bluuebunny/crossref_metadata_2025 huggingface dataset:
A Note on the Existence of the Location Parameter Estimate of the Three-Parameter Weibull Model Using the Weibull Plot
Authors: Park Chanseok
Published: October 2018

The Weibull model is one of the widely used distributions in reliability engineering. For the parameter estimation of the Weibull model, there are several existing methods. The method of the maximum likelihood estimation among others is preferred because of its attractive statistical properties. However, for the case of the three-parameter Weibull model, the method of the maximum likelihood estimation has several drawbacks. To avoid the drawbacks, the method using the sample correlation from the Weibull plot is recently suggested. In this paper, we provide the justification for using this new method by showing that the location estimate of the three-parameter Weibull model exists in a bounded interval.
Helicobacter pyloriEradication in Idiopathic Thrombocytopenic Purpura: A Meta-Analysis of Randomized Trials
Authors: Kim Bum Jun , Kim Hyeong Su , Jang Hyun Joo , Kim Jung Han
Published: October 2018

Objective.Several recent reviews of published studies have shown that the eradication ofH. pyloriinfection in patients with ITP improved thrombocytopenia in about half of the cases. However, most included studies were observational case series. We performed the first meta-analysis of randomized trials to gain a better insight into the effect ofH. pylorieradication in ITP patients.Methods.A systematic computerized search of the electronic databases including PubMed, EMBASE, Google Scholar, and Cochrane Library (up to December 2017) was conducted.Results.From six studies, a total of 241 patients (125 in eradication group and 116 in control group) were included in the meta-analysis. Patients in the eradication group showed significantly higher overall platelet response rate than those in the control group (odds ratio = 1.93, 95% confidence interval: 1.01–3.71,P=0.05). In the subgroup analysis, however, children in the eradication group failed to show statistically better response rate than those in the noneradication group (odds ratio = 1.80, 95% confidence interval: 0.88–3.65,P=0.11).Conclusions.This meta-analysis indicates thatH. pylorieradication has a significant therapeutic effect in patients with ITP. Considering the intrinsic limits in the design and sample size of the included studies, however, large randomized controlled trials are warranted to validate the therapeutic impact ofH. pylorieradication in adults as well as children with ITP.
Cerebellar Theta-Burst Stimulation Impairs Memory Consolidation in Eyeblink Classical Conditioning
Authors: Monaco Jessica , Rocchi Lorenzo , Ginatempo Francesca , D'Angelo Egidio , Rothwell John C.
Published: October 2018

Associative learning of sensorimotor contingences, as it occurs in eyeblink classical conditioning (EBCC), is known to involve the cerebellum, but its mechanism remains controversial. EBCC involves a sequence of learning processes which are thought to occur in the cerebellar cortex and deep cerebellar nuclei. Recently, the extinction phase of EBCC has been shown to be modulated after one week by cerebellar continuous theta-burst stimulation (cTBS). Here, we asked whether cerebellar cTBS could affect retention and reacquisition of conditioned responses (CRs) tested immediately after conditioning. We also investigated a possible lateralized cerebellar control of EBCC by applying cTBS on both the right and left cerebellar hemispheres. Both right and left cerebellar cTBSs induced a statistically significant impairment in retention and new acquisition of conditioned responses (CRs), the disruption effect being marginally more effective when the left cerebellar hemisphere was stimulated. These data support a model in which cTBS impairs retention and reacquisition of CR in the cerebellum, possibly by interfering with the transfer of memory to the deep cerebellar nuclei.
Behavior of a Dual Stator Induction Machine Fed by Neutral Point Clamped Multilevel Inverter
Authors: Khlifi Mohamed Arbi
Published: October 2018

Use of multilevel inverters with induction machines has become popular in most energy conversion and management systems. The present paper discusses the behavior of the dual stator-winding induction machine (DSIM) for the power source, which is a power supply with Neutral Point Clamped (NPC). Multilevel inverter with PWM technique control is analyzed. The DSIM control is obtained by the PWM technique to multicarrier PWM technique and after a comparative study of various characteristics of the DSIM taking into account the different electrical offsets between the two stars (0°, 30°, 60°). The gap between the two stars was considered, and it is impacted on torque and rates harmonic distortion of circulation currents.
Interaction between a Macrocrack and a Cluster of Microcracks by Muskhelishvili’s Complex Potential Method
Authors: Li Xu , Li Xiaotao , Yang Hongda , Jiang Xiaoyu
Published: October 2018

The interaction between a macrocrack and a cluster of microcracks has been investigated based on Muskhelishvili’s complex potential method. A step-by-step subproblem procedure is used to satisfy the stress boundary conditions on each crack surface. The interactions between a cluster of microcracks and a macrocrack and the interaction among microcracks are analyzed. Three damage configurations as chained, reverse-chained, and randomly distributed microcracks have been designed to simulate the damage around the macrocrack tip. The solution of an infinite elastic plane containing a macrocrack and a cluster of microcracks is presented for the plane subjected to a uniform tensile load. The stress intensity factor (SIF) at the macrocrack tip and the microcrack tips is obtained. The results show that the inclination angle of the microcrack and the distance between the macrocrack and microcracks have a great influence on SIF. When the inclination angle is small, the SIF at microcrack tips may be larger than other inclination angles. These results are helpful to analyze the fracture or damage behaviors of materials.
Deformation and Damping Characteristics of Lightweight Clay‐EPS Soil under Cyclic Loading
Authors: Zhou Yundong , Li Mingdong , He Qibao , Wen Kejun
Published: October 2018

Lightweight Clay‐EPS Soil (LCES) is a newly developed material which has many merits such as the adjustability of strength and density, simplicity for construction, and economical efficiency. It has been widely applied in practical engineering, e.g., soft ground improvement, the solvent of bridge head jump, earthfill of pipeline, and broadening of highway. Meanwhile, construction castoff and industrial waste can be recycled as a major ingredient in LCES. The dynamic deformation characteristics of LCES and clay were comprehensively studied using laboratory dynamic triaxial tests. It was found that the compressive strain of LCES increased while the growth rate of strain decreased with the increasing number of cycles, which conformed to a hyperbola model. The dynamic secant elastic modulus of LCES decreased with the increase of dynamic strain, which was represented by strain softening. The dynamic modulus of clay decreased sharply, while that of LCES decreased marginally. Moreover, the damping ratio of LCES tended to increase with the increasing dynamic strain. The damping ratio of LCES was lower than that of clay at the same strain level. It was also found that cement content had a negative relationship with the damping ratio of LCES, while the effect of EPS beads content was adverse. The damping ratio of both LCES and clay decreased moderately.
A Survey on Mobile Edge Computing: Focusing on Service Adoption and Provision
Authors: Peng Kai , Leung Victor C. M. , Xu Xiaolong , Zheng Lixin , Wang Jiabin , Huang Qingjia
Published: October 2018

Mobile cloud computing (MCC) integrates cloud computing (CC) into mobile networks, prolonging the battery life of the mobile users (MUs). However, this mode may cause significant execution delay. To address the delay issue, a new mode known as mobile edge computing (MEC) has been proposed. MEC provides computing and storage service for the edge of network, which enables MUs to execute applications efficiently and meet the delay requirements. In this paper, we present a comprehensive survey of the MEC research from the perspective of service adoption and provision. We first describe the overview of MEC, including the definition, architecture, and service of MEC. After that we review the existing MUs‐oriented service adoption of MEC, i.e., offloading. More specifically, the study on offloading is divided into two key taxonomies: computation offloading and data offloading. In addition, each of them is further divided into single MU offloading scheme and multi‐MU offloading scheme. Then we survey edge server‐ (ES‐) oriented service provision, including technical indicators, ES placement, and resource allocation. In addition, other issues like applications on MEC and open issues are investigated. Finally, we conclude the paper.
Prediction of Preterm Birth: Maternal Characteristics, Ultrasound Markers, and Biomarkers: An Updated Overview
Authors: Oskovi Kaplan Zeynep Asli , Ozgu-Erdinc A. Seval
Published: October 2018

There is not a single or combined screening method for preterm birth with high sensitivity which will truly identify the women at risk for preterm birth while also with high specificity to prevent unnecessary interventions and high treatment costs. Measurement of cervical length is the most cost-effective method that is used in clinical practice. Bedside tests have also been developed for detecting markers like fetal fibronectin, insulin-like growth factor binding protein-1 (IGFBP-1), interleukin-6, and placental alpha-macroglobulin-1. Taking the maternal history, health condition, and sociodemographical factors into consideration is recommended. Ultrasound markers apart from cervical length measurements as uterocervical angle and placental strain ratio are studied. Investigations on metabolomics, proteomics, and microRNA profiling have brought a new aspect on this subject. Maybe in the future, with clear identification of women at true risk for preterm birth, development of more effective preventive strategies will not be unfeasible.
Regulatory T Cells and Profile of FOXP3 Isoforms Expression in Peripheral Blood of Patients with Myelodysplastic Syndromes
Authors: Dudina Galina A. , Donetskova Almira D. , Litvina Marina M. , Mitin Alexander N. , Mitina Tatiana A. , Polyakov Sergey A.
Published: October 2018

We have investigated the frequencies of regulatory T cells and the level of FOXP3 isoforms expression in peripheral blood of patients with myelodysplastic syndromes and found the significant reduction of regulatory T cells at all stages of the disease. At the same time in untreated patients, we observed the shift in the FOXP3 isoforms expression profile towards the full-length molecule possibly due to inflammation. Based on the already known information about the potentially higher functional activity of FOXP3 molecule lacking exon 2, we have also hypothesized that our finding may explain the high risk of autoimmune disorders in this disease.
Support Needs of Patients with Cushing’s Disease and Cushing’s Syndrome: Results of a Survey Conducted in Germany and the USA
Authors: Kreitschmann-Andermahr Ilonka , Siegel Sonja , Gammel Christa , Campbell Karen , Edwin Leslie , Grzywotz Agnieszka , Kuhna Victoria , Koltowska-Häggström Maria , Müller Oliver , Buchfelder Michael , Kleist Bernadette
Published: October 2018

Background. Cushing’s disease (CD) and Cushing’s syndrome (CS) are chronic illnesses, characterized by symptoms of prolonged hypercortisolism, which often changes to hypocortisolism after successful treatment. In view of the high disease burden of CD/CS patients and long-term impaired quality of life, the present survey was conducted to gain information about subjective illness distress and patients’ specific needs in terms of supportive measures beyond medical interventions. Patients and Methods. Cross-sectional questionnaire study including patients with CD treated in 2 German neurosurgical tertiary referral centers and CD/CS patient members of a US-based patient support group completed a survey inquiring about disease burden, coping strategies, and support needs. Additionally, the degree of interest in different offers, e.g., internet-based programs and seminars, was assessed. Results. 84 US and 71 German patients answered the questionnaire. Patients in both countries indicated to suffer from Cushing-related symptoms, reduced performance, and psychological problems. 48.8% US patients and 44.4% German patients stated that good medical care and competent doctors helped them the most in coping with the illness. US patients were more interested in support groups (p=0.035) and in courses on illness coping (p=0.008) than the German patients, who stated to prefer brochures (p=0.001). 89.3% of US patients would attend internet-based programs compared to 75.4% of German patients (p=0.040). There were no differences between groups for the preferred duration of and the willingness to pay for such a program, but US patients would travel longer distances to attend a support meeting (p=0.027). Conclusion. Patients in both countries need skilled physicians and long-term medical care in dealing with the effects of CD/CS, whereas other support needs differ between patients of both countries. The latter implies that not only disease-specific but also culture-specific training programs would need to be considered to satisfy the needs of patients in different countries.
Evaluation of a Thermal-Based Flow Meter for Assessment of Mobile Resting Metabolic Rate Measures
Authors: Liu Nai-Yuan , Deng Yue , Tsow Francis , Bridgeman Devon , Xian Xiaojun , Dean Jane J. , Wilson Janet L. , Tao Nongjian , Kulick Doina , Forzani Erica
Published: October 2018

This work evaluates the use of a new flow meter to assess exhalation rate. A mobile indirect calorimeter (MIC) was designed and used to measure resting metabolic rate (RMR), which relies on the measure of O2 consumption rate (VO2) and CO2 production rate (VCO2). The device was produced from a commercially available and well-established indirect calorimeter and implemented with a new flow meter for the purpose of this study. VO2 and VCO2 were assessed by measuring exhalation rates using the new flow meter and O2 and CO2 concentrations in breath using the original colorimetric sensors of the indirect calorimeter. The new flow meter was based on a thermal flow meter (TFM) affixed to an orifice with a diameter of 6.8 mm used as a passage for exhaled breath from 16 subjects. The results were compared with a metabolic cart (Medical Graphics), which was connected in series to the modified device. We found that 69% of the results had more than a 10% difference between the modified MIC device and the reference instrument, suggesting that the sensitivity of the thermal flow meter changed over time, which precluded its use as a flow meter for breath flow rate measurement.
Zinc Deficiency and the Recurrence ofClostridium difficileInfection after Fecal Microbiota Transplant: A Retrospective Cohort Study
Authors: Niccum Blake A. , Stein Daniel J. , Behm Brian W. , Hays R. Ann
Published: October 2018

Background. Fecal microbiota transplant (FMT) is an effective therapy for recurrentClostridium difficileinfection (CDI). However, in 12% of patients treated with FMT, CDI recurs within one month. Zinc deficiency predicts increased diarrheal frequency in malnourished children, but little is known about its association with FMT outcome. We hypothesized that zinc levels were an independent predictor of CDI recurrence after FMT.Methods. We performed a retrospective cohort study of 80 patients (mean age, 66; 59 women) receiving FMT for CDI from 9/2013–9/2016 at a tertiary care center. Zinc levels were measured within 90 days before FMT. The primary outcome was CDI recurrence within 90 days after FMT. We controlled for risk factors for FMT failure using Cox regression. We also analyzed the effect of zinc supplementation in individuals with deficiency.Results. Forty-nine subjects had a normal zinc level, and 31 had a low level (<0.66 µg/mL). CDI recurred in 3/49 (6%) patients with normal zinc and 5/31 (16%) patients with low zinc (HR = 11.327, 95% CI = 2.162–59.336,p=0.004). Among low zinc subjects, 2 of 25 (8%) that received zinc supplements and 3 of 6 (50%) that did not receive zinc supplements had recurrence of CDI (HR = 0.102, 95% CI = 0.015–0.704,p=0.021).Conclusion. Zinc deficiency was associated with increased CDI recurrence after FMT. Among zinc-deficient patients, supplementation was associated with reduced recurrence. Further study is needed to determine whether zinc deficiency represents a pathophysiologic mechanism and target for therapy.
Bi-Level Programming Model of Cloud Manufacturing Services Based on Extension Theory
Authors: Zhao Jinhui , Zhou Yu
Published: October 2018

In order to select the proper cloud manufacturing services to satisfy both sides of supplier and demander, a bi-level programming model is proposed based on extension theory in this paper. Firstly, the cloud model is employed to convert qualitative concepts of language description into quantitative values. Then, according to multicriteria assessment information, the satisfactions of both providers and demanders are calculated by extension evaluation. Finally, respectively taking satisfactions of the demanders and providers as optimization goal of upper layer and lower layer, a mathematical model of bi-level programming is constructed which is solved by linear programming. Compared with traditional recommended methods, the proposed method takes full account of the interests of service providers which have long been neglected. Moreover, extension evaluation is applied to reflect the demand and preference of each subject in detail. Experimental results verify the effectiveness and applicability of the proposed model.
LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti–PD-1 Therapy against Brain Tumors
Authors: Eino Daisuke , Tsukada Yohei , Naito Hisamichi , Kanemura Yonehiro , Iba Tomohiro , Wakabayashi Taku , Muramatsu Fumitaka , Kidoya Hiroyasu , Arita Hideyuki , Kagawa Naoki , Fujimoto Yasunori , Takara Kazuhiro , Kishima Haruhiko , Takakura Nobuyuki
Published: October 2018

The structure and function of tumor blood vessels profoundly affects the tumor microenvironment. Signals mediated through the lysophosphatidic acid receptor 4 (LPA4) promote vascular network formation to restore normal vascular barrier function in subcutaneous tumors and thus improve drug delivery. However, the characteristics of the vasculature vary by organ and tumor types, and how drug delivery and leukocyte trafficking are affected by modification of vascular function by LPA in different cancers is unclear. Here, we show that LPA4 activation promotes the formation of fine vascular structures in brain tumors. RhoA/ROCK signaling contributed to LPA-induced endothelial cell–cell adhesion, and RhoA/ROCK activity following LPA4 stimulation regulated expression of VCAM-1. This resulted in increased lymphocyte infiltration into the tumor. LPA improved delivery of exogenous IgG into brain tumors and enhanced the anticancer effect of anti–programmed cell death-1 antibody therapy. These results indicate the effects of LPA on vascular structure and function apply not only to chemotherapy but also to immunotherapy.

Significance:

These findings demonstrate that lysophosphatidic acid, a lipid mediator, promotes development of a fine capillary network in brain tumors by inducing tightening of endothelial cell-to-cell adhesion, facilitating improved drug delivery, and lymphocyte penetration.
PRMT5 Circular RNA Promotes Metastasis of Urothelial Carcinoma of the Bladder through Sponging miR-30c to Induce Epithelial–Mesenchymal Transition
Authors: Chen Xin , Chen Ri-Xin , Wei Wen-Su , Li Yong-Hong , Feng Zi-Hao , Tan Lei , Chen Jie-Wei , Yuan Gang-Jun , Chen Si-Liang , Guo Sheng-Jie , Xiao Kang-Hua , Liu Zhuo-Wei , Luo Jun-Hang , Zhou Fang-Jian , Xie Dan
Published: October 2018

Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial–mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells’ EMT and explored their regulatory mechanisms and clinical significance in UCBs.

Experimental Design: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells’ EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA).

Results: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis.

Conclusions: CircPRMT5 exerts critical roles in promoting UCB cells’ EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.
The Relationship between the Fetal Volume-Corrected Renal Artery Pulsatility Index and Amniotic Fluid Volume
Authors: Seravalli Viola , Miller Jena L. , Block-Abraham Dana , McShane Cyrethia , Millard Sarah , Baschat Ahmet
Published: October 2018

Introduction: To evaluate if the volume-corrected renal artery pulsatility index (vcRA-PI) is more closely related to the amniotic fluid level than the uncorrected or the gestational age (GA)-adjusted RA-PI. Methods: RA-PI and kidney volume were measured in low- and high-risk pregnancies at 17–38 weeks. Fetal anomalies associated with nonrenal causes of abnormal amniotic fluid volume were excluded. The vcRA-PI was calculated by dividing the RA-PI by the renal volume. The RA-PI was adjusted for GA, to obtain the GA-adjusted RA-PI. The uncorrected, GA-adjusted, and the vcRA-PI were related to the amniotic fluid level using nonparametric tests and receiver operating characteristic (ROC) curve analyses. Results: 146 examinations from 59 pregnancies were reviewed. Of these, 16 had oligo- and 15 had polyhydramnios. A higher vcRA-PI was associated with oligohydramnios (OR 2.54, 95% CI 1.67–3.86, p < 0.001), while the uncorrected RA-PI and GA-adjusted RA-PI were not able to predict oligohydramnios. ROC curve analysis showed a high predictive accuracy of the vcRA-PI for oligohydramnios (AUC 0.84, 95% CI 0.72–0.94). On the other hand, the uncorrected RA-PI and GA-adjusted RA-PI significantly predicted polyhydramnios (p = 0.04 and 0.02, respectively), while the vcRA-PI did not. Conclusion: The vcRA-PI is superior to the uncorrected and the GA-adjusted RA-PI in predicting oligohydramnios.
Can Fetal Umbilical Venous Blood Be a Reliable Source for Admission Complete Blood Count and Culture in NICU Patients?
Authors: Greer Rocky , Safarulla Azif , Koeppel Robin , Aslam Muhammad , Bany-Mohammed Fayez M.
Published: October 2018

Background: Minimizing initial neonatal blood draws and their associated pain is important. The placenta has ample fetal blood that is otherwise discarded; obtaining admission laboratory evaluations from fetal umbilical venous blood (FUVB) may provide a suitable alternative. Objective: We hypothesized that obtaining an aerobic bacterial blood culture (BCX) and a complete blood count with manual differential (CBC/diff) from FUVB is feasible and yields results comparable to those obtained directly from the neonate. Study Design: BCX and CBC/diff were attempted on paired samples from FUVB (in the delivery room) and neonatal blood (shortly after NICU admission) of 110 patients. The paired t test, Pearson’s correlation coefficient (R), and multivariable linear regression were used for data analysis. Results: Positive BCXs were found in 9 of 108 FUVB samples compared to 1 of 91 neonatal samples. Three out of 9 FUVB cultures were true pathogens, including 2 Escherichia coli and 1 viridans group streptococcus, all with negative corresponding paired neonatal cultures. There was 1 positive neonatal BCX, E. coli, with a negative paired FUVB culture. Neonatal hemoglobin (Hb), platelets (PLT), and white blood cells (WBC) all significantly (p < 0.0001) correlated with the paired FUVB samples (R = 0.50, 0.49, and 0.84, respectively). Hb, PLT, and WBC values were clinically comparable but statistically higher in neonatal blood (the differences were 2.3 g/dL, 30,000 cells/μL, and 2,800 cells/μL, respectively; p < 0.007 for all comparisons). Conclusions: FUVB is suitable for obtaining CBC/diff. FUVB is an appropriate second source for BCX as it yields additional true pathogens. Our findings may support the presence of “culture-negative sepsis” in some neonates.
Onset of Retinal Pigment Epithelium Atrophy Subsequent to Anti-VEGF Therapy in Patients with Neovascular Age-Related Macular Degeneration
Authors: Sitnilska Vasilena , Altay Lebriz , Enders Philip , Hermann Manuel , Muether Philipp S. , Fauser Sascha
Published: October 2018

Purpose: The aim of this study was to evaluate risk factors for the development of retinal pigment epithelium (RPE) atrophy in patients with neovascular age-related macular degeneration (nAMD). Procedures: This post hoc analysis of the prospective RESPONSE study includes 52 therapy-naive nAMD patients without baseline RPE atrophy, who were treated with ≥9 anti-vascular endothelial growth factor (VEGF) injections for ≥3 years. RPE atrophy was assessed via multimodal imaging. Baseline aqueous VEGF and serum complement levels (C3d/C3) were measured. Risk factors for atrophy development were evaluated via logistic regression analysis. Results: Atrophy onset was significantly associated with the duration of nAMD (mean 5.34 years; odds ratio = 1.83, p = 0.012). Anti-VEGF injection number, age, C3d/C3 ratio, baseline intraocular VEGF, or delay to the first treatment had no influence on RPE atrophy. Conclusions: The duration of treatment-requiring nAMD was identified as primary risk factor for the onset of concomitant RPE atrophy after commencing therapy. Targeting concomitant atrophy in nAMD patients might improve the long-term prognosis of the disease.
Nintedanib for Advanced Epithelial Ovarian Cancer: A Change of Perspective? Summary of Evidence from a Systematic Review
Authors: Barra Fabio , Laganà Antonio Simone , Ghezzi Fabio , Casarin Jvan , Ferrero Simone
Published: October 2018

Background/Aims: Epithelial ovarian cancer (EOC) is the sixth most commonly diagnosed cancer among women. Results with available therapies are far from being satisfactory and, therefore, current research is focusing on new anticancer drugs to improve the clinical response of these patients. Nintedanib is an oral multiple tyrosine kinases inhibitor, which targets angiogenesis. Considering the current scenario, the aim of this systematic review is to highlight the prevailing knowledge about pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of Nintedanib for the treatment of advanced EOC. Methods: We performed a systematic review of the literature, screening all available articles about the treatment of advanced EOC with Nintedanib, including phase I, II, and III trials. Results: Although in early phase clinical trials, Nintedanib has demonstrated anticancer activity and tolerability as monotherapy or in combination with carboplatin and paclitaxel. In the phase III trial AGO-OVAR 12, it obtained a modest improvement in progression-free survival (PFS) as first-line combination therapy for patients with advanced EOC. Interestingly, a PFS increase was observed in patients with non-high progression risk or low tumor burden. Conclusion: Despite the promising results, further studies are needed to evaluate Nintedanib efficacy in women affected by EOC.
Pregnancy Outcomes of Patients Exposed to Adalimumab in Japan
Authors: Kawai Yumi , Tsuchiya Tsuyoshi , Aoki Shigeru
Published: October 2018

Background: This is the first retrospective report of pregnancy outcomes after exposure to adalimumab treatment in Japan. Methods: Using the AbbVie safety database, we analyzed pregnancy outcome data from patients who received adalimumab treatment from April 16, 2008, to May 15, 2017. Results: Data were extracted retrospectively for 74 pregnancies in 73 patients. More than half of the patients included in the study received adalimumab for the treatment of Crohn’s disease (37.8%) or ulcerative colitis (20.3%), while 9.5% received adalimumab for rheumatoid arthritis. Of the 53 pregnancies with available outcome data, 45 newborns (45/53 [84.9%]) were delivered. Of these births, 30 were full-term, 2 were preterm, and 13 were unknown. Apgar scores were available for 11 of the 16 newborns whose mothers were exposed to adalimumab in the third trimester; all scores were within the normal range. Low birth weight was observed in 5 infants out of the 30 full-term deliveries. There were also 5 miscarriages (5/53 [9.4%]), 2 induced abortions (2/53 [3.8%]), and 1 stillbirth (1/53 [1.9%]). Eight maternal adverse events were observed in 5 pregnancies; no serious adverse events occurred. Conclusion: Although safety concerns were inconclusive, these data do not report additional risk to pregnancy outcomes with adalimumab exposure.
Arrhythmogenic Remodeling of the Left Ventricle in a Porcine Model of Repaired Tetralogy of Fallot
Authors: Dubes Virginie , Benoist David , Roubertie François , Gilbert Stephen H. , Constantin Marion , Charron Sabine , Elbes Delphine , Vieillot Delphine , Quesson Bruno , Cochet Hubert , Haïssaguerre Michel , Rooryck Caroline , Bordachar Pierre , Thambo Jean-Benoit , Bernus Olivier
Published: October 2018

Background:

Ventricular arrhythmias are frequent in patients with repaired tetralogy of Fallot (rTOF), but their origin and underlying mechanisms remain unclear. In this study, the involvement of left ventricular (LV) electrical and structural remodeling was assessed in an animal model mimicking rTOF sequelae.

Methods:

Piglets underwent a tetralogy of Fallot repair–like surgery (n=6) or were sham operated (Sham, n=5). Twenty-three weeks post-surgery, cardiac function was assessed in vivo by magnetic resonance imaging. Electrophysiological properties were characterized by optical mapping. LV fibrosis and connexin-43 localization were assessed on histological sections and protein expression assessed by Western Blot.

Results:

Right ventricular dysfunction was evident, whereas LV function remained unaltered in rTOF pigs. Optical mapping showed longer action potential duration on the rTOF LV epicardium and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction in rTOF LVs but not in the transverse direction compared with Sham. An elevated collagen content was found in LV basal and apical sections from rTOF pigs. Moreover, a trend for connexin-43 lateralization with no change in protein expression was found in the LV of rTOFs. Finally, rTOF LVs had a lower threshold for arrhythmia induction using incremental pacing protocols.

Conclusions:

We found an arrhythmogenic substrate with prolonged heterogeneous action potential duration and reduced conduction velocity in the LV of rTOF pigs. This remodeling precedes LV dysfunction and is likely to contribute to ventricular arrhythmias and sudden cardiac death in patients with rTOF.
Common Coding Variants in
SCN10A
Are Associated With the Nav1.8 Late Current and Cardiac Conduction
Authors: Macri Vincenzo , Brody Jennifer A. , Arking Dan E. , Hucker William J. , Yin Xiaoyan , Lin Honghuang , Mills Robert W. , Sinner Moritz F. , Lubitz Steven A. , Liu Ching-Ti , Morrison Alanna C. , Alonso Alvaro , Li Ning , Fedorov Vadim V. , Janssen Paul M. , Bis Joshua C. , Heckbert Susan R. , Dolmatova Elena V. , Lumley Thomas , Sitlani Colleen M. , Cupples L. Adrienne , Pulit Sara L. , Newton-Cheh Christopher , Barnard John , Smith Jonathan D. , Van Wagoner David R. , Chung Mina K. , Vlahakes Gus J. , O’Donnell Christopher J. , Rotter Jerome I. , Margulies Kenneth B. , Morley Michael P. , Cappola Thomas P. , Benjamin Emelia J. , Muzny Donna , Gibbs Richard A. , Jackson Rebecca D. , Magnani Jared W. , Herndon Caroline N. , Rich Stephen S. , Psaty Bruce M. , Milan David J. , Boerwinkle Eric , Mohler Peter J. , Sotoodehnia Nona , Ellinor Patrick T. ,   Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) Sequencing Project, NHLBI Exome Sequencing Project†
Published: October 2018

Background:

Genetic variants at the
SCN5A
/
SCN10A
locus are strongly associated with electrocardiographic PR and QRS intervals. While
SCN5A
is the canonical cardiac sodium channel gene, the role of
SCN10A
in cardiac conduction is less well characterized.

Methods:

We sequenced the
SCN10A
locus in 3699 European-ancestry individuals to identify variants associated with cardiac conduction, and replicated our findings in 21,000 individuals of European ancestry. We examined association with expression in human atrial tissue. We explored the biophysical effect of variation on channel function using cellular electrophysiology.

Results:

We identified 2 intronic single nucleotide polymorphisms in high linkage disequilibrium (
r
 
2
=0.86) with each other to be the strongest signals for PR (rs10428132, β=−4.74,
P
=1.52×10
−14
) and QRS intervals (rs6599251, QRS β=−0.73;
P
=1.2×10
−4
), respectively. Although these variants were not associated with
SCN5A
or
SCN10A
expression in human atrial tissue (n=490), they were in high linkage disequilibrium (
r
 
2
≥0.72) with a common
SCN10A
missense variant, rs6795970 (V1073A). In total, we identified 7 missense variants, 4 of which (I962V, P1045T, V1073A, and L1092P) were associated with cardiac conduction. These 4 missense variants cluster in the cytoplasmic linker of the second and third domains of the SCN10A protein and together form 6 common haplotypes. Using cellular electrophysiology, we found that haplotypes associated with shorter PR intervals had a significantly larger percentage of late current compared with wild-type (I962V+V1073A+L1092P, 20.2±3.3%,
P
=0.03, and I962V+V1073A, 22.4±0.8%,
P
=0.0004 versus wild-type 11.7±1.6%), and the haplotype associated with the longest PR interval had a significantly smaller late current percentage (P1045T, 6.4±1.2%,
P
=0.03).

Conclusions:

Our findings suggest an association between genetic variation in
SCN10A
, the late sodium current, and alterations in cardiac conduction.
Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology
Authors: Lovering Ruth C. , Roncaglia Paola , Howe Douglas G. , Laulederkind Stanley J.F. , Khodiyar Varsha K. , Berardini Tanya Z. , Tweedie Susan , Foulger Rebecca E. , Osumi-Sutherland David , Campbell Nancy H. , Huntley Rachael P. , Talmud Philippa J. , Blake Judith A. , Breckenridge Ross , Riley Paul R. , Lambiase Pier D. , Elliott Perry M. , Clapp Lucie , Tinker Andrew , Hill David P.
Published: October 2018

Background:

A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products.

Methods and Results:

In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci.

Conclusions:

We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects.
High Salt Enhances Reactive Oxygen Species and Angiotensin II Contractions of Glomerular Afferent Arterioles From Mice With Reduced Renal Mass
Authors: Li Lingli , Lai En Yin , Luo Zaiming , Solis Glenn , Mendonca Margarida , Griendling Kathy K. , Wellstein Anton , Welch William J. , Wilcox Christopher S.
Published: October 2018

High salt, Ang II (angiotensin II), and reactive oxygen species enhance progression of chronic kidney disease. We tested the hypothesis that a high salt intake generates specific reactive oxygen species to enhance Ang II contractions of afferent arterioles from mice with reduced renal mass (RRM). C57BL/6 mice were subjected to surgical RRM or sham operations and received 6% or 0.4% NaCl salt diet for 3 months. Ang II contractions were measured in perfused afferent arterioles and superoxide (O
2
−
) and hydrogen peroxide (H
2
O
2
) by fluorescence microscopy. RRM enhanced the afferent arteriolar gene expression for p47
phox
and neutrophil oxidase (NOX) 2 and high salt intake in RRM mice enhanced gene expression for angiotensin type 1 receptors, POLDIP2 and NOX4 and reduced catalase. High salt in mice with RRM enhanced arteriolar O
2
−
and H
2
O
2
generation and maximal contractions to Ang II (10
–6
mol/L) that were dependent on O
2
−
because they were prevented by gene deletion of p47
phox
and on H
2
O
2
because they were prevented by transgenic smooth muscle cell expression of catalase (tg
CAT-SMC
) and
POLDIP2
gene deletion. Three months of tempol normalized arteriolar reactive oxygen species and Ang II contractions. However, arteriolar contractions to lower concentrations of Ang II (10
–8
to 10
–11
mol/L) were paradoxically inhibited by H
2
O
2
and POLDIP2. In conclusion, both O
2
−
from p47
phox
/NOX2 and H
2
O
2
from NOX4/POLDIP2 enhance maximal arteriolar Ang II contractions from RRM mice during high salt, but H
2
O
2
and NOX4/POLDIP2 reduce the sensitivity to lower concentrations of Ang II by >100-fold. Tempol prevents all of these changes in function.
GEÇİCİ GÖÇMENLİKTEN YERLEŞİKLİĞE : YÜKSEKÖĞRETİM GENÇLİĞİNİN GELECEKTEKİ GÖÇ POTANSİYELLERİ
Authors: ESGİN GÜNDER Esma
Published: October 2018

Toplumun yeniden yapılandırılması açısından göç olgusu
önemli bir role sahiptir. Göç, ekonomik, sosyal, kültürel ve politik bazı
değişikliklere yol açabileceği gibi aynı zamanda bu tür değişiklerden de
kaynaklanabilmektedir. Bu nedenle göç olgusu, temelinde yatan nedenleri ve
sonuçlarıyla birlikte sosyo-kültürel bir değişim aracı olarak
değerlendirilebilir. Günümüzde özellikle küreselleşme çerçevesinde bireylerin
gerek ulusal gerekse uluslararası hareketliliği bilişim teknolojileri
aracılığıyla bilginin akışıyla birlikte ele alınmaktadır.

Bu çalışmada göç ve eğitim ilişkisi bağlamında,
üniversite eğitimi alma amacıyla yaşadıkları şehirlerden öğrenim gördükleri
şehre “geçici” göç eden yükseköğretim öğrencilerinin göçe yönelik algıları ve
gelecekteki göç potansiyelleri irdelenmiştir. Bu amaçla çalışmada
nitel araştırma desenlerinden “olgu
bilim (fenomenoloji) deseni” kullanılmıştır. Çalışma grubunu, 2017-2018
öğretim yılı bahar döneminde Manisa Celal Bayar Üniversitesi Salihli  M.Y.O. Çocuk Gelişimi Programı'nda öğrenim
gören otuz iki son sınıf öğrencisi oluşturmaktadır. Elde edilen bulgular
yükseköğretim gençliğinin gündelik hayatı değiştirme ve öğrenim görme amacıyla
gerçekleştirdiği geçici göç hareketliliğinin istihdam amacıyla da süreklilik
göstereceği yönündedir.
Mobilizing the “State Papers” of Empire: John Bruce, Early Modernity, and the Bureaucratic Archives of Britain
Authors: Siddique Asheesh Kapur
Published: October 2018

This article examines John Bruce’s vision of the bureaucratic archives of the British state and empire at the end of the eighteenth century. As Historiographer to the East India Company and Keeper of State Papers in the 1790s and early 1800s, Bruce used the archives of corporate and state government as sources of bureaucratic knowledge to justify and plan imperial and domestic policy. In this way, Bruce deployed a strategy of governance by the authority of “state papers,” rooted in early modern political practice, across imperial and domestic government. The demise of Bruce’s influence signaled the waning of this role of the archive as a technology of governance in Britain during the nineteenth century.
Reflections on the Critical Edition of the Hebrew Text of Ben Sira. Between Eclecticism and Pragmatism
Authors: Rey Jean-Sébastien
Published: October 2018

This article aims to confront and question the theoretical distinction between textual criticism and redaction criticism from a pragmatic perspective. In order to accomplish this goal, we will examine the Hebrew manuscripts of Ben Sira as a test case and a paradigmatic example. The following situations will be examined: cases of irreducible divergences between the Hebrew witnesses, scribal “mistakes,” doublets in MSS A and B, and the so-called Hebrew II.
Platystele apoloae (Orchidaceae: Pleurothallidinae), a new species from Southwestern Ecuador
Authors: ZAMBRANO ROMERO BOSCO JAVIER , SOLANO RODOLFO , CORNEJO XAVIER
Published: October 2018

Platystele apoloae, a new orchid species is here described and illustrated. It was discovered in semi-deciduous premontane forest from Southwestern Ecuador, in the Amotape-Huancabamba zone. Information about its distribution, habitat, phenology, and conservation status is provided. The new taxon is compared with P. carl-lueriana, P. catiensis, P. cornejoi, P. ovalifolia, P. pedicellaris and P. propinqua, species to which it is morphologically similar.
Didymodon obtusus (Bryophyta, Pottiaceae), a new species from Tibet, China
Authors: KOU JIN , FENG CHAO , SHAO XIAO-MING
Published: October 2018

A new moss species, Didymodon obtusus J. Kou, X.-M. Shao & C. Feng, is described and illustrated from Tibet, China. It differs most saliently from congeners by the combination of ovate-lanceolate to oblong-lanceolate and appressed leaves when dry, bistratose leaf lamina, obtuse leaf apex, 2–3-stratose leaf margins, percurrent costa, cross-section of the costa with 2–3 layers of guide cells and without ventral stereids, and smooth laminal cells. This species is compared with similar species and its ecology is discussed.
Intraseasonal Variability in a Cloud-Permitting Near-Global Equatorial Aquaplanet Model
Authors: Khairoutdinov Marat F. , Emanuel Kerry
Published: October 2018

Recent studies have suggested that the Madden–Julian oscillation is a result of an instability driven mainly by cloud–radiation feedbacks, similar in character to self-aggregation of convection in nonrotating, cloud-permitting simulations of radiative–convective equilibrium (RCE). Here we bolster that inference by simulating radiative–convective equilibrium states on a rotating sphere with constant sea surface temperature, using the cloud-permitting System for Atmospheric Modeling (SAM) with 20-km grid spacing and extending to walls at 46° latitude in each hemisphere. Mechanism-denial experiments reveal that cloud–radiation interaction is the quintessential driving mechanism of the simulated MJO-like disturbances, but wind-induced surface heat exchange (WISHE) feedbacks are the primary driver of its eastward propagation. WISHE may also explain the faster Kelvin-like modes in the simulations. These conclusions are supported by a linear stability analysis of RCE states on an equatorial beta plane.
Comprehensive Evaluation of the IFloodS Radar Rainfall Products for Hydrologic Applications
Authors: Seo Bong-Chul , Krajewski Witold F. , Quintero Felipe , ElSaadani Mohamed , Goska Radoslaw , Cunha Luciana K. , Dolan Brenda , Wolff David B. , Smith James A. , Rutledge Steven A. , Petersen Walter A.
Published: October 2018

This study describes the generation and testing of a reference rainfall product created from field campaign datasets collected during the NASA Global Precipitation Measurement (GPM) mission Ground Validation Iowa Flood Studies (IFloodS) experiment. The study evaluates ground-based radar rainfall (RR) products acquired during IFloodS in the context of building the reference rainfall product. The purpose of IFloodS was not only to attain a high-quality ground-based reference for the validation of satellite rainfall estimates but also to enhance understanding of flood-related rainfall processes and the predictability of flood forecasting. We assessed the six RR estimates (IFC, Q2, CSU-DP, NWS-DP, Stage IV, and Q2-Corrected) using data from rain gauge and disdrometer networks that were located in the broader field campaign area of central and northeastern Iowa. We performed the analyses with respect to time scales ranging from 1 h to the entire campaign period in order to compare the capabilities of each RR product and to characterize the error structure at scales that are frequently used in hydrologic applications. The evaluation results show that the Stage IV estimates perform superior to other estimates, demonstrating the need for gauge-based bias corrections of radar-only products. This correction should account for each product’s algorithm-dependent error structure that can be used to build unbiased rainfall products for the campaign reference. We characterized the statistical error structures (e.g., systematic and random components) of each RR estimate and used them for the generation of a campaign reference rainfall product. To assess the hydrologic utility of the reference product, we performed hydrologic simulations driven by the reference product over the Turkey River basin. The comparison of hydrologic simulation results demonstrates that the campaign reference product performs better than Stage IV in streamflow generation.
Improving Patient Experience of Care Providers in a Multispecialty Ambulatory Pediatrics Practice
Authors: Fustino Nicholas J. , Moore Paige , Viers Sandy , Cheyne Ken
Published: October 2018

Patient experience is positively associated with superior medical outcomes, clinical quality, patient safety measures, physician job satisfaction, doctor-patient communication, and patient compliance with treatment recommendations. A concrete pediatrics-focused methodology for improving patient experience in a multispecialty ambulatory setting has not been described, nor has the impact on practice outcomes been assessed. The primary aim of this study was to improve patient experience care provider scores at a single multiclinic children’s hospital in the Midwest to the 70th percentile in a 5-year period. The secondary aim sought to determine the impact of quality improvement efforts on practice growth, patient complaint rate, and provider/staff engagement. Patient experience was measured by returned Press-Ganey surveys. Interventions involved establishing infrastructure, promoting feedback and transparency, providing education, and transforming culture. Provider scores improved from the 19th to the 70th percentile within 5 years. Practice volume increased by 17.1%; patient complaint/grievance frequency decreased 33-fold; and provider/staff engagement did not appreciably change.