bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Danish Language Version of the Manchester Foot Pain and Disability Index: Reproducibility and Construct Validity Testing
Authors: Pedersen Christian K. , Danneskiold-Samsøe Bente , Garrow Adam P. , Wæhrens Eva E. , Bliddal Henning , Christensen Robin , Bartels Else Marie
Published: March 2013

Introduction. The Manchester Foot Pain and Disability Index (MFPDI) is a 19-item questionnaire for the assessment of disability caused by foot pain. The aim was to develop a Danish language version of the MFPDI (MFPDI-DK) and evaluate its reproducibility and construct validity. Methods. A Danish version was created, following a forward-backward translation procedure. A sample of 84 adult patients with foot pain was recruited. Participants completed two copies of the MFPDI-DK within a 24- to 48-hour interval, along with the Medical Outcomes Study Short Form 36 (SF-36), and a pain Visual Analog Scale (VAS). Reproducibility was assessed using the intraclass correlation coefficient (ICC) and 95% limits of agreement (Bland-Altman plot). Construct validity was evaluated with Pearson’s Rho, using a priori hypothesized correlations with SF-36 subscales and VASmean. Results. The MFPDI-DK showed very good reliability with an ICC of 0.92 (0.88–0.95). The 95% limits of agreement ranged from −6.03 to 6.03 points. Construct validity was supported by moderate to very strong correlations with the SF-36 physical subscales and VASmean. Conclusion. The MFPDI-DK appears to be a valid and reproducible instrument in evaluating foot-pain-related disability in Danish adult patients in cross-sectional samples. Further research is needed to test the responsiveness of the MFPDI-DK.
Maternal Docosahexaenoic Acid Increases Adiponectin and Normalizes IUGR-Induced Changes in Rat Adipose Deposition
Authors: Bagley Heidi N. , Wang Yan , Campbell Michael S. , Yu Xing , Lane Robert H. , Joss-Moore Lisa A.
Published: March 2013

Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor-γ2 (PPARγ2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPARγincreases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPARγagonist, would normalize IUGR adipose deposition in association with increased PPARγ, adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPARγexpression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.
Spontaneous Intraperitoneal Rupture of a Hepatic Hydatid Cyst with Subsequent Anaphylaxis: A Case Report
Authors: Tinsley Benjamin , Abbara Aula , Kadaba Raghunandan , Sheth Hemant , Sandhu Gurjinder
Published: March 2013

Hydatid cyst rupture into the abdomen is a serious complication of cystic hydatid disease of the liver (Cystic Echinococcosis) with an incidence of up to 16% in some series and can result in anaphylaxis or anaphylactoid reactions in up to 12.5% of cases. At presentation, 36–40% of hydatid cysts have ruptured or become secondarily infected. Rupture can be microscopic or macroscopic and can be fatal without surgery. Hydatid disease of the liver is primarily caused by the tapewormEchinococcus granulosusand occurs worldwide, with incidence of up to 200 per 100,000 in endemic areas. Our case describes a 24-year-old Bulgarian woman presenting with epigastric pain and evidence of anaphylaxis. Abdominal CT demonstrated a ruptured hydatid cyst in the left lobe of the liver. A partial left lobe hepatectomy, cholecystectomy, and peritoneal washout was performed with good effect. She was treated for anaphylaxis and received antihelminthic treatment with Albendazole and Praziquantel. She made a good recovery following surgery and medical treatment and was well on follow-up. Intraperitoneal rupture with anaphylaxis is a rare occurrence, and there do not seem to be any reported cases from UK centres prior to this.
Ultrasound Common Carotid Artery Segmentation Based on Active Shape Model
Authors: Yang Xin , Jin Jiaoying , Xu Mengling , Wu Huihui , He Wanji , Yuchi Ming , Ding Mingyue
Published: March 2013

Carotid atherosclerosis is a major reason of stroke, a leading cause of death and disability. In this paper, a segmentation method based on Active Shape Model (ASM) is developed and evaluated to outline common carotid artery (CCA) for carotid atherosclerosis computer-aided evaluation and diagnosis. The proposed method is used to segment both media-adventitia-boundary (MAB) and lumen-intima-boundary (LIB) on transverse views slices from three-dimensional ultrasound (3D US) images. The data set consists of sixty-eight, 17 × 2 × 2, 3D US volume data acquired from the left and right carotid arteries of seventeen patients (eight treated with 80 mg atorvastatin and nine with placebo), who had carotid stenosis of 60% or more, at baseline and after three months of treatment. Manually outlined boundaries by expert are adopted as the ground truth for evaluation. For the MAB and LIB segmentations, respectively, the algorithm yielded Dice Similarity Coefficient (DSC) of 94.4% ± 3.2% and 92.8% ± 3.3%, mean absolute distances (MAD) of 0.26 ± 0.18 mm and 0.33 ± 0.21 mm, and maximum absolute distances (MAXD) of 0.75 ± 0.46 mm and 0.84 ± 0.39 mm. It took 4.3 ± 0.5 mins to segment single 3D US images, while it took 11.7 ± 1.2 mins for manual segmentation. The method would promote the translation of carotid 3D US to clinical care for the monitoring of the atherosclerotic disease progression and regression.
Sustained and Transient Contributions to the Rat Dark-Adapted Electroretinogram b-Wave
Authors: Dang Trung M. , Vingrys Algis J. , Bui Bang V.
Published: March 2013

The most dominant feature of the electroretinogram, the b-wave, is thought to reflect ON-bipolar cell responses. However, a number of studies suggest that the b-wave is made up of several components. We consider the composition of the rat b-wave by subtracting corneal negative components obtained using intravitreal application of pharmacological agents to remove postreceptoral responses. By analyzing the intensity-response characteristic of the PII across a range of fixed times during and after a light step, we find that the rat isolated PII has 2 components. The first has fast rise and decay characteristics with a low sensitivity to light. GABAc-mediated inhibitory pathways enhance this transient-ON component to manifest increased and deceased sensitivity to light at shorter (<160 ms) and longer times, respectively. The second component has slower temporal characteristics but is more sensitive to light. GABAc-mediated inhibition enhances this sustained-ON component but has little effect on its sensitivity to light. After stimulus offset, both transient and sustained components return to baseline, and a long latency sustained positive component becomes apparent. The light sensitivities of transient-ON and sustained-OFF components are consistent with activity arising from cone ON- and OFF-bipolar cells, whereas the sustained-ON component is likely to arise from rod bipolar cells.
Direct Fabrication of Cobalt Oxide Nanoparticles Employing Sucrose as a Combustion Fuel
Authors: Makhlouf M. Th. , Abu-Zied B. M. , Mansoure T. H.
Published: March 2013

Combustion method has been used as a fast and facile method to prepare nanocrystalline Co3O4spinel employing sucrose as a combustion fuel. The products were characterized by thermal analyses (TGA and DTA), X-ray diffraction technique (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. Experimental results revealed that the molar ratio of fuel/oxidizer (F/O) plays an important role in controlling the crystallite size of Co3O4nanoparticles. Transmission electron microscopy indicated that the crystallite size of Co3O4nanocrystals was in the range of 13–32 nm. X-ray diffraction confirmed the formation of CoO phase with spinel Co3O4. The effect of calcination temperature on crystallite size and morphology has been, also, discussed.
Changing Behavior among Nurses to Track Indwelling Urinary Catheters in Hospitalized Patients
Authors: Yoon Bona , McIntosh Samantha D. , Rodriguez Leslie , Holley Alma , Faselis Charles J. , Liappis Angelike P.
Published: March 2013

Catheter-associated urinary tract infections (CAUTIs) are preventable complications of hospitalization. An interdisciplinary team developed a curriculum to increase awareness of the presence of indwelling urinary catheters (IUCs) in hospitalized patients, addressed practical, primarily nurse-controlled inpatient risk-reduction interventions, and promoted the use of the IUC labels (“tags”). Five thirty-minute educational sessions were cycled over three daily nursing shifts on two inpatient medical floors over a 1-year period; participants were surveyed(n=152)to elicit feedback and provide real-time insight on the learning objectives. Nurse self-reported IUC tagging was early and sustained; after the IUC tag was introduced, there was a significant increase in tagging reported by the end of the block of educational sessions (from 46.2% to 84.6%,P=0.001). Early engagement combined with a targeted educational initiative led to increased knowledge, changes in behavior, and renewed CAUTI awareness in hospitalized patients with IUCs. The processes employed in this small-scale project can be applied to broader, hospitalwide initiatives and to large-scale initiatives for healthcare interventions. As first-line providers with responsibility for the placement and daily maintenance of IUCs, nurses are ideally positioned to implement efforts addressing CAUTIs in the hospital setting.
Contribution of Recycling of Municipal Solid Waste to the Social Inclusion in Brazil
Authors: Lino F. A. M. , Ismail K. A. R.
Published: March 2013

This paper proposes the selective collection and recycling as alternative ways to promote the social inclusion in Brazil and help the country to eradicate extreme poverty and misery and achieve the first of the Millennium Development Goals (MDG1) of the UN. This work is based on the data from a Brazilian metropolitan city of Campinas and is extended to Brazil. The results show that the municipality of Campinas collects monthly 8000 tons of recyclables which if recycled can avail jobs to nearly 13,000 waste collectors with a minimum national salary of R$ 622/month or alternatively can create 40,280 Family Grants of R$ 200/month. In Brazil, the collected recyclables potential is about 2.4 million tons per month which can avail jobs to 2,350945 waste collectors or alternatively create about 7.3 millions Family Grants.
The Discrete-Time Sliding Mode Control with Computation Time Delay for Repeatable Run-Out Compensation of Hard Disk Drives
Authors: Yan T. H. , He B. , Chen X. D. , Xu X. S.
Published: March 2013

The presented is a study on the problem of disturbance rejection, specifically the periodic disturbance, by applying discrete-time sliding mode control method. For perturbations such as modeling errors and external disturbances, their compensation is formulated using the designed sliding mode control. To eliminate the effect of these perturbations, the convergence rate between the disturbance and their compensation has been shaped by an additional parameter. Decoupling of the resultant perturbation estimation dynamics from the closed loop dynamics is achieved. Computation time delay is also presented to address the perturbation effects. The approach developed ensures the robustness of the sliding mode dynamics to parameter uncertainties and exogenous disturbances, in addition to the complete rejection of the periodic disturbance component. Satisfactory simulation results as well as experimental ones have been achieved based on a fast servo system of a modern hard disk drive to illustrate the validity of the controller for repeatable run-out (RRO) compensation.
Clinical and Pathological Characteristics of Organized Hematoma
Authors: Ohta Nobuo , Watanabe Tomoo , Ito Tsukasa , Kubota Toshinori , Suzuki Yusuke , Ishida Akihiro , Aoyagi Masaru , Matsubara Atsushi , Izuhara Kenji , Kakehata Seiji
Published: March 2013

Objective. To study the clinical and pathological characteristics of patients with organized hematoma with malignant features in maxillary sinuses.Subjects and Methods. This was a retrospective study of five patients who were treated surgically for organized hematoma. The preoperative CT and MRI findings were studied clinically. The expressions of CD31, CD34, and periostin in surgical samples were investigated by immunohistochemistry.Results. The clinical features of organized hematoma, such as a mass expanding from the maxillary sinus with bone destruction, resembled those of maxillary carcinoma. However, CT and MRI provided sufficient and useful information to differentiate this condition from malignancy. Surgical resection was the first-line treatment because of the presence of a firm capsule. Characteristic histopathological findings were a mixture of dilated vessels, hemorrhage, fibrin exudation, fibrosis, hyalinization, and neovascularization. The expressions of periostin, CD31, and CD34 were observed in organized hematoma of the maxillary sinus.Conclusion. The expressions of periostin, CD31, and CD34 were observed in organized hematoma of the maxillary sinus. Organized hematoma is characterized pathologically by a mixture of bleeding, dilated vessels, hemorrhage, fibrin exudation, fibrosis, hyalinization, and neovascularization. CT and MRI show heterogeneous findings reflecting a mixture of these pathological entities.
Mixed Red-Complex Bacterial Infection in Periodontitis
Authors: Suzuki N. , Yoneda M. , Hirofuji T.
Published: March 2013

The red complex, which includesPorphyromonas gingivalis,Treponema denticola, andTannerella forsythia(formerlyBacteroides forsythus), are recognized as the most important pathogens in adult periodontal disease. These bacteria are usually found together in periodontal pockets, suggesting that they may cause destruction of the periodontal tissue in a cooperative manner. This article discusses the interspecies pathogenic interactions within the red complex.
Existence and Stability for the 3D Linearized Constant-Coefficient Incompressible Current-Vortex Sheets
Authors: Catania Davide
Published: March 2013

We consider the free boundary problem for current-vortex sheets in ideal incompressible magnetohydrodynamics. The problem of current-vortex sheets arises naturally, for instance, in geophysics and astrophysics. We prove the existence of a unique solution to the constant-coefficient linearized problem and an a priori estimate with no loss of derivatives. This is a preliminary result to the study of linearized variable-coefficient current-vortex sheets, a first step to prove the existence of solutions to the nonlinear problem.
Applying an Extended Fuzzy Parametric Approach to the Problem of Water Allocations
Authors: Xu T. Y. , Qin X. S.
Published: March 2013

An extended fuzzy parametric programming (EFPP) model was proposed for supporting water resources allocation problems under uncertainty. EFPP deals with flexible constraints (i.e., fuzzy relationships) by allowing violation of constraints at certain satisfaction degrees (i.e.,αlevels) and employs fuzzy ranking method to handle trapezoidal-shaped fuzzy coefficients. The objective function is defuzzified by usingβcuts and weighting factors. The applicability of EFPP was demonstrated by a numerical example and a water resources allocation case. A series of decision alternatives at various satisfaction degrees were obtained. Generally, the higher theαlevel, the lower the system benefit. In comparison, theβlevel in the objective function posed less sensitive impacts on both objective function and model solutions. The reliability of EFPP was tested by comparing its solutions with those from fuzzy chance constrained programming (FCCP). The results indicated that EFPP performed equally well with FCCP in addressing parameter uncertainties, but it demonstrated a wider applicability due to its extended capacity of handling fuzzy relationships in the model constraints.
Oxidized Extracellular DNA as a Stress Signal in Human Cells
Authors: Ermakov Aleksei V. , Konkova Marina S. , Kostyuk Svetlana V. , Izevskaya Vera L. , Baranova Ancha , Veiko Natalya N.
Published: March 2013

The term “cell-free DNA” (cfDNA) was recently coined for DNA fragments from plasma/serum, while DNA present inin vitrocell culture media is known as extracellular DNA (ecDNA). Under oxidative stress conditions, the levels of oxidative modification of cellular DNA and the rate of cell death increase. Dying cells release their damaged DNA, thus, contributing oxidized DNA fragments to the pool of cfDNA/ecDNA. Oxidized cell-free DNA could serve as a stress signal that promotes irradiation-induced bystander effect. Evidence points to TLR9 as a possible candidate for oxidized DNA sensor. An exposure to oxidized ecDNA stimulates a synthesis of reactive oxygen species (ROS) that evokes an adaptive response that includes transposition of the homologous loci within the nucleus, polymerization and the formation of the stress fibers of the actin, as well as activation of the ribosomal gene expression, and nuclear translocation of NF-E2 related factor-2 (NRF2) that, in turn, mediates induction of phase II detoxifying and antioxidant enzymes. In conclusion, the oxidized DNA is a stress signal released in response to oxidative stress in the cultured cells and, possibly, in the human body; in particular, it might contribute to systemic abscopal effects of localized irradiation treatments.
Precursor B-Cell Acute Lymphoblastic Leukemia/Lymphoma with L3 Morphology, Philadelphia Chromosome, MYC Gene Translocation, and Coexpression of TdT and Surface Light Chains: A Case Report
Authors: Hirzel Alicia C. , Cotrell Aaron , Gasparini Robert , Sriganeshan Vathany
Published: March 2013

Acute lymphoblastic leukemia is predominantly found in children. It is a neoplasm of precursor cells or lymphoblasts committed to either a B- or T-cell lineage. The immature cells in B-acute lymphoblastic leukemia/lymphoma can be small or medium sized with scant or moderate cytoplasm and typically express B-cell markers such as CD19, cytoplasmic CD79a, and TdT without surface light chains. These markers, along with cytogenetic studies, are vital to the diagnosis, classification, and treatment of these neoplasms. We present an unusual case of a precursor B-cell ALL, in an 82-year-old woman, who presented with pancytopenia and widespread lymphadenopathy. The cells show L3 morphology (Burkitt-like lymphoma) with coexpression of TdT and surface light chains in addition to an MYC gene translocation and Philadelphia chromosome.
Factors Related to Oral Health-Related Quality of Life of Independent Brazilian Elderly
Authors: Ulinski Karla Giovana Bavaresco , do Nascimento Mariele Andrade , Lima Arinilson Moreira Chaves , Benetti Ana Raquel , Poli-Frederico Regina Célia , Fernandes Karen Barros Parron , Fracasso Marina Lourdes Calvo , Maciel Sandra Mara
Published: March 2013

The aim of this cross-sectional study was to assess the factors associated with the impact of oral health on the quality of life in a sample of 504 Brazilian independent elderly. Data collection included oral examinations and structured interviews. The simplified form of the Oral Health Impact Profile (OHIP-14) was used to measure OHRQoL. Information on sociodemographic characteristics, use of dental services, and subjective measures of health was collected. Poisson regression within a hierarchical model was used to data analyses. The following variables were associated with a negative impact on OHRQoL: female gender (PR = 1.40; CI 95%: 1.11–1.77); lower class (PR = 1.58; CI 95%: 1.13–2.20); up to 3 occluding pairs of posterior teeth (PR = 1.88; CI 95%: 1.13–3.14); at least one untreated caries (PR = 1.28; CI 95%: 1.06–1.54); curative reasons for the last dental appointment (PR = 1.52; CI 95%: 1.15–2.00); poor self-perception of oral health (PR = 2.49; CI 95%: 1.92–3.24); and poor perception of dental care provided (PR = 1.34; CI 95%: 1.12–1.59). The younger elderly also noticed this negative impact. These findings showed that the clinical, sociodemographic, and subjective factors evaluated exerted a negative impact on OHRQoL in elderly people. Health authorities must address all these factors when planning interventions on oral health for this population.
Therapeutic Efficacy of Fuzheng-Huayu Tablet Based Traditional Chinese Medicine Syndrome Differentiation on Hepatitis-B-Caused Cirrhosis: A Multicenter Double-Blind Randomized Controlled Trail
Authors: Song Ya-Nan , Sun Ji-Jia , Lu Yi-Yu , Xu Lie-Ming , Gao Yue-Qiu , Zhang Wei , Wang Xiao-Su , Xue Dong-Ying , Zheng Qing-Shan , Su Shi-Bing
Published: March 2013

Aim. To evaluate and predict the therapeutic efficacy of Fuzheng-Huayu tablet (FZHY) based traditional Chinese Medicine (TCM) syndrome differentiation or TCM symptoms on chronic hepatitis B caused cirrhosis (HBC).Methods.The trial was designed according to CONSORT statement. It was a multi-center, double-blind, randomized, placebo-controlled trail. Several clinical parameters, Child-Pugh classification and TCM symptoms were detected and evaluated. The FZHY efficacy was predicted by an established Bayes forecasting method following the Bayes classification model.Results.The levels of HA and TCM syndrome score in FZHY group were significantly decreased (P<0.05) compared to placebo group, respectively. The efficacy of FZHY on TCM syndrome score in HBC patients with some TCM syndromes was better. In TCM syndrome score evaluation, there were 53 effective and 22 invalid in FZHY group. TCM symptoms predicted FZHY efficacy on HBC were close to Child-Pugh score prediction.Conclusion.FZHY decreases the levels of HA and TCM syndrome scores, improves the life quality of HBC patients. Moreover, there were different therapeutic efficacies among different TCM syndromes, indicating that accurate TCM syndrome differentiation might guide the better TCM treatment. Furthermore, the FZHY efficacy was able to predict by Bayes forecasting method through the alteration of TCM symptoms.
Competing in the Global Solar Photovoltaic Industry: The Case of Taiwan
Authors: Su Yu-Shan
Published: March 2013

The top five solar cell supply countries in the world in sequential order are China, Taiwan, the United States of America, Japan, and Germany. The capacity of Taiwanese solar cell production is ranked top two in the globe. The competitive advantage of the Taiwanese electronics firms has facilitated the rapid developments to its solar photovoltaic industry. The Taiwanese solar photovoltaic industry possesses a large size and a complete value chain of upstream, midstream, and downstream sectors. In this study, I analyzed the trends and developments of the solar photovoltaic industry in Taiwan and in the globe. And I also investigated the positioning and competitive advantage of Taiwanese firms in the value chain of the global solar photovoltaic industry. I found that Taiwanese firms continue to have an important and indispensable role in the global solar photovoltaic industry by either differentiation or cost advantage.
PV Systems Installed in Marine Vessels: Technologies and Specifications
Authors: Kobougias Ioannis , Tatakis Emmanuel , Prousalidis John
Published: March 2013

Considerations are held about the specificationin whichthe PV plants have to fulfill so that they can be installed on marine vessels. Initially, a brief description of the typical electrical grid of ships is presented, distinguishing the main parts, reporting the typical electrical magnitudes, and choosing the most preferable installation areas. The technical specifications,in whichthe PV plants have to be compatible with, are fully described. They are determined by the special marine environmental conditions, taking into consideration parameters like wind, humidity, shading, corrosion, and limited installation area. The work is carried out with the presentation of the most popular trends in the field of solar cell types and PV system technologies and their ability to keep up with the aforementioned specifications.
On a Theorem of Khan in a Generalized Metric Space
Authors: Ahmad Jamshaid , Arshad Muhammad , Vetro Calogero
Published: March 2013

Existence and uniqueness of fixed points are established for a mapping satisfying a contractive condition involving a rational expression on a generalized metric space. Several particular cases and applications as well as some illustrative examples are given.
Hepatitis Viruses in Heamodialysis Patients: An Added Insult to Injury?
Authors: Kosaraju Kranthi , Faujdar Sameer Singh , Singh Aashima , Prabhu Ravindra
Published: March 2013

Hepatitis B (HBV) and hepatitis C (HCV) viruses are the most important causes of chronic liver disease in patients with end stage renal disease on hemodialysis. The prevalence of hepatitis infection among hemodialysis patients is high and varies between countries and between dialysis units within a single country. This case-control study was undertaken to estimate the occurrence of HBV and HCV infections in patients undergoing hemodialysis in our tertiary care center. All patients receving hemodialysis at our centre with HCV or HBV infection were included in the study. The total number of patients admitted for hemodialysis during the study period was 1710. Among these, 26 patients were positive for HBV, 19 were positive for HCV, and 2 were positive for both HCV and HBV. Mean age of the infected cases in our study was 48.63 years. Mean duration of dialysis for infected cases was 4.8 years while that of the noninfected controls was 3.18 years. The mean dialysis interval was twice a week. Interventions to reduce the occurrence of these infections are of utmost need to reduce the risk of long-term complications among hemodialysis patients.
The Triggering Receptor Expressed on Myeloid Cells 2: “TREM-ming” the Inflammatory Component Associated with Alzheimer's Disease
Authors: Rohn Troy T.
Published: March 2013

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by a progressive loss of memory and cognitive skills. Although much attention has been devoted concerning the contribution of the microscopic lesions, senile plaques, and neurofibrillary tangles to the disease process, inflammation has long been suspected to play a major role in the etiology of AD. Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD. Variants in TREM2 triple one's risk of developing late-onset AD. TREM2 is expressed on microglial cells, the resident macrophages in the CNS, and functions to stimulate phagocytosis on one hand and to suppress cytokine production and inflammation on the other hand. The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS. In this context, an overview of the pathways linking beta-amyloid, neurofibrillary tangles (NFTs), oxidative stress, and inflammation will be discussed.
Improvement of Core Performance by Introduction of Moderators in a Blanket Region of Fast Reactors
Authors: Wakabayashi Toshio
Published: March 2013

An application of deuteride moderator for fast reactor cores is proposed for power flattening that can mitigate thermal spikes and alleviate the decrease in breeding ratio, which sometimes occurs when hydrogen moderator is applied as a moderator. Zirconium deuteride is employed in a form of pin arrays at the inner most rows of radial blanket fuel assemblies, which works as a reflector in order to flatten the radial power distribution in the outer core region of MONJU. The power flattening can be utilized to increase core average burn-up by increasing operational time. The core characteristics have been evaluated with a continuous-energy model Monte Carlo code MVP and the JENDL-3.3 cross-section library. The result indicates that the discharged fuel burn-up can be increased by about 7% relative to that of no moderator in the blanket region due to the power flattening when the number of deuteride moderator pins is 61. The core characteristics and core safety such as void reactivity, Doppler coefficient, and reactivity insertion that occurred at dissolution of deuteron were evaluated. It was clear that the serious drawback did not appear from the viewpoints of the core characteristics and core safety.
Detection of Overhead Contact Lines with a 2D-Digital-Beamforming Radar System for Automatic Guidance of Trolley Trucks
Authors: Harter Marlene , Schipper Tom , Zwirello Lukasz , Ziroff Andreas , Zwick Thomas
Published: March 2013

The benefit of trolley truck systems is the substitution of the diesel fuel by the cheaper and more
ecological electrical energy. Trolley trucks are powered by electricity from two overhead contact
lines, where one is the supply and the other the return conductor. Such trolley trucks are used
for haulage at open pit mining sites but could also be used for freight traffic at roadways in the
future. Automatic guidance prevents the trolley-powered trucks from leaving the track and thus
allows higher operating speeds, higher loading capacity, and greater efficiency. Radar is the ideal
sensing technique for automatic guidance in such environments. The presented radar system
with two-dimensional digital beamforming capability offers a compact measurement solution as it
can be installed on top of the truck. Besides the distance measurement, this radar system allows
to detect the location and inclination of the overhead contact lines by digital beamforming in two
dimensions. Besides automatic guidance, the knowledge of the inclination of the overhead
contact lines could allow automatic speed adaption, which would help to achieve maximum speed
especially in hilly terrain.
Understanding the Pathogenesis of Kawasaki Disease by Network and Pathway Analysis
Authors: Lv Yu-wen , Wang Jing , Sun Ling , Zhang Jian-min , Cao Lei , Ding Yue-yue , Chen Ye , Dou Ji-juan , Huang Jie , Tang Yi-fei , Wu Wen-tao , Cui Wei-rong , Lv Hai-tao
Published: March 2013

Kawasaki disease (KD) is a complex disease, leading to the damage of multisystems. The pathogen that triggers this sophisticated disease is still unknown since it was first reported in 1967. To increase our knowledge on the effects of genes in KD, we extracted statistically significant genes so far associated with this mysterious illness from candidate gene studies and genome-wide association studies. These genes contributed to susceptibility to KD, coronary artery lesions, resistance to initial IVIG treatment, incomplete KD, and so on. Gene ontology category and pathways were analyzed for relationships among these statistically significant genes. These genes were represented in a variety of functional categories, including immune response, inflammatory response, and cellular calcium ion homeostasis. They were mainly enriched in the pathway of immune response. We further highlighted the compelling immune pathway of NF-AT signal and leukocyte interactions combined with another transcription factor NF-κB in the pathogenesis of KD. STRING analysis, a network analysis focusing on protein interactions, validated close contact between these genes and implied the importance of this pathway. This data will contribute to understanding pathogenesis of KD.
Serum 25-Hydroxyvitamin D and Cancer Risk in Older Adults: Results from a Large German Prospective Cohort Study
Authors: Ordóñez-Mena José M. , Schöttker Ben , Haug Ulrike , Müller Heiko , Köhrle Josef , Schomburg Lutz , Holleczek Bernd , Brenner Hermann
Published: March 2013

Background: Several observational studies assessed the relationship between serum 25-hydroxyvitamin D [25(OH)D] concentrations and the risk of cancer but results were inconclusive.

Methods: We measured 25(OH)D concentrations in a population-based cohort study of 9,949 men and women ages 50 to 74 years in Saarland, Germany. Comprehensively adjusted Cox regression models were applied to estimate HRs and 95% confidence intervals (CI) for the association between season-standardized 25(OH)D concentrations and total and site-specific cancer incidence.

Results: Overall, during a median of 8 years of follow-up, 873 subjects developed cancer; the most common being prostate (171), breast (137), lung (136), and colorectal (136) cancer. Low season-standardized 25(OH)D (<30, 35, 40, or 36 nmol/L in winter, spring, summer, and autumn, respectively) was neither significantly associated with total cancer incidence (HR, 1.10; 95% CI, 0.93–1.30) nor with site-specific cancer incidence. However, a significantly increased overall cancer risk was observed for low 25(OH)D among men, nonobese subjects and subjects reporting low fish consumption and for high 25(OH)D in nonsmokers and nonobese subjects. Accordingly, restricted cubic splines to investigate dose–response relationships curves showed an inverse association of 25(OH)D levels and total cancer risk in men but not in women.

Conclusions: 25(OH)D concentrations were significantly associated with overall cancer incidence in subgroups of this large cohort from Germany. No significant association was observed with site-specific cancers but this could be due to a limited statistical power for these endpoints.

Impact: Further research should clarify whether and to what extent specific risk groups might profit from vitamin D supplementation. Cancer Epidemiol Biomarkers Prev; 22(5); 905–16. ©2013 AACR.
Comparison of Nicotine and Carcinogen Exposure with Water Pipe and Cigarette Smoking
Authors: Jacob Peyton , Abu Raddaha Ahmad H. , Dempsey Delia , Havel Christopher , Peng Margaret , Yu Lisa , Benowitz Neal L.
Published: March 2013

Background: Smoking tobacco preparations in a water pipe (hookah) is widespread in many places of the world and is perceived by many as relatively safe. We investigated biomarkers of toxicant exposure with water pipe compared with cigarette smoking.

Methods: We conducted a crossover study to assess daily nicotine and carcinogen exposure with water pipe and cigarette smoking in 13 people who were experienced in using both products.

Results: When smoking an average of 3 water pipe sessions compared with smoking 11 cigarettes per day (cpd), water pipe use was associated with a significantly lower intake of nicotine, greater exposure to carbon monoxide (CO), and a different pattern of carcinogen exposure compared with cigarette smoking, with greater exposure to benzene, and high molecular weight polycyclic aromatic hydrocarbon (PAH), but less exposure to tobacco-specific nitrosamines, 1,3-butadiene, acrolein, acrylonitrile, propylene oxide, ethylene oxide, and low molecular weight PAHs.

Conclusions: A different pattern of carcinogen exposure might result in a different cancer risk profile between cigarette and water pipe smoking. Of particular concern is the risk of leukemia related to high levels of benzene exposure with water pipe use.

Impact: Smoking tobacco in water pipes has gained popularity in the United States and around the world. Many believe that water pipe smoking is not addictive and less harmful than cigarette smoking. We provide data on toxicant exposure that will help guide regulation and public education regarding water pipe health risk. Cancer Epidemiol Biomarkers Prev; 22(5); 765–72. ©2013 AACR.
Inflammatory Plasma Markers and Pancreatic Cancer Risk: A Prospective Study of Five U.S. Cohorts
Authors: Bao Ying , Giovannucci Edward L. , Kraft Peter , Qian Zhi Rong , Wu Chen , Ogino Shuji , Gaziano J. Michael , Stampfer Meir J. , Ma Jing , Buring Julie E. , Sesso Howard D. , Lee I-Min , Rifai Nader , Pollak Michael N. , Jiao Li , Lessin Lawrence , Cochrane Barbara B. , Manson JoAnn E. , Fuchs Charles S. , Wolpin Brian M.
Published: March 2013

Chronic inflammation may play a role in the development of pancreatic cancer. However, few prospective studies have examined the association between plasma inflammatory markers and pancreatic cancer risk. Therefore, we investigated the association of prediagnostic circulating C-reactive protein (CRP), interleukin-6 (IL-6), and TNF-α receptor II (TNF-αR2) with subsequent pancreatic cancer risk in a prospective, nested case–control study of 470 cases and 1,094 controls from Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, Women's Health Initiative, and Women's Health Study. The median follow-up time of cases was 7.2 years (range 1–26 years). No association was observed between plasma CRP, IL-6, and TNF-αR2 and the risk of pancreatic cancer. Comparing extreme quintiles, the multivariate ORs were 1.10 [95% confidence interval (CI), 0.74–1.63; Ptrend = 0.81] for CRP, 1.19 (95% CI, 0.81–1.76; Ptrend = 0.08) for IL-6, and 0.88 (95% CI, 0.58–1.33; Ptrend = 0.57) for TNF-αR2. In conclusion, prediagnostic levels of circulating CRP, IL-6, and TNF-αR2 were not associated with the risk of pancreatic cancer, suggesting that systemic inflammation as measured by circulating inflammatory factors is unlikely to play a major role in the development of pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 22(5); 855–61. ©2013 AACR.
Autophagy Inhibition Sensitizes Colon Cancer Cells to Antiangiogenic and Cytotoxic Therapy
Authors: Selvakumaran Muthu , Amaravadi Ravi K. , Vasilevskaya Irina A. , O'Dwyer Peter J.
Published: March 2013

Purpose: Autophagy is a critical survival pathway for cancer cells under conditions of nutrient or oxygen limitation, or cell stress. As a consequence of antiangiogenic therapy, solid tumors encounter hypoxia induction and imbalances in nutrient supply. We wished to determine the role of autophagy in protection of tumor cells from the effects of antiangiogenic therapy and chemotherapy. We examined the effect of inhibiting autophagy on hypoxic colon cancer cells in vitro and on bevacizumab- and oxaliplatin-treated mouse xenografts in vivo.

Experimental Design: The autophagic response to hypoxia and DNA-damaging agents was assessed by fluorescent microscopic imaging, autophagy-related gene expression, and by electron microscopic ultrastructural analysis. Pharmacologic and molecular approaches to autophagy inhibition were taken in a panel of colon cancer cell lines. Mouse xenograft models were treated with combinations of oxaliplatin, bevacizumab, and chloroquine to assess effects on tumor growth reduction and on pharmacodynamic markers of autophagy inhibition.

Results: Autophagy was induced in colon cancer models by exposure to both hypoxia and oxaliplatin. Inhibition of autophagy, either with chloroquine or by downregulation of beclin1 or of ATG5, enhanced sensitivity to oxaliplatin under normal and hypoxic conditions in a synergistic manner. Both bevacizumab and oxaliplatin treatments activate autophagy in HT29 murine xenografts. The addition of chloroquine to bevacizumab-based treatment provided greater tumor control in concert with evidence of autophagy inhibition.

Conclusions: These findings implicate autophagy as a mechanism of resistance to antiangiogenic therapies and support investigation of inhibitory approaches in the management of this disease. Clin Cancer Res; 19(11); 2995–3007. ©2013 AACR.
Abcc4 Together with Abcb1 and Abcg2 Form a Robust Cooperative Drug Efflux System That Restricts the Brain Entry of Camptothecin Analogues
Authors: Lin Fan , Marchetti Serena , Pluim Dick , Iusuf Dilek , Mazzanti Roberto , Schellens Jan H.M. , Beijnen Jos H. , van Tellingen Olaf
Published: March 2013

Purpose: Multidrug resistance–associated protein 4 (ABCC4) shares many features with P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), including broad substrate affinity and expression at the blood–brain barrier (BBB). However, the pharmacologic relevance of ABCC4 at the BBB is difficult to evaluate, as most drugs are also substrates of ABCB1 and/or ABCG2.

Experimental Design: We have created a mouse strain in which all these alleles are inactivated to assess their impact on brain delivery of camptothecin analogues, an important class of antineoplastic agents and substrates of these transporters. Wild-type (WT), Abcg2−/−, Abcb1a/b−/−, Abcc4−/−, Abcb1a/b;Abcg2−/−, Abcg2;Abcc4−/−, and Abcb1a/b;Abcg2;Abcc4−/− mice received i.v. topotecan, irinotecan, SN-38, or gimatecan alone or with concomitant oral elacridar. Drug levels were analyzed by high-performance liquid chromatography (HPLC).

Results: We found that additional deficiency of Abcc4 in Abcb1a/b;Abcg2−/− mice significantly increased the brain concentration of all camptothecin analogues by 1.2-fold (gimatecan) to 5.8-fold (SN-38). The presence of Abcb1a/b or Abcc4 alone was sufficient to reduce the brain concentration of SN-38 to the level in WT mice. Strikingly, the brain distribution of gimatecan in brain of WT mice was more than 220- and 40-fold higher than that of SN-38 and topotecan, respectively.

Conclusion: Abcc4 limits the brain penetration of camptothecin analogues and teams up with Abcb1a/b and Abcg2 to form a robust cooperative drug efflux system. This concerted action limits the usefulness of selective ABC transport inhibitors to enhance drug entry for treatment of intracranial diseases. Our results also suggest that gimatecan might be a better candidate than irinotecan for clinical evaluation against intracranial tumors. Clin Cancer Res; 19(8); 2084–95. ©2013 AACR.
Prediagnostic Leptin, Adiponectin, C-Reactive Protein, and the Risk of Postmenopausal Breast Cancer
Authors: Ollberding Nicholas J. , Kim Yeonju , Shvetsov Yurii B. , Wilkens Lynne R. , Franke Adrian A. , Cooney Robert V. , Maskarinec Gertraud , Hernandez Brenda Y. , Henderson Brian E. , Le Marchand Loïc , Kolonel Laurence N. , Goodman Marc T.
Published: March 2013

Obesity has been associated with an increased risk of postmenopausal breast cancer. Adipokines and systemic inflammation have been hypothesized to underlie this association. In a case–control study nested within the Multiethnic Cohort, conditional logistic regression was used to calculate the ORs and 95% confidence intervals (CI) for postmenopausal breast cancer associated with prediagnostic levels of serum leptin, adiponectin, the leptin:adiponectin ratio, and C-reactive protein (CRP). The 706 cases and 706 controls were matched on ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, hours fasting before blood draw, and hormone replacement therapy use at blood draw. Higher circulating levels of leptin [ORQ4 vs. Q1, 1.94 (1.37–2.75); Ptrend ≤ 0.001), the leptin:adiponectin ratio [OR, 1.91 (1.36–2.68); Ptrend = 0.005], and CRP [OR, 1.41 (1.01–1.96); Ptrend = 0.014] were associated with an increased risk of postmenopausal breast cancer. The positive associations for these markers remained after adjustment for body mass index (BMI). No associations were detected for adiponectin. These data suggest that adipokines and systemic inflammation may be associated with the risk of postmenopausal breast cancer independently of BMI. Further prospective studies examining the role of adipokines and inflammatory processes in the etiology of postmenopausal breast cancer are warranted. Cancer Prev Res; 6(3); 188–95. ©2013 AACR.
Abdominal Obesity, Independent from Caloric Intake, Accounts for the Development of Intestinal Tumors in Apc1638N/+ Female Mice
Authors: Huffman Derek M. , Augenlicht Leonard H. , Zhang Xueying , Lofrese John J. , Atzmon Gil , Chamberland John P. , Mantzoros Christos S.
Published: March 2013

To determine whether visceral fat (VF), independent of other confounders, is causally linked to intestinal tumorigenesis, we surgically removed visceral fat in Apc1638/N+ mice. At 15 weeks of age, male and female Apc1638/N+ mice were randomized to one of three groups: ad libitum, visceral fat removal (VF-) and ad libitum fed, or caloric restriction, and were studied for effects on tumorigenesis and survival. As compared with ad libitum, VF− and caloric restriction reduced macroadenomas to a similar extent (P < 0.05), but only caloric restriction significantly improved survival (P < 0.05). Given that a significant group × gender interaction was observed, we next examined males and females separately. In females, macroadenomas were markedly attenuated by VF− (1.33 ± 0.23 mean ± SE; P < 0.05), but not by caloric restriction (2.35 ± 0.25; P = 0.71), as compared with ad libitum (2.50 ± 0.34). In males, however, caloric restriction (1.71 ± 0.26; P < 0.01), but not VF− (2.94 ± 0.42; P = 0.29), reduced macroadenomas, as compared with ad libitum males (3.47 ± 0.30). In females, both VF− (P = 0.05) and caloric restriction (P < 0.01) improved survival, but not in male mice (P = 0.15). The benefits observed with caloric restriction were consistent with favorable metabolic adaptations, but protection conferred in VF− females was despite lower adiponectin levels (P < 0.05), and failure to reduce body mass, total adiposity, glucose, insulin, leptin, and chemokine (C–X–C motif) ligand 1 (CXCL-1) levels. In conclusion, these data provide the first causal evidence linking visceral fat to intestinal cancer risk, and suggest that factors, other than known metabolic mediators, may impact tumor development. Furthermore, these data emphasize that strategies designed to deplete visceral fat stores in humans should be considered in the prevention of intestinal cancer. Cancer Prev Res; 6(3); 177–87. ©2012 AACR.
Get the Fat Out!
Authors: Ignatenko Natalia A. , Gerner Eugene W.
Published: March 2013

Obesity is associated with increased risk of a number of cancers in humans, but the mechanism(s) responsible for these associations have not been established. It is estimated that 68% of adults are overweight or obese and that obesity may be causative in 4% to 7% of cancers in the United States. Several hypotheses have been put forward to explain the association between obesity and cancer including adipose-directed signaling (e.g., mTOR, AMPK), production of factors (e.g., insulin growth factor 1, fibroblast growth factor 1, and/or chronic inflammation associated with obesity. Huffman and colleagues used surgical methods to determine if visceral fat was causally related to intestinal tumorigenesis in the Apc1638/N+ mouse in a manner independent of confounding factors such as caloric restriction. They found that caloric restriction could extend survival in both male and female Apc1638/N+ mice but found that surgical removal of visceral fat was only effective in reducing macroadenomas in females. The results of this study do not identify the specific mechanism of association between visceral fat and intestinal carcinogenesis in female mice but do support the rationale for future cancer prevention trials that evaluate pharmacologic and behavioral strategies to reduce abdominal obesity in humans. Cancer Prev Res; 6(3); 161–4. ©2013 AACR.