bluuebunny/crossref_metadata_2025 huggingface dataset:
Observations of Anomalous Microwave Emission from HII Regions
Authors: Dickinson Clive
Published: February 2013

I give a summary of the observations of Anomalous Microwave Emission (AME) from HII regions. AME has been detected in, or in the vicinity of, HII regions. Given the difficulties in measuring accurate SEDs over a wide range of frequencies and in complex environments, many of these detections require more data to confirm them as emitting significant AME. The contribution from optically thick free-free emission from UCHII regions may be also be significant in some cases. The AME emissivity, defined as the ratio of the AME brightness to the 100 μm brightness, is comparable to the value observed in high-latitude diffuse cirrus in some regions, but is significantly lower in others. However, this value is dependent on the dust temperature. More data, both at high frequencies (>~5 GHz) and high resolution (~1′ or better) is required to disentangle the emission processes in such complex regions.
Bioequivalence Study of Pantoprazole Sodium-HPBCD and Conventional Pantoprazole Sodium Enteric-Coated Tablet Formulations
Authors: Kamdi Sandesh P. , Palkar Prashant J.
Published: February 2013

The objective of this study was to investigate the bioequivalence of two formulations of 40 mg pantoprazole sodium enteric-coated tablets: Tripepsa as the test and Pantocid as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 1-month washout period in 25 healthy Indian volunteers. After drug administration, serial blood samples were collected over a period of 30 hours. Plasma pantoprazole concentrations were measured by high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of and were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of and values of the test product over those of the reference product were 90.21 (83.69–97.24) and 108.68 (100.21–117.86), respectively (within the bioequivalence range of 80–125%). On the basis of pharmacokinetic parameters including , , and values, both the formulations were bioequivalent.
Cervical Thymic Cyst: A Rare Differential Diagnosis in Lateral Neck Swelling
Authors: Shenoy Vijendra , Kamath M. Panduranga , Hegde Mahesh Chandra , Rao Aroor Raghavendra , Maller Vijetha V.
Published: February 2013

Introduction. Thymic cysts are among the rarest cysts found in the neck. Nests of thymic tissue may be found anywhere along the descent of the thymic primordia from the angle of the mandible to the mediastinum. Mediastinal extension is seen in 50% of cervical thymic cysts.Case Report. We report an uncommon case of a 15-year-old male, who noted a painless, growing mass on left side of his neck of one-year duration. Computerised tomographic scan showed a multiloculated fluid density lesion with enhancing septae in the left parapharyngeal space, extending from the level of mandible up to C7 vertebral level. Here, we discuss the surgical aspect, histopathology, and management of this rare lateral neck swelling.Discussion. Clinically, in most cases, cervical thymic lesions present as a unilateral asymptomatic neck mass, commonly on the left side of the neck, and 75% of patients present before 20 years of age.Conclusion. Thymic cyst should be included as differential diagnosis of cystic neck masses. Greater awareness among the pathologists may decrease misdiagnosis.
Uniqueness Theorems of Difference Operator on Entire Functions
Authors: Ding Jie
Published: February 2013

We investigate the uniqueness questions of the difference operator on entire functions and obtain three uniqueness theorems using the idea of weight sharing.
Autism in Toddlers: Can Observation in Preschool Yield the Same Information as Autism Assessment in a Specialised Clinic?
Authors: Westman Andersson Gunilla , Miniscalco Carmela , Johansson Ulrika , Gillberg Christopher
Published: February 2013

We wanted to know whether preschool observation of children suspected of suffering from autism can provide the same information about core autism symptoms as the Autism Diagnostic Observation Schedule (ADOS) performed in a clinic. Forty 2–4‐year‐old children (9 girls, 31 boys), referred for assessment of suspected autism spectrum disorder participated in the study. The symptom areas covered by the ADOS algorithm were scored by an education specialist after free‐field observation of each child in the preschool without using the prescribed ADOS materials. The ADOS was then completed in a clinic setting by examiners blind to the preschool results. Excellent agreement across results obtained at the two different types/settings of observations was found. The only significant difference found was with regard to spontaneous initiation of joint attention. The present study does not address the issue of whether or not one of the methods used is superior to the other when it comes to determining the “true” level of “autism problems” in these children. However, it is of interest that free‐field preschool observation of children with suspected autism using a structured checklist yields very similar information as that obtained at ADOS assessment performed in a clinic setting.
Modeling the Dynamics of a Single-Species Model with Pollution Treatment in a Polluted Environment
Authors: Liu Bing , Luan Shi , Gao Yinghui
Published: February 2013

Without any question, environmental pollution is the main cause for the species extinction in recent times. In this paper, based on impulsive differential equation, the dynamics of a single-species model with impulsive pollution treatment at fixed time in a polluted environment is considered, in which we assume that the species is directly affected by the pollutants. Sufficient conditions for permanence and extinction of the species are given. The results show that the species is permanent when the impulsive period is less than some critical value, otherwise the species will be extinct. Although shortening the impulsive period can protect the species from extinction, it is expensive. To see how pollution treatment applications could be economical, we also establish a hybrid impulsive model involving periodic pollution treatment at fixed time with state-dependent pollution treatment applied when the pollution concentration reaches the given Environment Threshold (ET). It indicates that the hybrid method is the most effective method to protect the species from extinction. Numerical simulations confirm our theoretical results.
Hexagonal Manganites—(RMnO3): Class (I) Multiferroics with Strong Coupling of Magnetism and Ferroelectricity
Authors: Lorenz Bernd
Published: February 2013

Hexagonal manganites belong to an exciting class of materials exhibiting strong interactions between a highly frustrated magnetic system, the ferroelectric polarization, and the lattice. The existence and mutual interaction of different magnetic ions (Mn and rare earth) results in complex magnetic phase diagrams and novel physical phenomena. A summary and discussion of the various properties, underlying physical mechanisms, the role of the rare earth ions, and the complex interactions in multiferroic hexagonal manganites, are presented in this paper.
Mediators of Inflammation-Induced Bone Damage in Arthritis and Their Control by Herbal Products
Authors: Nanjundaiah Siddaraju M. , Astry Brian , Moudgil Kamal D.
Published: February 2013

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints leading to bone and cartilage damage. Untreated inflammatory arthritis can result in severe deformities and disability. The use of anti-inflammatory agents and biologics has been the mainstay of treatment of RA. However, the prolonged use of such agents may lead to severe adverse reactions. In addition, many of these drugs are quite expensive. These limitations have necessitated the search for newer therapeutic agents for RA. Natural plant products offer a promising resource for potential antiarthritic agents. We describe here the cellular and soluble mediators of inflammation-induced bone damage (osteoimmunology) in arthritis. We also elaborate upon various herbal products that possess antiarthritic activity, particularly mentioning the specific target molecules. As the use of natural product supplements by RA patients is increasing, this paper presents timely and useful information about the mechanism of action of promising herbal products that can inhibit the progression of inflammation and bone damage in the course of arthritis.
Ergonomic Fuzzy Evaluation of Firefighting Operation Motion
Authors: Yang Lifang , Zhao Tianjiao , Meng Fanyu
Published: February 2013

The firefighting operation motion has an important impact on the safety and comfort of firefighting operation. As a judgment criterion of the firefighting efficiency, the comfort level is hard to judge in that it is completely decided by human feeling, so the comprehensive fuzzy evaluation is utilized for evaluation of comfort level. In this paper, firstly the factor and judgment set of firefighting operation comfort level are determined, and the fuzzy weight evaluation is obtained by questionnaires and analytic hierarchy process. Secondly, the joint angles of some particular motions are determined by motion capture equipment, the moment is obtained by ergonomic engineering software, and then the comprehensive comfort evaluation on firefighting operation motion is completed. Finally, the objective evaluation system of firefighting operation comfort is established.
A Finite Difference Scheme for Compressible Miscible Displacement Flow in Porous Media on Grids with Local Refinement in Time
Authors: Liu Wei
Published: February 2013

Considering two-dimensional compressible miscible displacement flow in porous media, finite difference schemes on grids with local refinement in time are constructed and studied. The construction utilizes a modified upwind approximation and linear interpolation at the slave nodes. Error analysis is presented in the maximum norm and numerical examples illustrating the theory are given.
PSI Methodologies for Nuclear Data Uncertainty Propagation with CASMO-5M and MCNPX: Results for OECD/NEA UAM Benchmark Phase I
Authors: Wieselquist W. , Zhu T. , Vasiliev A. , Ferroukhi H.
Published: February 2013

Capabilities for uncertainty quantification (UQ) with respect to nuclear data have been developed at PSI in the recent years and applied to the UAM benchmark. The guiding principle for the PSI UQ development has been to implement nonintrusive “black box” UQ techniques in state-of-the-art, production-quality codes used already for routine analyses. Two complimentary UQ techniques have been developed thus far: (i) direct perturbation (DP) and (ii) stochastic sampling (SS). The DP technique is, first and foremost, a robust and versatile sensitivity coefficient calculation, applicable to all types of input and output. Using standard uncertainty propagation, the sensitivity coefficients are folded with variance/covariance matrices (VCMs) leading to a local first-order UQ method. The complementary SS technique samples uncertain inputs according to their joint probability distributions and provides a global, all-order UQ method. This paper describes both DP and SS implemented in the lattice physics code CASMO-5MX (a special PSI-modified version of CASMO-5M) and a preliminary SS technique implemented in MCNPX, routinely used in criticality safety and fluence analyses. Results are presented for the UAM benchmark exercises I-1 (cell) and I-2 (assembly).
Gastric Volvulus and Wandering Spleen: A Rare Surgical Emergency
Authors: Lianos Georgios , Vlachos Konstantinos , Papakonstantinou Nikolaos , Katsios Christos , Baltogiannis Georgios , Godevenos Dimitrios
Published: February 2013

Gastric volvulus is a rare but potentially life-threatening clinical entity due to possible gastric necrosis. A wandering spleen may also be associated with gastric volvulus. Patients presenting with the triad epigastralgia, vomiting followed by retching, and difficulty or inability to pass a nasogastric tube into the stomach are likely to have gastric volvulus. The operating surgeon should include this rare entity in the differential diagnosis when dealing with a patient with such a clinical profile. Herein, we present a case of gastric volvulus associated with a wandering spleen in a 28-year-old Caucasian woman and we provide a brief review of the literature on this issue.
Approximate Hamiltonian Symmetry Groups and Recursion Operators for Perturbed Evolution Equations
Authors: Nadjafikhah M. , Mokhtary A.
Published: February 2013

The method of approximate transformation groups, which was proposed by Baikov et al. (1988 and 1996), is extended on Hamiltonian and bi-Hamiltonian systems of evolution equations. Indeed, as a main consequence, this extended procedure is applied in order to compute the approximate conservation laws and approximate recursion operators corresponding to these types of equations. In particular, as an application, a comprehensive analysis of the problem of approximate conservation laws and approximate recursion operators associated to the Gardner equation with the small parameters is presented.
Validation of the Revised Stressful Life Event Questionnaire Using a Hybrid Model of Genetic Algorithm and Artificial Neural Networks
Authors: Sali Rasoul , Roohafza Hamidreza , Sadeghi Masoumeh , Andalib Elham , Shavandi Hassan , Sarrafzadegan Nizal
Published: February 2013

Objectives. Stressors have a serious role in precipitating mental and somatic disorders and are an interesting subject for many clinical and community-based studies. Hence, the proper and accurate measurement of them is very important. We revised the stressful life event (SLE) questionnaire by adding weights to the events in order to measure and determine a cut point.Methods. A total of 4569 adults aged between 18 and 85 years completed the SLE questionnaire and the general health questionnaire-12 (GHQ-12). A hybrid model of genetic algorithm (GA) and artificial neural networks (ANNs) was applied to extract the relation between the stressful life events (evaluated by a 6-point Likert scale) and the GHQ score as a response variable. In this model, GA is used in order to set some parameter of ANN for achieving more accurate results.Results. For each stressful life event, the number is defined as weight. Among all stressful life events, death of parents, spouse, or siblings is the most important and impactful stressor in the studied population. Sensitivity of 83% and specificity of 81% were obtained for the cut point 100.Conclusion. The SLE-revised (SLE-R) questionnaire despite simplicity is a high-performance screening tool for investigating the stress level of life events and its management in both community and primary care settings. The SLE-R questionnaire is user-friendly and easy to be self-administered. This questionnaire allows the individuals to be aware of their own health status.
rTMS as a Treatment of Alzheimer’s Disease with and without Comorbidity of Depression: A Review
Authors: Rutherford Grant , Gole Rebecca , Moussavi Zahra
Published: February 2013

With an ever-increasing population of Alzheimer’s disease (AD) patients worldwide, a noninvasive treatment for AD is needed. In this paper, the application of repetitive transcranial magnetic stimulus (rTMS) as a treatment for patients with probable AD is compared to the application of rTMS as a treatment for depression. Comorbidity of depression and dementia is discussed, as well as possible links between the two diseases. The possible confounding antidepressant effects of rTMS on cognitive improvements in AD patients are discussed.
The CULTEX RFS: A Comprehensive Technical Approach for theIn VitroExposure of Airway Epithelial Cells to the Particulate Matter at the Air-Liquid Interface
Authors: Aufderheide Michaela , Halter Beat , Möhle Niklas , Hochrainer Dieter
Published: February 2013

The EU Regulation on Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) demands the implementation of alternative methods for analyzing the hazardous effects of chemicals including particulate formulations. In the field of inhalation toxicology, a variety ofin vitromodels have been developed for such studies. To simulate thein vivosituation, an adequate exposure device is necessary for the direct exposure of cultivated lung cells at the air-liquid interface (ALI). The CULTEX RFS fulfills these requirements and has been optimized for the exposure of cells to atomized suspensions, gases, and volatile compounds as well as micro- and nanosized particles. This study provides information on the construction and functional aspects of the exposure device. By using the Computational Fluid Dynamics (CFD) analysis, the technical design was optimized to realize a stable, reproducible, and homogeneous deposition of particles. The efficiency of the exposure procedure is demonstrated by exposing A549 cells dose dependently to lactose monohydrate, copper(II) sulfate, copper(II) oxide, and micro- and nanoparticles. All copper compounds induced cytotoxic effects, most pronounced for soluble copper(II) sulfate. Micro- and nanosized copper(II) oxide also showed a dose-dependent decrease in the cell viability, whereby the nanosized particles decreased the metabolic activity of the cells more severely.
The Segmental Morphometric Properties of the Horse Cervical Spinal Cord: A Study of Cadaver
Authors: Bahar Sadullah , Bolat Durmus , Selcuk Muhammet Lutfi
Published: February 2013

Although the cervical spinal cord (CSC) of the horse has particular importance in diseases of CNS, there is very little information about its segmental morphometry. The objective of the present study was to determine the morphometric features of the CSC segments in the horse and possible relationships among the morphometric features. The segmented CSC from five mature animals was used. Length, weight, diameter, and volume measurements of the segments were performed macroscopically. Lengths and diameters of segments were measured histologically, and area and volume measurements were performed using stereological methods. The length, weight, and volume of the CSC were 61.6 ± 3.2 cm, 107.2 ± 10.4 g, and 95.5 ± 8.3 cm3, respectively. The length of the segments was increased from C1 to C3, while it decreased from C3 to C8. The gross section (GS), white matter (WM), grey matter (GM), dorsal horn (DH), and ventral horn (VH) had the largest cross‐section areas at C8. The highest volume was found for the total segment and WM at C4, GM, DH, and VH at C7, and the central canal (CC) at C3. The data obtained not only contribute to the knowledge of the normal anatomy of the CSC but may also provide reference data for veterinary pathologists and clinicians.
Active Aging Promotion: Results from theVital AgingProgram
Authors: Caprara Mariagiovanna , Molina María Ángeles , Schettini Rocío , Santacreu Marta , Orosa Teresa , Mendoza-Núñez Víctor Manuel , Rojas Macarena , Fernández-Ballesteros Rocío
Published: February 2013

Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, whereby aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describesVital Aging, an individual active aging promotion program implemented through three modalities: Life, Multimedia, and e-Learning. The program was developed on the basis of extensive evidence about individual determinants of active aging. The different versions ofVital Agingare described, and four evaluation studies (both formative and summative) are reported. Formative evaluation reflected participants’ satisfaction and expected changes; summative evaluations yielded some quite encouraging results using quasi-experimental designs: those who took part in the programs increased their physical exercise, significantly improved their diet, reported better memory, had better emotional balance, and enjoyed more cultural, intellectual, affective, and social activities than they did before the course, thus increasing their social relationships. These results are discussed in the context of the common literature within the field and, also, taking into account the limitations of the evaluations accomplished.
Umbral Calculus and the Frobenius-Euler Polynomials
Authors: Kim Dae San , Kim Taekyun , Lee Sang-Hun
Published: February 2013

We study some properties of umbral calculus related to the Appell sequence. From those properties, we derive new and interesting identities of the Frobenius-Euler polynomials.
p-ANCA-Associated Vasculitis Caused by Levamisole-Adulterated Cocaine: A Case Report
Authors: Carter Michelle R. , Amirhaeri Sorour
Published: February 2013

A rare case of a patient with an unusual skin rash after using cocaine is presented. A clinical diagnosis of levamisole-induced vasculitis was made based on initial presentation of purpuric skin lesions involving the ears and positive cocaine on urine toxicology screening. The diagnosis was confirmed after laboratory findings of neutropenia, positive serum levamisole, and a histopathologic test of the skin lesions. The pathophysiology of this condition is discussed. Treatment with methylprednisolone and prednisone led to the resolution of the neutropenia and complete recovery of the skin lesions. With the growing use of levamisole-tainted cocaine, clinicians should be aware of the symptoms of vasculitis and neutropenia induced by this combination of drugs to avoid unnecessary tests and delayed diagnosis.
A Streamlined Protocol for Molecular Testing of the DMD Gene within a Diagnostic Laboratory: A Combination of Array Comparative Genomic Hybridization and Bidirectional Sequence Analysis
Authors: Marquis-Nicholson Renate , Lai Daniel , Lan Chuan-Ching , Love Jennifer M. , Love Donald R.
Published: February 2013

Purpose. The aim of this study was to develop a streamlined mutation screening protocol for the DMD gene in order to confirm a clinical diagnosis of Duchenne or Becker muscular dystrophy in affected males and to clarify the carrier status of female family members. Methods. Sequence analysis and array comparative genomic hybridization (aCGH) were used to identify mutations in the dystrophin DMD gene. We analysed genomic DNA from six individuals with a range of previously characterised mutations and from eight individuals who had not previously undergone any form of molecular analysis. Results. We successfully identified the known mutations in all six patients. A molecular diagnosis was also made in three of the four patients with a clinical diagnosis who had not undergone prior genetic screening, and testing for familial mutations was successfully completed for the remaining four patients. Conclusion. The mutation screening protocol described here meets best practice guidelines for molecular testing of the DMD gene in a diagnostic laboratory. The aCGH method is a superior alternative to more conventional assays such as multiplex ligation-dependent probe amplification (MLPA). The combination of aCGH and sequence analysis will detect mutations in 98% of patients with the Duchenne or Becker muscular dystrophy.
Mucoepidermoid Carcinoma of the Tongue Base Mimicking an Ectopic Thyroid
Authors: Martellucci Salvatore , Pagliuca Giulio , de Vincentiis Marco , Rosato Chiara , Scaini Ettore , Gallipoli Camilla , Gallo Andrea
Published: February 2013

A 69-year-old woman with mucoepidermoid carcinoma (MEC) of the tongue base came under our observation complaining of repeated episodes of haemoptysis. Mucoepidermoid carcinoma of the tongue base gives rise to a rather vague and aspecific symptomatology. Early symptoms include foreign body sensation in the oral cavity, undefined paraesthesia, and sialorrhoea. With the progression of disease, dysphagia, otalgia, and painful swallowing are usually referred. We report a case of mucoepidermoid carcinoma of the tongue base mimicking an ectopic thyroid.
Peptide Receptor Targeting in Cancer: The Somatostatin Paradigm
Authors: Barbieri Federica , Bajetto Adriana , Pattarozzi Alessandra , Gatti Monica , Würth Roberto , Thellung Stefano , Corsaro Alessandro , Villa Valentina , Nizzari Mario , Florio Tullio
Published: February 2013

Peptide receptors involved in pathophysiological processes represent promising therapeutic targets. Neuropeptide somatostatin (SST) is produced by specialized cells in a large number of human organs and tissues. SST primarily acts as inhibitor of endocrine and exocrine secretion via the activation of five G-protein-coupled receptors, named sst1–5, while in central nervous system, SST acts as a neurotransmitter/neuromodulator, regulating locomotory and cognitive functions. Critical points of SST/SST receptor biology, such as signaling pathways of individual receptor subtypes, homo- and heterodimerization, trafficking, and cross-talk with growth factor receptors, have been extensively studied, although functions associated with several pathological conditions, including cancer, are still not completely unraveled. Importantly, SST exerts antiproliferative and antiangiogenic effects on cancer cells in vitro, and on experimental tumors in vivo. Moreover, SST agonists are clinically effective as antitumor agents for pituitary adenomas and gastro-pancreatic neuroendocrine tumors. However, SST receptors being expressed by tumor cells of various tumor histotypes, their pharmacological use is potentially extendible to other cancer types, although to date no significant results have been obtained. In this paper the most recent findings on the expression and functional roles of SST and SST receptors in tumor cells are discussed.
Oscillations of Numerical Solutions for Nonlinear Delay Differential Equations in the Control of Erythropoiesis
Authors: Wang Qi , Wen Jiechang
Published: February 2013

We consider the oscillations of numerical solutions for the nonlinear delay differential equations in the control of erythropoiesis. The exponentialθ-method is constructed and some conditions under which the numerical solutions oscillate are presented. Moreover, it is proven that every nonoscillatory numerical solution tends to the equilibrium point of the continuous system. Numerical examples are given to illustrate the main results.
Thymic Stromal Lymphopoietin Enhances Th2/Th22 and Reduces IL-17A in Protease-Allergen-Induced Airways Inflammation
Authors: Togbe Dieudonnée , Fauconnier Louis , Madouri Fahima , Marchiol Tiffany , Chenuet Pauline , Rouxel Nathalie , Ledru Aurélie , Erard François , Quesniaux Valerie , Ryffel Bernhard
Published: February 2013

Background. Thymic stromal lymphopoietin (TSLP) is induced in allergic skin and lung inflammation in man and mice. Methods. Allergic lung inflammation induced by two proteases allergens HDM and papain and a classical allergen ovalbumin was evaluated in vivo in mice deficient for TSLPR. Eosinophil recruitment, Th2 and Th17 cytokine and chemokine levels were determined in bronchoalveolar lavage fluid, lung homogenates and lung mononuclear cells ex vivo. Results. Here we report that mice challenged with house dust mite extract or papain in the absence of TSLPR have a drastic reduction of allergic inflammation with diminished eosinophil recruitment in BAL and lung and reduced mucus overproduction. TSLPR deficient DCs displayed diminished OVA antigen uptake and reduced capacity to activate antigen specific T cells. TSLPR deficient mice had diminished proinflammatory IL-1β, IL-13, and IL-33 chemokines production, while IL-17A, IL-12p40 and IL-10 were increased. Together with impaired Th2 cytokines, IL-17A expressing TCRβ+ T cells were increased, while IL-22 expressing CD4+ T cells were diminished in the lung. Conclusion. Therefore, TSLPR signaling is required for the development of both Th2 and Th22 responses and may restrain IL-17A. TSLP may mediate its effects in part by increasing allergen uptake and processing by DCs resulting in an exacerbated asthma.
Targeting the HGF/c-MET Pathway in Hepatocellular Carcinoma
Authors: Goyal Lipika , Muzumdar Mandar D. , Zhu Andrew X.
Published: February 2013

Hepatocellular carcinoma (HCC) is a significant cause of cancer-related morbidity and mortality worldwide. Despite improvements in local therapies, including surgical resection, liver transplantation, and transarterial embolization, the prognosis remains poor for the majority of patients who develop recurrence or present with advanced disease. Systemic therapy with the tyrosine kinase inhibitor sorafenib represents a milestone in advanced HCC but provides a limited survival benefit. Ongoing efforts to study hepatocarcinogenesis have identified an important role for c-MET signaling in the promotion of tumor growth, angiogenesis, and metastasis. In this review, we summarize the preclinical data from human tissue, cell lines, and animal models that implicate c-MET in the pathogenesis of HCC. We also evaluate potential biomarkers that may estimate prognosis or predict response to c-MET inhibitors for more rational clinical trial design. Finally, we discuss the latest clinical trials of c-MET inhibitors in advanced HCC. Clin Cancer Res; 19(9); 2310–8. ©2013 AACR.
Results of Adjuvant FOLFOX Regimens in Stage III Colorectal Cancer Patients: Retrospective Analysis of 667 Patients
Authors: Uncu Doğan , Aksoy Sercan , Çetin Bülent , Yetişyiğit Tarkan , Özdemir Nuriye , Berk Veli , Dane Faysal , İnal Ali , Harputluoğlu Hakan , Budakoğlu Burçin , Koca Doğan , Sevinç Alper , Cihan Şener , Gök Durnalı Ayşe , Özkan Metin , Öztürk Mehmet Akif , Işıkdoğan Abdurrahman , Büyükberber Süleyman , Benekli Mustafa , Köş Tuğba , Alkış Necati , Karaca Halit , Turhal Nazım Serdal , Zengin Nurullah ,   Anatolian Society of Medical Oncology
Published: February 2013

Objective: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. Methods: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. Results: The median age of the patients was 56 years (range 17–78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1–79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. Conclusion: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.
Alcohol and Illegal Drug Use Behaviors and Prescription Opioids Use: How Do Nonmedical and Medical Users Compare, and Does Motive to Use Really Matter?
Authors: Ghandour Lilian A. , El Sayed Donna S. , Martins Silvia S.
Published: February 2013

Background/Aims: This study compares illegal drug and alcohol use behaviors between medical and nonmedical users of prescription opioids (PO) and nonmedical users with distinct motives to use. Method: An ethically approved cross-sectional study (2010) was conducted on a representative sample of private university students (n = 570), using a self-filled anonymous questionnaire. Results: About 25% reported using PO only medically and 15% nonmedically. The prevalence of alcohol and illegal drug use was consistently higher among nonmedical than medical PO users. Adjusting for age and gender, lifetime medical users of PO were more likely to use marijuana only (OR = 1.8, 95% CI: 1.1, 2.8), while nonmedical users were at higher odds of using marijuana, ecstasy, cocaine/crack, and alcohol problematically. Compared to nonusers, students who took PO nonmedically for nontherapeutic reasons were more likely to use various illegal drugs, but nonmedical users who took PO to relieve pain/help in sleep were only more likely to use marijuana (OR = 2.5, 95% CI: 1.1, 5.4) and alcohol (e.g. alcohol abuse; OR = 3.8, 95% CI: = 1.4, 10.1). Conclusion: Youth who use PO nonmedically to self-treat have a different alcohol and illegal drug-using profile than those who take it for nontherapeutic reasons.
Novel Immunosuppression Compounds and Experimental Therapies for Chronic Graft-Versus-Host Disease
Authors: Michael Maria , Shimoni Avichai , Nagler Arnon
Published: February 2013

Chronic graft-versus-host disease (GVHD) is a severe complication of allogeneic stem cell transplantation, with a substantial impact on the quality of life and survival, still lacking with regard to an optimal therapeutic strategy. Corticosteroids are considered the standard of care for first-line treatment of chronic GVHD, but only a minority of the patients responds to them durably. Management of steroid-refractory chronic GVHD is not well defined. This review surveys novel treatment strategies, such as therapies that expand regulatory T cells, target B cells or target the processes implicated in fibrosis that may allow more effective control of chronic GVHD in the future. Most therapies are based solely on phase II trials or on retrospective analyses with a wide range of overall responses. Large, well-designed prospective studies are eagerly needed to establish better treatments, as well as valid biomarkers to identify the likelihood of the response to a drug in advance.
Presence of the JAK2 V617F Mutation in a Patient with Chronic Neutrophilic Leukemia and Effective Response to Interferon Alfa-2b
Authors: Zhang Xueya , Pan Jingxin , Guo Jianxin
Published: February 2013

Chronic neutrophilic leukemia (CNL) is a rare type of leukemia characterized by a proliferation mainly of mature neutrophils, elevated neutrophil-alkaline phosphatase activity, and no presence of the Philadelphia chromosome. The prognosis is generally poor and there is no consensus therapeutic strategy for the treatment of this disease. The JAK2 V617F mutation has been detected in patients with classical myeloproliferative disorders (MPD) including polycythemia vera and essential thrombocythemia and idiopathic myelofibrosis. In contrast, this same mutation has been detected in only 4 patients with CNL to date, suggesting that the JAK2 V617F mutation is a rare event in patients with atypical MPD. Here, we report a case of CNL with presence of the JAK2 V617F mutation. After treatment with interferon alfa-2b with 3 million units every other day for 1 month, the patient’s white blood cell count was well controlled below 10.0 ×109/l. At present, our patient remains symptomatically well and is maintained on interferon alfa-2b (3 million units twice a week), and his neutrophil count now averages around 8.0–10.0 ×109/l.
Function of eltrombopag-induced platelets compared to platelets from control patients with immune thrombocytopenia
Authors: Haselboeck Johanna , Kaider Alexandra , Pabinger Ingrid , Panzer Simon
Published: February 2013

Data on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce. To assess a possible influence of eltrombopag we compared platelet function of eltrombopag-treated immune thrombocytopenia (ITP) patients (group 1; n=10) after treatment response to that from control ITP patients (group 2; n=12). We further analysed platelet function at baseline and after one, three, and four weeks of eltrombopag treatment and estimated daily changes of platelet function during the eltrombopag-induced platelet rise. The formation of platelet-monocyte aggregates (PMA), P-selectin expression [MFI], and platelet adhesion under high shear conditions (surface coverage, SC) in vivo and after in vitro addition of agonists (ADP, TRAP-6, Collagen) were similar between both groups after response to eltrombopag treatment. Only TRAP-6 induced a lower SC in the eltrombopag group (p=0.03). All platelet function parameters except for Collagen-induced P-selectin expression changed significantly during treatment with eltrombopag. PMA, naïve and after addition of ADP or TRAP-6 increased with increasing platelet counts. P-selectin expression decreased, when measured without and upon addition of ADP, increased in the presence of TRAP-6, and remained unchanged after addition of Collagen. SC increased during the eltrombopag-induced platelet rise. All significant changes of platelet function correlated to changes in platelet counts. Two patients developed venous thromboses during eltrombopag treatment, but no association with any distinct single platelet function parameter or combinations thereof was identifiable. Thus, eltrombopag-induced platelets function similar to those from control ITP patients without discernible increased hyper-reactivity.
Effective elimination of dabigatran by haemodialysis
Authors: Formella Stephan , Wiegert Erol , Moschetti Viktoria , Slowinski Torsten , Neumayer Hans-H. , Liesenfeld Karl-Heinz , Lehr Thorsten , Härtter Sebastian , Friedman Jeffrey , Khadzhynov Dmytro , Wagner Frank , Peters Harm , Clemens Andreas
Published: February 2013

Dabigatran, a specific, reversible direct thrombin inhibitor, is used to prevent ischaemic and haemorrhagic strokes in patients with atrial fibrillation. As with every anticoagulant, there is a need to rapidly reverse its effects in emergency situations. In an open-label, single-centre phase I study with two fixed multiple dosing periods, we investigated the pharmacokinetics, pharmacodynamics and safety of dabigatran before, during and after 4 hour haemodialysis sessions with either 200 or 400 ml/min targeted blood flow in seven end-stage renal disease patients without atrial fibrillation. Dabigatran was administered over three days in a regimen designed to achieve peak plasma concentrations comparable to those observed in atrial fibrillation patients receiving 150 mg b.i.d. and to attain adequate distribution of dabigatran in the central and peripheral compartments. Plasma concentration-time profiles were similar in both periods on Day 3 (Cmax: 176 and 159 ng/ml). Four hours of haemodialysis removed 48.8% and 59.3% of total dabigatran from the central compartment with 200 and 400 ml/minute targeted blood flow, respectively. The anticoagulant activity of dabigatran was linearly related to its plasma levels. There was a minor redistribution of dabigatran (<16%) after the end of the haemodialysis session. In conclusion, a 4 hour haemodialysis session can rapidly eliminate a substantial amount of dabigatran from the central compartment with a concomitant marked reduction in its anticoagulant activity. There was a clinically negligible redistribution of dabigatran after haemodialysis. These results demonstrate that haemodialysis can be a suitable approach to eliminate dabigatran in emergency situations.
Cellular and molecular regulation of vascular permeability
Authors: Goddard Lauren , Iruela-Arispe Luisa
Published: February 2013

Vascular permeability is a highly coordinated process that integrates vesicular trafficking, complex junctional rearrangements, and refined cytoskeletal dynamics. In response to the extracellular environment, these three cellular activities have been previously assumed to work in parallel to regulate the passage of solutes between the blood and tissues. New developments in the area of vascular permeability, however have highlighted the interdependence between trans- and para-cellular pathways, the cross-communication between adherens and tight junctions, and the instructional role of pericytes on endothelial expression of barrier-related genes. Additionally, significant effort has been placed in understanding the molecular underpinings that contribute to barrier restoration following acute permeability events and in clarifying the importance of context-dependent signaling initiated by permeability mediators. Finally, recent findings have uncovered an unpredicted role for transcription factors in the coordination of vascular permeability and clarified how junctional complexes can transmit signals to the nucleus to control barrier function. The goal of this review is to provide a concise and updated view of vascular permeability, discuss the most recent advances in molecular and cellular regulation, and introduce integrated information on the central mechanisms involved in trans-endothelial transport.
Expression and functional characterisation of natural R147W and K150del variants of protein C in the Chinese population
Authors: Ding Qiulan , Yang Likui , Hassanian Seyed , Rezaie Alireza R.
Published: February 2013

Protein C is a vitamin K-dependent serine protease zymogen in plasma which upon activation to activated protein C (APC) by thrombin down-regulates the clotting cascade by limited proteolysis of the pro-coagulant cofactors Va and VIIIa. In addition to its anticoagulant activity, APC also exhibits potent cytoprotective and anti-inflammatory activities. While the anticoagulant activity of APC is enhanced by the cofactor function of protein S on membrane phospholipids, the cytoprotective intracellular signalling activity of APC requires complex formation with endothelial protein C receptor (EPCR) expressed on the vascular endothelium. Two natural variants of APC [Arg-147 to Trp substitution (R147W) and Lys-150 deletion (K150del)] have been identified in the Chinese population as hotspot mutants occurring with high frequencies of 27.8% and 13.9%, respectively, among 36 protein C-deficient subjects. The affected individuals exhibit variable thrombotic tendencies. To understand the underlying cause of the thrombotic phenotype in these patients, we expressed these two protein C variants in mammalian cells and characterised their anticoagulant and anti-inflammatory properties using established in vitro and cellular assays. Our results suggest that both R147W and K150del variants have normal amidolytic and proteolytic activities in the absence of cofactors. However, the R147W mutant exhibits ∼3 times lower affinity for binding to EPCR and the K150del variant has ∼2–3-fold impaired anticoagulant activity in the presence of protein S. These results provide some insight into the possible pathogenic mechanism of protein C deficiency in Chinese patients carrying these mutations.
Adrenal haemorrhage due to heparin-induced thrombocytopenia
Authors: Ketha Siva , Smithedajkul Patrick , Vella Adrian , Pruthi Rajiv , Wysokinski Waldemar , McBane Robert
Published: February 2013

Adrenal haemorrhage (AH) is a rare but potentially devastating complication of heparin-induced thrombocytopenia (HIT). Neither the prevalence nor the natural history of AH due to HIT are known. The objectives of this study were to identify the spectrum of AH causes, to characterise the frequency of AH due to HIT and determine the natural history of HIT-associated AH. All patients with incident adrenal haemorrhage from January 2002 through June 2012 seen at the Mayo Clinic were identified. Over this time frame, there were a total of 115 patients with AH of which 11 cases (10%; mean age 67 ± 8 years; 73% female) were associated with HIT. Of these, all but one occurred in the postoperative setting and involved both adrenal glands (89%) with acute adrenal insufficiency at the time of diagnosis. Cases were found incidentally during an evaluation for fever, shock, abdominal pain or mental status changes. All HIT patients experienced venous thrombosis at other locations including deep venous thromboses (n=14), pulmonary emboli (n= 4) and arterial thrombosis (n=2). Four patients undergoing total knee arthroplasty had “spontaneous HIT” with AH in the absence of identifiable heparin exposure. Other causes of AH included trauma (29%), sepsis (15%), antiphospholipid antibody syndrome (10%), and metastatic disease (12%). In conclusion, AH is an important but seldom recognised presumed thrombotic complication of HIT, which usually occurs in the postoperative period, especially after orthopaedic procedures. This syndrome can occur in the apparent absence of heparin exposure, especially following major joint replacement surgery.
Modification of Outcomes With Aspirin or Apixaban in Relation to CHADS
2
and CHA
2
DS
2
-VASc Scores in Patients With Atrial Fibrillation
Authors: Lip Gregory Y.H. , Connolly Stuart , Yusuf Salim , Shestakovska Olga , Flaker Greg , Hart Robert , Lanas Fernando , Xavier Denis , Eikelboom John
Published: February 2013

Background—

The impact of apixaban versus aspirin on ischemic stroke and major bleeding in relation to the CHADS
2
and CHA
2
DS
2
-VASc stroke risk scores in atrial fibrillation has not been investigated.

Methods and Results—

In this secondary analysis of the AVERROES trial, our principal objective was to assess the effect of treatment with aspirin or apixaban on ischemic stroke and major bleeding, in relation to the CHADS
2
/CHA
2
DS
2
-VASc scores. We found no significant heterogeneity for treatment efficacy on ischemic stroke for apixaban when subdivided by stroke risk strata, based on CHADS
2
/CHA
2
DS
2
-VASc. Effects were consistent irrespective of baseline risk, and thus, absolute benefits were greatest in the high-risk groups. There was also no significant heterogeneity for apixaban versus aspirin with regard to major bleeding, when subdivided by CHADS
2
/CHA
2
DS
2
-VASc scores. In multivariable analysis, significant predictors of stroke on aspirin were age ≥75 years, prior stroke or transient ischemic attack, estimated glomerular filtration rate <60 mL/min, and nonparoxysmal atrial fibrillation. Proportions of the study cohort classified as low/moderate/high risk using the CHADS
2
and CHA
2
DS
2
-VASc scores were 0.3%/71.7%/28.1% and <0.1%/10.5%/89.5%, respectively.

Conclusions—

In an atrial fibrillation population, apixaban was superior to aspirin for stroke prevention, with similar rates of major bleeding, in the presence of one or more stroke risk factors, with consistency of the treatment effect by CHADS
2
/CHA
2
DS
2
-VASc scores.