this therapy. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of childhood cancer. Clin Cancer Res; 18(10); 2780–90. ©2012 AACR.
Epigenetic Changes in Pediatric Solid Tumors: Promising New Targets
Authors: Lawlor Elizabeth R. , Thiele Carol J.
Published: May 2012

Cancer is being reinterpreted in the light of recent discoveries related to the histone code and the dynamic nature of epigenetic regulation and control of gene programs during development, as well as insights gained from whole cancer genome sequencing. Somatic mutations in or deregulated expression of genes that encode chromatin-modifying enzymes are being identified with high frequency. Nowhere is this more relevant than in pediatric embryonal solid tumors. A picture is emerging that shows that classic genetic alterations associated with these tumors ultimately converge on the epigenome to dysregulate developmental programs. In this review, we relate how alterations in components of the transcriptional machinery and chromatin modifier genes contribute to the initiation and progression of pediatric solid tumors. We also discuss how dramatic progress in our understanding of the fundamental mechanisms that contribute to epigenetic deregulation in cancer is providing novel avenues for targeted cancer therapy. Clin Cancer Res; 18(10); 2768–79. ©2012 AACR.
Promising Therapeutic Targets in Neuroblastoma
Authors: Matthay Katherine K. , George Rani E. , Yu Alice L.
Published: May 2012

Neuroblastoma, the most common extracranial solid tumor in children, is derived from neural crest cells. Nearly half of patients present with metastatic disease and have a 5-year event-free survival of <50%. New approaches with targeted therapy may improve efficacy without increased toxicity. In this review we evaluate 3 promising targeted therapies: (i) 131I-metaiodobenzylguanidine (MIBG), a radiopharmaceutical that is taken up by human norepinephrine transporter (hNET), which is expressed in 90% of neuroblastomas; (ii) immunotherapy with monoclonal antibodies targeting the GD2 ganglioside, which is expressed on 98% of neuroblastoma cells; and (iii) inhibitors of anaplastic lymphoma kinase (ALK), a tyrosine kinase that is mutated or amplified in ∼10% of neuroblastomas and expressed on the surface of most neuroblastoma cells. Early-phase trials have confirmed the activity of 131I-MIBG in relapsed neuroblastoma, with response rates of ∼30%, but the technical aspects of administering large amounts of radioactivity in young children and limited access to this agent have hindered its incorporation into treatment of newly diagnosed patients. Anti-GD2 antibodies have also shown activity in relapsed disease, and a recent phase III randomized trial showed a significant improvement in event-free survival for patients receiving chimeric anti-GD2 (ch14.18) combined with cytokines and isotretinoin after myeloablative consolidation therapy. A recently approved small-molecule inhibitor of ALK has shown promising preclinical activity for neuroblastoma and is currently in phase I and II trials. This is the first agent directed to a specific mutation in neuroblastoma, and marks a new step toward personalized therapy for neuroblastoma. Further clinical development of targeted treatments offers new hope for children with neuroblastoma. Clin Cancer Res; 18(10); 2740–53. ©2012 AACR.
GDC-0941, a Novel Class I Selective PI3K Inhibitor, Enhances the Efficacy of Docetaxel in Human Breast Cancer Models by Increasing Cell Death In Vitro and In Vivo
Authors: Wallin Jeffrey J. , Guan Jane , Prior Wei Wei , Lee Leslie B. , Berry Leanne , Belmont Lisa D. , Koeppen Hartmut , Belvin Marcia , Friedman Lori S. , Sampath Deepak
Published: May 2012

Purpose: Docetaxel is a front-line standard-of-care chemotherapeutic drug for the treatment of breast cancer. Phosphoinositide 3-kinases (PI3K) are lipid kinases that regulate breast tumor cell growth, migration, and survival. The current study was intended to determine whether GDC-0941, an orally bioavailable class I selective PI3K inhibitor, enhances the antitumor activity of docetaxel in human breast cancer models in vitro and in vivo.

Experimental Design: A panel of 25 breast tumor cell lines representing HER2+, luminal, and basal subtypes were treated with GDC-0941, docetaxel, or the combination of both drugs and assayed for cellular viability, modulation of PI3K pathway markers, and apoptosis induction. Drug combination effects on cellular viability were also assessed in nontransformed MCF10A human mammary epithelial cells. Human xenografts of breast cancer cell lines and patient-derived tumors were used to assess efficacy of GDC-0941 and docetaxel in vivo.

Results: Combination of GDC-0941 and docetaxel decreased the cellular viability of breast tumor cell lines in vitro but to variable degrees of drug synergy. Compared with nontransformed MCF10A cells, the addition of both drugs resulted in stronger synergistic effects in a subset of tumor cell lines that were not predicted by breast cancer subtype. In xenograft models, GDC-0941 enhanced the antitumor activity of docetaxel with maximum combination efficacy observed within 1 hour of administering both drugs. GDC-0941 increased the rate of apoptosis in cells arrested in mitosis upon cotreatment with docetaxel.

Conclusion: GDC-0941 augments the efficacy of docetaxel by increasing drug-induced apoptosis in breast cancer models. Clin Cancer Res; 18(14); 3901–11. ©2012 AACR.
Targeted Inhibition of Src Kinase with Dasatinib Blocks Thyroid Cancer Growth and Metastasis
Authors: Chan Christine M. , Jing Xia , Pike Laura A. , Zhou Qiong , Lim Dong-Jun , Sams Sharon B. , Lund Gregory S. , Sharma Vibha , Haugen Bryan R. , Schweppe Rebecca E.
Published: May 2012

Purpose: There are no effective therapies for patients with poorly differentiated papillary thyroid cancer (PTC) or anaplastic thyroid cancer (ATC), and metastasis to the bone represents a significantly worse prognosis. Src family kinases (SFKs) are overexpressed and activated in numerous tumor types and have emerged as a promising therapeutic target, especially in relation to metastasis. We recently showed that Src is overexpressed and activated in thyroid cancer. We therefore tested whether inhibition of Src with dasatinib (BMS-354825) blocks thyroid cancer growth and metastasis.

Experimental Design: The effects of dasatinib on thyroid cancer growth, signaling, cell cycle, and apoptosis were evaluated in vitro. The therapeutic efficacy of dasatinib was further tested in vivo using an orthotopic and a novel experimental metastasis model. Expression and activation of SFKs in thyroid cancer cells was characterized, and selectivity of dasatinib was determined using an Src gatekeeper mutant.

Results: Dasatinib treatment inhibited Src signaling, decreased growth, and induced cell-cycle arrest and apoptosis in a subset of thyroid cancer cells. Immunoblotting showed that c-Src and Lyn are expressed in thyroid cancer cells and that c-Src is the predominant SFK activated. Treatment with dasatinib blocked PTC tumor growth in an orthotopic model by more than 90% (P = 0.0014). Adjuvant and posttreatment approaches with dasatinib significantly inhibited metastasis (P = 0.016 and P = 0.004, respectively).

Conclusion: These data provide the first evidence that Src is a central mediator of thyroid cancer growth and metastasis, indicating that Src inhibitors may have a higher therapeutic efficacy in thyroid cancer, as both antitumor and antimetastatic agents. Clin Cancer Res; 18(13); 3580–91. ©2012 AACR.
CTLA-4 Blockade Expands Infiltrating T Cells and Inhibits Cancer Cell Repopulation during the Intervals of Chemotherapy in Murine Mesothelioma
Authors: Wu Licun , Yun Zhihong , Tagawa Tetsuzo , Rey-McIntyre Katrina , de Perrot Marc
Published: May 2012

Cancer immunotherapy has shown promising results when combined with chemotherapy. Blocking CTLA-4 signaling by monoclonal antibody between cycles of chemotherapy may inhibit cancer cell repopulation and enhance the antitumoral immune reaction, thus improve the efficacy of chemotherapy in mesothelioma. The impact of CTLA-4 blockade on the early stage of tumor development was evaluated in a subcutaneous murine mesothelioma model. CTLA-4 blocking antibody was administered following each cycle of chemotherapy, and monotherapy was included as controls. Antitumor effect was evaluated by tumor growth delay and survival of the animals. Tumor cell repopulation was quantified by bromodeoxyuridine incorporation and Ki67 by immunohistochemistry and/or flow cytometry. In vitro cell killing was determined by classic chromium-released assay, and reverse transcription PCR (RT-PCR) was carried out to determine the gene expression of associated cytokines. Anti-CTLA-4 monoclonal antibody was able to inhibit tumor growth at early stage of tumor development. Antitumor effect was achieved by administration of CTLA-4 blockade between cycles of chemotherapy. Tumor cell repopulation during the intervals of cisplatin was inhibited by CTLA-4 blockade. Anti-CTLA-4 therapy gave rise to an increased number of CD4 and CD8 T cells infiltrating the tumor. RT-PCR showed that the gene expression of interleukin IL-2, IFN-γ, granzyme B, and perforin increased in the tumor milieu. Blockade of CTLA-4 signaling showed effective anticancer effect, correlating with inhibiting cancer cell repopulation between cycles of chemotherapy and upregulating tumor-infiltrating T lymphocytes, cytokines, and cytolytic enzymes in a murine mesothelioma model. Mol Cancer Ther; 11(8); 1809–19. ©2012 AACR.
Comparison of Doppler-Based and Three-Dimensional Methods for Fetal Cardiac Output Measurement
Authors: DeKoninck Philip , Steenhaut Patricia , Van Mieghem Tim , Mhallem Mina , Richter Jute , Bernard Pierre , De Catte Luc , Deprest Jan
Published: May 2012

Objective: Fetal cardiac output is conventionally measured using two-dimensional (2D) and Doppler ultrasound (Doppler). New methods based on 3D measurements of ventricular size in systole and diastole have been proposed. Our aim was to validate these tools against the conventional Doppler-based methods. Methods: Fetal combined cardiac output was prospectively measured at 16, 20, and 24 weeks of gestation in 15 uncomplicated pregnancies using Doppler and three different 3D algorithms [virtual organ computer-aided analysis (VOCAL), sonographic automatic volume calculation (SonoAVC), and inversion mode]. We determined the inter- and intraobserver variability of the 3D techniques and assessed the correlation between Doppler and 3D. Results: The 3D techniques showed adequate inter- and intraobserver reproducibility (intraclass correlation coefficient 0.69–0.98), with the best reproducibility for SonoAVC and inversion mode. Bland-Altman analysis revealed low bias and relatively good correlations when comparing the 3D methods among each other, albeit with wide 95% confidence intervals. Doppler measurement of fetal weight-adjusted combined cardiac output (349.0 ml·min–1·kg–1) yielded significantly higher results than 3D CO measurements (177.2, 160.7, and 174.0 ml·min–1·kg–1 for VOCAL, SonoAVC, and inversion mode, respectively; p < 0.0001) and correlated poorly with the 3D methods. Conclusions: Although 3D volume-based cardiac output measurements are reproducible, results obtained with different methods are not interchangeable. SonoAVC and inversion have the highest intra- and interobserver reproducibility. Results of cardiac output measurement by 3D and Doppler cannot be interchanged.
Fecal Calprotectin Concentrations in Premature Infants Have a Lower Limit and Show Postnatal and Gestational Age Dependence
Authors: Zoppelli Luciano , Güttel Christian , Bittrich Hans-Jörg , Andrée Clemens , Wirth Stefan , Jenke Andreas
Published: May 2012

Background: There is a need for reliable diagnostic biomarkers in necrotizing enterocolitis (NEC). Whereas fecal calprotectin (fCP) has been reported to have insufficient sensitivity and specificity, no previous study has stratified for gestational and postnatal age. Objective: We aimed to provide developmental specific fCP data in premature infants and to analyze its value in detecting intestinal distress and episodes of NEC. Methods: Between April 2008 and December 2009, 1,899 fecal samples were obtained from 206 very low birth weight infants. Results: Mean gestational age (GA) was 28.5 weeks and birth weight 1,057 g. 19 (9.2%) patients developed NEC stage II+, of whom 5 had fulminant NEC with unusually low fCP concentrations in meconium and afterwards. fCP levels showed significant gestational and postnatal age dependent dynamics with particularly low levels in extremely premature infants. In infants with a GA <26 + 1 weeks using GA-adapted reference values, the sensitivity for discriminating moderate NEC from healthy infants and infants with intestinal distress was 0.89 for a cut-off of 180 and 210 µg/g, respectively, at onset of symptoms. Specificity was 0.96 and 0.84. Fulminant NEC was characterized by unusually low fCP concentrations with a cut-off of <24 µg/g having a sensitivity of 0.84 and a specificity of 0.72 for identifying those cases. Conclusions: fCP levels depend on gestational and postnatal age and in contrast to adults, there is a lower limit in premature infants. Taking these observations into account when defining reference values and interpreting fCP data in the clinical context, fCP can be a useful marker in identifying premature infants with gastrointestinal distress and NEC in particular.
Oral Sensorimotor Integration in Adults Who Stutter
Authors: Loucks Torrey M. , De Nil Luc F.
Published: May 2012

Objective: To investigate the relationship between tendon vibration sensitivity and oral motor control in adults who stutter (AWS). Patients and Methods: Ten controls and 10 AWS first made jaw-opening movements from a closed-mouth position to an 18-mm target. Then, masseter tendon vibration was applied during jaw opening in a separate condition to test whether accuracy and/or variability is related to movement undershoot. Results: AWS made less accurate and more variable jaw movements than controls without visual feedback. Among the normally fluent adult participants, higher accuracy and lower variability were significantly related to masseter vibration undershoot, but significant correlations were not observed for AWS. Conclusion: These results suggest that increased tendon vibration sensitivity may be related to more refined oral motor control. Subtle sensorimotor limitations could be present in stuttering that render speech more susceptible to breakdowns.
Cholesteryl Ester Transfer Protein and ATP-Binding Cassette Transporter A1 Genotype Alter the Atorvastatin and Simvastatin Efficacy
Authors: Kolovou Genovefa , Kolovou Vana , Mihas Constantinos , Giannakopoulou Vasiliki , Vasiliadis Iannis , Boussoula Elena , Kollia Aikaterini , Boutsikou Maria , Katsiki Niki , Mavrogeni Sophie
Published: May 2012

We compared the efficacy of atorvastatin with simvastatin according to cholesteryl ester transfer protein (CETP) and adenosine triphosphate-binding cassette transporter A1 ( ABCA1) genes. Patients treated with atorvastatin (n = 254) or simvastatin (n = 332) were genotyped for CETP (TaqIB and I405V) and ABCA1 (R219K) genetic variants. For genotype B1B2, atorvastatin compared with simvastatin treatment resulted in a greater decrease in total cholesterol (35.4% vs 31.6%, P = .035) and a lower increase in high-density lipoprotein cholesterol (2% vs 8%, P = .05). For genotype B2B2, atorvastatin compared with simvastatin treatment resulted in a lower decrease in low-density lipoprotein cholesterol (31.85 vs 42%, P = .029). For genotypes RR and KK, atorvastatin compared with simvastatin treatment resulted in a greater decrease of triglycerides (27% vs 17% and 35% vs 15%, respectively; P = .02 for all comparisons). The TaqIB and R219K (opposite to I405V) gene polymorphisms seem to modify the response to lipid-lowering therapy with simvastatin or atorvastatin treatment.
A Comparison of Embedded Total Task Instruction in Teaching Behavioral Chains to Massed One-on-One Instruction for Students With Intellectual Disabilities
Authors: Jameson J. Matt , Walker Ryan , Utley Kristen , Maughan Ryan
Published: May 2012

This study is a comparison of the embedded instruction of behavioral chains with more traditional (one-on-one massed trials in special education setting) instructional procedures for teaching behavioral chains to students with significant cognitive disabilities. Although embedded instruction has emerged as a promising potential instructional procedure, no literature has examined the efficacy of embedded instructional procedures to teach more complex chained behaviors. To date, all research on embedding instruction in general education settings has focused on teaching discrete skills. This study compares instruction of embedded total task chains with more traditional (one-on-one massed trials in special education setting) instructional procedures for teaching behavioral chains. The chains targeted for instruction were selected by state core educational needs and functional skill development.
The Effect of a Postoperative Course of Oral Prednisone on Postoperative Morbidity following Childhood Tonsillectomy
Authors: Macassey Emily , Dawes Patrick , Taylor Barry , Gray Andrew
Published: May 2012

Objective

Tonsillectomy is a common procedure with a wide range of described operative techniques and usage of perioperative medications. Single‐dose intraoperative dexamethasone has been shown to decrease postoperative nausea and pain and improve return to normal diet. The aim was to determine if a course of oral postoperative steroids would further decrease postoperative morbidity following tonsillectomy in children.

Study Design

Randomized, placebo‐controlled, double‐blinded trial. Power analysis recommended 198 participants.

Setting

A university hospital and private hospital.

Subjects and Methods

The authors compared a 5‐day course of oral prednisolone with placebo in a pediatric population (3‐16 years) undergoing tonsillectomy to assess effects on postoperative pain, nausea, and vomiting and return to normal function. They also assessed the effect of corticosteroids on sleep duration and aspects of sleep quality.

Results

The results showed no significant difference between the 2 groups when analyzed for differences in the above variables both overall and at each of the postoperative 10 time points (pain, P =. 478; nausea and vomiting, P =. 556; return to normal diet well, P =. 234; return to normal activity, P =. 668; bedtime, P =. 056; number of times awake during the night, P =. 593).

Conclusion

There is no evidence of benefit from postoperative administration of corticosteroids in pediatric patients recovering from tonsillectomy.
Metals in RDF and other high calorific value fractions from mechanical treatment of MSW: analysis and sampling errors
Authors: Skutan Stefan , Brunner Paul H
Published: May 2012

RDF and other high calorific value fractions derived from MSW by mechanical treatment processes contain goods such as cans, cables, zippers or batteries which are highly concentrated in metals. The objective of this study was to investigate the importance of these metal carriers (i) for total metal loads and (ii) for sampling errors. Six different products derived from MSW were analysed for carrier bound and total loads of Al, Cd, Cr, Cu, Fe, Ni, Pb and Zn. Sophisticated sample preparation procedures were applied in order to quantify the separate analyte loads from metallic carriers. Typical values for total metal contents and shares of carrier bound loads were found as follows: Al, 20 g kg−1 (30%); Cr, 0.4 g kg−1 (50%); Cu, 5 g kg−1 (80%); Fe, 40 g kg−1 (80%); Ni, 0.15 g kg−1 (70%); Pb, 0.4 g kg−1 (40%); and Zn, 2 g kg−1 (30%). NiCd-batteries were found in three materials representing 30–70 % of total Cd contents (total 6–20 mg kg−1). Sampling errors related to the distribution of analyte carriers were in most cases found in the range of 50–150 % relative standard deviation in spite of the large sample masses of 200–800 kg. The results demonstrate: (1) metal carriers are responsible for significant analyte loads; if they are not adequately considered, total metal contents may be severely underestimated; (2) sampling errors are dominated by the distribution of carriers; (3) correct analysis of total metal contents including loads from metallic components requires expensive sample preparation.
An Ecological Perspective on U.S. Latinos’ Health Communication Behaviors, Access, and Outcomes
Authors: Katz Vikki S. , Ang Alfonso , Suro Roberto
Published: May 2012

U.S. Latinos experience constrained access to formal health care resources, contributing to higher incidence of preventable diseases and chronic health conditions than the general population. The authors explore whether a rich set of informal health communication connections—to friends, family, radio, television, Internet, newspapers, magazines, churches, and community organizations—can compensate, even partially, for not having access to doctors. The authors find no evidence of any such compensatory mechanism among respondents to the Pew Hispanic Center/Robert Wood Johnson Latino Health Survey ( N = 3,899). Analyses revealed that the informal health communication ecologies of respondents with favorable immigration/nativity status and greater income, education, and language proficiencies were more diversified than those of respondents reporting less favorable social status. Further analyses revealed that diversified informal health communication ecologies related to health care access (regular doctor visits, uninterrupted health insurance, and regular health care location) and favorable health outcomes (self-ratings of general health, health-related efficacy, and knowledge of diabetes symptoms).
Patterns of Injury and Reported Violence Depending on Relationship to Assailant in Female Swedish Sexual Assault Victims
Authors: Möller Anna Sofia , Bäckström Torbjörn , Söndergaard Hans Peter , Helström Lotti
Published: May 2012

Earlier studies have explored the differences between known-assailant sexual assaults and stranger assaults and reported the stranger assaults as being more violent. Only a few studies have discriminated between sexual assaults by intimate partners from assaults by other known assailants when comparing with assaults by strangers. In this study, we explored differences in the extent of violence and physical injury in sexual assaults committed by intimate partners compared with assaults by strangers and acquaintances. Medical and forensic records of 690 consecutive women attending a sexual assault center in Stockholm, Sweden were reviewed. The final sample included in the analysis consisted of 503 patients. Our results showed that women sexually assaulted by their intimate partners more frequently reported physical violence ( OR = 4.1) than women assaulted by strangers ( OR = 2.0) and acquaintances ( OR = 1.0). Genital injuries were not found to be related to the victim–assailant relationship in this study. Extragenital injuries showed a tendency toward being more frequently found after intimate partner assaults compared with stranger and acquaintance assaults; however, this was not found to be significant in adjusted analyses. Previous history of sexual assault was more common, and seeking medical care within 72 hr as well as being under the influence of alcohol during the assault was less frequent among intimate partner victims. These results support the conclusion that sexual assaults committed by intimate partners, contradictory to earlier studies, are likely to involve more physical violence and result in injuries just as often as assaults committed by strangers.
Dermatopathy in juvenile Angus cattle due to vitamin A deficiency
Authors: Baldwin Thomas J. , Rood Kerry A. , Kelly E. Jane , Hall Jeffery O.
Published: May 2012

In juvenile cattle, vitamin A deficiency is reported most commonly as a neurological condition; only rarely are there dermatologic manifestations. In the current study, alopecia, severe epidermal and follicular orthokeratosis, and acanthosis due to hypovitaminosis A are reported in 2 of 32 Angus calves, with a third animal suspected. Affected animals responded to vitamin A supplementation, and no additional calves displayed signs. Vitamin A acts on skin by regulating DNA transcription in keratinocytes, reducing the number of tonofilaments and desmosomes, both involved in cell-to-cell adhesion. Hence, adequate levels of dietary vitamin A are necessary for normal keratinocyte turnover, and deficiencies result in retention of keratinized cells (orthokeratosis). The present report reminds diagnosticians to consider vitamin A deficiency in cases of orthokeratotic dermatopathy in cattle.
Heat-related injury in lambs
Authors: Sula Mee Ja M. , Winslow Christine M. , Boileau Melanie J. , Barker L. D. , Panciera Roger J.
Published: May 2012

The broad spectrum of heat-related injury (HRI) and its associated lesions is well described in the human literature, with rare reports of similar findings in farm animals. In the current case series, lesions from 4 of 8 lambs that presented with clinical signs of heat stress are reported. Gross lesions at necropsy consisted of acute renal swelling and pallor in 2 of 4 lambs, muscle pallor in 2 of 4 lambs, and chronic bronchointerstitial pneumonia in each of the 4 lambs. Histological lesions considered heat-related included acute renal tubular necrosis, pigment casts, tubular epithelial regeneration, multifocal myocyte degeneration, necrosis, and dropout with histiocytic influx and regeneration. Chronic, bronchointerstitial pneumonia, present in each lamb, was considered a condition predisposing to HRI. Compatibility between observed lesions and those reported in human beings with injury secondary to elevated body temperatures established a diagnosis of HRI in these animals. Diagnostic pathologists should consider HRI in lambs with histological evidence of renal tubular necrosis and/or rhabdomyolysis and even in cases where the clinical picture is strongly suggestive but lesions are not demonstrable.
Modeling, simulation and analysis of controllers for brushless direct current motor drives
Authors: Shanmugasundram Ramasami , Zakaraiah K Muhammad , Yadaiah N
Published: May 2012

Brushless direct current (BLDC) motors are widely used in industrial, aerospace, medical, machine tools, aerospace and control applications. Nowadays they are becoming popular due to their advantages such as reduced maintenance, better speed-torque characteristics, good dynamic performance, noiseless operation, wide speed range, compact size, high torque to volume ratio, low moment of inertia and high efficiency. However, very few control techniques are available for controlling the BLDC drive systems. This paper presents a MATLAB simulation of practically realizable control techniques such as a conventional proportional-integral-derivative (PID) controller, a fuzzy controller, an adaptive artificial neural network proportional-integral-derivative (ANN-PID) controller and a pulse width modulation technique based PID controller for achieving better performance during the operating conditions. The simulation results are presented to highlight the effectiveness of these controllers such as speed of response, overshoot and steady-state error etc.
History, culture and cognition: Towards a dynamic model of social memory
Authors: Hewer Christopher J , Roberts Ron
Published: May 2012

The term social memory refers to the dynamic interplay between history, culture and cognition. At the level of the individual, three sources of knowledge: history, collective memory and individual experience combine to create a subjective view of historical reality, a common sense narrative that is often expressed with identity objectives and within an autobiographical context. This model of social memory, which is informed by social representations theory, makes a distinction between (i) collective memory, which is resistant to change, and (ii) representations of the past discussed and disseminated within a social milieu, which have the potential to evolve into new or altered perspectives, particularly when they are vulnerable to generational shift.