bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Liver Biopsy in the Management of Patients with Liver Disease
Authors: Wong Florence
Published: March 2016

The role of liver biopsy in the diagnosis and management of liver disease is a controversial issue even among hepatologists. Although most causes of elevated liver enzymes can be determined, or at least suspected, on the basis of a careful history and laboratory tests, histological assessment remains the gold standard for most liver diseases. Histological evaluation can either confirm or refute clinical diagnoses and can provide information about the severity and stage of disease. Occasionally, the liver biopsy also provides an additional diagnosis. The spectrum of nonalcoholic fatty liver disease accounts for a substantial proportion of cases of chronically elevated liver enzymes and can be reliably diagnosed only by liver biopsy. Prognostic information can be obtained in patients with this disorder, as well as in those with alcoholic liver disease and viral hepatitis, and liver biopsy can be used as a guide to their management.
Ursodeoxycholic Acid and Atorvastatin in the Treatment of Nonalcoholic Steatohepatitis
Authors: Kiyici Murat , Gulten Macit , Gurel Selim , Nak Selim Giray , Dolar Enver , Savci Gursel , Adim Saduman Balaban , Yerci Omer , Memik Faruk
Published: March 2016

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is a serious disorder with the potential to gradually progress to cirrhosis. It is generally associated with obesity, diabetes and hyperlipidemia. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the effectiveness of atorvastatin and ursodeoxycholic acid (UDCA) in the treatment of NASH.

METHODS: This prospective study included 44 adult patients (24 men, 20 women) with a mean age of 48.90±7.69 years and mean body mass index (BMI) of 29.40±3.82. Ten patients had a history of diabetes. Serological markers for viral hepatitis were negative in all patients and there was no history of alcohol or drug abuse. Patients who had autoimmune hepatitis were excluded from the study. Liver biopsy was performed before therapy to confirm the diagnosis. Among NASH patients, 17 normolipidemic cases received UDCA 13 to 15 mg/kg/day (group 1), while hyperlipidemic cases (n=27) received atorvastatin 10 mg/day (group 2) for six months. The BMI, serum lipids, liver function tests and liver density, assessed by computerized tomography, were evaluated before and after the treatment period. The BMI, serum aminotransferase levels, histological parameters (steatosis, inflammation, fibrosis scores) and liver densities were not statistically different between the groups at the beginning of therapy.

RESULTS: The BMI, serum glucose, and triglyceride levels did not change in either group after the treatment period. In group 1, serum alanine aminotransferase (ALT) and gamma-glutamyl-transferase (GGT) levels reduced significantly, and in group 2, serum cholesterol, aspartate aminotransferase, ALT, alkaline phosphatase and GGT levels reduced significantly. Liver densities increased only in group 2, probably as a result of diminishing fat content of liver. The normalization of transaminases was also more prevalent in group 2. Liver steatosis was closely correlated with liver density, but inflammation and fibrosis were not.

CONCLUSIONS: The use of atorvastatin in NASH patients with hyperlipidemia was found to be both effective and safe. The benefit of statin and UDCA therapy in normolipidemic patients with NASH requires confirmation with further placebo-controlled trials.
Esophageal Foreign Body Causing Direct Aortic Injury
Authors: Lam ECS , Brown JA , Whittaker JS
Published: March 2016

Foreign bodies in the esophagus are uncommon causes of esophageal perforation. Many nonperforating cases are successfully managed by flexible gastroscopy. However, complicated foreign bodies such as those that result in esophageal perforation and vascular injury are best managed surgically. Gastroscopy remains the primary method of diagnosis. A case of a 59-year-old woman who developed retrosternal and intrascapular pain, odynophagia and hematemesis after eating fish is reported. Flexible gastroscopy showed arterial bleeding from the midthoracic esophagus. Computed tomography scan localized a 3 cm fish bone perforating the esophagus with surrounding hematoma. An aortogram did not reveal an actively bleeding aortoesophageal fistula. The fish bone was surgically removed and the patient recovered with no postoperative complications. This case illustrates the importance of early consideration for surgical intervention when confronted with a brisk arterial bleed from the esophagus with suggestive history of foreign body ingestion.
Robust Feature Selection from Microarray Data Based on Cooperative Game Theory and Qualitative Mutual Information
Authors: Mortazavi Atiyeh , Moattar Mohammad Hossein
Published: March 2016

High dimensionality of microarray data sets may lead to low efficiency and overfitting. In this paper, a multiphase cooperative game theoretic feature selection approach is proposed for microarray data classification. In the first phase, due to high dimension of microarray data sets, the features are reduced using one of the two filter-based feature selection methods, namely, mutual information and Fisher ratio. In the second phase, Shapley index is used to evaluate the power of each feature. The main innovation of the proposed approach is to employ Qualitative Mutual Information (QMI) for this purpose. The idea of Qualitative Mutual Information causes the selected features to have more stability and this stability helps to deal with the problem of data imbalance and scarcity. In the third phase, a forward selection scheme is applied which uses a scoring function to weight each feature. The performance of the proposed method is compared with other popular feature selection algorithms such as Fisher ratio, minimum redundancy maximum relevance, and previous works on cooperative game based feature selection. The average classification accuracy on eleven microarray data sets shows that the proposed method improves both average accuracy and average stability compared to other approaches.
TINF2Gene Mutation in a Patient with Pulmonary Fibrosis
Authors: Hoffman T. W. , van der Vis J. J. , van Oosterhout M. F. M. , van Es H. W. , van Kessel D. A. , Grutters J. C. , van Moorsel C. H. M.
Published: March 2016

Pulmonary fibrosis is a frequent manifestation of telomere syndromes. Telomere gene mutations are found in up to 25% and 3% of patients with familial disease and sporadic disease, respectively. The telomere geneTINF2encodes an eponymous protein that is part of the shelterin complex, a complex involved in telomere protection and maintenance. ATINF2gene mutation was recently reported in a family with pulmonary fibrosis. We identified a heterozygous Ser245Tyr mutation in theTINF2gene of previously healthy female patient that presented with progressive cough due to pulmonary fibrosis as well as panhypogammaglobulinemia at age 52. Retrospective multidisciplinary evaluation classified her as a case of possible idiopathic pulmonary fibrosis. Telomere length-measurement indicated normal telomere length in the peripheral blood compartment. This is the first report of a TINF2 mutation in a patient with sporadic pulmonary fibrosis, which represents another association betweenTINF2mutations and this disease. Furthermore, this case underlines the importance of telomere dysfunction and not telomere length alone in telomere syndromes and draws attention to hypogammaglobulinemia as a manifestation of telomere syndromes.
Optimal 25-Point Finite-Difference Subgridding Techniques for the 2D Helmholtz Equation
Authors: Wu Tingting , Chen Zhongying , Chen Jian
Published: March 2016

We present an optimal 25-point finite-difference subgridding scheme for solving the 2D Helmholtz equation with perfectly matched layer (PML). This scheme is second order in accuracy and pointwise consistent with the equation. Subgrids are used to discretize the computational domain, including the interior domain and the PML. For the transitional node in the interior domain, the finite difference equation is formulated with ghost nodes, and its weight parameters are chosen by a refined choice strategy based on minimizing the numerical dispersion. Numerical experiments are given to illustrate that the newly proposed schemes can produce highly accurate seismic modeling results with enhanced efficiency.
An Analysis of the Combination Frequencies of Constituent Medicinal Herbs in Prescriptions for the Treatment of Stroke in Korean Medicine: Determination of a Group of Candidate Prescriptions for Universal Use
Authors: Yun Byeong Cheol , Pae Seung Bin , Han Yoo Kyoung , Choi Moo Jin , Choi Byung Tae , Shin Hwa Kyoung , Baek Jin Ung
Published: March 2016

In contrast to Western medicine, which typically prescribes one medicine to treat a specific disease, traditional East Asian medicine uses any one of a large number of different prescriptions (mixtures of medicinal herbs), according to the patient’s characteristics. Although this can be considered an advantage, the lack of a universal prescription for a specific disease is considered a drawback of traditional East Asian medicine. The establishment of universally applicable prescriptions for specific diseases is therefore required. As a basic first step in this process, this study aimed to select prescriptions used in the treatment of stroke and, through the analysis of medicinal herb combination frequencies, select a high‐frequency medicinal herb combination group for further experimental and clinical research. As a result, we selected some candidates of a medicinal herb combination and 13 candidates of a medicinal herb for the treatment of stroke.
The Relationship between Constitution of Traditional Chinese Medicine in the First Trimester and Pregnancy Symptoms: A Longitudinal Observational Study
Authors: Jiang QiaoYu , Li Jue , Wang GuangHua , Wang Jing
Published: March 2016

Objective. We report on the distribution of traditional Chinese medicine (TCM) constitution in the first trimester and on the association between TCM constitution and maternal symptoms related to pregnancy. Methods. Participants were followed up until delivery to observe primary measures (gestational hypertension and gestational diabetes mellitus) and secondary measures (signs of miscarriage, miscarriage, nausea and vomiting, and sleepiness and defecation during pregnancy). Descriptive analysis, t‐tests, chi‐square tests, and logistic regression analysis were used in this study. Results. 61.8% of the participants had unbalanced constitutions. We did not find a significant association between the TCM constitution and gestational hypertension, gestational diabetes, miscarriage, signs of miscarriage, and defecation during pregnancy. And we found that women with unbalanced constitutions in early pregnancy had a greater likelihood of severe nausea and vomiting and poor sleep during pregnancy in the logistic regression analysis. Conclusions. These results have implications for female health care providers and policy makers. Identification of TCM constitution may be helpful for understanding nausea and vomiting and poor sleepiness during pregnancy, especially in the condition that can not be explained by modern medical science, and be helpful for making program to improve these uncomfortable symptoms.
Tracking Air-to-Air Missile Using Proportional Navigation Model with Genetic Algorithm Particle Filter
Authors: Liu Hongqiang , Yu Lei , Ruan Chenwei , Zhou Zhongliang
Published: March 2016

The purpose of this paper is to track the air-to-air missile. Here we put forward the PN-GAPF (Proportional Navigation motion model and Genetic Algorithm Particle Filter) method to solve the problem. The main jobs we have done can be listed as follows: firstly, we establish the missile state space model named as the Proportional Navigation (PN) motion model to simulate the real motion of the air-to-air missile; secondly, the PN-EKF and PN-PF methods are proposed to track the missile, through combining PN motion model with EKF and PF; thirdly, in order to solve the particle degeneracy and diversity loss, we introduce the intercross and variation in GA to the particles resampling step and then the PN-GAPF method is put forward. The simulation results show that the PN motion model is better than the CV and CA motion models for tracking the air-to-air missile and that the PN-GAPF method is more efficient than the PN-EKF and PN-PF.
Response ofSorghum bicolorL. to Residual Phosphate on Two Contrasting Soils Previously Planted to Cowpea or Maize
Authors: Olasunkanmi Tola Omolayo , Akinrinde Ezekiel Akinkunmi
Published: March 2016

Proper fertilizer nutrient management through adequate utilization of the residual value coupled with healthy crop rotation contributes significantly to sustainable crop production. This study was conducted to evaluate the direct and residual effects of two rock phosphate (RP) materials on two contrasting soils previously planted with either the cereal crop or the leguminous crop. The effectiveness of the RP materials as substitute for the conventional P fertilizers was evaluated using single superphosphate as reference at the Department of Agronomy, University of Ibadan, Ibadan, Nigeria. The experiments were 2 × 2 × 4 factorial in completely randomized design. The test crops in the first cropping performed better on the slightly acidic loamy sand than on the strongly acidic sandy clay loam. Performance of each crop was improved by P supply in the first and second cropping. Single superphosphate proved to be more efficient than the RPs in the first cropping but not as effective as MRP in the second cropping. In the second cropping, sorghum performed better on the soil previously cropped to cowpea while Morocco RP had the highest residual effect among the P-fertilizer sources. It is evident that rock phosphates are better substitutes to the conventional phosphorus fertilizers due to their long term residual effect in soils. The positive effects of healthy rotation of crops as well as the negative effects of low soil pH are also quite obvious.
Stall Flutter Control of a Smart Blade Section Undergoing Asymmetric Limit Oscillations
Authors: Li Nailu , Balas Mark J. , Nikoueeyan Pourya , Yang Hua , Naughton Jonathan W.
Published: March 2016

Stall flutter is an aeroelastic phenomenon resulting in unwanted oscillatory loads on the blade, such as wind turbine blade, helicopter rotor blade, and other flexible wing blades. Although the stall flutter and related aeroelastic control have been studied theoretically and experimentally, microtab control of asymmetric limit cycle oscillations (LCOs) in stall flutter cases has not been generally investigated. This paper presents an aeroservoelastic model to study the microtab control of the blade section undergoing moderate stall flutter and deep stall flutter separately. The effects of different dynamic stall conditions and the consequent asymmetric LCOs for both stall cases are simulated and analyzed. Then, for the design of the stall flutter controller, the potential sensor signal for the stall flutter, the microtab control capability of the stall flutter, and the control algorithm for the stall flutter are studied. The improvement and the superiority of the proposed adaptive stall flutter controller are shown by comparison with a simple stall flutter controller.
Cardioprotective Effects of Genistin in Rat Myocardial Ischemia‐Reperfusion Injury Studies by Regulation of P2X7/NF‐κB Pathway
Authors: Gu Meng , Zheng Ai-bin , Jin Jing , Cui Yue , Zhang Ning , Che Zhi-ping , Wang Yan , Zhan Jie , Tu Wen-juan
Published: March 2016

The present study aimed to assess the effects and mechanisms of genistin in the rat model of myocardial ischemia reperfusion injury. The rat hearts were exposed to the left anterior descending coronary artery (LAD) ligation for 30 min followed by 1 h of reperfusion. In the rat of myocardial ischemia/reperfusion (MI/R), it was found that genistin pretreatment reduced myocardial infarct size, improved the heart rate, and decreased creatine kinase (CK) and lactate dehydrogenase (LDH) levels in coronary flow. This pretreatment also increased catalase (CAT), superoxide dismutase (SOD) activities but decreased glutathione (GSH), malondialdehyde (MDA) levels. Furthermore, we determined that genistin can ameliorate the impaired mitochondrial morphology and oxidation system; interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), interleukin‐10 (IL‐10), and tumor necrosis factor‐α (TNF‐α) levels were also recovered. Besides, related‐proteins of nuclear factor kappa‐B (NF‐κB) signal pathway activated by P2X7 were investigated to determine the molecular mechanism of genistin and their expressions were measured by western blot. These results presented here demonstrated that genistin enhanced the protective effect on the rats with myocardial ischemia reperfusion injury. Therefore, the cardioprotective effects of genistin may rely on its antioxidant and anti‐inflammatory activities via suppression of P2X7/NF‐κB pathways.
Analysis of the Relationship between Risk Perception and Willingness to Pay for Nuclear Power Plant Risk Reduction
Authors: Yun Mirae , Lee Sang Hun , Kang Hyun Gook
Published: March 2016

With the adoption of new technologies, more risk is introduced into modern society. Important decisions about new technologies tend to be made by specialists, which can lead to a mismatch of risk perception between citizens and specialists, resulting in high social cost. Using contingent valuation methods, this paper analyzes the relationship between willingness to pay (WTP) and the factors expressed through people’s image of nuclear power plants (NPP), their perception of NPP safety, and how these can be affected by their scientific background level. Results indicate that groups with a high scientific background level tend to have low risk perception level, represented through their image and safety levels. Further, the results show that mean WTP is dependent on scientific background and image levels. It is believed that these results could help decision makers address the mismatch of trust between the public and specialists in terms of new policy.
Successful Treatment of Focal Segmental Glomerulosclerosis after Kidney Transplantation with Plasma Exchange and Abatacept in a Patient with Juvenile Rheumatoid Arthritis
Authors: Sprenger-Mähr Hannelore , Zitt Emanuel , Soleiman Afschin , Lhotta Karl
Published: March 2016

Recurrent focal segmental glomerulosclerosis (FSGS) after renal transplantation is difficult to treat. Recently a series of four patients unresponsive to plasma exchange (PE) and rituximab, who were successfully treated with abatacept, has been reported. We present a 26-year-old Caucasian patient who suffered from juvenile rheumatoid arthritis and developed severe proteinuria eleven days after transplantation. An allograft biopsy was suggestive of recurrent focal segmental glomerulosclerosis. He did not respond to PE therapy. A first dose of abatacept produced partial remission. Four weeks later proteinuria again increased and a second biopsy showed progression of disease. After another ineffective course of PE he was given a second dose of abatacept, which was followed by rapid, complete, and sustained resolution of proteinuria. This treatment caused a significant increase in BK and JC viremia. Whether abatacept ameliorated proteinuria via an effect on podocytes or on the patient’s primary disease remains speculative.
Epigenetic Profiling of H3K4Me3 Reveals Herbal Medicine Jinfukang‐Induced Epigenetic Alteration Is Involved in Anti‐Lung Cancer Activity
Authors: Lu Jun , Zhang Xiaoli , Shen Tingting , Ma Chao , Wu Jun , Kong Hualei , Tian Jing , Shao Zhifeng , Zhao Xiaodong , Xu Ling
Published: March 2016

Traditional Chinese medicine Jinfukang (JFK) has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK‐treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment (P < 0.05). Gene Ontology analysis indicates that these genes are involved in tumor‐related pathways, including pathway in cancer, basal cell carcinoma, apoptosis, induction of programmed cell death, regulation of transcription (DNA‐templated), intracellular signal transduction, and regulation of peptidase activity. In particular, we found that the levels of H3K4Me3 at the promoters of SUSD2, CCND2, BCL2A1, and TMEM158 are significantly altered in A549, NCI‐H1975, NCI‐H1650, and NCI‐H2228 cells, when treated with JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer‐related gene loci.
The Promotion Effect and Mechanism of Methanoic Acid on the Photoelectrocatalytic Degradation of Fulvic Acid
Authors: Dong Yifan , Li Jinhua , Li Xuejin , Bai Jing , Zhou Baoxue
Published: March 2016

A significant promotion effect of methanoic acid (MA) was proposed in the photoelectrocatalytic (PEC) degradation of fulvic acid (FA) and the degradation mechanism was also discussed. The PEC degradation property of FA and MA was investigated by an assembled thin-layer PEC reactor in which photoanode is TiO2nanotube arrays (TNAs) material. The result shows that only about 40% of FA was degraded, while MA could be completely degraded at the same condition. When mixing MA with FA, it shows a significant improvement in the degradation of FA. For instance, 50 mg/L FA mixed with 45 mg/L MA could achieve exhausted degradation. The results could be attributed to the promotion effect of MA that enhanced the generation of hydroxyl radicals, which maintain the continuous degradation of both FA and the intermediate products during the PEC process. This study proposed a new way of promoting the PEC degradation of FA as well as removing humus from the polluted water.
Sleep Promotion Program for Improving Sleep Behaviors in Adolescents: A Randomized Controlled Pilot Study
Authors: John Bindu , Bellipady Sumanth Shetty , Bhat Shrinivasa Undaru
Published: March 2016

Aims. The purpose of this pilot trial was to determine the efficacy of sleep promotion program to adapt it for the use of adolescents studying in various schools of Mangalore, India, and evaluate the feasibility issues before conducting a randomized controlled trial in a larger sample of adolescents.Methods. A randomized controlled trial design with stratified random sampling method was used. Fifty-eight adolescents were selected (mean age: 14.02 ± 2.15 years; intervention group,n=34; control group,n=24). Self-report questionnaires, including sociodemographic questionnaire with some additional questions on sleep and activities, Sleep Hygiene Index, Pittsburgh Sleep Quality Index, The Cleveland Adolescent Sleepiness Questionnaire, and PedsQL™Present Functioning Visual Analogue Scale, were used.Results. Insufficient weekday-weekend sleep duration with increasing age of adolescents was observed. The program revealed a significant effect in the experimental group over the control group in overall sleep quality, sleep onset latency, sleep duration, daytime sleepiness, and emotional and overall distress. No significant effect was observed in sleep hygiene and other sleep parameters. All target variables showed significant correlations with each other.Conclusion. The intervention holds a promise for improving the sleep behaviors in healthy adolescents. However, the effect of the sleep promotion program treatment has yet to be proven through a future research. This trial is registered withISRCTN13083118.
Blow-Up Phenomena for Nonlinear Reaction-Diffusion Equations under Nonlinear Boundary Conditions
Authors: Ding Juntang
Published: March 2016

This paper deals with blow-up and global solutions of the following nonlinear reaction-diffusion equations under nonlinear boundary conditions:g(u)t=∇·au∇u+fu  in  Ω×0,T,  ∂u/∂n=bx,u,t  on  ∂Ω×(0,T),  u(x,0)=u0(x)>0,  in  Ω¯,whereΩ⊂RN  (N≥2)is a bounded domain with smooth boundary∂Ω. We obtain the conditions under which the solutions either exist globally or blow up in a finite time by constructing auxiliary functions and using maximum principles. Moreover, the upper estimates of the “blow-up time,” the “blow-up rate,” and the global solutions are also given.
Support Vector Machine with Ensemble Tree Kernel for Relation Extraction
Authors: Liu Xiaoyong , Fu Hui , Du Zhiguo
Published: March 2016

Relation extraction is one of the important research topics in the field of information extraction research. To solve the problem of semantic variation in traditional semisupervised relation extraction algorithm, this paper proposes a novel semisupervised relation extraction algorithm based on ensemble learning (LXRE). The new algorithm mainly uses two kinds of support vector machine classifiers based on tree kernel for integration and integrates the strategy of constrained extension seed set. The new algorithm can weaken the inaccuracy of relation extraction, which is caused by the phenomenon of semantic variation. The numerical experimental research based on two benchmark data sets (PropBank and AIMed) shows that the LXRE algorithm proposed in the paper is superior to other two common relation extraction methods in four evaluation indexes (Precision, Recall,F-measure, and Accuracy). It indicates that the new algorithm has good relation extraction ability compared with others.
A Hybrid Approach for Fault Diagnosis of Railway Rolling Bearings Using STWD-EMD-GA-LSSVM
Authors: Yao Dechen , Yang Jianwei , Li Xi , Zhao Chunqing
Published: March 2016

Vibration signals resulting from railway rolling bearings are nonstationary by nature; this paper proposes a hybrid approach for the fault diagnosis of railway rolling bearings using segment threshold wavelet denoising (STWD), empirical mode decomposition (EMD), genetic algorithm (GA), and least squares support vector machine (LSSVM). The original signal is first denoised using STWD as a prefilter, which improves the subsequent decomposition into a number of intrinsic mode functions (IMFs) using EMD. Secondly, the IMF energy-torques are extracted as feature parameters. Concurrently, a GA is employed to optimize the LSSVM to improve the classification accuracy. Finally, the extracted features are used as inputs for classification by the GA-LSSVM. Actual railway rolling bearing vibration signals are used to experimentally verify the effectiveness of the proposed method. The results show that the novel method is effective and accurate for fault diagnosis of railway rolling bearings.
A Rare Case of Tolosa-Hunt-Like Syndrome in a Poorly Controlled Diabetes Mellitus
Authors: Lasam Glenmore , Kapur Sakshi
Published: March 2016

We report a case of a 50-year-old female with diabetes mellitus who presented with progressive second, third, fifth, sixth, and eighth cranial nerve palsy. Diagnostic investigation revealed hyperglycemic state, and brain imaging showed a right cavernous sinus enhancement suggestive of and consistent with Tolosa-Hunt syndrome. The patient was started on steroids with tight glycemic control for eight weeks; subsequently, the cranial nerve palsies resolved as well as documented resolution of the right cavernous sinus enhancement.
Pharmacodynamic Response of the MET/HGF Receptor to Small-Molecule Tyrosine Kinase Inhibitors Examined with Validated, Fit-for-Clinic Immunoassays
Authors: Srivastava Apurva K. , Hollingshead Melinda G. , Weiner Jennifer , Navas Tony , Evrard Yvonne A. , Khin Sonny A. , Ji Jiuping Jay , Zhang Yiping , Borgel Suzanne , Pfister Thomas D. , Kinders Robert J. , Bottaro Donald P. , Linehan W. Marston , Tomaszewski Joseph E. , Doroshow James H. , Parchment Ralph E.
Published: March 2016

Purpose: Rational development of targeted MET inhibitors for cancer treatment requires a quantitative understanding of target pharmacodynamics, including molecular target engagement, mechanism of action, and duration of effect.

Experimental Design: Sandwich immunoassays and specimen handling procedures were developed and validated for quantifying full-length MET and its key phosphospecies (pMET) in core tumor biopsies. MET was captured using an antibody to the extracellular domain and then probed using antibodies to its C-terminus (full-length) and epitopes containing pY1234/1235, pY1235, and pY1356. Using pMET:MET ratios as assay endpoints, MET inhibitor pharmacodynamics were characterized in MET-amplified and -compensated (VEGFR blockade) models.

Results: By limiting cold ischemia time to less than two minutes, the pharmacodynamic effects of the MET inhibitors PHA665752 and PF02341066 (crizotinib) were quantifiable using core needle biopsies of human gastric carcinoma xenografts (GTL-16 and SNU5). One dose decreased pY1234/1235 MET:MET, pY1235-MET:MET, and pY1356-MET:MET ratios by 60% to 80% within 4 hours, but this effect was not fully sustained despite continued daily dosing. VEGFR blockade by pazopanib increased pY1235-MET:MET and pY1356-MET:MET ratios, which was reversed by tivantinib. Full-length MET was quantifiable in 5 of 5 core needle samples obtained from a resected hereditary papillary renal carcinoma, but the levels of pMET species were near the assay lower limit of quantitation.

Conclusions: These validated immunoassays for pharmacodynamic biomarkers of MET signaling are suitable for studying MET responses in amplified cancers as well as compensatory responses to VEGFR blockade. Incorporating pharmacodynamic biomarker studies into clinical trials of MET inhibitors could provide critical proof of mechanism and proof of concept for the field. Clin Cancer Res; 22(14); 3683–94. ©2016 AACR.
Individual and Familial Susceptibility to MPTP in a Common Marmoset Model for Parkinson's Disease
Authors: Franke Sigrid K. , van Kesteren Ronald E. , Hofman Sam , Wubben Jacqueline A.M. , Smit August B. , Philippens Ingrid H.C.H.M.
Published: March 2016

Introduction: Insight into susceptibility mechanisms underlying Parkinson's disease (PD) would aid the understanding of disease etiology, enable target finding and benefit the development of more refined disease-modifying strategies. Methods: We used intermittent low-dose MPTP (0.5 mg/kg/week) injections in marmosets and measured multiple behavioral and neurochemical parameters. Genetically diverse monkeys from different breeding families were selected to investigate inter- and intrafamily differences in susceptibility to MPTP treatment. Results: We show that such differences exist in clinical signs, in particular nonmotor PD-related behaviors, and that they are accompanied by differences in neurotransmitter levels. In line with the contribution of a genetic component, different susceptibility phenotypes could be traced back through genealogy to individuals of the different families. Conclusion: Our findings show that low-dose MPTP treatment in marmosets represents a clinically relevant PD model, with a window of opportunity to examine the onset of the disease, allowing the detection of individual variability in disease susceptibility, which may be of relevance for the diagnosis and treatment of PD in humans.
Management of Large Prostate Gland in Men with Impaired Renal Function: Comparison of Safety, Efficacy and Outcomes of Monopolar, Bipolar Transurethral Resection and Open Prostatectomy
Authors: Srivastava Alok , Dhayal Ishwar R. , Rai Priyanka
Published: March 2016

Objective: The purpose of the study was to compare the safety, efficacy and outcome of monopolar transurethral resection of prostate (M-TURP), bipolar transurethral resection of prostate (BP-TURP) and open prostatectomy (OP) exclusively involving large prostate glands in men with renal impairment. Methods: Data of patients with gland size >90 g and serum creatinine >1.5 mg/dl, who were managed surgically at our institution from April 2009 to March 2014 were analyzed retrospectively. International Prostate Symptom Score (IPSS), quality of life (QoL) scores, PVR, serum creatinine and Q-max were recorded preoperatively and postoperatively at each follow-up visit. Follow-up was performed at 1, 3, 6 and 12 months. Results: M-TURP, BP-TURP and OP were the 3 types of surgeries performed. Preoperative characters were similar in all the groups. Hemoglobin drop, transfusion rates, irrigation time, catheter time and hospital days were significantly more in the OP group. Changes in sodium levels and incidence of transurethral syndrome were found to be more in the monopolar group. The follow-up data indicate a significant improvement in the IPSS, QoL, PVR and Q-max in all the groups. Conclusion: This category of patients can be managed safely and efficiently by all the 3 procedures, although BP-TURP has an advantage in terms of shorter catheterization, hospitalization and fewer complications like transurethral resection syndrome.
Glycogen Synthase Kinase-3β: Variation over Time and the Possible Association with Mood and Cognition in Healthy Individuals
Authors: Munkholm Klaus , Lenskjold Toke , Jacoby Anne Sophie , Miskowiak Kamilla Woznica , Vinberg Maj , Joaquim Helena Giroud Passarelli , Talib Leda Leme , Gattaz Wagner Farid , Kessing Lars Vedel
Published: March 2016

Evidence indicates a role for glycogen synthase kinase-3β (GSK-3β) in the pathophysiology of mood disorders and in cognitive disturbances; however, the natural variation in GSK-3β activity over time is unknown. We aimed to investigate GSK-3β activity over time and its possible correlation with emotional lability, subjective mood fluctuations and cognitive function in healthy individuals. Thirty-seven healthy subjects were evaluated with neuropsychological tests and blood samples at baseline and 12-week follow-up. Total GSK-3β and serine-9-phosphorylated GSK-3β in peripheral blood mononuclear cells were quantitated using enzyme immunometric assays. The activity of GSK-3β (serine-9-phosphorylated GSK-3β/total GSK-3β) was lower at baseline compared with follow-up. No significant mean change over time was observed in levels of total GSK-3β and serine-9-phosphorylated GSK-3β. Exploratory analysis revealed lower activity of GSK-3β in spring and summer compared with the fall season. No correlation was observed between GSK-3β activity and emotional lability, subjective mood fluctuations or cognitive function. The results suggest that intra- and interindividual variation in GSK-3β activity over time could contribute to the heterogeneity of findings in clinical studies. The stability of GSK-3β activity and the role of potential moderators of GSK-3β activity warrant further investigation. Clinical studies of GSK-3β should consider including repeated measures of both cases and healthy individuals.
Patient-Reported Experience of Modified Transperineal Template Guided Saturation Biopsy Under General Anaesthesia and without Prophylactic Catheterisation
Authors: Sarkar Debashis , Ekwueme Kingsley , Parr Nigel
Published: March 2016

Results of patient feedback questionnaire following transperineal template guided saturation biopsy (TPSB) without prophylactic catheterisation. Introduction and Objective: TPSB is increasingly utilised in the diagnosis and characterisation of prostate cancer. However, there is little data on patient experience after undergoing this procedure. We circulated a questionnaire to 511 consecutive patients from July 2007 to December 2014 and now analyse the responses. Materials and Methods: The mean age for the cohort was 64 (range 43-82). A mean of 28 biopsy cores (range 13-43) were taken under general anaesthesia (GA), as day case procedure. Patients received diclofenac 100 mg suppository on completion of the procedure. The questionnaire explored symptoms at 1 h, 1, 3 and 7 days postoperatively. Results: There were 301 responses (59%). Following TPSB, 38% initially experienced rectal bleeding, falling significantly to 3% on day 7 (p < 0.001) and it was not a serious condition in all cases. A majority reported haematuria at 1 h but persisting at 1 week in over one quarter (p < 0.001). Nevertheless, although initially often dark, none had other than pale pink by the end of the reporting period. In contrast, the incidence of haematospermia increased over 7 days, rising significantly to 38% by this stage (p < 0.001). Several patients commented that the procedure was more tolerable than their previous conventional TRUS biopsy and 20 (6.6%) with voiding difficulty required catheterisation. In all, 23% patients felt pain, and out of these 23% only 5% required minor analgesia at day 7. Conclusion: TPSB under GA without prophylactic catheterisation is well tolerated, carrying acceptable postoperative symptom rates. Interestingly, a significant proportion of patients ejaculate within 7 days, which again suggests good tolerance to the procedure. Patients should be provided with this data preoperatively when they are considering TPSB.
The Howard Wise Gallery Show Computer-Generated Pictures (1965): A 50th-Anniversary Memoir
Authors: Noll A. Michael
Published: March 2016

In April 1965, the Howard Wise Gallery in New York City held a show of computer-generated pictures by Bela Julesz and Michael Noll. This show was a very early public exhibit of digital art in the United States. This essay is a memoir of that show.
New species and new records of Clavariaceae (Agaricales) from Brazil
Authors: FURTADO ARIADNE N. M. , DANIËLS PABLO P. , NEVES MARIA ALICE
Published: March 2016

Fourteen species in three genera of Clavariaceae from the Atlantic Forest of Brazil are described (six Clavaria, seven Clavulinopsis and one Ramariopsis). Clavaria diverticulata, Clavulinopsis dimorphica and Clavulinopsis imperata are new species, and Clavaria gibbsiae, Clavaria fumosa and Clavulinopsis helvola are reported for the first time for the country. Illustrations of the basidiomata and the microstructures are provided for all taxa, as well as SEM images of ornamented basidiospores which occur in Clavulinopsis helvola and Ramariopsis kunzei. A key to the Clavariaceae of Brazil is also included.
Bilateral Coordination of Children who are Blind
Authors: Rutkowska Izabela , Lieberman Lauren J. , Bednarczuk Grzegorz , Molik Bartosz , Kazimierska-Kowalewska Kalina , Marszałek Jolanta , Gómez-Ruano Miguel-Ángel
Published: March 2016

The purpose of this study was to evaluate the bilateral coordination in children and adolescents with visual impairments aged 7 to 18 years in comparison to their sighted peers. An additional objective was to identify the influence of sex and age on bilateral coordination. Seventy-five individuals with congenital severe visual impairment (40 girls and 35 boys) comprised the visually impaired group. The Sighted group comprised 139 youth without visual impairment. Subtest 4 of the Bruininks-Oseretsky Test of Motor Proficiency was administered to test bilateral coordination. To analyze the effect of the independent variables in the results obtained in the Subtest 4, four linear regression models were applied according to group and sex. The results indicated that severe visual impairment and lack of visual sensation had a negative effect on the development of participants’ bilateral coordination, which however did not depend on sex or age.
A Model for Aligning Self-Determination and General Curriculum Standards
Authors: Konrad Moira , Walker Allison R. , Fowler Catherine H. , Test David W. , Wood Wendy M.
Published: March 2016

Ms. Smith and Ms. Alvarez, special education teachers at Harris Middle School, have had many conversations about how to balance all their responsibilities. They are accountable for teaching academic content standards, and they also must address their students' individual needs, including self-determination skills. They often wonder, “How can we do it all given our limited time and resources?”
Story Writing as a Problem-Solving Vehicle
Authors: Dehouske Ellen J.
Published: March 2016

The written word is a modality for self-expression, self-exploration, and problem-solving. Through story writing, students reveal their perceptions, attitudes, coping skills, and problem-solving strategies. Story writing tasks can be structured to encourage students to explore the decision-making process and identify behavioral alternatives and consequences.
Democratizing civil disobedience
Authors: Celikates Robin
Published: March 2016

The goal of this article is to show that mainstream liberal accounts of civil disobedience fail to fully capture the latter’s specific characteristics as a genuinely political and democratic practice of contestation that is not reducible to an ethical or legal understanding either in terms of individual conscience or of fidelity to the rule of law. In developing this account in more detail, I first define civil disobedience with an aim of spelling out why the standard liberal model, while providing a useful starting point, ultimately leads to an overly constrained, domesticated and sanitized understanding of this complex political practice. Second, I place the political practice of civil disobedience between two opposing poles: symbolic politics and real confrontation. I argue that the irreducible tension between these poles precisely accounts for its politicizing and democratizing potential. Finally, I briefly examine the role of civil disobedience in representative democracies, addressing a series of recent challenges made in response to this radically democratic understanding of disobedience.
Spatio-topological network analysis of hydrological infrastructure as a decision support tool for flood mitigation in coastal mega-cities
Authors: Ogie Robert , Holderness Tomas , Dunbar Michelle , Turpin Etienne
Published: March 2016

Hydrological infrastructure components such as pumps, floodgates, and flood gauges are invaluable assets for mitigating flooding, which threatens millions of lives and damages property worth billions of dollars in coastal mega-cities around the world. By improving the understanding of how these hydrological infrastructure components are both spatially and topologically connected through waterways (rivers, canals, streams, etc.) within coastal mega-cities, more precise decisions can be made regarding the most appropriate hydrological infrastructure components required to mitigate flooding during emergency conditions. This paper explores the use of graph theory to create a spatio-topological model of a real world hydrological infrastructure network for one of the most representative coastal mega-cities—Jakarta, Indonesia. The network is modeled as a directed multigraph, with hydrological infrastructure represented as network nodes and waterways as edges. The article demonstrates how the network model can be used as a real-time decision support tool for responding to flooding events by alerting decision makers to the occurrence of rising water levels in any given area and, suggesting the most appropriate infrastructure components to engage in order to prevent a given area from flooding.
Circulating non-hematological cells during cardiopulmonary bypass: new findings in cardiac surgery procedures
Authors: Santise Gianluca , Marinaro Cinzia , Maselli Daniele , Dominici Carmelo , Di Vito Anna , Donato Giuseppe , Camastra Caterina , Zeppa Pio , Barni Tullio , Rizzuto Antonia , Viglietto Giuseppe , Mignogna Chiara
Published: March 2016

Background:

Several factors have been historically advocated to explain the coagulative and inflammatory disorders following cardiopulmonary bypass (CPB). In this paper, we describe the presence of circulating non-hematological cells, introduced within the bloodstream during CPB. We defined the origin of the cells and tested their impact on coagulation.

Methods:

We collected peripheral arterial blood samples in twenty consecutive coronary artery bypass graft cases at four different surgical moments and assessed the presence and nature of circulating cells with the use of the CELLSEARCH® Test, immunocytochemistry and immunofluorescence, evaluating the expression of cytokeratin and calretinin. The effect of the circulating non-hematological cells on coagulation was tested in vitro, using the ROTEM assay.

Results:

A mean of 263.85 ± 57.5 (median 258.5) cells were present in the samples following the suction of blood from the surgical field while all the other samples were negative (zero cells) (p<0.00001). Immunologic tests confirmed the mesothelial origin of the cells. The ROTEM® assay of the blood samples contaminated by the mesothelial cells presented longer clotting times (53.4 ± 8.2 secs 48.3 ± 8.9 sec, p=0.05), longer clot formation times (137.1 ± 31.5 sec vs 111.9 ± 25.2 sec, p=0.009), smaller alfa angle amplitudes (66.7 ± 9.1° vs 71.1 ± 5.1°, p=0.04) and maximum clot firmness times (59.0 ± 5.4 sec vs 61.9 ±4.6 sec, p=0.004) than the controls.

Conclusion:

The presence of circulating non-hematological cells during CPB with a mesothelial immunophenotype alters in vitro coagulation assays. This finding can help to further understand the pathophysiology of CPB.
‘Nobody is sure of tomorrow’
Authors: Tade Oludayo , Nwanosike Precious Chiamaka
Published: March 2016

This study investigates factors underlying adoption of safety behaviours among vicarious victims of Boko Haram terrorism in Sabon Gari, a predominantly Christian community in Kano State. Using the Health Belief Model, data were generated from non-indigenes in Sabon Gari. Findings indicated that participants felt susceptible to being direct victims with expressions such as ‘nobody is safe or sure of tomorrow’ because of their identities as Christians and non-indigenes. Loss of lives, destruction of business, weakened bonds, and feelings of imaginary dangers captured perceived severity. Perceived cost of adopting safety behaviours included an outright ban on evangelism, utilization of visitation and isolation. Adopting cues to action, participants avoided crowded places, and relocated family members to reduce collateral damages of anticipated victimization. Implementation of personal (avoidance of vain talks) and institutional preventive measures (purchase of scanners and organization of security training) constituted control measures to prevent victimization. In conclusion, perceived susceptibility facilitated adoption of safe and secure behaviours.
Cangrelor Bridge Therapy for Gastroduodenal Biopsy
Authors: Cahoon William D. , Oswalt Allison K. , Francis Kerry E. , Magee Lauren C. , Lowe Denise K.
Published: March 2016

Dual antiplatelet therapy (DAPT) is the key for secondary prevention of acute coronary syndromes and percutaneous coronary intervention with stent placement. Premature discontinuation of DAPT can result in an increase in cardiac ischemic events and death. If early interruption of DAPT for urgent procedures or surgery is necessary, then ischemic and bleed risks must be balanced with bridging therapy. To date, no medications have a Food and Drug Administration indication for antiplatelet bridge therapy. We present a case of a woman with a history of gastrointestinal bleeding on DAPT for a drug-eluting stent who received cangrelor as bridge therapy prior to gastroduodenal biopsy.
Breast cancer patient with everolimus-induced angioedema: A rare occurrence with potential for serious consequences
Authors: Roe Neil , Twilla Jennifer D , Duhart Benjamin , Wheeler Brian
Published: March 2016

Background

The development of angioedema is a rare yet serious clinical event that may develop due to an adverse drug reaction. Rapid recognition and treatment of this adverse reaction is critical for optimal patient outcomes; however, prevention of this occurrence is preferred.

Case report

A 59-year-old woman presented to the emergency department with lingual angioedema caused by the addition of everolimus to her medication regimen. The patient improved after withdrawal of the offending agent and standard treatment. Early recognition by healthcare providers and management of everolimus-induced angioedema is vital for successful patient outcomes. This report increases awareness of everolimus as a potentially causative agent for the development of angioedema.