bluuebunny/crossref_metadata_2025 huggingface dataset:
Adsorption Properties of Typical Lung Cancer Breath Gases on Ni-SWCNTs through Density Functional Theory
Authors: Wan Qianqian , Xu Yancheng , Zhang Xiaoxing
Published: September 2017

A lot of useful information is contained in the human breath gases, which makes it an effective way to diagnose diseases by detecting the typical breath gases. This work investigated the adsorption of typical lung cancer breath gases: benzene, styrene, isoprene, and 1-hexene onto the surface of intrinsic and Ni-doped single wall carbon nanotubes through density functional theory. Calculation results show that the typical lung cancer breath gases adsorb on intrinsic single wall carbon nanotubes surface by weak physisorption. Besides, the density of states changes little before and after typical lung cancer breath gases adsorption. Compared with single wall carbon nanotubes adsorption, single Ni atom doping significantly improves its adsorption properties to typical lung cancer breath gases by decreasing adsorption distance and increasing adsorption energy and charge transfer. The density of states presents different degrees of variation during the typical lung cancer breath gases adsorption, resulting in the specific change of conductivity of gas sensing material. Based on the different adsorption properties of Ni-SWCNTs to typical lung cancer breath gases, it provides an effective way to build a portable noninvasive portable device used to evaluate and diagnose lung cancer at early stage in time.
Imaging, Histopathologic, and Treatment Nuances of Pulmonary Carcinosarcoma
Authors: Gleason Tyler , Haas Michael , Le Brian H.
Published: September 2017

A 76-year-old female with coronary artery disease, chronic obstructive pulmonary disease, diabetes mellitus type II, and 40 pack-year smoking history presented with a four-day history of cough, productive of green-yellow sputum. Chest X-ray revealed opacification of the left upper lung field, and computed tomography (CT) of the chest showed a large cavitary lesion invading the T2-T3 vertebral bodies, extending into the epidural space, giving rise to mild cord compression. Biopsy of the lesion revealed a poorly differentiated neoplasm composed of distinct epithelial and mesenchymal components, consistent with carcinosarcoma. A metastatic workup was negative. Primary lung carcinosarcoma is a rare tumour that can demonstrate an especially aggressive clinical course; diagnosis is often nuanced by limited sampling at initial presentation, especially in a setting of advanced disease and debility that precludes consideration for upfront resection or more extensive, invasive sampling.
Pulpo-Periodontal Regeneration: Management of Partial Failure Revascularization
Authors: Dhaimy Said , Dhoum Sara , Amarir Hind , El Merini Hafsa , Nadifi Sellama , Ouazzani Amal El
Published: September 2017

The aim of this work is to present a case of management of an open apex on a lower molar by using tissue engineering, with two endodontic procedures in the same tooth. We had to resort to pulp regeneration on the distal root and apexification with MTA on the mesial roots after the failure of regenerative therapy on those ones. The management consisted in scheduling regular follow-ups combined with X-rays. After 24 months, the radiological control has shown pulpo-periodontal regeneration associated with walls thickening and distal root elongation and periapical ad integrum healing.
On Consistency of Cross-Approximate Entropy in Cardiovascular and Artificial Environments
Authors: Skoric Tamara , Sarenac Olivera , Milovanovic Branislav , Japundzic-Zigon Nina , Bajic Dragana
Published: September 2017

Cross-approximate entropy(XApEn)quantifies the mutual orderliness of simultaneously recorded time series. Despite being derived from the firmly established solitary entropies, it has never reached their reputation and deployment. The aim of this study is to identify the problems that preclude widerXApEnimplementation and to develop a set of solutions. Exact expressions forXApEnand its constitutive parts are derived and compared to values estimated from artificial data. This comparison revealed vast regions within the parameter space that do not guarantee reliable probability estimation, makingXApEnestimates inconsistent. A simple correction to one of theXApEnprocedural steps is proposed. Three sets of formulae for joint parameter selection are derived. The first one is intended to maximize threshold profile. The remaining ones minimizeXApEninstability according to the strong and weak criteria. The derived expressions are verified using cardiovascular signals recorded from rats (long signals) and healthy volunteers (short clinical signals), proposing a change of traditional parameter guidelines.
Solving Boundary Value Problem for a Nonlinear Stationary Controllable System with Synthesizing Control
Authors: Kvitko Alexander N. , Firyulina Oksana S. , Eremin Alexey S.
Published: September 2017

An algorithm for constructing a control function that transfers a wide class of stationary nonlinear systems of ordinary differential equations from an initial state to a final state under certain control restrictions is proposed. The algorithm is designed to be convenient for numerical implementation. A constructive criterion of the desired transfer possibility is presented. The problem of an interorbital flight is considered as a test example and it is simulated numerically with the presented method.
Increased Melting Heat Transfer in the Latent Heat Energy Storage from the Tube-and-Shell Model to the Combine-and-Shell Model
Authors: Korawan Agus Dwi , Soeparman Sudjito , Wijayanti Widya , Widhiyanuriyawan Denny
Published: September 2017

The melting of paraffin in thermal storage tube-and-shell and combine-and-shell models was conducted with the numerical research aim of decreasing the charge time through changing the shape of the tube into combining form. The results discussed are temperature contour, liquid-solid interface contour, temperature distribution, liquid fraction, and the average Nusselt number. The results show that the charge time in the tube-and-shell model is 2000 s, while the combine-and-shell model is 1200 s, meaning an overall decrease in charge time in the combine-and-shell model by 40% when compared to that of the tube-and-shell model.
Global Measurement Method for Large-Scale Components Based on a Multiple Field of View Combination
Authors: Zhang Yang , Liu Wei , Lan Zhiguang , Zhang Zhiyuan , Ye Fan , Zhao Haiyang , Li Xiaodong , Jia Zhenyuan
Published: September 2017

Considering the limited measurement range of a machine vision method for the three-dimensional (3D) surface measurement of large-scale components, a noncontact and flexible global measurement method combining a multiple field of view (FOV) is proposed in this paper. The measurement system consists of two theodolites and a binocular vision system with a transfer mark. The process of multiple FOV combinations is described, and a new global calibration method is proposed to solve the coordinate system unification issue of different instruments in the measurement system. In addition, a high-precision image acquisition method, which is based on laser stripe scanning and centre line extraction, is discussed to guarantee the measurement efficiency. With the measured 3D data, surface reconstruction of large-scale components is accomplished by data integration. Experiments are also conducted to verify the precision and effectiveness of the global measurement method.
Validation of a Machine Learning Approach for Venous Thromboembolism Risk Prediction in Oncology
Authors: Ferroni Patrizia , Zanzotto Fabio M. , Scarpato Noemi , Riondino Silvia , Guadagni Fiorella , Roselli Mario
Published: September 2017

Using kernel machine learning (ML) and random optimization (RO) techniques, we recently developed a set of venous thromboembolism (VTE) risk predictors, which could be useful to devise a web interface for VTE risk stratification in chemotherapy-treated cancer patients. This study was designed to validate a model incorporating the two best predictors and to compare their combined performance with that of the currently recommended Khorana score (KS). Age, sex, tumor site/stage, hematological attributes, blood lipids, glycemic indexes, liver and kidney function, BMI, performance status, and supportive and anticancer drugs of 608 cancer outpatients were all entered in the model, with numerical attributes analyzed as continuous values. VTE rate was 7.1%. The VTE risk prediction performance of the combined model resulted in 2.30 positive likelihood ratio (+LR), 0.46 negative LR (−LR), and 4.88 HR (95% CI: 2.54–9.37), with a significant improvement over the KS [HR 1.73 (95% CI: 0.47–6.37)]. These results confirm that a ML approach might be of clinical value for VTE risk stratification in chemotherapy-treated cancer outpatients and suggest that the ML-RO model proposed could be useful to design a web service able to provide physicians with a graphical interface helping in the critical phase of decision making.
Successful Treatment of Klebsiella pneumoniae Harboring a Klebsiella pneumoniae Carbapenemase Isolated from Lumbar Wound Infection and Blood in a Patient with Hardware Retention
Authors: Bulbin Alan , Bono Carol , Philp Tena , Mariano Noriel , Urban Carl
Published: September 2017

Infections caused by carbapenem-resistant Enterobacteriaceae, especially carbapenemase producing Klebsiella pneumoniae, represent an urgent threat as outlined by the Centers for Disease Control and Prevention (CDC). We present a 66-year-old male with spinal stenosis who underwent elective L2-pelvis posterior spinal fusion at an outside institution and rapidly developed a complicated infection with Klebsiella pneumoniae harboring Klebsiella pneumoniae carbapenemase. This is the first described case of a patient with Klebsiella pneumoniae harboring Klebsiella pneumoniae carbapenemase causing postoperative lumbar wound infection and bacteremia, successfully treated with ceftazidime-avibactam in combination with additional synergistic antibacterials and without hardware removal.
Functional Nanohybrid Materials from Photosynthetic Reaction Center Proteins
Authors: Hajdu Kata , Szabó Tibor , Sarrai Abd Elaziz , Rinyu László , Nagy László
Published: September 2017

Application of technical developments in biology and vice versa or biological samples in technology led to the development of new types of functional, so-called “biohybrid” materials. These types of materials can be created at any level of the biological organization from molecules through tissues and organs to the individuals. Macromolecules and/or molecular complexes, membranes in biology, are inherently good representatives of nanosystems since they fall in the range usually called “nano.” Nanohybrid materials provide the possibility to create functional bionanohybrid complexes which also led to new discipline called “nanobionics” in the literature and are considered as materials for the future. In this publication, the special characteristics of photosynthetic reaction center proteins, which are “nature’s solar batteries,” will be discussed in terms of their possible applications for creating functional molecular biohybrid materials.
Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness
Authors: Zou Zhilu , Chen Yin , Shen Qinqin , Guo Xiaoyan , Zhang Yuxuan , Chen Gang
Published: September 2017

Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.
A Systematic Review on Recent Advances in mHealth Systems: Deployment Architecture for Emergency Response
Authors: Gonzalez Enrique , Peña Raul , Avila Alfonso , Vargas-Rosales Cesar , Munoz-Rodriguez David
Published: September 2017

The continuous technological advances in favor of mHealth represent a key factor in the improvement of medical emergency services. This systematic review presents the identification, study, and classification of the most up-to-date approaches surrounding the deployment of architectures for mHealth. Our review includes 25 articles obtained from databases such as IEEE Xplore, Scopus, SpringerLink, ScienceDirect, and SAGE. This review focused on studies addressing mHealth systems for outdoor emergency situations. In 60% of the articles, the deployment architecture relied in the connective infrastructure associated with emergent technologies such as cloud services, distributed services, Internet-of-things, machine-to-machine, vehicular ad hoc network, and service-oriented architecture. In 40% of the literature review, the deployment architecture for mHealth considered traditional connective infrastructure. Only 20% of the studies implemented an energy consumption protocol to extend system lifetime. We concluded that there is a need for more integrated solutions specifically for outdoor scenarios. Energy consumption protocols are needed to be implemented and evaluated. Emergent connective technologies are redefining the information management and overcome traditional technologies.
HbS-Sicilian (δβ)0-Thalassemia: A Rare Variant of Sickle Cell
Authors: Onimoe Grace , Smarzo Genine
Published: September 2017

Sickle cell disease (SCD) is caused by a mutation in the sixth codon of the β-globin gene on chromosome 11, which leads to a single amino acid substitution (glutamine to valine). Sickle-(δβ)0-thalassemia is a rare variant of sickle cell disease (delta-beta thalassemia occurring in association with sickle hemoglobin, HbS), sparsely reported in literature, and has been associated with symptomatology necessitating careful monitoring and follow-up. We describe a patient who presented with a newborn screen reported as “FS” and a negative family history for sickle cell disease and sickle cell trait. Subsequent gene sequencing studies demonstrated the presence of Sickle-(δβ)0-thalassemia. Clinical course has remained relatively stable for this patient now at 18 months of age without any SCD related symptomatology or complications. As this is a rare variant of SCD with potential complications, it is important to establish diagnosis towards planning comprehensive care.
Formation Tracking of Heterogeneous Mobile Agents Using Distance and Area Constraints
Authors: Hernandez-Martinez E. G. , Ferreira-Vazquez E. D. , Fernandez-Anaya G. , Flores-Godoy J. J.
Published: September 2017

This paper presents two formation tracking control strategies for a combined set of single and double integrator agents with an arbitrary undirected communication topology. The first approach is based on the design of distance-based potential functions with interagent collision avoidance using local information about the distance and orientation between agents and the desired trajectory. The second approach adds signed area constraints to the desired formation specification and a control strategy that uses distance as well as area terms is designed to achieve tracking convergence. Numerical simulations show the performance from both control laws.
Exercise-Induced Acute Bilateral Upper-Arm Compartment Syndrome
Authors: Traub Brian C. , Lane Mark K. , Traub Jeff A.
Published: September 2017

We present a rare case of acute exercise-induced bilateral upper-arm compartment syndrome in a patient who, after a year-long hiatus from exercise, subjected his upper-extremities to the stress of over 100 pushups. The patient presented with severe pain of the bilateral biceps and triceps and complaints of dark urine. Decompressive fasciotomy was performed followed by an intensive care unit (ICU) stay for associated myoglobinuria secondary to rhabdomyolysis. The patient suffered no long-term sequelae as a result of his conditions and recovered full function of the bilateral upper-extremities. Albeit rare, acute exercise-induced compartment syndrome should be considered as a diagnosis following unaccustomed bouts of exercise.
Developing an Optimization Model to Manage Unpaved Roads
Authors: Saha Promothes , Ksaibati Khaled
Published: September 2017

While approximately two-thirds of the total centerline miles are unpaved in the state of Wyoming, there is no optimization program for managing these roads. Unlike paved roads, unpaved roads deteriorate from excellent to failed conditions in sometimes less than a year. This deterioration rate necessitates developing a novel methodology for managing them efficiently. When funding is limited, it is important to identify the best mix of road preservation projects that provides the most benefits to society in terms of overall life cycle cost of the road network. This research intends to develop a management system using optimization techniques for managing unpaved roads within limited budget. The common factors that play the most important role for identifying projects are road condition parameters, unpaved road deterioration model, treatment types, cost-factors associated with selecting treatment types, traffic counts, budget, and treatment cost. Road condition parameters include cross section, roadside drainage, rutting, potholes, loose aggregate, dust, corrugation, and ride quality. This methodology will facilitate a statewide implementation of unpaved road management system for counties in Wyoming. The methodology can be easily adopted by other states interested in the management of gravel roads.
A Method for Stability Analysis of Periodic Delay Differential Equations with Multiple Time‐Periodic Delays
Authors: Jin Gang , Qi Houjun , Li Zhanjie , Han Jianxin , Li Hua
Published: September 2017

Delay differential equations (DDEs) are widely utilized as the mathematical models in engineering fields. In this paper, a method is proposed to analyze the stability characteristics of periodic DDEs with multiple time‐periodic delays. Stability charts are produced for two typical examples of time‐periodic DDEs about milling chatter, including the variable‐spindle speed milling system with one‐time‐periodic delay and variable pitch cutter milling system with multiple delays. The simulations show that the results gained by the proposed method are in close agreement with those existing in the past literature. This indicates the effectiveness of our method in terms of time‐periodic DDEs with multiple time‐periodic delays. Moreover, for milling processes, the proposed method further provides a generalized algorithm, which possesses a good capability to predict the stability lobes for milling operations with variable pitch cutter or variable‐spindle speed.
Cardiovascular Protective Effects of Salvianic Acid A on db/db Mice with Elevated Homocysteine Level
Authors: Gao Lei , Siu Parco M. , Chan Shun-wan , Lai Christopher W. K.
Published: September 2017

The onsets of left ventricular hypertrophy (LVH) and endothelial dysfunction (ED) in diabetics, especially in those with elevated homocysteine (Hcy), precede the development of cardiovascular (CV) events. Salvianic acid A (SAA) is a renowned Traditional Chinese Medicine (TCM) that has been applied in the treatment of cardiovascular disease for many decades. In this study, we aimed (1) to investigate the CV protective effects of SAA on ameliorating LVH and ED in db/db mice with elevated blood Hcy level and (2) to decipher whether the observed CV protective effects of SAA are associated with Hcy metabolism by modulating the methylation potential and redox status in the liver of the db/db mice with elevated blood Hcy level. Our results found that the administration of SAA could significantly slow down the build‐up of left ventricular mass and ameliorate ED. Immunological assay analysis on the mouse liver tissue also indicated that SAA treatment on db/db mice with elevated Hcy was associated with reduced methylation potential but improved redox status. In conclusion, we revealed that SAA has the potential to protect against the hyperglycemia‐ and hyperhomocysteinemia‐induced oxidative stress on diabetic mice via modulation in Hcy metabolism.
Amyand’s Hernia, State of the Art and New Points of View
Authors: Mantovani Guido , De Angelis Michela , Di Lecce Francesco , Pascariello Annalisa , Risio Domenico , Boccia Luigi
Published: September 2017

Background. Amyand’s hernia (AH) is an inguinal hernia containing the vermiform appendix, with an incidence between 0.4% and 1% of all inguinal hernias. Acute or perforated appendicitis can complicate AH.Case Presentation. A 75-year-old Caucasian man presented with incarceration of vermiform appendix in inguinal hernia sac. Diagnosis was posed preoperatively with computed tomography (CT) scan. Patient underwent urgent surgery and simultaneous appendectomy and hernia repair by Bassini’s technique were performed.Conclusions. Preoperative diagnosis of AH is rare; however it could be useful for surgeon to choose operative approach. Treatment of AH depends on grade of appendix inflammation and/or perforation. The technique utilized to repair hernia depends largely on surgeon’s preferences; the presence of inflamed or perforated appendix is not an absolute contraindication for using a prosthetic mesh.
Ventilation Series Similarity: A Study for Ventilation Calculation Using Deformable Image Registration and 4DCT to Avoid Motion Artifacts
Authors: Zhang Geoffrey G. , Latifi Kujtim , Feygelman Vladimir , Chou Kuei-Ting , Huang Tzung-Chi , Dilling Thomas J. , Perez Bradford A. , Moros Eduardo G.
Published: September 2017

The major problem with ventilation distribution calculations using DIR and 4DCT is the motion artifacts in 4DCT. Quite often not all phases would exhibit mushroom motion artifacts. If the ventilation series similarity is sufficiently robust, the ventilation distribution can be calculated using only the artifact-free phases. This study investigated the ventilation similarity among the data derived from different respiration phases. Fifteen lung cancer cases were analyzed. In each case, DIR was performed between the end-expiration phase and all other phases. Ventilation distributions were then calculated using the deformation matrices. The similarity was compared between the series ventilation distributions. The correlation between the majority phases was reasonably good, with average SCC values between 0.28 and 0.70 for the original data and 0.30 and 0.75 after smoothing. The better correlation between the neighboring phases, with average SCC values between 0.55 and 0.70 for the original data, revealed the nonlinear property of the dynamic ventilation. DSC analysis showed the same trend. To reduce the errors if motion artifacts are present, the phases without serious mushroom artifacts may be used. To minimize the effect of the nonlinearity in dynamic ventilation, the calculation phase should be chosen as close to the end-inspiration as possible.
Fault-Aware Resource Allocation for Heterogeneous Data Sources with Multipath Routing
Authors: Zhang Xiaomei , Chen Qiang , Shi Zhicai , Liang Jianru
Published: September 2017

With the rapid development of cloud computing and big data, diverse types of traffic generated from heterogeneous data sources are delivered throughout communication networks, which consist of various node kinds such as digital sensors and smart actuators, and different applications. Due to the shared medium, communication networks are vulnerable to misbehaving nodes, and it is a crucial aspect to maintain an acceptable level of service degradation. This paper studies the fault-aware resource allocation problem by exploiting multipath routing and dynamic rate assignment for heterogeneous sources. We estimate the impacts of faults and formulate the resource allocation as a lossy network flow optimization problem based on these estimates. The traditional flow optimization solutions focus on homogeneous traffic. In our work, we model the performance of heterogeneous applications as a relaxed utility function and develop an effective utility framework of rate control for heterogeneous sources with multipath routing in presence of misbehaving nodes. We design a distributed algorithm to decide the routing strategy and obtain the rate assignments on the available paths in a lossy utility fair manner. Extensive performance evaluations corroborate the significant performance of our algorithm in effective utility and utility fairness in the presence of misbehaving nodes.
Biomarker MicroRNAs for Diagnosis of Oral Squamous Cell Carcinoma Identified Based on Gene Expression Data and MicroRNA-mRNA Network Analysis
Authors: Zhang Hui , Li Tangxin , Zheng Linqing , Huang Xiangya
Published: September 2017

Oral squamous cell carcinoma is one of the most malignant tumors with high mortality rate worldwide. Biomarker discovery is critical for early diagnosis and precision treatment of this disease. MicroRNAs are small noncoding RNA molecules which often regulate essential biological processes and are good candidates for biomarkers. By integrative analysis of both the cancer-associated gene expression data and microRNA-mRNA network, miR-148b-3p, miR-629-3p, miR-27a-3p, and miR-142-3p were screened as novel diagnostic biomarkers for oral squamous cell carcinoma based on their unique regulatory abilities in the network structure of the conditional microRNA-mRNA network and their important functions. These findings were confirmed by literature verification and functional enrichment analysis. Future experimental validation is expected for the further investigation of their molecular mechanisms.
ImmunoPET of Malignant and Normal B Cells with 89Zr- and 124I-Labeled Obinutuzumab Antibody Fragments Reveals Differential CD20 Internalization In Vivo
Authors: Zettlitz Kirstin A. , Tavaré Richard , Knowles Scott M. , Steward Kristopher K. , Timmerman John M. , Wu Anna M.
Published: September 2017

Purpose: The B-cell antigen CD20 provides a target for antibody-based positron emission tomography (immunoPET). We engineered antibody fragments targeting human CD20 and studied their potential as immunoPET tracers in transgenic mice (huCD20TM) and in a murine lymphoma model expressing human CD20.

Experimental Design: Anti-CD20 cys-diabody (cDb) and cys-minibody (cMb) based on rituximab and obinutuzumab (GA101) were radioiodinated and used for immunoPET imaging of a murine lymphoma model. Pairwise comparison of obinutuzumab-based antibody fragments labeled with residualizing (89Zr) versus non-residualizing (124I) radionuclides by region of interest analysis of serial PET images was conducted both in the murine lymphoma model and in huCD20TM to assess antigen modulation in vivo.

Results: 124I-GAcDb and 124I-GAcMb produced high-contrast immunoPET images of B-cell lymphoma and outperformed the respective rituximab-based tracers. ImmunoPET imaging of huCD20TM showed specific uptake in lymphoid tissues. The use of the radiometal 89Zr as alternative label for GAcDb and GAcMb yielded greater target-specific uptake and retention compared with 124I-labeled tracers. Pairwise comparison of 89Zr- and 124I-labeled GAcDb and GAcMb allowed assessment of in vivo internalization of CD20/antibody complexes and revealed that CD20 internalization differs between malignant and endogenous B cells.

Conclusions: These obinutuzumab-based PET tracers have the ability to noninvasively and quantitatively monitor CD20-expression and have revealed insights into CD20 internalization upon antibody binding in vivo. Because they are based on a humanized mAb they have the potential for direct clinical translation and could improve patient selection for targeted therapy, dosimetry prior to radioimmunotherapy, and prediction of response to therapy. Clin Cancer Res; 23(23); 7242–52. ©2017 AACR.
Therapeutic Drug Monitoring of Carboplatin in High-Dose Protocol (TI-CE) for Advanced Germ Cell Tumors: Pharmacokinetic Results of a Phase II Multicenter Study
Authors: Moeung Sotheara , Chevreau Christine , Broutin Sophie , Guitton Jérôme , Lelièvre Bénédicte , Ciccolini Joseph , Massart Christophe , Fléchon Aude , Delva Rémy , Gravis Gwenaëlle , Lotz Jean-Pierre , Bay Jacques-Olivier , Gross-Goupil Marine , Paci Angelo , Marsili Sabrina , Malard Laurence , Chatelut Etienne , Thomas Fabienne
Published: September 2017

Purpose: We aimed to evaluate the performance of therapeutic drug monitoring (TDM) approach in controlling interpatient variability of carboplatin exposure (AUC) in patients treated with TI-CE high-dose chemotherapy for advanced germ cell tumors and to assess the possibility of using a formula-based dosing method as a possible alternative.

Experimental Design: Eighty-nine patients receiving carboplatin for 3 consecutive days during 3 cycles were evaluable for pharmacokinetic study. Blood samples were taken on day 1 to determine the carboplatin clearance using a Bayesian approach (NONMEM 7.2) and to adjust the dose on day 3 to reach the target AUC of 24 mg.min/mL over 3 days. On days 2 and 3, samples were taken for retrospective assessment of the actual AUC. A population pharmacokinetic analysis was also performed on 58 patients using NONMEM to develop a covariate equation for carboplatin clearance prediction adapted for future TI-CE patients, and its performance was prospectively evaluated on the other 29 patients along with different methods of carboplatin clearance prediction.

Results: The mean actual AUC was 24.4 mg.min/mL per cycle (22.4 and 26.8 for 10th and 90th percentiles, respectively). The new covariate equation [CL (mL/min) = 130.7 × (Scr/83)−0.826 × (BW/76)+0.907 × (Age/36)−0.223 with Scr in μmol/L, BW in kilograms, age in years] allows unbiased and more accurate prediction of carboplatin clearance compared with other equations.

Conclusions: TDM allows controlling and reaching the target AUC. Alternatively, the new equation of carboplatin clearance prediction, better adapted to these young male patients, could be used if TDM cannot be implemented. Clin Cancer Res; 23(23); 7171–9. ©2017 AACR.
VEGF and IGF Delivered from Alginate Hydrogels Promote Stable Perfusion Recovery in Ischemic Hind Limbs of Aged Mice and Young Rabbits
Authors: Anderson Erin M. , Silva Eduardo A. , Hao Yibai , Martinick Kathleen D. , Vermillion Sarah A. , Stafford Alexander G. , Doherty Elisabeth G. , Wang Lin , Doherty Edward J. , Grossman Paul M. , Mooney David J.
Published: September 2017

Biomaterial-based delivery of angiogenic growth factors restores perfusion more effectively than bolus delivery methods in rodent models of peripheral vascular disease, but the same success has not yet been demonstrated in clinically relevant studies of aged or large animals. These studies explore, in clinically relevant models, a therapeutic angiogenesis strategy for the treatment of peripheral vascular disease that overcomes the challenges encountered in previous clinical trials. Alginate hydrogels providing sustained release of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF) were injected into ischemic hind limbs in middle-aged and old mice, and also in young rabbits, as a test of the scalability of this local growth factor treatment. Spontaneous perfusion recovery diminished with increasing age, and only the combination of VEGF and IGF delivery from gels significantly rescued perfusion in middle-aged (13 months) and old (20 months) mice. In rabbits, the delivery of VEGF alone or in combination with IGF from alginate hydrogels, at a dose 2 orders of magnitude lower than the typical doses used in past rabbit studies, enhanced perfusion recovery when given immediately after surgery, or as a treatment for chronic ischemia. Capillary density measurements and angiographic analysis demonstrated the benefit of gel delivery. These data together suggest that alginate hydrogels providing local delivery of low doses of VEGF and IGF constitute a safe and effective treatment for hind-limb ischemia in clinically relevant animal models, thereby supporting the potential clinical translation of this concept.
Early Assessment of the Risk Factors for Diabetic Retinopathy Can Reduce the Risk of Peripheral Arterial and Cardiovascular Diseases in Type 2 Diabetes
Authors: Tang Juan , Li Tao , Li Pinhong , Ma Yuefei , Liu Momo , Shan Qiaoyun , Guo Fengqi , Zhou Ting , Wei Qianping
Published: September 2017

Backgrounds: There is still a lack of consensus about how to assess the risk of peripheral arterial disease (PAD) and cardiovascular disease (CVD) in patients with diabetic retinopathy (DR). Aims: We investigated the risk factors for DR and their association with PAD and CVD in patients with type 2 diabetes (T2D). Methods: A total of 1,421 patients diagnosed with T2D participated in this study. DR stages were classified as non-DR, nonproliferative DR (NPDR), or proliferative DR (PDR). Logistic regression analysis was employed to analyze risk factors associated with DR. Results: NPDR and PDR patients had higher systolic blood pressure (SBP) and higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) than the non-DR group (p < 0.05). The prevalence of abnormal ankle-brachial index (ABI) in the non-DR, NPDR, and PDR groups was 7.00, 10.80, and 13.96%, respectively (p < 0.05) and the prevalence of peripheral arterial plaques was 68.48, 81.38, and 80.56%, respectively (p < 0.001). Logistic regression analysis showed that DR (vs. non-DR) was associated with peripheral arterial plaques (OR = 2.07), SBP ≥130 mm Hg (OR = 1.53) and levels of hemoglobin (Hb)A1c (OR = 2.11) and TC (OR = 1.42). Conclusion: PAD is commonly associated with NPDR and PDR. Hypercholesterolemia is an important risk factor for the development of PAD and CVD in patients with DR. Our results suggest that a routine ABI test, duplex ultrasonography, and obtaining a lipid profile for DR patients may help to reduce the occurrence of PAD and CVD.
Inhibition of Erythrocyte Cell Membrane Scrambling by ASP3026
Authors: Bhuyan Abdulla Al Mamun , Bissinger Rosi , Cao Hang , Lang Florian
Published: September 2017

Background/Aims: The anaplastic lymphoma kinase (ALK) inhibitor ASP3026 is in clinical development for the treatment of ALK expressing non-small cell lung carcinoma (NSCLC). ASP3026 is in part effective by inducing apoptosis of tumor cells. Erythrocytes lack mitochondria and nuclei, key organelles in the execution of apoptosis, but are nevertheless able to enter suicidal death or eryptosis, which is characterized by cell membrane scrambling with phosphatidylserine translocation to the cell surface and by cell shrinkage. Eryptosis is triggered by cell stress, such as energy depletion, hyperosmotic shock, oxidative stress and excessive increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored, whether ASP3026 impacts on eryptosis. Methods: Human erythrocytes have been exposed to energy depletion (glucose withdrawal for 48 hours), oxidative stress (addition of 0.3 mM tert-butylhydroperoxide [tBOOH] for 50 min) or Ca2+ loading with Ca2+ ionophore ionomycin (1 µM for 60 min) in absence and presence of ASP3026 (1-4 µg/ml). Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, and cell volume from forward scatter. Results: Treatment with ASP3026 alone did not significantly modify annexin-V-binding or forward scatter. Energy depletion, oxidative stress and ionomycin, all markedly and significantly increased the percentage of annexin-V-binding erythrocytes, and decreased the forward scatter. ASP3026 significantly blunted the effect of energy depletion and oxidative stress, but not of ionomycin on annexin-V-binding. ASP3026 did not significantly influence the effect of any maneuver on forward scatter. Conclusions: ASP3026 is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion and oxidative stress.
Dynamics of Glucose Metabolism After Kidney Transplantation
Authors: Guthoff Martina , Wagner Robert , Weichbrodt Karoline , Nadalin Silvio , Königsrainer Alfred , Häring Hans-Ulrich , Fritsche Andreas , Heyne Nils
Published: September 2017

Background/Aims: Posttransplantation diabetes mellitus (PTDM) impacts patient and allograft survival after kidney transplantation. Prediabetes, which is an independent risk factor for PTDM, is modifiable also in a post-transplant setting. Understanding the risks and dynamics of impaired glucose metabolism after transplantation is a key component for targeted intervention. Methods: A retrospective chart analysis of all adult non-diabetic renal allograft recipients (n=251, 2007-2014) was performed. Longitudinal follow-up included fasting plasma glucose and HbA1c, as well as data on allograft function and immunosuppression at consecutive time points (months 3-6 to >5 years post transplantation). Results: Throughout follow-up, median prevalence of prediabetes and PTDM was 53.3 [52.4-55.7]% and 15.4 [15.0-16.5]%, respectively. Continuously high fluxes between states of glucose metabolism, with individual patients’ state deteriorating or improving over time, resulted in a high number of incident patients even long after transplantation. The greatest number of patients shifted between normal glucose tolerance and prediabetes, followed by those between prediabetes and PTDM. Conclusion: Prediabetes and PTDM are highly prevalent after kidney transplantation and incidences remain relevant throughout follow-up. Patient fluxes into and out of the prediabetic state show that glucose metabolism is highly dynamic after transplantation. This provides a continuous opportunity for intervention in an aim to reduce diabetes-associated complications.
Public Perceptions, Expectations, and Views of Community Pharmacy Practice in Kuwait
Authors: Awad Abdelmoneim I. , Al-Rasheedi Altaf , Lemay Jacinthe
Published: September 2017

Objectives: This study was designed to determine public patterns for use of community pharmacies, perceptions of pharmacists, confidence and trust in pharmacists, and expectations about the pharmacist's roles, and to explore the public views and satisfaction with the current pharmacy services. Subjects and Methods: A descriptive, cross-sectional survey was performed using a pretested self-administered questionnaire on a sample of 481 individuals selected using a 2-stage stratified cluster sampling design. Descriptive and multivariate logistic regression analyses were used for data analysis. p < 0.05 was considered statistically significant. Results: The most common reasons for visiting a pharmacy were to purchase medications (prescription: n = 338 [78.1%] and nonprescription: n = 296 [68.4%]). Of the 433 respondents, 87 believed that pharmacists had a good balance between health and business matters; regarding any drug-related problem, 229 (52.9%) identified the physician as the first person to contact, followed by the pharmacist (n = 140; 32.3%); 255 (58.9%) agreed that they trust pharmacists, while 237 (54.8%) agreed that pharmacists have the ability to answer drug- or disease-related questions. Of the 433 respondents, 236 (54.5%) did not expect the pharmacist's role to include monitoring health progress to ensure safe and effective use of medications, and 258 (59.6%) were satisfied with the current pharmacy services. Conclusion: The current study indicated that respondents had overall negative perceptions of community pharmacists, expressed moderate expectations of their role, and viewed the current pharmacy services as slightly positive. These findings highlight the need for designing multifaceted interventions targeting specific areas to advance the community pharmacy practice in Kuwait.
Founder’s Prize for New Scholars 2016: “Looking Down Time’s Telescope at Myself”: Reincarnation and Global Futures in David Mitchell’s Fictional Worlds
Authors: Harris-Birtill Rose
Published: September 2017

This essay explores the trope of reincarnation across the works of British author David Mitchell (b. 1969) as an alternative approach to linear temporality, whose spiralling cyclicality warns of the dangers of seeing past actions as separate from future consequences, and whose focus on human interconnection demonstrates the importance of collective, intergenerational action in the face of ecological crises. Drawing on the Buddhist philosophy of samsara, or the cycle of life, death, and rebirth, this paper identifies links between the author’s interest in reincarnation and its secular manifestation in the treatment of time in his fictions. These works draw on reincarnation in their structures and characterization as part of an ethical approach to the Anthropocene, using the temporal model of “reincarnation time” as a narrative strategy to demonstrate that a greater understanding of generational interdependence is urgently needed in order to challenge the linear “end of history” narrative of global capitalism.
Myths, Legends, and Contemporary Nigerian Theatre
Authors: Afejuku Tony E. , Adeleke E.B.
Published: September 2017

Femi Osofisan belongs to the new breed of writers, inadequately referred to as the ‘second generation of writers’. An accomplished writer whose works include plays, poems, essays, and novels, Osofisan is widely regarded as the most significant playwright in Africa after Soyinka. As a committed playwright, Osofisan focuses on the reappraisal of his immediate society and the challenges of living in this society. He calls attention to all that is undesirable in the politics, economy, and religion of contemporary Nigeria and asks for a change of attitude which, hopefully, will bring sanity to the country. One of the means by which Osofisan achieves his artistic objective is the use of lore from Yorùbá mythology. Specifically, we shall show in this essay that Osofisan makes use of the myths of Ṣango and Èṣù and the legends of Môrèmi and Solarin as a means of thematic exploitation. By so doing, he creates a unique contemporary Nigerian theatre which other playwrights emulate and develop. We shall use Many Colours Make the Thunder King, Esu and the Vagabond Minstrels, Morountodun, and Who’s Afraid of Solarin? as our illustrative texts.
A Fete of Lamentations
Authors: Solanke Stephen O.
Published: September 2017

The Nigerian political milieu has, for more than five decades since independence, been bedevilled by adventurist civilian and military leaders, coups d’ état, and a seemingly ‘docile’ citizenry (who receive the ‘fallout’ of bad governance). This political landscape saw a handful of democratic governments (two overthrown by putsch). These leadership swaps have resulted in no major changes in the socio-political and economic lives of the led. In his poem collection Songs of Odamolugbe, Ademola Dasylva explores imagery, realistic symbolism, and revolutionary poetry to paint, recall, and re-live various past and present debilitating national issues engendered by groups and personalities. This essay draws on Sigmund Freud’s psychoanalytical theory of the unconscious. Freud distinguishes between psychoanalysis as i) a method for investigating unconscious mental processes and ii) a method for treating neurotic disorders. There is the subtle examination of the mental workings of the leadership and the led in and towards governance. This essay seeks to explore how Dasylva exposes leaders’ mental flaws, egoistic behaviour, and wrongly placed ‘patriotism’ and seeks redeeming positives in his poetry of social protest and resistance. The poetry rejects the cerebral, laissez-faire ‘sit-down-look’ attitude of the people, encouraging instead a different type of analytical and active ‘patriotism’ imbued with the fresh spirit of ‘Naija’. The essay affirms that there should be full and positive participation in the polity and development of the country by both the leaders and the led.
Two new species of Psephenops Grouvelle (Coleoptera: Byrrhoidea: Psephenidae) from Panama
Authors: ARCE-PÉREZ ROBERTO , NOVELO-GUTIÉRREZ RODOLFO
Published: September 2017

Psephenops bifidus sp. nov. and Psephenops triangularis sp. nov. are described, based on specimens collected from Altos del María, Chame District, Panama, rising the total number of species assigned to this genus in the Mesoamerican region to twelve. Both species can be separated easily from other known Psephenops species by a combination of several features, but mainly by the prosternal process and the lateral projections of penis respectively.
A Matérn-Based Multivariate Gaussian Random Process for a Consistent Model of the Horizontal Wind Components and Related Variables
Authors: Hewer Rüdiger , Friederichs Petra , Hense Andreas , Schlather Martin
Published: September 2017

The integration of physical relationships into stochastic models is of major interest, for example, in data assimilation. Here, a multivariate Gaussian random field formulation is introduced that represents the differential relations of the two-dimensional wind field and related variables such as the streamfunction, velocity potential, vorticity, and divergence. The covariance model is based on a flexible bivariate Matérn covariance function for the streamfunction and velocity potential. It allows for different variances in the potentials, nonzero correlations between them, anisotropy, and a flexible smoothness parameter. The joint covariance function of the related variables is derived analytically. Further, it is shown that a consistent model with nonzero correlations between the potentials and positive definite covariance function is possible. The statistical model is fitted to forecasts of the horizontal wind fields of a mesoscale numerical weather prediction system. Parameter uncertainty is assessed by a parametric bootstrap method. The estimates reveal only physically negligible correlations between the potentials.
Considerations for Phased-Array Radar Data Use within the National Weather Service
Authors: Wilson Katie A. , Heinselman Pamela L. , Kuster Charles M.
Published: September 2017

Thirty National Weather Service forecasters worked with 1-, 2-, and 5-min phased-array radar (PAR) volumetric updates for a variety of weather events during the 2015 Phased Array Radar Innovative Sensing Experiment. Exposure to each of these temporal resolutions during simulated warning operations meant that these forecasters could provide valuable feedback on how rapidly updating PAR data impacted their warning decision processes. To capture this feedback, forecasters participated in one of six focus groups. A series of open-ended questions guided focus group discussions, and forecasters were encouraged to share their experiences and opinions from the experiment. Transcriptions of focus group discussions were thematically analyzed, and themes belonging to one of two groups were identified: 1) forecasters’ use of rapidly updating PAR data during the experiment and 2) how forecasters envision rapidly updating PAR data being integrated into warning operations. Findings from this thematic analysis are presented in this paper, and to illustrate these findings from the forecasters’ perspectives, dialogue that captures the essence of their discussions is shared. The identified themes provide motivation to integrate rapidly updating radar data into warning operations and highlight important factors that need to be addressed for the successful integration of these data.