bluuebunny/crossref_metadata_2025 huggingface dataset:
A new approach to detecting gravitational waves via the coupling of gravity to the zero-point energy of the phonon modes of a superconductor
Authors: Inan Nader A.
Published: November 2017

The response of a superconductor to a gravitational wave is shown to obey a London-like constituent equation. The Cooper pairs are described by the Ginzburg–Landau free energy density embedded in curved spacetime. The lattice ions are modeled by quantum harmonic oscillators characterized by quasi-energy eigenvalues. This formulation is shown to predict a dynamical Casimir effect since the zero-point energy of the ionic lattice phonons is modulated by the gravitational wave. It is also shown that the response to a gravitational wave is far less for the Cooper pair density than for the ionic lattice. This predicts a “charge separation effect” which can be used to detect the passage of a gravitational wave.
Robustness versus evolvability analysis for regulatory feed-forward loops
Authors: Choudhury Debika , Agarwal Amit , Saini Supreet
Published: November 2017

From the definition, it appears that phenotypic robustness and evolvability of an organism are inversely related to each other. However, a number of studies exploring this question have found conflicting evidences in this regard. This question motivated the current work where we explore the relationship between robustness and evolvability. As a model system, we pick the Feed Forward Loops (FFLs), and develop a framework to characterize their performance in terms of their ability to resist changes to steady state expression (robustness), and their ability to evolve towards novel phenotypes (evolvability). We demonstrate that robustness and evolvability are positively correlated in some FFL topologies. We compare this against other small regulatory topologies, and show that the same trend does not hold among them. We postulate that the ability to positively link robustness and evolvability could be an additional reason for over-representation of FFLs in living organisms, as compared to other regulatory topologies.
A Numerical Approach Technique for Solving Generalized Delay Integro-Differential Equations with Functional Bounds by Means of Dickson Polynomials
Authors: Kürkçü Ömür Kıvanç , Aslan Ersin , Sezer Mehmet , İlhan Özgül
Published: November 2017

In this study, we have considered the linear classes of differential-(difference), integro-differential-(difference) and integral equations by constituting a generalized form, which contains proportional delay, difference, differentiable difference or delay. To solve the generalized form numerically, we use the efficient matrix technique based on Dickson polynomials with the parameter-[Formula: see text] along with the collocation points. We also encode the useful computer program for susceptibility of the technique. The residual error analysis is implemented by using the residual function. The consistency of the technique is analyzed. Also, the numerical results illustrated in tables and figures are compared.
Convergence of an Iteration of Fifth-Order Using Weaker Conditions on First Order Fréchet Derivative in Banach Spaces
Authors: Singh Sukhjit , Gupta Dharmendra Kumar , Singh Randhir , Singh Mehakpreet , Martinez Eulalia
Published: November 2017

The convergence analysis both local under weaker Argyros-type conditions and semilocal under [Formula: see text]-condition is established using first order Fréchet derivative for an iteration of fifth order in Banach spaces. This avoids derivatives of higher orders which are either difficult to compute or do not exist at times. The Lipchitz and the Hölder conditions are particular cases of the [Formula: see text]-condition. Examples can be constructed for which the Lipchitz and Hölder conditions fail but the [Formula: see text]-condition holds. Recurrence relations are used for the semilocal convergence analysis. Existence and uniqueness theorems and the error bounds for the solution are provided. Different examples are solved and convergence balls for each of them are obtained. These examples include Hammerstein-type integrals to demonstrate the applicability of our approach.
Formation of a Chern–Simons cylindrical wormhole during evolution of manifolds
Authors: Sepehri Alireza , Ghaffary Tooraj , Naimi Yaghoob , Ghaforyan Hossein , Ebrahimzadeh Majid
Published: November 2017

In this paper, the formation of cylindrical wormhole during evolution of manifolds is studied. It is shown that this type of wormholes may be produced at two stages and then disappeared very fast at the third stage. First, one [Formula: see text]-dimensional is formed by joining point-like manifolds. Then, this manifold is torn and two child manifolds plus one Chern–Simons manifold appeared. Our universe is born on one of the child manifolds and connected to the other one by Chern–Simons manifold. At the third stage, this Chern–Simons manifold-which plays the role of cylindrical wormhole, dissolves into universes and gives its energy to them and causes inflation. Thus, the Chern–Simons cylindrical wormhole is unstable and dissolves in our four-dimensional universes and another universe very fast.
New process to approach linear Fredholm integral equations defined on large interval
Authors: Lemita Samir , Guebbai Hamza
Published: November 2017

To tackle a linear Fredholm integral equation on great interval, two numerical processes are involved: discretization and iterative scheme. The conventional numerical process is discretize first then use an iterative scheme as Jacobi’s method to approach the solutions of the huge algebraic system. In this paper, we propose an alternative numerical process, we apply an iterative scheme based on construction of a generalization of the iterative scheme for Jacobi method which is adapted to the system of linear bounded operators, then we use Nyström method to discretize only the diagonal part of the system. The convergence analysis of this new method is proved and numerical tests developed show its effectiveness.
Complete rewriting system for the Schützenberger product of n groups
Authors: Çetinalp Esra Kırmızı , Karpuz Eylem Güzel , Çevik Ahmet Sinan
Published: November 2017

In this paper, we obtain a complete rewriting system for monoid presentation of Schützenberger product of [Formula: see text] groups, which is firstly defined in [G. M. S. Gomes, H. Sezinando and J. E. Pin, Presentations of the Schützenberger product of [Formula: see text] groups, Comm. Algebra 34(4) (2006) 1213–1235]. It gives an algorithm for getting normal form of elements and hence solving the word problem in this group.
A method for automatic tuning of flight simulator motion platforms
Authors: Jones Michael
Published: November 2017

When tuning motion platforms, subjective opinion is usually regarded as sufficient for most applications, as it should provide verification that no false cueing occurs. However, often systems are not configured to fully utilize the available motion for the desired purpose. This paper presents a new method to objectively tune simulation motion platforms. Enhanced usage of the available platform motion space is shown through an example of its application to a specific mission task. The difference in motion filter settings for two simulator platform geometries is shown. This displays the suitability of the platforms for completion of the two-axis lateral reposition task.
Sparse Time-Frequency Decomposition for Multiple Signals with Same Frequencies
Authors: Hou Thomas Y. , Shi Zuoqiang
Published: November 2017

In this paper, we consider multiple signals sharing the same instantaneous frequencies. This kind of data is very common in scientific and engineering problems. To take advantage of this special structure, we modify our data-driven time-frequency analysis by updating the instantaneous frequencies simultaneously. Moreover, based on the simultaneous sparsity approximation and the Fast Fourier Transform, we develop several efficient algorithms to solve this problem. Since the information of multiple signals is used, this method is very robust to the perturbation of noise and it is applicable to the general nonperiodic signals even with missing samples or outliers. Several synthetic and real signals are used to demonstrate the robustness of this method. The performances of this method seems quite promising.
Improving Energy Efficiency in Wireless Network-on-Chip Architectures
Authors: Catania Vincenzo , Mineo Andrea , Monteleone Salvatore , Palesi Maurizio , Patti Davide
Published: November 2017

Wireless Network-on-Chip (WiNoC) represents a promising emerging communication technology for addressing the scalability limitations of future manycore architectures. In a WiNoC, high-latency and power-hungry long-range multi-hop communications can be realized by performance- and energy-efficient single-hop wireless communications. However, the energy contribution of such wireless communication accounts for a significant fraction of the overall communication energy budget. This article presents a novel energy managing technique for WiNoC architectures aimed at improving the energy efficiency of the main elements of the wireless infrastructure, namely, radio-hubs. The rationale behind the proposed technique is based on selectively turning off, for the appropriate number of cycles, all the radio-hubs that are not involved in the current wireless communication. The proposed energy managing technique is assessed on several network configurations under different traffic scenarios both synthetic and extracted from the execution of real applications. The obtained results show that the application of the proposed technique allows up to 25% total communication energy saving without any impact on performance and with a negligible impact on the silicon area of the radio-hub.
Towards Efficient Framework for Time-Aware Spatial Keyword Queries on Road Networks
Authors: Zhao Jingwen , Gao Yunjun , Chen Gang , Chen Rui
Published: November 2017

The spatial keyword query takes as inputs a query location and a set of query keywords and returns the answer objects by considering both their spatial distances to the query location and textual similarity with the query keywords. However, temporal information plays an important role in the spatial keyword query (where there is, to our knowledge, no prior work considering temporal information of the objects), since objects are not always valid. For instance, visitors may plan their trips according to the opening hours of attractions. Moreover, in real-life applications, objects are located on a predefined road network, and the spatial proximity of two objects is measured by the shortest path distance or travelling time between them. In this article, we study the problem of
time-aware spatial keyword
(TSK)
query
, which assumes that objects are located on the road network, and finds the
k
objects satisfying users’ spatio-temporal description and textual constraint. We first present the pruning strategy and algorithm based on an existing index. Then, we design an efficient index structure called
TG index
and propose several algorithms using the TG index that can prune the search space with both spatio-temporal and textual information simultaneously. Further, we show that the TG index technique can also be applied to improve the performance of time-travel text search and spatial keyword query. Extensive experiments using both real and synthetic datasets demonstrate the effectiveness and efficiency of the presented index and algorithms.
New Insights into Graft-Versus-Host Disease and Graft Rejection
Authors: Perkey Eric , Maillard Ivan
Published: November 2017

Allogeneic transplantation of foreign organs or tissues has lifesaving potential, but can lead to serious complications. After solid organ transplantation, immune-mediated rejection mandates the use of prolonged global immunosuppression and limits the life span of transplanted allografts. After bone marrow transplantation, donor-derived immune cells can trigger life-threatening graft-versus-host disease. T cells are central mediators of alloimmune complications and the target of most existing therapeutic interventions. We review recent progress in identifying multiple cell types in addition to T cells and new molecular pathways that regulate pathogenic alloreactivity. Key discoveries include the cellular subsets that function as potential sources of alloantigens, the cross talk of innate lymphoid cells with damaged epithelia and with the recipient microbiome, the impact of the alarmin interleukin-33 on alloreactivity, and the role of Notch ligands expressed by fibroblastic stromal cells in alloimmunity. While refining our understanding of transplantation immunobiology, these findings identify new therapeutic targets and new areas of investigation.
Baseline Oxidative Stress Is Associated with Memory Changes in Omega-3 Fatty Acid Treated Coronary Artery Disease Patients
Authors: Mazereeuw Graham , Herrmann Nathan , Andreazza Ana C. , Scola Gustavo , Ma David W. L. , Oh Paul I. , Lanctôt Krista L.
Published: November 2017

Objective. This study investigated whether pretreatment oxidative stress, measured by lipid hydroperoxides (LPH), 4-hydroxy-2-nonenal (4-HNE), 8-isoprostane (8-ISO), and malondialdehyde (MDA), was associated with improvement in immediate recall among n-3 PUFA-treated coronary artery disease patients.Methods. This was a secondary analysis of the CAROTID trial (NCT00981383). Composite immediate recall, measured using the California Verbal Learning Test, Second Edition, and the Brief Visuospatial Memory Test-Revised, was assessed. LPH, 4-HNE, 8-ISO, MDA, and n-3 PUFA concentrations were analysed from fasting blood. Patients then received either n-3 PUFA treatment or placebo for 12 weeks, after which composite immediate recall was reassessed. Linear regression was used to investigate relationships between lipid peroxidation markers and changes in composite immediate recall in each treatment group.Results. Eighty-five patients (age =61.1±8.5, 77% male, mean years of education =15.3±3.4) were included (n=46placebo,n=39n-3 PUFA). After adjusting for multiple comparisons and potential confounders, greater baseline concentrations of LPH (β= 0.45,p=.002) and 4-HNE (β= 0.38,p=.005) were associated with greater improvement in composite immediate recall among n-3 PUFA-treated patients. No other associations were observed.Conclusions. N-3 PUFA treatment may be more likely to improve immediate recall in patients with greater oxidative stress.
Usefulness of Endoscopic Managements in Patients with Ceftriaxone-Induced Pseudolithiasis Causing Biliary Obstruction
Authors: Doi Yasuhiro , Takii Yasushi , Ito Hiroyuki , Jingu Norihiko , To Kentaro , Kimura Sinichiro , Kimura Koichi , Sanefuji Kensaku , Ikeda Hirofumi , Tachibana Sayaka , Otsuka Takeshi
Published: November 2017

Ceftriaxone (CTRX) is known to cause reversible biliary stones/sludge, which is called biliary pseudolithiasis. We report two rare cases of biliary obstruction by pseudolithiasis shortly after completing CTRX treatment. Stones and sludge, which had not been detected before CTRX administration, appeared in the gallbladder and common bile duct and led to biliary obstruction and acute cholangitis. The obstructions were successfully treated with endoscopic retrograde biliary drainage and endoscopic sphincterotomy. CTRX-induced biliary pseudolithiasis has been reported mainly in children and adolescents but is also seen in adults with similar incidence rate. Although CTRX-induced biliary pseudolithiasis is usually asymptomatic and disappears spontaneously after discontinuing the drug, some patients develop biliary obstruction. Endoscopic managements should be considered in such cases.
Stability Analysis Method of Parallel Inverter
Authors: Li Jun , Chen Jie , Xue Yaru , Qiu Ruichang , Liu Zhigang
Published: November 2017

In order to further provide theoretical support for the stability of an auxiliary inverter parallel system, a new model which covers most of control parameters needs to be established. However, the ability of the small‐signal model established by the traditional method is extremely limited, so this paper proposes a new small‐signal modeling method for the parallel system. The new small‐signal model not only can analyze the influence of the droop parameters on the system performance, but also can analyze the influence of the output impedance of the inverter, the unbalanced and nonlinear loads, and the power calculation method and cut‐off frequency of the low‐pass filter on the system performance and stability. Based on this method, this paper carries out a comprehensive analysis on the performance of a parallel inverter system. And the correctness of the modeling method and analysis process of the system performance and stability are verified by the consistency of the simulation and experimental results.
Integrating a 19F MRI Tracer Agent into the Clinical Scale Manufacturing of a T-Cell Immunotherapy
Authors: O’Hanlon Charles F. , Fedczyna Tamara , Eaker Shannon , Shingleton William D. , Helfer Brooke M.
Published: November 2017

Leukocyte immunotherapies have made great progress in the treatment of cancer. Recent reports on the treatment of B-cell malignancies using Chimeric Antigen Receptor and affinity enhanced T-Cell Receptor therapies have demonstrated encouraging clinical results. As investigators begin to explore the treatment of solid tumors with these cells, the hurdle of evaluating T-cell homing to and persistence at the site of disease remain. Significant challenges regarding the GMP manufacture and administration of a therapeutic dose of millions to billions of transduced T-cells remain. Here we report on the application of a clinically authorized 19F MRI tracer agent to human T-cells, employing state-of-the-art methods and equipment in the manufacture of a cellular therapy. Using a general T-cell expansion protocol and clinical scale industrial bioreactors, we show 19F labeling without detriment to the product +/− cryopreservation. While the incorporation of the 19F tracer is not trivial, it is just one of the many steps that can aid in progression of a therapeutic to and though the clinic. Combining the MRI tracking capabilities, safety profiles, and clinical sensitivity of this method, this application demonstrates the ability of 19F MRI to be used in industrial scale applications to visualize the spatial fate of cellular therapeutics.
Recent Advances in ADAM17 Research: A Promising Target for Cancer and Inflammation
Authors: Moss Marcia L. , Minond Dmitry
Published: November 2017

Since its discovery, ADAM17, also known as TNFαconverting enzyme or TACE, is now known to process over 80 different substrates. Many of these substrates are mediators of cancer and inflammation. The field of ADAM metalloproteinases is at a crossroad with many of the new potential therapeutic agents for ADAM17 advancing into the clinic. Researchers have now developed potential drugs for ADAM17 that are selective and do not have the side effects which were seen in earlier chemical entities that targeted this enzyme. ADAM17 inhibitors have broad therapeutic potential, with properties ranging from tumor immunosurveillance and overcoming drug and radiation resistance in cancer, as treatments for cardiac hypertrophy and inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis. This review focuses on substrates and inhibitors identified more recently for ADAM17 and their role in cancer and inflammation.
Pancreatic Ductal Adenocarcinoma Subtyping Using the Biomarkers Hepatocyte Nuclear Factor-1A and Cytokeratin-81 Correlates with Outcome and Treatment Response
Authors: Muckenhuber Alexander , Berger Anne Katrin , Schlitter Anna Melissa , Steiger Katja , Konukiewitz Björn , Trumpp Andreas , Eils Roland , Werner Jens , Friess Helmut , Esposito Irene , Klöppel Günter , Ceyhan Güralp O. , Jesinghaus Moritz , Denkert Carsten , Bahra Marcus , Stenzinger Albrecht , Sprick Martin R. , Jäger Dirk , Springfeld Christoph , Weichert Wilko
Published: November 2017

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with a dismal prognosis and poor therapeutic response to current chemotherapy regimens in unselected patient populations. Recently, it has been shown that PDAC may be stratified into functionally and therapeutically relevant molecular subgroups and that some of these subtypes can be recapitulated by IHC for KRT81 [quasi-mesenchymal (QM)/squamous/basal-like] and HNF1A (non-QM, overlap with exocrine/ADEX subtype).

Experimental Design: We validated the different outcome of the HNF1A/KRT81 PDAC subtypes in two independent cohorts of surgically treated patients and examined the treatment response to chemotherapy in a third cohort of unresectable patients. The first two cohorts included 262 and 130 patients, respectively, and the third independent cohort comprised advanced-stage PDAC patients who were treated with either FOLFIRINOX (64 patients) or gemcitabine (61 patients).

Results: In both cohorts with resected PDAC, the HNF1A-positive subtype showed the best, the KRT81-positive subtype the worst, and the double-negative subtype an intermediate survival (P < 0.013 and P < 0.009, respectively). In the chemotherapy cohort, the survival difference between the double-negative and the HNF1A-positive subtype was lost, whereas the dismal prognosis of KRT81-positive PDAC patients was retained (P < 0.021). Patients with a KRT81-positive subtype did not benefit from FOLFIRINOX therapy, whereas those with HNF1A-positive tumors responded better compared with gemcitabine-based treatment (P < 0.038).

Conclusions: IHC stratification recapitulating molecular subtypes of PDAC using HNF1A and KRT81 is associated with significantly different outcomes and responses to chemotherapy. These results may pave the way toward future pretherapeutic biomarker-based stratification of PDAC patients. Clin Cancer Res; 24(2); 351–9. ©2017 AACR.
Gamma Knife Stereotactic Radiosurgery for the Treatment of Primary and Metastatic Ocular Malignancies
Authors: Arnett Andrea L.H. , Reynolds Margaret M. , Pulido Jose S. , Parney Ian F. , Laack Nadia N.
Published: November 2017

Background: Gamma knife radiosurgery (GKR) can be used for precise targeting of malignant lesions of the CNS when brachytherapy is not an appropriate option. Objectives: This study reports treatment technique, efficacy, and radiation-induced adverse effects in patients with primary and metastatic ocular lesions treated with Leksell GKR. Methods: A retrospective, single-institution review was conducted of 28 patients with primary or metastatic ocular disease, treated from 2000 to 2014. The dose to margin was 17-27 Gy (maximum dose 28-54 Gy). Primary outcomes included overall survival (OS), local control, progression-free survival (PFS), and enucleation. Results: The median age at diagnosis was 70 years, and the median follow-up was 26.4 months. Of the 28 patients, 11 (39%) had metastatic ocular disease, and 17 (61%) were diagnosed with primary ocular melanoma (stage T2a-T4e). The average maximum dose and dose to margin were 41 and 21 Gy, respectively. The mean dose to the optic nerve was 12.6 Gy. The 5-year OS was 46% (95% CI: 23.6-68.4%) for the entire cohort; the 5-year PFS for M0 patients who presented with primary ocular melanoma lesions was 90% (95% CI: 71-100%). Only 1 patient required enucleation after radiation treatment. Conclusion: GKR is an effective option, with acceptable levels of toxicity, in the treatment of primary and metastatic ocular lesions.
Immunohistochemical Localization of Calbindin D28k, Parvalbumin, and Calretinin in the Superior Olivary Complex of Circling Mice
Authors: Lee Jin-Koo , Maskey Dhiraj , Kim Myeung Ju
Published: November 2017

The circling mouse serves as a hearing loss model. It has spontaneous tmie gene mutations that cause hair cell and cochlear degeneration. However, little is known about the role of the tmie gene in superior olivary complex (SOC) regions, in which sound information from the two ears is integrated and primarily relayed to the nuclei of the lateral lemniscus and inferior colliculus. Several studies have reported that abnormal calcium (Ca2+) homeostasis is associated with the pathology of hearing loss. This study investigated the distribution of Ca2+-binding proteins (CaBPs), such as calbindin D28k, parvalbumin, and calretinin, in the SOC of the circling mouse on postnatal day 16. A comparison of wild-type (+/+), heterozygous (+/cir), and homozygous (cir/cir) mice showed that CaBP immunoreactivity was significantly decreased in the auditory nucleus of the SOC of homozygous (cir/cir) mice. A decline in the CaBPs level in the SOC may be the result of hearing loss through hair cell and cochlear degeneration following tmie gene mutation.
Significant Hemorrhage Rate Reduction after Gamma Knife Radiosurgery in Symptomatic Cavernous Malformations: Long-Term Outcome in 95 Case Series and Literature Review
Authors: López-Serrano Remedios , Martínez Nuria E. , Kusak M. Elena , Quirós Alicia , Martínez Roberto
Published: November 2017

Background: The natural history of cavernous malformations (CMs) has remained unclear. This lack of knowledge has made treatment decisions difficult. Indeed, the use of stereotactic radiosurgery is nowadays controversial. The purpose of this paper is to throw light on the effectiveness of Gamma Knife radiosurgery (GKRS) therapy. Methods: The authors reviewed data collected from a prospectively maintained database. A total of 95 patients (57 female and 38 male) underwent GKRS for high-surgical-risk CMs. A total of 76 cavernomas were deeply located (64 lesions in the brainstem and 12 lesions in the thalamus). All of them were located in eloquent regions. The median malformation volume was 1,570 mm3. The median tumor margin dose was 11.87 Gy, and the mean tumor maximum dose was 19.56 Gy. Results: Ninety-five cavernous CMs were managed from 1994 to 2014. All patients had experienced at least 1 symptomatic bleeding incident before treatment (only 1 hemorrhage event in 81%). The median length of follow-up review was 78 months. The pretreatment annual hemorrhage rate was 3.06% compared with 1.4% during the first 3-year latency interval, and 0.16% thereafter (p = 0.004). Four patients developed new location-dependent neurological deficits, and 3 patients had edema-related headache after radiosurgery. All of them presented full recovery. Conclusions: The best dosage range for preventing bleeding was identified as between 11 and 12 Gy in our series. Although the efficacy of radiosurgery in CMs remains impossible to quantify, a very significant reduction in the bleeding rate occurs after a 3-year latency interval. No permanent neurological morbidity is reported in our series. These results defend the safety of GKRS in surgical high-risk CM from the first bleeding event.
A 20-Year Retrospective Review of Retinoblastoma at Two Tertiary Academic Hospitals in Johannesburg, South Africa
Authors: Goolam Saadiah , Kana Hemant , Welsh Nicky , Wainwright Linda , Poole Janet , Mayet Ismail
Published: November 2017

Aim: This paper presents a 20-year review of retinoblastoma in Johannesburg, South Africa, aiming to better characterize the disease in this sub-Saharan setting. Methods: The study represents a retrospective case series of retinoblastoma patients presenting to Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital between January 1, 1992, and December 31, 2011. Results: The total number of cases identified was 282, with 245 meeting the study inclusion criteria. Retinoblastoma comprised 6.9% of the total pediatric oncology presentations; 65.3% were unilateral, 34.3% bilateral, and 0.4% trilateral. The overall male-to-female ratio was 1.08. The mean age at presentation overall was 32.6 months (median 28.0), in the unilateral group 39.4 months (median 33.0), and in the bilateral group 19.7 months (median 17.0). The mean delay to presentation overall was 7.0 months (median 4.0). The most frequent presenting symptoms were leukocoria (37.1%) and proptosis (34.7%). The distribution of disease stages at presentation (International Retinoblastoma Staging System) was 1.6% stage 0, 24.1% stage I, 27.8% stage II, 16.3% stage III, and 25.3% stage IV. 26.5% defaulted care. The 5-year Kaplan-Meier survival estimate was 57.7% overall. Conclusion: This study shows that delayed presentation and refusal of therapy remains a significant barrier to effective treatment in this African setting.
Characteristics of False-Negative Thyroid Fine-Needle Aspirates
Authors: Renshaw Andrew A. , Gould Edwin W.
Published: November 2017

Introduction: False-negative thyroid fine-needle aspirates (FNA) are not well characterized. Methods: We correlated the results of all thyroid aspirations from 1997 to 2016 with histologic follow-up. Results: There were 13,733 aspirates, 2,112 (15.3%) resections, and 678 malignancies (32.1%). Eighteen (2.7%) false-negative cases were identified (interpretation, n = 6; sampling, n = 7; and new nodules, n = 5). Interpretive false-negative cases were significantly less likely when the indeterminate rate was greater than 13% (p = 0.01). Interpretive errors involved rare cells with poorly developed features of malignancy. Sampling errors were not associated with scant cellularity in the specimen. The majority of false-negative cases were not resected because of a clinical suspicion of malignancy. The sensitivity of FNA for 9-mm papillary carcinomas was 44.3%. Conclusion: In this cohort, the false-negative rate of thyroid FNA was 2.7% and the risk of malignancy for a benign diagnosis was 3.5%. Interpretative errors involved rare cells with poorly developed features of malignancy. There is little evidence that either the false-negative rate or the risk of malignancy of a benign thyroid FNA is different in patients who do and do not undergo resection.
Comparison of Helicobacter pylori Eradication Rates of 2-Week Levofloxacin-Containing Triple Therapy, Levofloxacin-Containing Bismuth Quadruple Therapy, and Standard Bismuth Quadruple Therapy as a First-Line Regimen
Authors: Kahramanoğlu Aksoy Evrim , Pirinçci Sapmaz Ferdane , Göktaş Zeynep , Uzman Metin , Nazlıgül Yaşar
Published: November 2017

Objective: The aim of this study was to compare the efficacy and safety of 2-week levofloxacin-containing triple therapy, levofloxacin-containing bismuth quadruple therapy, and standard bismuth-containing quadruple therapy as a first-line regimen for the eradication of Helicobacter pylori.Methods: A total of 329 patients with H. pylori infection were randomly divided into 3 groups to receive one of the following regimens: (a) levofloxacin-containing bismuth quadruple therapy, RBAL (rabeprazole 20 mg, b.i.d., bismuth subsalicylate 562 mg, b.i.d., amoxicillin 1 g, b.i.d, levofloxacin 500 mg, once daily), (b) standard bismuth quadruple therapy, RBMT (rabeprazole 20 mg, b.i.d, subsalicylate 562 mg, b.i.d., metronidazole 500 mg, t.i.d, tetracycline 500 mg, q.i.d), or (c) levofloxacin-containing triple therapy, RAL (rabeprazole 20 mg, b.i.d., amoxicillin 1 g, b.i.d, levofloxacin 500 mg, once daily). The primary outcome was the eradication rate in the intention-to-treat (ITT) and per protocol (PP) analysis. Results: The eradication rates of the above 3 groups using ITT analysis were RBAL 83.8%, RBMT 88.3%, and RAL 74.8% compared with 91.2, 92.5, and 79.2%, respectively, using PP analysis. The eradication rate using RBMT was significantly higher than that of RAL (p = 0.029 in ITT analysis and p = 0.017 in PP analysis). Several side effects occurred in 156 patients (54.1%) in the RBAL group, 215 (52.3%) in the RBMT group, and 56 (26.2%) in the RAL group (p > 0.05, RBAL vs. RBMT; p < 0.001, RBMT vs. RAL; p < 0.001, RBAL vs. RAL). Conclusion: All bismuth-containing quadruple therapies had acceptable eradication rates, but levofloxacin-containing triple therapy was not as good as quadruple therapies. Hence, quadruple therapies should be considered the preferred first-line therapy for H. pylori infections.
Localized Optogenetic Targeting of Rotors in Atrial Cardiomyocyte Monolayers
Authors: Feola Iolanda , Volkers Linda , Majumder Rupamanjari , Teplenin Alexander , Schalij Martin J. , Panfilov Alexander V. , de Vries Antoine A.F. , Pijnappels Daniël A.
Published: November 2017

Background:

Recently, a new ablation strategy for atrial fibrillation has emerged, which involves the identification of rotors (ie, local drivers) followed by the localized targeting of their core region by ablation. However, this concept has been subject to debate because the mode of arrhythmia termination remains poorly understood, as dedicated models and research tools are lacking. We took a unique optogenetic approach to induce and locally target a rotor in atrial monolayers.

Methods and Results:

Neonatal rat atrial cardiomyocyte monolayers expressing a depolarizing light-gated ion channel (Ca
2+
-translocating channelrhodopsin) were subjected to patterned illumination to induce single, stable, and centralized rotors by optical S1-S2 cross-field stimulation. Next, the core region of these rotors was specifically and precisely targeted by light to induce local conduction blocks of circular or linear shapes. Conduction blocks crossing the core region, but not reaching any unexcitable boundary, did not lead to termination. Instead, electric waves started to propagate along the circumference of block, thereby maintaining reentrant activity, although of lower frequency. If, however, core-spanning lines of block reached at least 1 unexcitable boundary, reentrant activity was consistently terminated by wave collision. Lines of block away from the core region resulted merely in rotor destabilization (ie, drifting).

Conclusions:

Localized optogenetic targeting of rotors in atrial monolayers could lead to both stabilization and destabilization of reentrant activity. For termination, however, a line of block is required reaching from the core region to at least 1 unexcitable boundary. These findings may improve our understanding of the mechanisms involved in rotor-guided ablation.
Efficacy and Safety of the Use of Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Concomitant Aspirin Therapy
Authors: Bennaghmouch Naoual , de Veer Anne J.W.M. , Bode Kerstin , Mahmoodi Bakhtawar K. , Dewilde Willem J.M. , Lip Gregory Y.H. , Brueckmann Martina , Kleine Eva , ten Berg Jurriën M.
Published: November 2017

Background:

Current guidelines recommend non–vitamin K antagonist oral anticoagulants (NOACs) as the first-choice therapy in patients with nonvalvular atrial fibrillation because these drugs have several benefits over the vitamin K antagonists (VKAs). It is unknown whether these benefits remain when NOACs have to be combined with aspirin therapy. To assess the efficacy and safety of NOACs compared with VKAs in patients with atrial fibrillation and concomitant aspirin therapy, we conducted a systematic review and study–based meta-analysis of published randomized controlled trials.

Methods:

A systematic electronic literature search was done in MEDLINE, EMBASE, and Cochrane CENTRAL Register of Controlled Trials for studies including published data of patients ≥18 years of age with nonvalvular atrial fibrillation, randomized to either VKAs or NOACs, or receiving aspirin therapy at any time during the study that report all-cause stroke or systemic embolism, vascular death, myocardial infarction, major bleeding, or intracranial hemorrhage as an outcome. Hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome were extracted from the individual studies and pooled with random-effects meta-analysis.

Results:

This study-based meta-analysis was restricted to the subgroups of patients on aspirin therapy (n=21 722) from 4 randomized controlled trials comparing VKAs and NOACs (n=71 681) in nonvalvular atrial fibrillation. In this meta-analysis including patients on mainly low-dose aspirin, NOACs were found to be more effective (outcome of stroke or systemic embolism: HR, 0.78; 95% CI, 0.67–0.91; vascular death: HR, 0.85; 95% CI, 0.76–0.93) and as safe as VKAs with respect to major bleeding (HR, 0.83; 95% CI, 0.69–1.01). NOACs were safer with respect to the reduction of intracranial hemorrhage (HR, 0.38; 95% CI, 0.26–0.56).

Conclusions:

This study-based meta-analysis shows that it may be both safer and more effective to use NOACs compared with VKAs to treat patients with nonvalvular atrial fibrillation and concomitant aspirin therapy.
Increased Cardiac Arrhythmogenesis Associated With Gap Junction Remodeling With Upregulation of RNA-Binding Protein FXR1
Authors: Chu Miensheng , Novak Stefanie Mares , Cover Cathleen , Wang Anne A. , Chinyere Ikeotunye Royal , Juneman Elizabeth B. , Zarnescu Daniela C. , Wong Pak Kin , Gregorio Carol C.
Published: November 2017

Background:

Gap junction remodeling is well established as a consistent feature of human heart disease involving spontaneous ventricular arrhythmia. The mechanisms responsible for gap junction remodeling that include alterations in the distribution of, and protein expression within, gap junctions are still debated. Studies reveal that multiple transcriptional and posttranscriptional regulatory pathways are triggered in response to cardiac disease, such as those involving RNA-binding proteins. The expression levels of FXR1 (fragile X mental retardation autosomal homolog 1), an RNA-binding protein, are critical to maintain proper cardiac muscle function; however, the connection between FXR1 and disease is not clear.

Methods:

To identify the mechanisms regulating gap junction remodeling in cardiac disease, we sought to identify the functional properties of FXR1 expression, direct targets of FXR1 in human left ventricle dilated cardiomyopathy (DCM) biopsy samples and mouse models of DCM through BioID proximity assay and RNA immunoprecipitation, how FXR1 regulates its targets through RNA stability and luciferase assays, and functional consequences of altering the levels of this important RNA-binding protein through the analysis of cardiac-specific FXR1 knockout mice and mice injected with 3xMyc-FXR1 adeno-associated virus.

Results:

FXR1 expression is significantly increased in tissue samples from human and mouse models of DCM via Western blot analysis. FXR1 associates with intercalated discs, and integral gap junction proteins Cx43 (connexin 43), Cx45 (connexin 45), and ZO-1 (zonula occludens-1) were identified as novel mRNA targets of FXR1 by using a BioID proximity assay and RNA immunoprecipitation. Our findings show that FXR1 is a multifunctional protein involved in translational regulation and stabilization of its mRNA targets in heart muscle. In addition, introduction of 3xMyc-FXR1 via adeno-associated virus into mice leads to the redistribution of gap junctions and promotes ventricular tachycardia, showing the functional significance of FXR1 upregulation observed in DCM.

Conclusions:

In DCM, increased FXR1 expression appears to play an important role in disease progression by regulating gap junction remodeling. Together this study provides a novel function of FXR1, namely, that it directly regulates major gap junction components, contributing to proper cell-cell communication in the heart.
Cholesterol Control Among Uninsured Adults Did Not Improve From 2001‐2004 to 2009‐2012 as Disparities With Both Publicly and Privately Insured Adults Doubled
Authors: Egan Brent M. , Li Jiexiang , Sarasua Sara M. , Davis Robert A. , Fiscella Kevin A. , Tobin Jonathan N. , Jones Daniel W. , Sinopoli Angelo
Published: November 2017

Background

Low‐density lipoprotein cholesterol (LDL‐C) control is higher among insured than uninsured adults, but data on time trends and contributing factors are incomplete and important for improving health equity.

Methods and Results

Awareness, treatment, and control of elevated LDL‐C were compared among insured versus uninsured and publicly versus privately insured adults, aged 21 to 64 years, in National Health and Nutrition Examination Surveys from 2001 to 2004, 2005 to 2008, and 2009 to 2012 using Adult Treatment Panel‐3 criteria. Compared with insured adults, uninsured adults were younger; were more often minority; reported lower incomes, less education, and fewer healthcare encounters; and had lower awareness and treatment of elevated LDL‐C (
P
<0.0001). LDL‐C control was higher among insured than uninsured adults in 2001 to 2004 (mean±SEM, 21.4±1.6% versus 10.5±2.6%;
P
<0.01), and the gap widened by 2009 to 2012 (35.1±1.9% versus 11.3±2.2%;
P
<0.0001). Despite more minorities (
P
<0.01), greater poverty, and less education (
P
<0.001), publicly insured adults had more healthcare visits/year than privately insured adults (
P
<0.001) and similar awareness, treatment, and control of LDL‐C from 2001 to 2012. In multivariable logistic regression, significant positive predictors of cholesterol awareness, treatment, and control included more frequent health care (strongest), increasing age, private healthcare insurance versus uninsured, and hypertension. Public insurance (versus uninsured) was a significant positive predictor of LDL‐C control, whereas income <200% versus ≥200% of federal poverty was a significant negative predictor.

Conclusions

LDL‐C control improved similarly over time in publicly and privately insured adults but was stagnant among the uninsured. Healthcare insurance largely addresses socioeconomic barriers to effective LDL‐C management, yet poverty retains an independent adverse effect.
Climatic and Seasonal Circumstances of Hypertensive Intracerebral Hemorrhage in a Worldwide Cohort
Authors: Herweh Christian , Nordlohne Stefan , Sykora Marek , Uhlmann Lorenz , Bendszus Martin , Steiner Thorsten
Published: November 2017

Background and Purpose—

Numerous studies have investigated the influence of meteorologic factors and seasons on the incidence of spontaneous intracerebral hemorrhage (ICH) with ambiguous results. In the present study, data from a large, international multicenter trial in patients with ICH were used to identify seasonal and meteorologic determinants for hypertensive-ICH with greater applicability.

Methods—

Patients were grouped according to the presumptive ICH cause, that is, hypertensive when located in the basal ganglia brain stem as well as cerebellum and nonhypertensive when located lobar. Both groups were compared with regard to air temperature and air pressure and their occurrence during the year. A regression analysis was performed to identify independent predictors of hypertensive-ICH.

Results—

Only hypertensive-ICH showed a seasonal pattern and occurred with higher air pressure values and at younger age. Independent predictors of hypertensive-ICH were increased air pressure on the actual day of the event and younger age as well as higher temperature.

Conclusions—

In the present study with an international cohort, besides age air pressure, more than temperature, had an influence on the occurrence of hypertensive-ICH, only.
A phylogenetic framework for the Hylocereeae (Cactaceae) and implications for the circumscription of the genera
Authors: KOROTKOVA NADJA , BORSCH THOMAS , ARIAS SALVADOR
Published: November 2017

The tribe Hylocereeae are represented by mainly Central American-Mexican epiphytic, hemi-epiphytic and climbing cacti. They are popular due to their spectacular nocturnal flowers and have some importance as crops grown for their edible fruits. We present the first comprehensive phylogenetic study of the Hylocereeae sampling 60 out of the 63 currently accepted species and 17 out of 19 infraspecific taxa. Based on four plastid regions (trnK/matK, the rpl16 intron, rps3-rpl16, and trnL-F) we find a highly supported core Hylocereeae clade that also includes Acanthocereus and Peniocereus p.p., while Strophocactus is depicted as polyphyletic and is resolved outside of the Hylocereeae tribe. The clades found within Hylocereeae agree, in general terms, with the currently accepted genera but none of the genera are entirely monophyletic in their current circumscription. A new concept for the Hylocereeae is presented to include the genera Acanthocereus (incl. Peniocereus p.p.), Aporocactus, Disocactus, Epiphyllum, Selenicereus (incl. Hylocereus and Weberocereus p.p.), Pseudorhipsalis, Kimnachia gen. nov., and Weberocereus. New nomenclatural combinations are provided to make these genera monophyletic. The genus Deamia is reinstated for Strophocactus testudo and S. chontalensis, while Strophocactus is newly circumscribed to include S. wittii, Pseudoacanthocereus brasiliensis, and P. sicariguensis. Both genera are excluded from Hylocereeae. A taxonomic synopsis of Hylocereeae is provided.
Azimuthal Distribution of Deep Convection, Environmental Factors, and Tropical Cyclone Rapid Intensification: A Perspective from HWRF Ensemble Forecasts of Hurricane Edouard (2014)
Authors: Leighton Hua , Gopalakrishnan Sundararaman , Zhang Jun A. , Rogers Robert F. , Zhang Zhan , Tallapragada Vijay
Published: November 2017

Forecasts from the operational Hurricane Weather Research and Forecasting (HWRF)-based ensemble prediction system for Hurricane Edouard (2014) are analyzed to study the differences in both the tropical cyclone inner-core structure and large-scale environment between rapidly intensifying (RI) and nonintensifying (NI) ensemble members. An analysis of the inner-core structure reveals that as deep convection wraps around from the downshear side of the storm to the upshear-left quadrant for RI members, vortex tilt and asymmetry reduce rapidly, and rapid intensification occurs. For NI members, deep convection stays trapped in the downshear/downshear-right quadrant, and storms do not intensify. The budget calculation of tangential wind tendency reveals that the positive radial eddy vorticity flux for RI members contributes significantly to spinning up the tangential wind in the middle and upper levels and reduces vortex tilt. The negative eddy vorticity flux for NI members spins down the tangential wind in the middle and upper levels and does not help the vortex become vertically aligned. An analysis of the environmental flow shows that the cyclonic component of the storm-relative upper-level environmental flow in the left-of-shear quadrants aids the cyclonic propagation of deep convection and helps establish the configuration that leads to the positive radial vorticity flux for RI members. In contrast, the anticyclonic component of the storm-relative mid- and upper-level environmental flow in the left-of-shear quadrants inhibits the cyclonic propagation of deep convection and suppresses the positive radial eddy vorticity flux for NI members. Environmental moisture in the downshear-right quadrant is also shown to be important for the formation of deep convection for RI members.
The Relationships among Actual Weather Events, Perceived Unusual Weather, Media Use, and Global Warming Belief Certainty in China
Authors: Wang Xiao , Lin Lin
Published: November 2017

Previous research revealed that if individuals personally experience an unusual weather event as a result of global warming (vs no personal experience), they may hold higher belief certainty that global warming is happening and hence develop more favorable attitudes toward mitigation actions. However, much of the previous research focused on self-reported personal experience and global warming beliefs using cross-sectional surveys; reverse causality is thus possible. Based on weather records and survey data, the present research examined whether actual weather events can influence one’s perceptions of unusual weather and belief certainty. Severe Typhoon Fitow 2013, but not hot summer temperatures, directly predicted the Chinese perceived experience of unusual weather and indirectly predicted their belief certainty and attitudes toward mitigation behavior. However, the effects were relatively small. Possible explanations and implications for environmental education are discussed.