bluuebunny/crossref_metadata_2025 huggingface dataset:
Bifurcation Regulations Governed by Delay Self-Control Feedback in a Stochastic Birhythmic System
Authors: Ma Zhidan , Ning Lijuan
Published: January 2018

We aim to investigate bifurcation behaviors in a stochastic birhythmic van der Pol (BVDP) system subjected to delay self-control feedback. First, the harmonic approximation is adopted to drive the delay self-control feedback to state variables without delay. Then, Fokker–Planck–Kolmogorov (FPK) equation and stationary probability density function (SPDF) for amplitude are obtained by applying stochastic averaging method. Finally, dynamical scenarios of the change of delay self-control feedback as well as noise that markedly influence bifurcation performance are observed. It is found that: the big feedback strength and delay will suppress the large amplitude limit cycle (LC) while the relatively big noise strength facilitates the large amplitude LC, which imply the proposed regulation strategies are feasible. Interestingly enough, the inner LC is never destroyed due to noise. Furthermore, the validity of analytical results was verified by Monte Carlo simulation of the dynamics.
Chaos and Adaptive Control of the Fractional-Order Magnetic-Field Electromechanical Transducer
Authors: Luo Shaohua , Li Shaobo , Tajaddodianfar Farid
Published: January 2018

In this paper, we investigate chaos and adaptive control of the magnetic-field electromechanical transducer wherein the electric characteristics of the capacitor contain the fractional-order derivative. The phase diagrams for different values of the fractional-order exhibit chaotic characteristics of the magnetic-field electromechanical transducer. In the process of controller design, a continuous frequency distributed model is utilized to construct the indirect Lyapunov stability criterion and a Chebyshev neural network with weight, and fractional-order adaptive law is introduced to approximate the complicated unknown function. To suppress chaotic oscillation, an adaptive control scheme by fusing Chebyshev neural network and backstepping is presented to guarantee that the closed-loop system is globally asymptotically stable. To illustrate the feasibility of the proposed approach, simulation studies are done in the end.
CHARACTERIZATION OF THE HYDROCARBON POTENTIAL AND NON-POTENTIAL ZONES USING WAVELET-BASED FRACTAL ANALYSIS
Authors: MUKHERJEE BAPPA , ROY P. N. S.
Published: January 2018

The identification of prospective and dry zone is of major importance from well log data. Truthfulness in the identification of potential zone is a very crucial issue in hydrocarbon exploration. In this line, the problem has received considerable attention and many conventional techniques have been proposed. The purpose of this study is to recognize the hydrocarbon and non-hydrocarbon bearing portion within a reservoir by using the non-conventional technique. The wavelet based fractal analysis (WBFA) has been applied on the wire-line log data in order to obtain the pre-defined hydrocarbon (HC) and non-hydrocarbon (NHC) zones by their self-affine signal nature is demonstrated in this paper. The feasibility of the proposed technique is tested with the help of most commonly used logs, like self-potential, gamma ray, resistivity and porosity log responses. These logs are obtained from the industry to make out several HC and NHC zones of all wells in the study region belonging to the upper Assam basin. The results obtained in this study for a particular log response, where in the case of HC bearing zones, it is found that they are mainly situated in a variety of sandstones lithology which leads to the higher Hurst exponent. Further, the NHC zones found to be analogous to lithology with higher shale content having lower Hurst exponent. The above proposed technique can overcome the chance of miss interpretation in conventional reservoir characterization.
Ab initio STUDY OF POINT DEFECTS IN 2D GRAPHENE LAYER
Authors: HUSSAIN FAYYAZ , IMRAN MUHAMMAD , SIDDIQA AISHA , KHALIL RANA M. ARIF , RANA ANWAR MANZOOR , SATTAR M. ATIF , NIAZ NIAZ AHMAD , ULLAH HAFEEZ , AHMAD NADEEM
Published: January 2018

With a hexagonal (honeycomb) network of mono-layered carbon atoms, graphene has demonstrated outstanding electronic properties. This work describes the impact of deliberately introduced single, double and triple carbon vacancies in grapheme monolayer. In addition, these carbon vacancies were then substituted with gold atoms and their influence on the electronic properties of the two-dimensional (2D) graphene layers was investigated. In this regard, a first principle calculation was performed to examine electronic properties and formation energy of 2D graphene layer by applying density functional theory (DFT). Introduction of such defects appeared to increase the stability of the graphene sheet as confirmed by formation energy calculations. Moreover, decrease of formation energy was noticed to be significant with an increase in the number of defects. Band structure calculations described the shifting of localized states from valance to conduction bands which caused the transformation of semiconducting behavior into metallic one on the filling of carbon vacancies by gold atoms. Comparing this behavior with that of partial density of states (PDOS) it was noted that a lot of states existed in the valance band in the case of C-vacancies yielding charge free region around the vacancy. On the other hand, filling of C-vacancies by gold generated a large number of energy states in the conduction band illustrating the accumulation of charges near gold atom. Width of the peak across the Fermi level indicated the accumulative energy of electron to be almost 0.15[Formula: see text]eV. These calculated DOS and PDOS demonstrated metallic like behavior of the graphene monolayer with typical defect states.
LENGTH OF POLY-CYTIDINE REPEATS CONTROLS THE PHASE-VARIABLE EXPRESSION OF THE FIMBRIAL PROTEIN IN AVIBACTERIUM PARAGALLINARUM
Authors: Liu Chai-Chi , Ou Shan-Chia , Tan Dune-Huey , Hsieh Ming-Kun , Chang Poa-Chun
Published: January 2018

The FlfA fimbrial protein is an important virulence factor and vaccine candidate of Avibacterium paragallinarum. Although all Taiwanese field strains of A. paragallinarumwere shown to contain an intact flfA gene, only some of them express the flfA protein in vitro. The aim of this study was to investigate how flfA expression is controlled in A. paragallinarum. The results of quantitative reverse transcription-polymerase chain reaction, 5[Formula: see text] rapid amplification of cDNA ends, and sequencing analyses showed that flfA expression is controlled by the length of a poly-cytidine (poly-C) tract that is located at the promoter region of flfA. In vitro passage of A. paragallinarum in chickens led to a change in the length of the poly-C tract and subsequently turned off flfA expression. These findings are valuable for understanding the mechanism of pathogenicity of A. paragallinarum.
PLETH VARIABILITY INDEX-GUIDED FLUID THERAPY LOWERS POST-OPERATIVE LACTATE LEVELS IN DOGS UNDERGOING ELECTIVE ABDOMINAL SURGERY: A RANDOMIZED CONTROLLED TRIAL
Authors: Hu Chun-Hsiang , Hsu Tien-Huan , Chen Kuan-Sheng , Lee Wei-Ming , Wang Hsien-Chi
Published: January 2018

To evaluate the hemodynamic optimization effect of pleth variability index (PVI)-guided fluid therapy during abdominal surgery on tissue perfusion, 19 client-owned dogs that underwent elective abdominal surgery were randomized into control ([Formula: see text]) and PVI ([Formula: see text]) groups. In the control group, perioperative fluid management was based on the 2013 AAHA/AAFP Fluid Therapy Guidelines for Dogs and Cats. In the PVI group, the fluid rate was maintained based on basic daily requirements. If PVI was higher than 15% for [Formula: see text][Formula: see text]min, 3–5[Formula: see text]mL/kg of crystalloid fluid bolus was infused. The tissue perfusion indicator, lactate levels, was measured at the time of intubation, extubation, and 6, 12 and 24[Formula: see text]h postoperatively. There were no significant differences in total and average fluid infused between control and PVI groups. The control group had significantly higher lactate levels than that of the PVI group at 12[Formula: see text]h postoperatively ([Formula: see text][Formula: see text]mmol/L versus [Formula: see text][Formula: see text]mmol/L, [Formula: see text]) and overall postoperatively ([Formula: see text][Formula: see text]mmol/L versus [Formula: see text][Formula: see text]mmol/L, [Formula: see text]). The control group revealed more profound hemodilution, as indicated by significantly decreased postoperative blood urea nitrogen (BUN), creatinine, and total protein. PVI-guided fluid therapy lowers lactate levels after elective abdominal surgery in dogs. Therefore, based on the result of this study PVI may provide customized fluid therapy to improve tissue perfusion and avoid unnecessary fluid overload.
TRAUMA-RELATED DEATHS OF DOMESTICATED DOGS AND CATS IN TAIWAN
Authors: Huang Wei-Hsiang , Liao Albert Taiching , Chu Pei-Yi , Zhai Shao-Hua , Yen I-Feng , Liu Chen-Hsuan
Published: January 2018

The advancement of animal welfare has attracted much public attention in recent years in Taiwan. Trauma, as an important extrinsic cause of death in pet dogs and cats, is closely related to human activities and owner–pet relationships. This retrospective study aims to evaluate trauma-related deaths in domesticated dogs and cats in Taiwan, and further investigate demographic risk factors associated with specific traumatic causes. Data from 2252 dogs and 1325 cats were collected from a real-time reporting system for mortality of Taiwanese domesticated dogs and cats during 2012–2014. A total of 278 trauma-related deaths, including 177 dogs and 101 cats, were reported. The leading traumatic causes were car accidents (dog/cat:127/48), falls (dog/cat:18/15), and animal interactions (dog/cat:13/11). Frequencies of trauma deaths were higher for animals within the 0–6 years age group in both species. Dogs and cats dying at [Formula: see text]10 years of age, male and intact animals displayed increased risks of trauma deaths. Dogs, animals dying at [Formula: see text]10 years of age, and intact animals displayed increased risks of dying from car accidents. Animals dying at [Formula: see text]10 years of age displayed increased risks of dying from falls. Intact animals displayed increased risks of dying from animal interactions. A few cases raised strong suspicion of animal cruelty; such findings underscore the importance of the development of forensic veterinary medicine.
Influence of thermal conditions on the electrocaloric effect in a multilayer capacitor based on doped BaTiO3
Authors: Bondarev V. S. , Flerov I. N. , Gorev M. V. , Pogoreltsev E. I. , Molokeev M. S. , Mikhaleva E. A. , Shabanov A. V. , Es’kov A. V.
Published: January 2018

We present the results of studies of thermal expansion, heat capacity, permittivity, polarization and the influence of different thermal conditions on the intensive electrocaloric effect (ECE), [Formula: see text], in a commercial multilayer capacitor based on doped BaTiO3. Investigations in a wide temperature range revealed one anomaly in the behavior of the physical properties at about 290[Formula: see text]K characteristic for the relaxors. Direct measurements showed a high reversibility of ECE under equilibrium thermal conditions. Good agreement was found between the values of [Formula: see text] determined by direct and indirect measurements at the electric field up to 15.4[Formula: see text]kV/cm. Quasi-isothermal conditions lead, firstly, to decrease of large [Formula: see text]0.94[Formula: see text]K obtained in adiabatic conditions under [Formula: see text][Formula: see text]kV/cm to 0.87[Formula: see text]K, and, secondly, the appearance of a difference between the values of [Formula: see text] and [Formula: see text] determined when the electric field is applied and removed. Using this phenomenon and changing the frequency of the periodic electric field, [Formula: see text][Formula: see text]kV/cm, the effect of cooling was obtained equal to [Formula: see text][Formula: see text]K. The results obtained are useful for further development of the electrocaloric refrigeration technique without thermal switches.
Evaluation of Operating Performances Based on Median Damage Load Spectrum
Authors: Zhai Xinting , Wang Jixin , Li Yingying
Published: January 2018

Load spectrum is the basement of reliability analysis. Selecting a suitable operator for a certain model in a typical experiment field is of benefit to the acquisition of load spectrum. Different operating performances caused by different operators have the characteristics of multiple evaluation indicators. In this paper, a comprehensive evaluation method based on median damage is proposed. The method is applied to evaluate the actual operating performances in the experiment field of the excavator. Comparative results show that the proposed method is feasible, and will be more convenient when more indicators are involved. The proposed method provides a theoretical reference for the compiling of load spectrum acquisition specification, and proposes an additional method for the evaluation of the operating performances.
A Toolkit for Snow-Cover Area Calculation and Display Based on the Interactive Multisensor Snow and Ice Mapping System and an Example for the Tibetan Plateau Region
Authors: Tucker Tyler C. , Shen Samuel S. P.
Published: January 2018

This research develops a toolkit for snow-cover area calculation and display (SACD) based on the Interactive Multisensor Snow and Ice Mapping System (IMS). The paper uses the Tibetan Plateau region as an example to describe the toolkit’s method, results, and usage. The National Snow and Ice Data Center (NSIDC) provides to the public IMS a well-used system for monitoring the snow and ice cover. The newly developed toolkit is based on a simple shoe-lace formula for a grid box area on a sphere and can be conveniently used to calculate the total area of snow cover given the IMS data. The toolkit has been made available as an open source Python software on GitHub. The toolkit generates the time series of the daily snow-covered area for any region over the Northern Hemisphere from 4 February 1997. The toolkit also creates maps showing snow and ice coverage with an elevation background. The Tibetan Plateau (TP) region [Formula: see text]–[Formula: see text]N)[Formula: see text][Formula: see text]–[Formula: see text]E) is used as an example to demonstrate our work on SACD. The IMS products at 24, 4, and 1[Formula: see text]km resolutions include each grid’s latitude and longitude coordinates that are used to calculate the grid box’s area using the shoe-lace formula. The total TP area calculated by the sum of the areas of all the grid boxes approximates the true spherical TP surface area bounded by [Formula: see text]–[Formula: see text]N) [Formula: see text]–[Formula: see text]E) with a difference 0.046% for the 24[Formula: see text]km grid and 0.033% for the 4[Formula: see text]km grid. The differences in the snow-cover area reported by the 24[Formula: see text]km and 4[Formula: see text]km grids vary between [Formula: see text]% and 6.24%. The temporal variations of the daily TP snow cover are displayed in time series from 4 February 1997 to present with 4[Formula: see text]km and 24[Formula: see text]km resolutions.
Mining Timed Regular Specifications from System Traces
Authors: Narayan Apurva , Cutulenco Greta , Joshi Yogi , Fischmeister Sebastian
Published: January 2018

Temporal properties define the order of occurrence and timing constraints on event occurrence. Such specifications are important for safety-critical real-time systems. We propose a framework for automatically mining temporal properties that are in the form of timed regular expressions (TREs) from system traces. Using an abstract structure of the property, the framework constructs a finite state machine to serve as an acceptor. We analytically derive speedup for the fragment and confirm the speedup using empirical validation with synthetic traces. The framework is evaluated on industrial-strength safety-critical real-time applications using traces with more than 1 million entries.
State Capacity Redux: Integrating Classical and Experimental Contributions to an Enduring Debate
Authors: Berwick Elissa , Christia Fotini
Published: January 2018

What state capacity is and how to strengthen it remain open questions, as the underlying incentives of the state, its citizens, and its agents align in some areas of state activity and diverge in others. This article lays out a framework that integrates classical and experimental approaches within a common theoretical structure based on the diverse capacity challenges states face with respect to extraction, coordination, and compliance. Addressing each in turn, we show that state capacity is an interactive process, the product of institutions governing relations between the state, mass publics, and bureaucrats. We argue that the institutions ensuring capacity and the processes that bring them into being vary. Our review highlights trends in recent research, as well as relevant differences in opportunities for and obstacles to empirical work on the subject.
Topical Imiquimod for the Treatment of Relapsed Cutaneous Langerhans Cell Histiocytosis after Chemotherapy in an Elderly Patient
Authors: Imashuku Shinsaku , Kobayashi Miyako , Nishii Yoichi , Nishimura Keisuke
Published: January 2018

Diagnosis and treatment of Langerhans cell histiocytosis (LCH) in elderly patients are often difficult. We report here a 61-year-old female suffering from a refractory axillary ulcer for nearly a year, whose biopsy revealed LCH. It was also noted that the patient had other cutaneous papulovesicular eruptions of LCH as well as central diabetes insipidus. The patient was first successfully treated with multiagent chemotherapy (cytosine arabinoside/vinblastine/prednisolone). DDAVP also well controlled diabetes insipidus; however, the axillary ulcer and cutaneous LCH relapsed. Thereafter, we found topical imiquimod to be effective in the treatment of relapsed cutaneous LCH lesions.
Robustness Analysis of an Outranking Model Parameters’ Elicitation Method in the Presence of Noisy Examples
Authors: Rangel-Valdez Nelson , Fernandez Eduardo , Cruz-Reyes Laura , Gomez-Santillan Claudia , Rivera Gilberto , Florencia Rogelio
Published: January 2018

One of the main concerns in Multicriteria Decision Aid (MCDA) is robustness analysis. Some of the most important approaches to model decision maker preferences are based on fuzzy outranking models whose parameters (e.g., weights and veto thresholds) must be elicited. The so-called preference-disaggregation analysis (PDA) has been successfully carried out by means of metaheuristics, but this kind of works lacks a robustness analysis. Based on the above, the present research studies the robustness of a PDA metaheuristic method to estimate model parameters of an outranking-based relational system of preferences. The method is considered robust if the solutions obtained in the presence of noise can maintain the same performance in predicting preference judgments in a new reference set. The research shows experimental evidence that the PDA method keeps the same performance in situations with up to 10% of noise level, making it robust.
A Simple Scatter Reduction Method in Cone-Beam Computed Tomography for Dental and Maxillofacial Applications Based on Monte Carlo Simulation
Authors: Thanasupsombat Chalinee , Thongvigitmanee Saowapak S. , Aootaphao Sorapong , Thajchayapong Pairash
Published: January 2018

The quality of images obtained from cone-beam computed tomography (CBCT) is important in diagnosis and treatment planning for dental and maxillofacial applications. However, X-ray scattering inside a human head is one of the main factors that cause a drop in image quality, especially in the CBCT system with a wide-angle cone-beam X-ray source and a large area detector. In this study, the X-ray scattering distribution within a standard head phantom was estimated using the Monte Carlo method based on Geant4. Due to small variation of low-frequency scattering signals, the scattering signals from the head phantom can be represented as the simple predetermined scattering signals from a patient’s head and subtracted the projection data for scatter reduction. The results showed higher contrast and less cupping artifacts on the reconstructed images of the head phantom and real patients. Furthermore, the same simulated scattering signals can also be applied to process with higher-resolution projection data.
Taxi Driver’s Operation Behavior and Passengers’ Demand Analysis Based on GPS Data
Authors: Hu Xiaowei , An Shi , Wang Jian
Published: January 2018

The existing research outputs paid less attention to the relationship between land use and passenger demand, while the taxi drivers’ searching behavior for different lengths of observation period has not been explored. This paper is based on taxi GPS trajectories data from Shenzhen to explore taxi driver’s operation behavior and passengers’ demand. The taxi GPS trajectories data covers 204 hours in Shenzhen, China, which includes the taxi license number, time, longitude, latitude, speed, and whether passengers are in the taxi vehicle, to track the passenger’s pick-up and drop-off information. This paper focuses on these important topics: exploring the taxi driver operation behavior by the measurements of activity space and the connection between different activity spaces for different time duration; mainly focusing on eight traffic analysis zones (TAZs) of Shenzhen and exploring the customer’s real-time origin and destination demands on a spatial-temporal distribution on weekdays and weekends; taxi station optimization based on the passenger demand and expected customer waiting time distribution. This research can be helpful for taxi drivers to search for a new passenger and passengers to more easily find a taxi’s location.
Polyfunctional Modifiers for Bitumen and Bituminous Materials with High Performance
Authors: Kemalov Alim Feizrakhmanovich , Kemalov Ruslan Alimovich , Abdrafikova Ilmira Maratovna , Fakhretdinov Pavel Sagitovich , Valiev Dinar Zinnurovich
Published: January 2018

Over the last decade increase in capacity and the intensity of vehicular traffic has increased manifoldly, including heavy trucks, super singles, and higher tire pressures, resulting in significant increase of dynamic loads on the road surface which in turn lead to high quality requirements for bitumen in order to avoid premature wear and failure of asphalt concrete pavements. One of the possibilities to increase the quality of bitumen is to use special additives and modifiers that can provide a high adhesion to mineral filler and inhibit the aging and degradation processes in the asphalt coating. To achieve this, in the present study composite modifiers based on bisimidazolines derivatives were synthesized. The developed polyfunctional modifier (PFM) of complex action provides enhanced thermal stability, significantly improves the adhesion between bitumen binder and aggregates, and also improves the physical‐mechanical properties of the asphalt concrete. Based on the test results it is recommended to use the synthesized samples of the PFM additive with complex action in asphalt mixtures for road paving.
A Markov Chain Based Demand Prediction Model for Stations in Bike Sharing Systems
Authors: Zhou Yajun , Wang Lilei , Zhong Rong , Tan Yulong
Published: January 2018

Accurate transfer demand prediction at bike stations is the key to develop balancing solutions to address the overutilization or underutilization problem often occurring in bike sharing system. At the same time, station transfer demand prediction is helpful to bike station layout and optimization of the number of public bikes within the station. Traditional traffic demand prediction methods, such as gravity model, cannot be easily adapted to the problem of forecasting bike station transfer demand due to the difficulty in defining impedance and distinct characteristics of bike stations (Xu et al. 2013). Therefore, this paper proposes a prediction method based on Markov chain model. The proposed model is evaluated based on field data collected from Zhongshan City bike sharing system. The daily production and attraction of stations are forecasted. The experimental results show that the model of this paper performs higher forecasting accuracy and better generalization ability.
The Effects of Qigong on Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis
Authors: Meng Ding , Chunyan Wang , Xiaosheng Dong , Xiangren Yi
Published: January 2018

Objective. The purpose of this study was to investigate the effects of Qigong on type 2 diabetes mellitus (DM) using the systematic review and meta‐analysis. Methods. All prospective, randomized, controlled clinical trials published in English or Chinese and involving the use of Qigong by patients with DM were searched in 7 electronic databases from their respective inception to June 2016. The meta‐analysis was conducted using the Revman 5.2. The quality of the included trials was assessed using the Jadad rating scale. Two researchers independently completed the inclusion, data extraction, and quality assessment. Results. Twenty‐one trials with 1326 patients met the inclusion criteria and were reviewed. The meta‐analysis demonstrated that, compared with no exercise, the Qigong had significant effects on fasting blood glucose (MD = −0.99, 95% CI (−1.23, 0.75), P < 0.0001), HbA1c (MD = −0.84, 95% CI (−1.02, −0.65), P < 0.0001), and postprandial blood glucose (MD = −1.55, 95% CI (−2.19, −0.91), P < 0.00001). Conclusion. The Qigong training can improve the blood glucose status of the type 2 DM patients and has positive effects on the management of type 2 DM. However, future research with better quality still needs to be conducted to address the effects of Qigong on type 2 DM.
Methods Dealing with Complexity in Selecting Joint Venture Contractors for Large‐Scale Infrastructure Projects
Authors: Liang Ru , Sheng Zhaohan , Wang Xiangyu
Published: January 2018

The magnitude of business dynamics has increased rapidly due to increased complexity, uncertainty, and risk of large‐scale infrastructure projects. This fact made it increasingly tough to “go alone” into a contractor. As a consequence, joint venture contractors with diverse strengths and weaknesses cooperatively bid for bidding. Understanding project complexity and making decision on the optimal joint venture contractor is challenging. This paper is to study how to select joint venture contractors for undertaking large‐scale infrastructure projects based on a multiattribute mathematical model. Two different methods are developed to solve the problem. One is based on ideal points and the other one is based on balanced ideal advantages. Both of the two methods consider individual difference in expert judgment and contractor attributes. A case study of Hong Kong‐Zhuhai‐Macao‐Bridge (HZMB) project in China is used to demonstrate how to apply these two methods and their advantages.
Computational Analysis of Complex Population Dynamical Model with Arbitrary Order
Authors: Haq Fazal , Shah Kamal , Rahman Ghaus ur , Li Yongjin , Shahzad Muhammad
Published: January 2018

This paper considers the approximation of solution for a fractional order biological population model. The fractional derivative is considered in the Caputo sense. By using Laplace Adomian decomposition method (LADM), we construct a base function and provide deformation equation of higher order in a simple equation. The considered scheme gives us a solution in the form of rapidly convergent infinite series. Some examples are used to show the efficiency of the method. The results show that LADM is efficient and accurate for solving such types of nonlinear problems.
Targeting HER2 Aberrations in Non–Small Cell Lung Cancer with Osimertinib
Authors: Liu Shengwu , Li Shuai , Hai Josephine , Wang Xiaoen , Chen Ting , Quinn Max M. , Gao Peng , Zhang Yanxi , Ji Hongbin , Cross Darren A.E. , Wong Kwok-Kin
Published: January 2018

Purpose: HER2 (or ERBB2) aberrations, including both amplification and mutations, have been classified as oncogenic drivers that contribute to 2% to 6% of lung adenocarcinomas. HER2 amplification is also an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKI). However, due to limited preclinical studies and clinical trials, currently there is still no available standard of care for lung cancer patients with HER2 aberrations. To fulfill the clinical need for targeting HER2 in patients with non–small cell lung cancer (NSCLC), we performed a comprehensive preclinical study to evaluate the efficacy of a third-generation TKI, osimertinib (AZD9291).

Experimental Design: Three genetically modified mouse models (GEMM) mimicking individual HER2 alterations in NSCLC were generated, and osimertinib was tested for its efficacy against these HER2 aberrations in vivo.

Results: Osimertinib treatment showed robust efficacy in HER2wt overexpression and EGFR del19/HER2 models, but not in HER2 exon 20 insertion tumors. Interestingly, we further identified that combined treatment with osimertinib and the BET inhibitor JQ1 significantly increased the response rate in HER2-mutant NSCLC, whereas JQ1 single treatment did not show efficacy.

Conclusions: Overall, our data indicated robust antitumor efficacy of osimertinib against multiple HER2 aberrations in lung cancer, either as a single agent or in combination with JQ1. Our study provides a strong rationale for future clinical trials using osimertinib either alone or in combination with epigenetic drugs to target aberrant HER2 in patients with NSCLC. Clin Cancer Res; 24(11); 2594–604. ©2018 AACR.

See related commentary by Cappuzzo and Landi, p. 2470
Development and Validation of a Gene Signature for Patients with Head and Neck Carcinomas Treated by Postoperative Radio(chemo)therapy
Authors: Schmidt Stefan , Linge Annett , Zwanenburg Alex , Leger Stefan , Lohaus Fabian , Krenn Constanze , Appold Steffen , Gudziol Volker , Nowak Alexander , von Neubeck Cläre , Tinhofer Inge , Budach Volker , Sak Ali , Stuschke Martin , Balermpas Panagiotis , Rödel Claus , Bunea Hatice , Grosu Anca-Ligia , Abdollahi Amir , Debus Jürgen , Ganswindt Ute , Belka Claus , Pigorsch Steffi , Combs Stephanie E. , Mönnich David , Zips Daniel , Baretton Gustavo B. , Buchholz Frank , Baumann Michael , Krause Mechthild , Löck Steffen
Published: January 2018

Purpose: The aim of this study was to identify and independently validate a novel gene signature predicting locoregional tumor control (LRC) for treatment individualization of patients with locally advanced HPV-negative head and neck squamous cell carcinomas (HNSCC) who are treated with postoperative radio(chemo)therapy (PORT-C).

Experimental Design: Gene expression analyses were performed using NanoString technology on a multicenter training cohort of 130 patients and an independent validation cohort of 121 patients. The analyzed gene set was composed of genes with a previously reported association with radio(chemo)sensitivity or resistance to radio(chemo)therapy. Gene selection and model building were performed comparing several machine-learning algorithms.

Results: We identified a 7-gene signature consisting of the three individual genes HILPDA, CD24, TCF3, and one metagene combining the highly correlated genes SERPINE1, INHBA, P4HA2, and ACTN1. The 7-gene signature was used, in combination with clinical parameters, to fit a multivariable Cox model to the training data (concordance index, ci = 0.82), which was successfully validated (ci = 0.71). The signature showed improved performance compared with clinical parameters alone (ci = 0.66) and with a previously published model including hypoxia-associated genes and cancer stem cell markers (ci = 0.65). It was used to stratify patients into groups with low and high risk of recurrence, leading to significant differences in LRC in training and validation (P < 0.001).

Conclusions: We have identified and validated the first hypothesis-based gene signature for HPV-negative HNSCC treated by PORT-C including genes related to several radiobiological aspects. A prospective validation is planned in an ongoing prospective clinical trial before potential application in clinical trials for patient stratification. Clin Cancer Res; 24(6); 1364–74. ©2018 AACR.
Development and Preclinical Validation of a Cysteine Knottin Peptide Targeting Integrin αvβ6 for Near-infrared Fluorescent-guided Surgery in Pancreatic Cancer
Authors: Tummers Willemieke S. , Kimura Richard H. , Abou-Elkacem Lotfi , Beinat C. , Vahrmeijer Alexander L. , Swijnenburg Rutger-Jan , Willmann Juergen K. , Gambhir Sanjiv S.
Published: January 2018

Purpose: Intraoperative near-infrared fluorescence (NIRF) imaging could help stratification for the proper primary treatment for patients with pancreatic ductal adenocarcinoma (PDAC), and achieve complete resection, as it allows visualization of cancer in real time. Integrin αvβ6, a target specific for PDAC, is present in >90% of patients, and is able to differentiate between pancreatitis and PDAC. A clinically translatable αvβ6-targeting NIRF agent was developed, based on a previously developed cysteine knottin peptide for PET imaging, R01-MG, and validated in preclinical mouse models.

Experimental Design: The applicability of the agent was tested for cell and tissue binding characteristics using cell-based plate assays, subcutaneous, and orthotopic pancreatic models, and a transgenic mouse model of PDAC development (Pdx1-Cretg/+;KRasLSL G12D/+;Ink4a/Arf−/−). IRDye800CW was conjugated to R01-MG in a 1:1 ratio. R01-MG-IRDye800, was compared with a control peptide and IRDye800 alone.

Results: In subcutaneous tumor models, a significantly higher tumor-to-background ratio (TBR) was seen in BxPC-3 tumors (2.5 ± 0.1) compared with MiaPaCa-2 (1.2 ± 0.1; P < 0.001), and to the control peptide (1.6 ± 0.4; P < 0.005). In an orthotopic tumor model, tumor-specific uptake of R01-MG-IRDye800 was shown compared with IRDye800 alone (TBR 2.7 vs. 0.86). The fluorescent signal in tumors of transgenic mice was significantly higher, TBR of 3.6 ± 0.94, compared with the normal pancreas of wild-type controls, TBR of 1.0 ± 0.17 (P < 0.001).

Conclusions: R01-MG-IRDye800 shows specific targeting to αvβ6, and holds promise as a diagnostic and therapeutic tool to recognize PDAC for fluorescence-guided surgery. This agent can help improve the stratification of patients for a potentially curative, margin-negative resection. Clin Cancer Res; 24(7); 1667–76. ©2018 AACR.
Isolated Nail Pigmentation Associated with Chikungunya: A Hitherto Unreported Manifestation
Authors: Singal Archana , Pandhi Deepika
Published: January 2018

Chikungunya (CHK) fever is a re-emerging RNA viral infection caused by the bite of infected Aedes mosquitoes which presents with a multitude of mucocutaneous manifestations, including a characteristic morbilliform rash, centrofacial pigmentation, aphthae-like lesions, and vesiculobullous lesions sparing mucosae. The majority of these lesions resolve spontaneously and do not require specific therapy. With regular and cyclical outbreaks in many countries for many decades, it is obligatory for dermatologists to be aware of the different skin lesions in the wake of early diagnosis and the need for conservative management. We report 2 cases from India developing isolated melanonychia with CHK fever.
The International Regime for Treating Civil War, 1988–2017
Authors: Gowan Richard , Stedman Stephen John
Published: January 2018

The post–Cold War international order has promoted a “standard treatment” for civil wars involving the use of mediation to end conflicts and the deployment of peacekeeping forces to implement the resulting settlements. The United Nations has played a leading role in applying this standard treatment, which enjoys broad international support. By contrast, Western efforts to promote more robust humanitarian intervention as a standard response to civil wars remains controversial. While effective in relatively permissive postconflict environments, international mediation and peacekeeping efforts have proved insufficient to resolve harder cases of civil war, such as those in South Sudan and Syria. The UN has struggled to make the standard treatment work where governments refuse to cooperate or low-level violence is endemic. Growing major-power tensions could now undermine the post–Cold War regime for the treatment of civil wars, which, for all its faults, has made a significant contribution to international order.
Responsibility Beyond the Grave: Technological Mediation of Collective Moral Agency in Online Commemorative Environments
Authors: Matei Ştefania
Published: January 2018

Online platforms of donations in memoriam are technologies of commemoration that mediate a responsible mode of being in the world. They construct death as empowering for the deceased, and they open up new opportunities for collaborative action to emerge. By relying on existing conceptualizations of post-mortem personhood and technologically mediated agency, this article considers the socio-technical construction of the commemorative platform, MuchLoved, an online tribute charity; it focuses on its interaction design for online donations in memoriam. Through specific design options, MuchLoved stirs a distinctive form of distributed agency with a collective and moral character. This accomplishment of collective moral agency through technological mediations might redefine the space of symbolic immortality and change the human condition in relation with death.
Political Correction
Authors: Kochenash Michael
Published: January 2018

In Acts 9:36-43, Tabitha’s name is both transliterated from Aramaic (Tabitha) and translated into Greek (Dorcas). Because both names mean “deer” and this episode follows Peter’s healing of Aeneas, Tabitha’s name can be read as an allusion to Virgil’s Dido, juxtaposing the expansion of the kingdom of God with that of Rome. Virgil’s Aeneid characterizes Dido as a deer and Aeneas as her hunter. Luke initiates the expansion of the kingdom of God by emphasizing its compassion for marginalized individuals (in contrast to Roman disregard). Whereas Rome leaves women dead in the wake of its progression, the agents of the kingdom of God bring women back to life.
The Persuasive Arguments at Play in Heb 2:11 and 7:12
Authors: Doran Robert
Published: January 2018

The phrase ‘from one’ in Heb 2:11 does not refer to some common ancestor or creator, but is the commonplace that common predication connects those so predicated. At Heb 7:12, the author draws upon the accepted connection in the Mediterranean world between form of government and worldview/religion—to change one is to change the other—and so the argument is rhetorically persuasive.
The Muratorian Fragment as Roman Fake
Authors: Rothschild Clare K.
Published: January 2018

Today scholarship has reached an impasse as to the origin of the well-known fragment published by L. A. Muratori. Approximately half accepts a second-century Roman provenance based on views held by, for example, Adolf von Harnack and Samuel Tregelles. The other half, following Albert C. Sundberg Jr., accepts a fourth-century Eastern provenance. This paper argues that the Fragment represents an attempt to provide a venerable second-century precedent for a later position on canon. The present essay restricts itself to three aspects of the debate: (1) initial discovery; (2) Fraternity Legend and Catalogue of Heresies; and, (3) historical settings in which such a text might have emerged.
Technology Use in the Religious Communities in Israel: Combining Traditional Society and Advanced Communications
Authors: Katz Yaron
Published: January 2018

The technological development of the electronic media and the changes in their role create a process of transition to using alternative modes of communication, which combine mass media and inter-personal communication. These means are alternative to traditional media; they serve segments of the population which do not receive a suitable expression in the institutionalized media, and provide them with information and advertisement which bypass the limitations imposed on the media. The largest alternative activity taking place in Israel is targeted to the orthodox and Haredi (ultra-orthodox) population, mainly through advanced technological means, such as the internet and satellite transmissions. This study explores the ideological dilemma of using advanced communications technology by the religious public, while trying to avoid its cultural hazards and still using it effectively. It examines the characteristics of technology consumption and the use of new media among the religious target group in Israel.
Imaging Sacred Artifacts: Ethics and the Digitizing of Lichfield Cathedral's St Chad Gospels
Authors: Endres Bill
Published: January 2018

This essay examines complexities that attend digitizing a cultural heritage artifact that is sacred to a contemporary community. It argues that scholars must first determine how the artifact participates in the life of its community. If this participation is integral, scholars should treat the artifact as a present-day cultural phenomenon, inseparable from its community. To explain the implications of this shift, the author turns to ethnography, which has a lengthy tradition of interacting with communities for generating research. Photographing a sacred artifact is not unlike other ethnographic research, whether tape recording stories, collecting documents, or gathering information about social practices. To guide digital work, the essay proposes ethnographic ethical principles, demonstrating their value in digitizing the 8th-century St Chad Gospels at Lichfield Cathedral, England—supporting Jamie Bianco's recent call for an "ethical turn" in the digital humanities.
This Show Was Religious?!: Online Reactions to Religion in Lost and Battlestar Galactica Finales
Authors: Howell Charlotte
Published: January 2018

As the American populace is increasingly identifying as non-religious, religious representation is surprisingly also increasing on television, leading many to discuss the limits and boundaries of acceptable representations of religion through the cultural forum of television. The series finales of Lost and Battlestar Galactica serve as a particular pair of case studies I place in discussion with each other about religious-representational and generic concerns. Online reactions in discussion forums or comment sections to the religious elements in these finales generally occur in one of two ways: negative reactions that set the religious endings in opposition to the genre expectations viewers had for the shows or generally positive reactions that focus on the religious themes as successful affective tools that provided adequate or at least justified narrative closure. In both discursive strains, the tone was overwhelmingly respectful and occasionally aware that those entering into the discussions were engaging in larger cultural debates, providing one site of exploring the changing role of religion in popular television through a study of expectations of science fiction narratives and their conclusions.
“@God please open your fridge!” Twitter messages to @God in content analysis: Hopes, humor, spirituality, and profanities
Authors: Holmberg Kim , Bastubacka Johan , Thelwall Mike
Published: January 2018

This study investigates religious communication in social media by analyzing messages sent to God on Twitter. More specifically, the goal of this research is to map and analyze the various contexts in which God is addressed on Twitter, and how the tweets may reflect religious beliefs, ritual functions, and life issues. Using content analysis techniques and phenomenography, tweets addressing God were investigated. The results of this descriptive and indicative study show that religion and religiosity are communicated on Twitter in a manner that creates a unique sphere in which praise and profanities coexist. The tweets in the sample vary a great deal in their content and communicative function, ranging from profanities to prayers and from requests to win the lottery to conversations with and comments about God. Some tweets address God as a form of humour or satire, cursing, or otherwise without any deeper religious intention, while other tweets are apparently genuine messages directed to the transcendent, prayers, with which the senders want to show and share their belief with their followers on Twitter.
High-Dose Cytarabine (HIDAC) plus Daunorubicin for Remission Induction of Acute Myelogenous Leukemia
Authors: Waddell J. Aubrey , Doulaveris Paula , Solimando Dominic A.
Published: January 2018

The increasing complexity of cancer chemotherapy makes it mandatory that pharmacists be familiar with these highly toxic agents. This column focuses on the commercially available and investigational agents used to treat malignant diseases, reviewing issues related to the preparation, dispensing, and administration of cancer chemotherapy.
The Training Process (Part 1)
Authors: Miller Alicia S.
Published: January 2018

This continuing feature will inform readers about the process of implementing, maintaining, and supporting computerized prescriber order entry (CPOE) at the Ohio State University Medical Center. (By “prescribers,” we refer to health care professionals authorized to prescribe medications by their states.) Practical information on what worked and what failed will be provided, along with current updates on the status of CPOE at the Medical Center.
A Descriptive Report of Bleeding Complications Secondary to Warfarin Therapy
Authors: Bernard Daphne , Dutta Arjun P. , Daftary Monika N.
Published: January 2018

Purpose

This study identified factors that contributed to bleeding complications associated with warfarin therapy that were documented as adverse drug reactions (ADRs).

Methods

A retrospective chart review was performed using the Medical Records Department's “E” code list of anticoagulant-related ADRs. Descriptive statistics were used to identify common factors associated with bleeding complications related to warfarin use.

Results

Patients 60 years of age or older experienced 78% of all events; a majority (81%) of reports involved the presence of comorbid conditions such as congestive heart failure, carcinoma, or sepsis. A supratherapeutic INR was documented for 75% of patients with anticoagulant-related ADRS.

Conclusions

Age, comorbid conditions, and anticoagulation intensity were identified as possible factors contributing to documented ADRs associated with warfarin therapy.
Adefovir Dipivoxil
Authors: Cada Dennis J. , Levien Terri , Baker Danial E.
Published: January 2018

Each month, subscribers to The Formulary Monograph Service receive five to six well-documented monographs on drugs that are newly released or are in late Phase III trials. The monographs are targeted to your Pharmacy and Therapeutics Committee. Subscribers also receive monthly one-page summary monographs on the agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation (DUE) is also provided each month. The monographs are published in printed form and on diskettes that allow customization. Subscribers to the The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X.

Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. If you would like information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800–322–4349. The January 2003 monograph topics are ezetimibe, enfurvitide, aripiprazole, atomoxetine, and amoxicillin/clavulanate potassium extended-release tablets. The DUE is on ezetimibe.