bluuebunny/crossref_metadata_2025 huggingface dataset:
Stabilizing Parametric Region of Multiloop PID Controllers for Multivariable Systems Based on Equivalent Transfer Function
Authors: Luan Xiaoli , Chen Qiang , Albertos Pedro , Liu Fei
Published: May 2016

The aim of this paper is to determine the stabilizing PID parametric region for multivariable systems. Firstly, a general equivalent transfer function parameterization method is proposed to construct the multiloop equivalent process for multivariable systems. Then, based on the equivalent single loops, a model-based method is presented to derive the stabilizing PID parametric region by using the generalized Hermite-Biehler theorem. By sweeping over the entire ranges of feasible proportional gains and determining the stabilizing regions in the space of integral and derivative gains, the complete set of stabilizing PID controllers can be determined. The robustness of the design procedure against the approximation in getting the SISO plants is analyzed. Finally, simulation of a practical model is carried out to illustrate the effectiveness of the proposed technique.
Preliminary Design of a Small Unmanned Battery Powered Tailsitter
Authors: Wang Bo , Hou Zhongxi , Liu Zhaowei , Chen Qingyang , Zhu Xiongfeng
Published: May 2016

This paper presents a preliminary design methodology for small unmanned battery powered tailsitters. Subsystem models, including takeoff weight, power and energy consumption models, and battery discharge model, were investigated, respectively. Feasible design space was given by simulation with mission and weight constraints, while the influences of wing loading and battery ratio were analyzed. Case study was carried out according to the design process, and the results were validated by previous designs. The design methodology can be used to determine key parameters and make necessary preparations for detailed design and vehicle realization of small battery powered tailsitters.
Group B Streptococcus Colonization among Pregnant Women Attending Antenatal Care at Tertiary Hospital in Rural Southwestern Uganda
Authors: Namugongo Abdul , Bazira Joel , Fajardot Yarine , Joseph Ngonzi
Published: May 2016

Objectives.This study sought to determine the prevalence and factors associated with group B streptococcal anogenital colonization among pregnant women attending antenatal care at Mbarara Regional Referral Hospital, a tertiary hospital.Methods.Cross-sectional study where 309 pregnant women ≥ thirty-five weeks of gestation attending antenatal clinic were consecutively recruited between January and March 2015. Anovaginal swabs were collected and tested qualitatively using rapid visual immunoassay GBS test kits for presence of GBS antigens. Data was analyzed using STATA version 12. In univariate analysis, GBS colonized mothers were presented as percentages and numbers, and in multivariate analysis logistic regression analysis was applied to determine the associations of exposure variable and GBS colonization; a value of less than 0.05 was considered significant.Results.Mothers’ median age was 25 years, 14.6% mothers being obese. GBS prevalence was 28.8%, 95% CI: 23.7–33.9. Obesity was the only significant factor associated with anogenital GBS colonization with odds ratio of 3.78, 95% CI: 1.78–8.35, apvalue of 0.001. Maternal ages, educational level, residence, and gravidity were not associated with GBS anogenital colonization.Conclusion.Group B streptococcal anogenital colonization among pregnant women attending antenatal care at tertiary hospital, in Southwestern Uganda, is high.
The Influence of Bone Marrow-Secreted IL-10 in a Mouse Model of Cerulein-Induced Pancreatic Fibrosis
Authors: Lin Wey-Ran , Lim Siew-Na , Yen Tzung-Hai , Alison Malcolm R.
Published: May 2016

This study aimed to understand the role of IL-10 secreted from bone marrow (BM) in a mouse model of pancreatic fibrosis. The severity of cerulein-induced inflammation, fibrosis, and the frequency of BM-derived myofibroblasts were evaluated in the pancreas of mice receiving either a wild-type (WT) BM or an IL-10 knockout (KO) BM transplantation. The area of collagen deposition increased significantly in the 3 weeks after cerulein cessation in mice with an IL-10 KO BM transplant (13.7 ± 0.6% and 18.4 ± 1.1%,p< 0.05), but no further increase was seen in WT BM recipients over this time. The percentage of BM-derived myofibroblasts also increased in the pancreas of the IL-10 KO BM recipients after cessation of cerulein (6.7 ± 1.1% and 11.9 ± 1.3%,p< 0.05), while this figure fell in WT BM recipients after cerulein withdrawal. Furthermore, macrophages were more numerous in the IL-10 KO BM recipients than the WT BM recipients after cerulein cessation (23.2 ± 2.3 versus 15.3 ± 1.7 per HPF,p< 0.05). In conclusion, the degree of fibrosis, inflammatory cell infiltration, and the number of BM-derived myofibroblasts were significantly different between IL-10 KO BM and WT BM transplanted mice, highlighting a likely role of IL-10 in pancreatitis.
Hematological, Biochemical, and Serological Findings in Healthy Canine Blood Donors after the Administration of CaniLeish® Vaccine
Authors: Starita Chiara , Gavazza Alessandra , Lubas George
Published: May 2016

The aim of the study was to evaluate hematological, biochemical, and serological findings in healthy canine blood donors after the administration of CaniLeish® vaccine. Twenty-seven client-owned dogs were included in the study and arranged into 3 groups according to the vaccination stage. Complete blood count (CBC) with blood smear examination, serum biochemical profile (SBP), serum protein electrophoresis (SPE), and serological tests forL. infantumwere performed at different times. Additionally, in a subgroup of dogs IgA, IgM, and IgG were quantified. No statistical significance for CBC and SBP was found. In 10.7% of cases slight hyperproteinemia occurred. In SPE absolute valuesβ-1-globulins (Group 2 and Group 2-3) andβ-2-globulins (Group 3) were found modified (P<0.05). IgG values were statistically different (P<0.05) 6–8 months after the third immunisation (Group 2) and IgM and IgG values were statistically different after 2 months (Group 3). IFAT positive samples were 20.8% (Group 1), 15.0% (Group 2), and 52.8% (Group 3). Speed LeishK™tests were always negative. The modifications found were probably attributed to the development of immune or inflammatory response due to the vaccine. Administration of CaniLeish vaccine in canine blood donors could be a safe practice and did not affect their health status.
Impacts of Fog Characteristics, Forward Illumination, and Warning Beacon Intensity Distribution on Roadway Hazard Visibility
Authors: Bullough John D. , Rea Mark S.
Published: May 2016

Warning beacons are critical for the safety of transportation, construction, and utility workers. These devices need to produce sufficient luminous intensity to be visible without creating glare to drivers. Published standards for the photometric performance of warning beacons do not address their performance in conditions of reduced visibility such as fog. Under such conditions light emitted in directions other than toward approaching drivers can create scattered light that makes workers and other hazards less visible. Simulations of visibility of hazards under varying conditions of fog density, forward vehicle lighting, warning beacon luminous intensity, and intensity distribution were performed to assess their impacts on visual performance by drivers. Each of these factors can influence the ability of drivers to detect and identify workers and hazards along the roadway in work zones. Based on the results, it would be reasonable to specify maximum limits on the luminous intensity of warning beacons in directions that are unlikely to be seen by drivers along the roadway, limits which are not included in published performance specifications.
Using the Relevance Vector Machine Model Combined with Local Phase Quantization to Predict Protein-Protein Interactions from Protein Sequences
Authors: An Ji-Yong , Meng Fan-Rong , You Zhu-Hong , Fang Yu-Hong , Zhao Yu-Jun , Zhang Ming
Published: May 2016

We propose a novel computational method known as RVM-LPQ that combines the Relevance Vector Machine (RVM) model and Local Phase Quantization (LPQ) to predict PPIs from protein sequences. The main improvements are the results of representing protein sequences using the LPQ feature representation on a Position Specific Scoring Matrix (PSSM), reducing the influence of noise using a Principal Component Analysis (PCA), and using a Relevance Vector Machine (RVM) based classifier. We perform 5-fold cross-validation experiments onYeastandHumandatasets, and we achieve very high accuracies of 92.65% and 97.62%, respectively, which is significantly better than previous works. To further evaluate the proposed method, we compare it with the state-of-the-art support vector machine (SVM) classifier on theYeastdataset. The experimental results demonstrate that our RVM-LPQ method is obviously better than the SVM-based method. The promising experimental results show the efficiency and simplicity of the proposed method, which can be an automatic decision support tool for future proteomics research.
A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic
Authors: Daly Chris , Ghosh Peter , Jenkin Graham , Oehme David , Goldschlager Tony
Published: May 2016

Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored.
Experimental Research on High Temperature Resistance of Modified Lightweight Concrete after Exposure to Elevated Temperatures
Authors: He Ke-cheng , Guo Rong-xin , Ma Qian-min , Yan Feng , Lin Zhi-wei , Sun Yan-Lin
Published: May 2016

In order to improve the spalling resistance of lightweight aggregate concrete at high temperature, two types of modified materials were used to modify clay ceramsite lightweight aggregates by adopting the surface coating modification method. Spalling of the concrete specimens manufactured by using the modified aggregates was observed during a temperature elevation. Mass loss and residual axial compressive strength of the modified concrete specimens after exposure to elevated temperatures were also tested. Concrete specimens consisting of ordinary clay ceramsites and crushed limestone were manufactured as references for comparison. The results showed that the ordinary lightweight concrete specimens and the crushed limestone concrete specimens were completely spalled after exposure to target temperatures above 400°C and 1000°C, respectively, whereas the modified concrete specimens remained intact at 1200°C, at which approximately 25% to 38% of the residual compressive strength was retained. The results indicated that the modified lightweight concrete specimens have exhibited superior mechanical properties and resistance to thermal spalling after exposure to elevated temperatures.
Physicochemical and Nutritional Characterization of Starch Isolated fromColocasia antiquorumCultivated in Oaxaca, Mexico
Authors: Ríos-Ríos Karina , González-Mondragón Edith , Segura-Campos Maira , Ramírez-Jiménez Mariela , López-Luna Jesús , López-Martínez Irma , Betancur-Ancona David
Published: May 2016

The physicochemical and nutritional characteristics ofColocasia antiquorum(taro coconut or Chinese taro) starch cultivated in Oaxaca, Mexico, were determined. The granules ofColocasia antiquorumpresented a truncated ellipsoidal shape. The chemical composition analysis showed levels of moisture, ash, protein, fat, fiber, and NFE in a dry base of 10.29, 0.18, 2.0, 0.05, 0.01, and 97.76, respectively, as well as amylose and amylopectin contents of 13.05 and 86.95%, respectively. Gelatinization temperatures, onset (To), peak (Tp), and final (Tf), were 72.86, 82.91, and 93.05°C, respectively. Solubility, swelling power (SP), and water absorption capacity (WAC) correlate directly with increments in temperature. Transmittance value (% T) for taro coconut was 0.3% and its apparent viscosity ranged from 100 to 150 cp. The nutritional characterization ofColocasia antiquorum’s starch amounted to 97.88% of total starch (TS), while available (AS) and resistant starch (RS) were 93.47 and 3.70%, respectively.Colocasia antiquorum, grown in Oaxaca, Mexico, is an unconventional source of starch with added value due to its potential use as an ingredient in the development of new products or as a substitute for conventional starch sources in industrial processes.
Do Lactation-Induced Changes in Ghrelin, Glucagon-Like Peptide-1, and Peptide YY Influence Appetite and Body Weight Regulation during the First Postpartum Year?
Authors: Larson-Meyer D. Enette , Schueler Jessica , Kyle Erin , Austin Kathleen J. , Hart Ann Marie , Alexander Brenda M.
Published: May 2016

To determine whether fasting and meal-induced appetite-regulating hormones are altered during lactation and associated with body weight retention after childbearing, we studied 24 exclusively breastfeeding women (BMI = 25.2 ± 3.6 kg/m2) at 4-5 weeks postpartum and 20 never-pregnant controls (BMI = 24.0 ± 3.1 kg/m2). Ghrelin, PYY, GLP-1, and appetite ratings were measured before/and 150 minutes after a standardized breakfast and 60 minutes after anad libitumlunch. Body weight/composition were measured at 6 and 12 months. Fasting and area under-the-curve responses for appetite-regulating hormones did not differ between lactating and control groups;ghrelinacyl, however, tended to track higher after the standardized breakfast in lactating women and was higher (p<0.05) after thead libitumlunch despite a 24% higher energy intake (p< 0.05). By 12 months, lactating women lost 5.3 ± 2.2 kg (n=18), whereas control women (n=15) remained weight stable (p=0.019); fifteen of the lactating women returned to within ±2.0 kg of prepregnancy weight but three retained >6.0 kg. The retainers had greater (p<0.05) postmeal ghrelin rebound responses following breakfast. Overall these studies do not support the hypothesis that appetite-regulating hormones are altered during lactation and associated with postpartum weight retention. Altered ghrelin responses, however, deserve further exploration.
A Standalone Vision Sensing System for Pseudodynamic Testing of Tuned Liquid Column Dampers
Authors: Min Kyung-Won , Jang Seok-Jung , Kim Junhee
Published: May 2016

Experimental investigation of the tuned liquid column damper (TLCD) is a primal factory task prior to its installation at a site and is mainly undertaken by a pseudodynamic test. In this study, a noncontact standalone vision sensing system is developed to replace a series of the conventional sensors installed at the TLCD tested. The fast vision sensing system is based on binary pixel counting of the portion of images steamed in a pseudodynamic test and achieves near real-time measurements of wave height, lateral motion, and control force of the TLCD. The versatile measurements of the system are theoretically and experimentally evaluated through a wide range of lab scale dynamic tests.
Coccidioides immitisCervical Lymphadenitis Complicated by Esophageal Fistula
Authors: Loudin Michael , Clayburgh Daniel R. , Hakki Morgan
Published: May 2016

Coccidioidomycosis (valley fever) is caused by the dimorphic fungiCoccidioides immitisorCoccidioides posadasii. Most infections are asymptomatic or result in self-limited pneumonia; extrapulmonary dissemination via either hematogenous or lymphatic spread is rare. Here, we present a case of cervicalC. immitislymphadenitis that resulted in fistula formation to the esophagus via mediastinal extension. This case highlights a very unusual extrapulmonary manifestation of coccidioidomycosis, the difficulty in diagnosing coccidioidal infection when it is not suspected, and the importance of obtaining a thorough exposure history to assist with diagnosis.
Effector, Memory, and Dysfunctional CD8+T Cell Fates in the Antitumor Immune Response
Authors: Reiser John , Banerjee Arnob
Published: May 2016

The adaptive immune system plays a pivotal role in the host’s ability to mount an effective, antigen-specific immune response against tumors. CD8+tumor-infiltrating lymphocytes (TILs) mediate tumor rejection through recognition of tumor antigens and direct killing of transformed cells. In growing tumors, TILs are often functionally impaired as a result of interaction with, or signals from, transformed cells and the tumor microenvironment. These interactions and signals can lead to transcriptional, functional, and phenotypic changes in TILs that diminish the host’s ability to eradicate the tumor. In addition to effector and memory CD8+T cells, populations described as exhausted, anergic, senescent, and regulatory CD8+T cells have been observed in clinical and basic studies of antitumor immune responses. In the context of antitumor immunity, these CD8+T cell subsets remain poorly characterized in terms of fate-specific biomarkers and transcription factor profiles. Here we discuss the current characterization of CD8+T cell fates in antitumor immune responses and discuss recent insights into how signals in the tumor microenvironment influence TIL transcriptional networks to promote CD8+T cell dysfunction.
Preparation of Graphene Quantum Dots and Their Application in Cell Imaging
Authors: Zhang Jie , Ma Yong-qiang , Li Na , Zhu Jing-li , Zhang Ting , Zhang Wei , Liu Bin
Published: May 2016

Objective. This study aims to increase the fluorescence quantum yield by improving the conditions of preparing graphene quantum dots (GQDs) through the solvothermal route and observe the GQDs performance in imaging oral squamous cells.Methodology. The following experimental conditions of GQDs preparation through the solvothermal route were improved: graphene oxide (GO)/N-N dimethyl formamide (DMF) ratio, filling percentage, and reaction time. A fluorescence spectrophotometer was used to measure photoluminescence, and the peak values were compared. Methylthiazolyldiphenyl-tetrazolium (MTT) bromide was used to detect the cytotoxicity of GQDs, which was compared with that of cadmium telluride quantum dots (CdTe QDs). GQDs were cultured with tongue cancer cells. After the coculture, a laser scanning confocal microscope (LSCM) was used to observe cell imaging.Results. The optimal conditions of GQD preparation through the solvothermal route included the following: 10 mg/mL GO/DMF ratio, 80% filling percentage, 12 h reaction time, and 17.4% fluorescence quantum yield. As the cell concentration increased, the GQD and CdTe QD groups exhibited a decreasing cell survival rate, with the decrease in the CdTe QD group being more significant. The LSCM observations showed bright green fluorescence images.Conclusion. The improved experimental conditions increased the fluorescence quantum yield of GQDs. In this study, the prepared GQDs exhibited low cytotoxicity level and satisfactory cell imaging performance.
Improving Outcomes for Infants with Single Ventricle Physiology through Standardized Feeding during the Interstage
Authors: Weston Cindy , Husain S. Adil , Curzon Christopher L. , Neish Steve , Kennedy Gemma T. , Bonagurio Krista , Gosselin Kevin
Published: May 2016

Congenital heart disease is identified as the most common birth defect with single ventricle physiology carrying the highest mortality. Staged surgical palliation is required for treatment, with mortality historically as high as 22% in the four- to six-month period from the first- to second-stage surgical palliation, known as the interstage. A standardized postoperative feeding approach was implemented through an evidence-based protocol, parent engagement, and interprofessional team rounds. Five infants with single ventricle physiology preprotocol were compared with five infants who received the standardized feeding approach. Mann-WhitneyUtests were conducted to evaluate the hypotheses that infants in the intervention condition would consume more calories and have a positive change in weight-to-agez-score (WAZ) and shorter length of stay (LOS) following the first and second surgeries compared to infants in the control condition. After the protocol, the change in WAZ during the interstage increased by virtually one standard deviation from 0.05 to 0.91. Median LOS dropped 32% after the first surgery and 43% after the second surgery. Since first- and second-stage palliative surgeries occur within the same year of life, this represents savings of$500,000 to$800,000 per year in a 10-infant model. The standardized feeding approach improved growth in single ventricle infants while concurrently lowering hospital costs.
A Hybrid Neural Network Model for Sales Forecasting Based on ARIMA and Search Popularity of Article Titles
Authors: Omar Hani , Hoang Van Hai , Liu Duen-Ren
Published: May 2016

Enhancing sales and operations planning through forecasting analysis and business intelligence is demanded in many industries and enterprises. Publishing industries usually pick attractive titles and headlines for their stories to increase sales, since popular article titles and headlines can attract readers to buy magazines. In this paper, information retrieval techniques are adopted to extract words from article titles. The popularity measures of article titles are then analyzed by using the search indexes obtained from Google search engine. Backpropagation Neural Networks (BPNNs) have successfully been used to develop prediction models for sales forecasting. In this study, we propose a novel hybrid neural network model for sales forecasting based on the prediction result of time series forecasting and the popularity of article titles. The proposed model uses the historical sales data, popularity of article titles, and the prediction result of a time series, Autoregressive Integrated Moving Average (ARIMA) forecasting method to learn a BPNN-based forecasting model. Our proposed forecasting model is experimentally evaluated by comparing with conventional sales prediction techniques. The experimental result shows that our proposed forecasting method outperforms conventional techniques which do not consider the popularity of title words.
On Estimates of Deviation of Functions from Matrix Operators of Their Fourier Series by Some Expressions withr-Differences of the Entries
Authors: Łenski Włodzimierz , Szal Bogdan
Published: May 2016

We generalize the results of Krasniqi 2012 and Wei and Yu 2012 to the case ofr-differences.
MHM: A Multiple Handshaking MAC Protocol for Underwater Acoustic Sensor Networks
Authors: Lin Wen , Chen Keyu
Published: May 2016

Underwater acoustic sensor networks (UWASNs) are effective tools for exploring and observing the ocean. Due to the nonnegligible physical restrictions of the underwater acoustic communication, most MAC protocols applied in the existing terrestrial wireless networks become inapplicable. In this paper, we propose a multiple handshaking MAC protocol for UWASNs called multihandshaking MAC (MHM). Using the method of multiple handshaking and competitive mechanism of control packets, our protocol is proposed to make the contending nodes share the underwater acoustic channel much more fairly and more efficiently. The main idea of MHM is to allow multiple nodes to transmit and receive data packets at the same time without packet collisions. We also propose a competitive mechanism of control packets, which can guarantee that there will not be data collisions in the process of multiple packet transmissions. Simulation results show that our protocol can achieve better performance, including throughput, delay, and fairness.
BRAF Mutation Testing in Cell-Free DNA from the Plasma of Patients with Advanced Cancers Using a Rapid, Automated Molecular Diagnostics System
Authors: Janku Filip , Huang Helen J. , Claes Bart , Falchook Gerald S. , Fu Siqing , Hong David , Ramzanali Nishma M. , Nitti Giovanni , Cabrilo Goran , Tsimberidou Apostolia M. , Naing Aung , Piha-Paul Sarina A. , Wheler Jennifer J. , Karp Daniel D. , Holley Veronica R. , Zinner Ralph G. , Subbiah Vivek , Luthra Rajyalakshmi , Kopetz Scott , Overman Michael J. , Kee Bryan K. , Patel Sapna , Devogelaere Benoit , Sablon Erwin , Maertens Geert , Mills Gordon B. , Kurzrock Razelle , Meric-Bernstam Funda
Published: May 2016

Cell-free (cf) DNA from plasma offers an easily obtainable material for BRAF mutation analysis for diagnostics and response monitoring. In this study, plasma-derived cfDNA samples from patients with progressing advanced cancers or malignant histiocytosis with known BRAFV600 status from formalin-fixed paraffin-embedded (FFPE) tumors were tested using a prototype version of the Idylla BRAF Mutation Test, a fully integrated real-time PCR-based test with turnaround time about 90 minutes. Of 160 patients, BRAFV600 mutations were detected in 62 (39%) archival FFPE tumor samples and 47 (29%) plasma cfDNA samples. The two methods had overall agreement in 141 patients [88%; κ, 0.74; SE, 0.06; 95% confidence interval (CI), 0.63–0.85]. Idylla had a sensitivity of 73% (95% CI, 0.60–0.83) and specificity of 98% (95% CI, 0.93–1.00). A higher percentage, but not concentration, of BRAFV600 cfDNA in the wild-type background (>2% vs. ≤ 2%) was associated with shorter overall survival (OS; P = 0.005) and in patients with BRAF mutations in the tissue, who were receiving BRAF/MEK inhibitors, shorter time to treatment failure (TTF; P = 0.001). Longitudinal monitoring demonstrated that decreasing levels of BRAFV600 cfDNA were associated with longer TTF (P = 0.045). In conclusion, testing for BRAFV600 mutations in plasma cfDNA using the Idylla BRAF Mutation Test has acceptable concordance with standard testing of tumor tissue. A higher percentage of mutant BRAFV600 in cfDNA corresponded with shorter OS and in patients receiving BRAF/MEK inhibitors also with shorter TTF. Mol Cancer Ther; 15(6); 1397–404. ©2016 AACR.
LGR5-Targeted Antibody–Drug Conjugate Eradicates Gastrointestinal Tumors and Prevents Recurrence
Authors: Gong Xing , Azhdarinia Ali , Ghosh Sukhen C. , Xiong Wei , An Zhiqiang , Liu Qingyun , Carmon Kendra S.
Published: May 2016

Gastrointestinal cancer is one of the leading causes of cancer-related mortality in men and women worldwide. The adult stem cell marker LGR5 (leucine-rich repeat-containing, G protein–coupled receptor 5) is highly expressed in a significant fraction of gastrointestinal tumors of the colon, liver, pancreas, and stomach, relative to normal tissues. LGR5 is located on the cell surface and undergoes rapid, constitutive internalization independent of ligand. Furthermore, LGR5-high cancer cells have been shown to exhibit the properties of tumor-initiating cells or cancer stem cells (CSC). On the basis of these attributes, we generated two LGR5-targeting antibody–drug conjugates (ADC) by tethering the tubulin-inhibiting cytotoxic drug monomethyl auristatin E to a highly specific anti-LGR5 mAb via a protease cleavable or noncleavable chemical linker and compared them in receptor binding, cell internalization, and cytotoxic efficacy in cancer cells. Here, we show that both ADCs bind LGR5 with high specificity and equivalent nanomolar affinity and rapidly internalize to the lysosomes of LGR5-expressing gastrointestinal cancer cells. The anti-LGR5 ADCs effectively induced cytotoxicity in LGR5-high gastrointestinal cancer cells, but not in LGR5-negative or -knockdown cancer cell lines. Overall, we demonstrate that the cleavable ADC exhibited higher potency in vitro and was able to eradicate tumors and prevent recurrence in a xenograft model of colon cancer. These findings provide preclinical evidence for the potential of LGR5-targeting ADCs as effective new therapeutics for the treatment and eradication of gastrointestinal tumors and CSCs with high LGR5 expression. Mol Cancer Ther; 15(7); 1580–90. ©2016 AACR.
Restenosis following Percutaneous Renal Artery Revascularization
Authors: Kane Garvan C. , Hambly Niamh , Textor Stephen C. , Stanson Anthony W. , Garovic Vesna D.
Published: May 2016

Background/Aims: Restenosis following percutaneous transluminal renal angioplasty (PTRA) remains a concern even in the era of adjuvant stenting. The optimal form of therapy, and particularly the role of repeat PTRA in the treatment of recurrent hypertension associated with renal artery restenosis, is largely unknown. The aims of this study were to determine the risk factors for restenosis and to evaluate the blood pressure outcomes of patients who underwent repeat PTRA. Methods: Clinical and procedural characteristics of 32 patients who developed recurrent hypertension and renal artery restenosis were compared to a control group of patients who maintained renal artery patency and adequate blood pressure control after the first procedure. The groups were matched for sex and initial procedure date. Results: The restenosis group had a mean age of 71 ± 12 years, a female/male ratio of 24/8, an average blood pressure of 179/87 mm Hg, despite three antihypertensive medications, and a serum creatinine level of 1.5 ± 0.4 mg/dl. Repeat PTRA performed for clinically significant restenosis was 10.7 ± 8 months after the first procedure, and 17 of the 32 patients had a measurable blood pressure benefit at last follow-up (177 ± 119 weeks). The development of restenosis was positively associated with body weight (p = 0.003) and body mass index (p = 0.008), but independent of diabetes mellitus, hyperlipidemia, or statin therapy. Of the 15 patients who failed the second procedure, 4 went on to have third PTRA, none of whom had sustained benefit. Conclusions: An increased body mass index is associated with restenosis following initial PTRA. Patients with restenosis can be treated successfully with repeat PTRA which provides sustained improvement in blood pressure control in approximately half of these patients.
Heterogeneity of a Constitutional Complex Chromosomal Rearrangement in 2q
Authors: Del Rey Javier , Santos Mónica , González-Meneses Antonio , Milà Montserrat , Fuster Carme
Published: May 2016

Complex chromosome rearrangements (CCRs) are unusual structural chromosome alterations found in humans, and to date only a few have been characterized molecularly. New mechanisms, such as chromothripsis, have been proposed to explain the presence of the CCRs in cancer cells and in patients with congenital disorders and/or mental retardation. The aim of the present study was the molecular characterization of a constitutional CCR in a girl with multiple congenital disorders and intellectual disability in order to determine the genotype-phenotype relation and to clarify whether the CCR could have been caused by chromosomal catastrophic events. The present CCR was characterized by G-banding, high-resolution CGH, multiplex ligation-dependent probe amplification and subtelomeric 2q-FISH analyses. Preliminary results indicate that the de novo CCR is unbalanced showing a 2q37.3 deletion and 2q34q37.2 partial trisomy. Our patient shows some of the typical traits and intellectual disability described in patients with 2q37 deletion and also in carriers of 2q34q37.2 partial trisomy; thus, the clinical disorders could be explained by additional effects of both chromosome alterations (deletions and duplications). A posterior, sequential FISH study using BAC probes revealed the unexpected presence of at least 17 different reorganizations affecting 2q34q37.2, suggesting the existence of chromosome instability in this region. The present CCR is the first case described in the literature of heterogeneity of unbalanced CCRs affecting a small region of 2q, indicating that the mechanisms involved in constitutional chromosome rearrangement may be more complex than previously thought.
Aristotle and the Scope of Justice
Authors: Riesbeck David J
Published: May 2016

It is often thought that Aristotle restricts the scope of justice to existing communities.  Against prominent treatments of this problem, this paper argues that while Aristotle does indeed restrict the scope of justice, he recognizes eudaimonic reasons to cultivate co-operative and benevolent relations and to eschew manipulative and exploitative ones.  His limitation of justice to existing communities thereby avoids the unsavory implications often attributed to it.
Akrasia and the Rule of Appetite in Plato's Protagoras and Republic
Authors: Wilburn Joshua
Published: May 2016

According to a prevalent developmentalist line of interpretation, Plato’s introduction of the three-part soul in Republic 4 was motivated in part by his desire to acknowledge and account for cases of akratic action, and thereby to repudiate the psychology and the conclusions of the earlier dialogue Protagoras. In this paper I reject this interpretation, arguing that countenancing akrasia was never a major philosophical concern for Plato, and a fortiori that it was not his motivation for introducing the tripartite soul. I argue that his moral psychological focus and concern in the Republic was rather on the notion of psychic rule, and on illuminating various ways in which reasoning is corrupted by non-rational desires (rather than overcome by them through brute psychic ‘force’). I then offer an explanation of Plato’s lack of concern for akrasia by appealing to the Protagoras itself. I conclude with a rejection of sharp developmentalism between the two dialogues.
Carotid Intima‐Media Thickness and Arterial Stiffness and the Risk of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study, Multi‐Ethnic Study of Atherosclerosis (MESA), and the Rotterdam Study
Authors: Chen Lin Y. , Leening Maarten J. G. , Norby Faye L. , Roetker Nicholas S. , Hofman Albert , Franco Oscar H. , Pan Wei , Polak Joseph F. , Witteman Jacqueline C.M. , Kronmal Richard A. , Folsom Aaron R. , Nazarian Saman , Stricker Bruno H. , Heckbert Susan R. , Alonso Alvaro
Published: May 2016

Background

We evaluated the association of carotid intima‐media thickness (cIMT), carotid plaque, carotid distensibility coefficient (DC), and aortic pulse wave velocity (PWV) with incident atrial fibrillation (AF) and their role in improving AF risk prediction beyond the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)‐AF risk score.

Methods and Results

We analyzed data from 3 population‐based cohort studies: Atherosclerosis Risk in Communities (ARIC) Study (n=13 907); Multi‐Ethnic Study of Atherosclerosis (MESA; n=6640), and the Rotterdam Study (RS; n=5220). We evaluated the association of arterial indices with incident AF and computed the C‐statistic, category‐based net reclassification improvement (NRI), and relative integrated discrimination improvement (IDI) of incorporating arterial indices into the CHARGE‐AF risk score (age, race, height weight, systolic and diastolic blood pressure, antihypertensive medication use, smoking, diabetes, previous myocardial infarction, and previous heart failure). Higher cIMT (meta‐analyzed hazard ratio [95% CI] per 1‐SD increment, 1.12 [1.08–1.16]) and presence of carotid plaque (1.30 [1.19–1.42]) were associated with higher AF incidence after adjustment for CHARGE‐AF risk‐score variables. Lower DC and higher PWV were associated with higher AF incidence only after adjustment for the CHARGE‐AF risk‐score variables excepting height, weight, and systolic and diastolic blood pressure. Addition of cIMT or carotid plaque marginally improved CHARGE‐AF score prediction as assessed by the relative IDI (estimates, 0.025–0.051), but not when assessed with the C‐statistic and NRI.

Conclusions

Higher cIMT, presence of carotid plaque, and greater arterial stiffness are associated with higher AF incidence, indicating that atherosclerosis and arterial stiffness play a role in AF etiopathogenesis. However, arterial indices only modestly improve AF risk prediction.
Hospital Readmissions Following Endovascular Therapy for Critical Limb Ischemia: Associations With Wound Healing, Major Adverse Limb Events, and Mortality
Authors: Reed Grant W. , Raeisi‐Giglou Pejman , Kafa Rami , Malik Umair , Salehi Negar , Shishehbor Mehdi H.
Published: May 2016

Background

The significance of hospital readmission after endovascular therapy for critical limb ischemia (
CLI
) is not well established. We sought to investigate the incidence, timing, and causes of readmissions after endovascular therapy for
CLI
and whether readmission is associated with major adverse limb events (
MALE
) or mortality.

Methods and Results

This was a retrospective study of 252 patients treated with endovascular therapy for
CLI
. During median follow‐up of 381 days (interquartile range [
IQR
], 115–718), 140 (56%) were readmitted, with median time to readmission of 83 days (
IQR,
33–190). Readmission within 30 days occurred in 14% of patients (n=35; 25% of readmissions). Most readmissions occurred between 30 and 180 days (n=67; 48% of readmissions). The most frequent reason for readmission was unhealed wounds (n=63; 45% of readmissions). Independent predictors of readmission by Cox proportional hazards analysis were unhealed wounds, presence of multiple wounds, age ≥70, female sex, hemodialysis, and history of heart failure (
P
<0.05 for each). By Kaplan–Meier analysis, readmission was greatest in patients with unhealed wounds, followed by patients who never had a wound, and lowest in patients whose wounds completely healed (
P
<0.0001 overall, and
P
<0.01 between groups). After multivariable adjustment, readmission remained an independent predictor of composite
MALE
(major amputation, bypass, or endarterectomy) or mortality (adjusted hazard ratio, 3.1; 95%
CI
, 1.5–6.5;
P
=0.002).

Conclusions

Most readmissions occur 30 and 180 days after endovascular therapy for nonprocedural reasons. Unhealed wounds are an independent risk factor for readmission. Readmission is associated with increased
MALE
and mortality after endovascular therapy for
CLI
.
Intravenous Thrombolysis for Acute Ischemic Stroke in Patients Receiving Antiplatelet Therapy: A Systematic Review and Meta‐analysis of 19 Studies
Authors: Luo Shengyuan , Zhuang Mei , Zeng Wutao , Tao Jun
Published: May 2016

Background

The safety and long‐term outcome of systemic thrombolysis in patients receiving antiplatelet medications remain subjects of great clinical significance. The objective of this meta‐analysis was to determine how prestroke antiplatelet therapy affects the risks and benefits of intravenous thrombolysis in patients with acute ischemic stroke.

Methods and Results

A dual‐reviewer search was conducted in PubMed and
EMBASE
databases through November 2015, from which 19 studies involving a total of 108 588 patients with acute ischemic stroke were identified based on preset inclusion criteria. Information on study designs, patient characteristics, exposures, outcomes, and adjusting confounders was extracted, and estimates were combined by using random‐effects models. The pooled crude estimates suggested that taking long‐term antiplatelet medications was associated with higher odds of symptomatic intracranial hemorrhage (odds ratio [OR] 1.70, 95%
CI
1.47–1.97) and death (
OR
1.46, 95%
CI
1.22–1.75) and lower odds of favorable functional outcomes (
OR
0.86, 95%
CI
0.80–0.93). However, the combined confounder‐adjusted results only confirmed a relatively weak positive association between prior antiplatelet therapy and symptomatic intracranial hemorrhage (
OR
1.21, 95%
CI
1.02–1.44) and demonstrated no significant relationship between antiplatelet therapy and the other 2 outcomes (favorable outcome
OR
1.09, 95%
CI
0.96–1.24; death
OR
1.02, 95%
CI
0.98–1.07). Subgroup analyses revealed that the associations between prestroke antiplatelet therapy and outcomes were dependent on time and antiplatelet agents.

Conclusions

Patients with acute ischemic stroke receiving long‐term antiplatelet medications were associated with greater risks of developing symptomatic intracranial hemorrhage after systemic thrombolysis. However, the overall independent association between prestroke antiplatelet therapy and unfavorable outcomes or mortality was insignificant.
Stroke Ready Intervention: Community Engagement to Decrease Prehospital Delay
Authors: Skolarus Lesli E. , Zimmerman Marc A. , Bailey Sarah , Dome Mackenzie , Murphy Jillian B. , Kobrossi Christina , Dombrowski Stephan U. , Burke James F. , Morgenstern Lewis B.
Published: May 2016

Background

Time‐limited acute stroke treatments are underused, primarily due to prehospital delay. One approach to decreasing prehospital delay is to increase stroke preparedness, the ability to recognize stroke, and the intention to immediately call emergency medical services, through community engagement with high‐risk communities.

Methods and Results

Our community–academic partnership developed and tested “Stroke Ready,” a peer‐led, workshop‐based, health behavior intervention to increase stroke preparedness among African American youth and adults in Flint, Michigan. Outcomes were measured with a series of 9 stroke and nonstroke 1‐minute video vignettes; after each video, participants selected their intended response (primary outcome) and symptom recognition (secondary outcome), receiving 1 point for each appropriate stroke response and recognition. We assessed differences between baseline and posttest appropriate stroke response, which was defined as intent to call 911 for stroke vignettes and not calling 911 for nonstroke, nonemergent vignettes and recognition of stroke. Outcomes assessments were performed before workshop 1 (baseline), at the conclusion of workshop 2 (immediate post‐test), and 1 month later (delayed post‐test). A total of 101 participants completed the baseline assessment (73 adults and 28 youths), 64 completed the immediate post‐test, and 68 the delayed post‐test. All participants were African American. The median age of adults was 56 (interquartile range 35–65) and of youth was 14 (interquartile range 11–16), 65% of adults were women, and 50% of youths were women. Compared to baseline, appropriate stroke response was improved in the immediate post‐test (4.4 versus 5.2,
P
<0.01) and was sustained in the delayed post‐test (4.4 versus 5.2,
P
<0.01). Stroke recognition did not change in the immediate post‐test (5.9 versus 6.0,
P
=0.34), but increased in the delayed post‐test (5.9 versus 6.2,
P
=0.04).

Conclusions

Stroke Ready increased stroke preparedness, a necessary step toward increasing acute stroke treatment rates.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
. Unique identifier:
NCT
01499173.
Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Elevated in Patients With Peripheral Artery Disease and Associated With Metabolic Disorders and Dysfunction in Circulating Progenitor Cells
Authors: Chao Ting‐Hsing , Chen I‐Chih , Li Yi‐Heng , Lee Po‐Tseng , Tseng Shih‐Ya
Published: May 2016

Background

Proprotein convertase subtilisin/kexin type 9 (
PCSK
9) is involved in cholesterol homeostasis, inflammation, and oxidative stress. This study investigated the association of plasma
PCSK
9 levels with the presence and severity of peripheral artery disease (
PAD
) and with parameters of endothelial homeostasis.

Methods and Results

A post hoc analysis of 2 randomized trials (115 patients, 44 with
PAD
and 71 without atherosclerotic disease) was conducted. Patients with
PAD
had significantly higher plasma
PCSK
9 levels than those without (471.6±29.6 versus 302.4±16.1 ng/mL,
P
<0.001). Parameters for glucose homeostasis, endothelial progenitor cell functions, apoptotic circulating endothelial cell counts, and plasma levels of vascular endothelial growth factor–A165 and oxidized low‐density lipoprotein were correlated with
PCSK
9 concentration. By multivariable linear regression analysis, presence of
PAD
, plasma glucose or hemoglobin A1c levels, apoptotic
circulating endothelial cell
counts, and vascular endothelial growth factor–A165 concentration were found to be associated with
PCSK
9 levels after multivariable adjustment. Patients with extensive involvement of
PAD
or with severe
PAD
had significantly higher
PCSK
9 levels than those without PAD. Computed tomographic angiography showed that the numbers of chronic total occlusion sites and vessels involved were positively associated with
PCSK
9 levels in patients with
PAD
(
r
=0.40,
P
=0.01, and
r
=0.36,
P
=0.02, respectively).

Conclusion

PCSK
9 levels were significantly higher in patients with
PAD
, especially those with advanced
PAD
. Further large‐scale studies examining the effect of
PCSK
9‐targeting therapies or the modification of
PCSK
9 levels on cardiovascular outcomes in this clinical setting are warranted.

Clinical Trial Registration

Cohort 1: URL: ClinicalTrials.gov. Unique identifier: NCT01952756; cohort 2: URL: ClinicalTrials.gov. Unique identifier: NCT02194686.
I want to understand (what is happening to me)! Miguel Gutierrez Performs How to Be Okay in a Non-Utopia
Authors: Hamp Amanda
Published: May 2016

Miguel Gutierrez’s body of choreographic work, developed in the post-9/11 decade, converses with theories that glimpse potential utopias in performance and in the concept of queerness. Gutierrez’s work is significant not just for envisaging desirable futures, but also for how its difficult aesthetics demonstrate, embody, and perform ways to be in and move through the non-utopias of now.
Gestural Economies and Production Pedagogies in Deaf West’s Spring Awakening
Authors: Wilbur Sarah
Published: May 2016

In Deaf West’s Broadway revival of Spring Awakening, embodied gestures expose and challenge representational and infrastructural norms that drive commercial musical theatre. The company’s blend of ASL and spoken text extends the overarching message about failed sociocultural ideals to the realm of deaf culture. Micro-practical actions and interactions function tacitly to denaturalize audio-centric standards that guide theatrical reception, internal cueing, and technical production.
Scorning the Image of Virtue
Authors: McKee Patricia J.
Published: May 2016

There survives an extraordinary letter of 1616 by the prominent English stage player, Nathan Field. His missive is one of the only extant apologies for the theater written by a player. Field’s letter is a response to a sermon preached by Thomas Sutton, and it richly characterizes Field’s relationship to his parish and to the larger ecclesial powers. This discussion shows how Field ironically employs the very charges often levied by opponents of theater—deception, emotional indulgence, and idolatry—to indict Sutton for a public attack he wielded against Field from the Sunday pulpit. Field’s apology is read within the context of the era’s antitheatricalist polemics, Jacobean politics, Reformation theology, and Field’s history as the son of a radical puritan preacher. The letter invites deep consideration of church and theater—preaching and playing—as competing kinds of performance. Field’s apology also focuses attention on a neglected area in theater studies—the history of players and playing in early modernity. What was an actor’s idea of himself at a time when his profession was redefined by religious reforms? Further, this discussion offers preliminary suggestions for an early modern aesthetics of performance by inviting a dialogue between the era’s extreme antitheatricalism and concurrent prescriptions for effective oratory.