bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial infarction, ST-elevation and non-ST-elevation myocardial infarction and modelled daily pollution concentrations: a case-crossover analysis of MINAP data
Authors: Butland Barbara K , Atkinson Richard W , Milojevic Ai , Heal Mathew R , Doherty Ruth M , Armstrong Ben G , MacKenzie Ian A , Vieno Massimo , Lin Chun , Wilkinson Paul
Published: September 2016

Objectives

To investigate associations between daily concentrations of air pollution and myocardial infarction (MI), ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI).

Methods

Modelled daily ground-level gaseous, total and speciated particulate pollutant concentrations and ground-level daily mean temperature, all at 5 km×5 km horizontal resolution, were linked to 202 550 STEMI and 322 198 NSTEMI events recorded on the England and Wales Myocardial Ischaemia National Audit Project (MINAP) database. The study period was 2003–2010. A case-crossover design was used, stratified by year, month and day of the week. Data were analysed using conditional logistic regression, with pollutants modelled as unconstrained distributed lags 0–2 days. Results are presented as percentage change in risk per 10 µg/m3increase in the pollutant relevant metric, having adjusted for daily mean temperature, public holidays, weekly influenza consultation rates and a sine-cosine annual cycle.

Results

There was no evidence of an association between MI or STEMI and any of O3, NO2, PM2.5, PM10or selected PM2.5components (sulfate and elemental carbon). For NSTEMI, there was a positive association with daily maximum 1-hour NO2(0.27% (95% CI 0.01% to 0.54%)), which persisted following adjustment for O3and adjustment for PM2.5. The association appeared to be confined to the midland and southern regions of England and Wales.

Conclusions

The study found no evidence of an association between the modelled pollutants (including components) investigated and STEMI but did find some evidence of a positive association between NO2and NSTEMI. Confirmation of this association in other studies is required.
A once in 10 year drought alters the magnitude and quality of a floodplain prey subsidy to coastal river fishes
Authors: Boucek Ross E. , Soula Mariajesus , Tamayo Felipe , Rehage Jennifer S.
Published: September 2016

Disturbances that alter cross-habitat food web linkages can lead to whole-scale changes to aquatic systems. In coastal rivers of the Everglades (Florida, U.S.A.), increases in rainfall inundate adjacent floodplains, providing habitat for floodplain fish and macroinvertebrate species. In the dry season, rainfall decreases and floodplains dry, forcing floodplain prey into these river systems. These prey provide a prey subsidy for an estuarine predator, the common snook (Centropomus undecimalis). In 2011, severe drought impacted the region, likely affecting this prey subsidy. In this study, we ask (i) did the 2011 drought affect the magnitude and composition of floodplain prey subsidies to the common snook? and (ii) if species composition changed, were there energetic differences between the pre- and post-disturbance prey species? Results showed that 1 year after the drought, subsidies to the common snook decreased by 75%. On top of that decrease in overall flux, diet composition of the common snook switched from floodplain fishes to drought-tolerant floodplain macroinvertebrates. Lastly, energetic analyses showed that these postdrought macroinvertebrate prey subsidies had 43% less calories than floodplain fishes. Our findings illustrate the importance of considering not only the biomass that transfers from one food web to the next, but also how the species composition of the subsidy may affect incorporation into recipient food webs.
Production ofBacillus amyloliquefaciensOG and its metabolites in renewable media: valorisation for biodiesel production andp-xylene decontamination
Authors: Etchegaray Augusto , Coutte François , Chataigné Gabrielle , Béchet Max , dos Santos Ramon H.Z. , Leclère Valérie , Jacques Philippe
Published: September 2016

Biosurfactants are important in many areas; however, costs impede large-scale production. This work aimed to develop a global sustainable strategy for the production of biosurfactants by a novel strain of Bacillus amyloliquefaciens. Initially, Bacillus sp. strain 0G was renamed B. amyloliquefaciens subsp. plantarum (syn. Bacillus velezensis) after analysis of the gyrA and gyrB DNA sequences. Growth in modified Landy’s medium produced 3 main recoverable metabolites: surfactin, fengycin, and acetoin, which promote plant growth. Cultivation was studied in the presence of renewable carbon (as glycerol) and nitrogen (as arginine) sources. While diverse kinetics of acetoin production were observed in different media, similar yields (6–8 g·L–1) were obtained after 72 h of growth. Glycerol increased surfactin-specific production, while arginine increased the yields of surfactin and fengycin and increased biomass significantly. The specific production of fengycin increased ∼10 times, possibly due to a connecting pathway involving arginine and ornithine. Adding value to crude extracts and biomass, both were shown to be useful, respectively, for the removal of p-xylene from contaminated water and for biodiesel production, yielding ∼70 mg·g–1cells and glycerol, which could be recycled in novel media. This is the first study considering circular bioeconomy to lower the production costs of biosurfactants by valorisation of both microbial cells and their primary and secondary metabolites.
Chamomile and oregano extracts synergistically exhibit antihyperglycemic, antihyperlipidemic, and renal protective effects in alloxan-induced diabetic rats
Authors: Prasanna Rajagopalan , Ashraf Elbessoumy A. , Essam Mahmoud A.
Published: September 2016

The bio-activities of separate Matricaria chamomilla (chamomile) and Origanum vulgare (oregano) are well studied; however, the combined effects of both natural products in animal diabetic models are not well characterized. In this study, alloxan-induced male albino rats were treated with single dose aqueous suspension of chamomile or oregano at dose level of either 150 or 300 mg/kg body mass or as equal parts as combination by stomach tube for 6 weeks. After treatment, blood samples were assessed for diabetic, renal, and lipid profiles. Insulin, amylase activity, and diabetic renal apoptosis were further evaluated. Treatment with higher dose of the extracts (300 mg/kg) as individual or as mixture of low doses (150 mg/kg of both the extracts) had significant mass gain, hypoglycemic effect (p ≤ 0.05) with decreased amylase activity and increased serum insulin levels. Restoration of renal profile, lipid profile with increase in HDL-c (p ≤ 0.05) along with reversal of pro-apoptotic Bax and anti-apoptotic Bcl-2 were well observed with 300 mg/kg mixture, showing synergistic activity of the extracts compared with individual low dose of 150 mg/kg. Collectively, our results indicate that combination of chamomile and oregano extracts will form a new class of drugs to treat diabetic complications.
A Cross-Correlated Delay Shift Supervised Learning Method for Spiking Neurons with Application to Interictal Spike Detection in Epilepsy
Authors: Guo Lilin , Wang Zhenzhong , Cabrerizo Mercedes , Adjouadi Malek
Published: September 2016

This study introduces a novel learning algorithm for spiking neurons, called CCDS, which is able to learn and reproduce arbitrary spike patterns in a supervised fashion allowing the processing of spatiotemporal information encoded in the precise timing of spikes. Unlike the Remote Supervised Method (ReSuMe), synapse delays and axonal delays in CCDS are variants which are modulated together with weights during learning. The CCDS rule is both biologically plausible and computationally efficient. The properties of this learning rule are investigated extensively through experimental evaluations in terms of reliability, adaptive learning performance, generality to different neuron models, learning in the presence of noise, effects of its learning parameters and classification performance. Results presented show that the CCDS learning method achieves learning accuracy and learning speed comparable with ReSuMe, but improves classification accuracy when compared to both the Spike Pattern Association Neuron (SPAN) learning rule and the Tempotron learning rule. The merit of CCDS rule is further validated on a practical example involving the automated detection of interictal spikes in EEG records of patients with epilepsy. Results again show that with proper encoding, the CCDS rule achieves good recognition performance.
Absorption of a particle by a rotating black hole: The potential barrier
Authors: Heller Leon
Published: September 2016

For a test particle approaching a rapidly rotating black hole we find a range of values of the particle’s energy and angular momentum, on the order of 1% or more of the corresponding values of the hole, such that three conditions are satisfied. (1) The particle can reach the horizon. (2) After absorption the new hole still has a horizon. (3) The area of the new hole is less than the area of the original one, in apparent violation of a theorem of Hawking. We offer support for the claim that the test particle approximation is the cause of the violation.
Neutrino masses in the SU(4)L ⊗ U(1)X electroweak extension of the Standard Model
Authors: Palacio Guillermo
Published: September 2016

We study the neutrino mass generation in the [Formula: see text] electroweak extension of the Standard Model by considering nonrenormalizable dimension 5 effective operators. It is shown that there exist two topologies for the realizations of such an operator at the tree-level and for one of the three-family models the neutrino phenomenology is explored after extending its particle content with an [Formula: see text] fermion singlet and a scalar decuplet. Constraints in the available parameters space of the model are partially discussed.
On uniqueness of T-duality with spectators
Authors: Hlavatý Ladislav , Petrásek Filip
Published: September 2016

We investigate the dependence of non-Abelian T-duality on various identification of the isometry group of target space with its orbits, i.e. with respect to the location of the group unit on manifolds invariant under the isometry group. We show that T-duals constructed by isometry groups of dimension less than the dimension of the (pseudo)-Riemannian manifold may depend not only on the initial metric but also on the choice of manifolds defining positions of group units on each of the submanifold invariant under the isometry group. We investigate whether this dependence can be compensated by coordinate transformation.
Electronic and optical properties of K-doped ZnO: Ab initio study
Authors: Aimouch D. E. , Meskine S. , Hayn R. , Zaoui A. , Boukortt A.
Published: September 2016

We present the results of ab initio calculations of K-doped ZnO in the wurtzite structure using a supercell of 32 atoms and density functional theory. A complete analysis of its electronic, optical and magnetic properties is provided. The local spin density approximation (LSDA) has been used to analyze the density of states and to understand the K influence at different concentration values. The material is revealed to become a [Formula: see text]-type doped semiconductor. The optical constant or refractive index, the dielectric function, and the absorption coefficient were determined and show a good agreement with available experimental data. Potassium doping leads to an absorption peak at about 380 nm. That peak might improve the absorption characteristics of ZnO for solar cell or optical applications.
A New Structure for Nonisolated Boost DC–DC Converter
Authors: Shahir Farzad Mohammadzadeh , Babaei Ebrahim , Farsadi Murtaza
Published: September 2016

In this paper, a new structure of nonisolated boost DC–DC converters is proposed. The operation of the proposed structure in continuous conduction mode (CCM) and discontinuous conduction mode (DCM) is presented. Then, the critical inductance relation between CCM and DCM is obtained. The voltage gain and current stress of switches are calculated. Finally, the validity of the presented theoretical issues is reconfirmed by using simulation results obtained from PSCAD/EMTDC software.
Reconstructing spacetime from the hologram, even in the classical limit, requires physics beyond the Planck scale
Authors: Berenstein David , Miller Alexandra
Published: September 2016

In this paper, we argue that for classical configurations of gravity in the AdS/CFT setup, it is in general impossible to reconstruct the bulk geometry from the leading asymptotic behavior of the classical fields in gravity alone. This is possible sufficiently near the vacuum, but not more generally. We argue this by using a counter-example that utilizes the supersymmetric geometries constructed by Lin, Lunin, and Maldacena. In the dual quantum field theory, the additional data required to complete the geometry is encoded in modes that near the vacuum geometry lie beyond the Planck scale.
s-Wave holographic superconductor in different ensembles and its thermodynamic consistency
Authors: Yin Lei , Hou Defu
Published: September 2016

In this paper, we analytically study the consistency between the Ginzburg–Landau theory of the holographic superconductor in different ensembles and the fundamental thermodynamic relation, we derive the equation of motion of the scalar field which depicts the superconducting phase in canonical ensemble (CE) and a consistent formula to connect the holographic order-parameter to the Ginzburg–Landau coefficients in different thermodynamic ensembles, and we also study the spatially nonuniform Helmholtz free energy.
DEVELOPMENT OF FRACTAL DIMENSION AND CHARACTERISTIC ROUGHNESS MODELS FOR TURNED SURFACE OF CARBON STEELS
Authors: ZUO XUE , ZHU HUA , ZHOU YUANKAI , DING CONG , SUN GUODONG
Published: September 2016

Relationships between material hardness, turning parameters (spindle speed and feed rate) and surface parameters (surface roughness [Formula: see text]a, fractal dimension [Formula: see text] and characteristic roughness [Formula: see text] are studied and modeled using response surface methodology (RSM). The experiments are carried out on a CNC lathe for six carbon steel material AISI 1010, AISI 1020, AISI 1030, AISI 1045, AISI 1050 and AISI 1060. The profile of turned surface and the surface roughness value are measured by a JB-5C profilometer. Based on the profile data, [Formula: see text] and [Formula: see text] are computed through the root-mean-square method. The analysis of variance (ANOVA) reveals that spindle speed is the most significant factors affecting [Formula: see text]a, while material hardness is the most dominant parameter affecting [Formula: see text]. Material hardness and spindle speed have the same influence on [Formula: see text]. Feed rate has less effect on three surface parameters than spindle speed and material hardness. The second-order models of RSM are established for estimating [Formula: see text]a, [Formula: see text] and [Formula: see text]. The validity of the developed models is approximately 80%. The response surfaces show that a surface with small [Formula: see text]a and large [Formula: see text] and [Formula: see text] can be obtained by selecting a high speed and a large hardness material. According to the established models, [Formula: see text]a, [Formula: see text] and [Formula: see text] of six carbon steels surfaces can be predicted under cutting conditions studied in this paper. The results have an instructive meaning to estimate the surface quality before turning.
Tame failures of the unique branch hypothesis and models of ADℝ + Θ is regular
Authors: Sargsyan Grigor , Trang Nam
Published: September 2016

In this paper, we show that the failure of the unique branch hypothesis ([Formula: see text]) for tame iteration trees implies that in some homogenous generic extension of [Formula: see text] there is a transitive model [Formula: see text] containing [Formula: see text] such that [Formula: see text] is regular. The results of this paper significantly extend earlier works from [Non-tame mice from tame failures of the unique branch bypothesis, Canadian J. Math. 66(4) (2014) 903–923; Core models with more Woodin cardinals, J. Symbolic Logic 67(3) (2002) 1197–1226] for tame trees.
Instruction Clustering Analysis for Unknown Network Protocol's Abnormal Behavior
Authors: HU YANJING , PEI QINGQI , PANG LIAOJUN
Published: September 2016

Protocol's abnormal behavior analysis is an important task in protocol reverse analysis. Traditional protocol reverse analysis focus on the protocol message format, but protocol behavior especially the abnormal behavior is rare studied. In this paper, protocol behavior is represented by the labeled behavior instruction sequences. Similar behavior instruction sequences mean the similar protocol behavior. Using our developed virtual analysis platform HiddenDisc, we can capture a variety of known or unknown protocols' behavior instruction sequences. All kinds of executed or unexecuted instruction sequences can automatic clustering by our designed instruction clustering algorithm. Thereby we can distinguish and mine the unknown protocols' potential abnormal behavior. The mined potential abnormal behavior instruction sequences are executed, monitored and analyzed on HiddenDisc to determine whether it is an abnormal behavior and what is the behavior's nature. Using the instruction clustering algorithm, we have analyzed 1297 protocol samples, mined 193 potential abnormal instruction sequences, and determined 187 malicious abnormal behaviors by regression testing. Experimental results show that our proposed instruction clustering algorithm has high efficiency and accuracy, can mine unknown protocols' abnormal behaviors effectively, and enhance the initiative defense capability of network security.
Mathematical model for the ciliary-induced transport of seminal liquids through the ductuli efferentes
Authors: Farooq A. A. , Siddiqui A. M.
Published: September 2016

This study describes the consequences of the ciliary motion on the transport of seminal liquid through the ductus efferentes of the male reproductive tract. By assuming the seminal liquid as a couple stress fluid, we have formulated a mathematical model for a two-dimensional flow through an axially symmetric tube whose inner surface is ciliated in the form of a metachronal wave. The governing system consists of nonlinear coupled partial differential equations which is reduced to a system of ordinary differential equations by utilizing the long wavelength approximation in an environment of the inertia free flow. Exact solutions for the velocity distribution, the pressure gradient and the stream function are obtained in terms of the couple stress parameters and the ciliary metachronism. Special attention is given to the pumping and the trapping characteristics due to the cilia motility. The study reveals that the ciliary pumping has to be more efficient to transport a couple stress fluid as compared to a Newtonian fluid. Moreover, the theoretical results for the couple stress fluid are found to be in good agreement with those reported by [T. J. Lardner and W. J. Shack, Cilia transport, Bull. Math. Biophys. 34 (1972) 325–335]. The analytical results are also displayed in graphical form.
Review on Cooling System Energy Consumption in Internet Data Centers
Authors: Amoabeng Kofi Owura , Choi Jong Min
Published: September 2016

Due to the advancement of the telecommunication and information technology (IT) industry, internet data centers (IDCs) have become widespread in the public and private sectors. As such, energy demand in the center has also become increasingly prominent. Several technologies on energy management have been studied to determine the options available to minimize the energy required to operate the data center as well as reduce greenhouse gas emissions. The cooling system is required to remove the high heat dissipated by the IT electronic components especially the servers in order to ensure safe and reliable working condition. However, it utilizes more than one-third of the total energy consumption in the data center. In this study, the energy efficiency technologies that are usually applied to cooling systems in data centers were reviewed. The aim is to find out the strategies that will reduce the energy consumption of the cooling system since the cooling demand in data center is all year round. Prior to that, the performance metric tool that is mostly used in analyzing data center efficiency was discussed. The conventional cooling system technologies that are utilized in data centers were also provided. Lastly, innovative cooling technologies for future solutions in data centers were discussed.
Stability and Performance of Various Singular Value QR Implementations on Multicore CPU with a GPU
Authors: Yamazaki Ichitaro , Tomov Stanimire , Dongarra Jack
Published: September 2016

Singular Value QR (SVQR) can orthonormalize a set of dense vectors with the minimum communication (one global reduction between the parallel processing units, and BLAS-3 to perform most of its local computation). As a result, compared to other orthogonalization schemes, SVQR obtains superior performance on many of the current computers, where the communication has become significantly more expensive compared to the arithmetic operations. In this article, we study the stability and performance of various SVQR implementations on multicore CPUs with a GPU. Our focus is on the dense triangular solve, which performs half of the total floating-point operations of SVQR. As a part of this study, we examine an adaptive mixed-precision variant of SVQR, which decides if a lower-precision arithmetic can be used for the triangular solution at runtime without increasing the order of its orthogonality error (though its backward error is significantly greater). If the greater backward error can be tolerated, then our performance results with an NVIDIA Kepler GPU show that the mixed-precision SVQR can obtain a speedup of up to 1.36 over the standard SVQR.
Hepatocyte ERBB3 and EGFR are required for maximal CCl4-induced liver fibrosis
Authors: Scheving Lawrence A. , Zhang Xiuqi , Threadgill David W. , Russell William E.
Published: September 2016

Epidermal growth factor receptor (EGFR) and its ligands have been implicated in liver fibrosis. However, it has not been directly shown that hepatocellular genetic ablation of either this receptor tyrosine kinase or ERBB3, its interactive signaling partner, affects hepatic fibrosis. Carbon tetrachloride (CCl4)-induced liver fibrosis in hepatocyte-specific (HS) mouse models of EGFR and ERBB3 ablation was evaluated in both single gene knockouts and an HS-EGFR-ERBB3 double knockout (DKO). Loss of hepatocellular EGFR or ERBB3 did not impact cytochrome P450-2E1 expression, the extent of centrilobular injury, or the initial regenerative response, but it did diminish liver fibrosis induced by chronic intraperitoneal administration of CCl4. The reduction of liver fibrosis correlated with reduced α-smooth muscle actin expression. Maximal impact to fibrogenesis occurred in the ERBB3 and EGFR-ERBB3 DKO models, suggesting that EGFR-ERBB3 heterodimeric signaling in damaged hepatocytes may play a more important role in liver fibrosis than EGFR-EGFR homodimeric signaling. Immunohistochemical analyses of phospho-EGFR and phospho-ERBB3 isoforms revealed clear staining in hepatocytes, activated stellate cells, and macrophages. Our results support a role for the hepatocellular ERBB tyrosine kinases in fibrogenesis and suggest that pharmacologic inhibition of EGFR-ERBB3 signaling may reverse or retard hepatic fibrosis.
14,15-Epoxyeicosatrienoic acid suppresses cigarette smoke condensate-induced inflammation in lung epithelial cells by inhibiting autophagy
Authors: Li Yunxiao , Yu Ganggang , Yuan Shaopeng , Tan Chunting , Xie Jianlin , Ding Yasi , Lian Puqiao , Fu Lixia , Hou Qi , Xu Bo , Wang Haoyan
Published: September 2016

Epoxyeicosatrienoic acids (EETs) are metabolic products of free arachidonic acid, which are produced through cytochrome P-450 (CYP) epoxygenases. EETs have anti-inflammatory, antiapoptotic, and antioxidative activities. However, the effect of EETs on cigarette smoke-induced lung inflammation is not clear. Autophagy is believed to be involved in the pathogenesis of chronic obstructive pulmonary disease. In addition, nuclear erythroid-related factor 2 (Nrf2), a transcription factor that regulates many antioxidant genes, is thought to regulate antioxidant defenses in several lung diseases. In addition, interaction between EETs, autophagy, and Nrf2 has been reported. The aim of this study was to explore the effect of 14,15-EET on cigarette smoke condensate (CSC)-induced inflammation in a human bronchial epithelial cell line (Beas-2B), and to determine whether the underlying mechanisms involved in the regulation of Nrf2 through inhibition of autophagy. Autophagy and expression of autophagy signaling pathway proteins (LC3B, p62, PI3K, Akt, p-Akt, and p-mTOR) and anti-inflammatory proteins (Nrf2 and HO-1) were assessed via Western blot analysis. Autophagosomes and autolysosomes were detected by adenoviral mRFP-GFP-LC3 transfection. Inflammatory factors (IL-6, IL-8, and MCP-1) were detected by ELISA. Lentiviral vectors carrying p62 short hairpin RNA were used to interfere with p62 expression to evaluate the effect of p62 on Nrf2 expression. Nrf2 expression was determined through immunocytochemistry. 14,15-EET treatment resulted in a significant reduction in IL-6, IL-8, and MCP-1 secretion, and increased accumulation of Nrf2 and expression of HO-1. In addition, 14,15-EET inhibited CSC-induced autophagy in Beas-2B cells. The mechanism of the anti-inflammatory effect of 14,15-EET involved inhibition of autophagy and an increase in p62 levels, followed by translocation of Nrf2 into the nucleus, which then upregulated expression of the antioxidant enzyme HO-1. 14,15-EET protects against CSC-induced lung inflammation by promoting accumulation of Nrf2 via inhibition of autophagy.
Athletic training affects the uniformity of muscle and tendon adaptation during adolescence
Authors: Mersmann Falk , Bohm Sebastian , Schroll Arno , Marzilger Robert , Arampatzis Adamantios
Published: September 2016

With the double stimulus of mechanical loading and maturation acting on the muscle-tendon unit, adolescent athletes might be at increased risk of developing imbalances of muscle strength and tendon mechanical properties. This longitudinal study aims to provide detailed information on how athletic training affects the time course of muscle-tendon adaptation during adolescence. In 12 adolescent elite athletes (A) and 8 similar-aged controls (C), knee extensor muscle strength and patellar tendon mechanical properties were measured over 1 yr in 3-mo intervals. A linear mixed-effects model was used to analyze time-dependent changes and the residuals of the model to quantify fluctuations over time. The cosine similarity (CS) served as a measure of uniformity of the relative changes of tendon force and stiffness. Muscle strength and tendon stiffness increased significantly in both groups ( P < 0.01). However, the fluctuations of muscle strength were greater [A, 17 ± 7 (SD) N·m; C, 6 ± 2 N·m; P < 0.05] and the uniformity of changes of tendon force and stiffness was lower in athletes (CS A, −0.02 ± 0.5; C, 0.5 ± 0.4; P < 0.05). Further, athletes demonstrated greater maximum tendon strain (A, 7.6 ± 1.7%; C, 5.5 ± 0.9%; P < 0.05) and strain fluctuations (A, 0.9 ± 0.4; C, 0.3 ± 0.1; P < 0.05). We conclude that athletic training in adolescence affects the uniformity of muscle and tendon adaptation, which increases the demand on the tendon with potential implications for tendon injury.
Humanized Mouse Xenograft Models: Narrowing the Tumor–Microenvironment Gap
Authors: Morton J. Jason , Bird Gregory , Refaeli Yosef , Jimeno Antonio
Published: September 2016

Cancer research has long been hampered by the limitations of the current model systems. Both cultured cells and mouse xenografts grow in an environment highly dissimilar to that of their originating tumor, frequently resulting in promising treatments that are ultimately clinically ineffective. The development of highly immunodeficient mouse strains into which human immune systems can be engrafted can help bridge this gap. Humanized mice (HM) allow researchers to examine xenograft growth in the context of a human immune system and resultant tumor microenvironment, and recent studies have highlighted the increased similarities in attendant tumor structure, metastasis, and signaling to those features in cancer patients. This setting also facilitates the examination of investigational cancer therapies, including new immunotherapies. This review discusses recent advancements in the generation and application of HM models, their promise in cancer research, and their potential in generating clinically relevant treatments. This review also focuses on current efforts to improve HM models by engineering mouse strains expressing human cytokines or HLA proteins and implanting human bone, liver, and thymus tissue to facilitate immune cell maturation and trafficking. Finally, we discuss how these improvements may help direct future HM model cancer studies. Cancer Res; 76(21); 6153–8. ©2016 AACR.
Changes in Chromatin Structure in Curettage Specimens Identifies High-Risk Patients in Endometrial Cancer
Authors: Hveem Tarjei S. , Njølstad Tormund S. , Nielsen Birgitte , Syvertsen Rolf Anders , Nesheim John Arne , Kjæreng Marna L. , Kildal Wanja , Pradhan Manohar , Marcickiewicz Janusz , Tingulstad Solveig , Staff Anne C. , Haugland Hans K. , Eraker Runar , Oddenes Klaus , Rokne Jan A. , Tjugum Jostein , Lode Margaret S. , Amant Frederic , Werner Henrica M.J. , Bjørge Line , Albregtsen Fritz , Liestøl Knut , Salvesen Helga B. , Trovik Jone , Danielsen Håvard E.
Published: September 2016

Background: Most endometrial carcinoma patients are diagnosed at an early stage with a good prognosis. However, a relatively low fraction with lethal disease constitutes a substantial number of patients due to the high incidence rate. Preoperative identification of patients with high risk and low risk for poor outcome is necessary to tailor treatment. Nucleotyping refers to characterization of cell nuclei by image cytometry, including the assessment of chromatin structure by nuclear texture analysis. This method is a strong prognostic marker in many cancers but has not been evaluated in preoperative curettage specimens from endometrial carcinoma.

Methods: The prognostic impact of changes in chromatin structure quantified with Nucleotyping was evaluated in preoperative curettage specimens from 791 endometrial carcinoma patients prospectively included in the MoMaTEC multicenter trial.

Results: Nucleotyping was an independent prognostic marker of disease-specific survival in preoperative curettage specimens among patients with Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage I–II disease (HR=2.9; 95% CI, 1.2–6.5; P = 0.013) and significantly associated with age, FIGO stage, histologic type, histologic grade, myometrial infiltration, lymph node status, curettage histology type, and DNA ploidy.

Conclusions: Nucleotyping in preoperative curettage specimens is an independent prognostic marker for disease-specific survival, with potential to supplement existing parameters for risk stratification to tailor treatment.

Impact: This is the first study to evaluate the prognostic impact of Nucleotyping in curettage specimens from endometrial carcinoma and shows that this may be a clinically useful prognostic marker in endometrial cancer. External validation is warranted. Cancer Epidemiol Biomarkers Prev; 26(1); 61–67. ©2016 AACR.
Cervical Precancer and Cancer Risk by Human Papillomavirus Status and Cytologic Interpretation: Implications for Risk-Based Management
Authors: Castle Philip E. , Aslam Shagufta , Behrens Catherine
Published: September 2016

Background: Cervical cancer risks, estimated by using cervical intraepithelial neoplasia grade 3 (CIN3) or more severe diagnoses (≥CIN3) endpoints, have not been quantified for different combinations of results from currently approved screening methods. Understanding these risks will guide optimal patient management.

Methods: Women aged ≥25 years (n = 7,823) underwent high-risk human papillomavirus (hrHPV) and liquid-based cytology (LBC) testing. Women with hrHPV-positive results and/or abnormal LBC, plus a random subset of hrHPV and LBC negatives, underwent colposcopy; those without ≥CIN2 at baseline were screened annually by LBC and referred to colposcopy for an abnormal LBC (n = 7,392). One- and 3-year ≥CIN3 risks with 95% confidence intervals (95% CI) were calculated for paired hrHPV and LBC (hrHPV/LBC) results.

Results: One-year ≥CIN3 risks ranged from 81.27% (95% CI, 66.02%–90.65%) for HPV16 positive/high-grade to 0.33% (95% CI, 0.18%–0.62%) for hrHPV negative/negative for intraepithelial lesion or malignancy (NILM). One-year ≥CIN3 risk for HPV16/NILM (13.95%; 95% CI, 10.98%–17.58%) was greater than low-grade squamous intraepithelial lesion (LSIL; 7.90%; 95% CI, 5.99%–10.37%; P = 0.002) and similar to hrHPV-positive/LSIL (11.45%; 95% CI, 8.61%–15.07%; P = 0.3). Three-year ≥CIN3 risks for HPV16 positive/LSIL and HPV16/atypical squamous cells of undetermined significance was 24.79% (95% CI, 16.44%–35.58%) and 24.36% (95% CI, 15.86%–35.50%), respectively, and 0.72% (95% CI, 0.45%–1.14%) for hrHPV negative/NILM.

Conclusions: hrHPV and LBC results stratify cervical cancer risk by more than two orders of magnitude. HPV16-positive women, regardless of the LBC result, warrant immediate colposcopy. Women with concurrent HPV16 and high-grade LBC might consider treatment without a confirmatory biopsy with informed decision-making with their provider.

Impact: These results provide relevant benchmarks for risk-based cervical cancer screening and management. Cancer Epidemiol Biomarkers Prev; 25(12); 1595–9. ©2016 AACR.
Regulatory T Cells: Differentiation and Function
Authors: Plitas George , Rudensky Alexander Y.
Published: September 2016

The immune system of vertebrate animals has evolved to mount an effective defense against a diverse set of pathogens while minimizing transient or lasting impairment in tissue function that could result from the inflammation caused by immune responses to infectious agents. In addition, misguided immune responses to “self” and dietary antigens, as well as to commensal microorganisms, can lead to a variety of inflammatory disorders, including autoimmunity, metabolic syndrome, allergies, and cancer. Regulatory T cells expressing the X chromosome–linked transcription factor Foxp3 suppress inflammatory responses in diverse biological settings and serve as a vital mechanism of negative regulation of immune-mediated inflammation. Cancer Immunol Res; 4(9); 721–5. ©2016 AACR.
Topical Timolol Maleate 0.5% for Infantile Hemangioma: Its Effectiveness Compared to Ultrapotent Topical Corticosteroids - A Single-Center Experience of 278 Cases
Authors: Danarti Retno , Ariwibowo Lukman , Radiono Sunardi , Budiyanto Arief
Published: September 2016

Background: Infantile hemangioma (IH) may have implications on parental distress and cosmetic disfigurement. To date, ultrapotent corticosteroids are used as a treatment of choice for superficial IH. However, due to their side effects and sometimes lack of IH regression, it is necessary to find alternative topical therapies. Timolol maleate 0.5% solution and gel are nonselective β-blockers that could inhibit proliferation and trigger regression of IH. Objective: To evaluate the efficacy of topical ultrapotent corticosteroids and timolol maleate 0.5% solution and gel for superficial IH. Patients and Methods: The study design was prospective. Two hundred and seventy-eight patients diagnosed as having superficial IH were enrolled from the outpatient clinic of the Department of Dermatology and Venereology, Dr. Sardjito Hospital, Yogyakarta, Indonesia, from January 2009 to December 2014. Patients were divided into three groups: A = treated with topical ultrapotent corticosteroid, B = timolol maleate 0.5% solution and C = timolol maleate 0.5% gel. Patients were followed for 6 months to evaluate the lesion. Lesion size was measured from scaled photodocumentation with the software program ImageJ®. Results: There were significant differences in IH size after treatment with timolol maleate 0.5% solution compared with ultrapotent corticosteroids (p < 0.001) and timolol maleate 0.5% gel compared with ultrapotent corticosteroids (p < 0.001). There was no significant difference in IH lesions after treatment with timolol maleate 0.5% solution versus gel (p = 0.744). Conclusion: Timolol maleate 0.5% solution and gel were significantly superior to topical ultrapotent corticosteroids in size reduction of superficial IH.
Automated Measurement of the Angle of Progression in Labor: A Feasibility and Reliability Study
Authors: Youssef Aly , Salsi Ginevra , Montaguti Elisa , Bellussi Federica , Pacella Giuseppina , Azzarone Carlotta , Farina Antonio , Rizzo Nicola , Pilu Gianluigi
Published: September 2016

Objectives: The aim of this paper was to assess the feasibility and reliability of a new automated method for the measurement of the angle of progression (AoP) in labor. Methods: AoP was assessed using two-dimensional transperineal ultrasound by two operators in 52 women in active labor to evaluate intra- and interobserver reproducibility. The intermethod agreement between automated and manual techniques was analyzed by means of the intraclass correlation coefficient and Bland-Altman method. Results: Automated measurements were feasible in all cases. Automated assessments correctly depicted the pubic symphysis and fetal head in 133 (85.3%) out of 156 on first assessments and in all 156 after repeating measurements once in case of incorrect first evaluation. The automated technique showed good intra- and interobserver reproducibility and very good agreement with the manual technique. AoP measured by the automated method were significantly wider than those done by the manual technique (119 ± 20° vs. 130 ± 20°, p = 0.005). Conclusions: Automated assessment AoP is feasible and reproducible. However, measurements performed by the automated software are significantly different from those resulting from the previously published manual technique. In the light of our data, the automated technique does not seem ready yet for clinical use, and the AoP should be exclusively measured by the previously suggested manual technique.
Educación inclusiva en contextos inéditos: La implementación de la Pedagogía Hospitalaria
Authors: Palomares-Ruiz Ascensión , Sánchez-Navalón Belén , Garrote-Rojas Daniel
Published: September 2016

(analítico): El objetivo de este trabajo es analizar los beneficios de la Pedagogía Hospitalaria en las Unidades de Salud Mental que reciben pacientes en edad escolar que permanecen largos períodos ingresados. Esto los aparta del sistema escolar ordinario. Esta investigación la hemos desarrollado durante diez años con una metodología mixta. En la contextualización del marco teórico, estudiamos la evolución de esta disciplina y los factores que intervienen. Destacamos que el alumnado valora positivamente superar su curso académico con éxito, la enseñanza personalizada de los docentes del Aula Hospitalaria, y la posibilidad de evadirse del medio hospitalario. Estas conclusiones demandan una mayor implicación y formación del profesorado para un trabajo coordinado, y el uso de las TIC en conexión con los centros educativos, para propiciar una educación inclusiva.
Reintegração familiar e múltiplos acolhimentos institucionais
Authors: Aparecida Penso Maria , Ferreira de Souza Mora Patrícia Jakeliny
Published: September 2016

(analítico): Este artigo discute a reintegração de uma adolescente à sua mãe e os motivos que resultaram em múltiplas medidas de acolhimento institucional, a partir da abordagem sistêmica e da teoria das redes sociais. Os instrumentos foram mapa de rede, entrevistas análise documental. A análise das informações baseou-se na abordagem construtiva-interpretativa que resultou em duas zonas de sentido: "A repetição do abandono e as dificuldades no processo de reintegração familiarâ€ e "Eu não tinha ninguém para contarâ€ versus "Tem muita gente, mas de nada adiantaâ€. Conclui-se que as múltiplas medidas de acolhimento institucional da adolescente se devem a fragilidade de seus vínculos familiares e a falta de um trabalho integrado com as redes sociais.
Recurrent Aortic Dissection
Authors: Isselbacher Eric M. , Bonaca Marc P. , Di Eusanio Marco , Froehlich James , Bossone Eduardo , Sechtem Udo , Pyeritz Reed , Patel Himanshu , Khoynezhad Ali , Eckstein Hans-Henning , Jondeau Guillaume , Ramponi Fabio , Abbasi Mohammad , Montgomery Daniel , Nienaber Christoph A. , Eagle Kim , Lindsay Mark E.
Published: September 2016

Background:

Improved medical care after initial aortic dissection (AD) has led to increased survivorship and a population of individuals at risk for further cardiovascular events, including recurrent AD. Reports describing recurrent ADs have been restricted to small numbers of patients from single institutions. We used the IRAD (International Registry of Acute Aortic Dissection) database to examine the clinical profiles and outcomes of patients with recurrent AD.

Methods:

We identified 204 patients enrolled in IRAD with recurrent AD. For the primary analysis, patient characteristics, interventions, and outcomes were analyzed and compared with 3624 patients with initial AD. Iterative logistic modeling was performed to investigate variables associated with recurrent AD. Cox regression analyses were used to determine variables associated with 5-year survival. A subset of recurrent AD patients was analyzed for anatomic and demographic details of initial and recurrent ADs.

Results:

Patients with recurrent AD were more likely to have Marfan syndrome (21.5% versus 3.1%;
P
<0.001) but not bicuspid aortic valve (3.6% versus 3.2%;
P
=0.77). Descending aortic dimensions were greater in patients with recurrent AD than in patients with initial AD independently of sentinel dissection type (type A: 4.3 cm [3.5–5.6 cm] versus 3.3 cm [2.9–3.7 cm],
P
<0.001; type B: 5.0 cm [3.9–6.0 cm] versus 4.0 cm [3.5–4.8 cm],
P
<0.001), and this observation was accentuated among patients with Marfan syndrome. In multivariate analysis, the diagnosis of Marfan syndrome independently predicted recurrent AD (hazard ratio, 8.6; 95% confidence interval, 5.8–12.8;
P
<0.001). Patients with recurrent AD who presented with proximal followed by distal AD were younger than patients who experienced distal followed by proximal dissection AD (42.1±16.1 versus 54.3±14.8 years;
P
=0.004).

Conclusions:

Among those suffering acute aortic dissection, 5% have a history of a prior aortic dissection. Recurrent AD is strongly associated with Marfan syndrome.
Percutaneous Device Closure of Paravalvular Leak
Authors: Calvert Patrick A. , Northridge David B. , Malik Iqbal S. , Shapiro Leonard , Ludman Peter , Qureshi Shakeel A. , Mullen Michael , Henderson Robert , Turner Mark , Been Martin , Walsh Kevin P. , Casserly Ivan , Morrison Lindsay , Walker Nicola L. , Thomson John , Spence Mark S. , Mahadevan Vaikom S. , Hoye Angela , MacCarthy Philip A. , Daniels Matthew J. , Clift Paul , Davies William R. , Adamson Philip D. , Morgan Gareth , Aggarwal Suneil K. , Ismail Yasmin , Ormerod Julian O. M. , Khan Habib R. , Chandran Sujay Subash , de Giovanni Joseph , Rana Bushra S. , Ormerod Oliver , Hildick-Smith David
Published: September 2016

Background:

Paravalvular leak (PVL) occurs in 5% to 17% of patients following surgical valve replacement. Percutaneous device closure represents an alternative to repeat surgery.

Methods:

All UK and Ireland centers undertaking percutaneous PVL closure submitted data to the UK PVL Registry. Data were analyzed for association with death and major adverse cardiovascular events (MACE) at follow-up.

Results:

Three hundred eight PVL closure procedures were attempted in 259 patients in 20 centers (2004–2015). Patient age was 67±13 years; 28% were female. The main indications for closure were heart failure (80%) and hemolysis (16%). Devices were successfully implanted in 91% of patients, via radial (7%), femoral arterial (52%), femoral venous (33%), and apical (7%) approaches. Nineteen percent of patients required repeat procedures. The target valve was mitral (44%), aortic (48%), both (2%), pulmonic (0.4%), or transcatheter aortic valve replacement (5%). Preprocedural leak was severe (61%), moderate (34%), or mild (5.7%) and was multiple in 37%. PVL improved postprocedure (
P
<0.001) and was none (33.3%), mild (41.4%), moderate (18.6%), or severe (6.7%) at last follow-up. Mean New York Heart Association class improved from 2.7±0.8 preprocedure to 1.6±0.8 (
P
<0.001) after a median follow-up of 110 (7–452) days. Hospital mortality was 2.9% (elective), 6.8% (in-hospital urgent), and 50% (emergency) (
P
<0.001). MACE during follow-up included death (16%), valve surgery (6%), late device embolization (0.4%), and new hemolysis requiring transfusion (1.6%). Mitral PVL was associated with higher MACE (hazard ratio [HR], 1.83;
P
=0.011). Factors independently associated with death were the degree of persisting leak (HR, 2.87;
P
=0.037), New York Heart Association class (HR, 2.00;
P
=0.015) at follow-up and baseline creatinine (HR, 8.19;
P
=0.001). The only factor independently associated with MACE was the degree of persisting leak at follow-up (HR, 3.01;
P
=0.002).

Conclusion:

Percutaneous closure of PVL is an effective procedure that improves PVL severity and symptoms. Severity of persisting leak at follow-up is independently associated with both MACE and death. Percutaneous closure should be considered as an alternative to repeat surgery.
Effects of Atmospheric Surface Layer Stability on Turbulent Fluxes of Heat and Water Vapor across the Water–Atmosphere Interface
Authors: Yusup Yusri , Liu Heping
Published: September 2016

Widely used numerical models to estimate turbulent exchange of latent heat flux (LE) and sensible heat flux H across the water–atmosphere interface are based on the bulk transfer relations linked indirectly to atmospheric stability, even though the accurate prediction of the influence of stability on fluxes is uncertain. Here eddy covariance data collected over the water surface of Ross Barnett Reservoir, Mississippi, was analyzed to study how atmospheric stability and other variables (wind speed, vapor pressure gradient, and temperature gradient) in the atmospheric surface layer (ASL) modulated LE and H variations in different stability ranges. LE and H showed right-skewed, bell-shaped distributions as the ASL stability shifted from very unstable to near neutral and then stable conditions. The results demonstrate that the maximum (minimum) LE and H did not necessarily occur under the most unstable (stable) conditions, but rather in the intermediate stability ranges. No individual variables were able to explain the dependence of LE and H variations on stability. The coupling effects of stability, wind speed, and vapor pressure gradient (temperature gradient) on LE (H) primarily caused the observed variations in LE and H in different stability ranges. These results have important implications for improving parameterization schemes to estimate fluxes over water surfaces in numerical models.