bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving accuracy and usability of growth charts: case study in Rwanda
Authors: Brown Suzana , McSharry Patrick
Published: January 2016

Objectives

We evaluate and compare manually collected paper records against electronic records for monitoring the weights of children under the age of 5.

Setting

Data were collected by 24 community health workers (CHWs) in 2 Rwandan communities, 1 urban and 1 rural.

Participants

The same CHWs collected paper and electronic records. Paper data contain weight and age for 320 boys and 380 girls. Electronic data contain weight and age for 922 girls and 886 boys. Electronic data were collected over 9 months; most of the data is cross-sectional, with about 330 children with time-series data. Both data sets are compared with the international standard provided by the WHO growth chart.

Primary and secondary outcome measures

The plan was to collect 2000 individual records for the electronic data set—we finally collected 1878 records. Paper data were collected by the same CHWs, but most data were fragmented and hard to read. We transcribed data only from children for whom we were able to obtain the date of birth, to determine the exact age at the time of measurement.

Results

Mean absolute error (MAE) and mean absolute percentage error (MAPE) provide a way to quantify the magnitude of the error in using a given model. Comparing a model, log(weight)=a+b log(age), shows that electronic records provide considerable improvements over paper records, with 40% reduction in both performance metrics. Electronic data improve performance over the WHO model by 10% in MAPE and 7% in MAE. Results are statistically significant using the Kolmogorov-Smirnov test at p<0.01.

Conclusions

This study demonstrates that using modern electronic tools for health data collection is allowing better tracking of health indicators. We have demonstrated that electronic records facilitate development of a country-specific model that is more accurate than the international standard provided by the WHO growth chart.
Bereavement by suicide as a risk factor for suicide attempt: a cross-sectional national UK-wide study of 3432 young bereaved adults
Authors: Pitman Alexandra L , Osborn David P J , Rantell Khadija , King Michael B
Published: January 2016

Objectives

US and UK suicide prevention strategies suggest that bereavement by the suicide of a relative or friend is a risk factor for suicide. However, evidence is lacking that the risk exceeds that of any sudden bereavement, is specific to suicide, or applies to peer suicide. We conducted the first controlled UK-wide study to test the hypothesis that young adults bereaved by suicide have an increased risk of suicidal ideation and suicide attempt compared with young adults bereaved by other sudden deaths.

Design

National cross-sectional study.

Setting

Staff and students at 37 UK higher educational institutions in 2010.

Participants

3432 eligible respondents aged 18–40 exposed to sudden bereavement of a friend or relative after the age of 10.

Exposures

Bereavement by suicide (n=614), by sudden unnatural causes (n=712) and by sudden natural causes (n=2106).

Primary outcome measures

Incident suicidal ideation and suicide attempt.

Findings

Adults bereaved by suicide had a higher probability of attempting suicide (adjusted OR (AOR)=1.65; 95% CI 1.12 to 2.42; p=0.012) than those bereaved by sudden natural causes. There was no such increased risk in adults bereaved by sudden unnatural causes. There were no group differences in probability of suicidal ideation. The effect of suicide bereavement was similar whether bereaved participants were blood-related to the deceased or not. The significant association between bereavement by suicide and suicide attempt became non-significant when adding perceived stigma (AOR=1.11; 95% CI 0.74 to 1.67; p=0.610). When compared with adults bereaved by sudden unnatural causes, those bereaved by suicide did not show significant differences in suicide attempt (AOR=1.48; 95% CI 0.94 to 2.33; p=0.089).

Conclusions

Bereavement by suicide is a specific risk factor for suicide attempt among young bereaved adults, whether related to the deceased or not. Suicide risk assessment of young adults should involve screening for a history of suicide in blood relatives, non-blood relatives and friends.
Preliminary experience with Precipitating Hydrophobic Injectable Liquid (PHIL) in treating cerebral AVMs
Authors: Samaniego Edgar A , Kalousek Vladimir , Abdo German , Ortega-Gutierrez Santiago
Published: January 2016

Objective

To describe our early experience in treating cerebral arteriovenous malformations (AVMs) with the new Precipitating Hydrophobic Injectable Liquid (PHIL) embolic material.

Materials and methods

Between June and August 2015 five patients with cerebral AVMs were treated at two tertiary university hospitals. PHIL was used as complementary treatment to Onyx liquid embolic material or as the sole endovascular treatment.

Results

Five patients (average age 39 years (range 19–73)) with ruptured plexiform AVMs were treated. The group included one patient with Spetzler–Martin grade II AVMs, three grade III, and one grade IV. One grade II and two grade III AVMs were cured. A total of nine pedicles were embolized with an average of two pedicles per session. There were no procedural complications. One patient had a seizure after embolization but a brain CT scan showed no hemorrhage.

Conclusions

PHIL is a new embolic agent that can be used for the treatment of cerebral AVMs.
Differential DNA methylation patterns of homeobox genes in proximal and distal colon epithelial cells
Authors: Barnicle Alan , Seoighe Cathal , Golden Aaron , Greally John M. , Egan Laurence J.
Published: January 2016

Region and cell-type specific differences in the molecular make up of colon epithelial cells have been reported. Those differences may underlie the region-specific characteristics of common colon epithelial diseases such as colorectal cancer and inflammatory bowel disease. DNA methylation is a cell-type specific epigenetic mark, essential for transcriptional regulation, silencing of repetitive DNA and genomic imprinting. Little is known about any region-specific variations in methylation patterns in human colon epithelial cells. Using purified epithelial cells and whole biopsies ( n = 19) from human subjects, we generated epigenome-wide DNA methylation data (using the HELP-tagging assay), comparing the methylation signatures of the proximal and distal colon. We identified a total of 125 differentially methylated sites (DMS) mapping to transcription start sites of protein-coding genes, most notably several members of the homeobox ( HOX) family of genes. Patterns of differential methylation were validated with MassArray EpiTYPER. We also examined DNA methylation in whole biopsies, applying a computational technique to deconvolve variation in methylation within cell types and variation in cell-type composition across biopsies. Including inferred epithelial proportions as a covariate in differential methylation analysis applied to the whole biopsies resulted in greater overlap with the results obtained from purified epithelial cells compared with when the covariate was not included. Results obtained from both approaches highlight region-specific methylation patterns of HOX genes in colonic epithelium. Regional variation in methylation patterns has implications for the study of diseases that exhibit regional expression patterns in the human colon, such as inflammatory bowel disease and colorectal cancer.
A Matheuristic Approach Combining Local Search and Mathematical Programming
Authors: Lagos Carolina , Guerrero Guillermo , Cabrera Enrique , Niklander Stefanie , Johnson Franklin , Paredes Fernando , Vega Jorge
Published: January 2016

A novel matheuristic approach is presented and tested on a well-known optimisation problem, namely, capacitated facility location problem (CFLP). The algorithm combines local search and mathematical programming. While the local search algorithm is used to select a subset of promising facilities, mathematical programming strategies are used to solve the subproblem to optimality. Proposed local search is influenced by instance-specific information such as installation cost and the distance between customers and facilities. The algorithm is tested on large instances of the CFLP, where neither local search nor mathematical programming is able to find good quality solutions within acceptable computational times. Our approach is shown to be a very competitive alternative to solve large-scale instances for the CFLP.
Adaptive Window Size-Based Medium Access Control Protocol for Cognitive Radio Wireless Sensor Networks
Authors: Prasad Joshi Gyanendra , Nam Seung Yeob , Kim Sung Won , Kim Byung-Seo
Published: January 2016

Many existing medium access control protocols for cognitive radio wireless sensor networks waste bandwidth and suffer from delay because of the fixed channel negotiation period in the common control channel. In this paper, we propose a medium access control protocol for cognitive radio wireless sensor networks that adjusts the channel negotiation period based on network density. We simulate the proposed approach and compare it to the performance of the fixed channel negotiation period based approaches. The results show that the proposed approach efficiently utilizes white spaces and increases the aggregated goodput.
Potential Diagnostic and Prognostic Biomarkers of Epigenetic Drift within the Cardiovascular Compartment
Authors: Wallace Robert G. , Twomey Laura C. , Custaud Marc-Antoine , Moyna Niall , Cummins Philip M. , Mangone Marco , Murphy Ronan P.
Published: January 2016

Biomarkers encompass a wide range of different measurable indicators, representing a tangible link to physiological changes occurring within the body. Accessibility, sensitivity, and specificity are significant factors in biomarker suitability. New biomarkers continue to be discovered, and questions over appropriate selection and assessment of their usefulness remain. If traditional markers of inflammation are not sufficiently robust in their specificity, then perhaps alternative means of detection may provide more information. Epigenetic drift (epigenetic modifications as they occur as a direct function with age), and its ancillary elements, including platelets, secreted microvesicles (MVs), and microRNA (miRNA), may hold enormous predictive potential. The majority of epigenetic drift observed in blood is independent of variations in blood cell composition, addressing concerns affecting traditional blood-based biomarker efficacy. MVs are found in plasma and other biological fluids in healthy individuals. Altered MV/miRNA profiles may also be found in individuals with various diseases. Platelets are also highly reflective of physiological and lifestyle changes, making them extremely sensitive biomarkers of human health. Platelets release increased levels of MVs in response to various stimuli and under a plethora of disease states, which demonstrate a functional effect on other cell types.
The Impact of Lipoprotein‐Associated Oxidative Stress on Cell‐Specific Microvesicle Release in Patients with Familial Hypercholesterolemia
Authors: Nielsen M. H. , Irvine H. , Vedel S. , Raungaard B. , Beck-Nielsen H. , Handberg A.
Published: January 2016

Objective. Microvesicles (MVs) are small cell‐derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL‐C interaction with the CD36 receptor. To investigate the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs) may be markers of oxLDL‐C‐induced cell activation, cell‐specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile was studied. Approach and Results. Thirty FH patients with and without ATX and twenty‐three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs), erythrocytes (ErytMVs), monocytes (MMVs), and endothelial cells (EMVs), as well as tissue factor‐positive cells (TF+ MVs), were measured by flow cytometry. Total MVs, MMVs, EMVs, ErytMVs, and TF+ MVs were significantly increased in FH patients, compared to controls. CD36+ MVs derived from endothelial cells and monocytes were significantly higher in FH patients and oxLDL‐C predicted all the investigated cell‐specific CD36+ MVs in FH patients with ATX. Conclusions. MVs derived from cells involved in atherosclerosis were increased in FH and may contribute to elevated atherothrombosis risk. The increased cell‐specific CD36+ MVs observed in FH may represent markers of oxLDL‐C‐induced cell activation.
Uncertain Zero-One Law and Convergence of Uncertain Sequence
Authors: Zhang Zhiqiang , Liu Weiqi , Chen Xiumei
Published: January 2016

This paper is concerned with situations in which the uncertain measure of an event can only be zero or one, and the uncertain zero-one laws are derived within the framework of uncertainty theory that can be seen as the counterpart of Kolmogorov zero-one law and Borel-Cantelli lemma, which can be used as a tool for solving some problems concerning almost sure convergence of uncertain sequence.
Hamilton-Souplet-Zhang’s Gradient Estimates for Two Types of Nonlinear Parabolic Equations under the Ricci Flow
Authors: Huang Guangyue , Ma Bingqing
Published: January 2016

We consider gradient estimates for two types of nonlinear parabolic equations under the Ricci flow: one is the equationut=Δu+aulog⁡u+buwitha,bbeing two real constants; the other isut=Δu+λuαwithλ,αbeing two real constants. By a suitable scaling for the above two equations, we obtain Hamilton-Souplet-Zhang-type gradient estimates.
Arc-Induced Long Period Fiber Gratings
Authors: Rego Gaspar
Published: January 2016

Long period fiber gratings produced by the electric arc technique have found an increasing interest by the scientific community due to their ease to fabricate, virtually enabling the inscription in any kind of fiber, low cost, and flexibility. In 2005 we have presented the first review on this subject. Since then, important achievements have been reached such as the identification of the mechanisms responsible for gratings formation, the type of symmetry, the conditions to increase fabrication reproducibility, and their inscription in the turning points with grating periods below 200 μm. Several interesting applications in the sensing area, including those sensors working in reflection, have been demonstrated and others are expected, namely, related to the monitoring of extreme temperatures, cryogenic and high temperatures, and high sensitivity refractometric sensors resulting from combining arc-induced gratings in the turning points and the deposition of thin films in the transition region. Therefore, due to its pertinence, in this paper we review the main achievements obtained concerning arc-induced long period fiber gratings, with special focus on the past ten years.
Antibacterial and Anti‐Inflammatory Activities of Physalis Alkekengi var. franchetii and Its Main Constituents
Authors: Shu Zunpeng , Xing Na , Wang Qiuhong , Li Xinli , Xu Bingqing , Li Zhenyu , Kuang Haixue
Published: January 2016

This study was designed to determine whether the 50% EtOH fraction from AB‐8 macroporous resin fractionation of a 70% EtOH extract of P. Alkekengi (50‐EFP) has antibacterial and/or anti‐inflammatory activity both in vivo and in vitro and to investigate the mechanism of 50‐EFP anti‐inflammatory activity. Additionally, this study sought to define the chemical composition of 50‐EFP. Results indicated that 50‐EFP showed significant antibacterial activity in vitro and efficacy in vivo. Moreover, 50‐EFP significantly reduced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF‐α), interleukin 1 (IL‐1), and interleukin 6 (IL‐6) production in lipopolysaccharide‐ (LPS‐) stimulated THP‐1 cells. Nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) (examined at the protein level) in THP‐1 cells were suppressed by 50‐EFP, which inhibited nuclear translocation of p65. Consistent with this anti‐inflammatory activity in vitro, 50‐EFP reduced inflammation in both animal models. Finally, seventeen compounds (8 physalins and 9 flavones) were isolated as major components of 50‐EFP. Our data demonstrate that 50‐EFP has antibacterial and anti‐inflammatory activities both in vitro and in vivo. The anti‐inflammatory effect appears to occur, at least in part, through the inhibition of nuclear translocation of p65. Moreover, physalins and flavones are probably the active components in 50‐EFP that exert antibacterial and anti‐inflammatory activities.
Endosialin and Associated Protein Expression in Soft Tissue Sarcomas: A Potential Target for Anti-Endosialin Therapeutic Strategies
Authors: O’Shannessy Daniel J. , Dai Hongyue , Mitchell Melissa , Huntsman Shane , Brantley Stephen , Fenstermacher David , Reed Damon R.
Published: January 2016

Endosialin (CD248, TEM-1) is expressed in pericytes, tumor vasculature, tumor fibroblasts, and some tumor cells, including sarcomas, with limited normal tissue expression, and appears to play a key role in tumor-stromal interactions, including angiogenesis. Monoclonal antibodies targeting endosialin have entered clinical trials, including soft tissue sarcomas. We evaluated a cohort of 94 soft tissue sarcoma samples to assess the correlation between gene expression and protein expression by immunohistochemistry for endosialin and PDGFR-β, a reported interacting protein, across available diagnoses. Correlations between the expression of endosialin and 13 other genes of interest were also examined. Within cohorts of soft tissue diagnoses assembled by tissue type (liposarcoma, leiomyosarcoma, undifferentiated sarcoma, and other), endosialin expression was significantly correlated with a better outcome. Endosialin expression was highest in liposarcomas and lowest in leiomyosarcomas. A robust correlation between protein and gene expression data for both endosialin and PDGFR-βwas observed. Endosialin expression positively correlated with PDGFR-βand heparin sulphate proteoglycan 2 and negatively correlated with carbonic anhydrase IX. Endosialin likely interacts with a network of extracellular and hypoxia activated proteins in sarcomas and other tumor types. Since expression does vary across histologic groups, endosialin may represent a selective target in soft tissue sarcomas.
Evaluation ofLATS1andLATS2Promoter Methylation with the Risk of Pterygium Formation
Authors: Najafi Maryam , Kordi-Tamandani Dor Mohammad , Arish Mohammad
Published: January 2016

Purpose. Pterygium is a serious eye problem in countries with high exposure to UV. However, despite numerous studies, the molecular etiology of pterygium is unclear. Recent studies have indicated thatLATS1andLATS2genes are involved in DDR signaling pathways against continuous UV exposure. Our aim was to evaluate theLATS1andLATS2promoter methylation with the risk of pterygium formation.Methods. We evaluated the promoter methylation status ofLATS1andLATS2using methylation-specific PCR technique. Also, mRNA expression ofLATS1andLATS2was assessed in 14 cases of pterygium and 14 normal specimens by real-time PCR.Results. Promoter methylation ofLATS1andLATS2was detected significantly between pterygium tissues and normal tissues [LATS1; OR = 4.9; 95% CI: 1.54 to 15.48,P=0.003;LATS2; OR = 7.1; 95% CI: 1.53 to 33.19,P=0.004]. The gene expression analysis showed a statistically significant difference between pterygium tissues and healthy controls for bothLATS1andLATS2(P<0.05).Conclusions. The data of this study is the first report regarding the effect of promoter methylation of theLATS1andLATS2in the pterygium. To confirm these data, doing further studies in various genetic populations with large sample sizes using advanced molecular techniques is proposed.
Transmit/Receive Spatial Smoothing with Improved Effective Array Aperture for Angle and Mutual Coupling Estimation in Bistatic MIMO Radar
Authors: Liu Haomiao , Yang Xiaojun , Wang Rong , Jin Wei , Jia Weimin
Published: January 2016

We proposed a transmit/receive spatial smoothing with improved effective aperture approach for angle and mutual coupling estimation in bistatic MIMO radar. Firstly, the noise in each channel is restrained, by exploiting its independency, in both the spatial domain and temporal domain. Then the augmented transmit and receive spatial smoothing matrices with improved effective aperture are obtained, by exploiting the Vandermonde structure of steering vector with uniform linear array. The DOD and DOA can be estimated by utilizing the unitary ESPRIT algorithm. Finally, the mutual coupling coefficients of both the transmitter and the receiver can be figured out with the estimated angles of DOD and DOA. Numerical examples are presented to verify the effectiveness of the proposed method.
Inhibition of DNA Topoisomerase Type IIα(TOP2A) by Mitoxantrone and Its Halogenated Derivatives: A Combined Density Functional and Molecular Docking Study
Authors: Abu Saleh Md. , Solayman Md. , Hoque Mohammad Mazharol , Khan Mohammad A. K. , Sarwar Mohammed G. , Halim Mohammad A.
Published: January 2016

In this study, mitoxantrone and its halogenated derivatives have been designed by density functional theory (DFT) to explore their structural and thermodynamical properties. The performance of these drugs was also evaluated to inhibit DNA topoisomerase type IIα(TOP2A) by molecular docking calculation. Noncovalent interactions play significant role in improving the performance of halogenated drugs. The combined quantum and molecular mechanics calculations revealed that CF3containing drug shows better preference in inhibiting the TOP2A compared to other modified drugs.
Dynamic Analysis of Impact Model of Slipping Tramcar Prevention Equipment Based on an Energy Absorber
Authors: Xu Guiyun , Hu Shuo , Zhang Xiaoguang , Zhu Jiazhou , Zheng Huipeng , Wang Hongxin
Published: January 2016

The protection equipment of slipping tramcar in inclined shaft is the important safety equipment to ensure safety production in mine transportation and equipment. The Slipping Tramcar Prevention Equipment is mainly composed of an intercepting door and a buffering system, in which an energy absorber is the key component. The braking dynamic model of the energy absorber is studied by establishing a Lagrange equation and simulating the braking progress by the software of Simulink. The braking simulation distances curves of the energy absorber are obtained under the different initial conditions of tramcar mass and velocity, which shows that the tramcar velocity and mass both have a significant influence on the braking distance. The analysis on variance and range is developed for further comparison on the two key factors implying that tramcar mass is of the most great importance. Moreover, a braking distance formula is built based on the analysis results. On the other hand, field experiments are conducted in Qishan Mine, and experiment results show that the maximum error between the braking distance formula value and the experiment value is 11.98%, and the minimum error is 2.72%. The experimental results are consistent with the theoretical results.
Laboratory Indicators of Aggrecan Turnover in Juvenile Idiopathic Arthritis
Authors: Winsz-Szczotka Katarzyna , Kuźnik-Trocha Kornelia , Komosińska-Vassev Katarzyna , Jura-Półtorak Agnieszka , Olczyk Krystyna
Published: January 2016

Objectives. Evaluation of chondroitin sulfate (CS), as an early marker of aggrecan degradation, and chondroitin sulfate 846 epitope (CS846), as a biomarker of CS synthesis, is an attempt at answering the question whether the therapy used in juvenile idiopathic arthritis (JIA) patients contributes to the normalization of biochemical changes in aggrecan.Methods and Results. Serum levels of CS and CS846 as well as catalase (CT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities in erythrocyte were assessed in patients before and after treatment. In the course of JIA, aggrecan metabolism is disturbed, which is reflected by a decrease (p<0.001) in CS serum level and an increase (p<0.05) in CS846 concentration. Furthermore, increased (p<0.001) activities of CT, SOD, and GPx in untreated JIA patients were recorded. The anti-inflammatory treatment resulted in the normalization of CS846 level and SOD and GPx activities. In untreated patients, we have revealed a significant correlation between serum CS and CS846, CT, CRP, ESR, MMP-3, and ADAMTS-4, respectively, as well as between CS846 and CT, GPx, CRP, ESR, and TGF-β1, respectively.Conclusion. The observed changes of CS and CS846 in JIA patients indicate a further need of the therapy continuation aimed at protecting a patient from a possible disability.
H∞Optimal Inversion Feedforward and Robust Feedback Based 2DOF Control Approach for High Speed-Precision Positioning Systems
Authors: Peng Chao , Han Chongwei , Zou Jianxiao , Zhang Guanghui
Published: January 2016

This paper proposed a novelH∞optimal inversion feedforward and robust feedback based two-freedom-of-freedom (2DOF) control approach to address the positioning error caused by system uncertainties in high speed-precision positioning system. To minimize theH∞norm of the positioning error in the presence of model uncertainty, a linear matrix inequality (LMI) synthesis approach for optimal inversion feedforward controller design is presented. The specification of position resolution, control width, robustness, and output signal magnitude imposed on the entire 2DOF control system are taken as optimization objectives of feedback controller design. The robust feedback controller design approach integrates with feedforward controller systematically and is obtained via LMI optimization. The proposed approach was illustrated through a simulation example of nanopositioning control in atomic force microscope (AFM); the experiment results demonstrated that the proposed 2DOF control approach not only achieves the performance specification but also could improve the positioning control performance compared withH∞mixed sensitivity feedback control and inversion-based 2DOF control.
Continuity Results and Error Bounds on Pseudomonotone Vector Variational Inequalities via Scalarization
Authors: Zuo Xin , Wei Hong-Zhi , Chen Chun-Rong
Published: January 2016

Continuity (both lower and upper semicontinuities) results of the Pareto/efficient solution mapping for a parametric vector variational inequality with a polyhedral constraint set are established via scalarization approaches, within the framework of strict pseudomonotonicity assumptions. As a direct application, the continuity of the solution mapping to a parametric weak Minty vector variational inequality is also discussed. Furthermore, error bounds for the weak vector variational inequality in terms of two known regularized gap functions are also obtained, under strong pseudomonotonicity assumptions.
Hybrid Dynamic MCML Style: A High Speed Dynamic MCML Style
Authors: Pandey Neeta , Garg Damini , Gupta Kirti , Choudhary Bharat
Published: January 2016

This paper proposes hybrid dynamic current mode logic (H-DyCML) as an alternative to existing dynamic CML (DyCML) style for digital circuit design in mixed-signal applications. H-DyCML introduces complementary pass transistors for implementation of logic functions. This allows reduction in the stacked source-coupled transistor pair levels in comparison to the existing DyCML style. The resulting reduction in transistor pair levels permits significant speed improvement. SPICE simulations using TSMC 180 nm and 90 nm CMOS technology parameters are carried out to verify the functionality and to identify their advantages. Some issues related to the compatibility of the complementary pass transistor logic have been investigated and the appropriate solutions have been proposed. The performance of the proposed H-DyCML gates is compared with the existing DyCML gates. The comparison confirms that proposed H-DyCML gates is faster than the existing DyCML gates.
Utility of Activated Glassy Carbon and Pencil Graphite Electrodes for Voltammetric Determination of Nalbuphine Hydrochloride in Pharmaceutical and Biological Fluids
Authors: Elqudaby Hoda M. , Hendawy Hassan A. M. , Souaya Eglal R. , Mohamed Gehad G. , Eldin Ghada M. G.
Published: January 2016

This work compares voltammetric response of nalbuphine hydrochloride (NP·HCl) at both activated glassy carbon and pencil graphite electrodes. The electrochemical oxidation of the drug was studied using cyclic voltammetry (CV), differential pulse voltammetry (DPV), and square wave voltammetry (SWV) techniques. For analytical purpose a well-resolved irreversible diffusion controlled voltammetric peak was established in Britton-Robinson (B-R) buffer solution of pH 6.00 using pencil graphite electrode (PGE). Using activated glassy carbon electrode (GCE) a well-resolved irreversible diffusion controlled voltammetric peak was obtained at pH 7.00 using the same buffer solution. According to the linear relationship between the peak current and NP·HCl concentration, DPV and SWV methods were developed for their quantitative determination in pharmaceutical and human biological fluids. The linear response was obtained in the range from1.6×10-5to1.5×10-4 mol L−1using PGE and from12.5×10-6to13.75×10-5 mol L−1using a GC electrode, respectively. Precision and accuracy of the developed method were checked by recovery studies.
Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer
Authors: Brown-Glaberman Ursa , Marron Marilyn , Chalasani Pavani , Livingston Robert , Iannone Maria , Specht Jennifer , Stopeck Alison T.
Published: January 2016

Introduction. Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients.Methods. In control subjects we evaluated plasma CAIX stability via commercially available ELISA. We then similarly quantified plasma CAIX levels in (1) locally advanced breast cancer (LABC) patients treated with neoadjuvant paclitaxel + sunitinib (T + S) followed by doxorubicin and cyclophosphamide (AC); (2) metastatic breast cancer (MBC) patients treated with systemic chemotherapy.Results. Plasma CAIX levels were stable at room temperature for at least 48 hours in control subjects. Mean baseline plasma CAIX levels were lower in controls compared to patients with LABC or MBC. In LABC, CAIX levels rose significantly in response to administration of antiangiogenic therapy (T + S) (p=0.02) but not AC (p=0.37). In patients with MBC treated without an antiangiogenic agent CAIX levels did not change with therapy.Conclusions. Our results suggest that CAIX may be an easily obtained, stable measure of tumor associated hypoxia as well as a useful pharmacodynamic biomarker for antiangiogenic therapy.
Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer
Authors: Clark Owen , Yen Katharine , Mellinghoff Ingo K.
Published: January 2016

IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) and concomitantly produce reduced NADPH from NADP+. Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. The mutant protein loses its normal enzymatic activity and gains a new ability to produce the “oncometabolite” R(-)-2-hydroxyglutarate (R-2-HG). R-2-HG competitively inhibits α-KG–dependent enzymes which play crucial roles in gene regulation and tissue homeostasis. Expression of mutant IDH impairs cellular differentiation in various cell lineages and promotes tumor development in cooperation with other cancer genes. First-generation inhibitors of mutant IDH have entered clinical trials, and have shown encouraging results in patients with IDH-mutant AML. This article summarizes recent progress in our understanding of the role of mutant IDH in tumorigenesis. Clin Cancer Res; 22(8); 1837–42. ©2016 AACR.
Comprehensive Transcriptome Profiling Reveals Multigene Signatures in Triple-Negative Breast Cancer
Authors: Liu Yi-Rong , Jiang Yi-Zhou , Xu Xiao-En , Hu Xin , Yu Ke-Da , Shao Zhi-Ming
Published: January 2016

Purpose: By integrating expression profiles of mRNAs and long noncoding RNAs (lncRNA), we tried to develop and validate novel multigene signatures to facilitate individualized treatment of triple-negative breast cancer (TNBC) patients.

Experimental Design: We analyzed 165 TNBC samples and 33 paired normal breast tissues using transcriptome microarrays. Tumor-specific mRNAs and lncRNAs were identified and correlated with patients' recurrence-free survival (RFS). Using Cox regression model, we built two multigene signatures incorporating mRNAs and lncRNAs. The prognostic and predictive accuracy of the signatures were tested in a training set of 165 TNBC patients and validated in other 101 TNBC patients.

Results: We successfully developed an mRNA and an integrated mRNA–lncRNA signature based on eight mRNAs and two lncRNAs. In the training set, patients in the high-risk group were more likely to suffer from recurrent disease than patients in the low-risk group in both signatures [HR, 10.00; 95% confidence interval (CI), 2.53–39.47, P = 0.001; HR = 4.46, 95% CI, 1.34–14.91, P = 0.015 for integrated signature and mRNA signature, respectively). Results were validated in the validation set (P = 0.019 and 0.030, respectively). In addition, time-dependent receiver operating curve showed that the integrated mRNA–lncRNA signature had a better prognostic value than both the eight-mRNA-only signature and the clinicopathologic risk factors in both sets. We also found through interaction analysis that patients classified into the low-risk group by the integrated mRNA–lncRNA signature had a more favorable response to adjuvant taxane chemotherapy.

Conclusions: The multigene signature we developed can accurately predict clinical outcome and benefit of taxane chemotherapy in TNBC patients. Clin Cancer Res; 22(7); 1653–62. ©2016 AACR.
Effect of Single Intravitreal Bevacizumab on Ophthalmic and Middle Cerebral Arterial Blood Flow in Retinopathy of Prematurity
Authors: Gunay Murat , Tuten Abdulhamit , Sancak Selim , Celik Gokhan , Bardak Handan , Dincer Emre , Karatekin Guner , Erdogan Gurkan , Bardak Yavuz
Published: January 2016

Purpose: To evaluate the effect of a single intravitreal bevacizumab (IVB) injection on blood flow parameters in the ophthalmic artery (OA) and middle cerebral artery (MCA) in infants with retinopathy of prematurity (ROP). Materials and Methods: This prospective and interventional study included 15 infants with ROP who were treated with IVB. Peak systolic velocity (PSV), end-diastolic velocity, mean velocity (MV) and resistivity index were measured using pulse wave Doppler ultrasonography (Philips En Visor C, Amsterdam, The Netherlands) in the OA and MCA, before IVB injection and 1 day, 1 week and 1 month after IVB injection. Results: Measurements of PSV-OA, MV-OA and PSV-MCA showed significant changes after IVB treatment (p = 0.01, p = 0.02, p = 0.02, respectively). The PSV-OA measurements at 1 week and 1 month were significantly lower than the baseline PSV-OA measurement (p = 0.03 and p = 0.01, respectively). The MV-OA measurement was significantly lower at 1 month following IVB as compared to the baseline MV-OA measurement (p = 0.03). The PSV-MCA showed a significant decline 1 day after IVB injection (p = 0.03). Conclusions: The study demonstrated that IVB causes significant alterations in blood flow parameters in the OA and MCA predicted by Doppler ultrasonography in infants with ROP.
Care Transitions After Acute Myocardial Infarction for Transferred-In Versus Direct-Arrival Patients
Authors: Vora Amit N. , Peterson Eric D. , Hellkamp Anne S. , Sutton Nadia R. , Panacek Edward , Thomas Laine , de Lemos James A. , Wang Tracy Y.
Published: January 2016

Background—

Many patients in the United States require transfer from one hospital to another for acute myocardial infarction (MI) care. How well these transferred-in patients are transitioned back to their local community is unknown.

Methods and Results—

We used linked Medicare claims data to examine postdischarge outcomes of 39 136 patients with acute MI aged ≥65 years discharged alive from 451 US hospitals in Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines. Multivariable Cox modeling was used to compare the likelihood of outpatient clinic follow-up and risks of all-cause mortality and all-cause or cardiovascular readmission at 30 days post MI between transferred-in and direct-arrival patients. From 2007 to 2010, 14 060 of 39 136 patients (36%) required interhospital transfer for acute MI care, traveling a median of 43 miles (interquartile range, 27–68 miles; 77.6 km [interquartile range, 48.2–122.6 km]). Compared with those arriving directly, transferred-in patients with MI were slightly younger (median age, 73 versus 74;
P
<0.01) but less likely to have previous MI, heart failure, and previous revascularization than direct-arrival patients. Relative to direct-arrival patients, those transferred-in had a lower likelihood of outpatient follow-up within 30 days post discharge (risk-adjusted incidence, 69.9% versus 78.2%; hazard ratio [HR], 0.90; 95% confidence interval, 0.87–0.92) and higher adjusted 30-day all-cause and cardiovascular readmission risks (14.5% versus 14.0%; HR
all-cause
, 1.08; 95% confidence interval, 1.01–1.15 and 9.5% versus 9.1%; HR
cardiovascular
, 1.13; 95% confidence interval, 1.04–1.22). In contrast, risk-adjusted 30-day mortality was similar between transferred-in and direct arrivals (1.6% versus 1.6%; HR, 1.05; 95% confidence interval, 0.86–1.27).

Conclusions—

Transferred-in patients with acute MI are less likely to have outpatient clinic follow-up within 30 days and more likely to be readmitted within the first 30 days post discharge compared with direct-arrival patients. These results indicate room for improvement in the safe and seamless transition of care for transferred patients with MI traveling back to their home environments.
Future of the PCI Readmission Metric
Authors: Wasfy Jason H. , Yeh Robert W.
Published: January 2016

Between 2013 and 2014, the Centers for Medicare and Medicaid Services and the National Cardiovascular Data Registry publically reported risk-adjusted 30-day readmission rates after percutaneous coronary intervention (PCI) as a pilot project. A key strength of this public reporting effort included risk adjustment with clinical rather than administrative data. Furthermore, because readmission after PCI is common, expensive, and preventable, this metric has substantial potential to improve quality and value in American cardiology care. Despite this, concerns about the metric exist. For example, few PCI readmissions are caused by procedural complications, limiting the extent to which improved procedural technique can reduce readmissions. Also, similar to other readmission measures, PCI readmission is associated with socioeconomic status and race. Accordingly, the metric may unfairly penalize hospitals that care for underserved patients. Perhaps in the context of these limitations, Centers for Medicare and Medicaid Services has not yet included PCI readmission among metrics that determine Medicare financial penalties. Nevertheless, provider organizations may still wish to focus on this metric to improve value for cardiology patients. PCI readmission is associated with low-risk chest discomfort and patient anxiety. Therefore, patient education, improved triage mechanisms, and improved care coordination offer opportunities to minimize PCI readmissions. Because PCI readmission is common and costly, reducing PCI readmission offers provider organizations a compelling target to improve the quality of care, and also performance in contracts involve shared financial risk.
SIRT3–AMP-Activated Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction
Authors: Lai Yen-Chun , Tabima Diana M. , Dube John J. , Hughan Kara S. , Vanderpool Rebecca R. , Goncharov Dmitry A. , St. Croix Claudette M. , Garcia-Ocaña Adolfo , Goncharova Elena A. , Tofovic Stevan P. , Mora Ana L. , Gladwin Mark T.
Published: January 2016

Background—

Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly recognized clinical complication of metabolic syndrome. No adequate animal model of PH-HFpEF is available, and no effective therapies have been identified to date. A recent study suggested that dietary nitrate improves insulin resistance in endothelial nitric oxide synthase null mice, and multiple studies have reported that both nitrate and its active metabolite, nitrite, have therapeutic activity in preclinical models of pulmonary hypertension.

Methods and Results—

To evaluate the efficacy and mechanism of nitrite in metabolic syndrome associated with PH-HFpEF, we developed a 2-hit PH-HFpEF model in rats with multiple features of metabolic syndrome attributable to double-leptin receptor defect (obese ZSF1) with the combined treatment of vascular endothelial growth factor receptor blocker SU5416. Chronic oral nitrite treatment improved hyperglycemia in obese ZSF1 rats by a process that requires skeletal muscle SIRT3-AMPK-GLUT4 signaling. The glucose-lowering effect of nitrite was abolished in SIRT3-deficient human skeletal muscle cells, and in SIRT3 knockout mice fed a high-fat diet, as well. Skeletal muscle biopsies from humans with metabolic syndrome after 12 weeks of oral sodium nitrite and nitrate treatment (IND#115926) displayed increased activation of SIRT3 and AMP-activated protein kinase. Finally, early treatments with nitrite and metformin at the time of SU5416 injection reduced pulmonary pressures and vascular remodeling in the PH-HFpEF model with robust activation of skeletal muscle SIRT3 and AMP-activated protein kinase.

Conclusions—

These studies validate a rodent model of metabolic syndrome and PH-HFpEF, suggesting a potential role of nitrite and metformin as a preventative treatment for this disease.
Cortical Venous Filling on Dynamic Computed Tomographic Angiography
Authors: van den Wijngaard Ido R. , Wermer Marieke J.H. , Boiten Jelis , Algra Ale , Holswilder Ghislaine , Meijer Frederick J.A. , Dippel Diederik W.J. , Velthuis Birgitta K. , Majoie Charles B.L.M. , van Walderveen Marianne A.A.
Published: January 2016

Background and Purpose—

Venous flow in the downstream territory of an occluded artery may influence patient prognosis after ischemic stroke. Our aim was to study cortical venous filling (CVF) in a time-resolved manner with dynamic computed tomographic angiography and to assess the relationship with clinical outcome.

Methods—

Patients with a proximal middle cerebral artery occlusion underwent noncontrast CT and whole-brain CT perfusion/dynamic CT angiography within 9 hours after stroke-onset. We defined poor outcome as a modified Rankin Scale score of ≥3. Association between the extent and velocity of CVF and poor outcome at 3 months was analyzed with Poisson-regression. Prognostic value of optimal CVF (maximum opacification of cortical veins) in addition to age, stroke severity, treatment, Alberta Stroke Program Early CT score, cerebral blood flow, and collateral status was assessed with logistic regression and summarized with the area under the curve.

Results—

Eighty-eight patients were included, with a mean age of 67 years. By combining the extent and velocity of optimal CVF, we observed a decreased risk of poor outcome in patients with good and fast optimal CVF, risk ratio of 0.5 (95% confidence interval, 0.3–0.7). Extent and velocity of optimal CVF had additional prognostic value (area under the curve, 0.88; 95% confidence interval, 0.77–0.98;
P
<0.02) compared with a model without CVF information.

Conclusions—

The combination of extent and velocity of optimal CVF, as assessed with dynamic CT angiography, is useful to identify patients with acute middle cerebral artery stroke at higher risk of poor clinical outcome at 3-month follow-up.

Clinical Trial Registration—

URL:
http://www.trialregister.nl/trialreg
and
http://www.clinicaltrials.gov
. Unique identifier: NTR1804 and NCT00880113, respectively.
The Sacrificial Life and Death of the Servant (Isaiah 52:13-53:12)
Authors: Blenkinsopp Joseph
Published: January 2016

The argument presented in this article is that the term ‘asham’ in Isa 53:10 refers to the sacrificial ritual of the guilt offering, that this reference is supported by indications throughout Isaiah 53, and that therefore the suffering and death of this Servant of the lord is to be understood as sacrificial by analogy with the ritual of the guilt or reparation offering in the book of Leviticus. This conclusion, much contested in contemporary scholarship, is supported by a survey of the reception of this text in the period prior to early Christianity.
From lingua franca to lingua sacra: The Scripturalization of Tobit in 4QTobe
Authors: Perrin Andrew B.
Published: January 2016

In light of the growing consensus that the book of Tobit was originally penned in Aramaic, the fragmentary Hebrew copy 4QTobe is a singularly unique literary artifact of Second Temple Judaism. While a cluster of other Aramaic works were read and received as authoritative literature by at least some Jews at this time (e.g., Daniel 2-7, the booklets of 1 Enoch, and Aramaic Levi Document), Tobit alone was translated from the common language of the ancient Near East into the traditional Israelite mother tongue. This study explores how the shift from Aramaic to Hebrew should inform our conception of the status and reception of Tobit in ancient Judaism. By virtue of the new linguistic overlay given to 4QTobe, this manuscript should be considered a literary edition in its own right, with an ostensibly higher level or different degree of authority than its Aramaic language counterparts.
Sex or power? The function of male displays in rhesus macaques
Authors: Milich Krista M. , Maestripieri Dario
Published: January 2016

Male behavioral displays (e.g., branch-shaking) are common across Anthropoidea, but their function remains unclear. We examined free-ranging rhesus macaques on Cayo Santiago, Puerto Rico, to test three major hypotheses for the function of male displays: (1) mate attraction, (2) mate guarding and (3) male–male dominance competition. Focal and ad libitum behavioural data were recorded for 21 adult males across 9 groups during the mating season. Display rates were calculated for each male in each context (i.e., agonistic, mating). In stable groups, males with high mating success displayed more during consortships than in other contexts and displays were more likely to follow than to precede copulation, whereas males in unstable groups were more likely to displays in agonistic contexts. These results suggest that mate guarding and male–male dominance competition are the primary functions of male display behaviours in rhesus macaques.