bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of once-daily indacaterol maleate/mometasone furoate on exacerbation risk in adolescent and adult asthma: a double-blind randomised controlled trial
Authors: Beasley Richard W , Donohue James F , Mehta Rajendra , Nelson Harold S , Clay Michelle , Moton Allen , Kim Han-Joo , Hederer Bettina M
Published: February 2015

Objective

To investigate the safety and efficacy of QMF149, a once-daily, fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol maleate and inhaled corticosteroid (ICS) mometasone furoate (MF) for the treatment of persistent asthma. The hypothesis was that QMF149 would not increase the risk of serious asthma exacerbations.

Setting

174 research centres in nine countries.

Participants

1519 adolescents and adults with persistent asthma who were treated or qualified for treatment with combination LABA/ICS were randomised, and 1508 were included in the intention-to-treat analysis.

Intervention

Patients were randomised to QMF149 (indacaterol maleate 500 µg/MF 400 µg) or MF (400 µg) once daily via Twisthaler inhalation device in a double-blind, parallel-group study for 6–21 months.

Primary and secondary outcome measures

The primary end point was time to first serious asthma exacerbation (resulting in hospitalisation, intubation or death). The key secondary end point was annual rate of exacerbations requiring systemic corticosteroids.

Results

Treatment with QMF149 resulted in no significant difference in time to first serious exacerbation compared to MF (2 (0.3%) vs 6 events (0.8%); difference −0.52 percentage point; 95% CI −1.25 to 0.21, p=0.160, HR=0.31; 95% CI 0.06 to 1.54, p=0.151). QMF149 significantly reduced the annual rate of exacerbations requiring systemic corticosteroids (rate ratio=0.71; 95% CI 0.55 to 0.90, p=0.005). Proportions of patients experiencing adverse events were similar across groups (74.0% in the QMF149 group and 73.4% in the MF group). Serious adverse events occurred in 4% and 5.8% of patients in the QMF149 and MF groups, respectively.

Conclusions

No significant difference was observed in the primary outcome of time to first serious asthma exacerbation in patients treated with QMF149 compared with patients treated with MF. Long-term treatment with QMF149 once daily had a favourable safety/efficacy profile in adolescent and adult patients with persistent asthma.

Trial registration number

ClinicalTrials.gov;NCT00941798.
HIV research productivity and structural factors associated with HIV research output in European Union countries: a bibliometric analysis
Authors: Uusküla A , Toompere K , Laisaar K T , Rosenthal M , Pürjer M L , Knellwolf A , Läärä E , Des Jarlais D C
Published: February 2015

Objectives

To assess HIV/AIDS research productivity in the 27 countries of the European Union (EU), and the structural level factors associated with levels of HIV/AIDS research productivity.

Methods

A bibliometric analysis was conducted with systematic search methods used to locate HIV/AIDS research publications (period of 1 January 2002 to 31 December 2011; search databases: MEDLINE (Ovid, PubMed), EMBASE, ISI-Thomson Web of Science; no language restrictions).

The publication rate (number of HIV/AIDS research publications per million population in 10 years) and the rate of articles published in HIV/AIDS journals and selected journals with moderate to very high (IF ≥3) 5-year impact factors were used as markers for HIV research productivity. A negative binomial regression model was fitted to assess the impact of structural level factors (sociodemographic, health, HIV prevalence and research/development indicators) associated with the variation in HIV research productivity.

Results

The total numbers of HIV/AIDS research publications in 2002–2011 by country ranged from 7 to 9128 (median 319). The median publication rate (per million population in 10 years) was 45 (range 5–150) for all publications. Across all countries, 16% of the HIV/AIDS research was published in HIV/AIDS journals and 7% in selected journals with IF ≥3. Indicators describing economic (gross domestic product), demographic (size of the population) and epidemiological (HIV prevalence) conditions as well as overall scientific activity (total research output) in a country were positively associated with HIV research productivity.

Conclusions

HIV research productivity varies noticeably across EU countries, and this variation is associated with recognisable structural factors.
Ultrasound-guided retrieval of lost intrauterine devices using very fine grasping forceps: a case series
Authors: Moro Francesca , Knez Jure , Pateman Katie , Derdelis Grigorios , Foo Xulin , Jurkovic Davor
Published: February 2015

Aim

To assess the efficacy of a novel ultrasound-guided procedure for the retrieval of intrauterine contraceptive devices (IUDs) when the threads are not visible at the external cervical os (‘lost threads’).

Methods

This was a prospective cohort study of consecutive women referred for ultrasound examination because of lost IUD threads. The procedures were performed under local anaesthesia in the outpatient setting. After injection of local anaesthetic, the anterior cervical lip was grasped with a vulsellum forceps. A 5Fr hysteroscopy grasping forceps was introduced transcervically into the uterine cavity under continuous transabdominal ultrasound guidance. The IUD was then grasped and removed from the uterus. Patients’ demographic data, gynaecological history, ultrasound findings, duration of procedure, success rate and pain score were recorded.

Results

Twenty-three consecutive women were included in the study. Ultrasound examination showed an IUD correctly sited in the centre of the uterine cavity in 20/23 (87%), in 2/23 (9%) it was partially embedded in the myometrium and in 1/23 (4%) the IUD was partially sited in the cervical canal. In 8/23 (35%) women the IUD threads were not visible on ultrasound scan. Removal of the IUD was successful in 22/23 (96%) cases with a median operating time of 3 (interquartile range 1.25–4.75) minutes. 15/23 (65%) women experienced no or minimal pain (pain score ≤3), 4/23 (17%) reported moderate pain (pain score 4–6) and 4/23 (17%) described the pain as severe (pain score 7–10). No complications were recorded during or immediately after the procedure.

Conclusions

Ultrasound-guided retrieval of lost IUDs using fine hysteroscopy grasping forceps is a highly successful technique and is well tolerated by women.
Combined inhibition of key potassium currents has different effects on cardiac repolarization reserve and arrhythmia susceptibility in dogs and rabbits
Authors: Husti Zoltán , Tábori Katalin , Juhász Viktor , Hornyik Tibor , Varró András , Baczkó István
Published: February 2015

A reliable assessment of the pro-arrhythmic potential for drugs in the development phase remains elusive. Rabbits and dogs are commonly used to create models of pro-arrhythmia, but the differences between them with respect to repolarizing potassium currents are poorly understood. We investigated the incidence of drug-induced torsades de pointes (TdP) and measured conventional ECG parameters and the short-term variability of the QT interval (STVQT) following combined pharmacological inhibition of IK1+IKs and IK1+IKr in conscious dogs and anesthetized rabbits. A high incidence of TdP was observed following the combined inhibition of IK1+IKs in dogs (67% vs. 14% in rabbits). Rabbits exhibited higher TdP incidence after inhibition of IK1+IKr (72% vs. 14% in dogs). Increased TdP incidence was associated with significantly larger STVQT in both models. The relatively different roles of IK1 and IKs in dog and rabbit repolarization reserve should be taken into account when extrapolating the results from animal models of pro-arrhythmia to humans. A stronger repolarization reserve in dogs (likely due to stronger IK1 and IKs), and the more human-like susceptibility to arrhythmia of rabbits argues for the preferred use of rabbits in the evaluation of adverse pro-arrhythmic effects.
Further evidence for the role of gap junctions in the delayed antiarrhythmic effect of cardiac pacing
Authors: Miskolczi Gottfried , Gönczi Márton , Kovács Mária , Seprényi György , Végh Ágnes
Published: February 2015

The objective of this study was to provide evidence that gap junctions are involved in the delayed antiarrhythmic effect of cardiac pacing. Twenty-four dogs were paced through the right ventricle (4 × 5 min, rate of 240 beats/min) 24 h prior to a 25 min occlusion of the left anterior descending coronary artery. Some of these paced dogs were infused with 50 (n = 7) or 100 μmol/L (n = 7) of the gap junction uncoupler carbenoxolone (CBX), prior to and during the occlusion. Ten sham-paced dogs, subjected only to occlusion, served as the controls. Cardiac pacing markedly reduced the number of ectopic beats and episodes of ventricular tachycardia (VT), as well the incidence of VT and ventricular fibrillation during occlusion. The changes in severity of ischaemia and tissue electrical resistance were also less marked compared with the unpaced controls. Pacing also preserved the permeability of gap junctions, the phosphorylation of connexin43, and the structural integrity of the intercalated discs. The closing of gap junctions with CBX prior to and during ischaemia markedly attenuated or even abolished these protective effects of pacing. Conclusion: Our results support the previous findings that gap junctions play a role in the delayed antiarrhythmic effect of cardiac pacing.
Negligible energetic cost of sonar jamming in a bat–moth interaction
Authors: Corcoran A.J. , Woods H.A.
Published: February 2015

Energetic cost can constrain how frequently animals exhibit behaviors. The energetic cost of acoustic signaling for communication has been the subject of numerous studies; however, the cost of acoustic signaling for predator defense has not been addressed. We studied the energetic cost and efficiency of sound production for the clicks produced by the moth Bertholdia trigona (Grote, 1879) (Grote’s bertholdia) to jam the sonar of predatory bats. This moth is an excellent model species because of its extraordinary ability to produce sound—it clicks at the highest known rate of any moth, up to 4500 clicks·s–1. We measured the metabolic cost of clicking, resting, and flying from moths suspended in a respirometry chamber. Clicking was provoked by playing back an echolocation attack sequence. The cost of sound production for B. trigona was low (66% of resting metabolic rate) and the acoustic efficiency, or the percentage of metabolic power that is converted into sound, was moderately high (0.30% ± 0.15%) compared with other species. We discuss mechanisms that allow B. trigona to achieve their extraordinary clicking rates and high acoustic efficiency. Clicking for jamming bat sonar incurs negligible energetic cost to moths despite being the most effective known anti-bat defense. These results have implications for both the ecology of predator–prey interactions and the evolution of jamming signals.
Overtwisted discs in planar open books
Authors: Ito Tetsuya , Kawamuro Keiko
Published: February 2015

Using open book foliations we show that an overtwisted disc in a planar open book can be put in a topologically nice position. As a corollary, we prove that a planar open book whose fractional Dehn twist coefficients greater than one for all the boundary components supports a tight contact structure.
A discovery of an ultra-pure water detection method based on water mark
Authors: Cao Hui-Wen , Jing Yu-Peng , Zhao Shi-Rui , Xu Xin-Wei , Tian He , Xin Xin , Li Xiao-Ning , Liu Bo , Liu Rui-Tao , Wang Gang , Ge Jie , Cai Hua-Lin , Yang Yi , Ren Tian-Ling
Published: February 2015

The purity evaluation of deionized (DI) water is highly desirable for VLSI or ULSI industry, as the traditional "reverse osmosis filter" cannot always meet the requirement towards the DI water. The filtered DI water may still contain many contaminations which are not up to the standard for the wet cleaning of wafer surface. A novel method is presented by analyzing the residues of a water droplet after the low-temperature evaporation. The contamination contained in the water will remain during the gasification. By analyzing the residual contamination's morphology, the purity of the DI water can be estimated by employing merely a 3D laser microscope. Compared to the traditional fluorescence detecting system for water quality monitoring, it is simpler and has a lower cost. The paper describes an excellent water detection method which is meaningful for preparing ultra-pure water. Experimental results have shown that the deionized distilled (DID) water can repeatedly get a higher purity using this detection method. The DID water can be applied to the wet cleaning of wafer surface, preparation of chemical reagents and many other aspects.
A new dynamic bacterial foraging optimization and its application on model reduction
Authors: Wu Shenli , Wang Sun'an , Li Xiaohu
Published: February 2015

Inspired by the foraging behavior of E. coli bacteria, bacterial foraging optimization (BFO) has emerged as a powerful technique for solving optimization problems. However, BFO shows poor performance on complex and high-dimensional optimization problems. In order to improve the performance of BFO, a new dynamic bacterial foraging optimization based on clonal selection (DBFO-CS) is proposed. Instead of fixed step size in the chemotaxis operator, a new piecewise strategy adjusts the step size dynamically by regulatory factor in order to balance between exploration and exploitation during optimization process, which can improve convergence speed. Furthermore, reproduction operator based on clonal selection can add excellent genes to bacterial populations in order to improve bacterial natural selection and help good individuals to be protected, which can enhance convergence precision. Then, a set of benchmark functions have been used to test the proposed algorithm. The results show that DBFO-CS offers significant improvements than BFO on convergence, accuracy and robustness. A complex optimization problem of model reduction on stable and unstable linear systems based on DBFO-CS is presented. Results show that the proposed algorithm can efficiently approximate the systems.
Synthetic Biology for Specialty Chemicals
Authors: Markham Kelly A. , Alper Hal S.
Published: February 2015

In this review, we address recent advances in the field of synthetic biology and describe how those tools have been applied to produce a wide variety of chemicals in microorganisms. Here we classify the expansion of the synthetic biology toolbox into three different categories based on their primary function in strain engineering—for design, for construction, and for optimization. Next, focusing on recent years, we look at how chemicals have been produced using these new synthetic biology tools. Advances in producing fuels are briefly described, followed by a more thorough treatment of commodity chemicals, specialty chemicals, pharmaceuticals, and nutraceuticals. Throughout this review, an emphasis is placed on how synthetic biology tools are applied to strain engineering. Finally, we discuss organism and host strain diversity and provide a future outlook in the field.
Emotional Labor at a Crossroads: Where Do We Go from Here?
Authors: Grandey Alicia A. , Gabriel Allison S.
Published: February 2015

Three decades after its introduction as a concept, emotional labor—regulating emotions as part of the work role—is fully on the map in organizational behavior and organizational psychology. As research has accelerated, roadblocks, such as fuzzy construct conceptualizations, assumed but untested processes, and methodological stagnation, have emerged. To provide direction to new scholars and suggestions to seasoned emotional labor researchers, we review theoretical perspectives and evidence for emotional labor and its (a) construct development and measurement, (b) chronic and momentary determinants, (c) prediction of employee well-being, and (d) influence on organizational performance. On this path, we introduce emotional labor as a dynamic integration of three components (i.e., emotional requirements, emotion regulation, and emotion performance), interpret personal and organizational moderators, and point to innovative new methodological approaches. Overall, we provide a new road map to jump-start the field in exciting new directions.
Tan’s Epsilon-Determinant and Ranks of Matrices over Semirings
Authors: Mohindru Preeti , Pereira Rajesh
Published: February 2015

We use the ϵ-determinant introduced by Ya-Jia Tan to define a family of ranks of matrices over certain semirings. We show that these ranks generalize some known rank functions over semirings such as the determinantal rank. We also show that this family of ranks satisfies the rank-sum and Sylvester inequalities. We classify all bijective linear maps which preserve these ranks.
Characterization of Protein Complexes and Subcomplexes in Protein-Protein Interaction Databases
Authors: Zaki Nazar , Mohamed Elfadil A. , Mora Antonio
Published: February 2015

The identification and characterization of protein complexes implicated in protein-protein interaction data are crucial to the understanding of the molecular events under normal and abnormal physiological conditions. This paper provides a novel characterization of subcomplexes in protein interaction databases, stressing definition and representation issues, quantification, biological validation, network metrics, motifs, modularity, and gene ontology (GO) terms. The paper introduces the concept of “nested group” as a way to represent subcomplexes and estimates that around 15% of those nested group with the higher Jaccard index may be a result of data artifacts in protein interaction databases, while a number of them can be found in biologically important modular structures or dynamic structures. We also found that network centralities, enrichment in essential proteins, GO terms related to regulation, imperfect 5-clique motifs, and higher GO homogeneity can be used to identify proteins in nested complexes.
Microwave Assisted Healing of Thermally Mendable Composites
Authors: Sosa Edward D. , Darlington Thomas K. , Hanos Brian A. , O’Rourke Mary Jane E.
Published: February 2015

Polymer matrix composites offer high specific strength; however, their potential weight savings have been limited by the concern of damage tolerance. If microcracking and similar incurred damage could be autonomously sealed, composite structures could be built thinner and lighter while still addressing damage tolerance, thus achieving the weight savings they promise. Various self-healing mechanisms have been proposed to this end. Herein, a method of thermally reversible polymerization is investigated. To date, thermally activated repair of composites have been accomplished typically through resistive heating, which has certain inherent complexities. An alternate heating method, via microwave exposure of carbon nanotubes incorporated throughout a thermal reversible polymer matrix, is demonstrated. Carbon nanotube-doped composites exhibit enhanced microwave absorption over an undoped control sample. Furthermore, it is shown that these composites can be heated locally by a focused microwave source. The particular composite formulation and layup studied could be uniformly heated to the targeted healing temperature of 100°C in as little as 20 seconds, followed by a healing time on the scale of minutes with total time depending upon the extent of damage.
Analysis of theThinopyrum elongatumTranscriptome under Water Deficit Stress
Authors: Shu Yongjun , Zhang Jun , Ao You , Song Lili , Guo Changhong
Published: February 2015

The transcriptome ofThinopyrum elongatumunder water deficit stress was analyzed using RNA-Seq technology. The results showed that genes involved in processes of amplification of stress signaling, reductions in oxidative damage, creation of protectants, and roots development were expressed differently, which played an important role in the response to water deficit. TheTh. elongatumtranscriptome research highlights the activation of a large set of water deficit-related genes in this species and provides a valuable resource for future functional analysis of candidate genes in the water deficit stress response.
Study of Grape Polyphenols by Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC/QTOF) and Suspect Screening Analysis
Authors: Flamini Riccardo , De Rosso Mirko , Bavaresco Luigi
Published: February 2015

Suspect screening analysis is a targeted metabolomics method in which the identification of compounds relies on specific available information, such as their molecular formula and isotopic pattern. This method, coupled to liquid chromatography-high-resolution mass spectrometry, is effective in the study of grape metabolomics, in particular for characterization of flavonols, stilbene derivatives, and anthocyanins. For identification of compounds expected in the samples, a new database of putative compounds was expressly constructed by using the molecular information on potential metabolites of grape and wine from the literature and other electronic databases. Currently, this database contains around 1,100 compounds. The method allows identification of several hundred grape metabolites with two analyses (positive and negative ionization modes), and performing of data reprocessing using “untargeted” algorithms also provided the identification of some flavonols and resveratrol trimers and tetramers in grape for the first time. This approach can be potentially used in the study of metabolomics of varieties of other plant species.
On the Nonexistence of Order Isomorphisms between the Sets of All Self-Adjoint and All Positive Definite Operators
Authors: Molnár Lajos
Published: February 2015

We prove that there is no bijective map between the set of all positive definite operators and the set of all self-adjoint operators on a Hilbert space with dimension greater than 1 which preserves the usual order (the one coming from the concept of positive semidefiniteness) in both directions. We conjecture that a similar assertion is true for general noncommutativeC*-algebras and present a proof in the finite dimensional case.
Hybrid Swarm Intelligence Optimization Approach for Optimal Data Storage Position Identification in Wireless Sensor Networks
Authors: Mohanasundaram Ranganathan , Periasamy Pappampalayam Sanmugam
Published: February 2015

The current high profile debate with regard to data storage and its growth have become strategic task in the world of networking. It mainly depends on the sensor nodes called producers, base stations, and also the consumers (users and sensor nodes) to retrieve and use the data. The main concern dealt here is to find an optimal data storage position in wireless sensor networks. The works that have been carried out earlier did not utilize swarm intelligence based optimization approaches to find the optimal data storage positions. To achieve this goal, an efficient swam intelligence approach is used to choose suitable positions for a storage node. Thus, hybrid particle swarm optimization algorithm has been used to find the suitable positions for storage nodes while the total energy cost of data transmission is minimized. Clustering‐based distributed data storage is utilized to solve clustering problem using fuzzy‐C‐means algorithm. This research work also considers the data rates and locations of multiple producers and consumers to find optimal data storage positions. The algorithm is implemented in a network simulator and the experimental results show that the proposed clustering and swarm intelligence based ODS strategy is more effective than the earlier approaches.
Time for a Break: Admissions to an Urban Emergency Department after Working Out—A Retrospective Study from Switzerland
Authors: Imstepf Valentina A. , Braun Christian T. , Ricklin Meret E. , Exadaktylos Aristomenis K.
Published: February 2015

Background. The present retrospective study was intended to investigate whether working out and other low-speed sports can provoke cardiovascular, neurological, or traumatic damage.Material and Methods. Patient data from 2007 to 2013 was collected and saved at the university department of emergency medicine in an electronic patient record database.Results. Of the 138 patients included in this study, 83.3% (n=115) were male and 16.7% female (n=23). Most admissions were due to musculoskeletal accidents (n=77; 55.8%), followed by neurological incidents (n=23; 16.7%), cardiovascular incidents (n=19; 13.8%), soft tissue injuries (n=3; 2.2%), and others (n=16; 11.6%). The mean age of the allover injured people was 36.7 years. The majority of the patients (n=113; 81.9%) were treated as outpatients; 24 (17.4%) were inpatients.Discussion. In Switzerland, this is the first study that describes emergency department admissions after workout and examines trauma and neurological and cardiovascular incidents. As specific injuries, such as brain haemorrhages, STEMIs, and epileptic seizures, were relatively frequent, it was hypothesised that workout with its physiological changes may be an actual trigger for these injuries, at least for a specific population.Conclusion. Strenuous physical activity may trigger the risk of cardiovascular, neurological, or trauma events.
Crosstalk between Red Blood Cells and the Immune System and Its Impact on Atherosclerosis
Authors: Buttari Brigitta , Profumo Elisabetta , Riganò Rachele
Published: February 2015

Atherosclerosis is a chronic multifactorial disease of the arterial wall characterized by inflammation, oxidative stress, and immune system activation. Evidence exists on a pathogenic role of oxidized red blood cells (RBCs) accumulated in the lesion after intraplaque hemorrhage. This review reports current knowledge on the impact of oxidative stress in RBC modifications with the surface appearance of senescent signals characterized by reduced expression of CD47 and glycophorin A and higher externalization of phosphatidylserine. The review summarizes findings indicating that oxidized, senescent, or stored RBCs, due to surface antigen modification and release of prooxidant and proinflammatory molecules, exert an impaired modulatory activity on innate and adaptive immune cells and how this activity contributes to atherosclerotic disease. In particular RBCs from patients with atherosclerosis, unlike those from healthy subjects, fail to control lipopolysaccharide-induced DC maturation and T lymphocyte apoptosis. Stored RBCs, accompanied by shedding of extracellular vesicles, stimulate peripheral blood mononuclear cells to release proinflammatory cytokines, augment mitogen-driven T cell proliferation, and polarize macrophages toward the proinflammatory M1 activation pathway. Collectively, literature data suggest that the crosstalk between RBCs with immune cells represents a novel mechanism by which oxidative stress can contribute to atherosclerotic disease progression and may be exploited for therapeutic interventions.
Characteristics of DSSC Panels with Silicone Encapsulant
Authors: Kang Jun-Gu , Kim Jin-Hee , Jang Han-Bin , Kim Jun-Tae
Published: February 2015

Dye-sensitized solar cells (DSSC) allow light transmission and the application of various colors that make them especially suitable for building-integrated PV (BIPV) application. In order to apply DSSC modules to windows, the module has to be panelized: a DSSC module should be protected with toughened glass on the entire surface. Up to the present, it seems to be common to use double glazing with DSSC modules, with air gaps between the glass pane and the DSSC modules. Few studies have been conducted on the characteristics of various glazing methods with DSSC modules. This paper proposes a paneling method that uses silicone encapsulant, analyzing the performance through experimentation. Compared to a multilayered DSSC panel with an air gap, the encapsulant-applied panel showed 6% higher light transmittance and 7% higher electrical efficiency. The encapsulant also prevented electrolyte leakage by strengthening the seals in the DSSC module.
The Standard Molar Enthalpies of Formation of Nano‐ZnO Particles with Different Morphologies
Authors: Li Ya , Wu Xinmin
Published: February 2015

The thermodynamic properties of nano‐ZnO particles with different morphologies were studied. First, based on the measurements of XRD and SEM, the morphologies of the five nano‐ZnO products were determined as sheet, block, sieve, column, and rod, and their particle size was about 40 nm. Then, based on a designed thermodynamic cycle, the standard molar enthalpies of formation of the nano‐ZnO particles were determined by the RD496‐2000 microcalorimeter, and they are (sheet) = (−337.43  ±  0.47) kJ·mol−1, (block) = (−336.57  ±  0.43) kJ·mol−1, (sieve) = (−337.04  ±  0.57) kJ·mol−1, (column) = (−343.56  ±  0.39) kJ·mol−1, and (rod) = (−341.43  ±  0.41) kJ·mol−1. The results show that the bigger difference of the morphologies of nano‐ZnO, the bigger difference of the standard molar enthalpies of formation.
Pathfast Presepsin Assay for Early Diagnosis of Systemic Inflammatory Response Syndrome in Patients with Nephrolithiasis
Authors: Hou Yan-song , Wang Hua , Chen Hao , Wu Ling-feng , Lu Lin-feng , He Yi
Published: February 2015

It is relatively difficult to diagnose bacterial sepsis in nephrolithiasis patients. The aim of the study is to evaluate the diagnostic ability of presepsin in the differential diagnosis including SIRS, infection, or sepsis and to compare its diagnostic value with other markers, mainly as CRP, procalcitonin (PCT), and white blood cell (WBC) in patients of nephrolithiasis presenting with SIRS. 39 patients of nephrolithiasis who were diagnosed as SIRS were prospectively investigated. Plasma presepsin was detected by Pathfast presepsin assay system; CRP and PCT were measured as well. Additionally, 25 nephrolithiasis patients without SIRS were included. At all timing samples, patients were classified as SIRS or non-SIRS group. Median plasma presepsin levels were significantly increased in the SIRS group compared with non-SIRS group (452 pg/mL versus 178 ng/mL,P<0.001), and presepsin was markedly elevated even in the early stage of SIRS (584 pg/mL 6 h, 660 pg/mL 24 h versus 452 pg/mL,P<0.001). According to the receiver-operating characteristic (ROC) analysis, presepsin demonstrated a high diagnostic value compared with either PCT or CRP. In the early stage of SIRS, presepsin remained a highly sensitive (74.7%) and specific (88.4%) diagnostic marker compared with either PCT, CRP, or WBC. Moreover, the areas under the curve (AUCs) of presepsin (84.6%) were also superior to those seen in either PCT (79.6%) or CRP (71.8%). Thus plasma presepsin levels have comparable performance in SIRS for patients with nephrolithiasis.
Integral Sliding Mode Control for Helicopter via Disturbance Observer and Quantum Information Technique
Authors: Qu Qiang , Chen Fuyang , Jiang Bin , Tao Gang
Published: February 2015

A novel self-repairing control scheme is proposed for a helicopter with unknown disturbance. Firstly, a disturbance observer is introduced to observe the disturbance of the system, which can produce corresponding control signals according to the disturbance signals. Secondly, an integral sliding mode controller is designed to compensate the unobserved disturbance and uncertainties. All of the closed-loop poles can be arbitrarily placed and the output errors converge to zero effectively through the controller. Besides, a robust closed-loop system against disturbance and parameter uncertainties is achieved. In addition, quantum information technique is used to increase the self-repairing control accuracy of helicopter. Finally, simulation results demonstrate the effectiveness and feasibility of the proposed self-repairing control scheme.
Unconditional Positive Stable Numerical Solution of Partial Integrodifferential Option Pricing Problems
Authors: Fakharany M. , Company R. , Jódar L.
Published: February 2015

This paper is concerned with the numerical solution of partial integrodifferential equation for option pricing models under a tempered stable process known as CGMY model. A double discretization finite difference scheme is used for the treatment of the unbounded nonlocal integral term. We also introduce in the scheme the Patankar-trick to guarantee unconditional nonnegative numerical solutions. Integration formula of open type is used in order to improve the accuracy of the approximation of the integral part. Stability and consistency are also studied. Illustrative examples are included.
CYP3A5 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Regulating mTORC2/Akt Signaling
Authors: Jiang Feng , Chen Lei , Yang Ying-Cheng , Wang Xian-ming , Wang Ruo-Yu , Li Liang , Wen Wen , Chang Yan-Xin , Chen Cai-Yang , Tang Jing , Liu Gao-Mi-Yang , Huang Wen-Tao , Xu Lin , Wang Hong-Yang
Published: February 2015

CYP3A5 is a cytochrome P450 protein that functions in the liver metabolism of many carcinogens and cancer drugs. However, it has not been thought to directly affect cancer progression. In this study, we challenge this perspective by demonstrating that CYP3A5 is downregulated in many hepatocellular carcinomas (HCC), where it has an important role as a tumor suppressor that antagonizes the malignant phenotype. CYP3A5 was downregulated in multiple cohorts of human HCC examined. Lower CYP3A5 levels were associated with more aggressive vascular invasion, poor differentiation, shorter time to disease recurrence after treatment, and worse overall patient survival. Mechanistic investigations showed that CYP3A5 overexpression limited MMP2/9 function and suppressed HCC migration and invasion in vitro and in vivo by inhibiting AKT signaling. Notably, AKT phosphorylation at Ser473 was inhibited in CYP3A5-overexpressing HCC cells, an event requiring mTORC2 but not Rictor/mTOR complex formation. CYP3A5-induced ROS accumulation was found to be a critical upstream regulator of mTORC2 activity, consistent with evidence of reduced GSH redox activity in most clinical HCC specimens with reduced metastatic capacity. Taken together, our results defined CYP3A5 as a suppressor of HCC pathogenesis and metastasis with potential utility a prognostic biomarker. Cancer Res; 75(7); 1470–81. ©2015 AACR.
BH3 Inhibitor Sensitivity and Bcl-2 Dependence in Primary Acute Lymphoblastic Leukemia Cells
Authors: Alford Sarah E. , Kothari Anisha , Loeff Floris C. , Eichhorn Joshua M. , Sakurikar Nandini , Goselink Henriette M. , Saylors Robert L. , Jedema Inge , Falkenburg J.H. Frederik , Chambers Timothy C.
Published: February 2015

BH3 mimetic drugs may be useful to treat acute lymphoblastic leukemia (ALL) but the sensitivity of primary tumor cells has not been fully evaluated. Here, B-lineage ALL cell cultures derived from a set of primary tumors were studied with respect to sensitivity to the BH3 mimetics ABT-263 and ABT-199 and to Bcl-2 dependence and function. These ALL cells each expressed high levels of Bcl-2 and exhibited great sensitivity to ABT-263 and ABT-199, which induced rapid apoptotic cell death. BH3 profiling indicated that the ALL cultures were Bcl-2 dependent. Coimmunoprecipitation studies revealed a multifaceted role for Bcl-2 in binding proapoptotic partners including Bax, Bak, Bik, and Bim. ABT-263 disrupted Bcl-2:Bim interaction in cells. Mcl-1 overexpression rendered ALL cells resistant to ABT-263 and ABT-199, with Mcl-1 assuming the role of Bcl-2 in binding Bim. Freshly isolated pediatric ALL blasts also expressed high levels of Bcl-2 and exhibited high sensitivity to Bcl-2 inhibition by the BH3 mimetic compounds. Overall, our results showed that primary ALL cultures were both more sensitive to BH3 mimetics and more uniform in their response than established ALL cell lines that have been evaluated previously. Furthermore, the primary cell model characterized here offers a powerful system for preclinical testing of novel drugs and drug combinations to treat ALL. Cancer Res; 75(7); 1366–75. ©2015 AACR.
Interaction between p53 Mutation and a Somatic HDMX Biomarker Better Defines Metastatic Potential in Breast Cancer
Authors: Grawenda Anna M. , Møller Elen K. , Lam Suzanne , Repapi Emmanouela , Teunisse Amina F.A.S. , Alnæs Grethe I.G. , Børresen-Dale Anne-Lise , Kristensen Vessela N. , Goding Colin R. , Jochemsen Aart G. , Edvardsen Hege , Bond Gareth L.
Published: February 2015

TP53 gene mutation is associated with poor prognosis in breast cancer, but additional biomarkers that can further refine the impact of the p53 pathway are needed to achieve clinical utility. In this study, we evaluated a role for the HDMX-S/FL ratio as one such biomarker, based on its association with other suppressor mutations that confer worse prognosis in sarcomas, another type of cancer that is surveilled by p53. We found that HDMX-S/FL ratio interacted with p53 mutational status to significantly improve prognostic capability in patients with breast cancer. This biomarker pair offered prognostic utility that was comparable with a microarray-based prognostic assay. Unexpectedly, the utility tracked independently of DNA-damaging treatments and instead with different tumor metastasis potential. Finally, we obtained evidence that this biomarker pair might identify patients who could benefit from anti-HDM2 strategies to impede metastatic progression. Taken together, our work offers a p53 pathway marker, which both refines our understanding of the impact of p53 activity on prognosis and harbors potential utility as a clinical tool. Cancer Res; 75(4); 698–708. ©2015 AACR.
Survivorship in Immune Therapy: Assessing Chronic Immune Toxicities, Health Outcomes, and Functional Status among Long-term Ipilimumab Survivors at a Single Referral Center
Authors: Johnson Douglas B. , Friedman Debra L. , Berry Elizabeth , Decker Ilka , Ye Fei , Zhao Shilin , Morgans Alicia K. , Puzanov Igor , Sosman Jeffrey A. , Lovly Christine M.
Published: February 2015

Ipilimumab, a novel immune checkpoint inhibitor, is associated with long-term survival in approximately 20% of patients with advanced melanoma and is also being evaluated in the adjuvant setting. With this growing cohort of survivors, long-term health outcomes, chronic toxicities, and functional outcomes among survivors treated with ipilimumab need to be defined. Using retrospective medical record abstraction, we evaluated disease status, chronic immune- and non–immune-related health events, pharmacologic management of symptoms, and functional status in patients with melanoma, with overall survival ≥2 years following ipilimumab treatment at Vanderbilt University. Ninety patients received ipilimumab for metastatic disease or as adjuvant therapy between January 2006 and September 2012, and 33 patients survived ≥2 years, with a median overall survival of 60.1 months. Of these, 24 patients were alive at the last follow-up (73%), with 14 patients free of disease (42%). Gastrointestinal and dermatologic adverse events were frequent but largely transient. By contrast, patients with hypophysitis universally required ongoing corticosteroids, although largely remained asymptomatic with appropriate hormone replacement. Surviving patients generally had excellent performance status (ECOG 0–1 in 23 of 24). Chronic neurologic toxicities caused substantial morbidity and mortality in 2 patients who received whole-brain radiotherapy >5 years before analysis, and in one patient with chronic, painful peripheral neuropathy. No previously undescribed cardiac, pulmonary, gastrointestinal, hematologic, or neoplastic safety signals were identified. In conclusion, ipilimumab was associated with largely excellent functional outcomes among long-term survivors. Chronic endocrine dysfunction and occasional neurologic toxicity (primarily associated with whole-brain radiation) were observed in a small number of patients. Cancer Immunol Res; 3(5); 464–9. ©2015 AACR.
Long-Term Results after Acute Therapy of Obstructive Pyelonephritis
Authors: Vahlensieck Winfried , Friess Doris , Fabry Werner , Waidelich Raphaela , Bschleipfer Thomas
Published: February 2015

Introduction: To evaluate therapeutic results till 5 years after therapy of obstructive pyelonephritis (OPN) emphasizing regular follow-up. Material and Methods: During 5 years, 57 patients with OPN were treated. The patients' charts were reviewed retrospectively for clinical data. These were completed by a questionnaire. Results: In the group of 57 patients (average age 56 years), about two third were women. Urolithiasis (65%) and tumors (21%) were the main causes of obstruction; fever (91%) and loin pain (86%) the main symptoms. Three fourth of the patients showed renal insufficiency and nearly 50% anemia. E. coli and Proteus spp. were the dominating organisms. Sonography detected obstruction in 93% cases. In one third of cases, CT scan was added; 81% percutaneous nephrostomy and 19% ureteral stenting were the initial methods of urinary drainage. During therapy, 23% nephrectomies (19% complete, 4% partial) were performed. Long-term follow-up showed 11% recurrent OPN and 33% recurrent UTI. Conclusions: After diagnosis of OPN, primary nephrostomy or ureteral stenting and antibiotic therapy are the first measures. If recurrent urinary tract infections or OPN occur, long-term follow-up and low-dose antibiotic prophylaxis may be discussed.
Fetal MRI of Torsed Bronchopulmonary Sequestration with Tension Hydrothorax and Hydrops in a Twin Gestation
Authors: Coleman Alan M. , Merrow Arnold C. , Crombleholme Timothy M. , Jaekle Ronald , Lim Foong-Yen
Published: February 2015

While bronchopulmonary sequestration typically has a benign course, this congenital lung malformation has a high mortality rate when associated with untreated in utero tension hydrothorax and hydrops. Hydrops related to bronchopulmonary sequestration is believed to result from torsion of the mass with compromise of the associated blood supply. The impaired venous return of the mass then leads to tension hydrothorax with compression of the heart and mediastinal vessels, impairing global venous return. To our knowledge, this scenario has only been described prenatally by ultrasound. We present the imaging findings of a dichorionic, diamniotic twin gestation with one fetus developing tension hydrothorax and hydrops from presumed intermittent torsion of a bronchopulmonary sequestration. This diagnosis was only able to be confirmed by MRI prior to the use of ultrasound-guided interstitial laser photocoagulation for the treatment of this anomaly.
Differential Effect of B-Vitamin Therapy by Antiplatelet Use on Risk of Recurrent Vascular Events After Stroke
Authors: Arshi Baback , Ovbiagele Bruce , Markovic Daniela , Saposnik Gustavo , Towfighi Amytis
Published: February 2015

Background and Purpose—

Although several randomized controlled trials failed to show a benefit of B vitamin therapy on composite outcomes of cardiovascular death, myocardial infarction, and stroke among individuals with elevated homocysteine, recent post hoc analyses have suggested that several factors may interact with the effects of vitamin treatment. One post hoc analysis revealed an interaction between B vitamin therapy and antiplatelet use; however, those results have not been replicated in other studies or populations.

Methods—

We conducted a post hoc analysis of the Vitamin Intervention for Stroke Prevention (VISP) trial, a randomized controlled trial evaluating treatment with high- versus low-dose B vitamin therapy for secondary prevention of vascular events among stroke survivors with elevated homocysteine. Cox regression models were used to assess primary (recurrent stroke) and secondary (stroke, myocardial infarction, or vascular death) outcomes among individuals on high- versus low-dose vitamin therapy, categorized by antiplatelet use, after adjusting for covariates.

Results—

Among 3680 participants, 52% took antiplatelet medications. When compared with low-dose therapy, high-dose vitamin therapy was associated with higher stroke risk among individuals on antiplatelets (hazard ratio, 1.43; 95% confidence interval, 1.02–2.01), but trended toward lower risk among those not on antiplatelets (hazard ratio, 0.86; 95% confidence interval, 0.62–1.19).

Conclusions—

High-dose B vitamin therapy may be associated with a higher risk of recurrent stroke among stroke survivors taking antiplatelets, but does not have a significant effect on recurrent stroke risk in those who are not on antiplatelets. Future randomized controlled trials may consider evaluating the effect of homocysteine lowering among stroke survivors with elevated homocysteine who are not on antiplatelet therapy.
Biomarkers and Mortality After Transient Ischemic Attack and Minor Ischemic Stroke
Authors: Greisenegger Stefan , Segal Helen C. , Burgess Annette I. , Poole Debbie L. , Mehta Ziyah , Rothwell Peter M.
Published: February 2015

Background and Purpose—

Premature death after transient ischemic attack or stroke is more often because of heart disease or cancer than stroke. Previous studies found blood biomarkers not usefully predictive of nonfatal stroke but possibly of all-cause death. This association might be explained by potentially treatable occult cardiac disease or cancer. We therefore aimed to validate the association of a panel of biomarkers with all-cause death, particularly cardiac death and cancer death, despite the absence of associations with risk of nonfatal vascular events.

Methods—

Fifteen biomarkers were measured in 929 consecutive patients in a population-based study (Oxford Vascular Study), recruited from 2002 and followed up to 2013. Associations were determined by Cox regression. Model discrimination was assessed by
c
-statistic and the integrated discrimination improvement.

Results—

During 5560 patient-years of follow-up, none of the biomarkers predicted risk of nonfatal vascular events. However, soluble tumor necrosis factor α receptor-1, von Willebrand factor, heart-type fatty-acid-binding protein, and N-terminal pro-B-type natriuretic peptide were independently predictive of all-cause death (n=361; adjusted hazard ratio per SD, 95% confidence interval: heart-type fatty-acid-binding protein: 1.31, 1.12–1.56,
P
=0.002; N-terminal pro-B-type natriuretic peptide: 1.34, 1.11–1.62,
P
=0.002; soluble tumor necrosis factor α receptor-1: 1.45, 1.26–1.66,
P
=0.02; von Willebrand factor: 1.19, 1.04–1.36,
P
=0.01). The independent contribution of the four biomarkers taken together added prognostic information and improved model discrimination (integrated discrimination improvement=0.028,
P
=0.0001). N-terminal pro-B-type natriuretic peptide was most predictive of vascular death (adjusted hazard ratio=1.80, 95% confidence interval, 1.34–2.41,
P
<0.0001), whereas heart-type fatty-acid-binding protein predicted cancer deaths (1.64, 1.26–2.12,
P
=0.0002). Associations were strongest in patients without known prior cardiac disease or cancer.

Conclusions—

Several biomarkers predicted death of any cause after transient ischemic attack and minor stroke. N-terminal pro-B-type natriuretic peptide and heart-type fatty-acid-binding protein might improve patient selection for additional screening for occult cardiac disease or cancer, respectively. However, our results require validation in future studies.