Multilayer perceptron architecture optimization using parallel computing techniques.

PubMed

Castro, Wilson; Oblitas, Jimy; Santa-Cruz, Roberto; Avila-George, Himer

2017-01-01

The objective of this research was to develop a methodology for optimizing multilayer-perceptron-type neural networks by evaluating the effects of three neural architecture parameters, namely, number of hidden layers (HL), neurons per hidden layer (NHL), and activation function type (AF), on the sum of squares error (SSE). The data for the study were obtained from quality parameters (physicochemical and microbiological) of milk samples. Architectures or combinations were organized in groups (G1, G2, and G3) generated upon interspersing one, two, and three layers. Within each group, the networks had three neurons in the input layer, six neurons in the output layer, three to twenty-seven NHL, and three AF (tan-sig, log-sig, and linear) types. The number of architectures was determined using three factorial-type experimental designs, which reached 63, 2 187, and 50 049 combinations for G1, G2 and G3, respectively. Using MATLAB 2015a, a logical sequence was designed and implemented for constructing, training, and evaluating multilayer-perceptron-type neural networks using parallel computing techniques. The results show that HL and NHL have a statistically relevant effect on SSE, and from two hidden layers, AF also has a significant effect; thus, both AF and NHL can be evaluated to determine the optimal combination per group. Moreover, in the three study groups, it is observed that there is an inverse relationship between the number of processors and the total optimization time.

Multilayer perceptron architecture optimization using parallel computing techniques

PubMed Central

Castro, Wilson; Oblitas, Jimy; Santa-Cruz, Roberto; Avila-George, Himer

2017-01-01

The objective of this research was to develop a methodology for optimizing multilayer-perceptron-type neural networks by evaluating the effects of three neural architecture parameters, namely, number of hidden layers (HL), neurons per hidden layer (NHL), and activation function type (AF), on the sum of squares error (SSE). The data for the study were obtained from quality parameters (physicochemical and microbiological) of milk samples. Architectures or combinations were organized in groups (G1, G2, and G3) generated upon interspersing one, two, and three layers. Within each group, the networks had three neurons in the input layer, six neurons in the output layer, three to twenty-seven NHL, and three AF (tan-sig, log-sig, and linear) types. The number of architectures was determined using three factorial-type experimental designs, which reached 63, 2 187, and 50 049 combinations for G1, G2 and G3, respectively. Using MATLAB 2015a, a logical sequence was designed and implemented for constructing, training, and evaluating multilayer-perceptron-type neural networks using parallel computing techniques. The results show that HL and NHL have a statistically relevant effect on SSE, and from two hidden layers, AF also has a significant effect; thus, both AF and NHL can be evaluated to determine the optimal combination per group. Moreover, in the three study groups, it is observed that there is an inverse relationship between the number of processors and the total optimization time. PMID:29236744

Investigation of Optimal Time for Starting Betamethasone Using Fatigue Scores and Prognostic Nutritional Index in Terminally Ill Patients With Cancer-Related Fatigue.

PubMed

Koyama, Nanako; Matsumura, Chikako; Morii, Hiroaki; Hasegawa, Chiaki; Hira, Daiki; Daigo, Yataro; Terada, Tomohiro; Yano, Yoshitaka

2017-06-01

Corticosteroids are frequently used to treat cancer-related fatigue (CRF), but it is yet to be established as standard care, and few reports have defined the appropriate time to start treatment. We investigated the optimal time for starting betamethasone and evaluated the clinical validity of using the prognostic nutritional index (PNI) for this purpose. Data were retrospectively collected for patients with terminal cancer receiving betamethasone for palliative care. Fatigue strength was evaluated by the daily occurrence of fatigue, using proportion of adequate fatigue, AF(%), defined as the average of the daily score for all treatment days, AF(%) all , the initial 5 days, AF(%) initi5 , or the last 5 days, AF(%) last5 . We examined (1) the relationship between survival time and adequate fatigue for CRF and (2) the correlation between survival time and PNI (based on serum albumin and lymphocytes). Data from 24 patients were included. The AF(%) all was approximately 50% at 42 days before death and gradually decreased as the survival time shortened ( R 2 =.41, P <.001). There was a clear positive correlation between AF(%) all and AF(%) initi5 ( R 2 =.84, P <.001). At 42 days before death, PNI was approximately 30 and significantly correlated with the survival time ( R 2 = .873, P <.001). The adequate fatigue appears to be dependent on survival time, and PNI might be useful for identifying patients that will benefit from betamethasone use. It is hoped that these results will contribute to individualized pharmacotherapy of terminally ill patients with CRF.

The future of anticoagulation management in atrial fibrillation in Europe: An assessment of today's challenges with recommendations for the future.

PubMed

Lichten, Catherine A; Castle-Clarke, Sophie; Manville, Catriona; Horvath, Veronika; Robin, Enora; Krapels, Joachim; Parks, Sarah; Sim, Megan; van Zijverden, Olga; Chataway, Joanna

2015-11-30

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, affecting approximately 1-2 per cent of the population worldwide. Those who suffer from AF have a five times higher risk of stroke. AF prevalence increases with age and it affects roughly 18 per cent of the population over 85. Consequently, as populations age, AF is becoming an increasingly significant public health issue. Over recent years there have been developments in treatment and management options, both for treating the arrhythmia directly, and assessing and reducing the risk of AF-related stroke, but there is a need to ensure that available knowledge is applied optimally to benefit patients so that opportunities to prevent AF-related stroke are not missed. The aims of this project were to assess the current landscape and explore the direction of future developments in AF management in Europe, with a focus on the use of anticoagulants in the prevention of AF-related stroke. Through rapid evidence assessment, key informant interviews, PESTLE analysis and the development and exploration of future scenarios, we have developed sets of shorter- and longer-term recommendations for improving AF-related patient outcomes. The short-term recommendations are: i) improve AF awareness among the public and policymakers; ii) support education about AF management for healthcare professionals and patients; and iii) maintain engagement in AF-related research across the health services.

Coordination between airway facilities specialists and air traffic personnel.

DOT National Transportation Integrated Search

2002-04-01

Airway Facilities (AF) is responsible for providing services and conducting operations that deliver the highest possible levels of National Airspace System (NAS) safety and efficiency. To accomplish this, AF specialists perform maintenance tasks for ...

Ablation as targeted perturbation to rewire communication network of persistent atrial fibrillation

PubMed Central

Tao, Susumu; Way, Samuel F.; Garland, Joshua; Chrispin, Jonathan; Ciuffo, Luisa A.; Balouch, Muhammad A.; Nazarian, Saman; Spragg, David D.; Marine, Joseph E.; Berger, Ronald D.; Calkins, Hugh

2017-01-01

Persistent atrial fibrillation (AF) can be viewed as disintegrated patterns of information transmission by action potential across the communication network consisting of nodes linked by functional connectivity. To test the hypothesis that ablation of persistent AF is associated with improvement in both local and global connectivity within the communication networks, we analyzed multi-electrode basket catheter electrograms of 22 consecutive patients (63.5 ± 9.7 years, 78% male) during persistent AF before and after the focal impulse and rotor modulation-guided ablation. Eight patients (36%) developed recurrence within 6 months after ablation. We defined communication networks of AF by nodes (cardiac tissue adjacent to each electrode) and edges (mutual information between pairs of nodes). To evaluate patient-specific parameters of communication, thresholds of mutual information were applied to preserve 10% to 30% of the strongest edges. There was no significant difference in network parameters between both atria at baseline. Ablation effectively rewired the communication network of persistent AF to improve the overall connectivity. In addition, successful ablation improved local connectivity by increasing the average clustering coefficient, and also improved global connectivity by decreasing the characteristic path length. As a result, successful ablation improved the efficiency and robustness of the communication network by increasing the small-world index. These changes were not observed in patients with AF recurrence. Furthermore, a significant increase in the small-world index after ablation was associated with synchronization of the rhythm by acute AF termination. In conclusion, successful ablation rewires communication networks during persistent AF, making it more robust, efficient, and easier to synchronize. Quantitative analysis of communication networks provides not only a mechanistic insight that AF may be sustained by spatially localized sources and global connectivity, but also patient-specific metrics that could serve as a valid endpoint for therapeutic interventions. PMID:28678805

Experimentation on the anaerobic filter reactor for biogas production using rural domestic wastewater

NASA Astrophysics Data System (ADS)

Leju Celestino Ladu, John; Lü, Xi-wu; Zhong, Zhaoping

2017-08-01

The biogas production from anaerobic filter (AF) reactor was experimented in Taihu Lake Environmental Engineering Research Center of Southeast University, Wuxi, China. Two rounds of experimental operations were conducted in a laboratory scale at different Hydraulic retention time (HRT) and wastewater temperature. The biogas production rate during the experimentation was in the range of 4.63 to 11.78 L/d. In the first experimentation, the average gas production rate was 10.08 L/d, and in the second experimentation, the average gas production rate was 4.97 L/d. The experimentation observed the favorable Hydraulic Retention Time and wastewater temperature in AF was three days and 30.95°C which produced the gas concentration of 11.78 L/d. The HRT and wastewater temperature affected the efficiency of the AF process on the organic matter removal and nutrients removal as well. It can be deduced from the obtained results that HRT and wastewater temperature directly affects the efficiency of the AF reactor in biogas production. In conclusion, anaerobic filter treatment of organic matter substrates from the rural domestic wastewater increases the efficiency of the AF reactor on biogas production and gives a number of benefits for the management of organic wastes as well as reduction in water pollution. Hence, the operation of the AF reactor in rural domestic wastewater treatment can play an important element for corporate economy of the biogas plant, socio-economic aspects and in the development of effective and feasible concepts for wastewater management, especially for people in rural low-income areas.

Maximizing Performance: Augmented Feedback, Focus of Attention, and/or Reward?

PubMed

Wälchli, Michael; Ruffieux, Jan; Bourquin, Yann; Keller, Martin; Taube, Wolfgang

2016-04-01

Different approaches like providing augmented feedback (aF), applying an external focus of attention (EF), or rewarding participants with money (RE) have been shown to instantly enhance motor performance. So far, these approaches have been tested either in separate studies or directly against each other. However, there is no study that combined aF, EF, and/or RE to test whether this provokes additional benefits. The aim of the present study was therefore to identify the most powerful combination. Eighteen participants performed maximal countermovement jumps in six different conditions: neutral (NE), aF, RE, aF + EF, aF + RE, and aF + EF + RE. Participants demonstrated the highest jump heights with aF + EF, followed by aF + EF + RE, aF + RE, aF, RE, and finally, NE. Activity of the M. rectus femoris differed significantly between conditions resulting in lower muscular activity in aF + EF and aF + EF + RE compared with NE. All other parameters, such as ground reaction forces and joint angles, were comparable across conditions. This is the first study showing superior performance when combining aF with EF. As reduced muscular activity was found only in conditions with EF, it is argued in line with the constrained action hypothesis that adopting an EF improves movement efficiency. In contrast, aF seems to rather enhance (intrinsic) motivation. However, monetary reward did not further amplify performance.

Paving the way to a full chip gate level double patterning application

NASA Astrophysics Data System (ADS)

Haffner, Henning; Meiring, Jason; Baum, Zachary; Halle, Scott

2007-10-01

Double patterning lithography processes can offer significant yield enhancement for challenging circuit designs. Many decomposition (i.e. the process of dividing the layout design into first and second exposures) techniques are possible, but the focus of this paper is on the use of a secondary "cut" mask to trim away extraneous features left from the first exposure. This approach has the advantage that each exposure only needs to support a subset of critical features (e.g. dense lines with the first exposure, isolated spaces with the second one). The extraneous features ("printing assist features" or PrAFs) are designed to support the process window of critical features much like the role of the subresolution assist features (SRAFs) in conventional processes. However, the printing nature of PrAFs leads to many more design options, and hence a greater process and decomposition parameter exploration space, than are available for SRAFs. A decomposition scheme using PRAFs was developed for a gate level process. A critical driver of the work was to deliver improved across-chip linewidth variation (ACLV) performance versus an optimized single exposure process while providing support for a larger range of critical features. A variety of PRAF techniques were investigated by simulation, with a PrAF scheme similar to standard SRAF rules being chosen as the optimal solution [1]. This paper discusses aspects of the code development for an automated PrAF generation and placement scheme and the subsequent decomposition of a layout into two mask levels. While PrAF placement and decomposition is straightforward for layouts with pitch and orientation restrictions, it becomes rather complex for unrestricted layout styles. Because this higher complexity yields more irregularly shaped PrAFs, mask making becomes another critical driver of the optimum placement and clean-up strategies. Examples are given of how those challenges are met or can be successfully circumvented. During subsequent decomposition of the PrAF-enhanced layout into two independent mask levels, various geometric decomposition parameters have to be considered. As an example, the removal of PrAFs has to be guaranteed by a minimum required overlap of the cut mask opening past any PrAF edge. It is discussed that process assumptions such as CD tolerances and overlay as well as inter-level relationship ground rules need to be considered to successfully optimize the final decomposition scheme. Furthermore, simulation and experimental results regarding not only ACLV but also across-device linewidth variation (ADLV) are analyzed.

The why, when and how to test for obstructive sleep apnea in patients with atrial fibrillation.

PubMed

Desteghe, Lien; Hendriks, Jeroen M L; McEvoy, R Doug; Chai-Coetzer, Ching Li; Dendale, Paul; Sanders, Prashanthan; Heidbuchel, Hein; Linz, Dominik

2018-04-12

Sleep apnea is associated with increased cardiovascular risk and may be important in atrial fibrillation (AF) management. It is present in up to 62% of the AF population and is highly under-recognized and underdiagnosed. Obstructive sleep apnea (OSA) is strongly associated with AF and non-randomized trials have shown that its treatment can help to reduce AF recurrences and maintain sinus rhythm. The 2016 European Society of Cardiology guidelines for the management of AF recommend that AF patients should be questioned regarding the symptoms of OSA and that OSA-treatment should be optimized to improve AF treatment results. However, strategies on how to implement OSA testing in the standard work-up of AF patients are not provided in the guidelines. Additionally, overnight OSA monitoring rather than interrogation for OSA-related clinical signs alone may be necessary to reliably identify OSA in the majority of AF patients. This review summarizes the available clinical data on OSA in AF patients, and discusses the following key questions: Why and When is testing for OSA needed in AF patients? How and Where should it be performed and coordinated? and Who should test for OSA? To implement OSA testing in a cardiology or electrophysiology clinic, we propose a multidisciplinary integrated care approach based on a chronic care model. We describe the tools, infrastructure and coordination needed to test for OSA in the standard workup of patients with symptomatic AF prior to the initiation of directed invasive or pharmacological rhythm control management.

Overexpression of afsR and Optimization of Metal Chloride to Improve Lomofungin Production in Streptomyces lomondensis S015.

PubMed

Wang, Wei; Wang, Huasheng; Hu, Hongbo; Peng, Huasong; Zhang, Xuehong

2015-05-01

As a global regulatory gene in Streptomyces, afsR can activate the biosynthesis of many secondary metabolites. The effect of afsR on the biosynthesis of a phenazine metabolite, lomofungin, was studied in Streptomyces lomondensis S015. There was a 2.5-fold increase of lomofungin production in the afsR-overexpressing strain of S. lomondensis S015 N1 compared with the wild-type strain. Meanwhile, the transcription levels of afsR and two important genes involved in the biosynthesis of lomofungin (i.e., phzC and phzE) were significantly upregulated in S. lomondensis S015 N1. The optimization of metal chlorides was investigated to further increase the production of lomofungin in the afsR-overexpressing strain. The addition of different metal chlorides to S. lomondensis S015 N1 cultivations showed that CaCl2, FeCl2, and MnCl2 led to an increase in lomofungin biosynthesis. The optimum concentrations of these metal chlorides were obtained using response surface methodology. CaCl2 (0.04 mM), FeCl2 (0.33 mM), and MnCl2 (0.38 mM) gave a maximum lomofungin production titer of 318.0 ± 10.7 mg/l, which was a 4.1-fold increase compared with that of S. lomondensis S015 N1 without the addition of a metal chloride. This work demonstrates that the biosynthesis of phenazine metabolites can be induced by afsR. The results also indicate that metal chlorides addition might be a simple and useful strategy for improving the production of other phenazine metabolites in Streptomyces.

A systematic approach to designing reliable VV optimization methodology: assessment of internal validity of echocardiographic, electrocardiographic and haemodynamic optimization of cardiac resynchronization therapy.

PubMed

Kyriacou, Andreas; Li Kam Wa, Matthew E; Pabari, Punam A; Unsworth, Beth; Baruah, Resham; Willson, Keith; Peters, Nicholas S; Kanagaratnam, Prapa; Hughes, Alun D; Mayet, Jamil; Whinnett, Zachary I; Francis, Darrel P

2013-08-10

In atrial fibrillation (AF), VV optimization of biventricular pacemakers can be examined in isolation. We used this approach to evaluate internal validity of three VV optimization methods by three criteria. Twenty patients (16 men, age 75 ± 7) in AF were optimized, at two paced heart rates, by LVOT VTI (flow), non-invasive arterial pressure, and ECG (minimizing QRS duration). Each optimization method was evaluated for: singularity (unique peak of function), reproducibility of optimum, and biological plausibility of the distribution of optima. The reproducibility (standard deviation of the difference, SDD) of the optimal VV delay was 10 ms for pressure, versus 8 ms (p=ns) for QRS and 34 ms (p<0.01) for flow. Singularity of optimum was 85% for pressure, 63% for ECG and 45% for flow (Chi(2)=10.9, p<0.005). The distribution of pressure optima was biologically plausible, with 80% LV pre-excited (p=0.007). The distributions of ECG (55% LV pre-excitation) and flow (45% LV pre-excitation) optima were no different to random (p=ns). The pressure-derived optimal VV delay is unaffected by the paced rate: SDD between slow and fast heart rate is 9 ms, no different from the reproducibility SDD at both heart rates. Using non-invasive arterial pressure, VV delay optimization by parabolic fitting is achievable with good precision, satisfying all 3 criteria of internal validity. VV optimum is unaffected by heart rate. Neither QRS minimization nor LVOT VTI satisfy all validity criteria, and therefore seem weaker candidate modalities for VV optimization. AF, unlinking interventricular from atrioventricular delay, uniquely exposes resynchronization concepts to experimental scrutiny. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Prospective study of atrial fibrillation termination during ablation guided by automated detection of fractionated electrograms.

PubMed

Porter, Michael; Spear, William; Akar, Joseph G; Helms, Ray; Brysiewicz, Neil; Santucci, Peter; Wilber, David J

2008-06-01

Complex fractionated atrial electrograms (CFAE) may identify critical sites for perpetuation of atrial fibrillation (AF) and provide useful targets for ablation. Current assessment of CFAE is subjective; automated detection algorithms may improve reproducibility, but their utility in guiding ablation has not been tested. In 67 patients presenting for initial AF ablation (42 paroxysmal, 25 persistent), LA and CS mapping were performed during induced or spontaneous AF. CFAE were identified by an online automated computer algorithm and displayed on electroanatomical maps. A mean of 28 +/- 18 sites/patient were identified (20 +/- 13% of mapped sites), and were more frequent during persistent AF. CFAE occurred most commonly within the CS, on the atrial septum, and around the pulmonary veins. Ablation initially targeting CFAE terminated AF in 88% of paroxysmal AF, but only 20% of persistent AF (P < 0.001). Subsequently, additional ablation was performed in all patients (PV isolation for paroxysmal AF, PV isolation + mitral and roof lines for persistent AF). Minimum follow-up was 1 year. One-year freedom from recurrent atrial arrhythmias without antiarrhythmic drug therapy after a single procedure was 90% for paroxysmal AF, and 68% for persistent AF. Ablation guided by automated detection of CFAE proved feasible, and was associated with a high AF termination rate in paroxysmal, but not persistent AF. As an adjunct to conventional techniques, it was associated with excellent long-term single procedure outcomes in both groups. Criteria for identifying optimal CFAE sites for ablation, and selection of patients most likely to benefit, require additional study.

Continuous ECG monitoring for tracking down atrial fibrillation after stroke: Holter or automated analysis strategy?

PubMed

Suissa, Laurent; Lachaud, Sylvain; Mahagne, Marie-Hélène

2014-01-01

Tracking down atrial fibrillation (AF) in the stroke unit is a relevant challenge for the prevention of recurrent AF-related stroke. The optimal terms of use of continuous ECG monitoring (CEM) are unknown. We compared 24-hour routine Holter ECG with two different CEM analysis strategies for AF detection. We prospectively enrolled consecutive ischemic stroke patients. All AF-naïve patients received CEM during hospitalization. Two methods for reading CEM data were compared: manual analysis using the Holter function (hCEM) and semiautomated analysis using software (aCEM). The McNemar test was used to compare AF detection rates. Of the 362 patients included, 58 (16.0%) were non-AF-naïve patients and 304 were AF-naïve patients. AF-Naïve patients underwent CEM with a median duration of 5.3 days (3.4-9.7). We detected 22 new AF cases (7.2%) with first-24-hour hCEM, 31 (10.2%) with aCEM, and 42 (13.8%) with hCEM. hCEM and aCEM both significantly increased the AF detection rate compared to first-24-hour hCEM. hCEM detected more new AF cases than aCEM (+3.6%, p = 0.003). In stroke patients, early and prolonged aCEM and hCEM both increase the AF detection rate compared to first-24-hour hCEM. hCEM gives the best AF detection rate. We suggest that in aCEM, detection based only on the ventricular rhythm analysis explains its lower specificity and sensitivity. © 2014 S. Karger AG, Basel.

Identification of U2AF(35)-dependent exons by RNA-Seq reveals a link between 3′ splice-site organization and activity of U2AF-related proteins

PubMed Central

Kralovicova, Jana; Knut, Marcin; Cross, Nicholas C. P.; Vorechovsky, Igor

2015-01-01

The auxiliary factor of U2 small nuclear RNA (U2AF) is a heterodimer consisting of 65- and 35-kD proteins that bind the polypyrimidine tract (PPT) and AG dinucleotides at the 3′ splice site (3′ss). The gene encoding U2AF35 (U2AF1) is alternatively spliced, giving rise to two isoforms U2AF35a and U2AF35b. Here, we knocked down U2AF35 and each isoform and characterized transcriptomes of HEK293 cells with varying U2AF35/U2AF65 and U2AF35a/b ratios. Depletion of both isoforms preferentially modified alternative RNA processing events without widespread failure to recognize 3′ss or constitutive exons. Over a third of differentially used exons were terminal, resulting largely from the use of known alternative polyadenylation (APA) sites. Intronic APA sites activated in depleted cultures were mostly proximal whereas tandem 3′UTR APA was biased toward distal sites. Exons upregulated in depleted cells were preceded by longer AG exclusion zones and PPTs than downregulated or control exons and were largely activated by PUF60 and repressed by CAPERα. The U2AF(35) repression and activation was associated with a significant interchange in the average probabilities to form single-stranded RNA in the optimal PPT and branch site locations and sequences further upstream. Although most differentially used exons were responsive to both U2AF subunits and their inclusion correlated with U2AF levels, a small number of transcripts exhibited distinct responses to U2AF35a and U2AF35b, supporting the existence of isoform-specific interactions. These results provide new insights into function of U2AF and U2AF35 in alternative RNA processing. PMID:25779042

AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection

PubMed Central

Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

2015-01-01

Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes’ status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors’ detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability. PMID:26193280

Persistent atrial fibrillation vs paroxysmal atrial fibrillation: differences in management.

PubMed

Margulescu, Andrei D; Mont, Lluis

2017-08-01

Atrial fibrillation (AF) is the most common human arrhythmia. AF is a progressive disease, initially being nonsustained and induced by trigger activity, and progressing towards persistent AF through alteration of the atrial myocardial substrate. Treatment of AF aims to decrease the risk of stroke and improve the quality of life, by preventing recurrences (rhythm control) or controlling the heart rate during AF (rate control). In the last 20 years, catheter-based and, less frequently, surgical and hybrid ablation techniques have proven more successful compared with drug therapy in achieving rhythm control in patients with AF. However, the efficiency of ablation techniques varies greatly, being highest in paroxysmal and lowest in long-term persistent AF. Areas covered: In this review, we discuss the fundamental differences between paroxysmal and persistent AF and the potential impact of those differences on patient management, emphasizing the available therapeutic strategies to achieve rhythm control. Expert commentary: Treatment to prevent AF recurrences is suboptimal, particularly in patients with persistent AF. Emerging technologies, such as documentation of atrial fibrosis using magnetic resonance imaging and documentation of electrical substrate using advanced electrocardiographic imaging techniques are likely to provide valuable insights about patient-specific tailoring of treatments.

Computationally efficient method for localizing the spiral rotor source using synthetic intracardiac electrograms during atrial fibrillation.

PubMed

Shariat, M H; Gazor, S; Redfearn, D

2015-08-01

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an extremely costly public health problem. Catheter-based ablation is a common minimally invasive procedure to treat AF. Contemporary mapping methods are highly dependent on the accuracy of anatomic localization of rotor sources within the atria. In this paper, using simulated atrial intracardiac electrograms (IEGMs) during AF, we propose a computationally efficient method for localizing the tip of the electrical rotor with an Archimedean/arithmetic spiral wavefront. The proposed method deploys the locations of electrodes of a catheter and their IEGMs activation times to estimate the unknown parameters of the spiral wavefront including its tip location. The proposed method is able to localize the spiral as soon as the wave hits three electrodes of the catheter. Our simulation results show that the method can efficiently localize the spiral wavefront that rotates either clockwise or counterclockwise.

Antiferromagnetic vs. non-magnetic ε phase of solid oxygen. Periodic density functional theory studies using a localized atomic basis set and the role of exact exchange.

PubMed

Ramírez-Solís, A; Zicovich-Wilson, C M; Hernández-Lamoneda, R; Ochoa-Calle, A J

2017-01-25

The question of the non-magnetic (NM) vs. antiferromagnetic (AF) nature of the ε phase of solid oxygen is a matter of great interest and continuing debate. In particular, it has been proposed that the ε phase is actually composed of two phases, a low-pressure AF ε 1 phase and a higher pressure NM ε 0 phase [Crespo et al., Proc. Natl. Acad. Sci. U. S. A., 2014, 111, 10427]. We address this problem through periodic spin-restricted and spin-polarized Kohn-Sham density functional theory calculations at pressures from 10 to 50 GPa using calibrated GGA and hybrid exchange-correlation functionals with Gaussian atomic basis sets. The two possible configurations for the antiferromagnetic (AF1 and AF2) coupling of the 0 ≤ S ≤ 1 O 2 molecules in the (O 2 ) 4 unit cell were studied. Full enthalpy-driven geometry optimizations of the (O 2 ) 4 unit cells were done to study the pressure evolution of the enthalpy difference between the non-magnetic and both antiferromagnetic structures. We also address the evolution of structural parameters and the spin-per-molecule vs. pressure. We find that the spin-less solution becomes more stable than both AF structures above 50 GPa and, crucially, the spin-less solution yields lattice parameters in much better agreement with experimental data at all pressures than the AF structures. The optimized AF2 broken-symmetry structures lead to large errors of the a and b lattice parameters when compared with experiments. The results for the NM model are in much better agreement with the experimental data than those found for both AF models and are consistent with a completely non-magnetic (O 2 ) 4 unit cell for the low-pressure regime of the ε phase.

Audit and feedback interventions to improve endoscopist performance: Principles and effectiveness.

PubMed

Tinmouth, Jill; Patel, Jigisha; Hilsden, Robert J; Ivers, Noah; Llovet, Diego

2016-06-01

There is considerable variation in the quality of colonoscopy, attributable in part to endoscopist performance. Audit and feedback (A&F) provides health professionals with a summary of their performance over a period of time and is a common strategy used to improve provider performance. In this review, we discuss current understanding of the mechanism of A&F and describe specific features of effective A&F. To date, trials of A&F to improve colonoscopy performance report heterogeneous results, in part because colonoscopy is a complex procedural skill but also because the quality improvement interventions were sub-optimally implemented or inadequately evaluated. Nonetheless, evidence from a wide range of literature suggests that A&F has the potential to improve endoscopist performance. We discuss future directions for research in this area and provide guidance for providers or health system planners wishing to implement A&F to address quality of colonoscopy in their practice and/or jurisdiction. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Bcr Kinase Downregulates Ras Signaling by Phosphorylating AF-6 and Binding to Its PDZ Domain

PubMed Central

Radziwill, G.; Erdmann, R. A.; Margelisch, U.; Moelling, K.

2003-01-01

The protein kinase Bcr is a negative regulator of cell proliferation and oncogenic transformation. We identified Bcr as a ligand for the PDZ domain of the cell junction and Ras-interacting protein AF-6. The Bcr kinase phosphorylates AF-6, which subsequently allows efficient binding of Bcr to AF-6, showing that the Bcr kinase is a regulator of the PDZ domain-ligand interaction. Bcr and AF-6 colocalize in epithelial cells at the plasma membrane. In addition, Bcr, AF-6, and Ras form a trimeric complex. Bcr increases the affinity of AF-6 to Ras, and a mutant of AF-6 that lacks a specific phosphorylation site for Bcr shows a reduced binding to Ras. Wild-type Bcr, but not Bcr mutants defective in binding to AF-6, interferes with the Ras-dependent stimulation of the Raf/MEK/ERK pathway. Since AF-6 binds to Bcr via its PDZ domain and to Ras via its Ras-binding domain, we propose that AF-6 functions as a scaffold-like protein that links Bcr and Ras to cellular junctions. We suggest that this trimeric complex is involved in downregulation of Ras-mediated signaling at sites of cell-cell contact to maintain cells in a nonproliferating state. PMID:12808105

Asymmetric flow field flow fractionation with light scattering detection - an orthogonal sensitivity analysis.

PubMed

Galyean, Anne A; Filliben, James J; Holbrook, R David; Vreeland, Wyatt N; Weinberg, Howard S

2016-11-18

Asymmetric flow field flow fractionation (AF 4 ) has several instrumental factors that may have a direct effect on separation performance. A sensitivity analysis was applied to ascertain the relative importance of AF 4 primary instrument factor settings for the separation of a complex environmental sample. The analysis evaluated the impact of instrumental factors namely, cross flow, ramp time, focus flow, injection volume, and run buffer concentration on the multi-angle light scattering measurement of natural organic matter (NOM) molar mass (MM). A 2 (5-1) orthogonal fractional factorial design was used to minimize analysis time while preserving the accuracy and robustness in the determination of the main effects and interactions between any two instrumental factors. By assuming that separations resulting in smaller MM measurements would be more accurate, the analysis produced a ranked list of effects estimates for factors and interactions of factors based on their relative importance in minimizing the MM. The most important and statistically significant AF 4 instrumental factors were buffer concentration and cross flow. The least important was ramp time. A parallel 2 (5-2) orthogonal fractional factorial design was also employed on five environmental factors for synthetic natural water samples containing silver nanoparticles (NPs), namely: NP concentration, NP size, NOM concentration, specific conductance, and pH. None of the water quality characteristic effects or interactions were found to be significant in minimizing the measured MM; however, the interaction between NP concentration and NP size was an important effect when considering NOM recovery. This work presents a structured approach for the rigorous assessment of AF 4 instrument factors and optimal settings for the separation of complex samples utilizing efficient orthogonal factional factorial design and appropriate graphical analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Human amniotic fluid-derived mesenchymal stem cells as therapeutic vehicles: a novel approach for the treatment of bladder cancer.

PubMed

Bitsika, Vasiliki; Roubelakis, Maria G; Zagoura, Dimitra; Trohatou, Ourania; Makridakis, Manousos; Pappa, Kalliopi I; Marini, Frank C; Vlahou, Antonia; Anagnou, Nicholas P

2012-05-01

Recent studies support cell-based therapies for cancer treatment. An advantageous cell type for such therapeutic schemes are the mesenchymal stem cells (MSCs) that can be easily propagated in culture, genetically modified to express therapeutic proteins, and exhibit an innate tropism to solid tumors in vivo. Recently, we successfully isolated and expanded MSCs from second-trimester amniotic fluid (AF-MSCs). The main characteristic of AF-MSCs is their efficient and rapid expansion in vitro. Herein, we investigated the AF-MSCs tropism and capability to transport interferon beta (IFNβ) to the region of neoplasia in a bladder tumor model. To this end, we used the T24M bladder cancer cell line, previously generated from our studies, and developed a disease progression model in immunosuppressed mice, that can recapitulate the molecular events of bladder carcinogenesis. Our results documented that AF-MSCs exhibited high motility, when migrated either to T24M cells or to T24M-conditioned medium, and we further identified and studied the secreted factors which may trigger these enhanced migratory properties. Further, lentivirus-transduced AF-MSCs, expressing green fluorescent protein (GFP) or IFNβ, were intravenously administered to T24M tumor-bearing animals at multiple doses to examine their therapeutic effect. GFP- and IFNβ-AF-MSCs successfully migrated and colonized at the tumor site. Notably, significant inhibition of tumor growth as well as prolonged survival of mice were observed in the presence of IFNβ-AF-MSCs. Collectively, these results document the great potential of AF-MSCs as anti-cancer vehicles, implemented by the targeting of the tumor site and further facilitated by their high proliferation rate and expansion efficiency in culture.

Non-aqueous phase cold vapor generation and determination of trace cadmium by atomic fluorescence spectrometry.

PubMed

Lei, Zirong; Chen, Luqiong; Hu, Kan; Yang, Shengchun; Wen, Xiaodong

2018-06-05

Cold vapor generation (CVG) of cadmium was firstly accomplished in non-aqueous media by using solid reductant of potassium borohydride (KBH 4 ) as a derivation reagent. The mixture of surfactant Triton X-114 micelle and octanol was innovatively used as the non-aqueous media for the CVG and atomic fluorescence spectrometry (AFS) was used for the elemental determination. The analyte ions were firstly extracted into the non-aqueous media from the bulk aqueous phase of analyte/sample solution via a novelly established ultrasound-assisted rapidly synergistic cloud point extraction (UARS-CPE) process and then directly mixed with the solid redcutant KBH 4 to generate volatile elemental state cadmium in a specially designed reactor, which was then rapidly transported to a commercial atomic fluorescence spectrometer for detection. Under the optimal conditions, the limit of detection (LOD) for cadmium was 0.004 μg L -1 . Compared to conventional hydride generation (HG)-AFS, the efficiency of non-aqueous phase CVG and the analytical performance of the developed system was considerably improved. Copyright © 2018 Elsevier B.V. All rights reserved.

Excessive Exercise in Endurance Athletes: Is Atrial Fibrillation a Possible Consequence?

PubMed

Goodman, Jack M; Banks, Laura; Connelly, Kim A; Yan, Andrew; Backx, Peter H; Dorian, Paul

2018-05-29

Moderate physical activity levels are associated with increased longevity and lower risk of atrial fibrillation (AF). However, the relative risk of lone AF is 3-5 fold higher in intensive endurance-trained athletes compared to healthy adults. There is growing concern that 'excessive' endurance exercise may promote cardiac remodeling leading to long-term adverse consequences. The pathogenesis of exercise-induced AF is thought to arise from an interplay of multiple acute and chronic factors, including atrial enlargement, pro-fibrotic tendency, high vagal tone, and genotypic profile, which collectively promote adverse atrial remodeling. Clinical management of athletes with AF, while challenging, can be achieved using various strategies that may allow continued, safe exercise. Based on the overall risk-benefit evidence, it is premature to suggest 'excessive' exercise is unsafe or should be curtailed. Evidence-based assessment and treatment guidelines are required to ensure optimal and safe exercise among the growing number of endurance athletes with AF.

Addition of Carbon to the Culture Medium Improves the Detection Efficiency of Aflatoxin Synthetic Fungi

PubMed Central

Suzuki, Tadahiro; Iwahashi, Yumiko

2016-01-01

Aflatoxin (AF) is a harmful secondary metabolite that is synthesized by the Aspergillus species. Although AF detection techniques have been developed, techniques for detection of AF synthetic fungi are still required. Techniques such as plate culture methods are continually being modified for this purpose. However, plate culture methods require refinement because they suffer from several issues. In this study, activated charcoal powder (carbon) was added to a culture medium containing cyclodextrin (CD) to enhance the contrast of fluorescence and improve the detection efficiency for AF synthetic fungi. Two culture media, potato dextrose agar and yeast extract sucrose agar, were investigated using both plate and liquid cultures. The final concentrations of CD and carbon in the media were 3 mg/mL and 0.3 mg/mL, respectively. Addition of carbon improved the visibility of fluorescence by attenuating approximately 30% of light scattering. Several fungi that could not be detected with only CD in the medium were detected with carbon addition. The carbon also facilitated fungal growth in the potato dextrose liquid medium. The results suggest that addition of carbon to media can enhance the observation of AF-derived fluorescence. PMID:27854283

Nanoparticle separation with a miniaturized asymmetrical flow field-flow fractionation cartridge

PubMed Central

Müller, David; Cattaneo, Stefano; Meier, Florian; Welz, Roland; de Mello, Andrew J.

2015-01-01

Asymmetrical Flow Field-Flow Fractionation (AF4) is a separation technique applicable to particles over a wide size range. Despite the many advantages of AF4, its adoption in routine particle analysis is somewhat limited by the large footprint of currently available separation cartridges, extended analysis times and significant solvent consumption. To address these issues, we describe the fabrication and characterization of miniaturized AF4 cartridges. Key features of the down-scaled platform include simplified cartridge and reagent handling, reduced analysis costs and higher throughput capacities. The separation performance of the miniaturized cartridge is assessed using certified gold and silver nanoparticle standards. Analysis of gold nanoparticle populations indicates shorter analysis times and increased sensitivity compared to conventional AF4 separation schemes. Moreover, nanoparticulate titanium dioxide populations exhibiting broad size distributions are analyzed in a rapid and efficient manner. Finally, the repeatability and reproducibility of the miniaturized platform are investigated with respect to analysis time and separation efficiency. PMID:26258119

Nanoparticle separation with a miniaturized asymmetrical flow field-flow fractionation cartridge

NASA Astrophysics Data System (ADS)

Müller, David; Cattaneo, Stefano; Meier, Florian; Welz, Roland; deMello, Andrew

2015-07-01

Asymmetrical Flow Field-Flow Fractionation (AF4) is a separation technique applicable to particles over a wide size range. Despite the many advantages of AF4, its adoption in routine particle analysis is somewhat limited by the large footprint of currently available separation cartridges, extended analysis times and significant solvent consumption. To address these issues, we describe the fabrication and characterization of miniaturized AF4 cartridges. Key features of the scale-down platform include simplified cartridge and reagent handling, reduced analysis costs and higher throughput capacities. The separation performance of the miniaturized cartridge is assessed using certified gold and silver nanoparticle standards. Analysis of gold nanoparticle populations indicates shorter analysis times and increased sensitivity compared to conventional AF4 separation schemes. Moreover, nanoparticulate titanium dioxide populations exhibiting broad size distributions are analyzed in a rapid and efficient manner. Finally, the repeatability and reproducibility of the miniaturized platform are investigated with respect to analysis time and separation efficiency.

10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population.

PubMed

Kim, Daehoon; Yang, Pil-Sung; Jang, Eunsun; Yu, Hee Tae; Kim, Tae-Hoon; Uhm, Jae-Sun; Kim, Jong-Youn; Pak, Hui-Nam; Lee, Moon-Hyoung; Joung, Boyoung; Lip, Gregory Yh

2018-05-01

Most data on the clinical epidemiology of atrial fibrillation (AF) are reported from Western populations, and data for Asians are limited. We aimed to investigate the 10-year trends of the prevalence and incidence of non-valvular AF and provide prevalence projections till 2060 in Korea. We also investigated the annual risks of adverse outcomes among patients with AF. Using the Korean National Health Insurance Service database involving the entire Korean population, a total of 679,416 adults with newly diagnosed AF were identified from 2006 to 2015. The incidence and prevalence of AF and risk of adverse outcomes following AF onset were assessed. The prevalence of AF progressively increased by 2.10-fold from 0.73% in 2006 to 1.53% in 2015. The trend of its incidence was flat with a 10-year overall incidence of 1.77 per 1,000 person-years. The prevalence of AF is expected to reach 5.81% (2,290,591 patients with AF) in 2060. For a decade, the risk of all-cause mortality following AF declined by 30% (adjusted hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.68-0.72), heart failure by 52% (adjusted HR: 0.48, 95% CI: 0.44-0.51), and ischemic stroke by 9% (adjusted HR: 0.91, 95% CI: 0.88-0.93). The burden of AF among Asian patients is increasing. Although the overall risks of cardiovascular events and death following AF onset have decreased over a decade, the event rates are still high. Optimized management of any associated comorbidities should be part of the holistic management approach for patients with AF. Copyright © 2018. Published by Elsevier Inc.

Effect of authority figures for pedestrian evacuation at metro stations

NASA Astrophysics Data System (ADS)

Song, Xiao; Zhang, Zenghui; Peng, Gongzhuang; Shi, Guoqiang

2017-01-01

Most pedestrian evacuation literatures are about routing algorithm, human intelligence and behavior etc. Few works studied how to fully explore the function of authority/security figures, who know more of the environment by simply being there every day. To evaluate the effect of authority figure (AF) in complex buildings, this paper fully investigates the AF related factors that may influence the evacuation effect of crowd, such as the number and locations of AFs, their spread of direction, calming effect and distribution strategies etc. Social force based modeling and simulation results show that these factors of AFs play important roles in evacuation efficiency, which means fewer AFs with right guiding strategy can have good evacuation performance. For our case study, Zhichun Avenue station, the conclusion is that deployment of four AFs is a good choice to achieve relatively high evacuation performance yet save cost.

Atrial Fibrillation Management Strategies in Routine Clinical Practice: Insights from the International RealiseAF Survey

PubMed Central

Chiang, Chern-En; Naditch-Brûlé, Lisa; Brette, Sandrine; Silva-Cardoso, José; Gamra, Habib; Murin, Jan; Zharinov, Oleg J.; Steg, Philippe Gabriel

2016-01-01

Background Atrial fibrillation (AF) can be managed with rhythm- or rate-control strategies. There are few data from routine clinical practice on the frequency with which each strategy is used and their correlates in terms of patients’ clinical characteristics, AF control, and symptom burden. Methods RealiseAF was an international, cross-sectional, observational survey of 11,198 patients with AF. The aim of this analysis was to describe patient profiles and symptoms according to the AF management strategy used. A multivariate logistic regression identified factors associated with AF management strategy at the end of the visit. Results Among 10,497 eligible patients, 53.7% used a rate-control strategy, compared with 34.5% who used a rhythm-control strategy. In 11.8% of patients, no clear strategy was stated. The proportion of patients with AF-related symptoms (EHRA Class > = II) was 78.1% (n = 4396/5630) for those using a rate-control strategy vs. 67.8% for those using a rhythm-control strategy (p<0.001). Multivariate logistic regression analysis revealed that age <75 years or the paroxysmal or persistent form of AF favored the choice of a rhythm-control strategy. A change in strategy was infrequent, even in patients with European Heart Rhythm Association (EHRA) Class > = II. Conclusions In the RealiseAF routine clinical practice survey, rate control was more commonly used than rhythm control, and a change in strategy was uncommon, even in symptomatic patients. In almost 12% of patients, no clear strategy was stated. Physician awareness regarding optimal management strategies for AF may be improved. PMID:26800084

Strict sequential catheter ablation strategy targeting the pulmonary veins and superior vena cava for persistent atrial fibrillation.

PubMed

Yoshiga, Yasuhiro; Shimizu, Akihiko; Ueyama, Takeshi; Ono, Makoto; Fukuda, Masakazu; Fumimoto, Tomoko; Ishiguchi, Hironori; Omuro, Takuya; Kobayashi, Shigeki; Yano, Masafumi

2018-08-01

An effective catheter ablation strategy, beyond pulmonary vein isolation (PVI), for persistent atrial fibrillation (AF) is necessary. Pulmonary vein (PV)-reconduction also causes recurrent atrial tachyarrhythmias. The effect of the PVI and additional effect of a superior vena cava (SVC) isolation (SVCI) was strictly evaluated. Seventy consecutive patients with persistent AF who underwent a strict sequential ablation strategy targeting the PVs and SVC were included in this study. The initial ablation strategy was a circumferential PVI. A segmental SVCI was only applied as a repeat procedure when patients demonstrated no PV-reconduction. After the initial procedure, persistent AF was suppressed in 39 of 70 (55.7%) patients during a median follow-up of 32 months. After multiple procedures, persistent AF was suppressed in 46 (65.7%) and 52 (74.3%) patients after receiving the PVI alone and PVI plus SVCI strategies, respectively. In 6 of 15 (40.0%) patients with persistent AF resistant to PVI, persistent AF was suppressed. The persistent AF duration independently predicted persistent AF recurrences after multiple PVI alone procedures [HR: 1.012 (95% confidence interval: 1.006-1.018); p<0.001] and PVI plus SVCI strategies [HR: 1.018 (95% confidence interval: 1.011-1.025); p<0.001]. A receiver-operating-characteristic analysis for recurrent persistent AF indicated an optimal cut-off value of 20 and 32 months for the persistent AF duration using the PVI alone and PVI plus SVCI strategies, respectively. The outcomes of the PVI plus SVCI strategy were favorable for patients with shorter persistent AF durations. The initial SVCI had the additional effect of maintaining sinus rhythm in some patients with persistent AF resistant to PVI. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

[Atomic/ionic fluorescence in microwave plasma torch discharge excited by high current microsecond pulsed hollow cathode lamp-europium atomic/ionic fluorescence spectrometry].

PubMed

Gong, Z; Liang, F; Yang, P; Jin, Q; Huang, B

1999-06-01

Eu atomic and ionic fluorescence spectrometry in microwave plasma torch discharge excited by high current microsecond pulsed hollow cathode lamp (HCMP HCL-MPT AFS/IFS) was studied. Operating conditions were optimized. The best detection limits for AFS and IFS obtained with a desolvated ultrasonic nebulization system were 42.0 ng/mL for Eu I 462.7 nm and 21.8 ng/mL for Eu II 381.97 nm, respectively, both were better than those given by the instruction manual of a Baird ICP AFS-2000 spectrometer using pneumatic concentric nebulizer with desolvation for AFS, but were significantly higher than those obtained by using the Baird spectrometer with a mini-monochromator and a ultrasonic nebulzer system.

Graphene oxide-coated stir bar sorptive extraction of trace aflatoxins from soy milk followed by high performance liquid chromatography-laser-induced fluorescence detection.

PubMed

Ma, Haiyan; Ran, Congcong; Li, Mengjiao; Gao, Jinglin; Wang, Xinyu; Zhang, Lina; Bian, Jing; Li, Junmei; Jiang, Ye

2018-04-01

Mycotoxins are potential food pollutants produced by fungi. Among them, aflatoxins (AFs) are the most toxic. Therefore, AFs were selected as models, and a sensitive, simple and green graphene oxide (GO)-based stir bar sorptive extraction (SBSE) method was developed for extraction and determination of AFs with high performance liquid chromatography-laser-induced fluorescence detector (HPLC-LIF). This method improved the sensitivity of AFs detection and solved the deposition difficulty of the direct use of GO as adsorbent. Several parameters including a spiked amount of NaCl, stirring rate, extraction time and desorption time were investigated. Under optimal conditions, the quantitative method had low limits of detection of 2.4-8.0 pg/mL, which were better than some reported AFs analytical methods. The developed method has been applied to soy milk samples with good recoveries ranging from 80.5 to 102.3%. The prepared GO-based SBSE can be used as a sensitive screening technique for detecting AFs in soy milk.

Immune Regulatory Properties of CD117pos Amniotic Fluid Stem Cells Vary According to Gestational Age

PubMed Central

Di Trapani, Mariano; Bassi, Giulio; Fontana, Emanuela; Giacomello, Luca; Pozzobon, Michela; Guillot, Pascale V.; De Coppi, Paolo

2015-01-01

Amniotic Fluid Stem (AFS) cells are broadly multipotent fetal stem cells derived from the positive selection and ex vivo expansion of amniotic fluid CD117/c-kitpos cells. Considering the differentiation potential in vitro toward cell lineages belonging to the three germ layers, AFS cells have raised great interest as a new therapeutic tool, but their immune properties still need to be assessed. We analyzed the in vitro immunological properties of AFS cells from different gestational age in coculture with T, B, and natural killer (NK) cells. Nonactivated (resting) first trimester-AFS cells showed lower expression of HLA class-I molecules and NK-activating ligands than second and third trimester-AFS cells, whose features were associated with lower sensitivity to NK cell-mediated lysis. Nevertheless, inflammatory priming with interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) enhanced resistance of all AFS cell types to NK cytotoxicity. AFS cells modulated lymphocyte proliferation in a different manner according to gestational age: first trimester-AFS cells significantly inhibited T and NK cell proliferation, while second and third trimester-AFS cells were less efficient. In addition, only inflammatory-primed second trimester-AFS cells could suppress B cell proliferation, which was not affected by the first and third trimester-AFS cells. Indolamine 2,3 dioxygenase pathway was significantly involved only in T cell suppression mediated by second and third trimester-AFS cells. Overall, this study shows a number of significant quantitative differences among AFS cells of different gestational age that have to be considered in view of their clinical application. PMID:25072397

In vitro and biomechanical screening of polyethylene glycol and poly(trimethylene carbonate) block copolymers for annulus fibrosus repair.

PubMed

Long, Rose G; Rotman, Stijn G; Hom, Warren W; Assael, Dylan J; Illien-Jünger, Svenja; Grijpma, Dirk W; Iatridis, James C

2018-02-01

Herniated intervertebral discs (IVDs) are a common cause of back and neck pain. There is an unmet clinical need to seal annulus fibrosus (AF) defects, as discectomy surgeries address acute pain but are complicated by reherniation and recurrent pain. Copolymers of polyethylene glycol with trimethylene carbonate (TMC) and hexamethylene diisocyanate (HDI) end-groups were formulated as AF sealants as the HDI form covalent bonds with native AF tissue. TMC adhesives were evaluated and optimized using the design criteria: stable size, strong adherence to AF tissue, high cytocompatibility, restoration of IVD biomechanics to intact levels following in situ repair, and low extrusion risk. TMC adhesives had high adhesion strength as assessed with a pushout test (150 kPa), and low degradation rates over 3 weeks in vitro. Both TMC adhesives had shear moduli (220 and 490 kPa) similar to, but somewhat higher than, AF tissue. The adhesive with three TMC moieties per branch (TMC3) was selected for additional in situ testing because it best matched AF shear properties. TMC3 restored torsional stiffness, torsional hysteresis area and axial range of motion to intact states. However, in a failure test of compressive deformation under fixed 5 ° flexion, some herniation risk was observed with failure strength of 5.9 MPa compared with 13.5 MPa for intact samples; TMC3 herniated under cyclic organ culture testing. These TMC adhesives performed well during in vitro and in situ testing, but additional optimization to enhance failure strength is required to further this material to advanced screening tests, such as long-term degradation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Prognostic impact of heart rate in elderly with systolic heart failure and concomitant atrial fibrillation.

PubMed

Barywani, Salim; Petzold, Max

2017-08-01

The present study aimed to investigate the impact of resting heart rate (HR) on 5-year all-cause mortality in patients ≥80 years with heart failure (HF) with reduced ejection fraction (HFrEF) and concomitant atrial fibrillation (AF) after optimal up-titration of beta-blockers (BBs). Patients (n = 185) aged ≥80 years with HF and left ventricular ejection fraction ≤40% were included between January 2000 and January 2008 from two university hospitals, Sahlgrenska and Östra and retrospectively studied from January 2 to May 30, 2013. Up-titrations of guideline recommended medications were performed at HF outpatient clinics. Of whole study population, 54% (n= 100) had AF. After optimal up-titration of BBs and angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), mean HR in patients with AF was 73 ± 15 beats/minute (bpm), 36% had resting HR ≤65 bpm. Five-year all-cause mortality among patients with AF was significantly lower in patients with HR ≤65 bpm (63%) compared to HR >65 (80%). Cox proportional-hazard regression analysis adjusted for clinically important baseline variables and doses of ACEIs/ARBs and BBs demonstrated resting HR ≤65 bpm as an independent predictor of improved survival compared to resting HR >65 bpm (HR 0.3, 95%CI 0.1-0.7, P 0.005). In octogenarians with HFrEF and concomitant AF, lowering resting HR to levels as low as HR ≤65 bpm was still associated with improved survival from all-cause mortality. Our data indicate that mortality in AF became comparable to SR when patients were on maximally up-titrated beta-blocker doses with HR as low as 75 bpm.

Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs with Rivaroxaban.

PubMed

Gibson, C M; Hankey, G J; Nafee, T; Welsh, R C

2018-03-22

With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke. Schattauer.

Increased Heart Rate Is Associated With Higher Mortality in Patients With Atrial Fibrillation (AF): Results From the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF)

PubMed Central

Steinberg, Benjamin A; Kim, Sunghee; Thomas, Laine; Fonarow, Gregg C; Gersh, Bernard J; Holmqvist, Fredrik; Hylek, Elaine; Kowey, Peter R; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Chang, Paul; Peterson, Eric D; Piccini, Jonathan P

2015-01-01

Background Most patients with atrial fibrillation (AF) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF. Methods and Results We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time-dependent covariate in multivariable Cox models of all-cause and cause-specific mortality during a median follow-up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA2DS2-VASc scores, renal function, or left ventricular function. There were significant differences in race (P=0.001), sinus node dysfunction (P=0.004), and treatment with calcium-channel blockers (P=0.006) and anticoagulation (P=0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.15 per 5-bpm decrease; 95% CI, 1.01 to 1.32; P=0.04). Similarly, increasing heart rate >65 bpm was associated with higher all-cause mortality (adjusted HR, 1.10 per 5-bpm increase; 95% CI, 1.05 to 1.15; P<0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients. Conclusions Among patients with permanent AF, there is a J-shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control. Clinical Trial Registration URL: http://clinicaltrials.gov/. Unique identifier: NCT01165710. PMID:26370445

Increased Heart Rate Is Associated With Higher Mortality in Patients With Atrial Fibrillation (AF): Results From the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF).

PubMed

Steinberg, Benjamin A; Kim, Sunghee; Thomas, Laine; Fonarow, Gregg C; Gersh, Bernard J; Holmqvist, Fredrik; Hylek, Elaine; Kowey, Peter R; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Chang, Paul; Peterson, Eric D; Piccini, Jonathan P

2015-09-14

Most patients with atrial fibrillation (AF) require rate control; however, the optimal target heart rate remains under debate. We aimed to assess rate control and subsequent outcomes among patients with permanent AF. We studied 2812 US outpatients with permanent AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation. Resting heart rate was measured longitudinally and used as a time-dependent covariate in multivariable Cox models of all-cause and cause-specific mortality during a median follow-up of 24 months. At baseline, 7.4% (n=207) had resting heart rate <60 beats per minute (bpm), 62% (n=1755) 60 to 79 bpm, 29% (n=817) 80 to 109 bpm, and 1.2% (n=33) ≥110 bpm. Groups did not differ by age, previous cerebrovascular disease, heart failure status, CHA2DS2-VASc scores, renal function, or left ventricular function. There were significant differences in race (P=0.001), sinus node dysfunction (P=0.004), and treatment with calcium-channel blockers (P=0.006) and anticoagulation (P=0.009). In analyses of continuous heart rates, lower heart rate ≤65 bpm was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.15 per 5-bpm decrease; 95% CI, 1.01 to 1.32; P=0.04). Similarly, increasing heart rate >65 bpm was associated with higher all-cause mortality (adjusted HR, 1.10 per 5-bpm increase; 95% CI, 1.05 to 1.15; P<0.0001). This relationship was consistent across endpoints and in a broader sensitivity analysis of permanent and nonpermanent AF patients. Among patients with permanent AF, there is a J-shaped relationship between heart rate and mortality. These data support current guideline recommendations, and clinical trials are warranted to determine optimal rate control. URL: http://clinicaltrials.gov/. Unique identifier: NCT01165710. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Direct comparison of mid-regional pro-atrial natriuretic peptide with N-terminal pro B-type natriuretic peptide in the diagnosis of patients with atrial fibrillation and dyspnoea.

PubMed

Eckstein, Jens; Potocki, Mihael; Murray, Karsten; Breidthardt, Tobias; Ziller, Ronny; Mosimann, Tamina; Klima, Theresia; Hoeller, Rebeca; Moehring, Berit; Sou, Seoung Mann; Rubini Gimenez, Maria; Morgenthaler, Nils G; Mueller, Christian

2012-10-01

Due to different release mechanisms, mid-regional pro-atrial natriuretic peptide (MR proANP) may be superior to N-terminal pro-B-type natriuretic peptide (NT proBNP) in the diagnosis of acute heart failure (AHF) in patients with atrial fibrillation (AF). We compared MR proANP and NT proBNP for their diagnostic value in patients with AF and sinus rhythm (SR). Prospective cohort study. University hospital, emergency department. 632 consecutive patients presenting with acute dyspnoea. MR proANP and NT proBNP plasma levels were determined. The diagnosis of AHF was adjudicated by two independent cardiologists using all available data. Patients received long-term follow-up. AF was present in 151 patients (24%). MR proANP and NT proBNP levels were significantly higher in the AF group compared with the SR group (385 (258-598) versus 201 (89-375) pmol/l for MR proANP, p<0.001 and 4916 (2169-10285) versus 1177 (258-5166) pg/ml, p<0.001 for NT proBNP). Diagnostic accuracy in AF patients was similar for MR proANP (0.90, 95% CI 0.84 to 0.95) and NT proBNP (0.89, 95% CI 0.81 to 0.96). Optimal cut-off levels in AF patients were significantly higher compared with the optimal cut-off levels for patients in SR (MR proANP 240 vs 200 pmol/l; NT proBNP 2670 vs 1500 pg/ml respectively). After adjustment in multivariable Cox proportional hazard analysis, MR proANP strongly predicted one-year all-cause mortality (HR=1.13 (1.09-1.17), per 100 pmol/l increase, p<0.001). In AF patients, NT proBNP and MR proANP have similar diagnostic value for the diagnosis of AHF. The rhythm at presentation has to be taken into account because plasma levels of both peptides are significantly higher in patients with AF compared with SR.

The effect of electromagnetic radiation of wireless connections on morphology of amniotic fluid

NASA Astrophysics Data System (ADS)

Novikov, Vsevolod O.; Titova, Natalia; Azarhov, Olexand; Wójcik, Waldemar; GrÄ dz, Å.»aklin; Mussabekova, Assel

2016-09-01

The article considers the effect of wireless networks on the morphology of amniotic fluid (AF) to demonstrate possible risks involving pregnant women. The analysis of AF thesiograms after exposure of the model fluid to Wi-Fi, 3G and β- radiation was chosen as the research method. A comparative analysis of facies structures is carried out, and depth maps of the facies structure are created. This comparative analysis permits an evaluation of the efficiency of morphological changes. It is shown that AF control facies differ in the concentration of areas with a narrow peripheral area and ellipsoidal formations of crystalloids in circumferences center. After exposure of different types of radiation onto AF, the facies structures collapse and form their own conglomerates. The obtained results show that the considered types of radiation have a negative effect on AF.

Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis.

PubMed

Kishore, Amit; Vail, Andy; Majid, Arshad; Dawson, Jesse; Lees, Kennedy R; Tyrrell, Pippa J; Smith, Craig J

2014-02-01

Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%-14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%-18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%-8.3%). There was substantial heterogeneity even within specified subgroups. Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF.

Mechanisms of Atrial Fibrillation: Rotors, Ionic Determinants and Excitation Frequency

PubMed Central

Berenfeld, Omer; Jalife, José

2017-01-01

Summary Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. However its mechanisms are poorly understood and AF therapy is often sub-optimal. This article reviews recent experimental, numerical and clinical data on dynamics of wave propagation during AF and its mechanistic link to ionic and structural properties of the atria. At the outset, we review numerical and optical mapping data suggesting that the sustained activity of periodic drivers (rotors) with exceedingly high dominant frequencies (DF) of excitation underlies the spatial dispersion and irregularity of activation rates that characterize AF. We show how optical mapping of the fibrillating atria in isolated normal sheep hearts has revealed that the rotors tend to localize in the left atrium (LA). We then discuss exciting new data in the sheep model of tachypacing induced AF demonstrating that the DF of paroxysmal AF episodes increases progressively over days or weeks during the transition to persistent AF (PeAF) and that the rate of the DF increase predicts the onset of PeAF. The data show that the DF increase during the transition may be explained by rotor acceleration secondary to upregulation of IK1 and downregulation of ICaL. The article concludes with a discussion on how translation of experimentally derived knowledge on the behavior and frequency of rotors may find its way into the clinic. We focus on studies in which the analysis of the spatial patterns of DF distribution in the atria of patients with paroxysmal vs persistent has increased our understanding of human AF and how that knowledge might contribute to improve the outcome of AF ablation procedures. PMID:26968663

Cardiovascular risk profile and management of atrial fibrillation in India: Real world data from RealiseAF survey.

PubMed

Narasimhan, C; Verma, Jagmohan Singh; Ravi Kishore, A G; Singh, Balbir; Dani, Sameer; Chawala, Kamaldeep; Haque, Azizul; Khan, Aftab; Nair, Mohan; Vora, Amit; Rajasekhar, V; Thomas, Joy M; Gupta, Anoop; Naik, Ajay; Prakash, V S; Naditch, Lisa; Gabriel Steg, P

Atrial fibrillation (AF) is the most common sustained arrhythmia with high risk for many cardiovascular (CV) complications. Adherence to recommended management guidelines is important to avoid complications. In India, there is little knowledge on how AF is managed in real world. This is a cross-sectional study of patients in India enrolled in RealiseAF survey between February 2010 and March 2010 with a diagnosis of AF within the last 12 months. From 15 centers, 301 patients {mean age 59.9 years (14.4); 52.5% males} were recruited. AF was controlled in 50% of patients with 77 (26.7%) in sinus rhythm and 67 (23.3%) with heart rate <80beats/min. Hypertension (50.8%), valvular heart disease (40.7%), heart failure (25.9%), and diabetes (20.4%) were the most common underlying CV diseases. Increased risk for stroke (CHADS 2 score≥2) was present in 36.6%. Most of the patients (85%) were symptomatic. AF was paroxysmal, persistent, and permanent in 28.7%, 22.7%, and 34.3% respectively. In 14%, AF was diagnosed as first episode. Forty-six percent of patients had rate control, 35.2% rhythm control, 0.3% both strategies, and 18.4% received no therapy for AF before the visit. At the end of the visit, adoption to rate control strategy increased to 52.3% and patients with no therapy decreased to 7%. AF in India is not adequately controlled. Concomitant CV risk factors and risk of stroke are high. The study underscores the need for improved adoption of guideline-directed management for optimal control of AF and reducing the risk of stroke. Copyright © 2016. Published by Elsevier B.V.

Adapting detection sensitivity based on evidence of irregular sinus arrhythmia to improve atrial fibrillation detection in insertable cardiac monitors.

PubMed

Pürerfellner, Helmut; Sanders, Prashanthan; Sarkar, Shantanu; Reisfeld, Erin; Reiland, Jerry; Koehler, Jodi; Pokushalov, Evgeny; Urban, Luboš; Dekker, Lukas R C

2017-10-03

Intermittent change in p-wave discernibility during periods of ectopy and sinus arrhythmia is a cause of inappropriate atrial fibrillation (AF) detection in insertable cardiac monitors (ICM). To address this, we developed and validated an enhanced AF detection algorithm. Atrial fibrillation detection in Reveal LINQ ICM uses patterns of incoherence in RR intervals and absence of P-wave evidence over a 2-min period. The enhanced algorithm includes P-wave evidence during RR irregularity as evidence of sinus arrhythmia or ectopy to adaptively optimize sensitivity for AF detection. The algorithm was developed and validated using Holter data from the XPECT and LINQ Usability studies which collected surface electrocardiogram (ECG) and continuous ICM ECG over a 24-48 h period. The algorithm detections were compared with Holter annotations, performed by multiple reviewers, to compute episode and duration detection performance. The validation dataset comprised of 3187 h of valid Holter and LINQ recordings from 138 patients, with true AF in 37 patients yielding 108 true AF episodes ≥2-min and 449 h of AF. The enhanced algorithm reduced inappropriately detected episodes by 49% and duration by 66% with <1% loss in true episodes or duration. The algorithm correctly identified 98.9% of total AF duration and 99.8% of total sinus or non-AF rhythm duration. The algorithm detected 97.2% (99.7% per-patient average) of all AF episodes ≥2-min, and 84.9% (95.3% per-patient average) of detected episodes involved AF. An enhancement that adapts sensitivity for AF detection reduced inappropriately detected episodes and duration with minimal reduction in sensitivity. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology

Reference gene selection for molecular studies of dormancy in wild oat (Avena fatua L.) caryopses by RT-qPCR method.

PubMed

Ruduś, Izabela; Kępczyński, Jan

2018-01-01

Molecular studies of primary and secondary dormancy in Avena fatua L., a serious weed of cereal and other crops, are intended to reveal the species-specific details of underlying molecular mechanisms which in turn may be useable in weed management. Among others, quantitative real-time PCR (RT-qPCR) data of comparative gene expression analysis may give some insight into the involvement of particular wild oat genes in dormancy release, maintenance or induction by unfavorable conditions. To assure obtaining biologically significant results using this method, the expression stability of selected candidate reference genes in different data subsets was evaluated using four statistical algorithms i.e. geNorm, NormFinder, Best Keeper and ΔCt method. Although some discrepancies in their ranking outputs were noticed, evidently two ubiquitin-conjugating enzyme homologs, AfUBC1 and AfUBC2, as well as one homolog of glyceraldehyde 3-phosphate dehydrogenase AfGAPDH1 and TATA-binding protein AfTBP2 appeared as more stably expressed than AfEF1a (translation elongation factor 1α), AfGAPDH2 or the least stable α-tubulin homolog AfTUA1 in caryopses and seedlings of A. fatua. Gene expression analysis of a dormancy-related wild oat transcription factor VIVIPAROUS1 (AfVP1) allowed for a validation of candidate reference genes performance. Based on the obtained results it can be recommended that the normalization factor calculated as a geometric mean of Cq values of AfUBC1, AfUBC2 and AfGAPDH1 would be optimal for RT-qPCR results normalization in the experiments comprising A. fatua caryopses of different dormancy status.

Generation of Elliptically Polarized Terahertz Waves from Antiferromagnetic Sandwiched Structure.

PubMed

Zhou, Sheng; Zhang, Qiang; Fu, Shu-Fang; Wang, Xuan-Zhang; Song, Yu-Ling; Wang, Xiang-Guang; Qu, Xiu-Rong

2018-04-01

The generation of elliptically polarized electromagnetic wave of an antiferromagnetic (AF)/dielectric sandwiched structure in the terahertz range is studied. The frequency and external magnetic field can change the AF optical response, resulting in the generation of elliptical polarization. An especially useful geometry with high levels of the generation of elliptical polarization is found in the case where an incident electromagnetic wave perpendicularly illuminates the sandwiched structure, the AF anisotropy axis is vertical to the wave-vector and the external magnetic field is pointed along the wave-vector. In numerical calculations, the AF layer is FeF2 and the dielectric layers are ZnF2. Although the effect originates from the AF layer, it can be also influenced by the sandwiched structure. We found that the ZnF2/FeF2/ZnF2 structure possesses optimal rotation of the principal axis and ellipticity, which can reach up to about thrice that of a single FeF2 layer.

2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the management of atrial fibrillation.

PubMed

Chiang, Chern-En; Wu, Tsu-Juey; Ueng, Kwo-Chang; Chao, Tze-Fan; Chang, Kuan-Cheng; Wang, Chun-Chieh; Lin, Yenn-Jiang; Yin, Wei-Hsian; Kuo, Jen-Yuan; Lin, Wei-Shiang; Tsai, Chia-Ti; Liu, Yen-Bin; Lee, Kun-Tai; Lin, Li-Jen; Lin, Lian-Yu; Wang, Kang-Ling; Chen, Yi-Jen; Chen, Mien-Cheng; Cheng, Chen-Chuan; Wen, Ming-Shien; Chen, Wen-Jone; Chen, Jyh-Hong; Lai, Wen-Ter; Chiou, Chuen-Wang; Lin, Jiunn-Lee; Yeh, San-Jou; Chen, Shih-Ann

2016-11-01

Atrial fibrillation (AF) is the most common sustained arrhythmia. Both the incidence and prevalence of AF are increasing, and the burden of AF is becoming huge. Many innovative advances have emerged in the past decade for the diagnosis and management of AF, including a new scoring system for the prediction of stroke and bleeding events, the introduction of non-vitamin K antagonist oral anticoagulants and their special benefits in Asians, new rhythm- and rate-control concepts, optimal endpoints of rate control, upstream therapy, life-style modification to prevent AF recurrence, and new ablation techniques. The Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology aimed to update the information and have appointed a jointed writing committee for new AF guidelines. The writing committee members comprehensively reviewed and summarized the literature, and completed the 2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the Management of Atrial Fibrillation. This guideline presents the details of the updated recommendations, along with their background and rationale, focusing on data unique for Asians. The guidelines are not mandatory, and members of the writing committee fully realize that treatment of AF should be individualized. The physician's decision remains most important in AF management. Copyright © 2016. Published by Elsevier B.V.

Tone-deafness – a new disconnection syndrome?

PubMed Central

Loui, Psyche; Alsop, David; Schlaug, Gottfried

2009-01-01

Communicating with one’s environment requires efficient neural interaction between action and perception. Neural substrates ofsound perception and production are connected by the arcuate fasciculus (AF). While AF is known to be involved in language, its roles in non-linguistic functions are unexplored. Here we show that tone-deaf people, with impaired sound perception and production, have reduced AF connectivity. Diffusion tensor tractography and psychophysics were assessed in tone-deaf individuals and matched controls. Abnormally-reduced AF connectivity was observed in the tone-deaf. Furthermore, we observed relationships between AF and auditory-motor behavior: superior and inferior AF branches predict psychophysically-assessed pitch-discrimination and sound production-perception abilities respectively. This neural abnormality suggests that tone-deafness leads to a reduction in connectivity resulting in pitch-related impairments. Results support a dual-stream anatomy of sound production and perception implicated in vocal communications. By identifying white-matter differences and their psychophysical correlates, results contribute to our understanding of how neural connectivity subserves behavior. PMID:19692596

The Plant Alkaloid Camptothecin as a Novel Antifouling Compound for Marine Paints: Laboratory Bioassays and Field Trials.

PubMed

Feng, Dan Qing; He, Jian; Chen, Si Yu; Su, Pei; Ke, Cai Huan; Wang, Wei

2018-06-02

The extensive use of copper and booster biocides in antifouling (AF) paints has raised environmental concerns and the need to develop new AF agents. In the present study, 18 alkaloids derived from terrestrial plants were initially evaluated for AF activity using laboratory bioassays with the bryozoan Bugula neritina and the barnacle Balanus albicostatus. The results showed that 4 of the 18 alkaloids were effective in inhibiting larval settlement of B. neritina, with an EC 50 range of 6.18 to 43.11 μM, and 15 of the 18 alkaloids inhibited larval settlement of B. albicostatus, with EC 50 values ranging from 1.18 to 67.58 μM. Field trials that incorporated five alkaloids respectively into paints with 20% w/w indicated an in situ AF efficiency of evodiamine, strychnine, camptothecin (CPT), and cepharanthine, with the most potent compound being CPT, which also exhibited stronger AF efficiency than the commercial antifoulants cuprous oxide and zinc pyrithione in the field over a period of 12 months. Further field trials with different CPT concentrations (0.1 to 20% w/w) in the paints suggested a concentration-dependent AF performance in the natural environment, and the effective concentrations to significantly inhibit settlement of biofoulers in the field were ≥ 0.5% w/w (the efficiency of 0.5% w/w lasted for 2 months). Moreover, CPT toxicity against the crustacean Artemia salina, the planktonic microalgae Phaeodactylum tricornutum and Isochrysis galbana, was examined. The results showed that 24 h LC 50 of CPT against A. salina was 20.75 μM, and 96 h EC 50 (growth inhibition) values of CPT to P. tricornutum and I. galbana were 55.81 and 6.29 μM, respectively, indicating that CPT was comparatively less toxic than several commercial antifoulants previously reported. Our results suggest the novel potential application of CPT as an antifoulant.

Digital transceiver design for two-way AF-MIMO relay systems with imperfect CSI

NASA Astrophysics Data System (ADS)

Hu, Chia-Chang; Chou, Yu-Fei; Chen, Kui-He

2013-09-01

In the paper, combined optimization of the terminal precoders/equalizers and single-relay precoder is proposed for an amplify-and-forward (AF) multiple-input multiple-output (MIMO) two-way single-relay system with correlated channel uncertainties. Both terminal transceivers and relay precoding matrix are designed based on the minimum mean square error (MMSE) criterion when terminals are unable to erase completely self-interference due to imperfect correlated channel state information (CSI). This robust joint optimization problem of beamforming and precoding matrices under power constraints belongs to neither concave nor convex so that a nonlinear matrix-form conjugate gradient (MCG) algorithm is applied to explore local optimal solutions. Simulation results show that the robust transceiver design is able to overcome effectively the loss of bit-error-rate (BER) due to inclusion of correlated channel uncertainties and residual self-interference.

The burden of proof: The current state of atrial fibrillation prevention and treatment trials

PubMed Central

Zakeri, Rosita; Van Wagoner, David R.; Calkins, Hugh; Wong, Tom; Ross, Heather M.; Heist, E. Kevin; Meyer, Timothy E.; Kowey, Peter R.; Mentz, Robert J.; Cleland, John G.; Pitt, Bertram; Zannad, Faiez; Linde, Cecilia

2017-01-01

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015. PMID:28161513

An Experimental Investigation of Sewage Sludge Gasification in a Fluidized Bed Reactor

PubMed Central

Calvo, L. F.; García, A. I.; Otero, M.

2013-01-01

The gasification of sewage sludge was carried out in a simple atmospheric fluidized bed gasifier. Flow and fuel feed rate were adjusted for experimentally obtaining an air mass : fuel mass ratio (A/F) of 0.2 < A/F < 0.4. Fuel characterization, mass and power balances, produced gas composition, gas phase alkali and ammonia, tar concentration, agglomeration tendencies, and gas efficiencies were assessed. Although accumulation of material inside the reactor was a main problem, this was avoided by removing and adding bed media along gasification. This allowed improving the process heat transfer and, therefore, gasification efficiency. The heating value of the produced gas was 8.4 MJ/Nm, attaining a hot gas efficiency of 70% and a cold gas efficiency of 57%. PMID:24453863

Atrial fibrillation in Middle Eastern Arab and South Asian patients hospitalized with acute myocardial infarction: experience from a 20-year registry in qatar (1991-2010).

PubMed

Salam, Amar M; Al, Binali Hajar A; Singh, Rajvir; Gehani, Abdurrazzak; Asaad, Nidal; Al-Qahtani, Awad; Suwaidi, Jassim Al

2013-04-01

Recent evidence suggests that there are ethnic variations in atrial fibrillation (AF) susceptibility and incidence following acute myocardial infarction (AMI). The aim of this study was to evaluate the incidence and predictors of AF in the setting of AMI in Middle Eastern Arab and South Asian patients and its impact on in-hospital morbidity and mortality. A retrospective analysis of a prospective registry of all patients hospitalized with AMI in the state of Qatar from 1991 through 2010 was made. Clinical characteristics and outcomes of AMI patients with and without AF were compared. Sub-analysis according to ethnicity was also performed. During the 20-year period; a total of 12,881 patients were hospitalized with AMI. Of these 5028 were Arabs and 5985 were South Asians. A total of 227 had AF during hospitalization with an overall incidence of 1.8% (156 Arabs; incidence 3.1% and 48 South Asians; incidence 0.8%). The mean age of AF patients was 65 years (Arabs 69, South Asians 54). Patients with AF were significantly older and had more cardiovascular co-morbidities than patients without AF, and were more likely to have non-ST elevation AMI on presentation. Patients with AF had significantly higher in-hospital mortality rate (20.3% versus 7.1%; P=0.001) and stroke rates (1.8% versus 0.3%; P=0.001) when compared to patients without AF. Age was the only independent predictor of AF development in patients with AMI in our study. Our study reports variability in the prevalence of AF among AMI patients according to ethnicity using a 20-year registry from a Middle Eastern country. Advancing age was the major independent predictor of AF in our AMI patients. Further prospective studies are required evaluating optimal therapeutic approaches for these high-risk patients in order to reduce the high mortality observed.

Management of atrial fibrillation in Greece: the MANAGE-AF study.

PubMed

Andrikopoulos, George; Pastromas, Sokratis; Mantas, Ioannis; Sakellariou, Dimitris; Kyrpizidis, Christos; Makridis, Pantelis; Goumas, Georgios; Stakos, Dimitris; Gotsis, Alexandros; Kartalis, Athanasios; Kazianis, Georgios; Babalis, Dimitrios; Toli, Konstantina; Tzeis, Stylianos; Papavasileiou, Maria; Kalogeropoulos, Petros; Vardas, Panos

2014-01-01

Although atrial fibrillation (AF) is a highly prevalent health problem with high morbidity and mortality, data regarding the clinical characteristics and management of AF in the Greek population are scarce. The "Current Clinical Practice in the MANAGEment of Atrial Fibrillation in Greece" study (MANAGEAF) aimed to assess the epidemiological features as well as the daily clinical practice in the management of Greek patients with AF. Taking into consideration the distribution of the Greek population, 603 consecutive patients over 18 years of age, with any type of AF, presenting at the emergency departments or outpatient clinics of 27 different centers, were included in our study. The mean age of the patients was 68.5 ± 12.1 years, with male patients representing 52.5% of the study population. The most common AF type in our cohort was non-paroxysmal AF (60%), including the patients with permanent (24.1%), persistent (17.4%), long-standing (4.8%) and first diagnosed AF (13.8%). Hypertension was the most common comorbidity (70.3%). A history of stroke or transient ischemic attack was detected in 9.2% of the patients, while 6.2% had a history of gastrointestinal bleeding. About half of the patients (49.3%) were treated with anticoagulant drugs, mainly vitamin K antagonists (46.9%), while 34.2% were on antiplatelet drugs, aspirin and/or clopidogrel. The mean INR level (1.7 ± 0.8) was sub-therapeutic, although the mean values for CHADS2 and CHA2DS2-VASc scores were 1.6 ± 1.2 and 3.0 ± 1.7, respectively. The MANAGE-AF baseline results indicate unsatisfactory levels of compliance with the current guidelines for the management of AF in Greece. Considering the undisputed effectiveness of anticoagulant treatment for preventing AF-related strokes, MANAGE-AF demonstrates the need for optimization of our therapeutic strategies for the management of cardioembolic stroke risk.

Efficacy and safety of dronedarone: a review of randomized trials.

PubMed

Christiansen, Christine Benn; Torp-Pedersen, Christian; Køber, Lars

2010-01-01

Dronedarone is developed for treatment of atrial fibrillation (AF) or flutter (AFL). It is a noniodinized amiodarone analogue and believed to be without the adverse effects of amiodarone. However, long-term adverse effects are not yet well investigated. This is a review of seven studies on dronedarone. DAFNE established an effective dose to be 400 mg b.i.d. ADONIS and EURIDIS showed significant prevention of AF/AFL recurrence hazard ratio (HR 0.78 and 0.73) compared to placebo. In ATHENA, cardiovascular death/hospitalization was significantly reduced (HR 0.76) in patients with AF and additional risk factors. ANDROMEDA was stopped because dronedarone increased early mortality (HR 2.13) in advanced heart failure (HF). ERATO found that dronedarone significantly reduced heart rate compared to placebo in patients with AF. DIONYSOS showed that amiodarone was superior to dronedarone to maintain sinus rhythm in patients with AF/AFL. Dronedarone is superior to placebo but less efficient than amiodarone in maintaining sinus rhythm in patients with a history of AF. In patients with AF and risk factors dronedarone reduces cardiovascular mortality and morbidity, but in patients with severe HF dronedarone significantly increases mortality.

ECG Based Heart Arrhythmia Detection Using Wavelet Coherence and Bat Algorithm

NASA Astrophysics Data System (ADS)

Kora, Padmavathi; Sri Rama Krishna, K.

2016-12-01

Atrial fibrillation (AF) is a type of heart abnormality, during the AF electrical discharges in the atrium are rapid, results in abnormal heart beat. The morphology of ECG changes due to the abnormalities in the heart. This paper consists of three major steps for the detection of heart diseases: signal pre-processing, feature extraction and classification. Feature extraction is the key process in detecting the heart abnormality. Most of the ECG detection systems depend on the time domain features for cardiac signal classification. In this paper we proposed a wavelet coherence (WTC) technique for ECG signal analysis. The WTC calculates the similarity between two waveforms in frequency domain. Parameters extracted from WTC function is used as the features of the ECG signal. These features are optimized using Bat algorithm. The Levenberg Marquardt neural network classifier is used to classify the optimized features. The performance of the classifier can be improved with the optimized features.

Optimizing manufacturing and composition of a TLR4 nanosuspension: physicochemical stability and vaccine adjuvant activity

PubMed Central

2013-01-01

Background Nanosuspensions are an important class of delivery system for vaccine adjuvants and drugs. Previously, we developed a nanosuspension consisting of the synthetic TLR4 ligand glucopyranosyl lipid adjuvant (GLA) and dipalmitoyl phosphatidylcholine (DPPC). This nanosuspension is a clinical vaccine adjuvant known as GLA-AF. We examined the effects of DPPC supplier, buffer composition, and manufacturing process on GLA-AF physicochemical and biological activity characteristics. Results DPPC from different suppliers had minimal influence on physicochemical and biological effects. In general, buffered compositions resulted in less particle size stability compared to unbuffered GLA-AF. Microfluidization resulted in rapid particle size reduction after only a few passes, and 20,000 or 30,000 psi processing pressures were more effective at reducing particle size and recovering the active component than 10,000 psi. Sonicated and microfluidized batches maintained good particle size and chemical stability over 6 months, without significantly altering in vitro or in vivo bioactivity of GLA-AF when combined with a recombinant malaria vaccine antigen. Conclusions Microfluidization, compared to water bath sonication, may be an effective manufacturing process to improve the scalability and reproducibility of GLA-AF as it advances further in the clinical development pathway. Various sources of DPPC are suitable to manufacture GLA-AF, but buffered compositions of GLA-AF do not appear to offer stability advantages over the unbuffered composition. PMID:24359024

Reworking Practice through an AfL Project: An Analysis of Teachers' Collaborative Engagement with New Assessment Guidelines

ERIC Educational Resources Information Center

Hermansen, Hege; Nerland, Monika

2014-01-01

In recent years, the concept of Assessment for Learning (AfL) has travelled across countries, giving rise to a range of educational policy initiatives and school development projects. While researchers have focused on issues such as how formative assessment can support student learning and lead to more efficient classroom practices, less attention…

Uniaxial pressure effect on the magnetic ordered moment and transition temperatures in BaFe2 -xTxAs2 (T =Co,Ni )

NASA Astrophysics Data System (ADS)

Tam, David W.; Song, Yu; Man, Haoran; Cheung, Sky C.; Yin, Zhiping; Lu, Xingye; Wang, Weiyi; Frandsen, Benjamin A.; Liu, Lian; Gong, Zizhou; Ito, Takashi U.; Cai, Yipeng; Wilson, Murray N.; Guo, Shengli; Koshiishi, Keisuke; Tian, Wei; Hitti, Bassam; Ivanov, Alexandre; Zhao, Yang; Lynn, Jeffrey W.; Luke, Graeme M.; Berlijn, Tom; Maier, Thomas A.; Uemura, Yasutomo J.; Dai, Pengcheng

2017-02-01

We use neutron diffraction and muon spin relaxation to study the effect of in-plane uniaxial pressure on the antiferromagnetic (AF) orthorhombic phase in BaFe2As2 and its Co- and Ni-substituted members near optimal superconductivity. In the low-temperature AF ordered state, uniaxial pressure necessary to detwin the orthorhombic crystals also increases the magnetic ordered moment, reaching an 11% increase under 40 MPa for BaFe1.9Co0.1As2 , and a 15% increase for BaFe1.915Ni0.085As2 . We also observe an increase of the AF ordering temperature (TN) of about 0.25 K/MPa in all compounds, consistent with density functional theory calculations that reveal better Fermi surface nesting for itinerant electrons under uniaxial pressure. The doping dependence of the magnetic ordered moment is captured by combining dynamical mean field theory with density functional theory, suggesting that the pressure-induced moment increase near optimal superconductivity is closely related to quantum fluctuations and the nearby electronic nematic phase.

Asymmetric flow field flow fractionation for the characterization of globule size distribution in complex formulations: A cyclosporine ophthalmic emulsion case.

PubMed

Qu, Haiou; Wang, Jiang; Wu, Yong; Zheng, Jiwen; Krishnaiah, Yellela S R; Absar, Mohammad; Choi, Stephanie; Ashraf, Muhammad; Cruz, Celia N; Xu, Xiaoming

2018-03-01

Commonly used characterization techniques such as cryogenic-transmission electron microscopy (cryo-TEM) and batch-mode dynamic light scattering (DLS) are either time consuming or unable to offer high resolution to discern the poly-dispersity of complex drug products like cyclosporine ophthalmic emulsions. Here, a size-based separation and characterization method for globule size distribution using an asymmetric flow field flow fractionation (AF4) is reported for comparative assessment of cyclosporine ophthalmic emulsion drug products (model formulation) with a wide size span and poly-dispersity. Cyclosporine emulsion formulations that are qualitatively (Q1) and quantitatively (Q2) the same as Restasis® were prepared in house with varying manufacturing processes and analyzed using the optimized AF4 method. Based on our results, the commercially available cyclosporine ophthalmic emulsion has a globule size span from 30 nm to a few hundred nanometers with majority smaller than 100 nm. The results with in-house formulations demonstrated the sensitivity of AF4 in determining the differences in the globule size distribution caused by the changes to the manufacturing process. It is concluded that the optimized AF4 is a potential analytical technique for comprehensive understanding of the microstructure and assessment of complex emulsion drug products with high poly-dispersity. Published by Elsevier B.V.

Optimizing local capture of atrial fibrillation by rapid pacing: study of the influence of tissue dynamics.

PubMed

Uldry, Laurent; Virag, Nathalie; Jacquemet, Vincent; Vesin, Jean-Marc; Kappenberger, Lukas

2010-12-01

While successful termination by pacing of organized atrial tachycardias has been observed in patients, rapid pacing of AF can induce a local capture of the atrial tissue but in general no termination. The purpose of this study was to perform a systematic evaluation of the ability to capture AF by rapid pacing in a biophysical model of the atria with different dynamics in terms of conduction velocity (CV) and action potential duration (APD). Rapid pacing was applied during 30 s at five locations on the atria, for pacing cycle lengths in the range 60-110% of the mean AF cycle length (AFCL(mean)). Local AF capture could be achieved using rapid pacing at pacing sites located distal to major anatomical obstacles. Optimal pacing cycle lengths were found in the range 74-80% AFCL(mean) (capture window width: 14.6 ± 3% AFCL(mean)). An increase/decrease in CV or APD led to a significant shrinking/stretching of the capture window. Capture did not depend on AFCL, but did depend on the atrial substrate as characterized by an estimate of its wavelength, a better capture being achieved at shorter wavelengths. This model-based study suggests that a proper selection of the pacing site and cycle length can influence local capture results and that atrial tissue properties (CV and APD) are determinants of the response to rapid pacing.

Apoferritin fibers: a new template for 1D fluorescent hybrid nanostructures

NASA Astrophysics Data System (ADS)

Jurado, Rocío; Castello, Fabio; Bondia, Patricia; Casado, Santiago; Flors, Cristina; Cuesta, Rafael; Domínguez-Vera, José M.; Orte, Angel; Gálvez, Natividad

2016-05-01

Recently, research in the field of protein amyloid fibers has gained great attention due to the use of these materials as nanoscale templates for the construction of functional hybrid materials. The formation of apoferritin amyloid-like protein fibers is demonstrated herein for the first time. The morphology, size and stiffness of these one-dimensional structures are comparable to the fibers formed by β-lactoglobulin, a protein frequently used as a model in the study of amyloid-like fibrillar proteins. Nanometer-sized globular apoferritin is capable of self-assembling to form 1D micrometer-sized structures after being subjected to a heating process. Depending on the experimental conditions, fibers with different morphologies and sizes are obtained. The wire-like protein structure is rich in functional groups and allows chemical functionalization with diverse quantum dots (QD), as well as with different Alexa Fluor (AF) dyes, leading to hybrid fluorescent fibers with variable emission wavelengths, from green to near infrared, depending on the QD and AFs coupled. For fibers containing the pair AF488 and AF647, efficient fluorescence energy transfer from the covalently coupled donor (AF488) to acceptor tags (AF647) takes place. Apoferritin fibers are proposed here as a new promising template for obtaining hybrid functional materials.Recently, research in the field of protein amyloid fibers has gained great attention due to the use of these materials as nanoscale templates for the construction of functional hybrid materials. The formation of apoferritin amyloid-like protein fibers is demonstrated herein for the first time. The morphology, size and stiffness of these one-dimensional structures are comparable to the fibers formed by β-lactoglobulin, a protein frequently used as a model in the study of amyloid-like fibrillar proteins. Nanometer-sized globular apoferritin is capable of self-assembling to form 1D micrometer-sized structures after being subjected to a heating process. Depending on the experimental conditions, fibers with different morphologies and sizes are obtained. The wire-like protein structure is rich in functional groups and allows chemical functionalization with diverse quantum dots (QD), as well as with different Alexa Fluor (AF) dyes, leading to hybrid fluorescent fibers with variable emission wavelengths, from green to near infrared, depending on the QD and AFs coupled. For fibers containing the pair AF488 and AF647, efficient fluorescence energy transfer from the covalently coupled donor (AF488) to acceptor tags (AF647) takes place. Apoferritin fibers are proposed here as a new promising template for obtaining hybrid functional materials. Electronic supplementary information (ESI) available: TEM images of ferritin protein fiber formation, and apoferritin after 18 days of heat treatment; FLIM-PIE technique details; fluorescence emission spectra of apoferritin and β-lactoglobulin fibers functionalized with different QDs. See DOI: 10.1039/c6nr01044j

The burden of proof: The current state of atrial fibrillation prevention and treatment trials.

PubMed

Zakeri, Rosita; Van Wagoner, David R; Calkins, Hugh; Wong, Tom; Ross, Heather M; Heist, E Kevin; Meyer, Timothy E; Kowey, Peter R; Mentz, Robert J; Cleland, John G; Pitt, Bertram; Zannad, Faiez; Linde, Cecilia

2017-05-01

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3-5, 2015. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Identification of active atrial fibrillation sources and their discrimination from passive rotors using electrographical flow mapping.

PubMed

Bellmann, Barbara; Lin, Tina; Ruppersberg, Peter; Zettwitz, Marit; Guttmann, Selma; Tscholl, Verena; Nagel, Patrick; Roser, Mattias; Landmesser, Ulf; Rillig, Andreas

2018-05-09

The optimal ablation approach for the treatment of persistent atrial fibrillation (AF) is still under debate; however, the identification and elimination of AF sources is thought to play a key role. Currently available technologies for the identification of AF sources are not able to differentiate between active rotors or focal impulse (FI) and passive circular turbulences as generated by the interaction of a wave front with a functional obstacle such as fibrotic tissue. This study introduces electrographic flow (EGF) mapping as a novel technology for the identification and characterization of AF sources in humans. Twenty-five patients with AF (persistent: n = 24, long-standing persistent: n = 1; mean age 70.0 ± 8.3 years, male: n = 17) were included in this prospective study. Focal impulse and Rotor-Mapping (FIRM) was performed in addition to pulmonary vein isolation using radiofrequency in conjunction with a 3D-mapping-system. One-minute epochs were exported from the EP-recording-system and re-analyzed using EGF mapping after the procedure. 44 potential AF sources (43 rotors and one FI) were identified with FIRM and 39 of these rotors were targeted for ablation. EGF mapping verified 40 of these patterns and identified 24/40 (60%) as active sources while 16/40 (40%) were classified as passive circular turbulences. Four rotors were not identified by EGF mapping. EGF is the first method to identify active AF sources during AF ablation procedures in humans and discriminate them from passive rotational phenomena, which occur if the excitation wavefront passes conduction bariers. EGF mapping may allow improved guidance of AF ablation procedures.

Heating and Efficiency Comparison of a Fischer-Tropsch (FT) Fuel, JP-8+100, and Blends in a Three-Cup Combustor Sector

NASA Technical Reports Server (NTRS)

Thomas, Anna E.; Shouse, Dale T.; Neuroth, Craig; Lynch, Amy; Frayne, Charles W.; Stutrud, Jeffrey S.; Corporan, Edwin; Hankins, Terry; Saxena, Nikita T.; Hendricks, Robert C.

2012-01-01

In order to realize alternative fueling for military and commercial use, the industry has set forth guidelines that must be met by each fuel. These aviation fueling requirements are outlined in MIL-DTL-83133F(2008) or ASTM D 7566-Annex standards and are classified as drop-in fuel replacements. This paper provides combustor performance data for synthetic-paraffinic-kerosene- (SPK-) type (Fisher-Tropsch (FT)) fuel and blends with JP-8+100, relative to JP-8+100 as baseline fueling. Data were taken at various nominal inlet conditions: 75 psia (0.52 MPa) at 500 aF (533 K), 125 psia (0.86 MPa) at 625 aF (603 K), 175 psia (1.21 MPa) at 725 aF (658 K), and 225 psia (1.55 MPa) at 790 aF (694 K). Combustor performance analysis assessments were made for the change in flame temperatures, combustor efficiency, wall temperatures, and exhaust plane temperatures at 3%, 4%, and 5% combustor pressure drop (% P) for fuel:air ratios (F/A) ranging from 0.010 to 0.025. Significant general trends show lower liner temperatures and higher flame and combustor outlet temperatures with increases in FT fueling relative to JP-8+100 fueling. The latter affects both turbine efficiency and blade/vane life. In general, 100% SPK-FT fuel and blends with JP-8+100 produce less particulates and less smoke and have lower thermal impact on combustor hardware.

Halophilic viruses with varying biochemical and biophysical properties are amenable to purification with asymmetrical flow field-flow fractionation.

PubMed

Eskelin, Katri; Lampi, Mirka; Meier, Florian; Moldenhauer, Evelin; Bamford, Dennis H; Oksanen, Hanna M

2017-11-01

Viruses come in various shapes and sizes, and a number of viruses originate from extremities, e.g. high salinity or elevated temperature. One challenge for studying extreme viruses is to find efficient purification conditions where viruses maintain their infectivity. Asymmetrical flow field-flow fractionation (AF4) is a gentle native chromatography-like technique for size-based separation. It does not have solid stationary phase and the mobile phase composition is readily adjustable according to the sample needs. Due to the high separation power of specimens up to 50 µm, AF4 is suitable for virus purification. Here, we applied AF4 for extremophilic viruses representing four morphotypes: lemon-shaped, tailed and tailless icosahedral, as well as pleomorphic enveloped. AF4 was applied to input samples of different purity: crude supernatants of infected cultures, polyethylene glycol-precipitated viruses and viruses purified by ultracentrifugation. All four virus morphotypes were successfully purified by AF4. AF4 purification of culture supernatants or polyethylene glycol-precipitated viruses yielded high recoveries, and the purities were comparable to those obtained by the multistep ultracentrifugation purification methods. In addition, we also demonstrate that AF4 is a rapid monitoring tool for virus production in slowly growing host cells living in extreme conditions.

Chemistry of 1,1,2,2,9,9,10,10-octafluoro-[2,2]-paracyclophane: Its synthesis and reactions

NASA Astrophysics Data System (ADS)

Duan, Jian-Xin

This dissertation describes the first example of the synthesis of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane (AF4) under non-high-dilution conditions. Under very mild reaction conditions, bis-p-(chlorodifluoromethyl)benzene (TFPX dichloride) and its derivatives reacted with Zn dust in N,N-dimethyl acetamide (DMA) (Zinc method) affording the corresponding AF4 and its derivatives in moderate to good yields. Purification of products was also studied and an efficient purification process was developed. A new and very cheap method for preparation of TFPX dichloride is also disclosed. Using the very cheap fluorinating reagent, anhydrous hydrogen fluoride (AHF), 1,4-bis(trichloromethyl)benezene or its derivatives were converted to TFPX and its derivatives in high yields (F/Cl exchange reaction). With the success of the Zinc method and F/Cl exchange reaction, highly pure AF4 thus can be provided to the semiconductor industry and academy research scientists in large quantity and at a very low price. Starting from AF4, numerous AF4 derivatives were synthesized using convenient reaction conditions. Reaction of AF4 with fuming nitric acid at room temperature gave mono-nitroAF4 in almost quantitative yield. Reduction of the mono-nitroAF4 with iron powder in the presence of HCl in alcoholic solvent gave the aminoAF4 in 90% yield. Via the diazonium salt intermediate, iodoAF4 was also obtained in good yield. Under similar reaction conditions, disubstituted AF4 derivatives were also prepared in good yields. Heating a mixture of AF4, trifluoroacetyl peroxide and dichloromethane gave the trifluoromethylated dimeric AF4 as a mixture of diastereomers. When these products were heated to 170--180°C in the presence of I 2, 4-trifluoromethyl-AF4 was obtained in almost 87% yield. X-ray structural analysis showed that the C-C bond connecting the two cyclophane moieties to be longer than the normal C-C bond. Kinetic studies, conducted in the presence of excess amount of hydrogen donor, showed this bond to be quite weak. Oxidation of AF4 with HIO3 in the presence of catalytic amount of H2SO4 in trifluoroacetic acid gave AF4 quinone in one step. AF4 quinone can be easily reduced to the hydroquinone by Na 2S2O4 aqueous solution.

[Simultaneous determination of arsanilic, nitarsone and roxarsone residues in foods of animal origin by ASE-LC-AFS].

PubMed

Xiao, Ya-Bing; Zhang, Man; Wen, Hua-Wei

2014-04-01

A method for simultaneous determination of arsanilic, nitarsone and roxarsone (ROX) residues in foods of animal origin was developed by accelerated solvent extraction-liquid chromatography-atomic fluorescence spectrometry (ASE-LC-AFS). The ultrasound centrifugation extraction and accelerated solvent extraction were compared, and the accelerated solvent extraction conditions, namely the proportion of the extraction solvent, the extraction temperature, extraction time and extraction times, were optimized. The operating conditions of LC-AFS and the mobile phase were optimized. Under the optimal conditions, the calibration curves for ASA , NIT and ROX were linear over the concentration range of 0-2.0 mg x L(-1) and their correlation coefficients were 0.999 2-0.999 8. The detection limits of ASA, NIT and ROX were 2.4, 7.4 and 4.1 microg x L(-1) respectively. The average recoveries of ASA, NIT and ROX from two samples spiked at three levels of 0.5, 2, 5 mg x kg(-1) were in the ranges of 87.1%-93.2%, 85.2%-93.9%, and 84.2%-93.7% with RSDs of 1.4%-4.6%, 1.2%-4.2%, and 1.1%-4.5%, respectively. This method possesses the merits of convenience and good repeatability, and is a feasible method for analysis of ASA, NIT and ROX in foods of animal origin.

Atrial ectopy predicts late recurrence of atrial fibrillation after pulmonary vein isolation.

PubMed

Gang, Uffe J O; Nalliah, Chrishan J; Lim, Toon Wei; Thiagalingam, Aravinda; Kovoor, Pramesh; Ross, David L; Thomas, Stuart P

2015-06-01

Late recurrence of atrial fibrillation (AF) after radiofrequency ablation remains significant. Asymptomatic recurrence poses a difficult clinical problem as it is associated with an equally increased risk of stroke and death compared with symptomatic AF events. Meta-analyses reveal that no single preablation patient characteristic efficiently predicts these AF recurrences. This study aimed to evaluate the prognostic value of premature atrial complex (PAC) occurrence with regard to the risk of late AF recurrence after radiofrequency ablation. The study cohort consisted of 124 patients with 7-day Holter recordings at 6 months post radiofrequency ablation for AF. No patients had AF recurrence before this time. Patients were followed-up every 6 months. Holter-detected PACs were defined as any supraventricular complexes occurring >30% earlier than expected. During a median follow-up of 4.2 years (first quartile to third quartile [Q1-Q3]=1.6-4.5), 32 patients (26%) had late recurrences of AF at a median of 462 days (Q1-Q3=319-1026) post radiofrequency ablation. The number of PACs per 24 hours was 248 (Q1-Q3=62-1026) in patients with and 77 (Q1-Q3=24-448) in patients without recurrence of AF (P=0.02). Multivariate analysis of the risk of late AF recurrence found ≥142 PACs per 24 hours to have a hazard ratio 2.84 (confidence interval, 1.26-6.43), P=0.01. This study showed that occurrence of ≥142 PACs per day at 6 months after PVI was independently associated with a significantly increased risk of late AF recurrence. These results could have important clinical implications for the design of post-PVI follow-up. URL: http://www.anzctr.org.au. Unique identifier: ACRTN12606000467538. © 2015 American Heart Association, Inc.

Performance Enhancement of Organic Light-Emitting Diodes Using Electron-Injection Materials of Metal Carbonates

NASA Astrophysics Data System (ADS)

Shin, Jong-Yeol; Kim, Tae Wan; Kim, Gwi-Yeol; Lee, Su-Min; Shrestha, Bhanu; Hong, Jin-Woong

2016-05-01

Performance of organic light-emitting diodes was investigated depending on the electron-injection materials of metal carbonates (Li2CO3 and Cs2CO3 ); and number of layers. In order to improve the device efficiency, two types of devices were manufactured by using the hole-injection material (Teflon-amorphous fluoropolymer -AF) and electron-injection materials; one is a two-layer reference device ( ITO/Teflon-AF/Alq3/Al ) and the other is a three-layer device (ITO/Teflon-AF/Alq3/metal carbonate/Al). From the results of the efficiency for the devices with hole-injection layer and electron-injection layer, it was found that the electron-injection layer affects the electrical properties of the device more than the hole-injection layer. The external-quantum efficiency for the three-layer device with Li2CO3 and Cs2CO3 layer is improved by approximately six and eight times, respectively, compared with that of the two-layer reference device. It is thought that a use of electron-injection layer increases recombination rate of charge carriers by the active injection of electrons and the blocking of holes.

Measures of Body Size and Composition and Risk of Incident Atrial Fibrillation in Older People

PubMed Central

Karas, Maria G.; Yee, Laura M.; Biggs, Mary L.; Djoussé, Luc; Mukamal, Kenneth J.; Ix, Joachim H.; Zieman, Susan J.; Siscovick, David S.; Gottdiener, John S.; Rosenberg, Michael A.; Kronmal, Richard A.; Heckbert, Susan R.; Kizer, Jorge R.

2016-01-01

Various anthropometric measures, including height, have been associated with atrial fibrillation (AF). This raises questions about the appropriateness of using ratio measures such as body mass index (BMI), which contains height squared in its denominator, in the evaluation of AF risk. Among older adults, the optimal anthropometric approach to risk stratification of AF remains uncertain. Anthropometric and bioelectrical impedance measures were obtained from 4,276 participants (mean age = 72.4 years) free of cardiovascular disease in the Cardiovascular Health Study. During follow-up (1989–2008), 1,050 cases of AF occurred. BMI showed a U-shaped association, whereas height, weight, waist circumference, hip circumference, fat mass, and fat-free mass were linearly related to incident AF. The strongest adjusted association occurred for height (per each 1-standard-deviation increment, hazard ratio = 1.38, 95% confidence interval: 1.25, 1.51), which exceeded all other measures, including weight (hazard ratio = 1.21, 95% confidence interval: 1.13, 1.29). Combined assessment of log-transformed weight and height showed regression coefficients that departed from the 1 to −2 ratio inherent in BMI, indicating a loss of predictive information. Risk estimates for AF tended to be stronger for hip circumference than for waist circumference and for fat-free mass than for fat mass, which was explained largely by height. These findings highlight the prominent role of body size and the inadequacy of BMI as determinants of AF in older adults. PMID:27188936

Echocardiographic predictors of atrial fibrillation recurrence after catheter ablation: A literature review.

PubMed

Liżewska-Springer, Aleksandra; Dąbrowska-Kugacka, Alicja; Lewicka, Ewa; Drelich, Łukasz; Królak, Tomasz; Raczak, Grzegorz

2018-06-20

Catheter ablation (CA) is a well-known treatment option for patients with symptomatic drug-resistant atrial fibrillation (AF). Multiple factors have been identified to determine AF recurrence after CA, however their predictive value is rather small. Identification of novel predictors of CA outcome is therefore of primary importance to reduce health costs and improve long-term results of this intervention. The recurrence of AF following CA is related to the severity of left ventricular (LV) dysfunction, extend of atrial dilatation and fibrosis. The aim of this paper was to present and discuss the latest studies on utility of echocardiographic parameters in terms of CA effectiveness in patients with paroxysmal and persistent AF. PubMed, Google Scholar, EBSCO databases were searched for studies reporting echocardiographic preprocedural predictors of AF recurrence after CA. LV systolic and diastolic function, as well as atrial size, strain and dyssynchrony were taken into consideration. Twenty one full-text articles were analyzed, including three meta-analyses. Several echocardiographic parameters have been reported to determine a risk of AF recurrence after CA. There are conventional methods that measure left atrial (LA) size and volume, LV ejection fraction, parameters assessing LV diastolic dysfunction, and methods using more innovative technologies based on speckle tracking echocardiography (STE) to determine LA synchrony and strain. Each of these parameters has its own predictive value. Regarding CA effectiveness, every patient has to be evaluated individually to estimate the risk of AF recurrence, optimally using a combination of several echocardiographic parameters.

Clinical impact of rotor ablation in atrial fibrillation: a systematic review.

PubMed

Parameswaran, Ramanathan; Voskoboinik, Aleksandr; Gorelik, Alexandra; Lee, Geoffrey; Kistler, Peter M; Sanders, Prashanthan; Kalman, Jonathan M

2018-01-11

Rotor mapping and ablation have gained favour over the recent years as an emerging ablation strategy targeting drivers of atrial fibrillation (AF). Their efficacy, however, has been a topic of great debate with variable outcomes across centres. The aim of this study was to systematically review the recent medical literature to determine the medium-term outcomes of rotor ablation in patients with paroxysmal atrial fibrillation (PAF) and persistent atrial fibrillation (PeAF). A systematic search of the contemporary scientific literature (PubMed and EMBASE) was performed in August 2017. Only studies assessing arrhythmia-free survival from rotor ablation of AF were included. We used the random-effects model to assess the primary outcome of pooled medium-term single-procedure AF-free survival for both PAF and PeAF. Success rates from multiple procedures and complication rates were also examined. We included 11 observational studies (4 PAF and 10 PeAF) with a total of 556 patients (166 PAF and 390 PeAF). Pooled single-procedure freedom from AF was 37.8% [95% confidence interval 5.6-86.3%] at a mean follow-up period of 13.8 ± 1.8 months for PAF and 59.2% (95% CI 41.4-74.9%) at a mean follow-up period of 12.9 ± 6 months for PeAF. There was a marked heterogeneity between studies (I2 = 93.8% for PAF and 88.3% for PeAF). The mean complication rate of rotor ablation among the reported studies was 3.4%. The wide variability in success rate between different centres performing rotor ablations suggests that the optimal ablation strategy, particularly targeting rotors, is unclear. Results from randomized studies are necessary before this technique can be considered as an established clinical tool. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

Multivariate Analysis As a Support for Diagnostic Flowcharts in Allergic Bronchopulmonary Aspergillosis: A Proof-of-Concept Study.

PubMed

Vitte, Joana; Ranque, Stéphane; Carsin, Ania; Gomez, Carine; Romain, Thomas; Cassagne, Carole; Gouitaa, Marion; Baravalle-Einaudi, Mélisande; Bel, Nathalie Stremler-Le; Reynaud-Gaubert, Martine; Dubus, Jean-Christophe; Mège, Jean-Louis; Gaudart, Jean

2017-01-01

Molecular-based allergy diagnosis yields multiple biomarker datasets. The classical diagnostic score for allergic bronchopulmonary aspergillosis (ABPA), a severe disease usually occurring in asthmatic patients and people with cystic fibrosis, comprises succinct immunological criteria formulated in 1977: total IgE, anti- Aspergillus fumigatus ( Af ) IgE, anti- Af "precipitins," and anti- Af IgG. Progress achieved over the last four decades led to multiple IgE and IgG(4) Af biomarkers available with quantitative, standardized, molecular-level reports. These newly available biomarkers have not been included in the current diagnostic criteria, either individually or in algorithms, despite persistent underdiagnosis of ABPA. Large numbers of individual biomarkers may hinder their use in clinical practice. Conversely, multivariate analysis using new tools may bring about a better chance of less diagnostic mistakes. We report here a proof-of-concept work consisting of a three-step multivariate analysis of Af IgE, IgG, and IgG4 biomarkers through a combination of principal component analysis, hierarchical ascendant classification, and classification and regression tree multivariate analysis. The resulting diagnostic algorithms might show the way for novel criteria and improved diagnostic efficiency in Af -sensitized patients at risk for ABPA.

A performance analysis in AF full duplex relay selection network

NASA Astrophysics Data System (ADS)

Ngoc, Long Nguyen; Hong, Nhu Nguyen; Loan, Nguyen Thi Phuong; Kieu, Tam Nguyen; Voznak, Miroslav; Zdralek, Jaroslav

2018-04-01

This paper studies on the relaying selective matter in amplify-and-forward (AF) cooperation communication with full-duplex (FD) activity. Various relay choice models supposing the present of different instant information are investigated. We examine a maximal relaying choice that optimizes the instant FD channel capacity and asks for global channel state information (CSI) as well as partial CSI learning. To make comparison easy, accurate outage probability clauses and asymptote form of these strategies that give a diversity rank are extracted. From that, we can see clearly that the number of relays, noise factor, the transmittance coefficient as well as the information transfer power had impacted on their performance. Besides, the optimal relay selection (ORS) model can promote than that of the partial relay selection (PRS) model.

[Application of asymmetrical flow field-flow fractionation for size characterization of low density lipoprotein in egg yolk plasma].

PubMed

Zhang, Wenhui; Cai, Chunxue; Wang, Jing; Mao, Zhen; Li, Yueqiu; Ding, Liang; Shen, Shigang; Dou, Haiyang

2017-08-08

Home-made asymmetrical flow field-flow fractionation (AF4) system, online coupled with ultraviolet/visible (UV/Vis) detector was employed for the separation and size characterization of low density lipoprotein (LDL) in egg yolk plasma. At close to natural condition of egg yolk, the effects of cross flow rate, sample loading, and type of membrane on the size distribution of LDL were investigated. Under the optimal operation conditions, AF4-UV/Vis provides the size distribution of LDL. Moreover, the precision of AF4-UV/Vis method proposed in this work for the analysis of LDL in egg yolk plasma was evaluated. The intra-day precisions were 1.3% and 1.9% ( n =7) and the inter-day precisions were 2.4% and 2.3% ( n =7) for the elution peak height and elution peak area of LDL, respectively. Results reveal that AF4-UV/Vis is a useful tool for the separation and size characterization of LDL in egg yolk plasma.

Loss of Proliferation and Antigen Presentation Activity following Internalization of Polydispersed Carbon Nanotubes by Primary Lung Epithelial Cells

PubMed Central

Kumari, Mandavi; Sachar, Sumedha; Saxena, Rajiv K.

2012-01-01

Interactions between poly-dispersed acid functionalized single walled carbon nanotubes (AF-SWCNTs) and primary lung epithelial (PLE) cells were studied. Peritoneal macrophages (PMs, known phagocytic cells) were used as positive controls in this study. Recovery of live cells from cultures of PLE cells and PMs was significantly reduced in the presence of AF-SWCNTs, in a time and dose dependent manner. Both PLE cells as well as PMs could take up fluorescence tagged AF-SWCNTs in a time dependent manner and this uptake was significantly blocked by cytochalasin D, an agent that blocks the activity of acto-myosin fibers and therefore the phagocytic activity of cells. Confocal microscopic studies confirmed that AF-SWCNTs were internalized by both PLE cells and PMs. Intra-trachially instilled AF-SWCNTs could also be taken up by lung epithelial cells as well as alveolar macrophages. Freshly isolated PLE cells had significant cell division activity and cell cycling studies indicated that treatment with AF-SWCNTs resulted in a marked reduction in S-phase of the cell cycle. In a previously standardized system to study BCG antigen presentation by PLE cells and PMs to sensitized T helper cells, AF-SWCNTs could significantly lower the antigen presentation ability of both cell types. These results show that mouse primary lung epithelial cells can efficiently internalize AF-SWCNTs and the uptake of nanotubes interfered with biological functions of PLE cells including their ability to present BCG antigens to sensitized T helper cells. PMID:22384094

Intra-operative mapping of the atria: the first step towards individualization of atrial fibrillation therapy?

PubMed

Kik, Charles; Mouws, Elisabeth M J P; Bogers, Ad J J C; de Groot, Natasja M S

2017-07-01

Atrial fibrillation (AF), an age-related progressive disease, is becoming a worldwide epidemic with a prevalence rate of 33 million. Areas covered: In this expert review, an overview of important results obtained from previous intra-operative mapping studies is provided. In addition, our novel intra-operative high resolution mapping studies, its surgical considerations and data analyses are discussed. Furthermore, the importance of high resolution mapping studies of both sinus rhythm and AF for the development of future AF therapy is underlined by our most recent results. Expert commentary: Progression of AF is determined by the extensiveness of electropathology which is defined as conduction disorders caused by structural damage of atrial tissue. The severity of electropathology is a major determinant of therapy failure. At present, we do not have any diagnostic tool to determine the degree of electropathology in the individual patient and we can thus not select the most optimal treatment modality for the individual patient. An intra-operative, high resolution scale, epicardial mapping approach combined with quantification of electrical parameters may serve as a diagnostic tool to stage AF in the individual patient and to provide patient tailored therapy.

Spin Dynamics in the electron-doped high-Tc superconductors Pr0.88LaCe0.12CuO4-δ

NASA Astrophysics Data System (ADS)

Dai, Pengcheng

2007-03-01

We briefly review results of recent neutron scattering experiments designed to probe the evolution of antiferromagnetic (AF) order and spin dynamics in the electron- doped Pr0.88LaCe0.12CuO4-δ (PLCCO) as the system is tuned from its as-grown non-superconducting AF state into an optimally doped superconductor (Tc = 27.5 K) without static AF order [1-3]. For under doped materials, a quasi-two- dimensional spin-density wave was found to coexist with three- dimensional AF order and superconductivity. In addition, the low-energy spin excitations follow Bose statistics. In the case of optimally doped material, we have discovered a magnetic resonance intimately related to superconductivity analogous to the resonance in hole-doped materials. On the other hand, the low energy spin excitations have very weak temperature dependence and do not follow Bose statistics, in sharp contrast to the as-grown nonsuperconducting materials. 1 Stephen D. Wilson, Pengcheng Dai, Shiliang Li, Songxue Chi, H. J. Kang, and J. W. Lynn, Nature (London) 442, 59 (2006). 2 Stephen D. Wilson, Shiliang Li, Hyungje Woo, Pengcheng Dai, H. A. Mook, C. D. Frost, S. Komiya, and Y. Ando, Phys. Rev. Lett. 96, 157001 (2006). 3. Stephen D. Wilson, Shiliang Li, Pengcheng Dai, Wei Bao, J. H. Chung, H. J. Kang, S.-H. Lee, S. Komiya, and Y. Ando, Phys. Rev. B 74, 144514 (2006).

Elevated admission N-terminal pro-brain natriuretic peptide level predicts the development of atrial fibrillation in general surgical intensive care unit patients.

PubMed

Chokengarmwong, Nalin; Yeh, Daniel Dante; Chang, Yuchiao; Ortiz, Luis Alfonso; Kaafarani, Haytham M A; Fagenholz, Peter; King, David R; DeMoya, Marc; Butler, Kathryn; Lee, Jarone; Velmahos, George; Januzzi, James Louis; Lee-Lewandrowski, Elizabeth; Lewandrowski, Kent

2017-09-01

New onset atrial fibrillation (AF) in critically ill surgical patients is associated with significant morbidity and increased mortality. N-terminal pro-B type natriuretic peptide (NT-proBNP) is released by cardiomyocytes in response to stress and may predict AF development after surgery. We hypothesized that elevated NT-proBNP level at surgical intensive care unit (ICU) admission predicts AF development in a general surgical and trauma population. From July to October 2015, NT-proBNP concentrations were measured at ICU admission. Abnormal NT-proBNP concentrations were defined by age-adjusted cut-offs. We examined the relationship between the development of AF and demographics, clinical variables, and NT-proBNP level using univariate analysis and a multivariable logistic regression model. Three hundred eighty-seven subjects were included in the cohort, none of whom were in AF at ICU admission. The median age was 63 years (52-73 years), and 40.3% were women. The risk of developing AF was higher for abnormal versus normal NT-proBNP (22% vs. 4%; p < 0.0001). Using optimal derived cutoffs (regardless of age), the risk of developing AF was 2% for NT-proBNP less than 600 ng/L, 15% for NT-proBNP of 600 ng/L to 1,999 ng/L, and 27% for NT-proBNP of 2,000 ng/L or greater. Multiple logistic regression analysis identified three independent predictors for new-onset AF: age, older than 70 years (odds ratio [OR], 3.7, 95% confidence interval [CI], 1.5-9.3), history of AF (OR, 25.3; 95% CI, 9.6-67.0), and NT-proBNP of 600 or greater (OR, 4.3; 95% CI, 1.3-14.2). When none or only one predictor was present, AF incidence was less than 1%. When all three predictors were present, AF incidence was 66%. For subjects 70 years or older but no history of AF, AF incidence was 12.8% when NT-proBNP was 600 or greater compared with 0% when NT-proBNP was less than 600. For subjects younger than 70 years with a history of AF, AF incidence was 44.4% when NT-proBNP was 600 or higher compared to 0% when NT-proBNP was less than 600. Elevated NT-proBNP at ICU admission in general surgical and trauma patients is predictive of AF development in the first 3 ICU days. Addition of NT-proBNP measurement to known risk factors can improve predictive power and identify patients who might potentially benefit from evidence-based prophylactic treatment for AF.

A method for aircraft afterburner combustion without flameholders

NASA Astrophysics Data System (ADS)

Birmaher, Shai

2009-12-01

State of the art aircraft afterburners employ spray bars to inject fuel and flameholders to stabilize the combustion process. Such afterburner designs significantly increase the length (and thus weight), pressure losses, and observability of the engine. This thesis presents a feasibility study of a compact 'prime and trigger' (PAT) afterburner concept that eliminates the fuel spray bars and flameholders and, thus, eliminates the above-mentioned problems. In this concept, afterburner fuel is injected just upstream or in between the turbine stages. As the fuel travels through the turbine stages, it evaporates, mixes with the bulk flow, and undergoes some chemical reactions without any significant heat release, a process referred to as 'priming'. Downstream of the turbine stages, combustion could take place through autoignition. However, if fuel autoignition does not occur or if autoignition does not produce a combustion zone that is stable and highly efficient, then a low power pilot, or 'trigger', can be used to control the combustion process. The envisioned trigger for the PAT concept is a jet of product gas from ultra-rich hydrocarbon/air combustion that is injected through the afterburner liner. This 'partial oxidation' (POx) gas, which consists mostly of H2, CO, and diluents, rapidly produces radicals and heat that accelerate the autoignition of the primed mixture and, thus, provide an anchor point for the afterburner combustion process. The objective of this research was to demonstrate the feasibility of the PAT concept by showing that (1) combustion of fuel injected within or upstream of turbine stages can occur only downstream of the turbine stages, and (2) the combustion zone is compact, stable and efficient. This was accomplished using two experimental facilities, a developed theoretical model, and Chemkin simulations. The first facility, termed the Afterburner Facility (AF), simulated the bulk flow temperature, velocity and O2 content through a turbojet combustor, turbine stage and afterburner. To model the PAT concept, Jet-A was injected upstream of the simulated turbine stage and a H2 jet was used to trigger the primed Jet-A combustion process downstream of the turbine stage. H2 was used because POx gas was not available for experiments. The second facility, termed the Propane Autoignition Combustor (PAC), was essentially a scaled-down, simplified version of the AF. The PAC experiments focused on the trigger stage of the PAT concept, using H 2 in lieu of POx gas and employing measurement techniques that were in some ways more detailed than in the AF experiments. The developed model simulated the physics of fuel priming in the AF and predicted the Jet-A autoignition location. It was used to predict and interpret the AF results and to study the feasibility of the PAT concept at pressures outside the AF operating range. Finally, the Chemkin simulations were used to examine the effect of several POx gas compositions on the Jet-A/vitiated-air autoignition process; to compare the POx and H2 triggers; and to explore several reasons for why POx gas and H2 are suitable trigger mechanisms. he experimental, theoretical, and numerical results obtained in this investigation indicated that the PAT concept provides a feasible approach to afterburner combustion. The experiments in the AF showed that the ignition delay of Jet-A is sufficiently long to allow fuel injection within turbine stages without significant heat release upstream of the afterburner. In the AF experiments without the H2 trigger, Jet-A combustion was achieved through autoignition; however, the autoignition combustion zone exhibited large axial fluctuations and low combustion efficiency. The H2 trigger was able to shift the combustion zone upstream, make it more compact, reduce fluctuations in its axial position, and raise the combustion efficiency to nearly 100%. The PAC experiments also showed that a H2 trigger can shift the combustion zone upstream, make it more compact, and increase the combustion efficiency. The PAC results were obtained with lower O 2 content and higher equivalence ratios than in the AF. Therefore, the combined AF and PAC results suggested that the PAT concept is feasible over a wide range of operating conditions. The developed model showed good agreement with the AF results. It also predicted that the PAT concept is feasible at bulk flow pressures outside the AF operating range. Finally, the Chemkin results showed that both the H2 and POx gas triggers can significantly reduce the ignition delay time of primed Jet-A/vitiated air mixtures. Thus, POx gas is a suitable trigger for the PAT concept and should be tested in future experimental investigations.

Using Discrete Event Simulation to Model the Economic Value of Shorter Procedure Times on EP Lab Efficiency in the VALUE PVI Study.

PubMed

Kowalski, Marcin; DeVille, J Brian; Svinarich, J Thomas; Dan, Dan; Wickliffe, Andrew; Kantipudi, Charan; Foell, Jason D; Filardo, Giovanni; Holbrook, Reece; Baker, James; Baydoun, Hassan; Jenkins, Mark; Chang-Sing, Peter

2016-05-01

The VALUE PVI study demonstrated that atrial fibrillation (AF) ablation procedures and electrophysiology laboratory (EP lab) occupancy times were reduced for the cryoballoon compared with focal radiofrequency (RF) ablation. However, the economic impact associated with the cryoballoon procedure for hospitals has not been determined. Assess the economic value associated with shorter AF ablation procedure times based on VALUE PVI data. A model was formulated from data from the VALUE PVI study. This model used a discrete event simulation to translate procedural efficiencies into metrics utilized by hospital administrators. A 1000-day period was simulated to determine the accrued impact of procedure time on an institution's EP lab when considering staff and hospital resources. The simulation demonstrated that procedures performed with the cryoballoon catheter resulted in several efficiencies, including: (1) a reduction of 36.2% in days with overtime (422 days RF vs 60 days cryoballoon); (2) 92.7% less cumulative overtime hours (370 hours RF vs 27 hours cryoballoon); and (3) an increase of 46.7% in days with time for an additional EP lab usage (186 days RF vs 653 days cryoballoon). Importantly, the added EP lab utilization could not support the time required for an additional AF ablation procedure. The discrete event simulation of the VALUE PVI data demonstrates the potential positive economic value of AF ablation procedures using the cryoballoon. These benefits include more days where overtime is avoided, fewer cumulative overtime hours, and more days with time left for additional usage of EP lab resources.

Functional characterization of GH7 endo-1,4-β-glucanase from Aspergillus fumigatus and its potential industrial application.

PubMed

Bernardi, Aline Vianna; de Gouvêa, Paula Fagundes; Gerolamo, Luis Eduardo; Yonamine, Deborah Kimie; de Lourdes de Lima Balico, Laís; Uyemura, Sergio Akira; Dinamarco, Taisa Magnani

2018-04-30

A gene encoding an endo-1,4-β-glucanase (Afu6g01800) from A. fumigatus was cloned into the vector pET-28a(+) and expressed in the E. coli strain RosettaTM (DE3) pLysS. Sequence analysis indicated that the enzyme Af-EGL7 belonged to the GH7 family. The gene Af-egl7 encoded a protein comprising 460 amino acids, with a CBM1 domain at residues 424-460 and molecular mass of 52 kDa, as estimated by SDS-PAGE. This enzyme was optimally active at pH and temperatures ranging from 4.5 to 5.5 and from 40 to 60 °C, respectively. Mn 2+ addition significantly enhanced the Af-EGL7 cellulase activity by 233%, whereas SDS addition fully inhibited this activity. Higher activity was observed toward β-glucan than toward xyloglucan and CM-Cellulose, suggesting that the enzyme corresponds to a β-1,3-1,4-glucanase. qRT-PCR in different culture media helped to establish the time-course expression profile. Different polysaccharides induced the gene Af-egl7 in a time-dependent manner; in the particular case of the substrate sugarcane exploded bagasse (SEB), Af-egl7 was induced 2500-fold. Upon addition to a commercial cellulase cocktail, Af-EGL7 significantly improved SEB saccharification, which suggested that the enzyme Af-EGL7 had great potential to hydrolyze complex biomass. From a biotechnological point of view, A. fumigatus Af-EGL7 is a promising candidate to enhance enzyme cocktails used in biorefineries such as consolidated bioprocessing. Copyright © 2018 Elsevier Inc. All rights reserved.

HRS/NSA 2014 Survey of Atrial Fibrillation and Stroke: Gaps in Knowledge and Perspective, Opportunities for Improvement.

PubMed

Frankel, David S; Parker, Sarah E; Rosenfeld, Lynda E; Gorelick, Philip B

2015-08-01

The prevalence of atrial fibrillation (AF) is substantial and increasing. Stroke is common in AF and can have devastating consequences. Oral anticoagulants are effective in reducing stroke risk, but are underutilized. We sought to characterize the impact of stroke on AF patients and their caregivers, gaps in knowledge and perspective between physicians and patients, and barriers to effective communication and optimal anticoagulation use. A survey was administered to AF patients with and without history of stroke, caregivers of stroke survivors, and physicians across the range of specialties caring for AF and stroke patients. While AF patients (n = 499) had limited knowledge about stroke, they expressed great desire to learn more and take action to reduce their risk. They were often dissatisfied with the education they had received and desired high-quality written materials. Stroke survivors (n = 251) had poor functional outcomes and often underestimated the burden of caring for them. Caregivers (n = 203) also wished they had received more information about reducing stroke risk before their survivor's event. They commonly felt overwhelmed and socially isolated. Physicians (n = 504) did not prescribe anticoagulants as frequently as recommended by guidelines. Concerns about monitoring anticoagulation and patient compliance were commonly reported barriers. Physicians may underestimate patient willingness to take anticoagulants. We identified significant knowledge gaps among patients, caregivers, and physicians in relation to AF and stroke. Furthermore, gaps in perspective often lead to suboptimal communication and decision making. Increased education and better communication between all stakeholders are needed to reduce the impact of stroke in AF. Copyright © 2015 Heart Rhythm Society and National Stroke Association. Published by Elsevier Inc. All rights reserved.

HRS/NSA 2014 survey of atrial fibrillation and stroke: Gaps in knowledge and perspective, opportunities for improvement.

PubMed

Frankel, David S; Parker, Sarah E; Rosenfeld, Lynda E; Gorelick, Philip B

2015-08-01

The prevalence of atrial fibrillation (AF) is substantial and increasing. Stroke is common in AF and can have devastating consequences. Oral anticoagulants are effective in reducing stroke risk, but are underutilized. We sought to characterize the impact of stroke on AF patients and their caregivers, gaps in knowledge and perspective between physicians and patients, and barriers to effective communication and optimal anticoagulation use. A survey was administered to AF patients with and without history of stroke, caregivers of stroke survivors, and physicians across the range of specialties caring for AF and stroke patients. While AF patients (n = 499) had limited knowledge about stroke, they expressed great desire to learn more and take action to reduce their risk. They were often dissatisfied with the education they had received and desired high-quality written materials. Stroke survivors (n = 251) had poor functional outcomes and often underestimated the burden of caring for them. Caregivers (n = 203) also wished they had received more information about reducing stroke risk before their survivor's event. They commonly felt overwhelmed and socially isolated. Physicians (n = 504) did not prescribe anticoagulants as frequently as recommended by guidelines. Concerns about monitoring anticoagulation and patient compliance were commonly reported barriers. Physicians may underestimate patient willingness to take anticoagulants. We identified significant knowledge gaps among patients, caregivers, and physicians in relation to AF and stroke. Furthermore, gaps in perspective often lead to suboptimal communication and decision making. Increased education and better communication between all stakeholders are needed to reduce the impact of stroke in AF. Copyright © 2015 Heart Rhythm Society and National Stroke Association. Published by Elsevier Inc. All rights reserved.

Brain and kidney, victims of atrial microembolism in elderly hospitalized patients? Data from the REPOSI study.

PubMed

Corrao, S; Argano, C; Nobili, A; Marcucci, M; Djade, C D; Tettamanti, M; Pasina, L; Franchi, C; Marengoni, A; Salerno, F; Violi, F; Mannucci, P M; Perticone, F

2015-05-01

It is well known that atrial fibrillation (AF) and chronic kidney disease (CKD) are associated with a higher risk of stroke, and new evidence links AF to cognitive impairment, independently from an overt stroke (CI). Our aim was to investigate, assuming an underlying role of atrial microembolism, the impact of CI and CKD in elderly hospitalized patients with AF. We retrospectively analyzed the data collected on elderly patients in 66 Italian hospitals, in the frame of the REPOSI project. We analyzed the clinical characteristics of patients with AF and different degrees of CI. Multivariate logistic analysis was used to explore the relationship between variables and mortality. Among the 1384 patients enrolled, 321 had AF. Patients with AF were older, had worse CI and disability and higher rates of stroke, hypertension, heart failure, and CKD, and less than 50% were on anticoagulant therapy. Among patients with AF, those with worse CI and those with lower estimated glomerular filtration rate (eGFR) had a higher mortality risk (odds ratio 1.13, p=0.006). Higher disability levels, older age, higher systolic blood pressure, and higher eGFR were related to lower probability of oral anticoagulant prescription. Lower mortality rates were found in patients on oral anticoagulant therapy. Elderly hospitalized patients with AF are more likely affected by CI and CKD, two conditions that expose them to a higher mortality risk. Oral anticoagulant therapy, still underused and not optimally enforced, may afford protection from thromboembolic episodes that probably concur to the high mortality. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity.

PubMed

Misemer, Benjamin S; Skubitz, Amy P N; Carlos Manivel, J; Schmechel, Stephen C; Cheng, Edward Y; Henriksen, Jonathan C; Koopmeiners, Joseph S; Corless, Christopher L; Skubitz, Keith M

2014-02-01

Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Uniaxial pressure effect on the magnetic ordered moment and transition temperatures in BaFe 2 - x T x As 2 ( T = Co , Ni )

DOE PAGES

Tam, David W.; Song, Yu; Man, Haoran; ...

2017-02-17

In this paper, we use neutron diffraction and muon spin relaxation to study the effect of in-plane uniaxial pressure on the antiferromagnetic (AF) orthorhombic phase in BaFe 2As 2 and its Co- and Ni-substituted members near optimal superconductivity. In the low-temperature AF ordered state, uniaxial pressure necessary to detwin the orthorhombic crystals also increases the magnetic ordered moment, reaching an 11% increase under 40 MPa for BaFe 1.9Co 0.1As 2, and a 15% increase for BaFe 1.915Ni 0.085As 2. We also observe an increase of the AF ordering temperature (T N) of about 0.25 K/MPa in all compounds, consistent withmore » density functional theory calculations that reveal better Fermi surface nesting for itinerant electrons under uniaxial pressure. Finally, the doping dependence of the magnetic ordered moment is captured by combining dynamical mean field theory with density functional theory, suggesting that the pressure-induced moment increase near optimal superconductivity is closely related to quantum fluctuations and the nearby electronic nematic phase.« less

Thermophilic Ferritin: Versatile Nanohost

NASA Astrophysics Data System (ADS)

Pulsipher, Katherine W.

Thermophilic ferritin from Archaeoglobus fulgidus (AfFtn) is a 24meric, hollow, cage-like protein, whose native function is the oxidation, mineralization, and storage of iron. Unique among ferritins, its self-assembly is dependent on high ionic strength, reflecting the deep sea thermal vent environment where A. fulgidus is found. This ionic strength dependence can be used to encapsulate charged cargo within the AfFtn cavity. Its subunits self-assemble into tetrahedral symmetry, resulting in four, large (4.5 nm), triangular pores, not found in other ferritins. Due to its size (12 nm outer diameter, 8 nm inner diameter), self-assembly properties, and potential for both genetic and chemical modification, AfFtn is an ideal nanocontainer for a variety of cargo, including inorganic nanoparticles and proteins. We have sought to better understand the self-assembly of AfFtn and its encapsulation of various cargo. Guided by computational analysis and through mutagenesis, we have investigated the role of electrostatics along the AfFtn trimeric interface in self-assembly. We have developed a series of single point mutants with increasingly favorable cage assembly. One specific mutation, E65R, has a dramatic effect on AfFtn, almost entirely preventing disassembly and enhancing thermal stability by 14°C. By using a novel graphene-based microelectrode, we have determined that AfFtn maintains its quaternary structure upon encapsulation of a gold nanoparticle, developing a new tool for investigating protein-nanomaterial interactions. We have also shown that AfFtn can be used to template seeded gold nanoparticle growth and have explored two often neglected factors in ferritin-nanoparticle templating: the charge of the gold salt used, and the size of the protein pores. Our results demonstrate that the open, porous structure of AfFtn allows more efficient particle growth than typical closed-pore ferritins. Finally, we have expanded the cargo uptake of AfFtn beyond nanoparticles to include proteins, encapsulating supercharged GFP. The AfFtn-cargo complexes developed here have application in catalysis, nanomaterials synthesis, and targeted delivery.

Predictive value of CHADS2 and CHA2DS2-VASc scores for acute myocardial infarction in patients with atrial fibrillation.

PubMed

Pang, Hui; Han, Bing; Fu, Qiang; Zong, Zhenkun

2017-07-05

The presence of acute myocardial infarction (AMI) confers a poor prognosis in atrial fibrillation (AF), associated with increased mortality dramatically. This study aimed to evaluate the predictive value of CHADS 2 and CHA 2 DS 2 -VASc scores for AMI in patients with AF. This retrospective study enrolled 5140 consecutive nonvalvular AF patients, 300 patients with AMI and 4840 patients without AMI. We identified the optimal cut-off values of the CHADS 2 and CHA 2 DS 2 -VASc scores each based on receiver operating characteristic curves to predict the risk of AMI. Both CHADS 2 score and CHA 2 DS 2 -VASc score were associated with an increased odds ratio of the prevalence of AMI in patients with AF, after adjustment for hyperlipidaemia, hyperuricemia, hyperthyroidism, hypothyroidism and obstructive sleep apnea. The present results showed that the area under the curve (AUC) for CHADS 2 score was 0.787 with a similar accuracy of the CHA 2 DS 2 -VASc score (AUC 0.750) in predicting "high-risk" AF patients who developed AMI. However, the predictive accuracy of the two clinical-based risk scores was fair. The CHA 2 DS 2 -VASc score has fair predictive value for identifying high-risk patients with AF and is not significantly superior to CHADS 2 in predicting patients who develop AMI.

Structural and biochemical characterisation of Archaeoglobus fulgidus esterase reveals a bound CoA molecule in the vicinity of the active site.

PubMed

Sayer, Christopher; Finnigan, William; Isupov, Michail N; Levisson, Mark; Kengen, Servé W M; van der Oost, John; Harmer, Nicholas J; Littlechild, Jennifer A

2016-05-10

A new carboxyl esterase, AF-Est2, from the hyperthermophilic archaeon Archaeoglobus fulgidus has been cloned, over-expressed in Escherichia coli and biochemically and structurally characterized. The enzyme has high activity towards short- to medium-chain p-nitrophenyl carboxylic esters with optimal activity towards the valerate ester. The AF-Est2 has good solvent and pH stability and is very thermostable, showing no loss of activity after incubation for 30 min at 80 °C. The 1.4 Å resolution crystal structure of AF-Est2 reveals Coenzyme A (CoA) bound in the vicinity of the active site. Despite the presence of CoA bound to the AF-Est2 this enzyme has no CoA thioesterase activity. The pantetheine group of CoA partially obstructs the active site alcohol pocket suggesting that this ligand has a role in regulation of the enzyme activity. A comparison with closely related α/β hydrolase fold enzyme structures shows that the AF-Est2 has unique structural features that allow CoA binding. A comparison of the structure of AF-Est2 with the human carboxyl esterase 1, which has CoA thioesterase activity, reveals that CoA is bound to different parts of the core domain in these two enzymes and approaches the active site from opposite directions.

Structural and biochemical characterisation of Archaeoglobus fulgidus esterase reveals a bound CoA molecule in the vicinity of the active site

PubMed Central

Sayer, Christopher; Finnigan, William; Isupov, Michail N.; Levisson, Mark; Kengen, Servé W. M.; van der Oost, John; Harmer, Nicholas J.; Littlechild, Jennifer A.

2016-01-01

A new carboxyl esterase, AF-Est2, from the hyperthermophilic archaeon Archaeoglobus fulgidus has been cloned, over-expressed in Escherichia coli and biochemically and structurally characterized. The enzyme has high activity towards short- to medium-chain p-nitrophenyl carboxylic esters with optimal activity towards the valerate ester. The AF-Est2 has good solvent and pH stability and is very thermostable, showing no loss of activity after incubation for 30 min at 80 °C. The 1.4 Å resolution crystal structure of AF-Est2 reveals Coenzyme A (CoA) bound in the vicinity of the active site. Despite the presence of CoA bound to the AF-Est2 this enzyme has no CoA thioesterase activity. The pantetheine group of CoA partially obstructs the active site alcohol pocket suggesting that this ligand has a role in regulation of the enzyme activity. A comparison with closely related α/β hydrolase fold enzyme structures shows that the AF-Est2 has unique structural features that allow CoA binding. A comparison of the structure of AF-Est2 with the human carboxyl esterase 1, which has CoA thioesterase activity, reveals that CoA is bound to different parts of the core domain in these two enzymes and approaches the active site from opposite directions. PMID:27160974

Wireless Cooperative Networks: Self-Configuration and Optimization

DTIC Science & Technology

2011-09-09

TERMS wireless sensor networks , wireless cooperative networks, resource optimization, ultra-wideband, localization, ranging 16. SECURITY...Communications We consider two prevalent relay protocols for wireless sensor networks : decode-and-forward (DF) and amplify-and-forward (AF). To... sensor networks where each node may have its own sensing data to transmit, since they can maximally conserve energy while helping others as relays

Microbial community and performance of slaughterhouse wastewater treatment filters.

PubMed

Stets, M I; Etto, R M; Galvão, C W; Ayub, R A; Cruz, L M; Steffens, M B R; Barana, A C

2014-06-16

The performance of anaerobic filter bioreactors (AFs) is influenced by the composition of the substrate, support medium, and the microbial species present in the sludge. In this study, the efficiency of a slaughterhouse effluent treatment using three AFs containing different support media was tested, and the microbial diversity was investigated by amplified ribosomal DNA restriction analysis and 16S rRNA gene sequencing. The physicochemical analysis of the AF systems tested suggested their feasibility, with rates of chemical oxygen demand removal of 72±8% in hydraulic retention times of 1 day. Analysis of pH, alkalinity, volatile acidity, total solids, total volatile solids, total Kjeldahl nitrogen, and the microbial community structures indicated high similarity among the three AFs. The composition of prokaryotic communities showed a prevalence of Proteobacteria (27.3%) and Bacteroidetes (18.4%) of the Bacteria domain and Methanomicrobiales (36.4%) and Methanosarcinales (35.3%) of the Archaea domain. Despite the high similarity of the microbial communities among the AFs, the reactor containing pieces of clay brick as a support medium presented the highest richness and diversity of bacterial and archaeal operational taxonomic units.

Investigation of Single-Stage Modified Turbine of Mark 25 Torpedo Power Plant

NASA Technical Reports Server (NTRS)

Hoyt, Jack W.

1947-01-01

Efficiency investigations have been made on a single-stage modification of the turbine of a Mark 25 aerial torpedo to determine the performance of the unit with five different turbine nozzles. The output of the turbine blades was computed by analyzing the windage and mechanical-friction losses of the unit. The turbine was faund to be most efficient with a cast nozzle having sharp-edged inlets to the nine nozzle ports. An analysis af the effectiveness af the first and second stages of the standard Mark 25 torpedo turbine indicates that the first- stage turbine contributes nearly all the brake power produced at blade-jet speed ratios above 0.26.

Operations-Focused Optimized Theater Weather Sensing Strategies Using Preemptive Binary Integer Programming

DTIC Science & Technology

2009-03-01

8217 Clear old problem data Do While Trim(Sheets("Campaign").Range("AF" & CStr (LOOP_COUNTER))) <> "" LOOP_COUNTER = LOOP_COUNTER + 1 Loop Do While...Trim(Sheets("Campaign").Range("A" & CStr (LOOP_COUNTER))) <> "" ’ Loop through all problem instances Sheets("Campaign").Range("R1:AF1").Rows...total number of locations M = Sheets("Campaign").Range("F" & CStr (LOOP_COUNTER)) ’ Record total number of sensor types N

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2014-10-01

Y N 0.519 60 70 5 2 2 1.620 2 0.250 2 Yes - Current Smoker AF Jet fuel , Second-hand smoke Jet fuel , Second-hand smoke S0018 Squamous Cell...Second-hand smoke Second-hand smoke S0028 Squamous Cell Carcinoma Stage IIIB N N No - Quit Smoking 150 AF Jet fuel , Nuclear weapons, Second-hand... Jet fuel , Nuclear weapons, Second-hand S0029 Squamous Cell Carcinoma Stage IIA Y N 0.06 100 40 0 1 3 .571 1 8 .043 1 No - Quit Smoking AR Second

Value of high-sensitivity C-reactive protein assays in predicting atrial fibrillation recurrence: a systematic review and meta-analysis.

PubMed

Yo, Chia-Hung; Lee, Si-Huei; Chang, Shy-Shin; Lee, Matthew Chien-Hung; Lee, Chien-Chang

2014-02-20

We performed a systematic review and meta-analysis of studies on high-sensitivity C-reactive protein (hs-CRP) assays to see whether these tests are predictive of atrial fibrillation (AF) recurrence after cardioversion. Systematic review and meta-analysis. PubMed, EMBASE and Cochrane databases as well as a hand search of the reference lists in the retrieved articles from inception to December 2013. This review selected observational studies in which the measurements of serum CRP were used to predict AF recurrence. An hs-CRP assay was defined as any CRP test capable of measuring serum CRP to below 0.6 mg/dL. We summarised test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models. Meta-regression analysis was performed to explore the source of heterogeneity. We included nine qualifying studies comprising a total of 347 patients with AF recurrence and 335 controls. A CRP level higher than the optimal cut-off point was an independent predictor of AF recurrence after cardioversion (summary adjusted OR: 3.33; 95% CI 2.10 to 5.28). The estimated pooled sensitivity and specificity for hs-CRP was 71.0% (95% CI 63% to 78%) and 72.0% (61% to 81%), respectively. Most studies used a CRP cut-off point of 1.9 mg/L to predict long-term AF recurrence (77% sensitivity, 65% specificity), and 3 mg/L to predict short-term AF recurrence (73% sensitivity, 71% specificity). hs-CRP assays are moderately accurate in predicting AF recurrence after successful cardioversion.

In Vitro and In Vivo Development of Horse Cloned Embryos Generated with iPSCs, Mesenchymal Stromal Cells and Fetal or Adult Fibroblasts as Nuclear Donors.

PubMed

Olivera, Ramiro; Moro, Lucia Natalia; Jordan, Roberto; Luzzani, Carlos; Miriuka, Santiago; Radrizzani, Martin; Donadeu, F Xavier; Vichera, Gabriel

2016-01-01

The demand for equine cloning as a tool to preserve high genetic value is growing worldwide; however, nuclear transfer efficiency is still very low. To address this issue, we first evaluated the effects of time from cell fusion to activation (<1h, n = 1261; 1-2h, n = 1773; 2-3h, n = 1647) on in vitro and in vivo development of equine embryos generated by cloning. Then, we evaluated the effects of using different nuclear donor cell types in two successive experiments: I) induced pluripotent stem cells (iPSCs) vs. adult fibroblasts (AF) fused to ooplasts injected with the pluripotency-inducing genes OCT4, SOX2, MYC and KLF4, vs. AF alone as controls; II) umbilical cord-derived mesenchymal stromal cells (UC-MSCs) vs. fetal fibroblasts derived from an unborn cloned foetus (FF) vs. AF from the original individual. In the first experiment, both blastocyst production and pregnancy rates were higher in the 2-3h group (11.5% and 9.5%, respectively), respect to <1h (5.2% and 2%, respectively) and 1-2h (5.6% and 4.7%, respectively) groups (P<0.05). However, percentages of born foals/pregnancies were similar when intervals of 2-3h (35.2%) or 1-2h (35.7%) were used. In contrast to AF, the iPSCs did not generate any blastocyst-stage embryos. Moreover, injection of oocytes with the pluripotency-inducing genes did not improve blastocyst production nor pregnancy rates respect to AF controls. Finally, higher blastocyst production was obtained using UC-MSC (15.6%) than using FF (8.9%) or AF (9.3%), (P<0.05). Despite pregnancy rates were similar for these 3 groups (17.6%, 18.2% and 22%, respectively), viable foals (two) were obtained only by using FF. In summary, optimum blastocyst production rates can be obtained using a 2-3h interval between cell fusion and activation as well as using UC-MSCs as nuclear donors. Moreover, FF line can improve the efficiency of an inefficient AF line. Overall, 24 healthy foals were obtained from a total of 29 born foals.

Passive auto-focus for digital still cameras and camera phones: Filter-switching and low-light techniques

NASA Astrophysics Data System (ADS)

Gamadia, Mark Noel

In order to gain valuable market share in the growing consumer digital still camera and camera phone market, camera manufacturers have to continually add and improve existing features to their latest product offerings. Auto-focus (AF) is one such feature, whose aim is to enable consumers to quickly take sharply focused pictures with little or no manual intervention in adjusting the camera's focus lens. While AF has been a standard feature in digital still and cell-phone cameras, consumers often complain about their cameras' slow AF performance, which may lead to missed photographic opportunities, rendering valuable moments and events with undesired out-of-focus pictures. This dissertation addresses this critical issue to advance the state-of-the-art in the digital band-pass filter, passive AF method. This method is widely used to realize AF in the camera industry, where a focus actuator is adjusted via a search algorithm to locate the in-focus position by maximizing a sharpness measure extracted from a particular frequency band of the incoming image of the scene. There are no known systematic methods for automatically deriving the parameters such as the digital pass-bands or the search step-size increments used in existing passive AF schemes. Conventional methods require time consuming experimentation and tuning in order to arrive at a set of parameters which balance AF performance in terms of speed and accuracy ultimately causing a delay in product time-to-market. This dissertation presents a new framework for determining an optimal set of passive AF parameters, named Filter- Switching AF, providing an automatic approach to achieve superior AF performance, both in good and low lighting conditions based on the following performance measures (metrics): speed (total number of iterations), accuracy (offset from truth), power consumption (total distance moved), and user experience (in-focus position overrun). Performance results using three different prototype cameras are presented to further illustrate the real-world AF performance gains achieved by the developed approach. The major contribution of this dissertation is that the developed auto focusing approach can be successfully used by camera manufacturers in the development of the AF feature in future generations of digital still cameras and camera phones.

Functional characterization of the copper transcription factor AfMac1 from Aspergillus fumigatus.

PubMed

Park, Yong-Sung; Kim, Tae-Hyoung; Yun, Cheol-Won

2017-07-03

Although copper functions as a cofactor in many physiological processes, copper overload leads to harmful effects in living cells. Thus, copper homeostasis is tightly regulated. However, detailed copper metabolic pathways have not yet been identified in filamentous fungi. In this report, we investigated the copper transcription factor AfMac1 ( A spergillus f umigatus Mac1 homolog) and identified its regulatory mechanism in A. fumigatus AfMac1 has domains homologous to the DNA-binding and copper-binding domains of Mac1 from Saccharomyces cerevisiae , and AfMac1 efficiently complemented Mac1 in S. cerevisiae Expression of Afmac1 resulted in CTR1 up-regulation, and mutation of the DNA-binding domain of Afmac1 failed to activate CTR1 expression in S. cerevisiae The Afmac1 deletion strain of A. fumigatus failed to grow in copper-limited media, and its growth was restored by introducing ctrC We found that AfMac1 specifically bound to the promoter region of ctrC based on EMSA. The AfMac1-binding motif 5'-TGTGCTCA-3' was identified from the promoter region of ctrC , and the addition of mutant ctrC lacking the AfMac1-binding motif failed to up-regulate ctrC in A. fumigatus Furthermore, deletion of Afmac1 significantly reduced strain virulence and activated conidial killing activity by neutrophils and macrophages. Taken together, these results suggest that AfMac1 is a copper transcription factor that regulates cellular copper homeostasis in A. fumigatus . © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Identification of ligand efficient, fragment-like hits from an HTS library: structure-based virtual screening and docking investigations of 2H- and 3H-pyrazolo tautomers for Aurora kinase A selectivity.

PubMed

Sarvagalla, Sailu; Singh, Vivek Kumar; Ke, Yi-Yu; Shiao, Hui-Yi; Lin, Wen-Hsing; Hsieh, Hsing-Pang; Hsu, John T A; Coumar, Mohane Selvaraj

2015-01-01

Furanopyrimidine 1 (IC50 = 273 nM, LE = 0.36, LELP = 10.28) was recently identified by high-throughput screening (HTS) of an in-house library (125,000 compounds) as an Aurora kinase inhibitor. Structure-based hit optimization resulted in lead molecules with in vivo efficacy in a mouse tumour xenograft model, but no oral bioavailability. This is attributed to "molecular obesity", a common problem during hit to lead evolution during which degradation of important molecular properties such as molecular weight (MW) and lipophilicity occurs. This could be effectively tackled by the right choice of hit compounds for optimization. In this regard, ligand efficiency (LE) and ligand efficiency dependent lipophilicity (LELP) indices are more often used to choose fragment-like hits for optimization. To identify hits with appropriate LE, we used a MW cut-off <250, and pyrazole structure to filter HTS library. Next, structure-based virtual screening using software (Libdock and Glide) in the Aurora A crystal structure (PDB ID: 3E5A) was carried out, and the top scoring 18 compounds tested for Aurora A enzyme inhibition. This resulted in the identification of a novel tetrahydro-pyrazolo-isoquinoline hit 7 (IC50 = 852 nM, LE = 0.44, LELP = 8.36) with fragment-like properties suitable for further hit optimization. Moreover, hit 7 was found to be selective for Aurora A (Aurora B IC50 = 35,150 nM) and the possible reasons for selectivity investigated by docking two tautomeric forms (2H- and 3H-pyrazole) of 7 in Auroras A and B (PDB ID: 4AF3) crystal structures. This docking study shows that the major 3H-pyrazole tautomer of 7 binds in Aurora A stronger than in Aurora B.

Identification of ligand efficient, fragment-like hits from an HTS library: structure-based virtual screening and docking investigations of 2 H- and 3 H-pyrazolo tautomers for Aurora kinase A selectivity

NASA Astrophysics Data System (ADS)

Sarvagalla, Sailu; Singh, Vivek Kumar; Ke, Yi-Yu; Shiao, Hui-Yi; Lin, Wen-Hsing; Hsieh, Hsing-Pang; Hsu, John T. A.; Coumar, Mohane Selvaraj

2015-01-01

Furanopyrimidine 1 (IC50 = 273 nM, LE = 0.36, LELP = 10.28) was recently identified by high-throughput screening (HTS) of an in-house library (125,000 compounds) as an Aurora kinase inhibitor. Structure-based hit optimization resulted in lead molecules with in vivo efficacy in a mouse tumour xenograft model, but no oral bioavailability. This is attributed to "molecular obesity", a common problem during hit to lead evolution during which degradation of important molecular properties such as molecular weight (MW) and lipophilicity occurs. This could be effectively tackled by the right choice of hit compounds for optimization. In this regard, ligand efficiency (LE) and ligand efficiency dependent lipophilicity (LELP) indices are more often used to choose fragment-like hits for optimization. To identify hits with appropriate LE, we used a MW cut-off <250, and pyrazole structure to filter HTS library. Next, structure-based virtual screening using software (Libdock and Glide) in the Aurora A crystal structure (PDB ID: 3E5A) was carried out, and the top scoring 18 compounds tested for Aurora A enzyme inhibition. This resulted in the identification of a novel tetrahydro-pyrazolo-isoquinoline hit 7 (IC50 = 852 nM, LE = 0.44, LELP = 8.36) with fragment-like properties suitable for further hit optimization. Moreover, hit 7 was found to be selective for Aurora A (Aurora B IC50 = 35,150 nM) and the possible reasons for selectivity investigated by docking two tautomeric forms (2 H- and 3 H-pyrazole) of 7 in Auroras A and B (PDB ID: 4AF3) crystal structures. This docking study shows that the major 3 H-pyrazole tautomer of 7 binds in Aurora A stronger than in Aurora B.

The left atrial appendage: from embryology to prevention of thromboembolism.

PubMed

Patti, Giuseppe; Pengo, Vittorio; Marcucci, Rossella; Cirillo, Plinio; Renda, Giulia; Santilli, Francesca; Calabrò, Paolo; De Caterina, Alberto Ranieri; Cavallari, Ilaria; Ricottini, Elisabetta; Parato, Vito Maurizio; Zoppellaro, Giacomo; Di Gioia, Giuseppe; Sedati, Pietro; Cicchitti, Vincenzo; Davì, Giovanni; Golia, Enrica; Pariggiano, Ivana; Simeone, Paola; Abbate, Rosanna; Prisco, Domenico; Zimarino, Marco; Sofi, Francesco; Andreotti, Felicita; De Caterina, Raffaele

2017-03-21

The left atrial appendage (LAA) is the main source of thromboembolism in patients with non-valvular atrial fibrillation (AF). As such, the LAA can be the target of specific occluding device therapies. Optimal management of patients with AF includes a comprehensive knowledge of the many aspects related to LAA structure and thrombosis. Here we provide baseline notions on the anatomy and function of the LAA, and then focus on current imaging tools for the identification of anatomical varieties. We also describe pathogenetic mechanisms of LAA thrombosis in AF patients, and examine the available evidence on treatment strategies for LAA thrombosis, including the use of non-vitamin K antagonist oral anticoagulants and interventional approaches. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

PubMed Central

RUSSO, VINCENZO; DI MEO, FEDERICA; PAPA, ANDREA ANTONIO; CIOPPA, NADIA DELLA; PROIETTI, RICCARDO; RUSSO, MARIA GIOVANNA; CALABRÒ, RAFFAELE; POLITANO, LUISA

2014-01-01

P-wave dispersion is a non invasive indicator of intra-atrial conduction heterogeneity producing substrate for reentry, which is a pathophysiological mechanism of atrial fibrillation. The relationship between P-wave dispersion (PD) and atrial fibrillation (AF) in Myotonic dystrophy type 1 (DM1) patients is still unclear. Atrial Preference Pacing (APP) is an efficient algorithm to prevent paroxysmal AF in patients implanted with dual-chamber pacemaker. Aim of our study was to evaluate the possible correlation between atrial preference pacing algorithm, P-wave dispersion and AF burden in DM1 patients with normal cardiac function underwent permanent dual-chamber pacemaker implantation. We enrolled 50 patients with DM1 (age 50.3 ± 7.3; 11 F) underwent dual-chamber pacemaker implantation for various degree of atrioventricula block. The study population was randomized following 1 months stabilization period to APP algorithm features programmed OFF or ON. Patients were assessed every 3 months for the first year, and every 6 months thereafter up to 3 years. At each follow-up visit, we counted: the number of premature atrial beats, the number and the mean duration of AF episodes, AF burden and the percentage of atrial and ventricular pacing. APP ON Group showed lower number of AF episodes (117 ± 25 vs. 143 ± 37; p = 0.03) and AF burden (3059 ± 275 vs. 9010 ± 630 min; p < 0.04) than APP OFF Group. Atrial premature beats count (44903 ± 30689 vs. 13720 ± 7717 beats; p = 0.005) and Pwave dispersion values (42,1 ± 11 ms vs. 29,1 ± 4,2 ms, p = 0,003) were decreased in APP ON Group. We found a significant positive correlation between PD and AF burden (R = 0,8, p = 0.007). Atrial preference pacing algorithm, decreasing the number of atrial premature beats and the P-wave dispersion, reduces the onset and perpetuator factors of AF episodes and decreases the AF burden in DM1 patients underwent dual chamber pacemaker implantation for various degree of atrioventricular blocks and documented atrial fibrillation. PMID:25873781

Characterization of Gd loaded chitosan-TPP nanohydrogels by a multi-technique approach combining dynamic light scattering (DLS), asymetrical flow-field-flow-fractionation (AF4) and atomic force microscopy (AFM) and design of positive contrast agents for molecular resonance imaging (MRI)

NASA Astrophysics Data System (ADS)

Rigaux, G.; Gheran, C. V.; Callewaert, M.; Cadiou, C.; Voicu, S. N.; Dinischiotu, A.; Andry, M. C.; Vander Elst, L.; Laurent, S.; Muller, R. N.; Berquand, A.; Molinari, M.; Huclier-Markai, S.; Chuburu, F.

2017-02-01

Chitosan CS—tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA ⊂ CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter ϕ < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with ϕ < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point was clarified by atomic force microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA ⊂ CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial

PubMed Central

Deeks, Jonathan J; Griffith, Michael; Lip, Gregory YH; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

2017-01-01

Background and objective Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article, we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. Design and intervention The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Participants Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. Outcome measures The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. Ethics and dissemination East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications. Trial registration Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results. PMID:28729311

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial.

PubMed

Kotecha, Dipak; Calvert, Melanie; Deeks, Jonathan J; Griffith, Michael; Kirchhof, Paulus; Lip, Gregory Yh; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

2017-07-20

Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article , we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications. Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Inhibition of Carrageenan-Induced Acute Inflammation in Mice by Oral Administration of Anthocyanin Mixture from Wild Mulberry and Cyanidin-3-Glucoside

PubMed Central

Hassimotto, Neuza Mariko Aymoto; Moreira, Vanessa; do Nascimento, Neide Galvão; Souto, Pollyana Cristina Maggio de Castro; Teixeira, Catarina; Lajolo, Franco Maria

2013-01-01

Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements. PMID:23484081

Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidin-3-glucoside.

PubMed

Hassimotto, Neuza Mariko Aymoto; Moreira, Vanessa; do Nascimento, Neide Galvão; Souto, Pollyana Cristina Maggio de Castro; Teixeira, Catarina; Lajolo, Franco Maria

2013-01-01

Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements.

Low-cost humic acid-bonded silica as an effective solid-phase extraction sorbent for convenient determination of aflatoxins in edible oils.

PubMed

Zhou, Neng-Zhi; Liu, Ping; Su, Xiao-Chuan; Liao, Yan-Hua; Lei, Ning-Sheng; Liang, Yong-Hong; Zhou, Shao-Huan; Lin, Wen-Si; Chen, Jie; Feng, Yu-Qi; Tang, Yang

2017-06-01

Aflatoxins (AFs) are highly toxic, mutagenic, carcinogenic, and teratogenic secondary metabolites produced by the toxigenic fungi Aspergillus flavus and Aspergillus parasiticus. AFs tend to contaminate a wide range of foods which is a serious and recurring food safety problem worldwide. Currently, immunoaffinity chromatography (IAC) has become the most conventional sample clean-up method for determining AFs in foodstuffs. However, IAC method is limited in the large-scale food analysis because it requires the use of expensive disposable cartridges and the IA procedure is time-consuming. Herein, to achieve the cost-effective determination of AFs in edible oils, we developed a promising solid-phase extraction (SPE) method based on commercially available humic acid-bonded silica (HAS) sorbent, followed by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) analysis. In HAS-SPE, AFs can be captured by the HAS sorbent with both hydrophobic and hydrophilic interactions, whereas the oil matrix was captured only with the hydrophobic interactions. The oil matrix can be sufficiently washed off with isopropanol, while the AFs were still retained on the SPE packing, thus achieving selective extraction of AFs and clean-up of oil matrices. Under the optimal conditions of HAS-SPE, satisfactory recoveries ranging from 82% to 106% for four AFs (B 1 , B 2 , G 1 , and G 2 ) were achieved in various oil matrices, containing blended oil, tea oil, rapeseed oil, peanut oil, sunflower seed oil, corn oil, blended olive oil, rice oil, soybean oil, and sesame oil. Only minor matrix effects ranging from 99% to 105% for four AFs were observed. Moreover, the LODs of AFs between 0.012 and 0.035 μg/kg completely meet the regulatory levels fixed by the EU, China or other countries. The methodology was further validated for assaying the naturally contaminated peanut oils, and consistent results between the HAS-SPE and the referenced IAC were obtained. In addition, HAS-SPE can directly treat diluted oil sample without liquid-liquid extraction and is automatable, thus making it simple and convenient for the large-scale determination of AFs in edible oils. Using this method, we successfully detected four AFs in the naturally contaminated peanut oils, which is, to the best of our knowledge, the first report about the determination of AFs in edible oils using HA-based SPE. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence, Management, and Long-Term (6-Year) Outcomes of Atrial Fibrillation Among Patients Receiving Drug-Eluting Coronary Stents.

PubMed

Choi, Hyo-In; Ahn, Jung-Min; Kang, Se Hun; Lee, Pil Hyung; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Lee, Cheol Whan; Park, Seong-Wook; Park, Duk-Woo; Park, Seung-Jung

2017-06-12

This study sought to investigate the incidence, management, and clinical relevance of atrial fibrillation (AF) during and after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and evaluate outcomes of different antithrombotic strategies. Uncertainty exists regarding the optimal antithrombotic strategy in patients with AF who are undergoing PCI with DES. Using a consecutive series of 10,027 patients who underwent DES implantation between 2003 and 2011, we evaluated the overall prevalence and clinical impact of AF. In addition, we compared the efficacy and safety of dual antiplatelet therapy (DAPT) (aspirin plus clopidogrel) and triple therapy (DAPT plus warfarin) among patients with AF. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke. Overall, 711 (7.1%) patients had a diagnosis of AF at the index PCI. Patients with AF were older, had more comorbid conditions, and more often had a history of strokes; most patients with AF (88.4%) received DAPT rather than triple therapy (10.5%) at discharge. The rate of primary outcome after PCI during the 6-year follow-up period was significantly higher in patients with AF than in those without AF (22.1% vs. 8.0%; p < 0.001). This trend was consistent for major bleeding (4.5% vs. 1.5%; p < 0.001). After multivariable adjustment, the presence of AF was significantly associated with a higher risk of primary outcome (hazard ratio [HR]: 2.33; 95% confidence interval [CI]: 1.95 to 2.79; p < 0.001) and major bleeding (HR: 2.01; 95% CI: 1.32 to 3.06; p = 0.001). Among patients with AF, adjusted risk for the primary outcome was similar between the DAPT group and the triple therapy group (HR: 1.01; 95% CI: 0.60 to 1.69; p = 0.98), but triple therapy was associated with a significantly higher risk of hemorrhagic stroke (HR: 7.73; 95% CI: 2.14 to 27.91; p = 0.002) and major bleeding (HR: 4.48; 95% CI: 1.81 to 11.08; p = 0.001). Among patients receiving DES implantation, AF was not rare and was associated with increased ischemic and bleeding risk. In patients with AF, triple therapy was not associated with decreased ischemic events but was associated with increased bleeding risk compared to DAPT. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Value of high-sensitivity C-reactive protein assays in predicting atrial fibrillation recurrence: a systematic review and meta-analysis

PubMed Central

Yo, Chia-Hung; Lee, Si-Huei; Chang, Shy-Shin; Lee, Matthew Chien-Hung; Lee, Chien-Chang

2014-01-01

Objectives We performed a systematic review and meta-analysis of studies on high-sensitivity C-reactive protein (hs-CRP) assays to see whether these tests are predictive of atrial fibrillation (AF) recurrence after cardioversion. Design Systematic review and meta-analysis. Data sources PubMed, EMBASE and Cochrane databases as well as a hand search of the reference lists in the retrieved articles from inception to December 2013. Study eligibility criteria This review selected observational studies in which the measurements of serum CRP were used to predict AF recurrence. An hs-CRP assay was defined as any CRP test capable of measuring serum CRP to below 0.6 mg/dL. Primary and secondary outcome measures We summarised test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models. Meta-regression analysis was performed to explore the source of heterogeneity. Results We included nine qualifying studies comprising a total of 347 patients with AF recurrence and 335 controls. A CRP level higher than the optimal cut-off point was an independent predictor of AF recurrence after cardioversion (summary adjusted OR: 3.33; 95% CI 2.10 to 5.28). The estimated pooled sensitivity and specificity for hs-CRP was 71.0% (95% CI 63% to 78%) and 72.0% (61% to 81%), respectively. Most studies used a CRP cut-off point of 1.9 mg/L to predict long-term AF recurrence (77% sensitivity, 65% specificity), and 3 mg/L to predict short-term AF recurrence (73% sensitivity, 71% specificity). Conclusions hs-CRP assays are moderately accurate in predicting AF recurrence after successful cardioversion. PMID:24556243

Non-selective His bundle pacing with a biphasic waveform: enhancing septal resynchronization.

PubMed

Ortega, Daniel F; Barja, Luis D; Logarzo, Emilio; Mangani, Nicolas; Paolucci, Analia; Bonomini, Maria P

2018-05-01

His bundle pacing has shown to prevent detrimental effects from right ventricular apical pacing (RVA) and proved to resynchronize many conduction disturbances cases. However, the extent of His bundle pacing resynchronization is limited. An optimized stimulation waveform could expand this limit when implemented in His bundle pacing sets. In this work, we temporarily implemented RVA and Non-selective His bundle pacing with a biphasic anodal-first waveform (AF-nHB) and compared their effects against sinus rhythm (SR). Fifteen patients referred for electrophysiologic study with conduction disturbances, cardiomyopathy and ejection fraction below 35% were enrolled for the study. The following acute parameters were measured: QRS duration, left ventricular activation (RLVT), time of isovolumic contraction (IVCT), ejection fraction (EF), and dP/dtmax. QRS duration and RLVT decreased markedly under AF-nHB (SR: 169 ± 34 ms vs. nHB: 116 ± 31 ms, P < 0.0005) while RVA significantly increased QRS duration (SR: 169 ms vs. RVA: 198 ms, P < 0.05) and did not change RLVT (P = NS). Consistently, IVCT moderately decreased under AF-nHB (SR: 238 ms vs. RVA: 184 ms, P < 0.05 vs. SR) and dP/dtmax showed a 93.35 [mmHg] average increase under AF-nHB against SR. Also, T-wave inversions were observed during AF-nHB immediately after SR and RVA pacing suggesting the occurrence of cardiac memory. AF-nHB corrected bundle branch blocks in patients with severe conduction disturbances, even in those with dilated cardiomiopathy, outstanding from RVA. Also, the occurrence of cardiac memory during AF-nHB turned up as an observational finding of this study.

Atrial fibrillation in cardiac resynchronization therapy with a defibrillator: a risk factor for mortality, appropriate and inappropriate shocks.

PubMed

van Boven, Nick; Theuns, Dominic; Bogaard, Kjell; Ruiter, Jaap; Kimman, Geert; Berman, Lily; VAN DER Ploeg, Tjeerd; Kardys, Isabella; Umans, Victor

2013-10-01

Knowledge about predictive factors for mortality and (in)appropriate shocks in cardiac resynchronization therapy with a defibrillator (CRT-D) should be available and updated to predict clinical outcome. We retrospectively analyzed 543 consecutive patients assigned to CRT-D in 2 tertiary medical centers. The aim of this study was to assess risk factors for all-cause mortality, appropriate and inappropriate shocks. Mean follow-up time was 3.2 (±1.8) years. A total of 110 (20%) patients died, 71 (13%) received ≥1 appropriate shocks, and 33 (6.1%) received ≥1 inappropriate shocks. No patients received a His bundle ablation and biventricular pacing percentage was not analyzed. Multivariable Cox regression analysis showed that a history of atrial fibrillation (AF) (HR 1.74 CI 1.06-2.86), higher creatinine (HR 1.12; CI 1.08-1.16), and a poorer left ventricular ejection fraction (LVEF) (HR 0.97; CI 0.94-1.01) independently predict all-cause mortality. In the entire cohort, history of AF and secondary prevention were independent predictors of appropriate shocks and variables associated with inappropriate shocks were history of AF and QRS ≥150 milliseconds. In primary prevention patients, history of AF also predicted appropriate shocks as did ischemic cardiomyopathy and poorer LVEF. History of AF, QRS ≥150 milliseconds, and lower creatinine were associated with inappropriate shocks in this subgroup. Appropriate shocks increased mortality risk, but inappropriate shocks did not. In symptomatic CHF patients treated with CRT-D, history of AF is an independent risk factor not only for mortality, but also for appropriate and inappropriate shocks. Further efforts in AF management may optimize the care in CRT-D patients. © 2013 Wiley Periodicals, Inc.

Impact of preprocedural atrial fibrillation on immediate and long-term outcomes after successful percutaneous mitral valvuloplasty of significant mitral stenosis.

PubMed

Miura, Shiro; Arita, Takeshi; Domei, Takenori; Yamaji, Kyohei; Soga, Yoshimitsu; Hyodo, Makoto; Shirai, Shinichi; Ando, Kenji

2018-01-01

Optimal time to perform percutaneous mitral valvuloplasty (PMV) for patients with significant mitral stenosis (MS) and atrial fibrillation (AF) remains controversial. We sought to identify prognostic factors and evaluate long-term clinical outcomes after PMV of 77 consecutive patients with MS with a mitral valve area (MVA) <1.5 cm 2 . According to baseline heart rhythm, these patients were divided into sinus rhythm (SR; n = 24) and AF (n = 53) groups. The study endpoint was defined as a composite of all-cause mortality, admission for heart failure, mitral valve surgery, repeated PMV, and major cerebral vascular accident during follow-up. After successful PMV, there was no significant difference between the two groups in post-MVA and post-mitral mean pressure gradient. However, the New York Heart Association Functional Classification post-procedure was worse in the AF group (p < 0.01). In the AF group, event-free survival during follow-up was significantly lower compared with that of the SR group (p = 0.016). Independent predictors of clinical events were AF [hazard ratio (HR), 2.73; 95 % confidence interval (CI), 1.04-9.36; p = 0.03] and pulmonary artery systolic pressure (HR 2.57; 95 % CI 1.18-5.47; p = 0.017). Patients with AF at baseline were significantly associated with worse symptoms and higher event rates after successful PMV compared with those with SR. The clinical benefit of PMV may be considered for patients with MVA <1.5 cm 2 before the onset of AF.

Three-dimensional development of tensile pre-strained annulus fibrosus cells for tissue regeneration: An in-vitro study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuah, Yon Jin; Lee, Wu Chean; Wong, Hee Kit

Prior research has investigated the immediate response after application of tensile strain on annulus fibrosus (AF) cells for the past decade. Although mechanical strain can produce either catabolic or anabolic consequences to the cell monolayer, little is known on how to translate these findings into further tissue engineering applications. Till to date, the application and effect of tensile pre-strained cells to construct a three-dimensional (3D) AF tissue remains unknown. This study aims to investigate the effect of tensile pre-strained exposure of 1 to 24 h on the development of AF pellet culture for 3 weeks. Equibiaxial cyclic tensile strain wasmore » applied on AF monolayer cells over a period of 24 h, which was subsequently developed into a cell pellet. Investigation on cellular proliferation, phenotypic gene expression, and histological changes revealed that tensile pre-strain for 24 h had significant and lasting effect on the AF tissue development, with enhanced cell proliferation, and up-regulation of collagen type I, II, and aggrecan expression. Our results demonstrated the regenerative ability of AF cell pellets subjected to 24 h tensile pre-straining. Knowledge on the effects of tensile pre-strain exposure is necessary to optimize AF development for tissue reconstruction. Moreover, the tensile pre-strained cells may further be utilized in either cell therapy to treat mild disc degeneration disease, or the development of a disc construct for total disc replacement. - Highlights: • Establishment of tensile pre-strained cell line population for annulus development. • Tensile strain limits collagen gene expression declination in monolayer culture. • Tensile pre-strained cells up-regulate their matrix protein in 3D pellet culture.« less

Sensitivity of reentrant driver localization to electrophysiological parameter variability in image-based computational models of persistent atrial fibrillation sustained by a fibrotic substrate

NASA Astrophysics Data System (ADS)

Deng, Dongdong; Murphy, Michael J.; Hakim, Joe B.; Franceschi, William H.; Zahid, Sohail; Pashakhanloo, Farhad; Trayanova, Natalia A.; Boyle, Patrick M.

2017-09-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, causing morbidity and mortality in millions worldwide. The atria of patients with persistent AF (PsAF) are characterized by the presence of extensive and distributed atrial fibrosis, which facilitates the formation of persistent reentrant drivers (RDs, i.e., spiral waves), which promote fibrillatory activity. Targeted catheter ablation of RD-harboring tissues has shown promise as a clinical treatment for PsAF, but the outcomes remain sub-par. Personalized computational modeling has been proposed as a means of non-invasively predicting optimal ablation targets in individual PsAF patients, but it remains unclear how RD localization dynamics are influenced by inter-patient variability in the spatial distribution of atrial fibrosis, action potential duration (APD), and conduction velocity (CV). Here, we conduct simulations in computational models of fibrotic atria derived from the clinical imaging of PsAF patients to characterize the sensitivity of RD locations to these three factors. We show that RDs consistently anchor to boundaries between fibrotic and non-fibrotic tissues, as delineated by late gadolinium-enhanced magnetic resonance imaging, but those changes in APD/CV can enhance or attenuate the likelihood that an RD will anchor to a specific site. These findings show that the level of uncertainty present in patient-specific atrial models reconstructed without any invasive measurements (i.e., incorporating each individual's unique distribution of fibrotic tissue from medical imaging alongside an average representation of AF-remodeled electrophysiology) is sufficiently high that a personalized ablation strategy based on targeting simulation-predicted RD trajectories alone may not produce the desired result.

Speciation of antimony in airborne particulate matter using ultrasound probe fast extraction and analysis by HPLC-HG-AFS.

PubMed

Bellido-Martín, A; Gómez-Ariza, J L; Smichowsky, P; Sánchez-Rodas, D

2009-09-07

A fast extraction procedure has been developed for Sb(III) and Sb(V) oxoanions speciation in airborne particulate matter samples. Different extraction media (diammonium tartrate, hidroxilammonium clorhidrate, citric acid+ascorbic acid, phosphoric acid and citrate solutions) were tried, with assistance of an ultrasonic probe. The operation power and time of extraction were also optimized. The higher extraction recoveries were obtained with a 100 mmol L(-1) hidroxilammonium clorhidrate aqueous solution assisted by the ultrasound probe operated at 50 W during 3 min. The extracts were analyzed by HPLC-HG-AFS. The chromatographic separation of Sb(III) and Sb(V) was also optimized using diammonium tartrate and phthalic acid as mobile phases. The separation of both Sb species was performed in less than 3 min under isocratic conditions, using a 200 mmol L(-1) diammonium tartrate solution. The proposed extraction procedure and the HPLC-HG-AFS instrumental coupling have been successfully applied to airborne particulate matter samples, with high Sb content, collected in heavy traffic streets from Buenos Aires (Argentina). The results showed the presence of both Sb species at similar concentrations in the ng m(-3) level. The extraction yield was higher than 90% for all the analyzed samples.

Temperature-controlled airflow ventilation in operating rooms compared with laminar airflow and turbulent mixed airflow.

PubMed

Alsved, M; Civilis, A; Ekolind, P; Tammelin, A; Andersson, A Erichsen; Jakobsson, J; Svensson, T; Ramstorp, M; Sadrizadeh, S; Larsson, P-A; Bohgard, M; Šantl-Temkiv, T; Löndahl, J

2018-02-01

To evaluate three types of ventilation systems for operating rooms with respect to air cleanliness [in colony-forming units (cfu/m 3 )], energy consumption and comfort of working environment (noise and draught) as reported by surgical team members. Two commonly used ventilation systems, vertical laminar airflow (LAF) and turbulent mixed airflow (TMA), were compared with a newly developed ventilation technique, temperature-controlled airflow (T c AF). The cfu concentrations were measured at three locations in an operating room during 45 orthopaedic procedures: close to the wound (<40cm), at the instrument table and peripherally in the room. The operating team evaluated the comfort of the working environment by answering a questionnaire. LAF and T c AF, but not TMA, resulted in less than 10cfu/m 3 at all measurement locations in the room during surgery. Median values of cfu/m 3 close to the wound (250 samples) were 0 for LAF, 1 for T c AF and 10 for TMA. Peripherally in the room, the cfu concentrations were lowest for T c AF. The cfu concentrations did not scale proportionally with airflow rates. Compared with LAF, the power consumption of T c AF was 28% lower and there was significantly less disturbance from noise and draught. T c AF and LAF remove bacteria more efficiently from the air than TMA, especially close to the wound and at the instrument table. Like LAF, the new T c AF ventilation system maintained very low levels of cfu in the air, but T c AF used substantially less energy and provided a more comfortable working environment than LAF. This enables energy savings with preserved air quality. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multifunctional Composites with Applications to Energy Performance and Efficiency

DTIC Science & Technology

2011-08-01

surface for comparing the effects of processing. Parylene/ Teflon AF adhesion was measured using a modified tape test. Samples were razor cut (3-6...lines, 2 mm spacing ) at 0 and 90 degrees to the tape -pull direction. SEMicro CHT tape (synthetic rubber adhesive, 12 to 25 mm wide x 75 mm long) was...surface, a thin layer of Teflon AF (~200 nm) is spin- coated for hydrophobicity. Small drops of ionic liquids in contact with a conductive probe are

The Translation of Knowledge into Practice in the Management of Atrial Fibrillation in Singapore.

PubMed

Woo, Fong Yeong Brigitte; Lim, Toon Wei; Tam, Wai San Wilson

2018-03-12

Atrial fibrillation (AF) is a clinically significant cardiac arrhythmia known to increase the risk of stroke by at least four times. Stroke-risk assessment and thromboprophylaxis are vital components in AF management. Guidelines are available to standardise AF management, but physicians' adherence to the recommended guidelines has been low. The aims were to: 1. Examine and compare the level of knowledge and current practice in AF management between cardiologists and non-cardiologist physicians in Singapore; 2. Identify physicians' perceived barriers to prescribing oral anticoagulants (OACs) when indicated; 3. Identify strategies to optimise AF management. From June 2017 to August 2017, a cross-sectional online survey involving physicians was conducted in Singapore. The survey instrument was adapted from a previously developed instrument, and validated locally by five cardiologists. It explored the physicians' stroke-risk assessment practices, estimation of stroke risk and benefits of anticoagulation, likelihood of prescribing anticoagulation when indicated, perceived barriers to anticoagulation, and strategies to optimise AF management. Sixty-three physicians completed the survey (14 cardiologists and 49 non-cardiologist physicians). No significant difference was found between cardiologists and non-cardiologist physicians in their assessment and estimation of stroke risk for stable AF patients. However, when presented with an AF patient with stroke risk, cardiologists were more likely than non-cardiologist physicians to prescribe novel OACs (93% vs. 51%; χ 2 =7.933, p=0.004). Compared to cardiologists, the majority of the non-cardiologist physicians thought the risk of falls were usually or always barriers to prescribing OACs (29% vs 69%; χ 2 =7.579, p=0.006). Among the suggested strategies to support them in AF management, physicians have overwhelmingly rated two as "quite useful" and "very useful": the establishment of clinics for monitoring anticoagulated patients (100%); and involvement of pharmacists in managing patients on warfarin (98.4%). Physicians possess good knowledge about stroke-risk assessment in AF patients yet it is not translated into effective measures for stroke prevention. Physicians, especially non-cardiologist ones, were not anticoagulating AF patients when indicated. Although novel OACs are safer alternatives to warfarin, non-cardiologist physicians were less inclined to use them for stroke prevention. All physicians opined that establishing anticoagulation clinics and collaborating with pharmacists were useful strategies to optimise AF management. Existing barriers to anticoagulation impeded the translation of knowledge into practice in the management of AF patients in Singapore, for which optimal strategies to optimise AF management are ascertained. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Effect of pulsed electric field treatment during cold maceration and alcoholic fermentation on major red wine qualitative and quantitative parameters.

PubMed

El Darra, Nada; Rajha, Hiba N; Ducasse, Marie-Agnès; Turk, Mohammad F; Grimi, Nabil; Maroun, Richard G; Louka, Nicolas; Vorobiev, Eugène

2016-12-15

This work studies the effect of pulsed electric field (PEF) treatment at moderate and high field strengths (E=0.8kV/cm & 5kV/cm) prior and during alcoholic fermentation (AF) of red grapes on improving different parameters of pre-treated extracts: pH, °Brix, colour intensity (CI), total polyphenols content (TPI) of Cabernet Sauvignon red wine. Similar trends were observed for treating grapes using moderate and high electric field strength on the enhancement of CI and TPI of the wine after AF. The application of PEF using moderate strengths at different times during cold maceration (CM) (0, 2 and 4days) was more efficient for treatment during CM. The treatment during AF showed lower extraction rate compared to treating during CM and prior to AF. Our results clearly show that the best time for applying the PEF-treatment through the red fermentation is during the CM step. Copyright © 2016. Published by Elsevier Ltd.

Structural and magnetic phase transitions near optimal superconductivity in BaFe 2(As 1-xP x) 2

DOE PAGES

Hu, Ding; Lu, Xingye; Zhang, Wenliang; ...

2015-04-17

In this study, we use nuclear magnetic resonance (NMR), high-resolution x-ray and neutron scattering to study structural and magnetic phase transitions in phosphorus-doped BaFe 2(As 1-xP x) 2. Thus, previous transport, NMR, specific heat, and magnetic penetration depth measurements have provided compelling evidence for the presence of a quantum critical point (QCP) near optimal superconductivity at x = 0.3. However, we show that the tetragonal-to-orthorhombic structural (T s) and paramagnetic to antiferromagnetic (AF, T N) transitions in BaFe 2(As 1-xP x) 2 are always coupled and approach to T N ≈ T s ≥ T c (≈ 29 K) formore » x = 0.29 before vanishing abruptly for x ≥ 0.3. These results suggest that AF order in BaFe 2(As 1-xP x) 2 disappears in a weakly first order fashion near optimal superconductivity, much like the electron-doped iron pnictides with an avoided QCP.« less

Online version of the food allergy quality of life questionnaire-adult form: validity, feasibility and cross-cultural comparison.

PubMed

Goossens, N J; Flokstra-de Blok, B M J; Vlieg-Boerstra, B J; Duiverman, E J; Weiss, C C; Furlong, T J; Dubois, A E J

2011-04-01

Food-allergic reactions occur in 3-4% of the adult population in Western countries. It has been shown that food allergy may impair health-related quality of life (HRQL). Food allergy quality of life questionnaires (FAQLQs) have been developed and validated, including an adult form (FAQLQ-AF). These questionnaires may be particularly useful for cross-cultural comparisons. The aims of this study were to translate the FAQLQ-AF from Dutch into English and validate an online version in the United States. Additionally, HRQL of American and Dutch food-allergic adults was compared. The Dutch FAQLQ-AF was translated into English as set out by the World Health Organization and converted to an electronic online format. Participants (food allergic American adults) were recruited through the 'Food Allergy and Anaphylaxis Network' website and completed the questionnaire online. Construct validity, internal consistency, discriminative ability and feasibility were analysed. A cross-cultural comparison was made using the Dutch FAQLQ-AF scores. Data from 180 American participants were analysed. The online FAQLQ-AF had a good construct validity (correlation with FAIM: ρ=0.72; P<0.001), internal consistency (Cronbach's α=0.95) and was discriminative for 'anaphylaxis' vs. 'no anaphylaxis' and 'number of food allergies'. The most striking finding was a significantly greater impairment in HRQL in the American participants, as compared with their Dutch counterparts (the total FAQLQ-AF scores were 4.3 vs. 3.5, respectively; P<0.001, where 1 signifies no impairment and 7 signifies extreme impairment in HRQL). The online American FAQLQ-AF is a valid instrument to measure HRQL in food-allergic patients in the United States. Additionally, HRQL of American food-allergic adults may be more impaired than Dutch food-allergic adults. The FAQLQ-AF can now be used to determine the HRQL in American food-allergic adults and can assist clinicians in optimizing management strategies for food-allergic patients. © 2011 Blackwell Publishing Ltd.

Review of economics and cost-effectiveness analyses of anticoagulant therapy for stroke prevention in atrial fibrillation in the US.

PubMed

von Schéele, Birgitta; Fernandez, Maria; Hogue, Susan Lynn; Kwong, Winghan Jacqueline

2013-05-01

To summarize the available evidence on the issues in health economics related to oral anticoagulation for stroke prevention in atrial fibrillation (AF) in the US. A literature review was performed using PubMed, EMBASE, Cochrane Library, and International Pharmaceutical Abstracts, as well as the websites of professional organizations. The search was conducted according to a prespecified protocol, limiting articles to those published in English from 2001 to October 2012 and focused on the economics associated with AF and AF-related stroke in the US. Data from 27 studies were extracted and included in the review. Strokes in patients with AF are more debilitating and have higher recurrence rates and mortality compared with strokes unrelated to AF. However, data describing the long-term cost of AF-related stroke and stroke subtypes remain limited. The costs of major gastrointestinal (GI) bleeding and intracranial bleeding related to warfarin are significant, whereas the costs of the more frequent minor GI bleeding are relatively low. Overall, the cost-effectiveness of warfarin versus aspirin or no treatment in patients with at least 1 risk factor for stroke is well established. Economic evaluations based on results from randomized controlled clinical trials generally found that new anticoagulants were a cost-effective alternative to warfarin for stroke prevention in AF. However, these cost-effectiveness results are highly sensitive to how well optimal international normalized ratio control is maintained (within target of 2.0-3.0) for warfarin and the time horizon used for analysis. Time in therapeutic range for warfarin in routine clinical practice was lower than in clinical trials, as shown by previous studies. This review identified several areas of uncertainty regarding the economic benefit of anticoagulants. The generalizability of cost-effectiveness results of anticoagulant therapy in AF based on clinical trial data must be confirmed by comparative effectiveness research conducted in the real-world setting.

Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: Rationale and design of the ENTRUST-AF PCI trial.

PubMed

Vranckx, Pascal; Lewalter, Thorsten; Valgimigli, Marco; Tijssen, Jan G; Reimitz, Paul-Egbert; Eckardt, Lars; Lanz, Hans-Joachim; Zierhut, Wolfgang; Smolnik, Rüdiger; Goette, Andreas

2018-02-01

The optimal antithrombotic treatment after percutaneous coronary intervention (PCI) with stenting in patients with atrial fibrillation (AF) is unknown. In the ENGAGE AF-TIMI 48 trial, edoxaban was noninferior to a vitamin K antagonist (VKA) with respect to the prevention of stroke or systemic embolism and was associated with significantly lower rates of bleeding and cardiovascular death in patients with nonvalvular AF. The effects of edoxaban in combination with single- or dual-antiplatelet therapy in the setting of PCI are unexplored. The ENTRUST-AF PCI trial is a multinational, multicenter, randomized, open-label phase 3b trial with blinded end point evaluation involving 1,500 patients on oral anticoagulation for AF. Patients are randomized between 4 hours and 5 days after successful PCI to either an edoxaban-based strategy (experimental arm; 60 mg [or 30 mg according to dose reduction criteria] once daily plus a P2Y 12 antagonist [default clopidogrel, 75 mg once daily] for 12 months) or a VKA-based strategy (control arm; VKA plus a P2Y 12 antagonist [as above] plus acetylsalicylic acid [100 mg once daily] for 30 days to 12 months). The primary safety end point is the incidence of International Society on Thrombosis and Haemostasis-defined major or clinically relevant nonmajor bleeding. The main efficacy end point is the composite of cardiovascular death, stroke, systemic embolic events, spontaneous myocardial infarction, and definite stent thrombosis. The ENTRUST-AF PCI trial tests the hypothesis that an edoxaban-based antithrombotic strategy reduces the risk of bleeding complications after PCI compared with VKA plus conventional dual-antiplatelet therapy in patients with AF in need of oral anticoagulation. The relative risk of ischemic events between groups will be compared. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Optimization of medium composition and cultural conditions for production of antifungal substances by Streptomyces platensis 3-10 and evaluation of its efficacy in suppression of clubroot disease of oilseed rape

USDA-ARS?s Scientific Manuscript database

This study was conducted to optimize the medium composition and cultural conditions for improving production of antifungal substances (AFS) by Streptomyces 3-10 and for enhancing its efficacy in suppression of clubroot disease of oilseed rape caused by Plasmodiophora brassicae. Results showed that t...

[Atomic/ionic fluorescence in microwave plasma torch discharge with excitation of high current and microsecond pulsed hollow cathode lamp: Ca atomic/ionic fluorescence spectrometry].

PubMed

Gong, Zhen-bin; Liang, Feng; Yang, Peng-yuan; Jin, Qin-han; Huang, Ben-li

2002-02-01

A system of atomic and ionic fluorescence spectrometry in microwave plasma torch (MPT) discharge excited by high current microsecond pulsed hollow cathode lamp (HCMP HCL) has been developed. The operation conditions for Ca atomic and ionic fluorescence spectrometry have been optimized. Compared with atomic fluorescence spectrometry (AFS) in argon microwave induced plasma (MIP) and MPT with the excitation of direct current and conventional pulsed HCL, the system with HCMP HCL excitation can improve AFS and ionic fluorescence spectrometry (IFS) detection limits in MPT atomizer and ionizer. Detection limits (3 sigma) with HCMP HCL-MPT-AFS/IFS are 10.1 ng.mL-1 for Ca I 422.7 nm, 14.6 ng.mL-1 for Ca II 393.4 nm, and 37.4 ng.mL-1 for Ca II 396.8 nm, respectively.

Right atrium positioning for exposure of right pulmonary veins during off-pump atrial fibrillation ablation.

PubMed

Suwalski, Grzegorz; Emery, Robert; Mróz, Jakub; Kaczejko, Kamil; Gryszko, Leszek; Cwetsch, Andrzej; Skrobowski, Andrzej

2017-06-01

Concomitant surgical ablation of atrial fibrillation (AF) is recommended for patients undergoing off-pump coronary revascularization in the presence of this arrhythmia. Achievement of optimal visualization of pulmonary veins while maintaining stable haemodynamic conditions is crucial for proper completion of the ablation procedure. This study evaluates the safety and feasibility of right atrial positioning using a suction-based cardiac positioner as opposed to compressive manoeuvres for exposure during off-pump surgical ablation for AF. Thirty-four consecutive patients underwent pulmonary vein isolation, ganglionated plexi ablation and left atrial appendage occlusion during off-pump coronary artery bypass grafting. Right atrial suction positioning was used to visualize right pulmonary veins. Safety and feasibility end points were analysed intraoperatively and in the early postoperative course. In all patients, right atrial positioning created optimal conditions to complete transverse and oblique sinus blunt dissection, correct placement of a bipolar ablation probe, detection and ablation of ganglionated plexi and conduction block assessment. In all patients, this entire right-sided ablation procedure was completed with a single exposure manoeuvre. Feasibility end points were achieved in all study patients. This report documents the safety and feasibility of right atrial exposure using a suction-based cardiac positioner to complete ablation for AF concomitant with off-pump coronary revascularization. This technique may be widely adopted to create stable haemodynamic conditions and optimal visualization of the right pulmonary veins. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

An advanced anaerobic biofilter with effluent recirculation for phenol removal and methane production in treatment of coal gasification wastewater.

PubMed

Li, Yajie; Tabassum, Salma; Zhang, Zhenjia

2016-09-01

An advanced anaerobic biofilter (AF) was introduced for the treatment of coal gasification wastewater (CGW), and effluent recirculation was adopted to enhance phenol removal and methane production. The results indicated that AF was reliable in treating diluted CGW, while its efficiency and stability were seriously reduced when directly treating raw CGW. However, its performance could be greatly enhanced by effluent recirculation. Under optimal effluent recirculation of 0.5 to the influent, concentrations of chemical oxygen demand (COD) and total phenol in the effluent could reach as low as 234.0 and 14.2mg/L, respectively. Also, the rate of methane production reached 169.0mLCH4/L/day. Though CGW seemed to restrain the growth of anaerobic microorganisms, especially methanogens, the inhibition was temporary and reversible, and anaerobic bacteria presented strong tolerance. The activities of methanogens cultivated in CGW could quickly recover on feeding with glucose wastewater (GW). However, the adaptability of anaerobic bacteria to the CGW was very poor and the activity of methanogens could not be improved by long-term domestication. By analysis using the Haldane model, it was further confirmed that high effluent recirculation could result in high activity for hydrolytic bacteria and substrate affinity for toxic matters, but only suitable effluent recirculation could result in high methanogenic activity. Copyright © 2016. Published by Elsevier B.V.

Does permanent atrial fibrillation modify response to cardiac resynchronization therapy in heart failure patients?

PubMed

Abreu, Ana; Oliveira, Mário; Silva Cunha, Pedro; Santa Clara, Helena; Portugal, Guilherme; Gonçalves Rodrigues, Inês; Santos, Vanessa; Morais, Luís; Selas, Mafalda; Soares, Rui; Branco, Luísa; Ferreira, Rui; Mota Carmo, Miguel

2017-10-01

The benefits of cardiac resynchronization therapy (CRT) documented in heart failure (HF) may be influenced by atrial fibrillation (AF). We aimed to compare CRT response in patients in AF and in sinus rhythm (SR). We prospectively studied 101 HF patients treated by CRT. Rates of clinical, echocardiographic and functional response, baseline NYHA class and variation, left ventricular ejection fraction, volumes and mass, atrial volumes, cardiopulmonary exercise test (CPET) duration (CPET dur), peak oxygen consumption (VO 2 max) and ventilatory efficiency (VE/VCO 2 slope) were compared between AF and SR patients, before and at three and six months after implantation of a CRT device. All patients achieved ≥95% biventricular pacing, and 5.7% underwent atrioventricular junction ablation. Patients were divided into AF (n=35) and SR (n=66) groups; AF patients were older, with larger atrial volumes and lower CPET dur and VO 2 max before CRT. The percentages of clinical and echocardiographic responders were similar in the two groups, but there were more functional responders in the AF group (71% vs. 39% in SR patients; p=0.012). In SR patients, left atrial volume and left ventricular mass were significantly reduced (p=0.015 and p=0.021, respectively), whereas in AF patients, CPET dur (p=0.003) and VO 2 max (p=0.001; 0.083 age-adjusted) showed larger increases. Clinical and echocardiographic response rates were similar in SR and AF patients, with a better functional response in AF. Improvement in left ventricular function and volumes occurred in both groups, but left ventricular mass reduction and left atrial reverse remodeling were seen exclusively in SR patients (ClinicalTrials.gov identifier: NCT02413151; FCT code: PTDC/DES/120249/2010). Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Aspergillus fumigatus SidA is a highly specific ornithine hydroxylase with bound flavin cofactor.

PubMed

Chocklett, Samuel W; Sobrado, Pablo

2010-08-10

Ferrichrome is a hydroxamate-containing siderophore produced by the pathogenic fungus Aspergillus fumigatus under iron-limiting conditions. This siderophore contains N(5)-hydroxylated l-ornithines essential for iron binding. A. fumigatus siderophore A (Af SidA) catalyzes the flavin- and NADPH-dependent hydroxylation of l-ornithine in ferrichrome biosynthesis. Af SidA was recombinantly expressed and purified as a soluble tetramer and is the first member of this class of flavin monooxygenases to be isolated with a bound flavin cofactor. The enzyme showed typical saturation kinetics with respect to l-ornithine while substrate inhibition was observed at high concentrations of NADPH and NADH. Increasing amounts of hydrogen peroxide were measured as a function of reduced nicotinamide coenzyme concentration, indicating that inhibition was caused by increased uncoupling. Af SidA is highly specific for its amino acid substrate, only hydroxylating l-ornithine. An 8-fold preference in the catalytic efficiency was determined for NADPH compared to NADH. In the absence of substrate, Af SidA can be reduced by NADPH, and a C4a-(hydro)peroxyflavin intermediate is observed. The decay of this intermediate is accelerated by l-ornithine binding. This intermediate was only stabilized by NADPH and not by NADH, suggesting a role for NADP(+) in the stabilization of intermediates in the reaction of Af SidA. NADP(+) is a competitive inhibitor with respect to NADPH, demonstrating that Af SidA forms a ternary complex with NADP(+) and l-ornithine during catalysis. The data suggest that Af SidA likely proceeds by a sequential kinetic mechanism.

Development of novel high power-short time (HPST) microwave assisted commercial decontamination process for dried turmeric powder (Curcuma Longa L.).

PubMed

Behera, G; Sutar, P P; Aditya, S

2017-11-01

The commercially available dry turmeric powder at 10.34% d.b. moisture content was decontaminated using microwaves at high power density for short time. To avoid the loss of moisture from turmeric due to high microwave power, the drying kinetics were modelled and considered during optimization of microwave decontamination process. The effect of microwave power density (10, 33.5 and 57 W g -1 ), exposure time (10, 20 and 30 s) and thickness of turmeric layer (1, 2 and 3 mm) on total plate, total yeast and mold (YMC) counts, color change (∆E), average final temperature of the product (T af ), water activity (a w ), Page model rate constant (k) and total moisture loss (ML) was studied. The perturbation analysis was carried out for all variables. It was found that to achieve more than one log reduction in yeast and mold count, a substantial reduction in moisture content takes place leading to the reduced output. The microwave power density significantly affected the YMC, T af and a w of turmeric powder. But the thickness of sample and microwave exposure time showed effect only on T af , a w and ML. The colour of turmeric and Page model rate constant were not significantly changed during the process as anticipated. The numerical optimization was done at 57.00 W g -1 power density, 1.64 mm thickness of sample layer and 30 s exposure time. It resulted into 1.6 × 10 7 CFU g -1 YMC, 82.71 °C T af , 0.383 a w and 8.41% (d.b.) final moisture content.

Internal Medicine Physicians’ Perceptions Regarding Rate versus Rhythm Control for Atrial Fibrillation

PubMed Central

McCabe, James M.; Johnson, Colleen J; Marcus, Gregory M

2011-01-01

Atrial fibrillation (AF) is often managed by general internal medicine physicians. Available data suggest that guidelines regarding AF management are often not followed, but the reasons for this remain unknown. We sought to assess the knowledge and beliefs of internists regarding strategies to treat AF. We conducted a national electronic survey of internal medicine physicians regarding their perceptions of optimal AF management, with an emphasis on the rationale for choosing a rhythm or rate control strategy. One hundred and forty-eight physicians from 36 different states responded (representing at least 19% of unique e-mails opened). Half of the respondents reported managing their AF patients independently without referral to a cardiologist. Seventy-three percent of participants believe a rhythm control strategy conveys a decreased stroke risk, 64% believe there is a mortality benefit to rhythm control, and 55% think that it would help avoid long term anticoagulation. Comparing those who prefer a rhythm control strategy to everyone else, those who favor rhythm control statistically significantly more often believe that rhythm control reduces the risk for stroke (96% versus 67%, p=0.009) and that rhythm control allows for the discontinuation of anticoagulation therapy (76% versus 49%, p=0.045). In conclusion, contrary to available data in clinical trials and recent guidelines regarding the rationale for choosing a rhythm control strategy in treating AF, the majority of study participants believe that rhythm control decreases stroke risk, decreases mortality, and allows for discontinuation of anticoagulation therapy. These prevalent misconceptions may substantially contribute to guideline non-adherence. PMID:19195516

Purification and characterization of a novel endo-β-1,4-glucanases , AfEG22, from the giant snail, Achatina fulica frussac.

PubMed

Teng, Yigang; Yin, Qiuyu; ding, Ming; Zhao, Fukun

2010-10-01

In this study, we confirmed that at least three endo-β-1,4-glucanases existed in the digestive juice of the giant snail, Achatina fulica ferussac, by Congo red staining assay. One of these enzymes, a novel endo-β-1,4-glucanase (AfEG22), was purified 29.5-fold by gel filtration, anion exchange, and hydrophobic interaction chromatography. The carboxymethyl cellulose (CMC) hydrolytic activity of the purified enzyme was 12.3 U/mg protein. The molecular mass of AfEG22 was 22081 Da determined by MALDI-TOF. N-terminal amino acid sequencing revealed a sequence of EQRCTNQGGILKYYNT, which did not have significant homology with any proteins in BLAST database. The optimal pH and temperature for hydrolytic activity toward CMC were pH 4.0 and 50°C, respectively. AfEG22 was stable between pH 3.0 and pH 12.0 when incubated at 4°C for 3 h or at 37°C for 1 h. The enzyme remained more than 80% activity between pH 4.5 and pH 7.0 after incubation at 50°C for 1 h. AfEG22 possessed excellent thermostability as more than 70% activity was remained after incubation at 60°C for 3 h. Substrate specific analysis revealed that AfEG22 was a typical endo-β-1,4-glucanase. This is the first time to report a novel endo-β-1,4-glucanase with high stability from the digestive juice of A. fulica.

Active materials for automotive adaptive forward lighting Part 1: system requirements vs. material properties

NASA Astrophysics Data System (ADS)

Keefe, Andrew C.; Browne, Alan L.; Johnson, Nancy L.

2011-04-01

Adaptive Frontlighting Systems (AFS in GM usage) improve visibility by automatically optimizing the beam pattern to accommodate road, driving and environmental conditions. By moving, modifying, and/or adding light during nighttime, inclement weather, or in sharp turns, the driver is presented with dynamic illumination not possible with static lighting systems The objective of this GM-HRL collaborative research project was to assess the potential of active materials to decrease the cost, mass, and packaging volume of current electric stepper-motor AFS designs. Solid-state active material actuators, if proved suitable for this application, could be less expensive than electric motors and have lower part count, reduced size and weight, and lower acoustic and EMF noise1. This paper documents Part 1 of the collaborative study, assessing technically mature, commercially available active materials for use as actuators. Candidate materials should reduce cost and improve AFS capabilities, such as increased angular velocity on swivel. Additional benefits to AFS resulting from active materials actuators were to be identified as well such as lower part count. In addition, several notional approaches to AFS were documented to illustrate the potential function, which is developed more fully in Part 2. Part 1 was successful in verifying the feasibility of using two active materials for AFS: shape memory alloys, and piezoelectrics. In particular, this demonstration showed that all application requirements including those on actuation speed, force, and cyclic stability to effect manipulation of the filament assembly and/or the reflector could be met by piezoelectrics (as ultrasonic motors) and SMA wire actuators.

Short-Term Heparin Kinetics during Catheter Ablation of Atrial Fibrillation.

PubMed

Gabus, Vincent; Rollin, Anne; Maury, Philippe; Forclaz, Andrei; Pascale, Patrizio; Dhutia, Harshil; Bisch, Laurence; Pruvot, Etienne

2015-10-01

Percutaneous catheter ablation of atrial fibrillation (CA-AF) is a treatment option for symptomatic drug-refractory atrial fibrillation (AF). CA-AF carries a risk for thromboembolic complications that has been minimized by the use of intraprocedural intravenous unfractionated heparin (UFH). The optimal administration of UFH as well as its kinetics are not well established and need to be precisely determined. A total 102 of consecutive patients suffering from symptomatic drug-refractory AF underwent CA-AF. The mean age was 61 ± 10 years old. After transseptal puncture of the fossa ovalis, weight-adjusted UFH bolus (100 U/kg) was infused. A significant increase in activated clotting time (ACT) was observed from an average value of 100 ± 27 seconds at baseline, to 355 ± 94 seconds at 10 min (T10), to 375 ± 90 seconds at 20 min (T20). Twenty-four patients failed to reach the targeted ACT value of ≥300 seconds at T10 and more than half of these remained with subtherapeutic ACT values at T20. This subset of patients showed similar clinical characteristics and amount of UFH but were more frequently prescribed preprocedural vitamin K1 than the rest of the study population. In a typical intervention setting, UFH displays unexpected slow anticoagulation kinetics in a significant proportion of procedures up to 20 minutes after infusion. These findings support the infusion of UFH before transseptal puncture or any left-sided catheterization with early ACT measurements to identify patients with delayed kinetics. They are in line with recent guidelines to perform CA-AF under therapeutic anticoagulation. © 2015 Wiley Periodicals, Inc.

Persistent Atrial Fibrillation Ablation using the Tip-Versatile Ablation Catheter.

PubMed

Davies, Edward J; Clayton, Ben; Lines, Ian; Haywood, Guy A

2016-07-01

The mechanisms by which persistent atrial fibrillation (PsAF) develops are incompletely understood. Consequently, the optimal strategy for the ablative management of PsAF remains debated. Current methods are often time consuming, complex and non-reproducible. We assessed the Tip-Versatile Ablation Catheter (T-VAC) technique, a rapidly delivered, empirical technique based on the box-set concept using duty-cycled linear catheter ablation technology. Forty-four procedures in 40 patients undergoing PsAF ablation with the novel technique were prospectively entered onto a database: 27 de novo. Primary endpoint was freedom from arrhythmia at over two-year follow-up. Secondary endpoints were time to first arrhythmia recurrence, freedom from atrial fibrillation (AF) on and off antiarrhythmic drugs (AAD), procedural and fluoroscopy duration and complication rate. At mean follow-up of 33 months, absolute freedom from arrhythmia recurrence was 45% in the de novo group. Overall, at 33 (IQR 24-63) months, 60% of de novo patients were in sustained normal sinus rhythm and a further 15% reported only occasional paroxysms of AF at long-term follow-up. Procedure time was 192±25 mins, total energy delivered 2239±883s and fluoroscopy time was 60±10mins. In selected patients with persistent AF, a long-term rate of 60% arrhythmia free survival off AAD can be achieved using this novel T-VAC technique. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

[Microsecond Pulsed Hollow Cathode Lamp as Enhanced Excitation Source of Hydride Generation Atomic Fluorescence Spectrometry].

PubMed

Zhang, Shuo

2015-09-01

The spectral, electrical and atomic fluorescence characteristics of As, Se, Sb and Pb hollow cathode lamps (HCLs) powered by a laboratory-built high current microsecond pulse (HCMP) power supply were studied, and the feasibility of using HCMP-HCLs as the excitation source of hydride generation atomic fluorescence spectrometry (HG-AFS) was evaluated. Under the HCMP power supply mode, the As, Se, Sb, Pb HCLs can maintain stable glow discharge at frequency of 100~1000 Hz, pulse width of 4.0~20 μs and pulse current up to 4.0 A. Relationship between the intensity of characteristic emission lines and HCMP power supply parameters, such as pulse current, power supply voltage, pulse width and frequency, was studied in detail. Compared with the conventional pulsed (CP) HCLs used in commercial AFS instruments, HCMP-HCLs have a narrower pulse width and much stronger pulse current. Under the optimized HCMP power supply parameters, the intensity of atomic emission lines of As, Se, Sb HCLs had sharp enhancement and that indicated their capacity of being a novel HG-AFS excitation source. However, the attenuation of atomic lines and enhancement of ionic lines negated such feasibility of HCMP-Pb HCL. Then the HG-AFS analytical capability of using the HCMP-As/Se/Sb HCLs excitation source was established and results showed that the HCMP-HCL is a promising excitation source for HG-AFS.

Improving functional properties of pea protein isolate for microencapsulation of flaxseed oil.

PubMed

Bajaj, Poonam R; Bhunia, Kanishka; Kleiner, Leslie; Joyner Melito, Helen S; Smith, Denise; Ganjyal, Girish; Sablani, Shyam S

2017-03-01

Unhydrolysed pea protein (UN) forms very viscous emulsions when used at higher concentrations. To overcome this, UN was hydrolysed using enzymes alcalase, flavourzyme, neutrase, alcalase-flavourzyme, and neutrase-flavourzyme at 50 °C for 0 min, 30 min, 60 min, and 120 min to form hydrolysed proteins A, F, N, AF, and NF, respectively. All hydrolysed proteins had lower apparent viscosity and higher solubility than UN. Foaming capacity of A was the highest, followed by NF, N, and AF. Hydrolysed proteins N60, A60, NF60, and AF60 were prepared by hydrolysing UN for 60 min and used further for microencapsulation. At 20% oil loading (on a total solid basis), the encapsulated powder N60 had the highest microencapsulation efficiency (ME = 56.2). A decrease in ME occurred as oil loading increased to 40%. To improve the ME of N60, >90%, UN and maltodextrin were added. Flowability and particle size distribution of microencapsulated powders with >90% microencapsulation efficiency and morphology of all powders were investigated. This study identified a new way to improve pea protein functionality in emulsions, as well as a new application of hydrolysed pea protein as wall material for microencapsulation.

[Catheter ablation of atrial fibrillation: Health Technology Assessment Report from the Italian Association of Arrhythmology and Cardiac Pacing (AIAC)].

PubMed

Themistoclakis, Sakis; Tritto, Massimo; Bertaglia, Emanuele; Berto, Patrizia; Bongiorni, Maria Grazia; Catanzariti, Domenico; De Fabrizio, Giuseppe; De Ponti, Roberto; Grimaldi, Massimo; Pandozi, Claudio; Tondo, Claudio; Gulizia, Michele

2011-11-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and significantly impact patients' quality of life, morbidity and mortality. The number of affected patients is expected to increase as well as the costs associated with AF management, mainly driven by hospitalizations. Over the last decade, catheter ablation techniques targeting pulmonary vein isolation have demonstrated to be effective in treating AF and preventing AF recurrence. This Health Technology Assessment report of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC) aims to define the current role of catheter ablation of AF in terms of effectiveness, efficiency and appropriateness. On the basis of an extensive review of the available literature, this report provides (i) an overview of the epidemiology, clinical impact and socio-economic burden of AF; (ii) an evaluation of therapeutic options other than catheter ablation of AF; and (iii) a detailed presentation of clinical outcomes and cost-benefit ratio associated with catheter ablation. The costs of catheter ablation of AF in Italy were obtained using a bottom-up analysis of a resource utilization survey of 52 hospitals that were considered a representative sample, including 4 Centers that contributed with additional unit cost information in a separate questionnaire. An analysis of budget impact was also performed to evaluate the impact of ablation on the management costs of AF. Results of this analysis show that (1) catheter ablation is effective, safe and superior to antiarrhythmic drug therapy in maintaining sinus rhythm; (2) the cost of an ablation procedure in Italy typically ranges from €8868 to €9455, though current reimbursement remains insufficient, covering only about 60% of the costs; (3) the costs of follow-up are modest (about 8% of total costs); (4) assuming an adjustment of reimbursement to the real cost of an ablation procedure and a 5-10% increase in the annual rate of ablation procedures, after approximately 5-6 years this would result in significant incremental savings for the Italian Healthcare System. In conclusion, catheter ablation of AF is a cost-effective procedure that is inadequately reimbursed in Italy. Insufficient reimbursement may serve as disincentive to perform AF ablation, thereby limiting patient access to this treatment. Considering the healthcare system perspective, higher initial costs for ablation procedures in the short term may be offset by cost savings mainly associated with decreased hospitalizations over time.

Acute cardiovascular effects of diltiazem in anesthetized dogs with induced atrial fibrillation.

PubMed

Miyamoto, M; Nishijima, Y; Nakayama, T; Hamlin, R L

2001-01-01

Atrial fibrillation (AF) is one of the most important arrhythmias of dogs. In a previous study, we determined the dosage of intravenously administered diltiazem necessary to reduce ventricular response (VR), cardiac output (CO), and mean systemic arterial pressure (P(Ao)) to values similar to those observed during sinus rhythm (SR) before induction of AF. The present study was conducted to establish an acute, effective dosage of diltiazem given PO. AF was produced by rapid atrial pacing in healthy, anesthetized Beagle Hounds. Dogs were instrumented to record hemodynamic and electrophysiological parameters. Four dogs were given 2.5 mg/kg diltiazem, and another 4 dogs were given 5 mg/kg diltiazem by stomach tube, whereas 4 other dogs received vehicle in equivalent volumes. Plasma concentrations of diltiazem were measured at various intervals after dosing. A dosage of 5 mg/kg diltiazem produced plasma concentrations of 32-100 ng/mL 3 hours after administration, concentrations within the published effective range for dogs with naturally occurring AF. Between 2 and 3 hours after this dosage, the rate pressure product (RPP) and an index of left ventricular efficiency returned to values similar to those observed during SR. Thus, we believe that diltiazem at anorally administered dosages of 5 mg/kg should be considered to produce therapeutic blood concentrations and favorable hemodynamic effects in dogs with naturally occurring AF. These data must be extrapolated with caution to dogs with long-standing AF produced by natural causes.

Protein/oligonucleotide conjugates as a cell specific PNA carrier.

PubMed

Obara, K; Ishihara, T; Akaike, T; Maruyama, A

2001-01-01

We have focused on proteineus ligand conjugate with oligonucleotides (ODNs) as a cell-specific delivery vector for peptide nucleic acids (PNAs). Asialofetuin (AF), a hepatocyte-specific proteineus ligand, was conjugated with ODNs that served as binding sites for PNAs. Succinimidyl-transe-4(N-maleimidylmethyl)-cyclohexane-1-carboxylate (SMCC) modified AF was coupled with 5'-thiolated oligodeoxynucleotide (HS-ODN). The resulting conjugate held PNAs with sequence-specific manner. The PNA/DNA conjugate complex has resistance against nucleases in serum. The efficient release of PNA from the complex was observed when the complex was made in contact with a target nucleotide. PNA uptake to hepatocytes was greatly enhanced when hepatocytes was incubated with PNA/conjugate complex. Free AF thoroughly inhibited PNA uptake with the conjugate, evidencing asialoglycoprotein receptor (ASGP-R) mediated endocytosis to be a major-route for the cellular uptake.

Optimization and evaluation of asymmetric flow field-flow fractionation of silver nanoparticles.

PubMed

Loeschner, Katrin; Navratilova, Jana; Legros, Samuel; Wagner, Stephan; Grombe, Ringo; Snell, James; von der Kammer, Frank; Larsen, Erik H

2013-01-11

Asymmetric flow field-flow fractionation (AF(4)) in combination with on-line optical detection and mass spectrometry is one of the most promising methods for separation and quantification of nanoparticles (NPs) in complex matrices including food. However, to obtain meaningful results regarding especially the NP size distribution a number of parameters influencing the separation need to be optimized. This paper describes the development of a separation method for polyvinylpyrrolidone-stabilized silver nanoparticles (AgNPs) in aqueous suspension. Carrier liquid composition, membrane material, cross flow rate and spacer height were shown to have a significant influence on the recoveries and retention times of the nanoparticles. Focus time and focus flow rate were optimized with regard to minimum elution of AgNPs in the void volume. The developed method was successfully tested for injected masses of AgNPs from 0.2 to 5.0 μg. The on-line combination of AF(4) with detection methods including ICP-MS, light absorbance and light scattering was helpful because each detector provided different types of information about the eluting NP fraction. Differences in the time-resolved appearance of the signals obtained by the three detection methods were explained based on the physical origin of the signal. Two different approaches for conversion of retention times of AgNPs to their corresponding sizes and size distributions were tested and compared, namely size calibration with polystyrene nanoparticles (PSNPs) and calculations of size based on AF(4) theory. Fraction collection followed by transmission electron microscopy was performed to confirm the obtained size distributions and to obtain further information regarding the AgNP shape. Characteristics of the absorbance spectra were used to confirm the presence of non-spherical AgNP. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel Elastomeric Closed Cell Foam - Nonwoven Fabric Composite Material (Phase III)

DTIC Science & Technology

2008-10-01

increasing the polymer content of the foam. From laboratory studies, processing was found to improve by using different types of NBR rubber . The AF07 B...Foam Optimization (Task 1) Prior development of fire retarded closed cell foam yielded attractive candidates for scale-up. Nitrile-butadiene rubber ... NBR ) and polyvinyl chloride (PVC) blends provided the most cost effective solutions. Two types of formulas were chosen for optimization. The first

Tracking with a Cooperatively Controlled Swarm of GMTI Equipped UAVS

DTIC Science & Technology

2008-12-02

with Ground Optimal Placement of GMTI UAVs for ground target tracking Abhijit Sinha°, Thia. Kirubarajana and Yaakov Bar-Shalom6 " Electrical and...Storrs, CT 06269, USA Abstract—With the recent advent of moderate-cost unmanned (or uninhabited) aerial vehicles (UAV) and their success in...the sensor platforms are mobile one has to decide the optimal placement of sensors. With the recent advent of af- fordable unmanned aerial vehicles

Pre-clinical laboratory evaluation of the new 'AF' arterial line filter range.

PubMed

Yarham, Gemma; Mulholland, John

2010-07-01

The presence of emboli was recognised relatively early in the history of open heart surgery. The emboli produced during cardiopulmonary bypass have the predisposition to distribute into, and ultimately obstruct, microvessels of all tissues. The Sorin Group has recently developed a new range of arterial line filters. Before the Sorin AF range of filters was released for pre-launch clinical trials, our group performed in vitro laboratory testing of the AF range against a selection of commercially available filters on the global market. The Sorin AF620 and AF640 demonstrate both the smallest prime volume and smallest surface contact area (92ml and 290 cm(2), respectively).The results of the GME Handling Efficiency experiments ranged by 39.6%, from 95.9% to 56.3%. In terms of an air bolus handling, the results of the Limit Bolus experiment ranged by 97 ml, from 147.5 ml down to 50 ml. The pressure drop across all the filters was measured under steady state experimental conditions. All of the above investigations were considered against surface area and prime volume. It is clear from the results that some commercially available arterial line filters perform better than others, not only in overall performance, but also with regard to individual characteristics. Evaluating arterial line filters for hospital-specific use has to balance pressure drop, surface area, micro air handling, prime volume and gross air handling; all points need to be considered. In the AF620 and AF640, Sorin boast that they are the two smallest prime and smallest surface area filters commercially available on the global market. The Sorin AF filter range performs well in all of the areas we investigated and will be a competitive option for centres, irrespective of which characteristics they use to evaluate and select their arterial line filter.

Quantum dots as contrast agents for endoscopy: mathematical modeling and experimental validation of the optimal excitation wavelength

NASA Astrophysics Data System (ADS)

Roy, Mathieu; DaCosta, Ralph S.; Weersink, Robert; Netchev, George; Davidson, Sean R. H.; Chan, Warren; Wilson, Brian C.

2007-02-01

Our group is investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). Our studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. This work quantitatively evaluates the effect of the excitation wavelength on the SBR, using both experimental measurements and mathematical modeling. Experimental SBR measurements were done by imaging QD solutions placed onto (surface) or embedded in (sub-surface) ex vivo murine tissue samples (brain, kidney, liver, lung), using a polymethylmethacrylate (PMMA) microchannel phantom. The results suggest that the maximum contrast is reached when the excitation wavelength is set at 400+/-20 μm for the surface configuration. For the sub-surface configuration, the optimal excitation wavelength varies with the tissue type and QD emission wavelengths. Our mathematical model, based on an approximation to the diffusion equation, successfully predicts the optimal excitation wavelength for the surface configuration, but needs further modifications to be accurate in the sub-surface configuration.

Critical design criteria for minimal antibiotic-free plasmid vectors necessary to combine robust RNA Pol II and Pol III-mediated eukaryotic expression with high bacterial production yields

PubMed Central

Carnes, Aaron E.; Luke, Jeremy M.; Vincent, Justin M.; Anderson, Sheryl; Schukar, Angela; Hodgson, Clague P.; Williams, James A.

2010-01-01

Background For safety considerations, regulatory agencies recommend elimination of antibiotic resistance markers and nonessential sequences from plasmid DNA-based gene medicines. In the present study we analyzed antibiotic-free (AF) vector design criteria impacting bacterial production and mammalian transgene expression. Methods Both CMV-HTLV-I R RNA Pol II promoter (protein transgene) and murine U6 RNA Pol III promoter (RNA transgene) vector designs were studied. Plasmid production yield was assessed through inducible fed-batch fermentation. RNA Pol II-directed EGFP and RNA Pol III-directed RNA expression were quantified by fluorometry and quantitative real-time polymerase chain reaction (RT-PCR), respectively, after transfection of human HEK293 cells. Results Sucrose-selectable minimalized protein and therapeutic RNA expression vector designs that combined an RNA-based AF selection with highly productive fermentation manufacturing (>1,000 mg/L plasmid DNA) and high level in vivo expression of encoded products were identified. The AF selectable marker was also successfully applied to convert existing kanamycin-resistant DNA vaccine plasmids gWIZ and pVAX1 into AF vectors, demonstrating a general utility for retrofitting existing vectors. A minimum vector size for high yield plasmid fermentation was identified. A strategy for stable fermentation of plasmid dimers with improved vector potency and fermentation yields up to 1,740 mg/L was developed. Conclusions We report the development of potent high yield AF gene medicine expression vectors for protein or RNA (e.g. short hairpin RNA or microRNA) products. These AF expression vectors were optimized to exceed a newly identified size threshold for high copy plasmid replication and direct higher transgene expression levels than alternative vectors. PMID:20806425

The Patterns of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Use in Patients with Atrial Fibrillation in Seven Balkan Countries: a Report from the BALKAN-AF Survey.

PubMed

Potpara, Tatjana S; Trendafilova, Elina; Dan, Gheorghe-Andrei; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Gjini, Viktor; Pojskic, Belma; Popescu, Mircea Ioakim; Georgescu, Catalina Arsenescu; Dimitrova, Elena S; Kamenova, Delyana; Ekmeciu, Uliks; Mrsic, Denis; Nenezic, Ana; Brusich, Sandro; Milanov, Srdjan; Zeljkovic, Ivan; Lip, Gregory Y H

2017-08-01

Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs). A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants). Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20-3.56], rhythm control (OR 1.64, 1.25-2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51-3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis. NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.

Benefits of Atrial Substrate Modification Guided by Electrogram Similarity and Phase Mapping Techniques to Eliminate Rotors and Focal Sources Versus Conventional Defragmentation in Persistent Atrial Fibrillation.

PubMed

Lin, Yenn-Jiang; Lo, Men-Tzung; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Chao, Tze-Fan; Chung, Fa-Po; Liao, Jo-Nan; Lin, Chin-Yu; Kuo, Huan-Yu; Chang, Yi-Chung; Lin, Chen; Tuan, Ta-Chuan; Vincent Young, Hsu-Wen; Suenari, Kazuyoshi; Dan Do, Van Buu; Raharjo, Suunu Budhi; Huang, Norden E; Chen, Shih-Ann

2016-11-01

This prospective study compared the efficacy of atrial substrate modification guided by a nonlinear phase mapping technique with that of conventional substrate ablation. The optimal ablation strategy for persistent atrial fibrillation (AF) was unknown. In phase 1 study, we applied a cellular automation technique to simulate the electrical wave propagation to improve the phase mapping algorithm, involving analysis of high-similarity electrogram regions. In addition, we defined rotors and focal AF sources, using the physical parameters of the divergence and curvature forces. In phase 2 study, we enrolled 68 patients with persistent AF undergoing substrate modification into 2 groups, group-1 (n = 34) underwent similarity index (SI) and phase mapping techniques; group-2 (n = 34) received complex fractionated atrial electrogram ablation with commercially available software. Group-1 received real-time waveform similarity measurements in which a phase mapping algorithm was applied to localize the sources. We evaluated the single-procedure freedom from AF. In group-1, we identified an average of 2.6 ± 0.89 SI regions per chamber. These regions involved rotors and focal sources in 65% and 77% of patients in group-1, respectively. Group-1 patients had shorter ablation procedure times, higher termination rates, and significant reduction in AF recurrence compared to group-2 and a trend toward benefit for all atrial arrhythmias. Multivariate analysis showed that substrate mapping using nonlinear similarity and phase mapping was the independent predictor of freedom from AF recurrence (hazard ratio: 0.26; 95% confidence interval: 0.09 to 0.74; p = 0.01). Our study showed that for persistent AF ablation, a specified substrate modification guided by nonlinear phase mapping could eliminate localized re-entry and non-pulmonary focal sources after pulmonary vein isolation. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

AMP-forming acetyl-CoA synthetases in Archaea show unexpected diversity in substrate utilization

PubMed Central

Ingram-Smith, Cheryl; Smith, Kerry S.

2007-01-01

Adenosine monophosphate (AMP)-forming acetyl-CoA synthetase (ACS; acetate:CoA ligase (AMP-forming), EC 6.2.1.1) is a key enzyme for conversion of acetate to acetyl-CoA, an essential intermediate at the junction of anabolic and catabolic pathways. Phylogenetic analysis of putative short and medium chain acyl-CoA synthetase sequences indicates that the ACSs form a distinct clade from other acyl-CoA synthetases. Within this clade, the archaeal ACSs are not monophyletic and fall into three groups composed of both bacterial and archaeal sequences. Kinetic analysis of two archaeal enzymes, an ACS from Methanothermobacter thermautotrophicus (designated as MT-ACS1) and an ACS from Archaeoglobus fulgidus (designated as AF-ACS2), revealed that these enzymes have very different properties. MT-ACS1 has nearly 11-fold higher affinity and 14-fold higher catalytic efficiency with acetate than with propionate, a property shared by most ACSs. However, AF-ACS2 has only 2.3-fold higher affinity and catalytic efficiency with acetate than with propionate. This enzyme has an affinity for propionate that is almost identical to that of MT-ACS1 for acetate and nearly tenfold higher than the affinity of MT-ACS1 for propionate. Furthermore, MT-ACS1 is limited to acetate and propionate as acyl substrates, whereas AF-ACS2 can also utilize longer straight and branched chain acyl substrates. Phylogenetic analysis, sequence alignment and structural modeling suggest a molecular basis for the altered substrate preference and expanded substrate range of AF-ACS2 versus MT-ACS1. PMID:17350930

Atrial fibrillation ablation using very short duration 50 W ablations and contact force sensing catheters.

PubMed

Winkle, Roger A; Moskovitz, Ryan; Hardwin Mead, R; Engel, Gregory; Kong, Melissa H; Fleming, William; Salcedo, Jonathan; Patrawala, Rob A; Tranter, John H; Shai, Isaac

2018-06-01

The optimal radiofrequency (RF) power and lesion duration using contact force (CF) sensing catheters for atrial fibrillation (AF) ablation are unknown. We evaluate 50 W RF power for very short durations using CF sensing catheters during AF ablation. We evaluated 51 patients with paroxysmal (n = 20) or persistent (n = 31) AF undergoing initial RF ablation. A total of 3961 50 W RF lesions were given (average 77.6 ± 19.1/patient) for an average duration of only 11.2 ± 3.7 s. As CF increased from < 10 to > 40 g, the RF application duration decreased from 13.7 ± 4.4 to 8.6 ± 2.5 s (p < 0.0005). Impedance drops occurred in all ablations, and for patients in sinus rhythm, there was loss of pacing capture during RF delivery suggesting lesion creation. Only 3% of the ablation lesions were at < 5 g and 1% at > 40 g of force. As CF increased, the force time integral (FTI) increased from 47 ± 24 to 376 ± 102 gs (p < 0.0005) and the lesion index (LSI) increased from 4.10 ± 0.51 to 7.63 ± 0.50 (p < 0.0005). Both procedure time (101 ± 19.7 min) and total RF energy time (895 ± 258 s) were very short. For paroxysmal AF, the single procedure freedom from AF was 86% at 1 and 2 years. For persistent AF, it was 83% at 1 year and 72% at 2 years. There were no complications. Short duration 50 W ablations using CF sensing catheters are safe and result in excellent long-term freedom from AF for both paroxysmal and persistent AF with short procedure times and small amounts of total RF energy delivery.

Autofluorescence of liver tissue and bile: organ functionality monitoring during ischemia and reoxygenation.

PubMed

Croce, Anna C; Ferrigno, Andrea; Santin, Giada; Piccolini, Valeria M; Bottiroli, Giovanni; Vairetti, Mariapia

2014-07-01

Autofluorescence (AF) based optical biopsy of liver tissue is a powerful approach for the real-time diagnosis of its functionality. Since increasing attention is given to the bile production and composition to monitor the liver metabolic engagement in surgery and transplantation, we have investigated the bile AF properties as a potential, additional diagnostic parameter. Spectrofluorometric analysis has been performed in real time on a rat liver model of warm ischemia and reperfusion-60 minutes partial portal vein and hepatic artery clamping and subsequent restoration of blood circulation-in comparison with sham operated rats. The AF spectra have been recorded through a single fiber optic probe (366 nm excitation) from both liver tissue and bile, collected from the cannulated bile duct, and analyzed by means of curve fitting procedures. Bile composition has been also analyzed through biochemical assays of bilirubin, total bile acids (TBA) and proteins. Both liver and bile AF signal amplitude and spectral shape undergo changes during induction of ischemia and subsequent reperfusion. The liver tissue response is mainly ascribable to changes in NAD(P)H and flavins and their redox state, largely dependent on oxygen supply, and to the decrease of both vitamin A and fatty acid AF contributions. During comparable times, sham operated rat livers undergo smaller alterations in AF spectral shape, indicating a continuous, slight increase in the oxidized state. Bile AF emission shows a region in the 510-600 nm range ascribable to bilirubin, and resulting from the contribution of two bands, centered at about 515-523 and 570 nm, consistently with its bichromophore nature. Variations in the balance between these two bands depend on the influence of microenvironment on bilirubin intramolecular interchromophore energy transfer efficiency and are likely indicating alteration in a bile composition. This event is supported also by changes observed in the 400-500 nm emission region, ascribable to other bile components. In parallel with the intratissue AF properties, mainly reflecting redox metabolic activities, the bile AF analysis can provide additional information to assess alterations and recovery in the balance of liver metabolic activities. © 2014 Wiley Periodicals, Inc.

Oral Anticoagulation in Patients With Liver Disease.

PubMed

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Optical Magnetic Induction Tomography of the Heart

NASA Astrophysics Data System (ADS)

Marmugi, Luca; Renzoni, Ferruccio

2016-04-01

Atrial Fibrillation (AF) affects a significant fraction of the ageing population, causing a high level of morbidity and mortality. Despite its significance, the causes of AF are still not uniquely identified. This, combined with the lack of precise diagnostic and guiding tools, makes the clinical treatment of AF sub-optimal. We identify magnetic induction tomography as the most promising technique for the investigation of the causes of fibrillation and for its clinical practice. We therefore propose a novel optical instrument based on optical atomic magnetometers, fulfilling the requirements for diagnostic mapping of the heart’s conductivity. The feasibility of the device is here discussed in view of the final application. Thanks to the potential of atomic magnetometers for miniaturisation and extreme sensitivity at room temperature, a new generation of compact and non-invasive diagnostic instrumentation, with both bedside and intra-operative operation capability, is envisioned. Possible scenarios both in clinical practice and biomedical research are then discussed. The flexibility of the system makes it promising also for application in other fields, such as neurology and oncology.

Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study.

PubMed

Prabhu, Sandeep; Taylor, Andrew J; Costello, Ben T; Kaye, David M; McLellan, Alex J A; Voskoboinik, Aleksandr; Sugumar, Hariharan; Lockwood, Siobhan M; Stokes, Michael B; Pathik, Bhupesh; Nalliah, Chrishan J; Wong, Geoff R; Azzopardi, Sonia M; Gutman, Sarah J; Lee, Geoffrey; Layland, Jamie; Mariani, Justin A; Ling, Liang-Han; Kalman, Jonathan M; Kistler, Peter M

2017-10-17

Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy. The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF. This multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months. A total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p < 0.0001) and normalized (LVEF ≥50%) in 58% versus 9% (p = 0.0002). In those undergoing CA, the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF (10.7%; p = 0.0069) and normalization at 6 months (73% vs. 29%; p = 0.0093). AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Safe and rapid isolation of pulmonary veins using a novel circular ablation catheter and duty-cycled RF generator.

PubMed

Fredersdorf, Sabine; Weber, Stefan; Jilek, Clemens; Heinicke, Norbert; VON Bary, Christian; Jungbauer, Carsten; Riegger, Günter A; Hamer, Okka W; Jeron, Andreas

2009-10-01

Ablation of atrial fibrillation (AF) has been one of the most difficult and time-consuming electrophysiological procedures. Due to the rapidly increasing demand for ablation procedures, technical advances would be helpful to reduce complexity and procedure time in AF ablation. Therefore, we investigated the feasibility of a single-catheter technique for pulmonary vein (PV) isolation utilizing a decapolar catheter combined with a duty-cycled, unipolar-bipolar radiofrequency (RF) generator. AF mapping and ablation was performed in 21 consecutive patients (mean age 59 +/- 12 years, 9 males) with paroxysmal AF (n = 17) and persistent AF (n = 4). The ablation catheter was forwarded to the LA via single-transseptal puncture. All electrodes were energized in 2 to 5 applications per vein, followed by segmental RF applications, as needed, to achieve electrical isolation. To assess left atrial anatomy for purposes of catheter manipulation, and later evaluate the possibility of asymptomatic PV-stenosis, CT or MR imaging was performed both prior to ablation and at 6-month follow-up. Isolation could be achieved in 85/86 veins (99%). Procedure time for ablation was 81 +/- 13 minutes, and fluoroscopy time was 30 +/- 11 minutes. There were no procedural complications. Success rate at 6 months was 86% (18/21). MR or CT imaging excluded asymptomatic PV-stenosis. Mapping and ablation of PVs can be performed in a safe and efficient manner using a single-catheter technique, with short procedure times and minimal learning curve. Thus, this system may be of high interest not only for high volume but all centers performing AF ablation.

Comparisons of human amniotic mesenchymal stem cell viability in FDA-approved collagen-based scaffolds: Implications for engineered diaphragmatic replacement.

PubMed

Shieh, Hester F; Graham, Christopher D; Brazzo, Joseph A; Zurakowski, David; Fauza, Dario O

2017-06-01

We sought to examine amniotic fluid mesenchymal stem cell (afMSC) viability within two FDA-approved collagen-based scaffolds, as a prerequisite to clinical translation of afMSC-based engineered diaphragmatic repair. Human afMSCs were seeded in a human-derived collagen hydrogel and in a bovine-derived collagen sheet at 3 matching densities. Cell viability was analyzed at 1, 3, and 5days using an ATP-based 3D bioluminescence assay. Statistical comparisons were by ANOVA (P<0.05). There was a highly significant 3-way interaction between scaffold type, seeding density, and time in 3D culture as determinants of cell viability, clearly favoring the human hydrogel (P<0.001). In both scaffolds, cell viability was highest at the highest seeding density of 150,000 cells/mL. Time in 3D culture impacted cell viability at the optimal seeding density in the human hydrogel, with the highest levels on days 1 (P<0.001) and 5 (P=0.05) with no significant effect in the bovine sheet (P=0.39-0.96). Among clinically-approved cell delivery vehicles, mesenchymal stem cell viability is significantly enhanced in a collagen hydrogel when compared with a collagen sheet. Cell viability can be further optimized by seeding density and time in 3D culture. These data further support the regulatory viability of clinical trials of engineered diaphragmatic repair. N/A (animal and laboratory study). Copyright © 2017 Elsevier Inc. All rights reserved.

Aligning health care policy with evidence-based medicine: the case for funding direct oral anticoagulants in atrial fibrillation.

PubMed

Stone, James A; Earl, Karen M; O'Neill, Blair J; Sharma, Mukul; Huynh, Thao; Leblanc, Kori; Ward, Richard; Teal, Philip A; Cox, Jafna L

2014-10-01

Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PubMed Central

RUSSO, VINCENZO; NIGRO, GERARDO; RAGO, ANNA; ANTONIO PAPA, ANDREA; PROIETTI, RICCARDO; DELLA CIOPPA, NADIA; CRISTIANO, ANNA; PALLADINO, ALBERTO; CALABRÒ, RAFFAELE; POLITANO, LUISA

2013-01-01

The role that atrial pacing therapy plays on the atrial fibrillation (AF) burden is still unclear. Aim of the study was to evaluate the effect of the atrial preference pacing algorithm on AF burden in patients affected by Myotonic Dystrophy type 1 (DM1) followed for a long follow up period. Sixty DM1 patients were -implanted with a dual chamber pacemaker (PM) for first degree or symptomatic type 1/type 2 second degree atrio-ventricular blocks- were followed for 2-years after implantation, by periodical examination. After 1 month of stabilization, they were randomized into two groups: 1) Patients implanted with conventional dual-chamber pacing mode (DDDR group) and 2) Patients implanted with DDDR plus Atrial Preference Pacing (APP) algorithm (APP ON group). The results showed that atrial tachycardia (AT)/AF burden was significantly reduced at 1 year follow up in the APP ON group (2122 ± 428 minutes vs 4127 ± 388 minutes, P = 0.03), with a further reduction at the end of the 2 year follow up period (4652 ± 348 minutes vs 7564 ± 638 minutes, P = 0.005). The data here reported show that the APP is an efficient algorithm to reduce AT/AF burden in DM1 patients implanted with dual chamber pacemaker. PMID:24803841

Expression of endoglucanases in Pichia pastoris under control of the GAP promoter

PubMed Central

2014-01-01

Background Plant-derived biomass is a potential alternative to fossil feedstocks for a greener economy. Enzymatic saccharification of biomass has been studied extensively and endoglucanases have been found to be a prerequisite for quick initial liquefaction of biomass under industrial conditions. Pichia pastoris, widely used for heterologous protein expression, can be utilized for fungal endoglucanase production. The recently marketed PichiaPink™ expression system allows for rapid clone selection, and employs the methanol inducible AOX1 promoter to ensure high protein expression levels. However, methanol is toxic and poses a fire hazard, issues which become more significant at an industrial scale. It is possible to eliminate these risks and still maintain high productivity by switching to the constitutive GAP promoter. Results In the present study, a plasmid carrying the constitutive GAP promoter was created for PichiaPink™. We then studied expression of two endoglucanases, AfCel12A from Aspergillus fumigatus and TaCel5A from Thermoascus aurantiacus, regulated by either the AOX1 promoter or the GAP promoter. Initial experiments in tubes and small bioreactors showed that the levels of AfCel12A obtained with the constitutive promoter were similar or higher, compared to the AOX1 promoter, whereas the levels of TaCel5A were somewhat lower. After optimization of cultivation conditions using a 15-l bioreactor, the recombinant P. pastoris strains utilizing the GAP promoter produced ca. 3–5 g/l of total secreted protein, with CMCase activity equivalent to 1200 nkat/ml AfCel12A and 170 nkat/ml TaCel5A. Conclusions We present a strategy for constitutive recombinant protein expression in the novel PichiaPink™ system. Both AfCel12A and TaCel5A were successfully expressed constitutively in P. pastoris under the GAP promoter. Reasonable protein levels were reached after optimizing cultivation conditions. PMID:24742273

The association between plasma big endothelin-1 levels at admission and long-term outcomes in patients with atrial fibrillation.

PubMed

Wu, Shuang; Yang, Yan-Min; Zhu, Jun; Ren, Jia-Meng; Wang, Juan; Zhang, Han; Shao, Xing-Hui

2018-05-01

The prognostic role of big endothelin-1 (ET-1) in atrial fibrillation (AF) is unclear. We aimed to assess its predictive value in patients with AF. A total of 716 AF patients were enrolled and divided into two groups based on the optimal cut-off value of big ET-1 in predicting all-cause mortality. The primary outcomes were all-cause mortality and major adverse events (MAEs). Cox regression analysis and net reclassification improvement (NRI) analysis were performed to assess the predictive value of big ET-1 on outcomes. With the optimal cut-off value of 0.55 pmol/L, 326 patients were classified into the high big ET-1 levels group. Cardiac dysfunction and left atrial dilation were factors related to high big ET-1 levels. During a median follow-up of 3 years, patients with big ET-1 ≥ 0.55 pmol/L had notably higher risk of all-cause death (44.8% vs. 11.5%, p < 0.001), MAEs (51.8% vs. 17.4%, p < 0.001), cardiovascular death, major bleeding, and tended to have higher thromboembolic risk. After adjusting for confounding factors, high big ET-1 level was an independent predictor of all-cause mortality (hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.46-3.05; p < 0.001), MAEs (HR 2.05, 95% CI 1.50-2.80; p = 0.001), and cardiovascular death (HR 2.44, 95% CI 1.52-3.93; p < 0.001). NRI analysis showed that big ET-1 allowed a significant improvement of 0.32 in the accuracy of predicting the risk of both all-cause mortality and MAEs. Elevated big ET-1 levels is an independent predictor of long-term all-cause mortality, MAEs, and cardiovascular death in patients with AF. Copyright © 2018 Elsevier B.V. All rights reserved.

Expression of endoglucanases in Pichia pastoris under control of the GAP promoter.

PubMed

Várnai, Anikó; Tang, Campbell; Bengtsson, Oskar; Atterton, Andrew; Mathiesen, Geir; Eijsink, Vincent G H

2014-04-18

Plant-derived biomass is a potential alternative to fossil feedstocks for a greener economy. Enzymatic saccharification of biomass has been studied extensively and endoglucanases have been found to be a prerequisite for quick initial liquefaction of biomass under industrial conditions. Pichia pastoris, widely used for heterologous protein expression, can be utilized for fungal endoglucanase production. The recently marketed PichiaPink™ expression system allows for rapid clone selection, and employs the methanol inducible AOX1 promoter to ensure high protein expression levels. However, methanol is toxic and poses a fire hazard, issues which become more significant at an industrial scale. It is possible to eliminate these risks and still maintain high productivity by switching to the constitutive GAP promoter. In the present study, a plasmid carrying the constitutive GAP promoter was created for PichiaPink™. We then studied expression of two endoglucanases, AfCel12A from Aspergillus fumigatus and TaCel5A from Thermoascus aurantiacus, regulated by either the AOX1 promoter or the GAP promoter. Initial experiments in tubes and small bioreactors showed that the levels of AfCel12A obtained with the constitutive promoter were similar or higher, compared to the AOX1 promoter, whereas the levels of TaCel5A were somewhat lower. After optimization of cultivation conditions using a 15-l bioreactor, the recombinant P. pastoris strains utilizing the GAP promoter produced ca. 3-5 g/l of total secreted protein, with CMCase activity equivalent to 1200 nkat/ml AfCel12A and 170 nkat/ml TaCel5A. We present a strategy for constitutive recombinant protein expression in the novel PichiaPink™ system. Both AfCel12A and TaCel5A were successfully expressed constitutively in P. pastoris under the GAP promoter. Reasonable protein levels were reached after optimizing cultivation conditions.

Population size drives industrial Saccharomyces cerevisiae alcoholic fermentation and is under genetic control.

PubMed

Albertin, Warren; Marullo, Philippe; Aigle, Michel; Dillmann, Christine; de Vienne, Dominique; Bely, Marina; Sicard, Delphine

2011-04-01

Alcoholic fermentation (AF) conducted by Saccharomyces cerevisiae has been exploited for millennia in three important human food processes: beer and wine production and bread leavening. Most of the efforts to understand and improve AF have been made separately for each process, with strains that are supposedly well adapted. In this work, we propose a first comparison of yeast AFs in three synthetic media mimicking the dough/wort/grape must found in baking, brewing, and wine making. The fermentative behaviors of nine food-processing strains were evaluated in these media, at the cellular, populational, and biotechnological levels. A large variation in the measured traits was observed, with medium effects usually being greater than the strain effects. The results suggest that human selection targeted the ability to complete fermentation for wine strains and trehalose content for beer strains. Apart from these features, the food origin of the strains did not significantly affect AF, suggesting that an improvement program for a specific food processing industry could exploit the variability of strains used in other industries. Glucose utilization was analyzed, revealing plastic but also genetic variation in fermentation products and indicating that artificial selection could be used to modify the production of glycerol, acetate, etc. The major result was that the overall maximum CO(2) production rate (V(max)) was not related to the maximum CO(2) production rate per cell. Instead, a highly significant correlation between V(max) and the maximum population size was observed in all three media, indicating that human selection targeted the efficiency of cellular reproduction rather than metabolic efficiency. This result opens the way to new strategies for yeast improvement.

Population Size Drives Industrial Saccharomyces cerevisiae Alcoholic Fermentation and Is under Genetic Control▿†‡

PubMed Central

Albertin, Warren; Marullo, Philippe; Aigle, Michel; Dillmann, Christine; de Vienne, Dominique; Bely, Marina; Sicard, Delphine

2011-01-01

Alcoholic fermentation (AF) conducted by Saccharomyces cerevisiae has been exploited for millennia in three important human food processes: beer and wine production and bread leavening. Most of the efforts to understand and improve AF have been made separately for each process, with strains that are supposedly well adapted. In this work, we propose a first comparison of yeast AFs in three synthetic media mimicking the dough/wort/grape must found in baking, brewing, and wine making. The fermentative behaviors of nine food-processing strains were evaluated in these media, at the cellular, populational, and biotechnological levels. A large variation in the measured traits was observed, with medium effects usually being greater than the strain effects. The results suggest that human selection targeted the ability to complete fermentation for wine strains and trehalose content for beer strains. Apart from these features, the food origin of the strains did not significantly affect AF, suggesting that an improvement program for a specific food processing industry could exploit the variability of strains used in other industries. Glucose utilization was analyzed, revealing plastic but also genetic variation in fermentation products and indicating that artificial selection could be used to modify the production of glycerol, acetate, etc. The major result was that the overall maximum CO2 production rate (Vmax) was not related to the maximum CO2 production rate per cell. Instead, a highly significant correlation between Vmax and the maximum population size was observed in all three media, indicating that human selection targeted the efficiency of cellular reproduction rather than metabolic efficiency. This result opens the way to new strategies for yeast improvement. PMID:21357433

Simultaneous Alcoholic and Malolactic Fermentations by Saccharomyces cerevisiae and Oenococcus oeni Cells Co-immobilized in Alginate Beads

PubMed Central

Bleve, Gianluca; Tufariello, Maria; Vetrano, Cosimo; Mita, Giovanni; Grieco, Francesco

2016-01-01

Malolactic fermentation (MLF) usually takes place after the end of alcoholic fermentation (AF). However, the inoculation of lactic acid bacteria together with yeast starter cultures is a promising system to enhance the quality and safety of wine. In recent years, the use of immobilized cell systems has been investigated, with interesting results, for the production of different fermented foods and beverages. In this study we have carried out the simultaneous immobilization of Saccharomyces cerevisiae and Oenococcus oeni in alginate beads and used them in microvinifications tests to produce Negroamaro wine. The process was monitored by chemical and sensorial analyses and dominance of starters and cell leaking from beads were also checked. Co-immobilization of S. cerevisiae and O. oeni allowed to perform an efficient fermentation process, producing low volatile acidity levels and ethanol and glycerol concentrations comparable with those obtained by cell sequential inoculum and co-inoculum of yeast and bacteria cells in free form. More importantly, co-immobilization strategy produced a significant decrease of the time requested to complete AF and MLF. The immobilized cells could be efficiently reused for the wine fermentation at least three times without any apparent loss of cell metabolic activities. This integrated biocatalytic system is able to perform simultaneously AF and MLF, producing wines similar in organoleptic traits in comparison with wines fermented following traditional sequential AF and MLF with free cell starters. The immobilized-cell system, that we here describe for the first time in our knowledge, offers many advantages over conventional free cell fermentations, including: (i) elimination of non-productive cell growth phases; (ii) feasibility of continuous processing; (iii) re-use of the biocatalyst. PMID:27379072

The Influence of Physical Qualities on Activity Profiles of Female Australian Football Match Play.

PubMed

Black, Georgia M; Gabbett, Tim J; Johnston, Rich D; Cole, Michael H; Naughton, Geraldine; Dawson, Brian

2018-04-01

The transition of female Australian football (AF) players from amateur to semielite competitions has the potential for athletes to be underprepared for match play. To gain an understanding of the match demands of female football, the aims of this study were to highlight the physical qualities that discriminate selected and nonselected female AF players, investigate activity profiles of female AF players, and gain an understanding of the influence of physical qualities on performance in female AF Methods: Twenty-two female AF state academy players (mean [SD]: age = 23.2 [4.5] y) and 27 nonselected players (mean [SD]: age = 23.4 [4.9] y) completed a Yo-Yo intermittent recovery test level 1, countermovement jump, and 30-m sprint tests were completed prior to the competitive season. During 14 matches, players wore global positioning system units to describe the running demands of match play. Selected players were faster over 30 m (ES = 0.57; P = .04) and covered greater distances on the Yo-Yo IR1 (ES = 1.09; P < .001). Selected midfielders spent greater time on the field and covered greater total distances (ES = 0.73-0.85; P < .01). Players faster over 5 m (r = -.612) and 30 m (r = -.807) and who performed better on the Yo-Yo IR1 (r = .489) covered greater high-speed distances during match play. An emphasis should be placed on the development of physical fitness in this playing group to ensure optimal preparation for the national competition.

Efficacy and Safety of Uninterrupted Low-Intensity Warfarin for Radiofrequency Catheter Ablation of Atrial Fibrillation in the Elderly.

PubMed

Xing, Yangbo; Xu, Buyun; Xu, Chao; Peng, Fang; Yang, Biao; Qiu, Yufang; Sun, Yong; Wang, Shengkai; Guo, Hangyuan

2017-09-01

No previous studies exist investigating the optimal intensity of uninterrupted anticoagulation with warfarin during radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) in the elderly. Evaluate the efficacy and safety of continuous low-intensity warfarin therapy throughout the periprocedural period of RFCA for AF in the elderly. This is a prospective randomized study. We enrolled AF patients (age ≥ 70 years) who underwent first-time RFCA for AF. Enrolled patients were randomized to group A and group B. The international normalized ratios before ablation were maintained at 1.5 to 2.0 and 2.0 to 2.5 in group A and B, respectively. Primary end points were periprocedural thromboembolic complications and major bleeding. Secondary end points included periprocedural asymptomatic cerebral emboli (ACE) and minor bleeding. A total of 101 patients were enrolled in our study (group A: 52; group B: 49). Baseline characteristics were well balanced between the 2 groups. Only 1 patient suffered from stroke in group B. No major bleeding events occurred in either group. The incidence of new ACE lesions was comparable between the 2 groups (11.5% vs 8.2%, P = 0.82). Minor bleeding occurred in 1 of 52 (1.9%) patients in group A and in 5 of 49 (10.2%) patients in group B ( P = 0.10). Uninterrupted low-intensity warfarin for RFCA of AF might be as effective as standard-intensity warfarin in preventing periprocedural thromboembolic complications and might be associated with fewer bleeding events in the elderly.

Spotlight on unmet needs in stroke prevention: The PIONEER AF-PCI, NAVIGATE ESUS and GALILEO trials.

PubMed

Hemmrich, Melanie; Peterson, Eric D; Thomitzek, Karen; Weitz, Jeffrey I

2016-09-28

Atrial fibrillation (AF) is a major healthcare concern, being associated with an estimated five-fold risk of ischaemic stroke. In patients with AF, anticoagulants reduce stroke risk to a greater extent than acetylsalicylic acid (ASA) or dual antiplatelet therapy (DAPT) with ASA plus clopidogrel. Non-vitamin K antagonist oral anticoagulants (NOACs) are now a widely-accepted therapeutic option for stroke prevention in non-valvular AF (NVAF). There are particular patient types with NVAF for whom treatment challenges remain, owing to sparse clinical data, their high-risk nature or a need to harmonise anticoagulant and antiplatelet regimens if co-administered. This article focuses on three randomised controlled trials (RCTs) that are investigating the utility of rivaroxaban, a direct, oral, factor Xa inhibitor, in additional areas of stroke prevention where data for anticoagulants are lacking: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment (PIONEER AF-PCI); New Approach riVaroxoban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS); and Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO). Data from these studies present collaborative efforts to build upon existing registrational Phase III data for rivaroxaban, driving the need for effective and safe treatment of a wider range of patients for stroke prevention.

High incidence of echocardiographic abnormalities of the interatrial septum in patients undergoing ablation for atrial fibrillation.

PubMed

Schernthaner, Christiana; Danmayr, Franz; Daburger, Apollonia; Eichinger, Jörg; Hammerer, Matthias; Strohmer, Bernhard

2013-04-01

Atrial fibrosis or fatty deposition is known to increase the propensity for the development of atrial fibrillation (AF). Apart from the pulmonic veins, the interatrial septum (IAS) might play a role in the maintenance of AF. In contrast to left atrial anatomy and adjacent veins, the IAS cannot be visualized in detail with computed tomography. Thus, preprocedural transesophageal echocardiography (TEE) may provide important morphologic information beyond exclusion from atrial thrombi. The study comprised 108 consecutive patients (mean age 60 ± 11 years; 98 men). AF was paroxysmal in 91 (84%) and persistent in 17 (16%) patients. We investigated the morphological characteristics of the IAS by TEE in patients who underwent radiofrequency ablation of AF. The IAS was structurally abnormal in 46 (43%) patients, showing the following echocardiograhic findings: atrial septal hypermobility or aneurysm (n = 27) associated with a patent foramen ovale (PFO) (n = 11) or with a small atrial septal defect (ASD) (n = 2), a septal flap associated with a PFO or an ASD (n = 8), and an abnormally thickened IAS (n = 12). A thrombus in the left atrial appendage was discovered in only 2 (2%) patients. A structurally abnormal IAS was diagnosed in nearly half of the patients undergoing ablation therapy for AF. The information obtained by TEE is mandatory to exclude left atrial thrombi prior the ablation procedure. Moreover, detailed knowledge of morphologic characteristics of the IAS facilitates an optimized and safe performance of the transseptal puncture using long sheaths with large diameters. © 2012, Wiley Periodicals, Inc.

Asymmetric flow field flow fractionation of aqueous C60 nanoparticles with size determination by dynamic light scattering and quantification by liquid chromatography atmospheric pressure photo-ionization mass spectrometry.

PubMed

Isaacson, Carl W; Bouchard, Dermont

2010-02-26

A size separation method was developed for aqueous C60 fullerene aggregates (aqu/C60) using asymmetric flow field flow fractionation (AF4) coupled to a dynamic light scattering detector in flow through mode. Surfactants, which are commonly used in AF4, were avoided as they may alter suspension characteristics. Aqu/C60 aggregates generated by sonication in deionized water ranged in size from 80 to 260 nm in hydrodynamic diameter (Dh) as determined by DLS in flow through mode, which was corroborated by analysis of fractions by DLS in batch mode and by TEM. The mass of C60 in each fraction was determined by LC-APPI-MS. Only 5.2+/-6.7% of the total aqu/C60 mass had Dh less than 80 nm, while 58+/-32% of the total aqu/C60 mass had Dh between 80 and 150 nm and 14+/-9.2% of the total aqu/C60 were between 150 and 260 nm in Dh. With the optimal fractionation parameters, 77+/-5.8% of the aqu/C60 mass eluted from the AF4 channel, indicating deposition on the AF4 membrane had occurred during fractionation; use of alternative membranes did not reduce deposition. Channel flow splitting increased detector response although channel split ratios greater than 80% of the channel flow led to decreased detector response. This is the first report on the use of AF4 for fractionating a colloidal suspension of aqu/C60. Published by Elsevier B.V.

An accurate homogenized tissue phantom for broad spectrum autofluorescence studies: a tool for optimizing quantum dot-based contrast agents

NASA Astrophysics Data System (ADS)

Roy, Mathieu; Wilson, Brian C.

2008-02-01

We are investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). The present studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. These contrast optimization studies require optical phantoms that simulate tissue autofluorescence, absorption and scattering over the entire visible spectrum, while allowing us to control the optical thickness. We present an optical phantom made of fresh homogenized tissue diluted in water. The homogenized tissue is poured into a clear polymer tank designed to hold a QD-loaded silica capillary in its center. Because of the non-linear effects of absorption and scattering on measured autofluorescence, direct comparison between results obtained using tissue phantoms of different concentration is not possible. We introduce mathematical models that make it possible to perform measurements on diluted tissue homogenates and subsequently extrapolate the results to intact (non-diluted) tissue. Finally, we present preliminary QD contrast data showing that the 380-420 nm spectral window is optimal for surface QD imaging.

Generation by Reverse Genetics of an Effective, Stable, Live-Attenuated Newcastle Disease Virus Vaccine Based on a Currently Circulating, Highly Virulent Indonesian Strain

PubMed Central

Xiao, Sa; Nayak, Baibaswata; Samuel, Arthur; Paldurai, Anandan; Kanabagattebasavarajappa, Mallikarjuna; Prajitno, Teguh Y.; Bharoto, Eny E.; Collins, Peter L.; Samal, Siba K.

2012-01-01

Newcastle disease virus (NDV) can cause severe disease in chickens. Although NDV vaccines exist, there are frequent reports of outbreaks in vaccinated chickens. During 2009–2010, despite intense vaccination, NDV caused major outbreaks among commercial poultry farms in Indonesia. These outbreaks raised concern regarding the protective immunity of current vaccines against circulating virulent strains in Indonesia. In this study, we investigated whether a recombinant attenuated Indonesian NDV strain could provide better protection against prevalent Indonesian viruses. A reverse genetics system for the highly virulent NDV strain Banjarmasin/010/10 (Ban/010) isolated in Indonesia in 2010 was constructed. The Ban/010 virus is classified in genotype VII of class II NDV, which is genetically distinct from the commercial vaccine strains B1 and LaSota, which belong to genotype II, and shares only 89 and 87% amino acid identity for the protective antigens F and HN, respectively. A mutant virus, named Ban/AF, was developed in which the virulent F protein cleavage site motif “RRQKR↓F” was modified to an avirulent motif “GRQGR↓L” by three amino acid substitutions (underlined). The Ban/AF vaccine virus did not produce syncytia or plaques in cell culture, even in the presence of added protease. Pathogenicity tests showed that Ban/AF was completely avirulent. Ban/AF replicated efficiently during 10 consecutive passages in chickens and remained genetically stable. Serological analysis showed that Ban/AF induced higher neutralization and hemagglutination inhibition antibody titers against the prevalent viruses than the commercial vaccines B1 or LaSota. Both Ban/AF and commercial vaccines provided protection against clinical disease and mortality after challenge with virulent NDV strain Ban/010 (genotype VII) or GB Texas (genotype II). However, Ban/AF significantly reduced challenge virus shedding from the vaccinated birds compared to B1 vaccine. These results suggest that Ban/AF can provide better protection than commercial vaccines and is a promising vaccine candidate against NDV strains circulating in Indonesia. PMID:23285174

Magnetic and Electrical Characteristics of Cobalt-Based Amorphous Materials and Comparison to a Permalloy Type Polycrystalline Material

NASA Technical Reports Server (NTRS)

Wieserman, William R.; Schwarze, Gene E.; Niedra, Janis M.

2005-01-01

Magnetic component designers are always looking for improved soft magnetic core materials to increase the efficiency, temperature rating and power density of transformers, motors, generators and alternators, and energy density of inductors. In this paper, we report on the experimental investigation of commercially available cobalt-based amorphous alloys which, in their processing, were subjected to two different types of magnetic field anneals: A longitudinal magnetic field anneal or a transverse magnetic field anneal. The longitudinal field annealed material investigated was Metglas 2714A. The electrical and magnetic characteristics of this material were investigated over the frequency range of 1 to 200 kHz and temperature range of 23 to 150 C for both sine and square wave voltage excitation. The specific core loss was lower for the square than the sine wave voltage excitation for the same maximum flux density, frequency and temperature. The transverse magnetic field annealed core materials include Metglas 2714AF and Vacuumschmelze 6025F. These two materials were experimentally characterized over the frequency range of 10 to 200 kHz for sine wave voltage excitation and 23 C only. A comparison of the 2174A to 2714AF found that 2714AF always had lower specific core loss than 2714A for any given magnetic flux density and frequency and the ratio of specific core loss of 2714A to 2714AF was dependent on both magnetic flux density and frequency. A comparison was also made of the 2714A, 2714AF, and 6025F materials to two different tape thicknesses of the polycrystalline Supermalloy material and the results show that 2714AF and 6025F have the lowest specific core loss at 100 kHz over the magnetic flux density range of 0.1 to 0.4 Tesla.

Rationale and design of a home-based trial using wearable sensors to detect asymptomatic atrial fibrillation in a targeted population: The mHealth Screening To Prevent Strokes (mSToPS) trial.

PubMed

Steinhubl, Steven R; Mehta, Rajesh R; Ebner, Gail S; Ballesteros, Marissa M; Waalen, Jill; Steinberg, Gregory; Van Crocker, Percy; Felicione, Elise; Carter, Chureen T; Edmonds, Shawn; Honcz, Joseph P; Miralles, Gines Diego; Talantov, Dimitri; Sarich, Troy C; Topol, Eric J

2016-05-01

Efficient methods for screening populations for undiagnosed atrial fibrillation (AF) are needed to reduce its associated mortality, morbidity, and costs. The use of digital technologies, including wearable sensors and large health record data sets allowing for targeted outreach toward individuals at increased risk for AF, might allow for unprecedented opportunities for effective, economical screening. The trial's primary objective is to determine, in a real-world setting, whether using wearable sensors in a risk-targeted screening population can diagnose asymptomatic AF more effectively than routine care. Additional key objectives include (1) exploring 2 rhythm-monitoring strategies-electrocardiogram-based and exploratory pulse wave-based-for detection of new AF, and (2) comparing long-term clinical and resource outcomes among groups. In all, 2,100 Aetna members will be randomized 1:1 to either immediate or delayed monitoring, in which a wearable patch will capture a single-lead electrocardiogram during the first and last 2 weeks of a 4-month period beginning immediately or 4 months after enrollment, respectively. An observational, risk factor-matched control group (n = 4,000) will be developed from members who did not receive an invitation to participate. The primary end point is the incidence of new AF in the immediate- vs delayed-monitoring arms at the end of the 4-month monitoring period. Additional efficacy and safety end points will be captured at 1 and 3 years. The results of this digital medicine trial might benefit a substantial proportion of the population by helping identify and refine screening methods for undiagnosed AF. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of rivaroxaban compared with warfarin in patients with peripheral artery disease and non-valvular atrial fibrillation: insights from ROCKET AF.

PubMed

Jones, William Schuyler; Hellkamp, Anne S; Halperin, Jonathan; Piccini, Jonathan P; Breithardt, Gunter; Singer, Daniel E; Fox, Keith A A; Hankey, Graeme J; Mahaffey, Kenneth W; Califf, Robert M; Patel, Manesh R

2014-01-01

Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, amputation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm. ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02; interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11; interaction P = 0.037). Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to validate this subgroup analysis and determine the optimal treatment in this high-risk cohort of AF patients with PAD.

Detecting atrial fibrillation by deep convolutional neural networks.

PubMed

Xia, Yong; Wulan, Naren; Wang, Kuanquan; Zhang, Henggui

2018-02-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The incidence of AF increases with age, causing high risks of stroke and increased morbidity and mortality. Efficient and accurate diagnosis of AF based on the ECG is valuable in clinical settings and remains challenging. In this paper, we proposed a novel method with high reliability and accuracy for AF detection via deep learning. The short-term Fourier transform (STFT) and stationary wavelet transform (SWT) were used to analyze ECG segments to obtain two-dimensional (2-D) matrix input suitable for deep convolutional neural networks. Then, two different deep convolutional neural network models corresponding to STFT output and SWT output were developed. Our new method did not require detection of P or R peaks, nor feature designs for classification, in contrast to existing algorithms. Finally, the performances of the two models were evaluated and compared with those of existing algorithms. Our proposed method demonstrated favorable performances on ECG segments as short as 5 s. The deep convolutional neural network using input generated by STFT, presented a sensitivity of 98.34%, specificity of 98.24% and accuracy of 98.29%. For the deep convolutional neural network using input generated by SWT, a sensitivity of 98.79%, specificity of 97.87% and accuracy of 98.63% was achieved. The proposed method using deep convolutional neural networks shows high sensitivity, specificity and accuracy, and, therefore, is a valuable tool for AF detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protein cage assisted metal-protein nanocomposite synthesis: Optimization of loading conditions

NASA Astrophysics Data System (ADS)

Sana, Barindra; Calista, Marcia; Lim, Sierin

2012-11-01

Ferritin is an iron-storage protein in most living systems with a cage-like structure. It has inherent property to form metallic nanocore within its cavity. The metallic core formed within the Archaeoglobus fulgidus ferritin cavity is stabilized by modulating the protein structure by site directed mutagenesis. Encapsulation protocol of various metals within the engineered ferritin cage (AfFtn-AA) is optimized. Dense metallic cores are visualized using electron microscopy and the bound metal was quantified by ICP-spectrometry. The AfFtn-AA is loaded with up to about 350 cobalt, 2000 chromium, and as high as 7000 iron atoms, separately. The metal-protein nanocomposites formed by encapsulation of cobalt, chromium, and iron are studied. Magnetic resonance imaging of the agarose embedded nanocomposites shows brightening of T1-weighted images and signal loss of T2-weighted images with increasing concentration of the nanocomposites. Shortening of magnetic relaxation times in the presence of the nanocomposites confirm their ability to enhance magnetic relaxation rate and suggests that the nanocomposites have potential application as MRI contrast agent.

Optical Magnetic Induction Tomography of the Heart

PubMed Central

Marmugi, Luca; Renzoni, Ferruccio

2016-01-01

Atrial Fibrillation (AF) affects a significant fraction of the ageing population, causing a high level of morbidity and mortality. Despite its significance, the causes of AF are still not uniquely identified. This, combined with the lack of precise diagnostic and guiding tools, makes the clinical treatment of AF sub-optimal. We identify magnetic induction tomography as the most promising technique for the investigation of the causes of fibrillation and for its clinical practice. We therefore propose a novel optical instrument based on optical atomic magnetometers, fulfilling the requirements for diagnostic mapping of the heart’s conductivity. The feasibility of the device is here discussed in view of the final application. Thanks to the potential of atomic magnetometers for miniaturisation and extreme sensitivity at room temperature, a new generation of compact and non-invasive diagnostic instrumentation, with both bedside and intra-operative operation capability, is envisioned. Possible scenarios both in clinical practice and biomedical research are then discussed. The flexibility of the system makes it promising also for application in other fields, such as neurology and oncology. PMID:27040727

Wireless Energy Harvesting Two-Way Relay Networks with Hardware Impairments.

PubMed

Peng, Chunling; Li, Fangwei; Liu, Huaping

2017-11-13

This paper considers a wireless energy harvesting two-way relay (TWR) network where the relay has energy-harvesting abilities and the effects of practical hardware impairments are taken into consideration. In particular, power splitting (PS) receiver is adopted at relay to harvests the power it needs for relaying the information between the source nodes from the signals transmitted by the source nodes, and hardware impairments is assumed suffered by each node. We analyze the effect of hardware impairments [-20]on both decode-and-forward (DF) relaying and amplify-and-forward (AF) relaying networks. By utilizing the obtained new expressions of signal-to-noise-plus-distortion ratios, the exact analytical expressions of the achievable sum rate and ergodic capacities for both DF and AF relaying protocols are derived. Additionally, the optimal power splitting (OPS) ratio that maximizes the instantaneous achievable sum rate is formulated and solved for both protocols. The performances of DF and AF protocols are evaluated via numerical results, which also show the effects of various network parameters on the system performance and on the OPS ratio design.

Determination of total selenium in food samples by d-CPE and HG-AFS.

PubMed

Wang, Mei; Zhong, Yizhou; Qin, Jinpeng; Zhang, Zehua; Li, Shan; Yang, Bingyi

2017-07-15

A dual-cloud point extraction (d-CPE) procedure was developed for the simultaneous preconcentration and determination of trace level Se in food samples by hydride generation-atomic fluorescence spectrometry (HG-AFS). The Se(IV) was complexed with ammonium pyrrolidinedithiocarbamate (APDC) in a Triton X-114 surfactant-rich phase, which was then treated with a mixture of 16% (v/v) HCl and 20% (v/v) H 2 O 2 . This converted the Se(IV)-APDC into free Se(IV), which was back extracted into an aqueous phase at the second cloud point extraction stage. This aqueous phase was analyzed directly by HG-AFS. Optimization of the experimental conditions gave a limit of detection of 0.023μgL -1 with an enhancement factor of 11.8 when 50mL of sample solution was preconcentrated to 3mL. The relative standard deviation was 4.04% (c=6.0μgL -1 , n=10). The proposed method was applied to determine the Se contents in twelve food samples with satisfactory recoveries of 95.6-105.2%. Copyright © 2016 Elsevier Ltd. All rights reserved.

Radiofrequency catheter ablation of atrial fibrillation: Electrical modification suggesting transmurality is faster achieved with remote magnetic catheter in comparison with contact force use.

PubMed

Bun, Sok-Sithikun; Ayari, Anis; Latcu, Decebal Gabriel; Errahmouni, Abdelkarim; Saoudi, Nadir

2017-07-01

Remote magnetic navigation (RMN) and contact force (CF) sensing catheters are available technologies for radiofrequency (RF) catheter ablation of atrial fibrillation (AF). Our purpose was to compare time to electrogram (EGM) modification suggesting transmural lesions between RMN and CF-guided AF ablation. A total of 1,008 RF applications were analyzed in 21 patients undergoing RMN (n = 11) or CF-guided ablation (n = 10) for paroxysmal AF. All procedures were performed in sinus rhythm during general anesthesia. Time to EGM modification was measured until transmurality criteria were fulfilled: (1) complete disappearance of R if initial QR morphology; (2) diminution > 75% of R if initial QRS morphology; (3) complete disappearance of R' of initial RSR' morphology. Impedance drop as well as force time integral (FTI) were also assessed for each application. Mean CF at the beginning of each RF application in the CF group was 11 ± 2 g and mean FTI per application was 488 ± 163 gs. Time to EGM modification was significantly shorter in the RMN group (4.52 ± 0.1 seconds vs. 5.6 ± 0.09 seconds; P < 0.00001). There was no significant difference between other procedural parameters. Remote magnetic AF ablation is associated with faster EGM modification suggesting transmurality than optimized CF and FTI-guided catheter ablation. © 2017 Wiley Periodicals, Inc.

Use of oral anticoagulants in African-American and Caucasian patients with atrial fibrillation: is there a treatment disparity?

PubMed Central

Akinboboye, Olakunle

2015-01-01

Atrial fibrillation (AF) is a very common cardiac arrhythmia, and its prevalence is increasing along with aging in the developed world. This review discusses racial differences in the epidemiology and treatment of AF between African-American and Caucasian patients. Additionally, the effect of race on warfarin and novel oral anticoagulant use is discussed, as well as the role that physicians and patients play in achieving optimal treatment outcomes. Despite having a lower prevalence of AF compared with Caucasians, African-Americans suffer disproportionately from stroke and its sequelae. The possible reasons for this paradox include poorer access to health care, lower health literacy, and a higher prevalence of other stroke-risk factors among African-Americans. Consequently, it is important for providers to evaluate the effects of race, health literacy, access to health care, and cultural barriers on the use of anticoagulation in the management of AF. Warfarin-dose requirements vary across racial groups, with African-American patients requiring a higher dose than Caucasians to maintain a therapeutic international normalized ratio; the novel oral anticoagulants (dabigatran, rivaroxaban, and apixaban) seem to differ in this regard, although data are currently limited. Minority racial groups are not proportionally represented in either real-world studies or clinical trials, but as more information becomes available and other social issues are addressed, the treatment disparities between African-American and Caucasian patients should decrease. PMID:26056467

Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation

PubMed Central

Camm, A. John; Pinto, Fausto J.; Hankey, Graeme J.; Andreotti, Felicita; Hobbs, F.D. Richard

2015-01-01

Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers. PMID:26116685

European Society of Cardiology smartphone and tablet applications for patients with atrial fibrillation and their health care providers

PubMed Central

Kotecha, Dipak; Chua, Winnie W L; Fabritz, Larissa; Hendriks, Jeroen; Casadei, Barbara; Schotten, Ulrich; Vardas, Panos; Heidbuchel, Hein; Dean, Veronica; Kirchhof, Paulus

2018-01-01

Abstract We are in the midst of a digital revolution in health care, although the application of new and useful technology in routine clinical practice is variable. The Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly (CATCH ME) Consortium, in collaboration with the European Society of Cardiology (ESC), has funded the creation of two applications (apps) in atrial fibrillation (AF) for use in smartphones and tablets. The patient app aims to enhance patient education, improve communication between patients and health care professionals, and encourage active patient involvement in the management of their condition. The health care professional app is designed as an interactive management tool incorporating the new ESC Practice Guidelines on AF and supported by the European Heart Rhythm Association (EHRA), with the aim of improving best practice approaches for the care of patients with AF. Both stand-alone apps are now freely available for Android and iOS devices though the Google Play, Amazon, and Apple stores. In this article, we outline the rationale for the design and implementation of these apps. Our objective is to demonstrate the value of integrating novel digital technology into clinical practice, with the potential for patient engagement, optimization of pharmacological and interventional therapy in AF, and ultimately to improve patient outcomes. PMID:29040548

Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2

PubMed Central

Diener, Hans-Christoph; Aisenberg, James; Ansell, Jack; Atar, Dan; Breithardt, Günter; Eikelboom, John; Ezekowitz, Michael D.; Granger, Christopher B.; Halperin, Jonathan L.; Hohnloser, Stefan H.; Hylek, Elaine M.; Kirchhof, Paulus; Lane, Deirdre A.; Verheugt, Freek W.A.; Veltkamp, Roland; Lip, Gregory Y.H.

2017-01-01

The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In addition, we discuss the timing of initiation of anticoagulation. In the second of a two-part review, we discuss the use of NOAC for stroke prevention in the following subgroups of patients with AF: (vii) secondary stroke prevention in patients after stroke or transient ischaemic attack (TIA), (viii) patients with acute stroke requiring thrombolysis or thrombectomy, (ix) those initiating or restarting OAC treatment after stroke or TIA, (x) those with renal impairment on dialysis, (xi) the elderly, (xii) those at high risk of gastrointestinal bleeding, and (xiii) those with hypertension. In addition, we discuss adherence and compliance. Finally, we present a summary of treatment suggestions. In specific subgroups of patients with AF, evidence supports the use of particular NOACs and/or particular doses of anticoagulant. The appropriate choice of treatment for these subgroups will help to promote optimal clinical outcomes. PMID:26848150

Contributions to accelerating atmospheric CO2 growth from economic activity, carbon intensity, and efficiency of natural sinks.

PubMed

Canadell, Josep G; Le Quéré, Corinne; Raupach, Michael R; Field, Christopher B; Buitenhuis, Erik T; Ciais, Philippe; Conway, Thomas J; Gillett, Nathan P; Houghton, R A; Marland, Gregg

2007-11-20

The growth rate of atmospheric carbon dioxide (CO(2)), the largest human contributor to human-induced climate change, is increasing rapidly. Three processes contribute to this rapid increase. Two of these processes concern emissions. Recent growth of the world economy combined with an increase in its carbon intensity have led to rapid growth in fossil fuel CO(2) emissions since 2000: comparing the 1990s with 2000-2006, the emissions growth rate increased from 1.3% to 3.3% y(-1). The third process is indicated by increasing evidence (P = 0.89) for a long-term (50-year) increase in the airborne fraction (AF) of CO(2) emissions, implying a decline in the efficiency of CO(2) sinks on land and oceans in absorbing anthropogenic emissions. Since 2000, the contributions of these three factors to the increase in the atmospheric CO(2) growth rate have been approximately 65 +/- 16% from increasing global economic activity, 17 +/- 6% from the increasing carbon intensity of the global economy, and 18 +/- 15% from the increase in AF. An increasing AF is consistent with results of climate-carbon cycle models, but the magnitude of the observed signal appears larger than that estimated by models. All of these changes characterize a carbon cycle that is generating stronger-than-expected and sooner-than-expected climate forcing.

Contributions to accelerating atmospheric CO2 growth from economic activity, carbon intensity, and efficiency of natural sinks

PubMed Central

Canadell, Josep G.; Le Quéré, Corinne; Raupach, Michael R.; Field, Christopher B.; Buitenhuis, Erik T.; Ciais, Philippe; Conway, Thomas J.; Gillett, Nathan P.; Houghton, R. A.; Marland, Gregg

2007-01-01

The growth rate of atmospheric carbon dioxide (CO2), the largest human contributor to human-induced climate change, is increasing rapidly. Three processes contribute to this rapid increase. Two of these processes concern emissions. Recent growth of the world economy combined with an increase in its carbon intensity have led to rapid growth in fossil fuel CO2 emissions since 2000: comparing the 1990s with 2000–2006, the emissions growth rate increased from 1.3% to 3.3% y−1. The third process is indicated by increasing evidence (P = 0.89) for a long-term (50-year) increase in the airborne fraction (AF) of CO2 emissions, implying a decline in the efficiency of CO2 sinks on land and oceans in absorbing anthropogenic emissions. Since 2000, the contributions of these three factors to the increase in the atmospheric CO2 growth rate have been ≈65 ± 16% from increasing global economic activity, 17 ± 6% from the increasing carbon intensity of the global economy, and 18 ± 15% from the increase in AF. An increasing AF is consistent with results of climate–carbon cycle models, but the magnitude of the observed signal appears larger than that estimated by models. All of these changes characterize a carbon cycle that is generating stronger-than-expected and sooner-than-expected climate forcing. PMID:17962418

Implantable cardioverter defibrillator does not cure the heart.

PubMed

Sławuta, Agnieszka; Boczar, Krzysztof; Ząbek, Andrzej; Gajek, Jacek; Lelakowski, Jacek; Vijayaraman, Pugazhendhi; Małecka, Barbara

2018-01-23

A man with non-ischemic cardiomyopathy, EF 22%, permanent AF and ICD was admitted for elective device replacement. The need for the optimization of the ventricular rate and avoidance of right ventricular pacing made it necessary to up-grade the existing pacing system using direct His bundle pacing and dual chamber ICD. This enabled the regularization of ventricular rate, avoiding the RV pacing and optimize the beta-blocker dose. The one month follow-up already showed reduction in left ventricle diameter, improvement in ejection fraction, NYHA class decrease to II. The His bundle pacing enabled the optimal treatment of the patient resulting in excellent clinical improvement.

Novel robotic catheter manipulation system integrated with remote magnetic navigation for fully remote ablation of atrial tachyarrhythmias: a two-centre evaluation.

PubMed

Nölker, Georg; Gutleben, Klaus-Jürgen; Muntean, Bogdan; Vogt, Jürgen; Horstkotte, Dieter; Dabiri Abkenari, Lara; Akca, Ferdi; Szili-Torok, Tamas

2012-12-01

Studies have shown that remote magnetic navigation is safe and effective for ablation of atrial arrhythmias, although optimal outcomes often require frequent manual manipulation of a circular mapping catheter. The Vdrive robotic system ('Vdrive') was designed for remote navigation of circular mapping catheters to enable a fully remote procedure. This study details the first human clinical experience with remote circular catheter manipulation in the left atrium. This was a prospective, multi-centre, non-randomized consecutive case series that included patients presenting for catheter ablation of left atrial arrhythmias. Remote systems were used exclusively to manipulate both the circular mapping catheter and the ablation catheter. Patients were followed through hospital discharge. Ninety-four patients were included in the study, including 23 with paroxysmal atrial fibrillation (AF), 48 with persistent AF, and 15 suffering from atrial tachycardias. The population was predominately male (77%) with a mean age of 60.5 ± 11.7 years. The Vdrive was used for remote navigation between veins, creation of chamber maps, and gap identification with segmental isolation. The intended acute clinical endpoints were achieved in 100% of patients. Mean case time was 225.9 ± 70.5 min. Three patients (3.2%) crossed over to manual circular mapping catheter navigation. There were no adverse events related to the use of the remote manipulation system. The results of this study demonstrate that remote manipulation of a circular mapping catheter in the ablation of atrial arrhythmias is feasible and safe. Prospective randomized studies are needed to prove efficiency improvements over manual techniques.

A new method for quasi-reagent-free biomonitoring of mercury in human urine.

PubMed

Schlathauer, Maria; Reitsam, Verena; Schierl, Rudolf; Leopold, Kerstin

2017-05-01

A novel analytical method for sampling and extraction of mercury (Hg) from human urine is presented in this work. The method is based on selective accumulation and separation of Hg from fresh urine sample onto active nanogold-coated silica material by highly efficient solid-phase extraction. After thermal desorption of Hg from the extractant, detection is performed by atomic fluorescence spectrometry (AFS). The feasibility and validity of the optimized, quasi-reagent-free approach was confirmed by recovery experiments in spiked real urine (recovery rate 96.13 ± 5.34%) and by comparison of found Hg concentrations in real urine samples - originating from occupationally exposed persons - with values obtained from reference methods cold vapor - atomic absorption spectrometry (CVAAS) and cold vapor - atomic fluorescence spectrometry (CV-AFS). A very good agreement of the found values reveals the validity of the proposed approach. The limit of detection (LOD) was found to be as low as 0.004 μg Hg L -1 and a high reproducibility with a relative standard deviations ≤4.2% (n = 6) is given. Moreover, storage of the samples for up to one week at an ambient temperature of 30 °C reveals no analyte losses or contamination. In conclusion, the proposed method enables easy-to-handle on-site extraction of total Hg from human urine ensuring at the same time reagent-free sample stabilization, providing quick and safe sampling, which can be performed by untrained persons. Copyright © 2017 Elsevier B.V. All rights reserved.

Antithrombotic Therapy for Atrial Fibrillation

PubMed Central

You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.

2012-01-01

Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach. PMID:22315271

Transesophageal echocardiography (TEE) in atrial fibrillation.

PubMed

Thamilarasan, M; Klein, A L

2000-11-01

Transesophageal echocardiography has given new insight into the pathogenesis of the thromboembolic sequelae of AF and expanded the available therapeutic options. Studies to date indicate that TEE-guided cardioversion is a safe and reasonable approach when the clinical situation warrants prompt restoration of sinus rhythm. Whether widespread use of this strategy offers further benefit remains to be established, although there are theoretical advantages to such an approach. The potential for earlier cardioversion using a TEE-guided approach may facilitate the achievement and maintenance of sinus rhythm. In the long term, earlier restoration of sinus rhythm prevents adverse atrial remodeling, lowers embolic risk, and may improve cardiac performance and functional status. Thromboembolic sequelae (either cardioversion-related or as a result of chronic AF) remain the most devastating complications of AF. Every attempt to minimize this risk should be pursued aggressively. Information gathered from TEE has helped to elucidate the mechanisms responsible for postcardioversion embolism and has emphasized the importance of anticoagulation during and after the restoration of sinus rhythm. TEE also has the potential to further risk stratify patients with AF. Ultimately, a subset of patients may be identified who require more intense anticoagulation (i.e., those with dense SEC or thrombus, or persistent thrombus after prolonged anticoagulation) or in whom cardioversion may be deferred entirely. Likewise, TEE also may prove to be useful in identifying patients with a low-clinical risk profile who may be treated with aspirin alone and patients in whom warfarin may be superior. The results of the ACUTE study should help to further define the role of TEE in the management of patients with AF. Additional clinical studies are needed to address some of the issues that have been raised and to allow for optimal use of TEE in this patient population.

Randomized ablation strategies for the treatment of persistent atrial fibrillation: RASTA study.

PubMed

Dixit, Sanjay; Marchlinski, Francis E; Lin, David; Callans, David J; Bala, Rupa; Riley, Michael P; Garcia, Fermin C; Hutchinson, Mathew D; Ratcliffe, Sarah J; Cooper, Joshua M; Verdino, Ralph J; Patel, Vickas V; Zado, Erica S; Cash, Nancy R; Killian, Tony; Tomson, Todd T; Gerstenfeld, Edward P

2012-04-01

The single-procedure efficacy of pulmonary vein isolation (PVI) is less than optimal in patients with persistent atrial fibrillation (AF). Adjunctive techniques have been developed to enhance single-procedure efficacy in these patients. We conducted a study to compare 3 ablation strategies in patients with persistent AF. Subjects were randomized as follows: arm 1, PVI + ablation of non-PV triggers identified using a stimulation protocol (standard approach); arm 2, standard approach + empirical ablation at common non-PV AF trigger sites (mitral annulus, fossa ovalis, eustachian ridge, crista terminalis, and superior vena cava); or arm 3, standard approach + ablation of left atrial complex fractionated electrogram sites. Patients were seen at 6 weeks, 6 months, and 1 year; transtelephonic monitoring was performed at each visit. Antiarrhythmic drugs were discontinued at 3 to 6 months. The primary study end point was freedom from atrial arrhythmias off antiarrhythmic drugs at 1 year after a single-ablation procedure. A total of 156 patients (aged 59±9 years; 136 males; AF duration, 47±50 months) participated (arm 1, 55 patients; arm 2, 50 patients; arm 3, 51 patients). Procedural outcomes (procedure, fluoroscopy, and PVI times) were comparable between the 3 arms. More lesions were required to target non-PV trigger sites than a complex fractionated electrogram (33±9 versus 22±9; P<0.001). The primary end point was achieved in 71 patients and was worse in arm 3 (29%) compared with arm 1 (49%; P=0.04) and arm 2 (58%; P=0.004). These data suggest that additional substrate modification beyond PVI does not improve single-procedure efficacy in patients with persistent AF. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00379301.

Intraoperative Inducibility of Atrial Fibrillation Does Not Predict Early Postoperative Atrial Fibrillation.

PubMed

Lanters, Eva A H; Teuwen, Christophe P; Yaksh, Ameeta; Kik, Charles; van der Does, Lisette J M E; Mouws, Elisabeth M J P; Knops, Paul; van Groningen, Nicole J; Hokken, Thijmen; Bogers, Ad J J C; de Groot, Natasja M S

2018-03-10

Early postoperative atrial fibrillation (EPoAF) is associated with thromboembolic events, prolonged hospitalization, and development of late PoAF (LPoAF). It is, however, unknown if EPoAF can be predicted by intraoperative AF inducibility. The aims of this study are therefore to explore (1) the value of intraoperative inducibility of AF for development of both EPoAF and LPoAF and (2) the predictive value of de novo EPoAF for recurrence of LPoAF. Patients (N=496, 75% male) undergoing cardiothoracic surgery for coronary and/or valvular heart disease were included. AF induction was attempted by atrial pacing, before extracorporeal circulation. All patients were on continuous rhythm monitoring until discharge to detect EPoAF. During a follow-up period of 2 years, LPoAF was detected by ECGs and Holter recordings. Sustained AF was inducible in 56% of patients. There was no difference in patients with or without AF before surgery ( P =0.159), or between different types of surgery ( P =0.687). In patients without a history of AF, incidence of EPoAF and LPoAF was 37% and 2%, respectively. EPoAF recurred in 58% patients with preoperative AF, 53% developed LPoAF. There were no correlations between intraoperative inducibility and EPoAF or LPoAF ( P >0.05). EPoAF was not correlated with LPoAF in patients without a history of AF ( P =0.116), in contrast to patients with AF before surgery ( P <0.001). Intraoperative AF inducibility does not predict development of either EPoAF or LPoAF. In patients with AF before surgery, EPoAF is correlated with LPoAF recurrences. This correlation is absent in patients without AF before surgery. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Factors Determining the Efficiency of Porcine Somatic Cell Nuclear Transfer: Data Analysis with Over 200,000 Reconstructed Embryos

PubMed Central

Liu, Tianbin; Dou, Hongwei; Xiang, Xi; Li, Yong; Pang, Xinzhi; Zhang, Yijie; Chen, Yu; Luan, Jing; Xu, Ying; Yang, Zhenzhen; Yang, Wenxian; Liu, Huan; Li, Feida; Wang, Hui; Yang, Huanming; Bolund, Lars; Vajta, Gabor

2015-01-01

Abstract Data analysis in somatic cell nuclear transfer (SCNT) research is usually limited to several hundreds or thousands of reconstructed embryos. Here, we report mass results obtained with an established and consistent porcine SCNT system (handmade cloning [HMC]). During the experimental period, 228,230 reconstructed embryos and 82,969 blastocysts were produced. After being transferred into 656 recipients, 1070 piglets were obtained. First, the effects of different types of donor cells, including fetal fibroblasts (FFs), adult fibroblasts (AFs), adult preadipocytes (APs), and adult blood mesenchymal (BM) cells, were investigated on the further in vitro and in vivo development. Compared to adult donor cells (AFs, APs, BM cells, respectively), FF cells resulted in a lower blastocyst/reconstructed embryo rate (30.38% vs. 37.94%, 34.65%, and 34.87%, respectively), but a higher overall efficiency on the number of piglets born alive per total blastocysts transferred (1.50% vs. 0.86%, 1.03%, and 0.91%, respectively) and a lower rate of developmental abnormalities (10.87% vs. 56.57%, 24.39%, and 51.85%, respectively). Second, recloning was performed with cloned adult fibroblasts (CAFs) and cloned fetal fibroblasts (CFFs). When CAFs were used as the nuclear donor, fewer developmental abnormalities and higher overall efficiency were observed compared to AFs (56.57% vs. 28.13% and 0.86% vs. 1.59%, respectively). However, CFFs had an opposite effect on these parameters when compared with CAFs (94.12% vs. 10.87% and 0.31% vs. 1.50%, respectively). Third, effects of genetic modification on the efficiency of SCNT were investigated with transgenic fetal fibroblasts (TFFs) and gene knockout fetal fibroblasts (KOFFs). Genetic modification of FFs increased developmental abnormalities (38.96% and 25.24% vs. 10.87% for KOFFs, TFFs, and FFs, respectively). KOFFs resulted in lower overall efficiency compared to TFFs and FFs (0.68% vs. 1.62% and 1.50%, respectively). In conclusion, this is the first report of large-scale analysis of porcine cell nuclear transfer that provides important data for potential industrialization of HMC technology. PMID:26655078

Spin-Hall Switching of In-plane Exchange Biased Heterostructures

NASA Astrophysics Data System (ADS)

Mann, Maxwell; Beach, Geoffrey

The spin Hall effect (SHE) in heavy-metal/ferromagnet bilayers generates a pure transverse spin current from in-plane charge current, allowing for efficient switching of spintronic devices with perpendicular magnetic anisotropy. Here, we demonstrate that an AFM deposited adjacent to the FM establishes a large in-plane exchange bias field, allowing operation at zero HIP. We sputtered Pt(3nm)/Co(0.9nm)/Ni80Co20O(tAF) stacks at room-temperature in an in-plane magnetic field of 3 kOe. The current-induced effective field was estimated in Hall cross devices by measuring the variation of the out-of-plane switching field as a function of JIP and HIP. The spin torque efficiency, dHSL/dJIP, is measured versus HIP for a sample with tAF =30 nm, and for a control in which NiCoO is replaced by TaOx. In the latter, dHSL/dJIP varied linearly with HIP. In the former, dHSL/dJIP varied nonlinearly with HIP and exhibited an offset indicating nonzero spin torque efficiency with zero HIP. The magnitude of HEB was 600 Oe in-plane.

The non-equilibrium allele frequency spectrum in a Poisson random field framework.

PubMed

Kaj, Ingemar; Mugal, Carina F

2016-10-01

In population genetic studies, the allele frequency spectrum (AFS) efficiently summarizes genome-wide polymorphism data and shapes a variety of allele frequency-based summary statistics. While existing theory typically features equilibrium conditions, emerging methodology requires an analytical understanding of the build-up of the allele frequencies over time. In this work, we use the framework of Poisson random fields to derive new representations of the non-equilibrium AFS for the case of a Wright-Fisher population model with selection. In our approach, the AFS is a scaling-limit of the expectation of a Poisson stochastic integral and the representation of the non-equilibrium AFS arises in terms of a fixation time probability distribution. The known duality between the Wright-Fisher diffusion process and a birth and death process generalizing Kingman's coalescent yields an additional representation. The results carry over to the setting of a random sample drawn from the population and provide the non-equilibrium behavior of sample statistics. Our findings are consistent with and extend a previous approach where the non-equilibrium AFS solves a partial differential forward equation with a non-traditional boundary condition. Moreover, we provide a bridge to previous coalescent-based work, and hence tie several frameworks together. Since frequency-based summary statistics are widely used in population genetics, for example, to identify candidate loci of adaptive evolution, to infer the demographic history of a population, or to improve our understanding of the underlying mechanics of speciation events, the presented results are potentially useful for a broad range of topics. Copyright © 2016 Elsevier Inc. All rights reserved.

Studies on the mechanism of electron bifurcation catalyzed by electron transferring flavoprotein (Etf) and butyryl-CoA dehydrogenase (Bcd) of Acidaminococcus fermentans.

PubMed

Chowdhury, Nilanjan Pal; Mowafy, Amr M; Demmer, Julius K; Upadhyay, Vikrant; Koelzer, Sebastian; Jayamani, Elamparithi; Kahnt, Joerg; Hornung, Marco; Demmer, Ulrike; Ermler, Ulrich; Buckel, Wolfgang

2014-02-21

Electron bifurcation is a fundamental strategy of energy coupling originally discovered in the Q-cycle of many organisms. Recently a flavin-based electron bifurcation has been detected in anaerobes, first in clostridia and later in acetogens and methanogens. It enables anaerobic bacteria and archaea to reduce the low-potential [4Fe-4S] clusters of ferredoxin, which increases the efficiency of the substrate level and electron transport phosphorylations. Here we characterize the bifurcating electron transferring flavoprotein (EtfAf) and butyryl-CoA dehydrogenase (BcdAf) of Acidaminococcus fermentans, which couple the exergonic reduction of crotonyl-CoA to butyryl-CoA to the endergonic reduction of ferredoxin both with NADH. EtfAf contains one FAD (α-FAD) in subunit α and a second FAD (β-FAD) in subunit β. The distance between the two isoalloxazine rings is 18 Å. The EtfAf-NAD(+) complex structure revealed β-FAD as acceptor of the hydride of NADH. The formed β-FADH(-) is considered as the bifurcating electron donor. As a result of a domain movement, α-FAD is able to approach β-FADH(-) by about 4 Å and to take up one electron yielding a stable anionic semiquinone, α-FAD, which donates this electron further to Dh-FAD of BcdAf after a second domain movement. The remaining non-stabilized neutral semiquinone, β-FADH(•), immediately reduces ferredoxin. Repetition of this process affords a second reduced ferredoxin and Dh-FADH(-) that converts crotonyl-CoA to butyryl-CoA.

Studies on the Mechanism of Electron Bifurcation Catalyzed by Electron Transferring Flavoprotein (Etf) and Butyryl-CoA Dehydrogenase (Bcd) of Acidaminococcus fermentans*

PubMed Central

Chowdhury, Nilanjan Pal; Mowafy, Amr M.; Demmer, Julius K.; Upadhyay, Vikrant; Koelzer, Sebastian; Jayamani, Elamparithi; Kahnt, Joerg; Hornung, Marco; Demmer, Ulrike; Ermler, Ulrich; Buckel, Wolfgang

2014-01-01

Electron bifurcation is a fundamental strategy of energy coupling originally discovered in the Q-cycle of many organisms. Recently a flavin-based electron bifurcation has been detected in anaerobes, first in clostridia and later in acetogens and methanogens. It enables anaerobic bacteria and archaea to reduce the low-potential [4Fe-4S] clusters of ferredoxin, which increases the efficiency of the substrate level and electron transport phosphorylations. Here we characterize the bifurcating electron transferring flavoprotein (EtfAf) and butyryl-CoA dehydrogenase (BcdAf) of Acidaminococcus fermentans, which couple the exergonic reduction of crotonyl-CoA to butyryl-CoA to the endergonic reduction of ferredoxin both with NADH. EtfAf contains one FAD (α-FAD) in subunit α and a second FAD (β-FAD) in subunit β. The distance between the two isoalloxazine rings is 18 Å. The EtfAf-NAD+ complex structure revealed β-FAD as acceptor of the hydride of NADH. The formed β-FADH− is considered as the bifurcating electron donor. As a result of a domain movement, α-FAD is able to approach β-FADH− by about 4 Å and to take up one electron yielding a stable anionic semiquinone, α-FAD⨪, which donates this electron further to Dh-FAD of BcdAf after a second domain movement. The remaining non-stabilized neutral semiquinone, β-FADH•, immediately reduces ferredoxin. Repetition of this process affords a second reduced ferredoxin and Dh-FADH− that converts crotonyl-CoA to butyryl-CoA. PMID:24379410

A Proposal to Perform New Theoretical and Experimental Research on HumanEfficiency Through Developments Within Systems Factorial Technology (SFT)

DTIC Science & Technology

2017-05-26

Mathematical psychology. In APA Handbook of Research Methods in Psychology, Vol. 2: Research Designs: Quantitative , Qualitative, DISTRIBUTION A: Distribution...AFRL-AFOSR-VA-TR-2017-0108 A Proposal to Perform New Theoretical and Experimental Research on Human Efficiency Through Developments Within Systems...release. AF Office Of Scientific Research (AFOSR)/ RTA2 Arlington, Virginia 22203 Air Force Research Laboratory Air Force Materiel Command a. REPORT

Human Cardiomyocytes Prior to Birth by Integration-Free Reprogramming of Amniotic Fluid Cells

PubMed Central

Jiang, Guihua; Herron, Todd J.; Di Bernardo, Julie; Walker, Kendal A.; O’Shea, K. Sue

2016-01-01

The establishment of an abundant source of autologous cardiac progenitor cells would represent a major advance toward eventual clinical translation of regenerative medicine strategies in children with prenatally diagnosed congenital heart disease. In support of this concept, we sought to examine whether functional, transgene-free human cardiomyocytes (CMs) with potential for patient-specific and autologous applications could be reliably generated following routine amniocentesis. Under institutional review board approval, amniotic fluid specimens (8–10 ml) at 20 weeks gestation were expanded and reprogrammed toward pluripotency using nonintegrating Sendai virus (SeV) expressing OCT4, SOX2, cMYC, and KLF4. Following exposure of these induced pluripotent stem cells to cardiogenic differentiation conditions, spontaneously beating amniotic fluid-derived cardiomyocytes (AF-CMs) were successfully generated with high efficiency. After 6 weeks, quantitative gene expression revealed a mixed population of differentiated atrial, ventricular, and nodal AF-CMs, as demonstrated by upregulation of multiple cardiac markers, including MYH6, MYL7, TNNT2, TTN, and HCN4, which were comparable to levels expressed by neonatal dermal fibroblast-derived CM controls. AF-CMs had a normal karyotype and demonstrated loss of NANOG, OCT4, and the SeV transgene. Functional characterization of SIRPA+ AF-CMs showed a higher spontaneous beat frequency in comparison with dermal fibroblast controls but revealed normal calcium transients and appropriate chronotropic responses after β-adrenergic agonist stimulation. Taken together, these data suggest that somatic cells present within human amniotic fluid can be used to generate a highly scalable source of functional, transgene-free, autologous CMs before a child is born. This approach may be ideally suited for patients with prenatally diagnosed cardiac anomalies. Significance This study presents transgene-free human amniotic fluid-derived cardiomyocytes (AF-CMs) for potential therapy in tissue engineering and regenerative medicine applications. Using 8–10 ml of amniotic fluid harvested at 20 weeks gestation from normal pregnancies, a mixed population of atrial, ventricular, and nodal AF-CMs were reliably generated after Sendai virus reprogramming toward pluripotency. Functional characterization of purified populations of beating AF-CMs revealed normal calcium transients and appropriate chronotropic responses after β-adrenergic agonist stimulation in comparison with dermal fibroblast controls. Because AF-CMs can be generated in fewer than 16 weeks, this approach may be ideally suited for eventual clinical translation at birth in children with prenatally diagnosed cardiac anomalies. PMID:27465073

Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation.

PubMed

Camm, A John; Pinto, Fausto J; Hankey, Graeme J; Andreotti, Felicita; Hobbs, F D Richard

2015-07-01

Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Fitting the right non-vitamin K antagonist oral anticoagulant to the right patient with non-valvular atrial fibrillation: an evidence-based choice.

PubMed

Li, Yan-Guang; Pastori, Daniele; Lip, Gregory Y H

2018-06-01

Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with an increased risk of ischemic stroke (IS) and systemic embolism (SE). Stroke prevention is a key element for the overall management of AF patients. The non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, apixaban and edoxaban, are at least as effective as warfarin in reducing IS/SE with a lower rate of major bleeding. Various analyses from the large Phase III randomized trials demonstrated different efficacy and safety of NOACs in specific subgroups of patients. The randomized trials are supplemented by effectiveness and safety data from real-world observational cohorts following the availability of these drugs for use in everyday clinical practice. Given the clinical heterogeneity of AF patients, the available data from trials and real-world studies allow us to fit the right NOAC to the particular patient's characteristics, with the aim of optimizing outcomes for the individual patient. This review article aims to provide a summary of the evidence on the performance of NOACs in AF patients with specific clinical characteristics. Evidence-based suggestions are presented to provide a simple and viable strategy for clinicians for the choice of a particular NOAC. KEY MESSAGE Given the different performance of the new-oral anticoagulants in patients with the different clinical situation, evidence-based choice of fitting the right new-oral anticoagulants to the patients is provided in this review article.

[Stroke prevention in atrial fibrillation in Germany. Situational analysis of treatment reality based on retrospective data].

PubMed

Mergenthaler, Ulrike; Kostev, Karel; Moosmang, Sven; Thate-Waschke, Inga-Marion; Haas, Sylvia

2017-12-01

Guideline-based, risk-adjusted therapy with anticoagulants reduce thromboembolic stroke risk in patients with atrial fibrillation (AF). This study analyzed use of oral anticoagulation in German AF-patients. Access to anonymized patient records was made via IMS Health Disease Analyzer database (sample size: 113,619 patients with ICD-10 Code I48.-; observation period: 11/2010-10/2013). Results were subsequently extrapolated to all general practitioners' (GPs) and cardiological practices in Germany. In 2011 12-month AF-prevalence was extrapolated to 2.1 million patients (first diagnosed: n = 537.548). In 2012 AF-prevalence gone up to 2.2 million cases (first diagnosed: n = 537.548) and in 2013 to 2.8 million (first diagnosed: n = 636.571). Commonly prescribed oral anticoagulants (OAC) were vitamin K antagonists (VKA). Unstable INR setting, private health insurance, hospital admission, heart failure or hypertension increased probability of change from VKA to non-vitamin K antagonist oral anticoagulants (NOAC). 17.3-36.5% of patients with CHA 2 DS 2 -VASc-score ≥ 2 did not receive any thromboembolism prophylaxis; 38.5% with CHA 2 DS 2 -VASc-score = 0 received unnecessarily OACs. For 2013 a potential of 29.749 ischemic strokes in GP practices was calculated, which possibly can be avoided by thromboembolism prophylaxis according to guidelines. Risk-based anticoagulation showed requirements for optimization. Use of OACs, according to guideline recommendations, would minimize bleeding risks, reduce ischemic strokes and could release resources.

European Society of Cardiology smartphone and tablet applications for patients with atrial fibrillation and their health care providers.

PubMed

Kotecha, Dipak; Chua, Winnie W L; Fabritz, Larissa; Hendriks, Jeroen; Casadei, Barbara; Schotten, Ulrich; Vardas, Panos; Heidbuchel, Hein; Dean, Veronica; Kirchhof, Paulus

2018-02-01

We are in the midst of a digital revolution in health care, although the application of new and useful technology in routine clinical practice is variable. The Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly (CATCH ME) Consortium, in collaboration with the European Society of Cardiology (ESC), has funded the creation of two applications (apps) in atrial fibrillation (AF) for use in smartphones and tablets. The patient app aims to enhance patient education, improve communication between patients and health care professionals, and encourage active patient involvement in the management of their condition. The health care professional app is designed as an interactive management tool incorporating the new ESC Practice Guidelines on AF and supported by the European Heart Rhythm Association (EHRA), with the aim of improving best practice approaches for the care of patients with AF. Both stand-alone apps are now freely available for Android and iOS devices though the Google Play, Amazon, and Apple stores. In this article, we outline the rationale for the design and implementation of these apps. Our objective is to demonstrate the value of integrating novel digital technology into clinical practice, with the potential for patient engagement, optimization of pharmacological and interventional therapy in AF, and ultimately to improve patient outcomes. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.

Performance of handheld electrocardiogram devices to detect atrial fibrillation in a cardiology and geriatric ward setting.

PubMed

Desteghe, Lien; Raymaekers, Zina; Lutin, Mark; Vijgen, Johan; Dilling-Boer, Dagmara; Koopman, Pieter; Schurmans, Joris; Vanduynhoven, Philippe; Dendale, Paul; Heidbuchel, Hein

2017-01-01

To determine the usability, accuracy, and cost-effectiveness of two handheld single-lead electrocardiogram (ECG) devices for atrial fibrillation (AF) screening in a hospital population with an increased risk for AF. Hospitalized patients (n = 445) at cardiological or geriatric wards were screened for AF by two handheld ECG devices (MyDiagnostick and AliveCor). The performance of the automated algorithm of each device was evaluated against a full 12-lead or 6-lead ECG recording. All ECGs and monitor tracings were also independently reviewed in a blinded fashion by two electrophysiologists. Time investments by nurses and physicians were tracked and used to estimate cost-effectiveness of different screening strategies. Handheld recordings were not possible in 7 and 21.4% of cardiology and geriatric patients, respectively, because they were not able to hold the devices properly. Even after the exclusion of patients with an implanted device, sensitivity and specificity of the automated algorithms were suboptimal (Cardiology: 81.8 and 94.2%, respectively, for MyDiagnostick; 54.5 and 97.5%, respectively, for AliveCor; Geriatrics: 89.5 and 95.7%, respectively, for MyDiagnostick; 78.9 and 97.9%, respectively, for AliveCor). A scenario based on automated AliveCor evaluation in patients without AF history and without an implanted device proved to be the most cost-effective method, with a provider cost to identify one new AF patient of €193 and €82 at cardiology and geriatrics, respectively. The cost to detect one preventable stroke per year would be €7535 and €1916, respectively (based on average CHA 2 DS 2 -VASc of 3.9 ± 2.0 and 5.0 ± 1.5, respectively). Manual interpretation increases sensitivity, but decreases specificity, doubling the cost per detected patient, but remains cheaper than sole 12-lead ECG screening. Using AliveCor or MyDiagnostick handheld recorders requires a structured screening strategy to be effective and cost-effective in a hospital setting. It must exclude patients with implanted devices and known AF, and requires targeted additional 12-lead ECGs to optimize specificity. Under these circumstances, the expenses per diagnosed new AF patient and preventable stroke are reasonable. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Optical probes of symmetry breaking in magnetic and superconducting BaFe2(As1-xPx)2

NASA Astrophysics Data System (ADS)

Orenstein, Joseph

The discovery of iron pnictide superconductors has opened promising new directions in the effort to fully understand the phenomenon of high-Tc, with a focus on the connections between superconductivity, magnetism, and electronic nematicity. The BaFe2(As1-xPx)2 (P:Ba122) system in particular has received attention because isovalent substitution of As for P generates less disorder than doping on the Fe site. The phase diagram of P:Ba122 is characterized by a line of simultaneous antiferromagnetic (AF) and tetragonal-to-orthorhombic transitions, Ts (x) , that penetrates the superconducting dome at x =0.28, just below optimal doping (xopt = 0.30). In this work, we use spatially-resolved optical polarimetry and photomodulated reflectance to detect linear birefringence and therefore breaking of 4-fold rotational (C4) symmetry. In underdoped (x<0.28) samples, birefringence appears at T>Tsand grows continuously with decreasing T . The birefringence is unidirectional in a large (300 μm x300 μm) field of view, suggesting that C4 breaking in this range of T is caused by residual strain that couples to a diverging nematic susceptibility. Birefringence maps just below Ts (x) show the appearance of domains, indicating the onset of spontaneous symmetry breaking to an AF ground state. Surprisingly, in samples with x>0.28, in which the low T phase is superconducting/ tetragonal rather than AF/orthorhombic, C4 breaking is observed as well, with an abrupt onset and domain formation at 55 K. We tentatively associate these features with a transition to an AF phase induced by residual strain, as previously proposed [H.-H. Kuo et al. Phys. Rev. B86, 134507 (2012)] to account for structure in resistivity vs. T. Time-resolved photomodulation allow us to follow the amplitude of the AF order with time following pulsed photoexcitation. Below Tc the AF order at first weakens , but then strengthens in response to the photoinduced weakening of superconductivity. This complex time evolution is accounted for quantitatively by a model based on the coexistence and competition of AF and superconducting order. We gratefully acknowledge support by the U.S. Department of Energy, Office of Science, Materials Sciences and Engineering Division, and the Gordon and Betty Moore Foundation's EPiQS Initiative through Grant GBMF4537.

Atrial Fibrillation During an Exploration Class Mission

NASA Technical Reports Server (NTRS)

Lipset, Mark A.; Lemery, Jay; Polk, J. D.; Hamilton, Douglas R.

2010-01-01

Background: A long-duration exploration class mission is fraught with numerous medical contingency plans. Herein, we explore the challenges of symptomatic atrial fibrillation (AF) occurring during an exploration class mission. The actions and resources required to ameliorate the situation, including the availability of appropriate pharmaceuticals, monitoring devices, treatment modalities, and communication protocols will be investigated. Challenges of Atrial Fibrillation during an Exploration Mission: Numerous etiologies are responsible for the initiation of AF. On Earth, we have the time and medical resources to evaluate and determine the causative situation for most cases of AF and initiate therapy accordingly. During a long-duration exploration class mission resources will be severely restricted. How is one to determine if new onset AF is due to recent myocardial infarction, pulmonary embolism, fluid overload, thyrotoxicosis, cardiac structural abnormalities, or CO poisoning? Which pharmaceutical therapy should be initiated and what potential side effects can be expected? Should anti-coagulation therapy be initiated? How would one monitor the therapeutic treatment of AF in microgravity? What training would medical officers require, and which communication strategies should be developed to enable the best, safest therapeutic options for treatment of AF during a long-duration exploration class mission? Summary: These questions will be investigated with expert opinion on disease elucidation, efficient pharmacology, therapeutic monitoring, telecommunication strategies, and mission cost parameters with emphasis on atrial fibrillation being just one illustration of the tremendous challenges that face a long-duration exploration mission. The limited crew training time, medical hardware, and drugs manifested to deal with such an event predicate that aggressive primary and secondary prevention strategies be developed to protect a multibillion-dollar asset like the International Space Station or a mission to the Moon or Mars. Learning Objectives: The audience will become familiar with the risks and challenges inherent to developing a therapeutic strategy for the treatment of atrial fibrillation during a long-term exploration class mission.

Size fractionation and size characterization of nanoemulsions of lipid droplets and large unilamellar lipid vesicles by asymmetric-flow field-flow fractionation/multi-angle light scattering and dynamic light scattering.

PubMed

Vezočnik, Valerija; Rebolj, Katja; Sitar, Simona; Ota, Katja; Tušek-Žnidarič, Magda; Štrus, Jasna; Sepčić, Kristina; Pahovnik, David; Maček, Peter; Žagar, Ema

2015-10-30

Asymmetric-flow field-flow fractionation technique coupled to a multi-angle light-scattering detector (AF4-MALS) was used together with dynamic light-scattering (DLS) in batch mode and transmission electron microscopy (TEM) to study the size characteristics of the trioleoylglycerol lipid droplets covered by a monolayer of sphingomyelin and cholesterol, in water phase. These lipid droplet nanoemulsions (LD) were formed by ultrasonication. In parallel, the size characteristics of large unilamellar lipid vesicles (LUV) prepared by extrusion and composed of sphingomyelin and cholesterol were determined. LD and LUV were prepared at two different molar ratios (1/1, 4/1) of sphingomyelin and cholesterol. In AF4-MALS, various cross-flow conditions and mobile phase compositions were tested to optimize the separation of LD or LUV particles. The particle radii, R, as well as the root-mean-square radii, Rrms, of LD and LUV were determined by AF4-MALS, whereas the hydrodynamic radii, Rh, were obtained by DLS. TEM visualization revealed round shape particles of LD and LUV. Copyright © 2015 Elsevier B.V. All rights reserved.

43 CFR 418.38 - Maximum allowable diversion.

Code of Federal Regulations, 2010 CFR

2010-10-01

... water right holder the full water entitlement for irrigable eligible acres and includes distribution... deliveries at farm headgates have been approximately 90 percent of entitlements. This practice is expected to... efficiency target for the examples shown in the Newlands Project Water Budget table would be: 285,243 AF and...

43 CFR 418.38 - Maximum allowable diversion.

Code of Federal Regulations, 2011 CFR

2011-10-01

... water right holder the full water entitlement for irrigable eligible acres and includes distribution... deliveries at farm headgates have been approximately 90 percent of entitlements. This practice is expected to... efficiency target for the examples shown in the Newlands Project Water Budget table would be: 285,243 AF and...

Assessment of left atrial appendage function by transthoracic pulsed Doppler echocardiography: Comparing against transesophageal interrogation and predicting echocardiographic risk factors for stroke.

PubMed

Wai, Shin Hnin; Kyu, Kyu; Galupo, Mary Joyce; Songco, Geronica G; Kong, William K F; Lee, Chi Hang; Yeo, Tiong Cheng; Poh, Kian Keong

2017-10-01

Transesophageal echocardiographic (TEE) findings of left atrial appendage (LAA) thrombus, spontaneous echo contrast (SEC), and LAA dysfunction are established risk factors of cardioembolic stroke. The semi-invasive nature of TEE limits its utility as a routine risk stratification tool. We aim to correlate TEE and transthoracic echocardiography (TTE) pulsed Doppler measurements of LAA flow velocities and use TTE measurements to predict TEE findings. We prospectively measured pulsed Doppler LAA flow velocities in 103 consecutive patients on TEE and TTE. There was a strong correlation between TEE and TTE LAA emptying velocity (LAA E) (r = .88, P < .001) and a moderate correlation between LAA filling velocities (r = .50, P < .001). TTE LAA E predicted the presence of thrombus or SEC independent of atrial fibrillation (AF). To predict the presence of thrombus or SEC, the optimal TTE LAA E cutoff was ≤30 cm/s in all patients (75% sensitive, 90% specific) and ≤31 cm/s in AF patients (80% sensitive, 79% specific). To predict LAA dysfunction (TEE E ≤ 20 cm/s), the optimal TTE LAA E cutoff was ≤27 cm/s (100% sensitive, 89% specific in all patients and 100% sensitive, 74% specific in AF patients). TTE assessment of LAA function is feasible and correlates well with the more invasive TEE method. It predicts the presence of thrombus, SEC, and LAA dysfunction on TEE. TTE LAA assessment has incremental value in thromboembolic risk stratification and should be utilized more frequently. © 2017, Wiley Periodicals, Inc.

Development of a two-step protocol for culture expansion of human annulus fibrosus cells with TGF-β1 and FGF-2.

PubMed

Chou, Po-Hsin; Wang, Shih-Tien; Ma, Hsiao-Li; Liu, Chien-Lin; Chang, Ming-Chau; Lee, Oscar Kuang-Sheng

2016-07-12

Different biologic approaches to treat disc regeneration, including growth factors (GFs) application, are currently under investigation. Human annulus fibrosus (hAF) repair or regeneration is one of the key elements for maintenance and restoration of nucleus pulposus function. However, so far there is no effective treatment for this purpose. The aim of the present study was to investigate the response of hAF cells to different combinations of GFs, and develop a protocol for efficient culture expansion. hAF cells were harvested from degenerated disc tissues during surgical intervertebral disc removal, and hAF cells were expanded in a monolayer. The experiments were categorized based on different protocols with transforming growth factor (TGF-β1) and fibroblast growth factor (FGF-2) culture for 14 days: group 1 had no GFs (control group); group 2 received TGF-β1; group 3 received FGF-2; group 4 received both GFs; and group 5 (two-step) received both GFs for the first 10 days and TGF-β1 only for the next 4 days. Cell proliferation, collagen, and noncollagen extracellular matrix (ECM) production and genes expression were compared among these groups. At days 3, 7 and 10 of cultivation, groups 4 and 5 had significantly more cell numbers and faster cell proliferation rates than groups 1, 2, and 3. At 14 days of cultivation, significantly more cell numbers were observed in groups 3 and 4 than in group 5. The group 4 had the most cell numbers and the fastest proliferation rate at 14 days of cultivation. After normalization for cell numbers, group 5 (two-step) produced the most collagen and noncollagen ECM at 10 and 14 days of cultivation among the five groups. In group 5, ECM gene expression was significantly upregulated. High expression of matrix metalloproteinase-1 was upregulated with FGF-2 on the different days as compared to the other groups. Annulus fibrosus cell phenotypes were only marginally retained under the different protocols based on quantitative polymerase chain reaction results. Taken together, the two-step protocol was the most efficient among these different protocols with the most abundant ECM production after normalization for cell numbers for culture expansion of hAF cells. The protocol may be useful in further cell therapy and tissue engineering approaches for disc regeneration.

How are patients with atrial fibrillation approached and informed about their risk profile and available therapies in Europe? Results of the European Heart Rhythm Association Survey.

PubMed

Potpara, Tatjana S; Pison, Laurent; Larsen, Torben B; Estner, Heidi; Madrid, Antonio; Blomström-Lundqvist, Carina

2015-03-01

This European Heart Rhythm (EHRA) Scientific Initiatives Committee EP Wire Survey aimed at exploring the common practices in approaching patients with atrial fibrillation (AF) and informing them about their risk profiles and available therapies in Europe. In the majority of 53 responding centres, patients were seen by cardiologists (86.8%) or arrhythmologists (64.2%). First- and follow-up visits most commonly lasted 21-30 and 11-20 min (41.5 and 69.8% of centres, respectively). In most centres (80.2%) stroke and bleeding risk had the highest priority for discussion with AF patients; 50.9% of centres had a structured patient education programme for stroke prevention. Individual patient stroke risk was assessed at every visit in 69.2% of the centres; 46.1% of centres had a hospital-based anticoagulation clinic. Information about non-vitamin K oral anticoagulants (NOACs) was communicated to all AF patients eligible for oral anticoagulation (38.5% of centres) or to warfarin-naive/unstable patients (42.3%). Only two centres (3.8%) had a structured NOAC adherence follow-up programme; in eight centres (15.4%) patients were requested to sign the statement they have been informed about the risks of non-adherence to NOAC therapy, and three centres (5.8%) had a patient education programme. Patient preferences were of the highest relevance regarding oral anticoagulation and AF ablation (64.7 and 49.0% of centres, respectively). This EP Wire Survey shows that in Europe considerable amount of time and resources are used in daily clinical practice to inform AF patients about their risk profile and available therapies. However, a diversity of strategies used across the European hospitals was noted, and further research is needed to better define optimal strategies for informing AF patients about their risk profile and treatment options. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

What is needed to implement a web-based audit and feedback intervention with outreach visits to improve care quality: A concept mapping study among cardiac rehabilitation teams.

PubMed

van Engen-Verheul, Mariëtte M; Peek, Niels; Haafkens, Joke A; Joukes, Erik; Vromen, Tom; Jaspers, Monique W M; de Keizer, Nicolette F

2017-01-01

Evidence on successful quality improvement (QI) in health care requires quantitative information from randomized clinical trials (RCTs) on the effectiveness of QI interventions, but also qualitative information from professionals to understand factors influencing QI implementation. Using a structured qualitative approach, concept mapping, this study determines factors identified by cardiac rehabilitation (CR) teams on what is needed to successfully implement a web-based audit and feedback (A&F) intervention with outreach visits to improve the quality of CR care. Participants included 49 CR professionals from 18 Dutch CR centres who had worked with the A&F system during a RCT. In three focus group sessions participants formulated statements on factors needed to implement QI successfully. Subsequently, participants rated all statements for importance and feasibility and grouped them thematically. Multi dimensional scaling was used to produce a final concept map. Forty-two unique statements were formulated and grouped into five thematic clusters in the concept map. The cluster with the highest importance was QI team commitment, followed by organisational readiness, presence of an adequate A&F system, access to an external quality assessor, and future use and functionalities of the A&F system. Concept mapping appeared efficient and useful to understand contextual factors influencing QI implementation as perceived by healthcare teams. While presence of a web-based A&F system and external quality assessor were seen as instrumental for gaining insight into performance and formulating QI actions, QI team commitment and organisational readiness were perceived as essential to actually implement and carry out these actions. These two sociotechnical factors should be taken into account when implementing and evaluating the success of QI implementations in future research. Copyright © 2016. Published by Elsevier Ireland Ltd.

Impact of a Novel Catheter Tracking System on Radiation Exposure during the Procedural Phases of Atrial Fibrillation and Flutter Ablation.

PubMed

Malliet, Nicolas; Andrade, Jason G; Khairy, Paul; Thanh, Hien Kiem Nguyen; Venier, Sandrine; Dubuc, Marc; Dyrda, Katia; Guerra, Peter; Mondésert, Blandine; Rivard, Léna; Tadros, Rafik; Talajic, Mario; Thibault, Bernard; Roy, Denis; Macle, Laurent

2015-07-01

Fluoroscopic guidance is used to position catheters during cardiac ablation. We evaluated the impact of a novel nonfluoroscopic sensor-guided electromagnetic navigation system (MG) on radiation exposure during catheter ablation of atrial fibrillation (AF) or atrial flutter (AFL). A total of 134 consecutive patients referred for ablation of AF (n = 44) or AFL (n = 90) ablation were prospectively enrolled. In one group the MG system was used for nonfluoroscopic catheter positioning, whereas in the conventional group standard fluoroscopy was utilized. Fluoroscopy times were assessed for each stage of procedure and total radiation exposure was quantified. Patient characteristics were similar between the groups. The procedural end point was achieved in all. Median (interquartile range [IQR]) fluoroscopy times were 12.5 minutes (7.6, 17.4) MG group versus 21.5 minutes (15.3, 23.0) conventional group (P < 0.0001) for AF ablation, and 0.8 minutes (0.4, 2.5) MG group versus 9.9 minutes (5.1, 22.5) conventional group (P < 0.0001) for AFL ablation. Median (IQR) total radiation exposure (μGy·m(2)) was 1,107 (906, 2,033) MG group versus 2,835 (1,688, 3,855) conventional group (P = 0.0001) for AF ablation, and 161 (65, 537) MG group versus 1,651 (796, 4,569) conventional group (P < 0.0001) for AFL ablation. No difference in total procedural time was seen. The use of a novel nonfluoroscopic catheter tracking system is associated with a significant reduction in radiation exposure during AF and AFL ablation (61% and 90% reduction, respectively). In the era of heightened awareness of the importance of radiation reduction, this system represents a safe and efficient tool to decrease radiation exposure during electrophysiological ablation procedures. ©2015 Wiley Periodicals, Inc.

Influenza vaccination reduces hemorrhagic stroke risk in patients with atrial fibrillation: A population-based cohort study.

PubMed

Liu, Ju-Chi; Wang, Ta-Jung; Sung, Li-Chin; Kao, Pai-Feng; Yang, Tsung-Yeh; Hao, Wen-Rui; Chen, Chun-Chao; Hsu, Yi-Ping; Wu, Szu-Yuan

2017-04-01

The risk of hemorrhagic stroke in patients with atrial fibrillation (AF) is low but the consequences of its occurrence are extremely severe. In this study, we investigated the association of influenza vaccination with the risk of hemorrhagic stroke to develop an efficient strategy for reducing this risk in patients with AF. In this study, data were retrieved from the Taiwan National Health Insurance Research Database. The study cohort comprised all patients who received a diagnosis of AF (n=14,454) before January 1, 2005 (index date) and were followed until December 31, 2012. Propensity scores were calculated using a logistic regression model to determine the effects of vaccination by accounting for covariates that predict receiving the intervention (vaccine). A time-dependent Cox proportional hazard model was used to calculate the hazard ratios (HRs) for hemorrhagic stroke in vaccinated and unvaccinated patients with AF. The study population comprised 6570 patients who did (2547 [38.77%]) and did not receive (4023 [61.23%]) influenza vaccination. The adjusted HRs (aHRs) for hemorrhagic stroke were lower in the vaccinated patients than in the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs=0.97 [0.59-1.60], 0.51 [0.30-0.87], and 0.72 [0.50-1.03], respectively). Influenza vaccination exerts dose-response and synergistic protective effects against hemorrhagic stroke in patients with AF who have a high risk of hemorrhagic stroke (i.e., male sex, age≥75years, Charlson comorbidity index ≥3, and hypertension) and reduces the incidence of hemorrhagic stroke. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Determination of cadmium by HG-aFS in soil of virescent zone in Chengdu city].

PubMed

Chen, Yuan; Zeng, Ying; Wu, Hong-ji; Wang, Qin-er

2008-12-01

The different speciations of cadmium in soil samples from Chengdu greenbelt were extracted by Tessier sequential extraction method. The contents of total cadmium and different speciation cadmium were determined using HG-AFS. Under optimization condition of HG-AFS and using 2% HCl as medium, and 30 g x L(-1) KBH4 as reductive reagent, 1 mg x L(-1) Co2+ acting together with 10 g x L(-1) CH4N2S can advance the generating efficiency of cadmium compound. The effects of the coexisting elements in soil on the determination of cadmium can be reduced if certain amount of Na4P2O7, K2SO4 and BaCl2 are added. The linear range is 0-10 mg x L(-1) with r=0.9991 and the detection limit is 0.016 mg x L(-1). The recovery is 97.80%-100.2% with RSD of 1.93%. The analytical method is very sensitive and accurate. The distribution of average percentage of five speciations of cadmium in experimental soil samples is: residual fraction (62.1%) > exchangeable fraction (11.7%) > Fe-Mn oxide-bound (9.71%) > carbonate-bound (4.17%) > organic-bound (3.47%). Although residual fraction is the main speciation of cadmium in soil, the content of exchangeable fraction is relatively high. Thus the bioactivity of cadmium in the research area should be recognized. The concentration of cadmium exceeds the country standard in 19 soil sample, accounting for 86. 4% of all soil samples. The soil from Chengdu greenbelt located in 1st ring road, 2nd ring road and 3rd ring road was polluted to different degree. The relative pollution magnitude of them is: 2nd ring road > 1st ring road > 3rd ring road.

Multi-pair two-way massive MIMO AF relaying with ZFR/ZFT beamforming and imperfect CSI over ricean fading channels

NASA Astrophysics Data System (ADS)

Xu, Kui; Sun, Xiaoli; Zhang, Dongmei

2016-10-01

This paper investigates the spectral and energy efficiencies of a multi-pair two-way amplify-and-forward (AF) relay system over Ricean fading channels, where multiple user-pairs exchange information within pair through a relay with very large number of antennas, while each user equipped with a single antenna. Firstly, beamforming matrixe of zero-forcing reception/zero-forcing transmission (ZFR/ZFT) with imperfect channel state information (CSI) at the relay is given. Then, the unified asymptotic signal-to-interference-plus-noise ratio (SINR) expressions with imperfect CSI are obtained analytically. Finally, two power scaling schemes are proposed and the asymptotic spectral and energy efficiencies based on the proposed power scaling schemes are derived and verified by the Monte-Carlo simulations. Theoretical analyses and simulation results show that with imperfect CSI, if the number of relay antennas grows asymptotically large, we need cut down the transmit power of each user and relay to different proportion when the Ricean K-factor is non-zero and zero (Rayleigh fading) in order to maintain a desirable rate.

Understanding the cellulolytic system of Trichoderma harzianum P49P11 and enhancing saccharification of pretreated sugarcane bagasse by supplementation with pectinase and α-L-arabinofuranosidase.

PubMed

Delabona, Priscila da Silva; Cota, Júnio; Hoffmam, Zaira Bruna; Paixão, Douglas Antonio Alvaredo; Farinas, Cristiane Sanchez; Cairo, João Paulo Lourenço Franco; Lima, Deise Juliana; Squina, Fábio Marcio; Ruller, Roberto; Pradella, José Geraldo da Cruz

2013-03-01

Supplementation of cellulase cocktails with accessory enzymes can contribute to a higher hydrolytic capacity in releasing fermentable sugars from plant biomass. This study investigated which enzymes were complementary to the enzyme set of Trichoderma harzianum in the degradation of sugarcane bagasse. Specific activities of T. harzianum extract on different substrates were compared with the extracts of Penicillium echinulatum and Trichoderma reesei, and two commercial cellulase preparations. Complementary analysis of the secretome of T. harzianum was also used to identify which enzymes were produced during growth on pretreated sugarcane bagasse. These analyses enabled the selection of the enzymes pectinase and α-L-arabinofuranosidase (AF) to be further investigated as supplements to the T. harzianum extract. The effect of enzyme supplementation on the efficiency of sugarcane bagasse saccharification was evaluated using response surface methodology. The supplementation of T. harzianum enzymatic extract with pectinase and AF increased the efficiency of hydrolysis by up to 116%. Copyright © 2012 Elsevier Ltd. All rights reserved.

Optimizing radiofrequency ablation of paroxysmal and persistent atrial fibrillation by direct catheter force measurement-a case-matched comparison in 198 patients.

PubMed

Sigmund, Elisabeth; Puererfellner, Helmut; Derndorfer, Michael; Kollias, Georgios; Winter, Siegmund; Aichinger, Josef; Nesser, Hans-Joachim; Martinek, Martin

2015-02-01

Sufficient electrode-tissue contact is crucial for adequate lesion formation in radiofrequency catheter ablation (RFCA). We assessed the impact of direct catheter force measurement on acute procedural parameters and outcome of RFCA for paroxysmal and persistent atrial fibrillation (AF). Ninety-nine consecutive patients (70% men) with paroxysmal (63.6%) or persistent AF underwent left atrial RFCA using a 3.5-mm open-irrigated-tip (OIT) catheter with contact force measurement capabilities (group 1). For comparison a case-matched cohort with standard OIT catheters was used (99 patients; group 2). Case matching included gender, type of AF, number or RFCA procedures, and type of procedure. Procedural data showed a significant decline in radiofrequency ablation time from 52 ± 20 to 44 ± 16 minutes (P = 0.003) with a remarkable mean reduction in overall procedure time of 34 minutes (P = 0.0001; 225.8 ± 53.1 vs 191.9 ± 53.3 minutes). In parallel, the total fluoroscopy time could be significantly reduced from 28.5 ± 11.0 to 19.9 ± 9.3 minutes (P = 0.0001) as well as fluoroscopy dose from 74.1 ± 58.0 to 56.7 ± 38.9 Gy/cm(2) (P = 0.016). Periprocedural complications were similar in both groups. The use of contact force sensing technology is able to significantly reduce ablation, procedure, and fluoroscopy times as well as dose in RFCA of AF in a mixed case-matched group of paroxysmal and persistent AF. Energy delivery is substantially reduced by avoiding radiofrequency ablation in positions with insufficient surface contact. Additionally 12-month outcome data showed increased efficacy. Such time saving and equally safe technology may have a relevant impact on laboratory management and increased cost effectiveness. © 2014 Wiley Periodicals, Inc.

Use of concomitant aspirin in patients with atrial fibrillation: Findings from the ROCKET AF trial.

PubMed

Shah, Rohan; Hellkamp, Anne; Lokhnygina, Yuliya; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Fox, Keith A A; Nessel, Christopher C; Mahaffey, Kenneth W; Piccini, Jonathan P; Singer, Daniel E; Patel, Manesh R

2016-09-01

We aimed to investigate the relationship between aspirin use and clinical outcomes in patients enrolled in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), in particular, those with known coronary artery disease (CAD). Patients in ROCKET AF, comparing rivaroxaban and warfarin, were analyzed. Aspirin use was assessed at baseline. Stroke and systemic embolism, myocardial infarction, death, and major or nonmajor clinically relevant (NMCR) bleeding were compared between groups. Multivariable modeling was done adjusting for baseline risk factors. A total of 5,205 (36.5%) patients were receiving aspirin at baseline (mean dose 99.2mg); 30.6% of those had known CAD. Patients receiving aspirin were more likely to have prior myocardial infarction (22% vs 14%; P<.001) and heart failure (68% vs 59%; P<.001). Relative efficacy of rivaroxaban versus warfarin was similar with and without aspirin use for both stroke/systemic embolism (P=.95 for interaction), and major or NMCR bleeding (P=.76 for interaction). After adjustment, aspirin use was associated with similar rates of stroke/systemic embolism (hazard ratio [HR] 1.16, 95% CI 0.98-1.37; P=.094) but higher rates of all-cause death (HR 1.27, 95% CI 1.13-1.42; P<.0001) and major or NMCR bleeding (HR 1.32, 95% CI 1.21-1.43; P<.0001). There was a significant interaction between no CAD at baseline and aspirin for all-cause death (P=.009). Aspirin use at baseline was associated with an increased risk for bleeding and all-cause death in ROCKET AF, a risk most pronounced in patients without known CAD. Although these findings may reflect unmeasured clinical factors, further investigation is warranted to determine optimal aspirin use in patients with AF. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of Dual Antiplatelet Therapy and Patient Outcomes in Those Undergoing Percutaneous Coronary Intervention: The ROCKET AF Trial.

PubMed

Sherwood, Matthew W; Cyr, Derek D; Jones, W Schuyler; Becker, Richard C; Berkowitz, Scott D; Washam, Jeffrey B; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Singer, Daniel E; Piccini, Jonathan P; Nessel, Christopher C; Mahaffey, Kenneth W; Patel, Manesh R

2016-08-22

The authors assessed the use of dual antiplatelet therapy (DAPT) and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). The frequency, patterns, and outcomes when adding DAPT to non-vitamin K antagonist oral anticoagulants in the setting of PCI in patients with AF are largely unknown. The study population included all patients in the treatment group of the ROCKET AF trial divided by the receipt of PCI during follow-up. Clinical characteristics, PCI frequency, and rates of DAPT were reported. Clinical outcomes were adjudicated independently as part of the trial. Among 14,171 patients, 153 (1.1%) underwent PCI during a median 806 days of follow-up. Patients treated with rivaroxaban were significantly less likely to undergo PCI compared with warfarin-treated patients (61 vs. 92; p = 0.01). Study drug was continued during PCI in 81% of patients. Long-term DAPT (≥30 days) was used in 37% and single antiplatelet therapy in 34%. A small number switched from DAPT to monotherapy within 30 days of PCI (n = 19 [12.3%]) and 15% of patients received no antiplatelet therapy after PCI. Rates of stroke/systemic embolism and major bleeding events were high in post-PCI patients (4.5/100 patient-years and 10.2/100 patient-years) in both treatment groups. In patients with AF at moderate to high risk for stroke, PCI occurred in <1% per year. DAPT was used in a variable manner, with the majority of patients remaining on study drug after PCI. Rates of both thrombotic and bleeding events were high after PCI, highlighting the need for studies to determine the optimal antithrombotic therapy. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[Recent and upcoming randomized trials for left atrial appendage occlusion : Need for a definite assessment of the situation].

PubMed

Skurk, Carsten; Hartung, Johannes Jakob; Landmesser, Ulf

2017-12-01

Atrial fibrillation (AF) is the most common arrhythmia affecting more than 1.6 million patients in Germany. Based on demographic developments, an the number is expected to increase. Embolic strokes in AF patients are particularly severe, and individualized new oral anticoagulant (NOAC) therapy reduces the incidence of stroke in these patients by approximately 70%. Besides vitamin K antagonists, the NOACs rivaroxaban, dabigatran, apixaban, and edoxaban have been introduced into clinical practice; however, major bleeding still occurs at a rate of 2-3% per year. Moreover, randomized studies and real-life registries suggest that >20% of patients with AF and an indication for anticoagulation cannot tolerate chronic oral anticoagulant therapy. Therefore, an alternative method for stroke prevention in AF patients has been developed, i. e., catheter-based exclusion of the left atrial appendage (LAA), a location that is prone for thrombus formation in these patients. The randomized trials of catheter-based LAA occlusion have compared this interventional therapy with vitamin K antagonists. In the future, however, LAA exclusion needs to be compared with NOAC therapy. Moreover, percutaneous LAA exclusion in clinical practice is mostly offered to patients ineligible for long-term oral anticoagulation or with high bleeding risk. However, no controlled, randomized trial data exist for this patient population. These data are needed for appropriate clinical judgment and optimal clinical management. Ongoing studies and scientific questions that are important to define the future for catheter-based LAA closure are discussed in this review.

Navigating the fine line between benefit and risk in chronic atrial fibrillation: rationale and design of the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY).

PubMed

Carrington, Melinda J; Ball, Jocasta; Horowitz, John D; Marwick, Thomas H; Mahadevan, Gnanadevan; Wong, Chiew; Abhayaratna, Walter P; Haluska, Brian; Thompson, David R; Scuffham, Paul A; Stewart, Simon

2013-06-20

Health outcomes associated with atrial fibrillation (AF) continue to be poor and standard management often does not provide clinical stability. The Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY) compares the efficacy of a post-discharge, nurse-led, multi-disciplinary programme to optimise AF management with usual care. SAFETY is a prospective, multi-centre, randomised controlled trial with blinded-endpoint adjudication. A target of 320 hospitalised patients with a chronic form of AF will be randomised (stratified by "rate" versus "rhythm" control) to usual post-discharge care or the SAFETY Intervention (SI). The SI involves home-based assessment, extensive clinical profiling and the application of optimal gold-standard pharmacology which is individually tailored according to a "traffic light" framework based on clinical stability, risk profile and therapeutic management. The primary endpoint is event-free survival from all-cause death or unplanned readmission during 18-36 months follow-up. Secondary endpoints include rate of recurrent hospital stay, treatment success (i.e. maintenance of rhythm or rate control and/or application of anti-thrombotic therapy without a bleeding event) and cost-efficacy. With study recruitment to be completed in early 2012, the results of this study will be available in early 2014. If positive, SAFETY will represent a potentially cost-effective and readily applicable strategy to improve health outcomes in high risk individuals discharged from hospital with chronic AF. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Mutations in GPR143/OA1 and ABCA4 Inform Interpretations of Short-Wavelength and Near-Infrared Fundus Autofluorescence

PubMed Central

Paavo, Maarjaliis; Zhao, Jin; Kim, Hye Jin; Lee, Winston; Zernant, Jana; Cai, Carolyn; Allikmets, Rando; Tsang, Stephen H.; Sparrow, Janet R.

2018-01-01

Purpose We sought to advance interpretations and quantification of short-wavelength fundus autofluorescence (SW-AF) emitted from bisretinoid lipofuscin and near-infrared autofluoresence (NIR-AF) originating from melanin. Methods Carriers of mutations in X-linked GPR143/OA1, a common form of ocular albinism; patients with confirmed mutations in ABCA4 conferring increased SW-AF; and subjects with healthy eyes were studied. SW-AF (488 nm excitation, 500–680 nm emission) and NIR-AF (excitation 787 nm, emission >830 nm) images were acquired with a confocal scanning laser ophthalmoscope. SW-AF images were analyzed for quantitative autofluoresence (qAF). Analogous methods of image acquisition and analysis were performed in albino and pigmented Abca4−/− mice and wild-type mice. Results Quantitation of SW-AF (qAF), construction of qAF color-coded maps, and examination of NIR-AF images from GPR143/OA1 carriers revealed mosaics in which patches of fundus exhibiting NIR-AF signal had qAF levels within normal limits whereas the hypopigmented areas in the NIR-AF image corresponded to foci of elevated qAF. qAF also was increased in albino versus pigmented mice. Although melanin contributes to fundus infrared reflectance, the latter appeared to be uniform in en face reflectance images of GPR143/OA1-carriers. In patients diagnosed with ABCA4-associated disease, NIR-AF increased in tandem with increased qAF originating in bisretinoid lipofuscin. Similarly in Abca4−/− mice having increased SW-AF, NIR-AF was more pronounced than in wild-type mice. Conclusions These studies corroborate RPE melanin as the major source of NIR-AF but also indicate that bisretinoid lipofuscin, when present at sufficient concentrations, contributes to the NIR-AF signal. Ocular melanin attenuates the SW-AF signal.

Screening for asymptomatic atrial fibrillation while monitoring the blood pressure at home: trial of regular versus irregular pulse for prevention of stroke (TRIPPS 2.0).

PubMed

Wiesel, Joseph; Abraham, Saji; Messineo, Frank C

2013-06-01

Asymptomatic atrial fibrillation (AF) is a common cause of strokes. Physician screening for AF has been recommended. Home screening for AF may increase the likelihood of detecting asymptomatic AF in patients at risk for stroke because of AF. The aim of this study was to assess the feasibility and accuracy of screening for AF when taking home blood pressure (BP) measurements using an automatic AF-detecting BP monitor. Subjects aged >64 years or those with hypertension, diabetes, congestive heart failure, or previous stroke were enrolled by their primary physicians and given the AF-BP monitor and an electrocardiographic event monitor to use at home for 30 days. The AF-BP monitor reading was compared with the electrocardiographic reading to calculate the sensitivity and specificity of the device for detecting AF. A total of 160 subjects were enrolled, with 10 withdrawing, 1 excluded, and 10 with no AF-BP monitor logs or electrocardiographic recordings. Of the 139 subjects included, 14 had known AF. There was a total of 3,316 days with AF-BP monitor readings and electrocardiographic readings. On the basis of the initial daily AF-BP monitor readings, the AF-BP monitor demonstrated sensitivity of 99.2% and specificity of 92.9% for detecting AF. Two subjects with no histories of AF had AF-BP monitor readings of AF that were confirmed by the electrocardiographic monitor. One of these subjects was started on warfarin. In conclusion, home screening for asymptomatic AF while taking BP measurements can be performed accurately. This can be used to detect new AF, allowing treatment with anticoagulation to reduce the future risk for stroke. Copyright © 2013 Elsevier Inc. All rights reserved.

The association between atrial fibrillation and cognitive function in patients with heart failure.

PubMed

Yang, Huifeng; Niu, Weihua; Zang, Xiaoying; Lin, Mei; Zhao, Yue

2017-02-01

Atrial fibrillation (AF) is associated with cognitive impairment in heart failure (HF). The purpose of this study was to examine whether AF independently predicted cognitive function in HF patients after controlling for more demographic, medical and psychological characteristics, and whether the timing of AF onset in relation to HF diagnosis independently contributed to cognitive function in HF patients with AF. A total of 188 hospitalized HF patients (62.8% male, age 66.3±10.6 years) completed cognitive function assessment with the Montreal Cognitive Assessment (MoCA). A history of AF, along with other medical characteristics, was ascertained through a review of participants' medical charts. The timing of AF onset in relation to HF diagnosis was categorized into AF occurring prior to HF diagnosis (i.e. prior AF) and AF developing after HF diagnosis (i.e. incident AF). Altogether 72 participants had a positive diagnostic history of AF. Specifically, 41 had prior AF, and 31 developed AF subsequently. In HF patients, AF was associated with poorer performance on cognitive function after controlling for more confounders (β=-0.112, ΔR 2 =0.010, p=0.046). Among HF patients with AF, incident AF independently predicted poorer cognitive function (β=-0.238, ΔR 2 =0.027, p=0.047). AF independently contributes to cognitive function in HF patients after adjusting for more confounding variables. The timing of AF onset in relation to HF diagnosis independently predicts cognitive function in HF patients with AF. Prospective studies are needed to elucidate possible mechanisms for the association between AF and cognitive function in HF populations.

Magnetic viscosity phenomena in exchange coupled CoFe /MnIr bilayers

NASA Astrophysics Data System (ADS)

Kim, Dong Young; Kim, C. O.; Tsunoda, M.; Yamaguchi, M.; Yabugami, S.; Takahashi, M.

2007-05-01

The complex permeability spectra were measured in the low (10Hz-1MHz) and microwave (100MHz-9GHz) frequency ranges in CoFe /MnIr bilayers. The low frequency permeability spectra showed the magnetic viscosity effect below the critical antiferromagnet thickness (tcAF), but not at tAFtcAF. The discrepancies between dynamic and quasistatic measurements of the Jc only begin to appear in the vicinity of the tcAF and dominate at tAF

Clinical, biomarker, and genetic predictors of specific types of atrial fibrillation in a community-based cohort: data of the PREVEND study.

PubMed

Hobbelt, Anne H; Siland, Joylene E; Geelhoed, Bastiaan; Van Der Harst, Pim; Hillege, Hans L; Van Gelder, Isabelle C; Rienstra, Michiel

2017-02-01

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries.

PubMed

Steinberg, Benjamin A; Gao, Haiyan; Shrader, Peter; Pieper, Karen; Thomas, Laine; Camm, A John; Ezekowitz, Michael D; Fonarow, Gregg C; Gersh, Bernard J; Goldhaber, Samuel; Haas, Sylvia; Hacke, Werner; Kowey, Peter R; Ansell, Jack; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Turpie, Alexander; Verheugt, Freek; Piccini, Jonathan P; Kakkar, Ajay; Peterson, Eric D; Fox, Keith A A

2017-12-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment. Demographics, comorbidities, and stroke risk of the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF II (n=11,602) registries were compared (overall N=73,004 from 35 countries). Stroke prevention therapies were assessed among patients with new-onset AF (≤6 weeks). Patients from GARFIELD-AF were less likely to be white (63% vs 89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19% vs 36% and 27%), but had similar stroke risk (85% CHA 2 DS 2 -VASc ≥2 vs 91% and 85%) and lower bleeding risk (11% with HAS-BLED ≥3 vs 24% and 15%). Oral anticoagulant use was 46% and 57% for patients with a CHA 2 DS 2 -VASc=0 and 69% and 87% for CHA 2 DS 2 -VASc ≥2 in GARFIELD-AF and ORBIT-AF II, respectively, but with substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93% [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non-vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016 for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II). Among new-onset AF patients, non-vitamin K antagonist oral anticoagulant use has increased and antiplatelet monotherapy has decreased. However, anticoagulation is used frequently in low-risk patients and inconsistently in those at high risk of stroke. Significant geographic variability in anticoagulation persists and represents an opportunity for improvement. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Correlations Among Near-Infrared and Short-Wavelength Autofluorescence and Spectral-Domain Optical Coherence Tomography in Recessive Stargardt Disease

PubMed Central

Duncker, Tobias; Marsiglia, Marcela; Lee, Winston; Zernant, Jana; Tsang, Stephen H.; Allikmets, Rando; Greenstein, Vivienne C.; Sparrow, Janet R.

2014-01-01

Purpose. Short-wavelength (SW) fundus autofluorescence (AF) is considered to originate from lipofuscin in retinal pigment epithelium (RPE) and near-infrared (NIR) AF from melanin. In patients with recessive Stargardt disease (STGD1), we correlated SW-AF and NIR-AF with structural information obtained by spectral-domain optical coherence tomography (SD-OCT). Methods. Twenty-four STGD1 patients (45 eyes; age 8 to 61 years) carrying confirmed disease-associated ABCA4 mutations were studied prospectively. Short-wavelength AF, NIR-AF, and SD-OCT images were acquired. Results. Five phenotypes were identified according to features of the central lesion and extent of fundus change. Central zones of reduced NIR-AF were typically larger than areas of diminished SW-AF and reduced NIR-AF usually approximated areas of ellipsoid zone (EZ) loss identified by SD-OCT (group 1; r, 0.93, P < 0.0001). In patients having a central lesion with overlapping parafoveal rings of increased NIR-AF and SW-AF (group 3), the extent of EZ loss was strongly correlated with the inner diameter of the NIR-AF ring (r, 0.89, P < 0.0001) and the eccentricity of the outer border of the NIR-AF ring was greater than that of the SW-AF ring. Conclusions. Lesion areas were more completely delineated in NIR-AF images than with SW-AF. In most cases, EZ loss was observed only at locations where NIR-AF was reduced or absent, indicating that RPE cell atrophy occurs in advance of photoreceptor cell degeneration. Because SW-AF was often increased within the central area of EZ disruption, degenerating photoreceptor cells may produce lipofuscin at accelerated levels. Consideration is given to mechanisms underlying hyper–NIR-AF in conjunction with increased SW-AF. PMID:25342616

Operation of an anaerobic filter compared with an anaerobic moving bed bioreactor for the treatment of waste water from hydrothermal carbonisation of fine mulch.

PubMed

Meier, J F; Austermann-Haun, U; Fettig, J; Liebe, H; Wichern, M

2017-10-01

This experimental study investigates the anaerobic digestion of waste water from hydrothermal carbonisation of fine mulch (wood chips) in combination with a co-substrate for the first time. Two anaerobic reactors, an anaerobic filter (AF) and an anaerobic moving bed bioreactor (AnMBBR), were operated over a period of 131 days at mesophilic conditions. The organic loading rate was increased to a maximum of 8.5 g L -l d -1 in the AF and the AnMBBR. Both reactors achieved similarly efficient chemical oxygen demand removal rates of 80% approximately (approx.) and high methane production rates of approx. 2.7 L L -1 d -1 . Nevertheless, signs of an inhibition were observed during the experiments.

Dronedarone: current evidence for its safety and efficacy in the management of atrial fibrillation.

PubMed

Schweizer, Patrick A; Becker, Rüdiger; Katus, Hugo A; Thomas, Dierk

2011-01-06

Atrial fibrillation (AF) is the most common sustained arrhythmia. Management of AF includes rate control, rhythm control if necessary, prevention of thromboembolic events, and treatment of the underlying disease. Rate control is usually achieved by pharmacological suppression of calcium currents or by applying β-blockers or digitalis compounds. In contrast, the number of compounds available for rhythm control is still limited. Class Ic agents increase mortality in patients with structural heart disease, and amiodarone harbors an extensive side effect profile despite its efficacy in maintaining sinus rhythm. Furthermore, rhythm control by these compounds has not been shown to reduce patient mortality. Dronedarone is a new anti-arrhythmic drug that has been developed to provide rhythm and rate control in AF patients with fewer side effects compared with amiodarone. This review primarily focuses on clinical trials evaluating efficacy and safety of the novel drug. Conclusions from these studies are critically reviewed, and recommendations for clinical practice are discussed. Dronedarone significantly reduced the incidence of hospitalization due to cardiovascular events or death in high-risk patients with atrial fibrillation (ATHENA trial). However, dronedarone was less efficient than amiodarone in maintaining normal sinus rhythm (DIONYSOS trial) and is contraindicated in severe or deteriorating heart failure (ANDROMEDA trial). In summary, dronedarone represents a valuable addition to the limited spectrum of antiarrhythmic drugs and is currently recommended in patients with paroxysmal and persistent AF to achieve rate and rhythm control, excluding cases of severe or unstable congestive heart failure.

Atrial Fibrillation Burden: Moving Beyond Atrial Fibrillation as a Binary Entity: A Scientific Statement From the American Heart Association.

PubMed

Chen, Lin Y; Chung, Mina K; Allen, Larry A; Ezekowitz, Michael; Furie, Karen L; McCabe, Pamela; Noseworthy, Peter A; Perez, Marco V; Turakhia, Mintu P

2018-05-15

Our understanding of the risk factors and complications of atrial fibrillation (AF) is based mostly on studies that have evaluated AF in a binary fashion (present or absent) and have not investigated AF burden. This scientific statement discusses the published literature and knowledge gaps related to methods of defining and measuring AF burden, the relationship of AF burden to cardiovascular and neurological outcomes, and the effect of lifestyle and risk factor modification on AF burden. Many studies examine outcomes by AF burden classified by AF type (paroxysmal versus nonparoxysmal); however, quantitatively, AF burden can be defined by longest duration, number of AF episodes during a monitoring period, and the proportion of time an individual is in AF during a monitoring period (expressed as a percentage). Current guidelines make identical recommendations for anticoagulation regardless of AF pattern or burden; however, a review of recent evidence suggests that higher AF burden is associated with higher risk of stroke. It is unclear whether the risk increases continuously or whether a threshold exists; if a threshold exists, it has not been defined. Higher burden of AF is also associated with higher prevalence and incidence of heart failure and higher risk of mortality, but not necessarily lower quality of life. A structured and comprehensive risk factor management program targeting risk factors, weight loss, and maintenance of a healthy weight appears to be effective in reducing AF burden. Despite this growing understanding of AF burden, research is needed into validation of definitions and measures of AF burden, determination of the threshold of AF burden that results in an increased risk of stroke that warrants anticoagulation, and discovery of the mechanisms underlying the weak temporal correlations of AF and stroke. Moreover, developments in monitoring technologies will likely change the landscape of long-term AF monitoring and could allow better definition of the significance of changes in AF burden over time. © 2018 American Heart Association, Inc.

Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

PubMed Central

Johnson, Timothy D.; Dittgen, Felix; Nichols, Thomas E.; Malzahn, Uwe; Veltkamp, Roland

2017-01-01

Objective Atrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke. Methods Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke. Results 582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF. Conclusions In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations. PMID:28542605

Classification of Alzheimer's Disease Based on Eight-Layer Convolutional Neural Network with Leaky Rectified Linear Unit and Max Pooling.

PubMed

Wang, Shui-Hua; Phillips, Preetha; Sui, Yuxiu; Liu, Bin; Yang, Ming; Cheng, Hong

2018-03-26

Alzheimer's disease (AD) is a progressive brain disease. The goal of this study is to provide a new computer-vision based technique to detect it in an efficient way. The brain-imaging data of 98 AD patients and 98 healthy controls was collected using data augmentation method. Then, convolutional neural network (CNN) was used, CNN is the most successful tool in deep learning. An 8-layer CNN was created with optimal structure obtained by experiences. Three activation functions (AFs): sigmoid, rectified linear unit (ReLU), and leaky ReLU. The three pooling-functions were also tested: average pooling, max pooling, and stochastic pooling. The numerical experiments demonstrated that leaky ReLU and max pooling gave the greatest result in terms of performance. It achieved a sensitivity of 97.96%, a specificity of 97.35%, and an accuracy of 97.65%, respectively. In addition, the proposed approach was compared with eight state-of-the-art approaches. The method increased the classification accuracy by approximately 5% compared to state-of-the-art methods.

Locally adaptive parallel temperature accelerated dynamics method

NASA Astrophysics Data System (ADS)

Shim, Yunsic; Amar, Jacques G.

2010-03-01

The recently-developed temperature-accelerated dynamics (TAD) method [M. Sørensen and A.F. Voter, J. Chem. Phys. 112, 9599 (2000)] along with the more recently developed parallel TAD (parTAD) method [Y. Shim et al, Phys. Rev. B 76, 205439 (2007)] allow one to carry out non-equilibrium simulations over extended time and length scales. The basic idea behind TAD is to speed up transitions by carrying out a high-temperature MD simulation and then use the resulting information to obtain event times at the desired low temperature. In a typical implementation, a fixed high temperature Thigh is used. However, in general one expects that for each configuration there exists an optimal value of Thigh which depends on the particular transition pathways and activation energies for that configuration. Here we present a locally adaptive high-temperature TAD method in which instead of using a fixed Thigh the high temperature is dynamically adjusted in order to maximize simulation efficiency. Preliminary results of the performance obtained from parTAD simulations of Cu/Cu(100) growth using the locally adaptive Thigh method will also be presented.

Human anatomy: let the students tell us how to teach.

PubMed

Davis, Christopher R; Bates, Anthony S; Ellis, Harold; Roberts, Alice M

2014-01-01

Anatomy teaching methods have evolved as the medical undergraduate curriculum has modernized. Traditional teaching methods of dissection, prosection, tutorials and lectures are now supplemented by anatomical models and e-learning. Despite these changes, the preferences of medical students and anatomy faculty towards both traditional and contemporary teaching methods and tools are largely unknown. This study quantified medical student and anatomy faculty opinion on various aspects of anatomical teaching at the Department of Anatomy, University of Bristol, UK. A questionnaire was used to explore the perceived effectiveness of different anatomical teaching methods and tools among anatomy faculty (AF) and medical students in year one (Y1) and year two (Y2). A total of 370 preclinical medical students entered the study (76% response rate). Responses were quantified and intergroup comparisons were made. All students and AF were strongly in favor of access to cadaveric specimens and supported traditional methods of small-group teaching with medically qualified demonstrators. Other teaching methods, including e-learning, anatomical models and surgical videos, were considered useful educational tools. In several areas there was disharmony between the opinions of AF and medical students. This study emphasizes the importance of collecting student preferences to optimize teaching methods used in the undergraduate anatomy curriculum. © 2013 American Association of Anatomists.

Automatic p wave analysis over 24 hours in patients with paroxysmal or persistent atrial fibrillation.

PubMed

Bitzen, Alexander; Sternickel, Karsten; Lewalter, Thorsten; Schwab, Jörg Otto; Yang, Alexander; Schrickel, Jan Wilko; Linhart, Markus; Wolpert, Christian; Jung, Werner; David, Peter; Lüderitz, Berndt; Nickenig, Georg; Lickfett, Lars

2007-10-01

Patients with atrial fibrillation (AF) often exhibit abnormalities of P wave morphology during sinus rhythm. We examined a novel method for automatic P wave analysis in the 24-hour-Holter-ECG of 60 patients with paroxysmal or persistent AF and 12 healthy subjects. Recorded ECG signals were transferred to the analysis program where 5-10 P and R waves were manually marked. A wavelet transform performed a time-frequency decomposition to train neural networks. Afterwards, the detected P waves were described using a Gauss function optimized to fit the individual morphology and providing amplitude and duration at half P wave height. >96% of P waves were detected, 47.4 +/- 20.7% successfully analyzed afterwards. In the patient population, the mean amplitude was 0.073 +/- 0.028 mV (mean variance 0.020 +/- 0.008 mV(2)), the mean duration at half height 23.5 +/- 2.7 ms (mean variance 4.2 +/- 1.6 ms(2)). In the control group, the mean amplitude (0.105 +/- 0.020 ms) was significantly higher (P < 0.0005), the mean variance of duration at half height (2.9 +/- 0.6 ms(2)) significantly lower (P < 0.0085). This method shows promise for identification of triggering factors of AF.

Evolution of Force Sensing Technologies.

PubMed

Shah, Dipen

2017-06-01

In order to Improve the procedural success and long-term outcomes of catheter ablation techniques for atrial fibrillation (AF), an Important unfulfilled requirement is to create durable electrophysiologically complete lesions. Measurement of contact force (CF) between the catheter tip and the target tissue can guide physicians to optimise both mapping and ablation procedures. Contact force can affect lesion size and clinical outcomes following catheter ablation of AF. Force sensing technologies have matured since their advent several years ago, and now allow the direct measurement of CF between the catheter tip and the target myocardium in real time. In order to obtain complete durable lesions, catheter tip spatial stability and stable contact force are important. Suboptimal energy delivery, lesion density/contiguity and/or excessive wall thickness of the pulmonary vein-left atrial (PV-LA) junction may result in conduction recovery at these sites. Lesion assessment tools may help predict and localise electrical weak points resulting in conduction recovery during and after ablation. There is increasing clinical evidence to show that optimal use of CF sensing during ablation can reduce acute PV re-conduction, although prospective randomised studies are desirable to confirm long-term favourable clinical outcomes. In combination with optimised lesion assessment tools, contact force sensing technology has the potential to become the standard of care for all patients undergoing AF catheter ablation.

Activation function 2 (AF2) of estrogen receptor-α is required for the atheroprotective action of estradiol but not to accelerate endothelial healing

PubMed Central

Billon-Galés, Audrey; Krust, Andrée; Fontaine, Coralie; Abot, Anne; Flouriot, Gilles; Toutain, Céline; Berges, Hortense; Gadeau, Alain-Pierre; Lenfant, Françoise; Gourdy, Pierre; Chambon, Pierre; Arnal, Jean-François

2011-01-01

17β-Estradiol (E2) regulates estrogen receptor-α (ERα) target gene transcription through the two independent activation functions (AFs), AF1 and AF2, located in the N-terminal and ligand binding domain of ERα, respectively. We previously reported that ERα is required for the E2 atheroprotective action as well as for its accelerative action on endothelial healing, but its AF1 function is dispensable. Here, we investigated the role of ERαAF2 in these two major beneficial actions of E2 by electively targeting ERαAF2 (named ERαAF20). Our results prove four points. (i) Compared with WT ERα, the ability of ERαAF20 to stimulate the C3 complement or the estrogen response element-thymidine kinase promoter in two cell lines was dramatically decreased, confirming the importance of AF2 in the E2-induced transcriptional activity of ERα. (ii) The uterotrophic action of E2 was totally absent in ERαAF20 mice, showing the crucial role of ERαAF2 in E2-induced uterus hyperplasia. (iii) ERαAF2 was dispensable for the accelerative action of E2 on endothelial healing, underlining the functionality of ERαAF20 in vivo. (iv) Finally, the atheroprotective effect of E2 was abrogated in ERαAF20 LDL-r−/− mice. Thus, whereas ERαAF1 and ERαAF2 are both required for the uterotrophic action of E2, we show that only ERαAF2 is necessary for its atheroprotective effect. PMID:21788522

Development of Lattice Trapped Paramagnetic Polar Molecules for Quantum Simulation

DTIC Science & Technology

2015-06-23

2015 DISTRIBUTION A: Distribution approved for public release. AF Office Of Scientific Research (AFOSR)/ RTB Arlington, Virginia 22203 Air Force...Arlington, VA 22203 10. SPONSOR/MONITOR’S ACRONYM(S) AFRL/AFOSR RTB 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION /AVAILABILITY STATEMENT A... DISTRIBUTION UNLIMITED: PB Public Release 13. SUPPLEMENTARY NOTES 14. ABSTRACT We have demonstrated optimized production and spatial manipulation of Li

Relay Selection for Cooperative Relaying in Wireless Energy Harvesting Networks

NASA Astrophysics Data System (ADS)

Zhu, Kaiyan; Wang, Fei; Li, Songsong; Jiang, Fengjiao; Cao, Lijie

2018-01-01

Energy harvesting from the surroundings is a promising solution to provide energy supply and extend the life of wireless sensor networks. Recently, energy harvesting has been shown as an attractive solution to prolong the operation of cooperative networks. In this paper, we propose a relay selection scheme to optimize the amplify-and-forward (AF) cooperative transmission in wireless energy harvesting cooperative networks. The harvesting energy and channel conditions are considered to select the optimal relay as cooperative relay to minimize the outage probability of the system. Simulation results show that our proposed relay selection scheme achieves better outage performance than other strategies.

Resonance energy transfer between the active sites of creatine kinase from rabbit brain.

PubMed

Grossman, S H

1990-09-03

Resonance energy transfer was measured between the active site domains of the brain isozyme of creatine kinase (CK-BB). The reactive thiol near the active sites, one on each subunit of the dimeric protein, was derivatized using 5-[2-[iodoacetyl)amino)ethyl]aminonaphthalene-1-sulfonic acid (AED), 2-[4'-iodoacetamidoanilino]naphthalene-6-sulfonic acid (AANS) and 5-iodoacetamidofluorescein (AF). Suitable donor/acceptor protein conjugated hybrids were prepared by controlled kinetics producing CK-BB-AED/AF and CK-BB-AANS/AF. Transfer efficiencies, measured from the quenching of the donor lifetime and steady-state sensitized acceptor emission, ranged from 0.10 to 0.17. From determination of the donor/acceptor overlap integrals, donor quantum yields and attempts to delimit the orientation factor using steady-state and phase-resolved anisotropy measurements, it was found that a suitable estimate of the range between the active sites was between 45 and 57 A. This range is similar to that reported previously for the muscle isozyme of creatine kinase (Grossman, S.H. (1989) Biochemistry 28, 4894-4902) but is a significantly greater distance than detected for the hybrid, myocardial specific isozyme (Grossman, S.H. (1983) Biochemistry 22, 5369-5375).

High burden of Aspergillus fumigatus infection among chronic respiratory diseases.

PubMed

Fukuda, Yosuke; Homma, Tetsuya; Suzuki, Shintaro; Takuma, Takahiro; Tanaka, Akihiko; Yokoe, Takuya; Ohnishi, Tsukasa; Niki, Yoshihito; Sagara, Hironori

2018-01-01

Aspergillus fumigatus (AF) is a ubiquitous fungus in our environment and causes severe airway disorders. Chronic respiratory diseases (CRDs) are a series of chronic airway and lung diseases. Although both are chronic disorders, however, the relationships between AF and CRDs are still unclear. Therefore, we examined 104 Aspergillus species (spp.) isolated samples in our hospital during three consecutive years to further elucidate the relationships between Aspergillus spp. and CRDs. Based on sample isolates, we then grouped these into two groups, AF and non-AF, to retrospectively analyse the clinical features and to clarify the relationships between AF and CRDs. Importantly, the manifestation of CRD was more frequent in the AF group than in the non-AF group ( p = 0.035). Among CRDs, lung fibrosis was more evident in the AF group ( p = 0.025). Moreover, diabetes mellitus was tended to be evident in AF group than non-AF group ( p = 0.035). In conclusion, CRDs, especially lung fibrosis, were highly prevalent in AF group than non-AF group.

Quantitative analysis of arsenic speciation in guano and ornithogenic sediments using microwave-assisted extraction followed by high-performance liquid chromatography coupled to hydride generation atomic fluorescence spectrometry.

PubMed

Lou, Chuangneng; Liu, Wenqi; Liu, Xiaodong

2014-10-15

Seabird guano is one of the main sources of nutrient fertilizers in remote coastal island areas, but guano-derived contaminants such as arsenic may cause serious threats to local ecosystems and public health issues. In this study, a new method was developed to analyze arsenic speciation in guano and ornithogenic sediments. Good extraction efficiencies of As(III) (arsenite), DMA (dimethylarsinate), MMA (monomethylarsonate) and As(V) (arsenate) were obtained by using 1.0molL(-1) orthophosphoric acid and 0.1molL(-1) ascorbic acid, followed by microwave-assisted extraction and high-performance liquid chromatography coupled to hydride generation atomic fluorescence spectrometry (HPLC-HG-AFS) detection. Under the optimized conditions, the extraction efficiencies of four arsenic species were over 80%. The relative standard deviations (RSDs) were 9.60, 6.15, 6.34 and 2.93% (n=7), and the detection limits (μgL(-1)) were 0.82, 2.38, 1.45 and 2.31 for As(III), DMA, MMA and As(V), respectively. This method was successfully used to determine arsenic speciation in the guano samples collected from the Xisha Islands of the South China Sea, and the results indicated that As(III) and As(V) were the dominant arsenic species in modern and ancient guano, respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

Theory-based and evidence-based design of audit and feedback programmes: examples from two clinical intervention studies.

PubMed

Hysong, Sylvia J; Kell, Harrison J; Petersen, Laura A; Campbell, Bryan A; Trautner, Barbara W

2017-04-01

Audit and feedback (A&F) is a common intervention used to change healthcare provider behaviour and, thus, improve healthcare quality. Although A&F can be effective its effectiveness varies, often due to the details of how A&F interventions are implemented. Some have suggested that a suitable conceptual framework is needed to organise the elements of A&F and also explain any observed differences in effectiveness. Through two examples from applied research studies, this article demonstrates how a suitable explanatory theory (in this case Kluger & DeNisi's Feedback Intervention Theory (FIT)) can be systematically applied to design better feedback interventions in healthcare settings. Case 1: this study's objective was to reduce inappropriate diagnosis of catheter-associated urinary tract infections (CAUTI) in inpatient wards. Learning to identify the correct clinical course of action from the case details was central to this study; consequently, the feedback intervention featured feedback elements that FIT predicts would best activate learning processes (framing feedback in terms of group performance and providing of correct solution information). We designed a highly personalised, interactive, one-on-one intervention with healthcare providers to improve their capacity to distinguish between CAUTI and asymptomatic bacteruria (ASB) and treat ASB appropriately. Case 2: Simplicity and scalability drove this study's intervention design, employing elements that FIT predicted positively impacted effectiveness yet still facilitated deployment and scalability (eg, delivered via computer, delivered in writing). We designed a web-based, report-style feedback intervention to help primary care physicians improve their care of patients with hypertension. Both studies exhibited significant improvements in their desired outcome and in both cases interventions were received positively by feedback recipients. A&F has been a popular, yet inconsistently implemented and variably effective tool for changing healthcare provider behaviour and, improving healthcare quality. Through the systematic use of theory such as FIT, robust feedback interventions can be designed that yield greater effectiveness. Future work should look to comparative effectiveness of specific design elements and contextual factors that identify A&F as the optimal intervention to effectuate healthcare provider behaviour change. NCT01052545, NCT00302718; post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Heterogeneous polymer modification: Polyolefin maleation in supercritical carbon dioxide and amorphous fluoropolymer surface modification

NASA Astrophysics Data System (ADS)

Hayes, Heather J.

1999-11-01

Three distinct heterogeneous polymer modification reactions are explored in this work. The first is a bulk reaction commonly conducted on polyolefins---the free radical addition of maleic anhydride. This reaction was run using supercritical carbon dioxide (SC CO2) as the solvent. The second was the chemical surface modification of an amorphous fluorocopolymer of tetrafluoroethylene and a perfluorodioxole monomer (Teflon AF). Several reactions were explored to reduce the surface of the fluorocopolymer for the enhancement of wettability. The last modification was also on Teflon AF and involved the physical modification of the surface through the transport polymerization of xylylene in order to synthesize a novel bilayer membrane. The bulk maleation of poly-4-methyl-1-pentene (PMP) was the focus of the first project. SC CO2 was utilized as both solvent and swelling agent to promote this heterogeneous reaction and led to successful grafting of anhydride groups on both PMP and linear low density polyethylene. Varying the reaction conditions and reagent concentrations allowed optimization of the reaction. The grafted anhydride units were found to exist as single maleic and succinic grafts, and the PMP became crosslinked upon maleation. The surface of a fluoropolymer can be difficult to alter. An examination of three reactions was made to determine the reactivity of Teflon AF: sodium naphthalenide treatment (Na-Nap), aluminum metal modification through deposition and dissolution, and mercury/ammonia photosensitization. The fluorocopolymer with the lower perfluorodioxole percentage was found to be more reactive towards modification with the Na-Nap treatment. The other modification reactions appeared to be nearly equally reactive toward both fluorocopolymers. The functionality of the Na-Nap-treated surface was examined in detail with the use of several derivatization reactions. In the final project, an asymmetric gas separation membrane was synthesized using Teflon AF as the highly permeable support layer and chemical vapor deposited poly(p-xylylene) (PPX) as the thin selective layer. This bilayer membrane has oxygen and nitrogen permeability values close to those predicted by the series resistance model. To enhance the weak adhesive bond between Teflon AF and PPX, Na-Nap reduction was used to modify the Teflon AF surface prior to the vapor deposition polymerization of di-p-xylylene monomer.

A comparative evaluation of risk-adjustment models for benchmarking amputation-free survival after lower extremity bypass.

PubMed

Simons, Jessica P; Goodney, Philip P; Flahive, Julie; Hoel, Andrew W; Hallett, John W; Kraiss, Larry W; Schanzer, Andres

2016-04-01

Providing patients and payers with publicly reported risk-adjusted quality metrics for the purpose of benchmarking physicians and institutions has become a national priority. Several prediction models have been developed to estimate outcomes after lower extremity revascularization for critical limb ischemia, but the optimal model to use in contemporary practice has not been defined. We sought to identify the highest-performing risk-adjustment model for amputation-free survival (AFS) at 1 year after lower extremity bypass (LEB). We used the national Society for Vascular Surgery Vascular Quality Initiative (VQI) database (2003-2012) to assess the performance of three previously validated risk-adjustment models for AFS. The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL), Finland National Vascular (FINNVASC) registry, and the modified Project of Ex-vivo vein graft Engineering via Transfection III (PREVENT III [mPIII]) risk scores were applied to the VQI cohort. A novel model for 1-year AFS was also derived using the VQI data set and externally validated using the PIII data set. The relative discrimination (Harrell c-index) and calibration (Hosmer-May goodness-of-fit test) of each model were compared. Among 7754 patients in the VQI who underwent LEB for critical limb ischemia, the AFS was 74% at 1 year. Each of the previously published models for AFS demonstrated similar discriminative performance: c-indices for BASIL, FINNVASC, mPIII were 0.66, 0.60, and 0.64, respectively. The novel VQI-derived model had improved discriminative ability with a c-index of 0.71 and appropriate generalizability on external validation with a c-index of 0.68. The model was well calibrated in both the VQI and PIII data sets (goodness of fit P = not significant). Currently available prediction models for AFS after LEB perform modestly when applied to national contemporary VQI data. Moreover, the performance of each model was inferior to that of the novel VQI-derived model. Because the importance of risk-adjusted outcome reporting continues to increase, national registries such as VQI should begin using this novel model for benchmarking quality of care. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverter-defibrillator. For the Worldwide Jewel AF Investigators.

PubMed

Swerdlow, C D; Schsls, W; Dijkman, B; Jung, W; Sheth, N V; Olson, W H; Gunderson, B D

2000-02-29

To distinguish prolonged episodes of atrial fibrillation (AF) that require cardioversion from self-terminating episodes that do not, an atrial implantable cardioverter-defibrillator (ICD) must be able to detect AF continuously for extended periods. The ICD should discriminate between atrial tachycardia/flutter (AT), which may be terminated by antitachycardia pacing, and AF, which requires cardioversion. We studied 80 patients with AT/AF and ventricular arrhythmias who were treated with a new atrial/dual-chamber ICD. During a follow-up period lasting 6+/-2 months, we validated spontaneous, device-defined AT/AF episodes by stored electrograms in all patients. In 58 patients, we performed 80 Holter recordings with telemetered atrial electrograms, both to validate the continuous detection of AT/AF and to determine the sensitivity of the detection of AT/AF. Detection was appropriate in 98% of 132 AF episodes and 88% of 190 AT episodes (98% of 128 AT episodes with an atrial cycle length <300 ms). Intermittent sensing of far-field R waves during sinus tachycardia caused 27 inappropriate AT/AF detections; these detections lasted 2.6+/-2.0 minutes. AT/AF was detected continuously in 27 of 28 patients who had spontaneous episodes of AT/AF (96%). The device memory recorded 90 appropriate AT/AF episodes lasting >1 hour, for a total of 2697 hours of continuous detection of AT/AF. During Holter monitoring, the sensitivity of the detection of AT/AF (116 hours) was 100%; the specificity of the detection of non-AT/AF rhythms (1290 hours) was 99.99%. Of 166 appropriate episodes detected as AT, 45% were terminated by antitachycardia pacing. A new ICD detects AT/AF accurately and continuously. Therapy may be programmed for long-duration AT/AF, with a low risk of underdetection. Discrimination of AT from AF permits successful pacing therapy for a significant fraction of AT.

Aspergillus fumigatus (Af) Hydroxamate Siderophores Protect Formation of Af Biofilms from the Pseudomonas aeruginosa (Pa) Product Pyoverdine

PubMed Central

Sass, Gabriele; Stevens, David A

2017-01-01

Abstract Background Pa and Af are pathogens frequently found together in airways of immunocompromised patients and patients with cystic fibrosis (CF). Hence, interactions of Pa and Af require understanding. Both Pa and Af are crucially dependent on the availability of iron, and therefore are competitors in their microenvironment. We have shown, using deletion mutants of Pa, that the Pa siderophore pyoverdine, the dominant Pa inhibitor of Af, interferes with Af biofilms by iron chelation, and denial of iron to the fungus. Methods Protective compounds in Af supernatants were evaluated using assays for the quantification of Af biofilm metabolism by XTT measurement, spectrometric pyoverdine measurement, as well as Chrome Azorole S (CAS) assay for the determination of siderophore production. Results Here we provide evidence that whereas iron usage by Af promotes pyoverdine production by Pa, Af has developed a defense mechanism against anti-fungal pyoverdine effects. The ability of Af to produce hydroxamate siderophores, and shed these into the surrounding medium, where they sequester and transport iron, is a key factor for Af self-defense against Pa. Under low iron conditions, such as in the presence of high amounts of the Pa siderophore pyoverdine, siderophore-bound iron is then fed to Af, protecting the fungus from iron starvation. Af with a deletion mutation in sidA, a gene essential for the production of hydroxamate siderophores, was significantly more sensitive to Pa supernatants, as well as pure pyoverdine, than wild-type Af. Af supernatants, produced in the presence of celastrol, an inhibitor of SidA-generated biosynthesis of siderophores, or produced by the sidA mutant, were not able to protect Af from iron starvation. Conclusion Interference with the iron-dependent Af self-defense mechanism might represent a new approach for therapy against aspergillosis. Disclosures All authors: No reported disclosures.

Magnitude of increase in QTc interval after initiation of dofetilide in patients with persistent atrial fibrillation is associated with increased rates of pharmacological cardioversion and long-term freedom from recurrent atrial fibrillation.

PubMed

Huang, Henry D; Waks, Jonathan W; Steinhaus, Daniel A; Zimetbaum, Peter

2016-07-01

Dofetilide is a class III antiarrhythmic drug approved for the treatment of atrial fibrillation (AF). Dofetilide-induced corrected QT (QTc) interval prolongation is a surrogate for the degree of drug effect, but the relationships between drug-induced QTc interval prolongation, pharmacological cardioversion (PCV), and freedom from recurrent AF are unclear. The purpose of this study was to assess associations between QTc interval change during dofetilide initiation and PCV and long-term AF recurrence. We performed retrospective analyses of a prospective cohort of patients with AF admitted for dofetilide initiation between 2001 and 2014. Clinical characteristics and electrocardiographic variables were assessed. We evaluated outcomes of successful PCV in patients with persistent AF and time to recurrence of AF in patients with paroxysmal and persistent AF. During the study, 243 patients with persistent AF and 176 patients with paroxysmal AF initiated dofetilide. PCV occurred in 93/243 (41.7%) patients with persistent AF. After multivariable adjustment, QTc interval change was associated with PCV (adjusted odds ratio 1.21; P = .003 per 10-ms QTc increase). Inhospital QTc interval change was associated with long-term freedom from AF in patients with persistent AF (adjusted hazard ratio 0.92; P = .011 at 4 years per 10-ms QTc increase), but not in patients with paroxysmal AF. In patients with persistent AF, PCV was also associated with long-term freedom from recurrent AF (adjusted hazard ratio 0.62; P = .009 at 4 years). The magnitude of QTc interval prolongation during dofetilide initiation is an independent predictor of successful PCV and long-term freedom from arrhythmia in patients with persistent AF. QTc interval change had no association with AF recurrence in patients with paroxysmal AF, suggesting that different mechanisms of arrhythmogenesis may be operant in different AF types. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Complex Transcriptional Control of the Antibiotic Regulator afsS in Streptomyces: PhoP and AfsR Are Overlapping, Competitive Activators▿

PubMed Central

Santos-Beneit, Fernando; Rodríguez-García, Antonio; Martín, Juan F.

2011-01-01

The afsS gene of several Streptomyces species encodes a small sigma factor-like protein that acts as an activator of several pathway-specific regulatory genes (e.g., actII-ORF4 and redD in Streptomyces coelicolor). The two pleiotropic regulators AfsR and PhoP bind to overlapping sequences in the −35 region of the afsS promoter and control its expression. Using mutated afsS promoters containing specific point mutations in the AfsR and PhoP binding sequences, we proved that the overlapping recognition sequences for AfsR and PhoP are displaced by 1 nucleotide. Different nucleotide positions are important for binding of AfsR or PhoP, as shown by electrophoretic mobility shift assays and by reporter studies using the luxAB gene coupled to the different promoters. Mutant promoter M5 (with a nucleotide change at position 5 of the consensus box) binds AfsR but not PhoP with high affinity (named “superAfsR”). Expression of the afsS gene from this promoter led to overproduction of actinorhodin. Mutant promoter M16 binds PhoP with extremely high affinity (“superPhoP”). Studies with ΔafsR and ΔphoP mutants (lacking AfsR and PhoP, respectively) showed that both global regulators are competitive transcriptional activators of afsS. AfsR has greater influence on expression of afsS than PhoP, as shown by reverse transcriptase PCR (RT-PCR) and promoter reporter (luciferase) studies. These two high-level regulators appear to integrate different nutritional signals (particularly phosphate limitation sensed by PhoR), S-adenosylmethionine, and other still unknown environmental signals (leading to AfsR phosphorylation) for the AfsS-mediated control of biosynthesis of secondary metabolites. PMID:21378195

Ethnic distribution of ECG predictors of atrial fibrillation and its impact on understanding the ethnic distribution of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Soliman, Elsayed Z; Prineas, Ronald J; Case, L Douglas; Zhang, Zhu-ming; Goff, David C

2009-04-01

The paradox of the reported low prevalence of atrial fibrillation (AF) in blacks compared with whites despite higher stroke rates in the former could be related to limitations in the current methods used to diagnose AF in population-based studies. Hence, this study aimed to use the ethnic distribution of ECG predictors of AF as measures of AF propensity in different ethnic groups. The distribution of baseline measures of P-wave terminal force, P-wave duration, P-wave area, and PR duration (referred to as AF predictors) were compared by ethnicity in 15 429 participants (27% black) from the Atherosclerosis Risk in Communities (ARIC) study by unpaired t test, chi(2), and logistic-regression analysis, as appropriate. Cox proportional-hazards analysis was used to separately examine the association of AF predictors with incident AF and ischemic stroke. Whereas AF was significantly less common in blacks compared with whites (0.24% vs 0.95%, P<0.0001), similar to what has been reported in previous studies, blacks had significantly higher and more abnormal values of AF predictors (P<0.0001 for all comparisons). Black ethnicity was significantly associated with abnormal AF predictors compared with whites; odds ratios for different AF predictors ranged from 2.1 to 3.1. AF predictors were significantly and independently associated with AF and ischemic stroke with no significant interaction between ethnicity and AF predictors, findings that further justify using AF predictors as an earlier indicator of future risk of AF and stroke. There is a disconnect between the ethnic distribution of AF predictors and the ethnic distribution of AF, probably because the former, unlike the latter, do not suffer from low sensitivity. These results raise the possibility that blacks might actually have a higher prevalence of AF that might have been missed by previous studies owing to limited methodology, a difference that could partially explain the greater stroke risk in blacks.

Association of a Family History of Atrial Fibrillation With Incidence and Outcomes of Atrial Fibrillation: A Population-Based Family Cohort Study.

PubMed

Chang, Shang-Hung; Kuo, Chang-Fu; Chou, I-Jun; See, Lai-Chu; Yu, Kuang-Hui; Luo, Shue-Fen; Huang, Lu-Hsiang; Zhang, Weiya; Doherty, Michael; Wen, Ming-Shien; Kuo, Chi-Tai; Yeh, Yung-Hsin

2017-08-01

The heritability of atrial fibrillation (AF), the contribution of genetic and environmental factors, and the association of a family history of AF with prognosis are unclear. To measure genetic and environmental factors in the familial aggregation of AF and to estimate the association of a family history of AF with major adverse cardiovascular events (MACE). In this Taiwanese nationwide population-based study among more than 23 million people, a custom data set was obtained using the data of all patients having a diagnosis of AF recorded between January 1996 and December 2013 in the Taiwan National Health Insurance Research Database. The study population comprised all 23 422 955 individuals registered with the database in 2013, of whom 177 770 had a diagnosis of AF and were included in the heritability estimation. From the latter, a subgroup of patients having newly diagnosed AF with a first-degree relative affected by AF between 2000 and 2010 were selected and matched 1:4 to controls without a family history for estimating MACE-free survival. The dates of analysis were January 2010 to December 2013. The prevalence and relative risk of AF in relatives of patients with AF, as well as the relative contributions of heritability and shared and nonshared environmental factors to AF susceptibility. Also measured was MACE-free survival after AF was diagnosed. In total, 1510 patients (204 [13.5%] female; mean [SD] age, 57.9 [9.2] years) had newly diagnosed AF with a first-degree relative affected by AF. Individuals with a first-degree relative affected by AF had a relative risk of 1.92 (95% CI, 1.84-1.99) for AF. The accountability for the phenotypic variance of AF was 19.9% for genetic factors (heritability), 3.5% for shared environmental factors, and 76.6% for nonshared environmental factors. After matching for age, sex, hypertension, type 2 diabetes, previous stroke, and anticoagulation, incident AF patients with vs without an affected first-degree relative had similar MACE-free survival. Genetic and environmental factors were associated with AF, with nonshared environmental factors accounting for three-fourths of the phenotypic variance in Taiwan. Patients having AF with a first-degree relative affected by AF did not have more MACE. Therefore, family history may not be particularly informative in the diagnosis or management of AF.

Rhythm vs. rate control of atrial fibrillation meta-analysed by number needed to treat.

PubMed

Kumana, Cyrus R; Cheung, Bernard M Y; Cheung, Giselle T Y; Ovedal, Tori; Pederson, Bjorn; Lauder, Ian J

2005-10-01

Whenever feasible, rhythm control of atrial fibrillation (AF) was generally preferred over rate control, in the belief that it offered better symptomatic relief and quality of life, and eliminated the need for anticoagulation. However, recent trials appear to challenge these assumptions. To explore the desirability of rhythm vs. rate control of AF by systematic review of pertinent, published, randomized controlled trials (RCTs) and a meta-analysis by number needed to treat (NNT) year(-1), with respect to diverse clinically important outcomes. RCTs of outcome primarily comparing rate vs. rhythm control in patients with spontaneous AF were identified. For each outcome and assuming rhythm control to be the active treatment, relative risk reduction (RRR) and NNT year(-1) were derived for individual trials together with an NNT year(-1) for all trials combined; corresponding 95% confidence intervals (CI) were also calculated. Adverse drug reaction (ADR) and quality of life reporting were also assessed. In all, data from five suitable RCTs (entailing 5239 patients) were analysed. For hospitalization, available RRRs and NNT year(-1) values were all clinically and statistically significant. Overall, one additional patient was hospitalized for every 35 assigned to rhythm control (95% CI 27, 48). For the endpoints of death, 'ischaemic' stroke and 'non-CNS' bleeding, there was no significant difference. ADRs were significantly more common in rhythm control patients, whereas quality of life assessments revealed no difference. Thromboembolism was associated with cessation of or subtherapeutic anticoagulation, irrespective of treatment assignment. Reduced risk of hospitalization and non-inferiority for other endpoints all favour rate control, the less costly strategy. If symptoms of AF are not a problem, treatment should target optimizing rate control and more widespread and effective prophylactic anticoagulation.

Antithrombotic therapy for atrial fibrillation and coronary artery disease in older patients

PubMed Central

Hess, Connie N.; Broderick, Samuel; Piccini, Jonathan P.; Alexander, Karen P.; Newby, L. Kristin; Shaw, Linda K.; Mahaffey, Kenneth W.; Alexander, John H.; Peterson, Eric D.; Granger, Christopher B.; Lopes, Renato D.

2013-01-01

Background Older patients with atrial fibrillation (AF) and coronary artery disease (CAD) face high risk of stroke and bleeding with antithrombotic therapy. Balancing safe and effective use of aspirin, clopidogrel, and warfarin in this population is important. Methods From the Duke Databank for Cardiovascular Disease, we identified patients with AF ≥65 years old with angiographically confirmed CAD from 2000 to 2010. Antithrombotic use was described across age and Congestive heart failure, Hypertension, Age >75 years, Diabetes, prior Stroke/transient ischemic attack (CHADS2) stroke risk and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding scores. Death and the composite of death, myocardial infarction, and stroke by antithrombotic strategy were reported. Results Of 2,122 patients ≥65 years old with AF and CAD, 477 (22.5%) were ≥80 years old; 1,133 (53.4%) had acute coronary syndromes. Overall rates of aspirin, clopidogrel, and warfarin use were 83.4%, 34.6%, and 38.9%, respectively. Compared with patients 65 to 79 years old, more patients ≥80 years old were at high stroke risk (CHADS2 ≥2, 84.7% vs 57.8%) and high bleeding risk (ATRIA 5-10, 55.8% vs 23.3%). Warfarin use in both age groups increased with higher CHADS2 scores and decreased with higher ATRIA scores. Of patients ≥80 years old with CHADS2 ≥2, 150 (38.2%) received warfarin. Antithrombotic strategy was not associated with improved 1-year adjusted outcomes. Conclusions Among older patients with AF and CAD, overall warfarin use was low. Patients ≥80 years old at highest stroke risk received warfarin in similar proportions to the overall cohort. Further investigation into optimizing antithrombotic strategies in this population is warranted. PMID:23067921

Antithrombotic therapy for atrial fibrillation and coronary artery disease in older patients.

PubMed

Hess, Connie N; Broderick, Samuel; Piccini, Jonathan P; Alexander, Karen P; Newby, L Kristin; Shaw, Linda K; Mahaffey, Kenneth W; Alexander, John H; Peterson, Eric D; Granger, Christopher B; Lopes, Renato D

2012-10-01

Older patients with atrial fibrillation (AF) and coronary artery disease (CAD) face high risk of stroke and bleeding with antithrombotic therapy. Balancing safe and effective use of aspirin, clopidogrel, and warfarin in this population is important. From the Duke Databank for Cardiovascular Disease, we identified patients with AF ≥65 years old with angiographically confirmed CAD from 2000 to 2010. Antithrombotic use was described across age and Congestive heart failure, Hypertension, Age >75 years, Diabetes, prior Stroke/transient ischemic attack (CHADS(2)) stroke risk and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding scores. Death and the composite of death, myocardial infarction, and stroke by antithrombotic strategy were reported. Of 2,122 patients ≥65 years old with AF and CAD, 477 (22.5%) were ≥80 years old; 1,133 (53.4%) had acute coronary syndromes. Overall rates of aspirin, clopidogrel, and warfarin use were 83.4%, 34.6%, and 38.9%, respectively. Compared with patients 65 to 79 years old, more patients ≥80 years old were at high stroke risk (CHADS(2) ≥2, 84.7% vs 57.8%) and high bleeding risk (ATRIA 5-10, 55.8% vs 23.3%). Warfarin use in both age groups increased with higher CHADS(2) scores and decreased with higher ATRIA scores. Of patients ≥80 years old with CHADS(2) ≥2, 150 (38.2%) received warfarin. Antithrombotic strategy was not associated with improved 1-year adjusted outcomes. Among older patients with AF and CAD, overall warfarin use was low. Patients ≥80 years old at highest stroke risk received warfarin in similar proportions to the overall cohort. Further investigation into optimizing antithrombotic strategies in this population is warranted. Copyright © 2012 Mosby, Inc. All rights reserved.

Cost-effectiveness of apixaban versus warfarin and aspirin in Sweden for stroke prevention in patients with atrial fibrillation.

PubMed

Lanitis, Tereza; Kongnakorn, Thitima; Jacobson, Lena; De Geer, Anna

2014-08-01

Atrial fibrillation (AF), one of the major risk factors for stroke, imposing a substantial burden to the Swedish health care system. Apixaban has demonstrated superiority to warfarin and aspirin in stroke prevention amongst patients with AF in two large randomised clinical trials. The aim of this study was to assess the economic implications of apixaban against warfarin and aspirin in these patients from a Swedish societal perspective. A Markov cohort model was constructed to characterise the consequences of anticoagulant treatment with regards to thromboembolic and bleeding events, as well as the associated health care costs, life-years and quality-adjusted life years (QALYs) for patients with AF treated with apixaban, warfarin or aspirin. Incremental cost-effectiveness ratios (ICERs) per QALY gained of apixaban relative to warfarin (among patients suitable for warfarin treatment) and aspirin (among patients unsuitable for warfarin treatment) were calculated. Costs (in 2011 SEKs) and QALYs were discounted at 3% per annum. The model estimated the ICER of apixaban versus warfarin amongst patients who are suitable for warfarin therapy to be SEK 33,458/QALY gained and that of apixaban versus aspirin amongst those unsuitable for warfarin therapy to be SEK 41,453/QALY gained. Probabilistic sensitivity analyses indicate that apixaban is an optimal treatment option compared with warfarin and aspirin, when the willingness-to-pay is above SEK 35,000 and SEK 45,000 per QALY, respectively. Apixaban was found to be a cost-effective alternative to warfarin and aspirin for stroke prevention in patients with AF in Sweden. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Significant effects of atrioventricular node ablation and pacemaker implantation on left ventricular function and long-term survival in patients with atrial fibrillation and left ventricular dysfunction.

PubMed

Ozcan, Cevher; Jahangir, Arshad; Friedman, Paul A; Munger, Thomas M; Packer, Douglas L; Hodge, David O; Hayes, David L; Gersh, Bernard J; Hammill, Stephen C; Shen, Win-Kuang

2003-07-01

Control of ventricular rate by atrioventricular node ablation and pacemaker implantation in patients with drug-refractory atrial fibrillation (AF) is associated with improved left ventricular (LV) function. The objective of this study was to determine the effect of atrioventricular node ablation on long-term survival in patients with AF and LV dysfunction. Survival was determined by the Kaplan-Meier method for 56 study patients with LV ejection fraction (EF) < or =40% who underwent atrioventricular node ablation and pacemaker implantation and 56 age- and gender-matched control patients with AF and LVEF >40%, and age- and gender-matched control subjects from Minnesota. Groups were compared using the log-rank test. In study patients (age 69 +/- 10 years; 45 men), LVEF was 26% +/- 8% and 34% +/- 13% (p <0.001) before and after ablation, respectively. During follow-up (40 +/- 23 months), 23 patients died. Observed survival was worse than that of normal subjects (p <0.001) and control patients (p = 0.005). After ablation, LVEF nearly normalized (> or =45%) in 16 study patients (29%), in whom observed survival was comparable to that of normal subjects (p = 0.37). Coronary artery disease, hyperlipidemia, chronic renal failure, previous myocardial infarction, and coronary artery operation were independent predictors for mortality. Near normalization of LVEF occurred in 29% of study patients, suggesting that AF-induced EF reduction is reversible in many patients. Normal survival in patients with reversible LV dysfunction highlights potential survival benefits of rate control. Poor survival in patients with persistent LV dysfunction confirms the importance of optimal medical therapy.

Growth differentiation factor 15 is associated with left atrial/left atrial appendage thrombus in patients with nonvalvular atrial fibrillation.

PubMed

Hu, Xiao Feng; Zhan, Rui; Xu, Shanhu; Wang, Junjun; Wu, Jiong; Liu, Xiaoli; Li, Yaguo; Chen, Linhui

2018-01-01

There is evidence suggesting that growth differentiation factor 15 (GDF-15) appears to be associated with stroke in patients with atrial fibrillation (AF). AF-related thromboembolic stroke is predominantly attributed to the thrombus from the left atrium (LA) or left atrial appendage (LAA). GDF-15 is related to LA/LAA thrombus in nonvalvular AF (NVAF) patients. A total of 894 patients with NVAF without anticoagulation therapy were included in this study. All patients routinely underwent transesophageal echocardiography for detection of LA/LAA thrombus. GDF-15 was measured by enzyme-linked immunosorbent assay. Logistic regression models were used to test for association. LA/LAA thrombus was detected by transesophageal echocardiography in 69 (7.72%) patients with AF. The GDF-15 levels in the patients with LA/LAA thrombus were significantly higher than those without LA/LAA thrombus (log 10 GDF-15: 2.989 ± 0.023 ng/L vs 2.831 ± 0.007 ng/L; P < 0.001). Logistic regression analysis showed that GDF-15 was an independent risk factor for LA/LAA thrombus (odds ratio [per quarter]: 1.799, 95% confidence interval: 1.381-2.344, P < 0.001) after adjusting for potential clinical risk factors. The optimal cutoff point for GDF-15 predicting LA/LAA thrombus was 809.9 ng/L (sensitivity, 75.3%; specificity, 61.5%), determined by ROC curve. The area under the curve was 0.709 (95% confidence interval: 0.644-0.770, P < 0.001). Elevated GDF-15 indicated a significantly increased risk for LA/LAA thrombus in NVAF patients. Thus, GDF-15 might be a potentially useful adjunct in discriminating LA/LAA thrombus in NVAF patients. © 2018 Wiley Periodicals, Inc.

Rate versus rhythm control and outcomes in patients with atrial fibrillation and chronic kidney disease: data from the GUSTO-III Trial.

PubMed

Williams, Eric S; Thompson, Vivian P; Chiswell, Karen E; Alexander, John H; White, Harvey D; Ohman, E Magnus; Al-Khatib, Sana M

2013-01-01

Atrial fibrillation (AF) and chronic kidney disease (CKD) have both been shown to portend worse outcomes after acute myocardial infarction (MI); however, the benefit of a rhythm control strategy in patients with CKD post-MI is unclear. We prospectively studied 985 patients with new-onset AF post-MI in the GUSTO-III trial, of whom 413 (42%) had CKD (creatinine clearance < 60 mL/min). A rhythm control strategy, defined as the use of an antiarrhythmic medication and/or electrical cardioversion, was used in 346 (35%) of patients. A rhythm control strategy was used in 34% of patients with CKD and 36% of patients with no CKD. At hospital discharge, sinus rhythm was present in 487 (76%) of patients treated with a rate control strategy, vs. 276 (80%) in those treated with rhythm control (p = 0.20). CKD was associated with a lower odds of sinus rhythm at discharge (unadjusted OR 0.56, 95% CI 0.38-0.84, p < 0.001). However, in multivariable analyses, treatment with a rhythm control strategy was not associated with discharge rhythm (HR 1.068, 95% CI 0.69-1.66, p = 0.77), 30-day mortality (HR 0.78, 95% CI 0.54-1.12, p = 0.18) or mortality from day 30 to 1 year (HR 1.00, 95% CI 0.59-1.69, p = 0.99). CKD status did not significantly impact the relationship between rhythm control and outcomes. Treatment with a rhythm or rate control strategy does not signifi cantly impact short-term or long-term mortality in patients with post-MI AF, regardless of kidney disease status. Future studies to investigate the optimal management of AF in CKD patients are needed.

Common Atrial Fibrillation Risk Alleles at 4q25 Predict Recurrence after Catheter-based Atrial Fibrillation Ablation

PubMed Central

Shoemaker, M. Benjamin; Muhammad, Raafia; Parvez, Babar; White, Brenda W.; Streur, Megan; Song, Yanna; Stubblefield, Tanya; Kucera, Gayle; Blair, Marcia; Rytlewski, Jason; Parvathaneni, Sunthosh; Nagarakanti, Rangadham; Saavedra, Pablo; Ellis, Christopher; Whalen, S. Patrick; Roden, Dan M; Darbar, Dawood

2012-01-01

Background Common single nucleotide polymorphisms (SNPs) at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical AF. Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5–30% of AF cases. Objective To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases. Methods Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years, 71% male, 89% typical AF) between 2004 and 2011. The primary endpoint was time to recurrence of any non-sinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF; [AT/AF]). Results Two-hundred AT/AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76 95% confidence interval [CI] 0.6–0.95, P=0.016) compared with wild-type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio = 0.79, 95% CI 0.62–0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio = 0.61, 95% CI 0.37–1.0) (P=0.037). Conclusion Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of predominately typical AF patients. Our findings suggest the rs2200733 polymorphism may hold promise as an as an objectively measured patient characteristic that can used as a clinical tool for selection of patients for AF ablation. PMID:23178686

A Specific Antibody to Neuropeptide AF1 (KNEFIRFamide) Recognizes a Small Subset of Neurons in Ascaris suum: Differences from Caenorhabditis elegans

PubMed Central

Sithigorngul, Paisarn; Jarecki, Jessica L.; Stretton, Antony O.W.

2016-01-01

A monoclonal antibody, AF1-003, highly specific to the Ascaris suum neuropeptide AF1 (KNEFIRFamide), was generated. This antibody binds strongly to AF1 and extremely weakly to other peptides with C-terminal FIR-Famide: AF5 (SGKPTFIRFamide), AF6 (FIRFamide), and AF7 (AGPRFIRFamide). It does not recognize 35 other AF (A. suum FMRFamide-like) peptides at the highest concentration tested, nor does it recognize FMRFamide. When crude peptide extracts of A. suum are fractionated by two-step HPLC, the only fractions recognized by AF1-003 are those comigrating with synthetic AF1. By immunocytochemistry, antibody AF1-003 recognizes a small subset of the 298 neurons of A. suum: these include the paired URX and RIP neurons, two pairs of lateral ganglion neurons in the head, and the unpaired PQR and PDA or -B tail neurons that send processes to the head along the dorsal and ventral nerve cords, respectively. AF1 immunoreactivity is also seen in three pairs of pharyngeal neurons. Mass spectroscopy (MS) shows the presence of AF1 in the head, pharynx, and dorsal and ventral nerve cords. In A. suum, the neurons that contain AF1 show little overlap with neurons that express green fluorescent protein constructs targeting the flp-8 gene, which encodes AF1 in Caenorhabditis elegans (Kim and Li [2004] J. Comp. Neurol. 475:540– 550); the URX neurons express AF1 in both species, but, in C. elegans, flp-8 expression was not detected in RIP, PQR, and PDA or -B or in the pharynx. Other, less specific monoclonal antibodies recognize AF1, as well as other peptides to differing degrees; these antibodies are useful reagents for determination of neuronal morphology. PMID:21452223

Atrial Fibrillation Detection During 24-Hour Ambulatory Blood Pressure Monitoring: Comparison With 24-Hour Electrocardiography.

PubMed

Kollias, Anastasios; Destounis, Antonios; Kalogeropoulos, Petros; Kyriakoulis, Konstantinos G; Ntineri, Angeliki; Stergiou, George S

2018-07-01

This study assessed the diagnostic accuracy of a novel 24-hour ambulatory blood pressure (ABP) monitor (Microlife WatchBP O3 Afib) with implemented algorithm for automated atrial fibrillation (AF) detection during each ABP measurement. One hundred subjects (mean age 70.6±8.2 [SD] years; men 53%; hypertensives 85%; 17 with permanent AF; 4 paroxysmal AF; and 79 non-AF) had simultaneous 24-hour ABP monitoring and 24-hour Holter monitoring. Among a total of 6410 valid ABP readings, 1091 (17%) were taken in ECG AF rhythm. In reading-to-reading ABP analysis, the sensitivity, specificity, and accuracy of ABP monitoring in detecting AF were 93%, 87%, and 88%, respectively. In non-AF subjects, 12.8% of the 24-hour ABP readings indicated false-positive AF, of whom 27% were taken during supraventricular premature beats. There was a strong association between the proportion of false-positive AF readings and that of supraventricular premature beats ( r =0.67; P <0.001). Receiver operating characteristic curve revealed that in paroxysmal AF and non-AF subjects, AF-positive readings at 26% during 24-hour ABP monitoring had 100%/85% sensitivity/specificity (area under the curve 0.91; P <0.01) for detecting paroxysmal AF. These findings suggest that in elderly hypertensives, a novel 24-hour ABP monitor with AF detector has high sensitivity and moderate specificity for AF screening during routine ABP monitoring. Thus, in elderly hypertensives, a 24-hour ABP recording with at least 26% of the readings suggesting AF indicates a high probability for AF diagnosis and should be regarded as an indication for performing 24-hour Holter monitoring. © 2018 American Heart Association, Inc.

Cyclic variations of fuel-droplet distribution during the early intake stroke of a lean-burn stratified-charge spark-ignition engine

NASA Astrophysics Data System (ADS)

Aleiferis, P. G.; Hardalupas, Y.; Taylor, A. M. K. P.; Ishii, K.; Urata, Y.

2005-11-01

Lean-burn spark-ignition engines exhibit higher efficiency and lower specific emissions in comparison with stoichiometrically charged engines. However, as the air-to-fuel (A/F) ratio of the mixture is made leaner than stoichiometric, cycle-by-cycle variations in the early stages of in-cylinder combustion, and subsequent indicated mean effective pressure (IMEP), become more pronounced and limit the range of lean-burn operation. Viable lean-burn engines promote charge stratification, the mixture near the spark plug being richer than the cylinder volume averaged value. Recent work has shown that cycle-by-cycle variations in the early stages of combustion in a stratified-charge engine can be associated with variations in both the local value of A/F ratio near the spark plug around ignition timing, as well as in the volume averaged value of the A/F ratio. The objective of the current work was to identify possible sources of such variability in A/F ratio by studying the in-cylinder field of fuel-droplet distribution during the early intake stroke. This field was visualised in an optical single-cylinder 4-valve pentroof-type spark-ignition engine by means of laser-sheet illumination in planes parallel to the cylinder head gasket 6 and 10 mm below the spark plug. The engine was run with port-injected isooctane at 1500 rpm with 30% volumetric efficiency and air-to-fuel ratio corresponding to both stoichiometric firing (A/F=15, Φ =1.0) and mixture strength close to the lean limit of stable operation (A/F=22, Φ =0.68). Images of Mie intensity scattered by the cloud of fuel droplets were acquired on a cycle-by-cycle basis. These were studied in order to establish possible correlations between the cyclic variations in size, location and scattered-light intensity of the cloud of droplets with the respective variations in IMEP. Because of the low level of Mie intensity scattered by the droplets and because of problems related to elastic scattering on the walls of the combustion chamber, as well as problems related to engine “rocking” at the operating conditions close to the misfire limit, the acquired images were processed for background subtraction by using a PIV-based data correction algorithm. After this processing, the arrival and leaving timings of fuel droplets into the illuminated plane were found not to vary significantly on a cycle-by-cycle basis but the recorded cycle-by-cycle variations in Mie intensity suggested that the amount of fuel in the cylinder could have been 6 26% greater for the “strong” cycles with IMEP 115% higher than the average IMEP, than the ones imaged for “weak” cycles at less than 85% the average IMEP. This would correspond to a maximum cyclic variability in the in-cylinder equivalence ratio Φ of the order of 0.17.

Incident Atrial Fibrillation and the Risk of Congestive Heart Failure, Myocardial Infarction, End-Stage Kidney Disease, and Mortality Among Patients With a Decreased Estimated GFR.

PubMed

Massicotte-Azarniouch, David; Kuwornu, John Paul; Carrero, Juan-Jesus; Lam, Ngan N; Molnar, Amber O; Zimmerman, Deborah; McCallum, Megan K; Garg, Amit X; Sood, Manish M

2018-02-01

The association of atrial fibrillation (AF), estimated glomerular filtration rate (eGFR), and adverse events remains unknown. Population-based retrospective cohort study from Ontario, Canada. 1,422,978 adult residents with eGFRs < 90mL/min/1.73m 2 from April 1, 2006, through March 31, 2015. A diagnosis of AF at hospitalization. Congestive heart failure (CHF), myocardial infarction (MI), end-stage kidney disease, all-cause mortality. All adverse events were more frequent in individuals with AF (93,414 propensity score matched) compared to no AF, and this difference was more pronounced within the first 6 months of the index date (CHF: 3.04% [AF] vs 0.28% [no AF], subdistribution HR [sHR] of 11.57 [95% CI, 10.26-13.05]; MI: 0.97% [AF] vs 0.21% [no AF], sHR of 4.76 [95% CI, 4.17-5.43]; end-stage kidney disease: 0.16% [AF] vs 0.03% [no AF], sHR of 5.84 [95% CI, 3.82-8.93]; and all-cause mortality: 6.11% [AF] vs 2.50% [no AF], HR of 2.62 [95% CI, 2.50-2.76]) than in the period more than 6 months after the index date (CHF: 6.87% [AF] vs 2.87% [no AF], sHR of 2.64 [95% CI, 2.55-2.74]; MI: 2.21% [AF] vs 1.81% [no AF], sHR of 1.24 [95% CI, 1.18-1.30]; end-stage kidney disease: 0.52% [AF] vs 0.32% [no AF], sHR of 1.75 [95% CI, 1.57-1.95]; and all-cause mortality: 15.55% [AF] vs 15.10% [no AF], HR of 1.07 [95% CI, 1.04-1.10]). The results accounted for the competing risk for mortality. eGFR level modified the effect of AF on CHF (P for interaction < 0.05). Observational study design does not permit determination of causality; only a single outpatient eGFR measure was used; medication data were not included. Incident AF is associated with a high risk for adverse outcomes in patients with eGFRs < 90mL/min/1.73m 2 . Because the risk is exceedingly high within the first 6 months after AF diagnosis, therapeutic interventions and monitoring may improve outcomes. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Health Information in Somali (Af-Soomaali )

MedlinePlus

... Af-Soomaali (Somali) Bilingual PDF Health Information Translations Pendulum Exercises for Shoulder - Af-Soomaali (Somali) Bilingual PDF ... Af-Soomaali (Somali) Bilingual PDF Health Information Translations Pendulum Exercises for Shoulder - Af-Soomaali (Somali) Bilingual PDF ...

Relationship of Preexisting Cardiovascular Comorbidities to Newly Diagnosed Atrial Fibrillation After Ischemic Stroke.

PubMed

Bisson, Arnaud; Clementy, Nicolas; Bodin, Alexandre; Angoulvant, Denis; Babuty, Dominique; Lip, Gregory Y H; Fauchier, Laurent

2017-10-01

There remains uncertainty as whether newly diagnosed atrial fibrillation (AF) after ischemic stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms. We aimed to determine whether cardiovascular comorbidities in patients with new AF after ischemic stroke differ from patients with previous known AF or without AF. This French longitudinal cohort study was based on the database covering hospital care from 2009 to 2012 for the entire population. Of 336 291 patients with ischemic stroke, 240 459 (71.5%) had no AF and 95 832 (28.5%) had previously known AF at baseline. Patients without previous AF had a mean CHA 2 DS 2 -VASc score of 4.98±1.63 SD. During a mean follow-up of 7.9±11.5 months, 14 095 (5.9%) of these patients had incident AF, representing an annual incidence of AF after ischemic stroke of 8.9 per 100 person-years (95% confidence interval, 8.8-9.0). New AF patients had higher CHA 2 DS 2 -VASc score, more likely comorbidities, and more frequent history of previous transient ischemic attack than patients with previous known AF or without AF. Preexisting cardiovascular comorbidities underlie AF newly diagnosed after stroke. Consequently, these high-risk patients should be closely monitored for incident AF to facilitate an earlier diagnosis of AF and avoid stroke with appropriate thromboprophylaxis. © 2017 American Heart Association, Inc.

Early, de novo atrial fibrillation after coronary artery bypass grafting: Facts and features.

PubMed

Yaksh, Ameeta; Kik, Charles; Knops, Paul; van Ettinger, Maarten J B; Bogers, Ad J J C; de Groot, Natasja M S

2017-02-01

Knowledge of the mechanism underlying post-operative atrial fibrillation (PoAF) is essential for development of preventive measures. The incidence and characteristics of both PoAF and supraventricular premature beats triggering PoAF, their interrelationship and alterations over time have never been examined. The goal of this study is therefore to examine the correlation between the incidence and characteristics of supraventricular premature beats (SVPBs) and PoAF episodes in patients undergoing CABG in the first five post-operative days. PoAF episodes (N=327) and SVPBs (N=141,873) were characterized in 29 patients (63±9 years; 22 (76%) male) undergoing coronary artery bypass grafting and compared with a control group of patients without PoAF by using continuous cardiac rhythm monitoring during the first 5 days after surgery. Most patients (N=18, 62%) had multiple PoAF episodes; the median number of PoAF episodes per patient was 3 and varied between 1 and 139. The majority of PoAF episodes developed on the second and third post-operative day (55%). The averaged median duration of PoAF episodes per patient was 469±1085 min. Patients with PoAF had a higher SVPBs burden compared to subjects without PoAF (0.9% vs 0.2%, P<.001). SVPBs initiating PoAF had shorter coupling intervals than SVPBs which did not initiate PoAF episodes (58% vs 64% (P<.001) and were preceded by heart rate acceleration. PoAF episodes are mainly repetitive though transient in nature. There was a considerable inter-individual variation in both AF and SVPB characteristics, despite a similar underlying clinical profile. The SVPB burden is higher in patients with PoAF and the mode of onset is characterized by short coupled SVPBs. Determination of individual post-operative dysrhythmia profiles enables identification of patients at risk for developing PoAF. Copyright © 2016 Elsevier Inc. All rights reserved.

Is HATCH score a reliable predictor of atrial fibrillation after cavotricuspid isthmus ablation for typical atrial flutter?

PubMed

García-Seara, Javier; Gude Sampedro, Francisco; Martínez Sande, Jose L; Fernández López, Xesus Alberte; Rodríguez Mañero, Moisés; González Melchor, Laila; Alvarez Alvarez, Belén; Iglesias Alvarez, Diego; González Juanatey, José Ramón

2016-09-01

We determined the effectiveness of the HATCH score in patients with typical atrial flutter (AFl) undergoing cavotricuspid isthmus (CTI) ablation to predict long-term atrial fibrillation (AF). We conducted an observational retrospective single-center cohort study including all patients admitted to our hospital for a CTI ablation between 1998 and 2010. The patients were divided into four categories: 1) new-onset AF (no prior AF and AF during follow-up (FU)); 2) old AF (prior AF and no AF during FU); 3) prior and post AF (AF prior and post CTI ablation); and 4) no AF. Four hundred and eight patients were included. In patients without prior AF, the hazard ratio (HR) for new-onset AF during FU was 0.98 (CI 95%: 0.65-1.50; p = 0.95) and 1.00 (CI 95%: 0.57-1.77; p = 0.98) for HATCH ≥ 2 and HATCH ≥ 3, respectively. In patients with prior AF, the HR for AF was 1.41 (CI 95%: 0.87-2.28; p = 0.17) and 1.79 (CI 95%: 0.96-3.35; p = 0.06), for HATCH ≥ 2 and HATCH ≥ 3, respectively. Left atrial enlargement was positively correlated with the occurrence of AF during FU, especially in the subgroup without prior AF, which had a HR of 2.44 (CI 95%: 1.35-4.40; p = 0.003), a HR of 2.88 (CI 95%: 1.36-6.10; p = 0.006) and a HR of 3.68 (CI 95%: 1.71-7.94; p = 0.001), for slight, moderate and severely dilated left atrial dimension, respectively, compared with a normal value. HATCH score did not predict AF in patients with typical AFl who underwent CTI ablation. Basal left atrium dimension could help predict new-onset AF.

The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

DTIC Science & Technology

2015-10-01

mutation, U2AF1(S34F), on hematopoiesis and pre-mRNA splicing in vivo, we created doxycycline-inducible U2AF1(WT) and U2AF1(S34F) transgenic mice...U2AF1(S34F) versus U2AF1(WT). Together, these results suggest that mutant U2AF1 expression contributes to the altered hematopoiesis and pre-mRNA...Spliceosome, Mouse Model, Hematopoiesis , RNA-seq, U2AF1 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME

Installation Restoration Program. Phase 1 - Records Search AAC-Northern Region, Galena AFS, Campion AFS, Cape Lisburne AFS, Fort Yukon AFS, Indian Mountain AFS, Kotzebue AFS, Murphy Dome AFS, and Tin City AFS

DTIC Science & Technology

1985-09-01

GM SILTY GRAVEL GP POORLY GRADED GRAVEL SM SILTY SAND SP POORLY GRADED SAND SW WELL GRADED SAND ML LOW PLASTICITY SILT SOURCE: INSTALLATION DOCUMENTS... plastic on the side toward th’e beach in an attempt to prevent migration of fuel. to the beach. During the site visit for this Phase I IRP study the...Force have included garbage, refuse, incinerator ash (since 1975), wood, metal, plastic and bulky - materials such as construction and demolition debris

Ion-exchange chromatography purification of extracellular vesicles.

PubMed

Kosanović, Maja; Milutinović, Bojana; Goč, Sanja; Mitić, Ninoslav; Janković, Miroslava

2017-08-01

Despite numerous studies, isolating pure preparations of extracellular vesicles (EVs) has proven challenging. Here, we compared ion-exchange chromatography (IEC) to the widely used sucrose density gradient (SDG) centrifugation method for the purification of EVs. EVs in bulk were isolated from pooled normal human amniotic fluid (AF) by differential centrifugation followed by IEC or sucrose density gradient separation. The purity of the isolated EVs was evaluated by electrophoresis and lectin blotting/immuno blotting to monitor the distribution of total proteins, different EVs markers, and selected N-glycans. Our data showed efficient separation of negatively charged EVs from other differently charged molecules, while comparative profiling of EVs using SDG centrifugation confirmed anion-exchange chromatography is advantageous for EV purification. Finally, although this IEC-based method was validated using AF, the approach should be readily applicable to isolation of EVs from other sources as well.

Factors effecting impact of Aspergillus fumigatus sensitization in cystic fibrosis.

PubMed

Kanthan, Senthooran Kathirgama; Bush, Andrew; Kemp, Michael; Buchdahl, Roger

2007-09-01

The clinical impact of Aspergillus fumigatus (Af) sensitization in cystic fibrosis (CF) is controversial. We examined the effect of Af sensitization (Afs) on pulmonary function and growth using a retrospective cohort analysis over two 5-year study periods: 1996-2000 (19 Afs cases and 19 controls) and 2001-2005 (24 Afs cases and 23 controls). Sensitization was defined as Af specific radioallergosorbent test (RAST) >or= 17.5 iu/ml and total serum IgE level >or=150 iu/ml. We examined the impact of changing treatment schedules over these periods. Afs cases had lower median FEV(1) %predicted (%PR) compared to matched controls 1996: 67 versus 80, P < 0.01; 2001: 78 versus 93, P < 0.01. Afs cases in the 2001 cohort had a higher FEV(1) %PR compared to Afs cases in the 1996 cohort: 78 versus 67, P < 0.01. For the 1996 Afs cohort FEV(1) %PR fell significantly over 5 years but not for the 2001 Afs cohort. Af RAST and total IgE reflected the changes in pulmonary function. Children in the 2001 Afs cohort were prescribed significantly more oral antifungal treatment (odds ratio 4.3, 95%CI 1.2-15.7, P = 0.03). Afs children continue to have poorer lung function compared to controls but this observational, hypothesis generating study, suggests that the use of antifungal treatment is associated with better lung function. (c) 2007 Wiley-Liss, Inc.

Effect of the Epicardial Adipose Tissue Volume on the Prevalence of Paroxysmal and Persistent Atrial Fibrillation.

PubMed

Oba, Kageyuki; Maeda, Minetaka; Maimaituxun, Gulinu; Yamaguchi, Satoshi; Arasaki, Osamu; Fukuda, Daiju; Yagi, Shusuke; Hirata, Yukina; Nishio, Susumu; Iwase, Takashi; Takao, Shoichiro; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Harada, Masafumi; Masuzaki, Hiroaki; Sata, Masataka; Shimabukuro, Michio

2018-05-25

Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling.Methods and Results:Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m 2 ) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m 2 , P<0.01). The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.

Determining the Optimal Dose of Adenosine for Unmasking Dormant Pulmonary Vein Conduction Following Atrial Fibrillation Ablation: Electrophysiological and Hemodynamic Assessment. DORMANT-AF Study.

PubMed

Prabhu, Sandeep; Mackin, Vincent; McLellan, Alex J A; Phan, Tuong; McGlade, Desmond; Ling, Liang-Han; Peck, Kah Y; Voskoboinik, Alexandr; Pathik, Bupesh; Nalliah, Chrishan J; Wong, Geoff R; Azzopardi, Sonia M; Lee, Geoffrey; Mariani, Justin; Taylor, Andrew J; Kalman, Jonathan M; Kistler, Peter M

2017-01-01

ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. The significance of adenosine induced dormant pulmonary vein (PV) conduction in atrial fibrillation (AF) ablation remains controversial. The optimal dose of adenosine to determine dormant PV conduction is yet to be systematically explored. ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. Consecutive patients undergoing index AF ablation received 3 adenosine doses (12, 18, and 24 mg) in a randomized blinded order, immediately after pulmonary vein isolation (PVI). Electrophysiological (PR prolongation, AV block (AVB) and PV reconnection) and hemodynamic (BP) parameters were measured. A total, 339 doses (113/dose) assessed 191 PVs in 50 patients (66% male, 72% PAF, 52% hypertensive). Dormant PV conduction occurred in 28% of patients (16.5% [32] of PVs). All cases were associated with AVB (AVB: PV reconnection vs. no PV reconnection 100% vs. 83%, P = 0.007). AVB occurred more frequently at 24 mg versus 12 mg (92% vs. 82%, P = 0.019) but not versus 18 mg (91%, P = 0.62). AVB duration progressed between 12 mg (12.0 ± 8.9 seconds), 18 mg (16.1 ± 9.1 seconds, P = 0.001), and 24 mg (19.0 ± 9.3 seconds, P < 0.001) doses. MBP fell further at 24 mg (ΔMBP: 27 ± 12 mmHg) and 18 mg (26 ± 13 mmHg) doses compared to 12 mg (22 ± 10 mmHg vs., P < 0.001). A significant reduction in AVB in patients >110 kg (65% vs. 91% in 70-110 kg group, P < 0.001) in response to adenosine was seen. ELECTROPHYSIOLOGICAL AND HEMODYNAMIC ASSESSMENT. An adenosine dose producing AVB is required to unmask dormant PV conduction. AVB is significantly reduced in patients >110 kg. Weight and dosing variability may in part explain the conflicting results of studies evaluating the clinical utility of adenosine in PVI. © 2016 Wiley Periodicals, Inc.

Left-to-right atrial inward rectifier potassium current gradients in patients with paroxysmal versus chronic atrial fibrillation.

PubMed

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2010-10-01

Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right-dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K(+) currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of I(K1) (Kir2.1 and Kir2.3) and I(K,ACh) (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) I(K,ACh) was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced I(K,ACh) in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches.

Ethnic Distribution of ECG Predictors of Atrial Fibrillation and Its Impact on Understanding the Ethnic Distribution of Ischemic Stroke in the Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Soliman, Elsayed Z.; Prineas, Ronald J.; Case, L. Douglas; Zhang, Zhu-ming; Goff, David C.

2009-01-01

Background and Purpose The paradox of the reported low prevalence of atrial fibrillation (AF) in blacks compared with whites despite higher stroke rates in the former could be related to limitations in the current methods used to diagnose AF in population-based studies. Hence, this study aimed to use the ethnic distribution of ECG predictors of AF as measures of AF propensity in different ethnic groups. Methods The distribution of baseline measures of P-wave terminal force, P-wave duration, P-wave area, and PR duration (referred to as AF predictors) were compared by ethnicity in 15 429 participants (27% black) from the Atherosclerosis Risk in Communities (ARIC) study by unpaired t test, χ2, and logistic-regression analysis, as appropriate. Cox proportional-hazards analysis was used to separately examine the association of AF predictors with incident AF and ischemic stroke. Results Whereas AF was significantly less common in blacks compared with whites (0.24% vs 0.95%, P<0.0001), similar to what has been reported in previous studies, blacks had significantly higher and more abnormal values of AF predictors (P<0.0001 for all comparisons). Black ethnicity was significantly associated with abnormal AF predictors compared with whites; odds ratios for different AF predictors ranged from 2.1 to 3.1. AF predictors were significantly and independently associated with AF and ischemic stroke with no significant interaction between ethnicity and AF predictors, findings that further justify using AF predictors as an earlier indicator of future risk of AF and stroke. Conclusions There is a disconnect between the ethnic distribution of AF predictors and the ethnic distribution of AF, probably because the former, unlike the latter, do not suffer from low sensitivity. These results raise the possibility that blacks might actually have a higher prevalence of AF that might have been missed by previous studies owing to limited methodology, a difference that could partially explain the greater stroke risk in blacks. PMID:19213946

Left-to-Right Atrial Inward Rectifier Potassium Current Gradients in Patients With Paroxysmal Versus Chronic Atrial Fibrillation

PubMed Central

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R.; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2018-01-01

Background Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right–dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K+ currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Methods and Results Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of IK1 (Kir2.1 and Kir2.3) and IK,ACh (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) IK,ACh was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced IK,ACh in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Conclusions Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches. PMID:20657029

Silent Atrial Fibrillation in Elderly Pacemaker Users: A Randomized Trial Using Home Monitoring.

PubMed

Lima, Ceb; Martinelli, M; Peixoto, G L; Siqueira, S F; Wajngarten, Maurício; Silva, Rodrigo Tavares; Costa, Roberto; Filho, Roberto; Ramires, José Antônio Franchini

2016-05-01

Pacemaker with remote monitoring (PRM) may be useful for silent atrial fibrillation (AF) detection. The aims of this study were to evaluate the incidence of silent AF, the role of PRM, and to determine predictors of silent AF occurrence. Three hundred elderly patients with permanent pacemaker (PPM) were randomly assigned to the remote group (RG) or control group (CG). All patients received PPM with remote monitoring capabilities. Primary end point was AF occurrence rate and the secondary end points were time to AF detection and number of days with AF. During the average follow-up of 15.7±7.7 months, AF episodes were detected in 21.6% (RG = 24% vs CG = 19.3%, P = 0.36]. There was no difference in the time to detect the first AF episode. However, the median time to detect AF recurrence in the RG was lower than that in the CG (54 days vs 100 days, P = 0.004). The average number of days with AF was 16.0 and 51.2 in the RG and CG, respectively (P = 0.028). Predictors of silent AF were left atrial diameter (odds ratio [OR] 1.2; 95% CI = 1.1-1.3; P < 0.001) and diastolic dysfunction (OR 4.8; 95% CI = 1.6-14.0; P = 0.005). The incidence of silent AF is high in elderly patients with pacemaker; left atrial diameter and diastolic dysfunction were predictors of its occurrence. AF monitoring by means of pacemaker is a valuable tool for silent AF detection and continuous remote monitoring allows early AF recurrence detection and reduces the number of days with AF. © 2015 Wiley Periodicals, Inc.

Association of Left Atrial Function Index With Late Atrial Fibrillation Recurrence after Catheter Ablation.

PubMed

Sardana, Mayank; Ogunsua, Adedotun A; Spring, Matthew; Shaikh, Amir; Asamoah, Owusu; Stokken, Glenn; Browning, Clifford; Ennis, Cynthia; Donahue, J Kevin; Rosenthal, Lawrence S; Floyd, Kevin C; Aurigemma, Gerard P; Parikh, Nisha I; McManus, David D

2016-12-01

Although catheter ablation (CA) for atrial fibrillation (AF) is commonly used to improve symptoms, AF recurrence is common and new tools are needed to better inform patient selection for CA. Left atrial function index (LAFI), an echocardiographic measure of atrial mechanical function, has shown promise as a noninvasive predictor of AF. We hypothesized that LAFI would relate to AF recurrence after CA. All AF patients undergoing index CA were enrolled in a prospective institutional AF Treatment Registry between 2011 and 2014. LAFI was measured post hoc from pre-ablation clinical echocardiographic images in 168 participants. Participants were mostly male (33% female), middle-aged (60 ± 10 years), obese and had paroxysmal AF (64%). Mean LAFI was 25.9 ± 17.6. Over 12 months of follow-up, 78 participants (46%) experienced a late AF recurrence. In logistic regression analyses adjusting for factors known to be associated with AF, lower LAFI remained associated with AF recurrence after CA [OR 0.04 (0.01-0.67), P = 0.02]. LAFI discriminated AF recurrence after CA slightly better than CHADS2 (C-statistic 0.60 LAFI, 0.57 CHADS2). For participants with persistent AF, LAFI performed significantly better than CHADS2 score (C statistic = 0.79 LAFI, 0.56 CHADS2, P = 0.02). LAFI, an echocardiographic measure of atrial function, is associated with AF recurrence after CA and has improved ability to discriminate AF recurrence as compared to the CHADS-2 score, especially among persistent AF patients. Since LAFI can be calculated using standard 2D echocardiographic images, it may be a helpful tool for predicting AF recurrence. © 2016 Wiley Periodicals, Inc.

MUNICIPAL WASTE COMBUSTION MULTIPOLLUTANT STUDY EMISSION TEST REPORT, MAINE ENERGY RECOVERY COMPANY, REFUSE DERIVED FUEL FACILITY, BIDDEFORD, MAINE - VOLUME II: APPENDICES A-F

EPA Science Inventory

The report gives results of an emission test of a new municipal solid waste combustor, in Biddeford, ME, that burns refuse-derived fuel and is equipped with a lime spray dryer fabric filter (SD/FF) emission control system. Control efficiency of the SD/FF emission control system ...

DISCORDANCE BETWEEN BLUE-LIGHT AUTOFLUORESCENCE AND NEAR-INFRARED AUTOFLUORESCENCE IN AGE-RELATED MACULAR DEGENERATION.

PubMed

Heiferman, Michael J; Fawzi, Amani A

2016-12-01

To identify the origin and significance of discordance between blue-light autofluorescence (BL-AF; 488 nm) and near-infrared autofluorescence (NI-AF; 787 nm) in patients with age-related macular degeneration (AMD). A total of 86 eyes of 59 patients with a diagnosis of AMD were included in this cross-sectional study conducted between March 9, 2015 and May 1, 2015. A masked observer examined the BL-AF, NI-AF, and spectral-domain optical coherence tomography images. Areas with discordance of autofluorescence patterns between NI-AF and BL-AF images were correlated with structural findings at the corresponding location in optical coherence tomography scans. Seventy-nine eyes had discordance between BL-AF and NI-AF. The most common optical coherence tomography finding accounting for these discrepancies was pigment migration accounting for 35 lesions in 21 eyes. The most clinically relevant finding was geographic atrophy missed on BL-AF in 7 eyes. Our findings indicate that variations in the distribution of lipofuscin, melanin and melanolipofuscin account for the majority of discordance between BL-AF and NI-AF. Given our finding of missed geographic atrophy lesions on BL-AF in 24% of eyes with geographic atrophy (7/29 eyes), clinicians should consider multimodal imaging, including NI-AF and optical coherence tomography, especially in clinical trials of geographic atrophy.

Discordance between Blue-Light Autofluorescence and Near-Infrared Autofluorescence in Age-Related Macular Degeneration

PubMed Central

Heiferman, Michael J.; Fawzi, Amani A.

2016-01-01

Purpose To identify the origin and significance of discordance between blue-light autofluorescence (BL-AF; 488nm) and near-infrared autofluorescence (NI-AF; 787nm) in patients with age-related macular degeneration (AMD). Methods A total of 86 eyes of 59 patients with a diagnosis of AMD were included in this cross-sectional study conducted between March 9, 2015 and May 1, 2015. A masked observer examined the BL-AF, NI-AF, and spectral-domain optical coherence tomography (OCT) images. Areas with discordance of autofluorescence patterns between NI-AF and BL-AF images were correlated with structural findings at the corresponding location in OCT scans. Results 79 eyes had discordance between BL-AF and NI-AF. The most common OCT finding accounting for these discrepancies was pigment migration accounting for 35 lesions in 21 eyes. The most clinically relevant finding was geographic atrophy missed on BL-AF in seven eyes. Conclusions Our findings indicate that variations in the distribution of lipofuscin, melanin and melanolipofuscin account for the majority of discordance between BL-AF and NI-AF. Given our finding of missed geographic atrophy lesions on BL-AF in 24% of eyes with geographic atrophy (7/29 eyes), clinicians should consider multimodal imaging, including NI-AF and OCT, especially in clinical trials of geographic atrophy. PMID:28005672

Genetic diversity in cassava landraces grown on farms in Alta Floresta-MT, Brazil.

PubMed

Tiago, A V; Rossi, A A B; Tiago, P V; Carpejani, A A; Silva, B M; Hoogerheide, E S S; Yamashita, O M

2016-09-02

Brazil is considered one of the domestication centers of cassava (Manihot esculenta), containing a large part of the biological diversity and traditional knowledge of the species. The aim of the present study was to evaluate the genetic diversity of cassava landraces grown by farmers in the north of Mato Grosso State, Brazil, using inter simple sequence repeat (ISSR) molecular markers. The study was carried out in the municipality of Alta Floresta, MT, on farms located in two rural areas. Seventeen cassava landraces were selected. The DNA was extracted and polymerase chain reaction amplifications were performed using 15 ISSR primers. Genetic similarity estimates were calculated using Jaccard's index and the generated matrix was used for clustering the genotypes by using UPGMA and Tocher's methods. The 15 ISSR primers amplified 120 fragments, revealing 61.67% polymorphism. The polymorphism information content ranged from 0.04 to 0.61, averaging 0.39. The most similar genotypes were AF5 and AF8, whereas the least similar were AF1 and AF16. The UPGMA clustering method formed five groups. Group I included twelve landraces, Group II contained two, and the other groups contained one landrace each. Tocher's method resulted in six groups: 12 landraces clustered in one group, and the other groups each contained one landrace. The ISSR markers proved efficient in revealing genetic diversity among the cassava landraces. The landraces grown by farmers in the two rural areas of Alta Floresta have a great variability and, thus, can be exploited in programs for breeding and preservation of the species.

A QoS scheme for a congestion core network based on dissimilar QoS structures in smart-phone environments.

PubMed

Hong, Sung-Ryong; Na, Wonshik; Kang, Jang-Mook

2010-01-01

This study suggests an approach to effective transmission of multimedia content in a rapidly changing Internet environment including smart-phones. Guaranteeing QoS in networks is currently an important research topic. When transmitting Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand, network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this case, the AF1 packets that received the best quality of service in network A will receive the lowest in network B, which may result in dropping of packets in network B and vice versa. This study suggests a way to guarantee QoS between hosts by minimizing the loss of AF packet class when one network transmits AF class packets to another network with differing principles. It is expected that QoS guarantees and their experimental value may be utilized as principles which can be applied to various mobile-web environments based on smart-phones.

A QoS Scheme for a Congestion Core Network Based on Dissimilar QoS Structures in Smart-Phone Environments

PubMed Central

Hong, Sung-Ryong; Na, Wonshik; Kang, Jang-Mook

2010-01-01

This study suggests an approach to effective transmission of multimedia content in a rapidly changing Internet environment including smart-phones. Guaranteeing QoS in networks is currently an important research topic. When transmitting Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand, network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this case, the AF1 packets that received the best quality of service in network A will receive the lowest in network B, which may result in dropping of packets in network B and vice versa. This study suggests a way to guarantee QoS between hosts by minimizing the loss of AF packet class when one network transmits AF class packets to another network with differing principles. It is expected that QoS guarantees and their experimental value may be utilized as principles which can be applied to various mobile-web environments based on smart-phones. PMID:22163453

Performance and age of African and non-African runners in half- and full marathons held in Switzerland, 2000–2010

PubMed Central

Aschmann, André; Knechtle, Beat; Cribari, Marco; Rüst, Christoph Alexander; Onywera, Vincent; Rosemann, Thomas; Lepers, Romuald

2013-01-01

Background Endurance running performance of African (AF) and non-African (NAF) athletes is investigated, with better performances seen for Africans. To date, no study has compared the age of peak performance between AF and NAF runners. The present research is an analysis of the age and running performance of top AF and NAF athletes, using the hypothesis that AF athletes were younger and faster than NAF athletes. Methods Age and performance of male and female AF and NAF athletes in half-marathons and marathons held in Switzerland in 2000–2010 were investigated using single and multilevel hierarchical regression analyses. Results For half-marathons, male NAF runners were older than male AF runners (P = 0.02; NAF, 31.1 years ± 6.4 years versus AF, 26.2 years ± 4.9 years), and their running time was longer (P = 0.02; NAF, 65.3 minutes ± 1.7 minutes versus AF, 64.1 minutes ± 0.9 minutes). In marathons, differences between NAF and AF male runners in age (NAF, 33.0 years ± 4.8 years versus AF, 28.6 years ± 3.8 years; P < 0.01) and running time (NAF, 139.5 minutes ± 5.6 minutes versus AF, 133.3 minutes ± 2.7 minutes; P < 0.01) were more pronounced. There was no difference in age (NAF, 31.0 years ± 7.0 years versus AF, 26.7 years ± 6.0 years; P > 0.05) or running time (NAF, 75.0 minutes ± 3.7 minutes versus AF, 75.6 minutes ± 5.3 minutes; P > 0.05) between NAF and AF female half-marathoners. For marathoners, NAF women were older than AF female runners (P = 0.03; NAF, 31.6 years ± 4.8 years versus AF, 27.8 years ± 5.3 years), but their running times were similar (NAF, 162.4 minutes ± 7.2 minutes versus AF, 163.0 minutes ± 7.0 minutes; P > 0.05). Conclusion In Switzerland, the best AF male half-marathoners and marathoners were younger and faster than the NAF counterpart runners. In contrast to the results seen in men, AF and NAF female runners had similar performances. Future studies need to investigate performance and age of AF and NAF marathoners in the World Marathon Majors Series. PMID:24379724

Estrogen Receptor α L543A,L544A Mutation Changes Antagonists to Agonists, Correlating with the Ligand Binding Domain Dimerization Associated with DNA Binding Activity*

PubMed Central

Arao, Yukitomo; Hamilton, Katherine J.; Coons, Laurel A.; Korach, Kenneth S.

2013-01-01

A ligand-dependent nuclear transcription factor, ERα has two transactivating functional domains (AF), AF-1 and AF-2. AF-1 is localized in the N-terminal region, and AF-2 is distributed in the C-terminal ligand-binding domain (LBD) of the ERα protein. Helix 12 (H12) in the LBD is a component of the AF-2, and the configuration of H12 is ligand-inducible to an active or inactive form. We demonstrated previously that the ERα mutant (AF2ER) possessing L543A,L544A mutations in H12 disrupts AF-2 function and reverses antagonists such as fulvestrant/ICI182780 (ICI) or 4-hydoxytamoxifen (OHT) into agonists in the AF2ER knock-in mouse. Our previous in vitro studies suggested that the mode of AF2ER activation is similar to the partial agonist activity of OHT for WT-ERα. However, it is still unclear how antagonists activate ERα. To understand the molecular mechanism of antagonist reversal activity, we analyzed the correlation between the ICI-dependent estrogen-responsive element-mediated transcription activity of AF2ER and AF2ER-LBD dimerization activity. We report here that ICI-dependent AF2ER activation correlated with the activity of AF2ER-LBD homodimerization. Prevention of dimerization impaired the ICI-dependent ERE binding and transcription activity of AF2ER. The dislocation of H12 caused ICI-dependent LBD homodimerization involving the F-domain, the adjoining region of H12. Furthermore, F-domain truncation also strongly depressed the dimerization of WT-ERα-LBD with antagonists but not with E2. AF2ER activation levels with ICI, OHT, and raloxifene were parallel with the degree of AF2ER-LBD homodimerization, supporting a mechanism that antagonist-dependent LBD homodimerization involving the F-domain results in antagonist reversal activity of H12-mutated ERα. PMID:23733188

Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation.

PubMed

Lip, G Y H; Frison, L; Grind, M

2008-07-01

To test the hypothesis that stroke and systemic embolic events (SEE) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) III and V trials are different between paroxysmal and persistent atrial fibrillation (AF). Data analysis from two cohorts of patients enrolled in the prospective SPORTIF III and V clinical trials (n = 7329); 836 subjects (11.4%) with paroxysmal AF [mean age 70.1 years (SD = 9.5)] were compared with 6493 subjects with persistent AF for this ancillary study. The annual event rates for stroke/SEE are 1.73% for persistent AF and 0.93% for paroxysmal AF. In a multivariate analysis, after adjusting for stroke risk factors, gender and aspirin usage, the differences remained statistically significant with a higher hazard ratio (HR) for stroke/SEE in persistent AF [vs. paroxysmal AF, HR 1.87, 95% confidence interval (CI) 1.04-3.36; P = 0.037]. In 'high risk' patients (with >or=2 stroke risk factors) annual event rates for stroke/SEE were 2.08% for persistent AF and 1.27% for paroxysmal AF (adjusted HR = 1.68, 95% CI 0.91-3.1, P = 0.098). Elderly patients had annual event rates for stroke/SEE of 2.38% for persistent AF and 1.13% for paroxysmal AF (adjusted HR = 2.27, 95% CI 0.92-5.59, P = 0.075). Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate, compared with 0.61% for previous VKA takers (HR = 0.33, 95% CI 0.11-1.01, P = 0.052). In this large clinical trial cohort of anticoagulated AF patients, those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF, although both groups had broadly similar stroke risk factors. Subjects with paroxysmal AF at 'high risk' had stroke/SEE rates that were not significantly different to persistent AF subjects.

Impact of acute atrial fibrillation termination and prolongation of atrial fibrillation cycle length on the outcome of ablation of persistent atrial fibrillation: A substudy of the STAR AF II trial.

PubMed

Kochhäuser, Simon; Jiang, Chen-Yang; Betts, Timothy R; Chen, Jian; Deisenhofer, Isabel; Mantovan, Roberto; Macle, Laurent; Morillo, Carlos A; Haverkamp, Wilhelm; Weerasooriya, Rukshen; Albenque, Jean-Paul; Nardi, Stefano; Menardi, Endrj; Novak, Paul; Sanders, Prashanthan; Verma, Atul

2017-04-01

Controversy exists about the impact of acute atrial fibrillation (AF) termination and prolongation of atrial fibrillation cycle length (AFCL) during ablation on long-term procedural outcome. The purpose of this study was to analyze the influence of AF termination and AFCL prolongation on freedom from AF in patients from the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial-Part II) trial. Acute changes in AFCL and AF termination were collected during the index procedure of the STAR AF II trial and compared to recurrence of AF at 18 months. Recurrence was assessed by ECG, Holter (3, 6, 9, 12, 18 months), and weekly transtelephonic ECG monitoring for 18 months. AF terminated in 8% of the pulmonary vein isolation (PVI) arm, 45% in the PVI+complex electrogram arm, and 22% of the PVI+linear ablation arm (P <.001), but freedom from AF did not differ among the 3 groups (P = .15). Freedom from AF was significantly higher in patients who presented to the laboratory in sinus rhythm (SR) compared to those without AF termination (63% vs 44%, P = .007). Patients with AF termination had an intermediate outcome (53%) that was not significantly different from those in SR (P = .84) or those who did not terminate (P = .08). AF termination was a univariable predictor of success (P = .007), but by multivariable analysis, presence of early SR was the strongest predictor of success (hazard ratio 0.67, P = .004). Prolongation of AFCL was not predictive of 18-month freedom from AF. Acute AF termination and prolongation in AFCL did not consistently predict 18-month freedom from AF. Presence of SR before or early during the ablation was the strongest predictor of better outcome. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Stroke as the Initial Manifestation of Atrial Fibrillation: The Framingham Heart Study.

PubMed

Lubitz, Steven A; Yin, Xiaoyan; McManus, David D; Weng, Lu-Chen; Aparicio, Hugo J; Walkey, Allan J; Rafael Romero, Jose; Kase, Carlos S; Ellinor, Patrick T; Wolf, Philip A; Seshadri, Sudha; Benjamin, Emelia J

2017-02-01

To prevent strokes that may occur as the first manifestation of atrial fibrillation (AF), screening programs have been proposed to identify patients with undiagnosed AF who may be eligible for treatment with anticoagulation. However, the frequency with which patients with AF present with stroke as the initial manifestation of the arrhythmia is unknown. We estimated the frequency with which AF may present as a stroke in 1809 community-based Framingham Heart Study participants with first-detected AF and without previous strokes, by tabulating the frequencies of strokes occurring on the same day, within 30 days before, 90 days before, and 365 days before first-detected AF. Using previously reported AF incidence rates, we estimated the incidence of strokes that may represent the initial manifestation of AF. We observed 87 strokes that occurred ≤1 year before AF detection, corresponding to 1.7% on the same day, 3.4% within 30 days before, 3.7% within 90 days before, and 4.8% ≤1 year before AF detection. We estimated that strokes may present as the initial manifestation of AF at a rate of 2 to 5 per 10 000 person-years, in both men and women. We observed that stroke is an uncommon but measureable presenting feature of AF. Our data imply that emphasizing cost-effectiveness of population-wide AF-screening efforts will be important given the relative infrequency with which stroke represents the initial manifestation of AF. © 2017 American Heart Association, Inc.

Proof of Concept Study to Assess Fetal Gene Expression in Amniotic Fluid by NanoArray PCR

PubMed Central

Massingham, Lauren J.; Johnson, Kirby L.; Bianchi, Diana W.; Pei, Shermin; Peter, Inga; Cowan, Janet M.; Tantravahi, Umadevi; Morrison, Tom B.

2011-01-01

Microarray analysis of cell-free RNA in amniotic fluid (AF) supernatant has revealed differential fetal gene expression as a function of gestational age and karyotype. Once informative genes are identified, research moves to a more focused platform such as quantitative reverse transcriptase-PCR. Standardized NanoArray PCR (SNAP) is a recently developed gene profiling technology that enables the measurement of transcripts from samples containing reduced quantities or degraded nucleic acids. We used a previously developed SNAP gene panel as proof of concept to determine whether fetal functional gene expression could be ascertained from AF supernatant. RNA was extracted and converted to cDNA from 19 AF supernatant samples of euploid fetuses between 15 to 20 weeks of gestation, and transcript abundance of 21 genes was measured. Statistically significant differences in expression, as a function of advancing gestational age, were observed for 5 of 21 genes. ANXA5, GUSB, and PPIA showed decreasing gene expression over time, whereas CASC3 and ZNF264 showed increasing gene expression over time. Statistically significantly increased expression of MTOR and STAT2 was seen in female compared with male fetuses. This study demonstrates the feasibility of focused fetal gene expression analysis using SNAP technology. In the future, this technique could be optimized to examine specific genes instrumental in fetal organ system function, which could be a useful addition to prenatal care. PMID:21827969

[AFNET. A translational research network develops into an academic research organization].

PubMed

Kirchhof, Paulus; Goette, Andreas; Näbauer, Michael; Schotten, Ulrich

2016-04-01

"The whole is greater than the sum of its parts" (Aristotle).Atrial fibrillation (AF) is the most common sustained arrhythmia and affects 1-2 % of the population in developed countries, especially the elderly. We expect that the prevalence of AF will double in the next few decades. The last decades have seen important improvements in the management of atrial fibrillation, but many questions remain regarding the optimal diagnosis and management of the condition. The German Atrial Fibrillation NETwork (AFNET) was one of three cardiovascular competence networks in medicine funded by the German Ministry of Education and Research between 2003-2014. AFNET has contributed to the understanding of atrial fibrillation, and AFNET-led studies have led to improved clinical practices and practice guidelines in Germany and in Europe. This work has been expanded and is continuing in the AFNET association (AFNET e. V.). The AFNET association, founded in 2010 and continuing to this day, has developed into a small but fully formed academic research organisation that conducts investigator-initiated clinical trials as the responsible sponsor in Germany, Europe, and beyond. The AFNET association currently cooperates with EHRA (The European Heart Rhythm Association), ESC (The European Society of Cardiology) and DZHK (The German Centre for Cardiovascular Research) and receives funding from the European Union to generate evidence that can in the future lead to better prevention and management of AF.

Triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a viewpoint.

PubMed

Gwyn, Jennifer C V; Thomas, Mark R; Kirchhof, Paulus

2017-07-01

Patients undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy to reduce the risk of subsequent myocardial infarction (MI) and stent thrombosis. Approximately 5-10% of patients undergoing PCI also have atrial fibrillation (AF). Patients with AF have an additional requirement for anticoagulation, as dual antiplatelet therapy alone is insufficient to adequately reduce the risk of stroke in patients with AF. However, it is now well established that combining anticoagulants with dual antiplatelet therapy also causes a significant increase in the risk of bleeding. Hence, there is great interest in discovering the optimal blend of antiplatelet therapy and oral anticoagulation in this situation, aiming to reduce the risk of stent thrombosis, recurrent MI, and stroke, while also minimizing the risk of bleeding. Recent studies have experimented with combining oral anticoagulation with a single antiplatelet agent, rather than combining oral anticoagulation with dual antiplatelet therapy. These studies show that this reduces the risk of bleeding but are underpowered to determine whether this still provides as much cardiovascular benefit. This review summarizes the currently available evidence on this topic and highlights the key questions that remain to be answered including ongoing clinical trials in the field. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Layout optimization with assist features placement by model based rule tables for 2x node random contact

NASA Astrophysics Data System (ADS)

Jun, Jinhyuck; Park, Minwoo; Park, Chanha; Yang, Hyunjo; Yim, Donggyu; Do, Munhoe; Lee, Dongchan; Kim, Taehoon; Choi, Junghoe; Luk-Pat, Gerard; Miloslavsky, Alex

2015-03-01

As the industry pushes to ever more complex illumination schemes to increase resolution for next generation memory and logic circuits, sub-resolution assist feature (SRAF) placement requirements become increasingly severe. Therefore device manufacturers are evaluating improvements in SRAF placement algorithms which do not sacrifice main feature (MF) patterning capability. There are known-well several methods to generate SRAF such as Rule based Assist Features (RBAF), Model Based Assist Features (MBAF) and Hybrid Assisted Features combining features of the different algorithms using both RBAF and MBAF. Rule Based Assist Features (RBAF) continue to be deployed, even with the availability of Model Based Assist Features (MBAF) and Inverse Lithography Technology (ILT). Certainly for the 3x nm node, and even at the 2x nm nodes and lower, RBAF is used because it demands less run time and provides better consistency. Since RBAF is needed now and in the future, what is also needed is a faster method to create the AF rule tables. The current method typically involves making masks and printing wafers that contain several experiments, varying the main feature configurations, AF configurations, dose conditions, and defocus conditions - this is a time consuming and expensive process. In addition, as the technology node shrinks, wafer process changes and source shape redesigns occur more frequently, escalating the cost of rule table creation. Furthermore, as the demand on process margin escalates, there is a greater need for multiple rule tables: each tailored to a specific set of main-feature configurations. Model Assisted Rule Tables(MART) creates a set of test patterns, and evaluates the simulated CD at nominal conditions, defocused conditions and off-dose conditions. It also uses lithographic simulation to evaluate the likelihood of AF printing. It then analyzes the simulation data to automatically create AF rule tables. It means that analysis results display the cost of different AF configurations as the space grows between a pair of main features. In summary, model based rule tables method is able to make it much easier to create rule tables, leading to faster rule-table creation and a lower barrier to the creation of more rule tables.

Retrospective Evaluation of the Effect of Heart Rate on Survival in Dogs with Atrial Fibrillation.

PubMed

Pedro, B; Dukes-McEwan, J; Oyama, M A; Kraus, M S; Gelzer, A R

2018-01-01

Atrial fibrillation (AF) usually is associated with a rapid ventricular rate. The optimal heart rate (HR) during AF is unknown. Heart rate affects survival in dogs with chronic AF. Forty-six dogs with AF and 24-hour ambulatory recordings were evaluated. Retrospective study. Holter-derived HR variables were analyzed as follows: mean HR (meanHR, 24-hour average), minimum HR (minHR, 1-minute average), maximum HR (maxHR, 1-minute average). Survival times were recorded from the time of presumed adequate rate control. The primary endpoint was all-cause mortality. Cox proportional hazards analysis identified variables independently associated with survival; Kaplan-Meier survival analysis estimated the median survival time of dogs with meanHR <125 bpm versus ≥125 bpm. All 46 dogs had structural heart disease; 31 of 46 had congestive heart failure (CHF), 44 of 46 received antiarrhythmic drugs. Of 15 dogs with cardiac death, 14 had CHF. Median time to all-cause death was 524 days (Interquartile range (IQR), 76-1,037 days). MeanHR was 125 bpm (range, 62-203 bpm), minHR was 82 bpm (range, 37-163 bpm), maxHR was 217 bpm (range, 126-307 bpm). These were significantly correlated with all-cause and cardiac-related mortality. For every 10 bpm increase in meanHR, the risk of all-cause mortality increased by 35% (hazard ratio, 1.35; 95% CI, 1.17-1.55; P < 0.001). Median survival time of dogs with meanHR<125 bpm (n = 23) was significantly longer (1,037 days; range, 524-open) than meanHR ≥125 bpm (n = 23; 105 days; range, 67-267 days; P = 0.0012). Mean HR was independently associated with all-cause and cardiovascular mortality (P < 0.003). Holter-derived meanHR affects survival in dogs with AF. Dogs with meanHR <125 bpm lived longer than those with meanHR ≥ 125 bpm. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Protective effects of Urtica dioica seed extract in aflatoxicosis: histopathological and biochemical findings.

PubMed

Uyar, A; Yener, Z; Dogan, A

2016-04-01

The ameliorative potential and antioxidant capacity of an extract of Urtica dioica seeds (UDS) was investigated using histopathological changes in liver and kidney, measuring serum marker enzymes, antioxidant defence systems and lipid peroxidation (malondialdehyde (MDA)) content in various tissues of broilers exposed to aflatoxin (AF). A total of 32 broilers were divided randomly into 4 groups: control, UDS extract-treated, AF-treated and AF+UDS extract-treated. Broilers in control and UDS extract-treated groups were fed on a diet without AF. The AF-treated group and AF+UDS extract-treated groups were treated with an estimated 1 mg total AF/kg feed. The AF+UDS extract groups received in addition 30 ml UDS extract/kg diet for 21 d. The AF-treated group had significantly decreased body weight gain when compared to the other groups. Biochemical analysis showed a small increase in the concentrations of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and lactate dehydrogenase in the AF-treated group compared to that of the control group, whereas concentrations of these enzymes were decreased in the AF+UDS group compared to that of the AF-treated group. Administration of supplementary UDS extract helped restore the AF-induced increase in MDA and reduced the antioxidant system towards normality, particularly in the liver, brain, kidney and heart. Hepatorenal protection by UDS extracts was further supported by the almost normal histology in AF+UDS extract-treated group as compared to the degenerative changes in the AF-treated broilers. It was concluded that UDS extract has a protective hepatorenal effect in broilers affected by aflatoxicosis, probably acting by promoting the antioxidative defence systems.

Anticoagulation therapy and clinical outcomes in patients with recently diagnosed atrial fibrillation: Insights from the ARISTOTLE trial.

PubMed

Guimarães, Patrícia O; Wojdyla, Daniel M; Alexander, John H; Thomas, Laine; Alings, Marco; Flaker, Greg C; Al-Khatib, Sana M; Hanna, Michael; Horowitz, John D; Wallentin, Lars; Granger, Christopher B; Lopes, Renato D

2017-01-15

Evidence supporting use of antithrombotic therapy in atrial fibrillation (AF) is based mainly on data from patients with permanent, persistent, or paroxysmal AF. Less is known about the risk following a new diagnosis of AF and the efficacy and safety of apixaban in these patients. Using data from ARISTOTLE, we assessed the relationship between timing of AF diagnosis and clinical outcomes and the efficacy and safety of apixaban versus warfarin in these patients. Recently diagnosed AF was defined as a new diagnosis of AF within 30days prior to enrollment. Cox proportional hazards models were used to determine the association between recently diagnosed AF and clinical outcomes. We also assessed the efficacy and safety of apixaban versus warfarin according to time since AF diagnosis. In ARISTOTLE, 1899 (10.5%) patients had recently diagnosed AF. After adjustment, patients with recently versus remotely diagnosed AF had a similar risk of stroke/systemic embolism (HR=1.07, 95% CI=0.80-1.42; p=0.67), but higher mortality was seen in patients with recently diagnosed AF (adjusted HR=1.21, 95% CI=1.02-1.43; p=0.03). The beneficial effects of apixaban, compared with warfarin, on clinical outcomes were consistent, irrespective of timing of AF diagnosis (all interaction p-values >0.12). Patients with recently diagnosed AF had a similar risk of stroke but higher mortality than patients with remotely diagnosed AF, suggesting that they are not at "low risk" and warrant stroke prevention strategies. The benefits of apixaban over warfarin were preserved, irrespective of timing of AF diagnosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators.

PubMed

Hart, R G; Pearce, L A; Rothbart, R M; McAnulty, J H; Asinger, R W; Halperin, J L

2000-01-01

This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation (AF). Although intermittent AF is common, relatively little is known about the attendant risk of stroke. A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years. Independent risk factors for ischemic stroke were identified by multivariate analysis. Patients with intermittent AF were, on average, younger (66 vs. 70 years, p < 0.001), were more often women (37% vs. 26% p < 0.001) and less often had heart failure (11% vs. 21%, p < 0.001) than those with sustained AF. The annualized rate of ischemic stroke was similar for those with intermittent (3.2%) and sustained AF (3.3%). In patients with intermittent AF, independent predictors of ischemic stroke were advancing age (relative risk [RR] = 2.1 per decade, p < 0.001), hypertension (RR = 3.4, p = 0.003) and prior stroke (RR = 4.1, p = 0.01). Of those with intermittent AF predicted to be high risk (24%), the observed stroke rate was 7.8% per year (95% confidence interval 4.5 to 14). In this large cohort of AF patients given aspirin, those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors. Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation. High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF.

Clinical predictors of risk for atrial fibrillation: implications for diagnosis and monitoring.

PubMed

Brunner, Kyle J; Bunch, T Jared; Mullin, Christopher M; May, Heidi T; Bair, Tami L; Elliot, David W; Anderson, Jeffrey L; Mahapatra, Srijoy

2014-11-01

To create a risk score using clinical factors to determine whom to screen and monitor for atrial fibrillation (AF). The AF risk score was developed based on the summed odds ratios (ORs) for AF development of 7 accepted clinical risk factors. The AF risk score is intended to assess the risk of AF similar to how the CHA2DS2-VASc score assesses stroke risk. Seven validated risk factors for AF were used to develop the AF risk score: age, coronary artery disease, diabetes mellitus, sex, heart failure, hypertension, and valvular disease. The AF risk score was tested within a random population sample of the Intermountain Healthcare outpatient database. Outcomes were stratified by AF risk score for OR and Kaplan-Meier analysis. A total of 100,000 patient records with an index follow-up from January 1, 2002, through December 31, 2007, were selected and followed up for the development of AF through the time of this analysis, May 13, 2013, through September 6, 2013. Mean ± SD follow-up time was 3106±819 days. The ORs of subsequent AF diagnosis of patients with AF risk scores of 1, 2, 3, 4, and 5 or higher were 3.05, 12.9, 22.8, 34.0, and 48.0, respectively. The area under the curve statistic for the AF risk score was 0.812 (95% CI, 0.805-0.820). We developed a simple AF risk score made up of common clinical factors that may be useful to possibly select patients for long-term monitoring for AF detection. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Calreticulin overexpression correlates with integrin-α5 and transforming growth factor-β1 expression in the atria of patients with rheumatic valvular disease and atrial fibrillation.

PubMed

Zhao, Fei; Zhang, Shijiang; Shao, Yongfeng; Wu, Yanhu; Qin, Jianwei; Chen, Yijiang; Chen, Liang; Gu, Haitao; Wang, Xiaowei; Huang, Chenjun; Zhang, Wei

2013-10-03

The aim of this study was to determine whether altered calreticulin expression and distribution contribute to the pathogenesis of atrial fibrillation (AF) associated with valvular heart disease (VHD). AF affects electrophysiological and structural changes that exacerbate AF. Atrial remodeling reportedly underlies AF generation, but the precise mechanism of atrial remodeling in AF remains unclear. Right and left atrial specimens were obtained from 68 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR; n=25), paroxysmal AF (PaAF; n=11), and persistent AF (PeAF; AF lasting >6 months; n=32) groups. Calreticulin, integrin-α5, and transforming growth factor-β1 (TGF-β1) mRNA and protein expression were measured. We also performed immunoprecipitation for calreticulin with either calcineurin B or integrin-α5. Calreticulin, integrin-α5, and TGF-β1 mRNA and protein expression were increased in the AF groups, especially in the left atrium in patients with mitral valve disease. Calreticulin interacted with both calcineurin B and integrin-α5. Integrin-α5 expression correlated with TGF-β1 expression, while calreticulin expression correlated with integrin-α5 and TGF-β1 expression. Despite similar cardiac function classifications, calreticulin expression was greater in the PeAF group than in the SR group. Calreticulin, integrin-α5, and TGF-β1 expression was increased in atrial tissue in patients with AF and was related to AF type, suggesting that calreticulin is involved in the pathogenesis of AF in VHD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Targeting Stable Rotors to Treat Atrial Fibrillation.

PubMed

Narayan, Sanjiv M; Krummen, David E

2012-09-01

Therapy for atrial fibrillation (AF) remains suboptimal, in large part because its mechanisms are unclear. While pulmonary vein ectopy may trigger AF, it remains uncertain how AF, once triggered, is actually sustained. Recent discoveries show that human AF is maintained by a small number of rotors or focal sources. AF sources are widely distributed in patient-specific locations, often remote from pulmonary veins and in the right atrium and stable for prolonged periods of time. In a multicentre experience, brief targeted ablation at sources (focal impulse and rotor modulation [FIRM]) terminated AF predominantly to sinus rhythm prior to pulmonary vein isolation and eliminated AF on rigorous followup. This review summarises the evidence for stable rotors and focal sources of human AF and their clinical role as ablation targets to eliminate paroxysmal, persistent and long-standing persistent AF.

Obstructive Sleep Apnoea and Atrial Fibrillation

PubMed Central

Zhang, Ling; Hou, Yuemei; Po, Sunny S

2015-01-01

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is associated with significant morbidity and mortality. Obstructive sleep apnoea (OSA) is common among patients with AF. Growing evidence suggests that OSA is associated with the initiation and maintenance of AF. This association is independent of obesity, body mass index and hypertension. OSA not only promotes initiation of AF but also has a significant negative impact on the treatment of AF. Patients with untreated OSA have a higher AF recurrence rate with drug therapy, electrical cardioversion and catheter ablation. Treatment with continuous positive airway pressure (CPAP) has been shown to improve AF control in patients with OSA. In this article, we will review and discuss the pathophysiological mechanisms of OSA that may predispose OSA patients to AF as well as the standard and emerging therapies for patients with both OSA and AF. PMID:26835094

Genetic Risk Prediction of Atrial Fibrillation

PubMed Central

Lubitz, Steven A.; Yin, Xiaoyan; Lin, Henry J.; Kolek, Matthew; Smith, J. Gustav; Trompet, Stella; Rienstra, Michiel; Rost, Natalia S.; Teixeira, Pedro L.; Almgren, Peter; Anderson, Christopher D.; Chen, Lin Y.; Engström, Gunnar; Ford, Ian; Furie, Karen L.; Guo, Xiuqing; Larson, Martin G.; Lunetta, Kathryn L.; Macfarlane, Peter W.; Psaty, Bruce M.; Soliman, Elsayed Z.; Sotoodehnia, Nona; Stott, David J.; Taylor, Kent D.; Weng, Lu-Chen; Yao, Jie; Geelhoed, Bastiaan; Verweij, Niek; Siland, Joylene E.; Kathiresan, Sekar; Roselli, Carolina; Roden, Dan; van der Harst, Pim; Darbar, Dawood; Jukema, J. Wouter; Melander, Olle; Rosand, Jonathan; Rotter, Jerome I.; Heckbert, Susan R.; Ellinor, Patrick T.; Alonso, Alvaro; Benjamin, Emelia J.

2017-01-01

Background Atrial fibrillation (AF) is common and has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. Methods To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 controls. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1×10−3 to <1×10−8 in a prior independent genetic association study. Results Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13–1.46; P=1.5×10−4) to 1.67 (25 variants; 95%CI, 1.47–1.90; P=9.3×10−15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629–0.811; maximum ΔC statistic from clinical score alone, 0.009–0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke, versus those in the lowest quartile (95%CI, 1.39–4.58; P=2.7×10−3). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20–4.40; P=0.01). Conclusions Comprehensive AF genetic risk scores were associated with incident AF beyond clinical AF risk factors, with magnitudes of risk comparable to other clinical risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts to determine whether AF genetic risk may improve identification of subclinical AF or distinguish stroke mechanisms are warranted. PMID:27793994

Impact of pre-existing or new-onset atrial fibrillation on 30-day clinical outcomes following transcatheter aortic valve replacement: Results from the BRAVO 3 randomized trial.

PubMed

Hengstenberg, Christian; Chandrasekhar, Jaya; Sartori, Samantha; Lefevre, Thierry; Mikhail, Ghada; Meneveau, Nicolas; Tron, Christophe; Jeger, Raban; Kupatt, Christian; Vogel, Birgit; Farhan, Serdar; Sorrentino, Sabato; Sharma, Madhav; Snyder, Clayton; Husser, Oliver; Boekstegers, Peter; Hambrecht, Rainer; Widder, Julian; Hildick-Smith, David; De Carlo, Marco; Wijngaard, Peter; Deliargyris, Efthymios; Bernstein, Debra; Baber, Usman; Mehran, Roxana; Anthopoulos, Prodromos; Dangas, George

2017-11-15

Prior studies have suggested that patients with atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR) are at higher risk for adverse cardiovascular events. Whether procedural bivalirudin compared with unfractionated heparin (UFH) has a beneficial effect on early outcomes in these patients is unknown. We examined for the effect of baseline or new-onset AF within 30 days of TAVR and explored for the effect of bivalirudin versus UFH by AF status, on 30-day outcomes from the BRAVO 3 trial. The BRAVO-3 trial multicenter randomized trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin or UFH. We compared AF and no-AF groups and examined for 30-day Bleeding Academic Research Consortium type ≥3b bleeding, major vascular complications and all ischemic endpoints. Adjusted outcomes were analyzed using logistic regression methods. Of the study population, 41.4% (n = 332) patients had baseline or new-onset AF within 30 days of TAVR, whereas 58.6% (n = 470) had no AF. Patients with AF had greater prevalence of renal dysfunction, lower left ventricular ejection fraction, and higher euroSCORE I compared with their counterparts without AF. Among AF and no-AF patients, there were no significant baseline differences between bivalirudin and UFH groups. At 30 days the incidence of death (6.0 vs. 4.5%, P = 0.324) and stroke (3.9 vs. 2.6%, P = 0.274) was similar in AF vs. no-AF patients. However, new-onset AF (n = 38) was associated with significantly greater crude risk of 30-day stroke compared with no AF (HR 4.49, 95% CI 1.37-14.67). Regardless of AF status, there were no differences in 30-day death (P-int = 0.652) or stroke (P-int = 0.066) by anticoagulation type. Prior or new-onset AF is noted in more than one-third of patients undergoing transfemoral TAVR. Despite greater baseline comorbidities than non-AF patients, AF was not associated with significantly higher risk of adjusted 30-day outcomes. In the BRAVO 3 trial, early outcomes were similar regardless of anticoagulant strategy in each group. © 2017 Wiley Periodicals, Inc.

Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping

PubMed Central

Zaman, Junaid A. B.; Narayan, Sanjiv M.

2015-01-01

Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes. PMID:26306123

Characteristic appearances of fundus autofluorescence in treatment-naive and active polypoidal choroidal vasculopathy: a retrospective study of 170 patients.

PubMed

Zhao, Xinyu; Xia, Song; Chen, Youxin

2018-06-01

To investigate the characteristic appearances of fundus autofluorescence (FAF) in patients with treatment-naive and active polypoidal choroidal vasculopathy (PCV). Cases with the diagnosis of treatment-naive and active PCV from November 2012 to May 2017 at Peking Union Medical College Hospital were retrospectively reviewed. All patients underwent comprehensive ophthalmologic examination. Autofluorescence (AF) findings were described at the retinal sites of the corresponding lesions identified and diagnosed using indocyanine green angiography and spectral-domain optical coherence tomography. One hundred seventy patients with 192 affected eyes were included. The logMAR BCVA of the patients were 0.53 ± 0.28. The six AF patterns of 243 polypoidal lesions were confluent hypo-AF with hyper-AF ring (49.8%), confluent hypo-AF (22.6%), hyper-AF with hypo-AF ring (3.7%), granular hypo-AF (7.0%), blocked hypo-AF due to hemorrhage (8.6%), and polyps without apparent AF changes (8.2%). For 146 branching vascular networks (BVNs), 97.3% were granular hypo-AF, and others were blocked hypo-AF due to hemorrhage. In eyes with treatment-naive and active PCV, the polypoidal lesions and BVNs induce characteristic FAF changes. FAF images provide reliable adjunct reference for the diagnosis of PCV.

Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping.

PubMed

Zaman, Junaid A B; Narayan, Sanjiv M

2015-01-01

Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes.

Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene

PubMed Central

Catalina, Purificación; Rodríguez, René; Melen, Gustavo J.; Bueno, Clara; Arriero, Mar; García-Sánchez, Félix; Lassaletta, Alvaro; García-Sanz, Ramón

2009-01-01

MLL-AF4 fusion is a hallmark genetic abnormality in infant B-acute lymphoblastic leukemia (B-ALL) known to arise in utero. The cellular origin of leukemic fusion genes during human development is difficult to ascertain. The bone marrow (BM) microenvironment plays an important role in the pathogenesis of several hematological malignances. BM mesenchymal stem cells (BM-MSC) from 38 children diagnosed with cytogenetically different acute leukemias were screened for leukemic fusion genes. Fusion genes were absent in BM-MSCs of childhood leukemias carrying TEL-AML1, BCR-ABL, AML1-ETO, MLL-AF9, MLL-AF10, MLL-ENL or hyperdiploidy. However, MLL-AF4 was detected and expressed in BM-MSCs from all cases of MLL-AF4+ B-ALL. Unlike leukemic blasts, MLL-AF4+ BM-MSCs did not display monoclonal Ig gene rearrangements. Endogenous or ectopic expression of MLL-AF4 exerted no effect on MSC culture homeostasis. These findings suggest that MSCs may be in part tumor-related, highlighting an unrecognized role of the BM milieu on the pathogenesis of MLL-AF4+ B-ALL. MLL-AF4 itself is not sufficient for MSC transformation and the expression of MLL-AF4 in MSCs is compatible with a mesenchymal phenotype, suggesting a differential impact in the hematopoietic system and mesenchyme. The absence of monoclonal rearrangements in MLL-AF4+ BM-MSCs precludes the possibility of cellular plasticity or de-differentiation of B-ALL blasts and suggests that MLL-AF4 might arise in a population of prehematopoietic precursors. PMID:19995953

African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative.

PubMed

Perez, Marco V; Hoffmann, Thomas J; Tang, Hua; Thornton, Timothy; Stefanick, Marcia L; Larson, Joseph C; Kooperberg, Charles; Reiner, Alex P; Caan, Bette; Iribarren, Carlos; Risch, Neil

2013-09-01

Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk. The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses. Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort. African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans. © 2013.

Depression and Physical Inactivity as Confounding the Effect of Obesity on Atrial Fibrillation.

PubMed

Garimella, Roja S; Sears, Samuel F; Gehi, Anil K

2016-06-01

Obesity is associated with an increased likelihood for the development of atrial fibrillation (AF) and with worsened AF symptom severity. However, other factors that are correlated with obesity may confound or mediate the relation of obesity with AF symptom severity. The purpose of this study was to determine if depression and physical inactivity may confound the association of obesity and AF symptom severity. Health status and demographic data were captured by questionnaire for 332 outpatients with documented AF. Weight/height was measured and body mass index (kg/m(2)) calculated. Recent depression symptom severity was assessed using the Patient Health Questionnaire-9 questionnaire. Physical activity during the last month was assessed by questionnaire. AF symptom severity was assessed using the University of Toronto AF Severity scale. Multivariate linear regression was used to evaluate which factors were associated with AF symptom severity. Obesity in patients with AF is associated with increased depression severity. In bivariate analysis, increasing body mass index (p = 0.001), lower levels of physical activity (p <0.001), and more severe depression (p <0.001) were associated with worsened AF symptom severity. In multivariate analysis, only physical activity and depression persisted as significant predictors of AF symptom severity. In conclusion, although obesity likely contributes to the substrate predisposing to the development of AF, other factors may contribute to or mediate the worsened AF symptoms associated with obesity. Depression symptoms and physical inactivity, factors closely correlated with obesity, may exacerbate symptoms in patients with AF. Copyright © 2016 Elsevier Inc. All rights reserved.

Incidence, type of atrial fibrillation and risk factors for stroke: a population-based cohort study

PubMed Central

Johansson, Cecilia; Dahlqvist, Erik; Andersson, Jonas; Jansson, Jan-Håkan; Johansson, Lars

2017-01-01

Purpose The aims of this study were to estimate the incidence of atrial fibrillation and atrial flutter (AF), to assess the presence of provoking factors and risk factors for stroke and systemic embolism, and to determine the type of AF in patients with first-diagnosed AF. Patients and methods This cohort study was performed in northern Sweden between January 1, 2011 and December 31, 2012. Diagnosis registries were searched for the International Classification of Diseases-10 code for AF (I48) to identify cases of incident AF. All AF diagnoses were electrocardiogram-verified. Data pertaining to provoking factors, type of AF and presence of risk factors for stroke and systemic embolism according to the CHA2DS2-VASc score were obtained from medical records. Results The incidence of AF in the entire population was 4.0 per 1,000 person-years. The incidence was 27.5 per 1,000 person-years in patients aged ≥80 years. A total of 21% of all patients had a provoking factor in association with the first-diagnosed episode of AF. The CHA2DS2-VASc score was 2 or higher in 81% of the patients. Permanent AF was the most common type of AF (29%). Conclusion There was a considerable increase in the incidence of AF with age, and a provoking factor was found in one-fifth. The most common type of AF was permanent AF. Four in five patients had a CHA2DS2-VASc score of 2 or more. PMID:28182159

Towards Optimization of Macrocognitive Processes: Automating Analysis of the Emergence of Leadership in Ad Hoc Teams

DTIC Science & Technology

2014-04-21

Journal of Sociotechnology and Knowledge Development (IJSKD), 4(3), 17-37. Anders S, Schweikhart S, Woods DD, Ebright P, Patterson ES. (2012) The Effects...Ergonomics Society, 282-286. • Patterson ES, Rayo MF, Weiss C, Woods Z, Mount-Campbell AF. Online Training for Resilience Communication Strategies during...Shift Change Handovers, in Proceedings of the Human Factors and Ergonomics Society Annual Meeting. (Sep 2013). 57 (1). 1427- 1431. Woods Z, Beecroft

Mobile, Multimodal, Label-Free Imaging Probe Analysis of Choroidal Oximetry and Retinal Hypoxia

DTIC Science & Technology

2017-12-01

these same eye injuries. Primary blast-induced injury (PBI), which can occur in eyes that are not punctured or ruptured by the blast, is correlated ...optimization. (1A-F) The component of our PBI- devices, output pressure detection sensor, amplifier, and input pressure panel. (1G) Correlation between...by changing the setting of blast generator. (2A-B) Correlation between output pressure and blast time duration. (2C) After PBI- treatment, the eyes of

Translation of an Engineered Nanofibrous Disc-like Angle Ply Structure for Intervertebral Disc Replacement in a Small Animal Model

PubMed Central

Martin, John T.; Milby, Andrew H.; Chiaro, Joseph A.; Kim, Dong Hwa; Hebela, Nader M.; Smith, Lachlan J.; Elliott, Dawn M.; Mauck, Robert L.

2015-01-01

Intervertebral disc degeneration has been implicated in the etiology of low back pain; however the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF), and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(ε-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, have functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilize the motion segment by external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the peri-implant space, and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements. PMID:24560621

Validated LC–MS-MS Method for Multiresidual Analysis of 13 Illicit Phenethylamines in Amniotic Fluid

PubMed Central

Burrai, Lucia; Nieddu, Maria; Carta, Antonio; Trignano, Claudia; Sanna, Raimonda; Boatto, Gianpiero

2016-01-01

A multi-residue analytical method was developed for the determination in amniotic fluid (AF) of 13 illicit phenethylamines, including 12 compounds never investigated in this matrix before. Samples were subject to solid-phase extraction using; hydrophilic–lipophilic balance cartridges which gave good recoveries and low matrix effects on analysis of the extracts. The quantification was performed by liquid chromatography electrospray tandem mass spectrometry. The water–acetonitrile mobile phase containing 0.1% formic acid, used with a C18 reversed phase column, provided adequate separation, resolution and signal-to-noise ratio for the analytes and the internal standard. The final optimized method was validated according to international guidelines. A monitoring campaign to assess fetal exposure to these 13 substances of abuse has been performed on AF test samples obtained from pregnant women. All mothers (n = 194) reported no use of drugs of abuse during pregnancy, and this was confirmed by the analytical data. PMID:26755540

A brief history of 'lone' atrial fibrillation: from 'a peculiar pulse irregularity' to a modern public health concern.

PubMed

Potpara, Tatjana S; Lip, Gregory Y H

2015-01-01

Ever since the original description of a 'peculiar pulse irregularity', atrial fibrillation (AF) has been studied extensively and has come a long journey from the recognition of its cardiac origins, to the modern concept of AF as a serious public health challenge with profound social and economic implications. This arrhythmia affects around 2% of adult population, and the most common underlying heart diseases accompanying AF in the modern era are hypertension, heart failure and coronary artery disease, as well as valvular heart diseases and numerous other cardiac as well as non-cardiac disorders which have been shown to predispose to AF. On occasions, AF occurs in young otherwise apparently healthy individuals (so called 'lone AF'). For a long time, 'lone' AF has been believed to bear a favourable prognosis as compared to AF with underlying structural heart disease, but increasing evidence suggests that 'lone' AF patients represent a rather heterogeneous cohort, with highly variable individual risk profiles due to the presence of various subclinical cardiovascular risk factors or genetically determined subtle alterations at the cellular or molecular level. For these reasons, the existence of truly 'lone' AF has recently been questioned. In this review article, we present a brief history of the recognition of the public health burden of AF. We discuss some of the misconceptions and breakthroughs on modern knowledge on AF, including the rise (and fall) of the 'lone' AF concept.

Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering.

PubMed

Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

2007-08-01

Engineering a functional replacement for the annulus fibrosus (AF) of the intervertebral disc is contingent upon recapitulation of AF structure, composition, and mechanical properties. In this study, we propose a new paradigm for AF tissue engineering that focuses on the reconstitution of anatomic fiber architecture and uses constitutive modeling to evaluate construct function. A modified electrospinning technique was utilized to generate aligned nanofibrous polymer scaffolds for engineering the basic functional unit of the AF, a single lamella. Scaffolds were tested in uniaxial tension at multiple fiber orientations, demonstrating a nonlinear dependence of modulus on fiber angle that mimicked the nonlinearity and anisotropy of native AF. A homogenization model previously applied to native AF successfully described scaffold mechanical response, and parametric studies demonstrated that nonfibrillar matrix, along with fiber connectivity, are key contributors to tensile mechanics for engineered AF. We demonstrated that AF cells orient themselves along the aligned scaffolds and deposit matrix that contributes to construct mechanics under loading conditions relevant to the in vivo environment. The homogenization model was applied to cell-seeded constructs and provided quantitative measures for the evolution of matrix and interfibrillar interactions. Finally, the model demonstrated that at fiber angles of the AF (28 degrees -44 degrees ), engineered material behaved much like native tissue, suggesting that engineered constructs replicate the physiologic behavior of the single AF lamella. Constitutive modeling provides a powerful tool for analysis of engineered AF neo-tissue and native AF tissue alike, highlighting key mechanical design criteria for functional AF tissue engineering.

Structural Analysis on the Pathologic Mutant Glucocorticoid Receptor Ligand-Binding Domains.

PubMed

Hurt, Darrell E; Suzuki, Shigeru; Mayama, Takafumi; Charmandari, Evangelia; Kino, Tomoshige

2016-02-01

Glucocorticoid receptor (GR) gene mutations may cause familial or sporadic generalized glucocorticoid resistance syndrome. Most of the missense forms distribute in the ligand-binding domain and impair its ligand-binding activity and formation of the activation function (AF)-2 that binds LXXLL motif-containing coactivators. We performed molecular dynamics simulations to ligand-binding domain of pathologic GR mutants to reveal their structural defects. Several calculated parameters including interaction energy for dexamethasone or the LXXLL peptide indicate that destruction of ligand-binding pocket (LBP) is a primary character. Their LBP defects are driven primarily by loss/reduction of the electrostatic interaction formed by R611 and T739 of the receptor to dexamethasone and a subsequent conformational mismatch, which deacylcortivazol resolves with its large phenylpyrazole moiety and efficiently stimulates transcriptional activity of the mutant receptors with LBP defect. Reduced affinity of the LXXLL peptide to AF-2 is caused mainly by disruption of the electrostatic bonds to the noncore leucine residues of this peptide that determine the peptide's specificity to GR, as well as by reduced noncovalent interaction against core leucines and subsequent exposure of the AF-2 surface to solvent. The results reveal molecular defects of pathologic mutant receptors and provide important insights to the actions of wild-type GR.

Microbial species delineation using whole genome sequences

PubMed Central

Varghese, Neha J.; Mukherjee, Supratim; Ivanova, Natalia; Konstantinidis, Konstantinos T.; Mavrommatis, Kostas; Kyrpides, Nikos C.; Pati, Amrita

2015-01-01

Increased sequencing of microbial genomes has revealed that prevailing prokaryotic species assignments can be inconsistent with whole genome information for a significant number of species. The long-standing need for a systematic and scalable species assignment technique can be met by the genome-wide Average Nucleotide Identity (gANI) metric, which is widely acknowledged as a robust measure of genomic relatedness. In this work, we demonstrate that the combination of gANI and the alignment fraction (AF) between two genomes accurately reflects their genomic relatedness. We introduce an efficient implementation of AF,gANI and discuss its successful application to 86.5M genome pairs between 13,151 prokaryotic genomes assigned to 3032 species. Subsequently, by comparing the genome clusters obtained from complete linkage clustering of these pairs to existing taxonomy, we observed that nearly 18% of all prokaryotic species suffer from anomalies in species definition. Our results can be used to explore central questions such as whether microorganisms form a continuum of genetic diversity or distinct species represented by distinct genetic signatures. We propose that this precise and objective AF,gANI-based species definition: the MiSI (Microbial Species Identifier) method, be used to address previous inconsistencies in species classification and as the primary guide for new taxonomic species assignment, supplemented by the traditional polyphasic approach, as required. PMID:26150420

Opportunistic screening of atrial fibrillation by automatic blood pressure measurement in the community.

PubMed

Omboni, Stefano; Verberk, Willem J

2016-04-12

Timely detection of atrial fibrillation (AF) may effectively prevent cardiovascular consequences. However, traditional diagnostic tools are either poorly reliable (pulse palpation) or not readily accessible (ECG) in general practice. We tested whether an automatic oscillometric blood pressure (BP) monitor embedded with an algorithm for AF detection might be effective for opportunistic screening of asymptomatic AF in the community. A community-based screening campaign in an unselected population to verify the feasibility of AF screening with a Microlife WatchBP Office BP monitor with a patented AFIB algorithm. When possible AF was detected (≥2 of 3 BP measurements reporting AF), a doctor immediately performed a single-lead ECG in order to confirm or exclude the presence of the arrhythmia. The main demographic and clinical data were also collected. 220 consecutive participants from an unselected sample of individuals in a small Italian community. Number of patients detected with AF and diagnosed risk factors for AF. In 12 of 220 participants, the device detected possible AF during the BP measurement: in 4 of them (1.8%), the arrhythmia was confirmed by the ECG. Patients with AF were more likely to be older (77.0±1.2 vs 57.2±15.2 years, p=0.010), obese (50.0 vs 14.4%, p=0.048) and to suffer from a cardiovascular disease (50.0 vs 10.6%, p=0.014) than patients without AF. Participants with a positive BP AF reading and non-AF arrhythmias (n=8) did not differ in their general characteristics from participants with a negative BP AF reading and were younger than patients with AF (mean age 56.4±14.8, p=0.027; 5 of 8 participants aged <65 years). Opportunistic screening of AF by BP measurement is feasible to diagnose this arrhythmia in unaware participants, particularly in those older than 65 years, who are the target patient group recommended by current AF screening guidelines. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Preventing Gut Leakiness and Endotoxemia Contributes to the Protective Effect of Zinc on Alcohol-Induced Steatohepatitis in Rats123

PubMed Central

Zhong, Wei; Li, Qiong; Sun, Qian; Zhang, Wenliang; Zhang, Jiayang; Sun, Xinguo; Yin, Xinmin; Zhang, Xiang; Zhou, Zhanxiang

2015-01-01

Background: Zinc deficiency has been well documented in alcoholic liver disease. Objective: This study was undertaken to determine whether dietary zinc supplementation provides beneficial effects in treating alcohol-induced gut leakiness and endotoxemia. Methods: Male Sprague Dawley rats were divided into 3 groups and pair-fed (PF) Lieber-DeCarli liquid diet for 8 wk: 1) control (PF); 2) alcohol-fed (AF; 5.00–5.42% wt:vol ethanol); and 3) AF with zinc supplementation (AF/Zn) at 220 ppm zinc sulfate heptahydrate. The PF and AF/Zn groups were pair-fed with the AF group. Hepatic inflammation and endotoxin signaling were determined by immunofluorescence and quantitative polymerase chain reaction (qPCR). Alterations in intestinal tight junctions and aldehyde dehydrogenases were assessed by qPCR and Western blot analysis. Results: The AF rats had greater macrophage activation and cytokine production (P < 0.05) in the liver compared with the PF rats, whereas the AF/Zn rats showed no significant differences (P > 0.05). Plasma endotoxin concentrations of the AF rats were 136% greater than those of the PF rats, whereas the AF/Zn rats did not differ from the PF rats. Ileal permeability was 255% greater in the AF rats and 19% greater in the AF/Zn rats than in the PF rats. The AF group had reduced intestinal claudin-1, occludin, and zona occludens-1 (ZO-1) expression, and the AF/Zn group had upregulated claudin-1 and ZO-1 expression (P < 0.05) compared with the PF group. The intestinal epithelial expression and activity of aldehyde dehydrogenases were elevated (P < 0.05) in the AF/Zn rats compared with those of the AF rats. Furthermore, the ileal expression and function of hepatocyte nuclear factor 4α, which was impaired in the AF group, was significantly elevated in the AF/Zn group compared with the PF group. Conclusions: The results demonstrate that attenuating hepatic endotoxin signaling by preserving the intestinal barrier contributes to the protective effect of zinc on alcohol-induced steatohepatitis in rats. PMID:26468492

In vitro evaluation of gaseous microemboli handling of cardiopulmonary bypass circuits with and without integrated arterial line filters.

PubMed

Liu, Saifei; Newland, Richard F; Tully, Phillip J; Tuble, Sigrid C; Baker, Robert A

2011-09-01

The delivery of gaseous microemboli (GME) by the cardiopulmonary bypass circuit should be minimized whenever possible. Innovations in components, such as the integration of arterial line filter (ALF) and ALFs with reduced priming volumes, have provided clinicians with circuit design options. However, before adopting these components clinically, their GME handling ability should be assessed. This study aims to compare the GME handling ability of different oxygenator/ALF combinations with our currently utilized combination. Five commercially available oxygenator/ALF combinations were evaluated in vitro: Terumo Capiox SX25RX and Dideco D734 (SX/D734),Terumo Capiox RX25R and AF125 (RX/AF125), Terumo FX25R (FX), Sorin Synthesis with 102 microm reservoir filter (SYN102), and Sorin Synthesis with 40 microm reservoir filter (SYN40). GME handling was studied by introducing air into the venous return at 100 mL/min for 60 seconds under two flow/ pressure combinations: 3.5 L/min, 150 mmHg and 5 L/min, 200 mmHg. Emboli were measured at three positions in the circuit using the Emboli Detection and Classification (EDAC) Quantifier and analyzed with the General Linear Model. All circuits significantly reduced GME. The SX/D734 and SYN40 circuits were most efficient in GME removal whilst the SYN102 handled embolic load (count and volume) least efficiently (p < .001). A greater number of emboli <70 microm were observed for the SYN102, FX and RX/AF125 circuits (p < .001). An increase in embolic load occurred with higher flow/pressure in all circuits (p < .001). The venous reservoir significantly influences embolic load delivered to the oxygenator (p < .001). The majority of introduced venous air was removed; however, significant variation existed in the ability of the different circuits to handle GME. Venous reservoir design influenced the overall GME handling ability. GME removal was less efficient at higher flow and pressure, and for smaller sized emboli. The clinical significance of reducing GME requires further investigation.

An investigation of co-combustion municipal sewage sludge with biomass in a 20kW BFB combustor under air-fired and oxygen-enriched condition.

PubMed

Kumar, Rajesh; Singh, Ravi Inder

2017-12-01

The behavior of municipal sewage sludge (MSS) with biomass (Guar stalks (GS), Mustard Husk (MH), Prosopis Juliflora Wood (PJW)) has been investigated in a 20kW bubbling fluidized bed (BFB) combustor under both air-fired (A-F) and oxygen-enriched (O-E) conditions. The work presented is divided into three parts, first part cover the thermogravimetric analysis (TGA), second part cover the experimental investigation of BFB combustor, and third part covers the ash analysis. TGA was performed with a ratio of 50%MSS/50%biomass (GS, MH, PJW) and results show that 50%MSS/50%GS has highest combustion characteristic factor (CCF). The experimental investigation of BFB combustor was performed for two different ratios of MSS/biomass (50%/50% and 25%/75%) and the combustion characteristics of blends were distinctive under both A-F and O-E condition. Despite 50%MSS/50%GS showing the highest combustion performance in TGA analysis, it formed agglomerates during burning in BFB. Due to this formation of large amount of agglomerates, de-fluidization was observed in the combustor bed after 65-75min in A-F conditions. The rate of de-fluidization increased under O-E condition. The de-fluidization problem disappeared when the share of MSS was reduced to 25%, but small amounts of the agglomerate were still present in the bed. With oxygen enhancement, the combustion efficiency of BFB combustor was improved and flue gasses were found within permissible limit. The maximum conceivable combustion efficiency (97.1%) for BFB combustor was accomplished by using 50% MSS/50%PJW under O-E condition. Results show that a ratio of 25%MSS/75%biomass combusted successfully inside the BFB combustor and extensive work is required for efficient utilization of significant share of MSS with biomass. SEM/EDS analyses were performed for agglomerate produced and for the damaged heater to study the surface morphology and compositions. The elemental heterogeneity of fly ash generated during MSS/biomass combustion was analyzed using Microwave Plasma-Atomic Emission Spectroscopy (MP-AES). Copyright © 2017 Elsevier Ltd. All rights reserved.

Supersonic nonlinear potential analysis

NASA Technical Reports Server (NTRS)

Siclari, M. J.

1984-01-01

The NCOREL computer code was established to compute supersonic flow fields of wings and bodies. The method encompasses an implicit finite difference transonic relaxation method to solve the full potential equation in a spherical coordinate system. Two basic topic to broaden the applicability and usefulness of the present method which is encompassed within the computer code NCOREL for the treatment of supersonic flow problems were studied. The first topic is that of computing efficiency. Accelerated schemes are in use for transonic flow problems. One such scheme is the approximate factorization (AF) method and an AF scheme to the supersonic flow problem is developed. The second topic is the computation of wake flows. The proper modeling of wake flows is important for multicomponent configurations such as wing-body and multiple lifting surfaces where the wake of one lifting surface has a pronounced effect on a downstream body or other lifting surfaces.

A Study on Homogeneous Charge Compression Ignition Gasoline Engines

NASA Astrophysics Data System (ADS)

Kaneko, Makoto; Morikawa, Koji; Itoh, Jin; Saishu, Youhei

A new engine concept consisting of HCCI combustion for low and midrange loads and spark ignition combustion for high loads was introduced. The timing of the intake valve closing was adjusted to alter the negative valve overlap and effective compression ratio to provide suitable HCCI conditions. The effect of mixture formation on auto-ignition was also investigated using a direct injection engine. As a result, HCCI combustion was achieved with a relatively low compression ratio when the intake air was heated by internal EGR. The resulting combustion was at a high thermal efficiency, comparable to that of modern diesel engines, and produced almost no NOx emissions or smoke. The mixture stratification increased the local A/F concentration, resulting in higher reactivity. A wide range of combustible A/F ratios was used to control the compression ignition timing. Photographs showed that the flame filled the entire chamber during combustion, reducing both emissions and fuel consumption.

Coherent states formulation of polymer field theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Man, Xingkun; Villet, Michael C.; Materials Research Laboratory, University of California, Santa Barbara, California 93106

2014-01-14

We introduce a stable and efficient complex Langevin (CL) scheme to enable the first direct numerical simulations of the coherent-states (CS) formulation of polymer field theory. In contrast with Edwards’ well-known auxiliary-field (AF) framework, the CS formulation does not contain an embedded nonlinear, non-local, implicit functional of the auxiliary fields, and the action of the field theory has a fully explicit, semi-local, and finite-order polynomial character. In the context of a polymer solution model, we demonstrate that the new CS-CL dynamical scheme for sampling fluctuations in the space of coherent states yields results in good agreement with now-standard AF-CL simulations.more » The formalism is potentially applicable to a broad range of polymer architectures and may facilitate systematic generation of trial actions for use in coarse-graining and numerical renormalization-group studies.« less

The efficacy of intraoperative atrial radiofrequency ablation for atrial fibrillation during concomitant cardiac surgery-the Surgical Atrial Fibrillation Suppression (SAFS) Study.

PubMed

Veasey, Rick A; Segal, Oliver R; Large, Janet K; Lewis, Michael E; Trivedi, Uday H; Cohen, Andrew S; Hyde, Jonathan A J; Sulke, A Neil

2011-10-01

Studies assessing radiofrequency ablation (RFA) for atrial fibrillation (AF) performed at the time of concomitant cardiac surgery have reported high success rates. The efficacy of this treatment has primarily been determined by a single electrocardiogram (ECG) or 24-h Holter monitor at follow-up. We sought to assess the true efficacy of this procedure using prolonged cardiac rhythm monitoring. One hundred patients with paroxysmal (n = 47) and persistent AF (n = 53) requiring cardiac surgery were enrolled. Patients were clinically reviewed 6 weeks post-operatively and were monitored with 7-day Holter with full disclosure, 6 months post-surgery. A cohort of 50 patients also underwent 7 day Holter monitoring preoperatively. AF recurrence was defined as >30 s of AF. At 6 months, 75% of patients were in sinus rhythm according to a single ECG. However, only 62% of patients were free from AF on 7-day Holter; all AF episodes in these patients were asymptomatic. The procedure resulted in a significant decrease in AF burden from 56.2% at baseline to 27.5% at 6 months follow-up, (p < 0.001). Predictors of AF recurrence were (1) pre-operative AF duration; (2) persistent compared with paroxysmal AF; (3) increasing left atrial diameter and (4) requirement for mitral valve surgery. Surgical RFA for the treatment of AF, during concomitant cardiac surgery, is a successful procedure and significantly reduces AF burden. However, 13% of patients have asymptomatic AF episodes only identified with continuous monitoring. This has important implications for post-operative anti-arrhythmic and anticoagulant management and for the definition of surgical AF ablation success.

Comparison of the origin and coupling interval between ectopy with and without atrial fibrillation initiation.

PubMed

Kanda, Takashi; Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Sunaga, Akihiro; Tsujimura, Takuya; Matsuda, Yasuhiro; Ohashi, Takuya; Uematsu, Masaaki

2018-01-01

Differentiation of atrial fibrillation (AF) trigger ectopy from other ectopy is often difficult. The purpose of this study was to compare the origin and coupling intervals (CI) between AF-trigger and non-AF-trigger ectopy. This study consisted of 120 patients with AF who underwent an initial ablation. Isoproterenol was infused up to 20μg/min to provoke ectopy and AF. We measured the CI of all ectopy provoked by an isoproterenol infusion. The %CI was calculated as the CI of the ectopy/P-P interval of the preceding 2 beats. A total of 117 patients had at least one ectopy, and AF was induced in 56 (47%) patients. Of the 276 ectopies observed in this study, 211 (76%) originated from pulmonary veins and 77 (28%) were AF-trigger ectopy. AF-trigger ectopy more frequently originated from pulmonary veins (PVs) (74 vs. 3, p<0.001) and had a significantly shorter CI (201±70ms vs. 365±147ms, p<0.001) and lower %CI (29±11% vs. 55±14%, p<0.001) than that of non-AF-trigger ectopy. A receiver operating characteristics analysis revealed that a %CI of 40% was the best cut-off value for differentiating whether it was an AF-trigger or not. The identified trigger group, including patients with provoked AF-trigger ectopy or ectopy with a low %CI (<40%), had a significantly better AF recurrence-free survival rate than the other group (88% vs. 65%, p=0.004). AF-trigger ectopy predominantly originated from PVs and had a short CI. These findings may be useful for estimating whether ectopies are an AF-trigger or not. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms.

PubMed

Lubitz, Steven A; Parsons, Owen E; Anderson, Christopher D; Benjamin, Emelia J; Malik, Rainer; Weng, Lu-Chen; Dichgans, Martin; Sudlow, Cathie L; Rothwell, Peter M; Rosand, Jonathan; Ellinor, Patrick T; Markus, Hugh S; Traylor, Matthew

2017-06-01

Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relationship between AF and noncardioembolic stroke subtypes are unclear. Because AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes. We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2374 ambulatory individuals with ischemic stroke and 5175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression. We calculated AF genetic risk scores using single-nucleotide polymorphisms associated with AF in a previous independent analysis across a range of preselected significance thresholds. There were 460 (19.4%) individuals with cardioembolic stroke, 498 (21.0%) with large vessel, 474 (20.0%) with small vessel, and 814 (32.3%) individuals with strokes of undetermined cause. Most AF genetic risk scores were associated with stroke, with the strongest association ( P =6×10 - 4 ) attributed to scores of 944 single-nucleotide polymorphisms (each associated with AF at P <1×10 - 3 in a previous analysis). Associations between AF genetic risk and stroke were enriched in the cardioembolic stroke subset (strongest P =1.2×10 - 9 , 944 single-nucleotide polymorphism score). In contrast, AF genetic risk was not significantly associated with noncardioembolic stroke subtypes. Comprehensive AF genetic risk scores were specific for cardioembolic stroke. Incomplete workups and subtype misclassification may have limited the power to detect associations with strokes of undetermined pathogenesis. Future studies are warranted to determine whether AF genetic risk is a useful biomarker to enhance clinical discrimination of stroke pathogeneses. © 2017 American Heart Association, Inc.

Impact of Atrial Fibrillation on Healthcare Utilization in the Community: The Atherosclerosis Risk in Communities Study

PubMed Central

Bengtson, Lindsay G. S.; Lutsey, Pamela L.; Loehr, Laura R.; Kucharska‐Newton, Anna; Chen, Lin Y.; Chamberlain, Alanna M.; Wruck, Lisa M.; Duval, Sue; Stearns, Sally C.; Alonso, Alvaro

2014-01-01

Background Atrial fibrillation (AF) is associated with increased risk of hospitalization. Little is known about the impact of AF on utilization of noninpatient health care or about sex or race differences in AF‐related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities study. Methods and Results Participants with incident AF enrolled in fee‐for‐service Medicare for at least 12 continuous months between 1991 and 2009 (n=932) were matched on age, sex, race and field center with up to 3 participants without AF (n=2729). Healthcare utilization was ascertained from Medicare claims and classified by primary International Classification of Diseases, ninth revision code. The average annual numbers of days hospitalized were 13.2 (95% CI 11.6 to 15.0) and 2.8 (95% CI 2.5 to 3.1) for those with and without AF, respectively. The corresponding numbers of annual outpatient claims were 53.3 (95% CI 50.5 to 56.3) and 22.9 (95% CI 22.1 to 23.8) for those with and without AF, respectively. Most utilization among AF patients was attributable to non‐AF conditions. The adjusted rate ratio for annual days hospitalized for other cardiovascular disease–related reasons was 4.58 (95% CI: 3.41 to 6.16) for those with AF versus those without AF. The association between AF and healthcare utilization was similar among men and women and among white and black participants. Conclusions Participants with AF had considerably greater healthcare utilization, and the difference in utilization for other cardiovascular disease–related reasons was substantial. In addition to rate or rhythm treatment, AF management should focus on the accompanying cardiovascular comorbidities. PMID:25359400

Increasing atrial fibrillation prevalence in acute ischemic stroke and TIA.

PubMed

Otite, Fadar Oliver; Khandelwal, Priyank; Chaturvedi, Seemant; Romano, Jose G; Sacco, Ralph L; Malik, Amer M

2016-11-08

To evaluate trends in atrial fibrillation (AF) prevalence in acute ischemic stroke (AIS) and TIA in the United States. We used the Nationwide Inpatient Sample to retrospectively compute weighted prevalence of AF in AIS (n = 4,355,140) and TIA (n = 1,816,459) patients admitted to US hospitals from 2004 to 2013. Multivariate-adjusted models were used to evaluate the association of AF with clinical factors, mortality, length of stay, and cost. From 2004 to 2013, AF prevalence increased by 22% in AIS (20%-24%) and by 38% in TIA (12%-17%). AF prevalence varied by age (AIS: 6% in 50-59 vs 37% in ≥80 years; TIA: 4% in 50-59 vs 24% in ≥80 years), sex (AIS: male 19% vs female 25%; TIA: male 15% vs female 14%), race (AIS: white 26% vs black 12%), and region (AIS: Northeast 25% vs South 20%). Advancing age, female sex, white race, high income, and large hospital size were associated with increased odds of AF in AIS. AF in AIS was a risk factor for in-hospital death (odds ratio 1.93, 95% confidence interval 1.89-1.98) but mortality in AIS with AF decreased from 11.6% to 8.3% (p < 0.001). Compared to no AF, AF was associated with increased cost of $2,310 and length of stay 1.1 days in AIS. AF prevalence in AIS and TIA has continued to increase. Disparity in AF prevalence in AIS and TIA exists by patient and hospital factors. AF is associated with increased mortality in AIS. Innovative AIS preventive strategies are needed in patients with AF, especially in the elderly. © 2016 American Academy of Neurology.

Evaluating the HATCH score for predicting progression to sustained atrial fibrillation in ED patients with new atrial fibrillation.

PubMed

Barrett, Tyler W; Self, Wesley H; Wasserman, Brian S; McNaughton, Candace D; Darbar, Dawood

2013-05-01

Atrial fibrillation (AF) is often first detected in the emergency department (ED). Not all AF patients progress to sustained AF (ie, episodes lasting >7 days), which is associated with increased morbidity. The HATCH score stratifies patients with paroxysmal AF according to their risk for progression to sustained AF within 1 year. The HATCH score has previously never been tested in ED patients. We evaluated the accuracy of the HATCH score to predict progression to sustained AF within 1 year of initial AF diagnosis in the ED. We conducted a retrospective cohort study of 253 ED patients with new onset AF and known rhythm status for 1 year following the initial AF detection. The exposure variable was the HATCH score at initial ED evaluation. The primary outcome was rhythm status at 1 year following initial AF diagnosis. We constructed a receiver operating characteristic curve and calculated the area under the curve to estimate the HATCH score's accuracy of predicting progression to sustained AF. Overall, 61 (24%) of 253 of patients progressed to sustained AF within 1 year of initial detection, and the HATCH score receiver operating characteristic area under the curve was 0.62 (95% confidence interval, 0.54-0.70). Among ED patients with new onset AF, the HATCH score was a modest predictor of progression to sustained AF. Because only 2 patients had a HATCH greater than 5, this previously recommended cut-point was not useful in identifying high-risk patients in this cohort. Refinement of this decision aid is needed to improve its prognostic accuracy in the ED population. Copyright © 2013 Elsevier Inc. All rights reserved.

Co-inoculation of aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus to study fungal invasion, colonization, and competition in maize kernels

PubMed Central

Hruska, Zuzana; Rajasekaran, Kanniah; Yao, Haibo; Kincaid, Russell; Darlington, Dawn; Brown, Robert L.; Bhatnagar, Deepak; Cleveland, Thomas E.

2014-01-01

A currently utilized pre-harvest biocontrol method involves field inoculations with non-aflatoxigenic Aspergillus flavus strains, a tactic shown to strategically suppress native aflatoxin-producing strains and effectively decrease aflatoxin contamination in corn. The present in situ study focuses on tracking the invasion and colonization of an aflatoxigenic A. flavus strain (AF70), labeled with green fluorescent protein (GFP), in the presence of a non-aflatoxigenic A. flavus biocontrol strain (AF36), to better understand the competitive interaction between these two strains in seed tissue of corn (Zea mays). Corn kernels that had been co-inoculated with GFP-labeled AF70 and wild-type AF36 were cross-sectioned and observed under UV and blue light to determine the outcome of competition between these strains. After imaging, all kernels were analyzed for aflatoxin levels. There appeared to be a population difference between the co-inoculated AF70-GFP+AF36 and the individual AF70-GFP tests, both visually and with pixel count analysis. The GFP allowed us to observe that AF70-GFP inside the kernels was suppressed up to 82% when co-inoculated with AF36 indicating that AF36 inhibited progression of AF70-GFP. This was in agreement with images taken of whole kernels where AF36 exhibited a more robust external growth compared to AF70-GFP. The suppressed growth of AF70-GFP was reflected in a corresponding (upto 73%) suppression in aflatoxin levels. Our results indicate that the decrease in aflatoxin production correlated with population depression of the aflatoxigenic fungus by the biocontrol strain supporting the theory of competitive exclusion through robust propagation and fast colonization by the non-aflatoxigenic fungus. PMID:24734028

Co-inoculation of aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus to study fungal invasion, colonization, and competition in maize kernels.

PubMed

Hruska, Zuzana; Rajasekaran, Kanniah; Yao, Haibo; Kincaid, Russell; Darlington, Dawn; Brown, Robert L; Bhatnagar, Deepak; Cleveland, Thomas E

2014-01-01

A currently utilized pre-harvest biocontrol method involves field inoculations with non-aflatoxigenic Aspergillus flavus strains, a tactic shown to strategically suppress native aflatoxin-producing strains and effectively decrease aflatoxin contamination in corn. The present in situ study focuses on tracking the invasion and colonization of an aflatoxigenic A. flavus strain (AF70), labeled with green fluorescent protein (GFP), in the presence of a non-aflatoxigenic A. flavus biocontrol strain (AF36), to better understand the competitive interaction between these two strains in seed tissue of corn (Zea mays). Corn kernels that had been co-inoculated with GFP-labeled AF70 and wild-type AF36 were cross-sectioned and observed under UV and blue light to determine the outcome of competition between these strains. After imaging, all kernels were analyzed for aflatoxin levels. There appeared to be a population difference between the co-inoculated AF70-GFP+AF36 and the individual AF70-GFP tests, both visually and with pixel count analysis. The GFP allowed us to observe that AF70-GFP inside the kernels was suppressed up to 82% when co-inoculated with AF36 indicating that AF36 inhibited progression of AF70-GFP. This was in agreement with images taken of whole kernels where AF36 exhibited a more robust external growth compared to AF70-GFP. The suppressed growth of AF70-GFP was reflected in a corresponding (upto 73%) suppression in aflatoxin levels. Our results indicate that the decrease in aflatoxin production correlated with population depression of the aflatoxigenic fungus by the biocontrol strain supporting the theory of competitive exclusion through robust propagation and fast colonization by the non-aflatoxigenic fungus.

Impact of catheter ablation with remote magnetic navigation on procedural outcomes in patients with persistent and long-standing persistent atrial fibrillation.

PubMed

Jin, Qi; Pehrson, Steen; Jacobsen, Peter Karl; Chen, Xu

2015-11-01

The objectives of this study were to assess the procedural outcomes of persistent and long-standing persistent atrial fibrillation (PsAF and L-PsAF) ablation guided by remote magnetic navigation (RMN), and to detect factors predicting acute restoration of sinus rhythm (SR) by ablation with RMN. A total of 313 patients (275 male, age 59 ± 9.5 years) with PsAF (187/313) or L-PsAF (126/313) undergoing ablation using RMN were included. Patients' disease history, pulmonary venous anatomy, left atrial (LA) volume, procedure time, mapping plus ablation time, radiofrequency (RF) ablation time, fluoroscopy time, radiation dose, and complications were assessed. Stepwise regression was used to predict which variable could best predict acute restoration from AF to SR by ablation. Compared to PsAF, procedure time and RF ablation time were significantly increased in patients with L-PsAF (P = 0.01 and P < 0.001, respectively). No major complications occurred during the procedures in either PsAF or L-PsAF patients. Fifty five of 313 patients converted directly to SR by ablation. Compared to L-PsAF, the rate of SR restoration was significantly higher in PsAF (21 vs 12%, P = 0.03). Stepwise regression analysis showed LA volume was the primary parameter affecting SR restoration (P = 0.01). The LA volume of patients without direct SR restoration by ablation was 24% greater than that of patients with SR restoration (P < 0.001). Catheter ablation using RMN is a safe and effective method for PsAF and L-PsAF. LA volume could be a predictor of direct restoration of SR from sustaining AF by ablation using RMN.

Benefit of Anticoagulation Therapy in Hyperthyroidism-Related Atrial Fibrillation.

PubMed

Chan, Pak-Hei; Hai, Jojo; Yeung, Chun-Yip; Lip, Gregory Y H; Lam, Karen Siu-Ling; Tse, Hung-Fat; Siu, Chung-Wah

2015-08-01

Existing data on the risk of ischemic stroke in hyperthyroidism-related atrial fibrillation (AF) and the impact of long-term anticoagulation in these patients, particularly those with self-limiting AF, remain inconclusive. Risk of stroke in hyperthyroidism-related AF is the same as nonhyperthyroid counterparts. This was a single-center observational study of 9727 Chinese patients with nonvalvular AF from July 1997 to December 2011. Patients with AF diagnosed concomitantly with hyperthyroidism were identified. Primary and secondary endpoints were defined as hospitalization with ischemic stroke and intracranial hemorrhage in the first 2 years. Patient characteristics, duration of AF, and choice of antithrombotic therapy were recorded. Self-limiting AF was defined as <7 days' duration. Out of 9727 patients, 642 (6.6%) had concomitant hyperthyroidism and AF at diagnosis. For stroke prevention, 136 and 243 patients (21.1% and 37.9%) were prescribed warfarin and aspirin, respectively, whereas the remaining patients (41.0%) received no therapy. Ischemic stroke occurred in 50 patients (7.8%), and no patient developed hemorrhagic stroke. Patients with CHA2 DS2 -VASc of 0 did not develop stroke. Warfarin effectively reduced the incidence of stroke compared with aspirin or no therapy in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF, but not in those with self-limiting AF or CHA2 DS2 -VASc of 0. Presence of hyperthyroidism did not confer additional risk of ischemic stroke compared with nonhyperthyroid AF. Patients with hyperthyroidism-related AF are at high risk of stroke (3.9% per year). Warfarin confers stroke prevention in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF. Overall stroke risk was lower in hyperthyroid non-self-limiting AF patients compared with nonhyperthyroid counterparts. © 2015 Wiley Periodicals, Inc.

Influence of atrial fibrillation on the mortality of patients with heart failure with preserved ejection fraction.

PubMed

Franco, Jonathan; Formiga, Francesc; Cepeda, Jose; Llacer, Pau; Arévalo-Lorido, Juan; Cerqueiro, Jose; González-Franco, Alvaro; Epelde, Francesc; Manzano, Luis; Montero Pérez-Barquero, Manuel

2018-05-23

The impact of atrial fibrillation (AF) on the prognosis of heart failure with preserved ejection fraction (HFpEF) is still the subject of debate. We analysed the influence of AF on the prognosis on mortality and readmission in patients with HFpEF. Prospective observational study in 1,971 patients with HFpEF, who were admitted for acute heart failure. Patients were divided into 2 groups according to the presence or absence of AF. We analysed mortality, readmissions and combined mortality/readmissions at one year follow-up. A total of 1,177 (59%) patients had AF, mean age 80.3 (7.8) years and 1,233 (63%) were women. Patients with HFpEF and AF were older, female, greater valvular aetiology and lower comorbidity measured by the Charlson index. At the one year follow-up, 430 (22%) patients had died and 840 (43%) had been readmitted. In the 2 groups analysed, there was no difference in all-cause mortality (22 vs. 21%; P=.739, AF vs. no-AF, respectively) or cardiovascular causes (9.6 vs. 8.2%; P=.739, AF vs. no-AF, respectively). In the multivariable analysis, factors associated with higher mortality were: age, male, valvular aetiology, uric acid, and comorbidity. In the analysis of the subgroup with HFpEF with AF, the presence of chronic AF compared to de novo AF was associated with higher mortality (HR 1,716; 95% CI 1,099-2,681; P=.018). In patients with HFpEF, the presence of AF is frequent. During the one-year follow-up, the presence of AF does not influence mortality or readmissions in patients with HFpEF. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Atrial Fibrillation in Hypertrophic Cardiomyopathy: Prevalence, Clinical Correlations, and Mortality in a Large High‐Risk Population

PubMed Central

Siontis, Konstantinos C.; Geske, Jeffrey B.; Ong, Kevin; Nishimura, Rick A.; Ommen, Steve R.; Gersh, Bernard J.

2014-01-01

Background Atrial fibrillation (AF) is a common sequela of hypertrophic cardiomyopathy (HCM), but evidence on its prevalence, risk factors, and effect on mortality is sparse. We sought to evaluate the prevalence of AF, identify clinical and echocardiographic correlates, and assess its effect on mortality in a large high‐risk HCM population. Methods and Results We identified HCM patients who underwent evaluation at our institution from 1975 to 2012. AF was defined by known history (either chronic or paroxysmal), electrocardiogram, or Holter monitoring at index visit. We examined clinical and echocardiographic variables in association with AF. The effect of AF on overall and cause‐specific mortality was evaluated with multivariate Cox proportional hazards models. Of 3673 patients with HCM, 650 (18%) had AF. Patients with AF were older and more symptomatic (P<0.001). AF was less common among patients with obstructive HCM phenotype and was associated with larger left atria, higher E/e’ ratios, and worse cardiopulmonary exercise tolerance (all P values<0.001). During median (interquartile range) follow‐up of 4.1 (0.2 to 10) years, 1069 (29%) patients died. Patients with AF had worse survival compared to those without AF (P<0.001). In multivariate analysis adjusted for established risk factors of mortality in HCM, the hazard ratio (95% confidence interval) for the effect of AF on overall mortality was 1.48 (1.27 to 1.71). AF did not have an effect on sudden or nonsudden cardiac death. Conclusions In this large referral HCM population, approximately 1 in 5 patients had AF. AF was a strong predictor of mortality, even after adjustment for established risk factors. PMID:24965028

Morphologies of the atria and pulmonary veins in relation to lone atrial fibrillation progression: a dual-source computed tomography scan study.

PubMed

Liu, Xing-Peng; Xu, Xia; Tian, Ying; Tang, Ri-Bo; Yu, Rong-Hui; Long, De-Yong; Sang, Cai-Hua; Jiang, Chen-Xi; Ning, Man; Dong, Jian-Zeng; Ma, Chang-Sheng

2012-11-01

Atrial Remodeling and Lone Atrial Fibrillation. We sought to investigate the role of anatomic remodeling of the atria and pulmonary veins (PVs) in the progression of lone atrial fibrillation (AF) using dual-source computed tomography (DSCT). From 1,308 consecutive patients referred for an index ablation procedure for AF, we prospectively enrolled 29 consecutive patients with recently developed (<3 months) lone persistent AF (PsAF) and 23 consecutive patients with short-lasting (6-12 months) lone PsAF, all of whom had a history of paroxysmal AF (PAF). The control group consisted of 33 patients with lone PAF. On DSCT, the recently developed PsAF group showed more extensive atrial anatomic remodeling than the PAF group as shown by ∼40% higher spot biatrial volume, even though the mean duration of continuous AF was only 6 weeks. In contrast, the DSCT variables in the recently developed PsAF group and the short-lasting PsAF group were comparable, despite the fact that the mean duration of continuous AF in the latter group was 8 months. Series of cross-sectional areas of the ostial 1.5 cm of PV trunks were comparable in the PAF and PsAF groups in all but 3 ostial planes. A higher spot left atrial volume was the only independent factor associated with the progression of lone PAF to PsAF (OR: 1.06, 95% CI: 1.03-1.09, P<0.0001) on logistic regression. Prominent anatomic remodeling of the atria, rather than the PVs, underlies the mechanism of recent progression of lone paroxysmal AF to the persistent variety. © 2012 Wiley Periodicals, Inc.

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial

PubMed Central

Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Breithardt, Günter; Hankey, Graeme J.; Becker, Richard C.; Singer, Daniel E.; Halperin, Jonathan L.; Hacke, Werner; Nessel, Christopher C.; Berkowitz, Scott D.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

2015-01-01

Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Methods and results Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. PMID:25209598

An illness-specific version of the Revised Illness Perception Questionnaire in patients with atrial fibrillation (AF IPQ-R): Unpacking beliefs about treatment control, personal control and symptom triggers.

PubMed

Taylor, Elaina C; O'Neill, Mark; Hughes, Lyndsay D; Moss-Morris, Rona

2018-04-01

This study modified the Revised Illness Perception Questionnaire (IPQ-R) in patients with persistent atrial fibrillation (AF). Qualitative interviews and think-aloud techniques informed modification of the IPQ-R to be specific to AF patients. Confirmatory Factor Analysis (CFA) (n = 198) examined the validity of the modified IPQ-R (AF-IPQ-R). Exploratory factor analysis (EFA) examined the new AF-triggers scale. Construct validity examined associations between the AF-IPQ-R, quality of life (QoL) and beliefs about medicines. Test-retest and internal reliability were examined. Interviews indicated that patients viewed triggers of AF rather than initial causes of illness as more applicable. Patients believed specific behaviours such as rest could control AF. Treatment control beliefs related to pharmacological and procedural treatments. These data were used to modify the IPQ-R subscales and to develop a triggers of AF scale. CFA indicated good model fit. EFA of the triggers scale indicated three factors: emotional; health behaviours; and over-exertion triggers. Expected correlations were found between the AF-IPQ-R, QoL and treatment beliefs, evidencing good construct validity. The AF-IPQ-R showed sound psychometric properties. It provides more detailed specification than the IPQ-R of beliefs that may help to understand poor QoL in AF patients, and guidance for future interventions in this area.

Modulated exchange bias in NiFe/CoO/α-Fe2O3 trilayers and NiFe/CoO bilayers

NASA Astrophysics Data System (ADS)

Li, X.; Lin, K.-W.; Yeh, W.-C.; Desautels, R. D.; van Lierop, J.; Pong, Philip W. T.

2017-02-01

While the exchange bias in ferromagnetic/antiferromagnetic (FM/AF) bilayer and FM1/AF/FM2 trilayer configurations has been widely investigated, the role of an AF2 layer in FM/AF1/AF2 trilayer configurations is still not well understood. In this work, the magnetic properties of NiFe/CoO, NiFe/α-Fe2O3 bilayers, and NiFe/CoO/α-Fe2O3 trilayer were studied comparatively. The microstructure and chemical composition were characterized. Temperature dependent magnetometry reveals increased irreversibility temperature in NiFe/CoO/α-Fe2O3 trilayer compared with NiFe/CoO bilayer. The magnetic hysteresis loops show that the exchange bias (Hex) and coercivity (Hc) depend strongly on the anisotropy of AF layer (CoO, α-Fe2O3 and CoO/α-Fe2O3). Our work shows that the AF1/AF2 interfacial interactions can be used effectively for tuning the exchange bias in FM/AF1/AF2 trilayers.

Clinical and Economic Implications of AF Related Stroke.

PubMed

Ali, Ali N; Abdelhafiz, Ahmed

2016-01-01

A major cause of morbidity and mortality among patients with atrial fibrillation (AF) relates to the increased risk of stroke. The burden of illness that AF imparts on stroke is likely to increase with our aging populations and increasingly sophisticated cardiac monitoring techniques. Understanding the clinical and economic differences between AF related ischaemic stroke and non-AF related stroke is important if we are to improve future cost effectiveness analyses of potential preventative treatments, but also to help educate clinical and policy decision makers on use or availability of treatments to prevent AF related stroke. In this article we review the existing evidence that highlights differences in the clinical characteristics and outcomes between AF and non-AF stroke, as well as differences in their economic impact and discuss ways to improve future economic analyses.

In permanent atrial fibrillation, PDE3 reduces force responses to 5‐HT, but PDE3 and PDE4 do not cause the blunting of atrial arrhythmias

PubMed Central

Schwarz, Simon; Ravens, Ursula; Knaut, Michael

2016-01-01

Abstract Background and Purpose 5‐HT increases force and L‐type Ca2 + current (ICa,L) and causes arrhythmias through 5‐HT4 receptors in human atrium. In permanent atrial fibrillation (peAF), atrial force responses to 5‐HT are blunted, arrhythmias abolished but ICa,L responses only moderately attenuated. We investigated whether, in peAF, this could be due to an increased function of PDE3 and/or PDE4, using the inhibitors cilostamide (300 nM) and rolipram (1 μM) respectively. Experimental Approach Contractile force, arrhythmic contractions and ICa,L were assessed in right atrial trabeculae and myocytes, obtained from patients with sinus rhythm (SR), paroxysmal atrial fibrillation (pAF) and peAF. Key Results Maximum force responses to 5‐HT were reduced to 15% in peAF, but not in pAF. Cilostamide, but not rolipram, increased both the blunted force responses to 5‐HT in peAF and the inotropic potency of 5‐HT fourfold to sevenfold in trabeculae of patients with SR, pAF and peAF. Lusitropic responses to 5‐HT were not decreased in peAF. Responses of ICa,L to 5‐HT did not differ and were unaffected by cilostamide or rolipram in myocytes from patients with SR or peAF. Concurrent cilostamide and rolipram increased 5‐HT's propensity to elicit arrhythmias in trabeculae from patients with SR, but not with peAF. Conclusions and Implications PDE3, but not PDE4, reduced inotropic responses to 5‐HT in peAF, independently of lusitropy and ICa,L, but PDE3 activity was the same as that in patients with SR and pAF. Atrial remodelling in peAF abolished the facilitation of 5‐HT to induce arrhythmias by inhibition of PDE3 plus PDE4. PMID:27238373

Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation in Patients with Atrial Fibrillation.

PubMed

Kumar, Sanjay; Qu, Sarah; Kassotis, John T

2012-01-01

Atrial fibrillation (AF) is the most common sustained atrial arrhythmia conferring a higher morbidity and mortality. Despite the increasing incidence of AF; available therapies are far from perfect. Dietary fish oils, containing omega 3 fatty acids, also called polyunsaturated fatty acid [PUFA] have demonstrated beneficial electrophysiological, autonomic and anti-inflammatory effects on both atrial and ventricular tissue. Multiple clinical trials, focusing on various subsets of patients with AF, have studied the role of PUFA and their potential role in reducing the incidence of this common arrhythmia. While PUFA appears to have a beneficial effect in the primary prevention of AF in the elderly with structural heart disease, this benefit has not been universally observed. In the secondary prevention of AF, PUFA seems to have a greater impact in the reducing AF in patients with paroxysmal or persistent AF, stages of AF associated with less atrial fibrosis and negative structural remodeling. However, AF suppression has not been consistently demonstrated in clinical trials. In patients undergoing heart surgery, increasing PUFA intake has yielded mixed results in terms of AF prevention post-operatively; however, increased PUFA has been associated with a reduction in hospital stay. Therefore recommending the use of PUFA for the purpose of AF reduction remains controversial. This is in part attributable to the complexity of AF. Other conflicting variables include: heterogeneous patient populations studied; variable dosing; duration of follow-up; comorbidities; and, concomitant pharmacotherapy. This review article reviews in detail available basic and clinical research studies of fish oil in the treatment of AF, and its role in the treatment of this common disorder. AF=Atrial fibrillation, CHS=Cardiovascular Health Study,CABG=Coronary artery bypass surgery, d=Day, DHA=Docosahexaenoic acid, EPA=Eicosapentaenoic acid, ERP= Effective refractory period, g=Gram, PAF= Paroxysmal atrial fibrillation, PeAF= Persistent atrial fibrillation PUFA= Polyunsaturated fatty acid.

Injectable trace minerals (selenium, copper, zinc, and manganese) alleviates inflammation and oxidative stress during an aflatoxin challenge in lactating multiparous Holstein cows.

PubMed

Pate, R T; Cardoso, F C

2018-06-20

Trace minerals are vital in the antioxidant response during oxidative stress; however, limited research is available on the effects of trace mineral supplementation during an aflatoxin (AF) challenge. The objective of the study was to determine the effects of 2 subcutaneous injections of 15 mg/mL of Cu, 5 mg/mL of Se, 60 mg/mL of Zn, and 10 mg/mL of Mn (Multimin 90, Multimin North America, Fort Collins, CO) given at 1 mL/90.7 kg of average body weight in response to an AF challenge. Fifty-eight Holstein cows [body weight (mean ± SD) = 734 ± 6 0kg; days in milk = 191 ± 93] were assigned to 1 of 3 treatments in a randomized complete block design. The experimental period (63 d) was divided into an adaptation phase (d 1-56) and a measurement phase (d 57-63). From d 57 to 59, cows received an AF challenge that consisted of 100 μg of aflatoxin B 1 /kg of dietary dry matter intake (DMI) administered orally via balling gun. Treatments were saline injection and no AF challenge (NEG), saline injection and AF challenge (POS), and trace mineral injection and AF challenge (MM). Injections were performed subcutaneously on d 1 and 29. Milk was sampled 3 times daily from d 56 to 63, blood was sampled on d 0, 56, 60, and 63, and liver samples were taken on d 0 and 60. Two treatment orthogonal contrasts [CONT1 (NEG vs. POS) and CONT2 (POS vs. MM)] were made. Cows in NEG had lower AF excretion in milk and greater 3.5% fat-corrected milk (32.1 ± 1.37 kg/d) compared with cows in POS (28.6 ± 1.43 kg/d). Feed efficiencies (3.5% fat-corrected milk/DMI, energy-corrected milk/DMI, and milk/DMI) were greater for cows in NEG (1.42 ± 0.07, 1.46 ± 0.07, and 1.45 ± 0.07, respectively) than cows in POS (1.16 ± 0.08, 1.18 ± 0.08, and 1.22 ± 0.07, respectively). Cows in POS had greater milk urea nitrogen and blood urea nitrogen than cows in MM. Liver concentrations of Se and Fe were greater for cows in MM compared with cows in POS. Cows in MM tended to have greater plasma glutathione peroxidase activity compared with cows in POS. An upregulation of liver GPX1 was observed for cows in POS compared with cows in MM. In conclusion, subcutaneous injection of trace minerals maintained an adequate antioxidant response when an AF challenge was present. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Photosynthesis Is Not Involved in the Mechanism of Action of Acifluorfen in Cucumber (Cucumis sativus L.)

PubMed Central

Duke, Stephen O.; Kenyon, William H.

1986-01-01

The possible role of photosynthesis in the mechanism of action of the herbicide acifluorfen (2-chloro-4-(trifluoromethyl)phenoxy-2-nitrobenzoate; AF) was examined. The sensitivity to AF of cotyledons of cucumber (Cucumis sativus L.) which had been grown under far red light (FR) and white light were compared. FR grown tissues which were photosynthetically imcompetent were hypersensitive to AF under white light and had approximately the same relative response to AF under blue and red light as green, white-light-grown tissues. Ultrastructural damage was apparent in FR-grown, AF-treated tissues within an hour after exposure to white light, with cytoplasmic and plastidic disorganization occurring simultaneously. In cucumber cotyledon tissue which had been greening for various time periods, there was no correlation between photosynthetic capacity and herbicidal efficacy of AF. PSII inhibitors (atrazine and DCMU) and the photophosphorylation inhibitor, tentoxin, had no effect on AF activity. Atrazine did not reduce AF activity at any concentration or light intensity tested, indicating that there is no second, photosynthetic-dependent mechanism of action operating at low AF concentrations or low fluence rates. Carbon dioxide-dependent O2 evolution of intact chloroplasts of spinach (Spinacia oleracea L.) had an AF I50 of 125 micromolar compared to 1000 micromolar for cucumber, whereas AF was much more herbicidally active in tissues of cucumber than of spinach. Differences in activity could not be accounted for by differences in uptake of AF. Our results indicate that there is no photosynthetic involvement in the mechanism of action of AF in cucumber. Images Fig. 2 PMID:16664919

Clinical presentation, management, and outcomes in the Indian Heart Rhythm Society-Atrial Fibrillation (IHRS-AF) registry.

PubMed

Vora, A; Kapoor, A; Nair, M; Lokhandwala, Y; Narsimhan, C; Ravikishore, A G; Dwivedi, S K; Namboodiri, N; Hygriv, R; Saxena, A; Nabar, A; Garg, S; Bardoloi, N; Yadav, R; Nambiar, A; Pandurangi, U; Jhala, D; Naik, A; Nagmallesh; Rajagopal, S; Selvaraj, R; Arora, V; Thachil, A; Thomas, J; Panicker, G

A national atrial fibrillation (AF) registry was conducted under the aegis of the Indian Heart Rhythm Society (IHRS), to capture epidemiological data-type of AF, clinical presentation and comorbidities, current treatment practices, and 1-year follow-up outcomes. A total of 1537 patients were enrolled from 24 sites in India in the IHRS-AF registry from July 2011 to August 2012. Their baseline characteristics and follow-up data were recorded in case report forms and subsequently analyzed. The average age of Indian AF patients was 54.7 years. There was a marginal female preponderance - 51.5% females and 48.5% males. At baseline, 20.4% had paroxysmal AF; 33% had persistent AF; 35.1% had permanent AF and 11% had first AF episode. At one-year follow-up, 45.6% patients had permanent AF. Rheumatic valvular heart disease (RHD) was present in 47.6% of patients. Hypertension, heart failure, coronary artery disease, and diabetes were seen in 31.4%, 18.7%, 16.2%, and 16.1%, respectively. Rate control was the strategy used in 75.2% patients, digoxin and beta-blockers being the most frequently prescribed rate-control drugs. Oral anticoagulation (OAC) drugs were used in 70% of patients. The annual mortality was 6.5%, hospitalization 8%, and incidence of stroke 1%. In India, AF patients are younger and RHD is still the most frequent etiology. Almost two-third of the patients have persistent/permanent AF. At one-year follow-up, there is a significant mortality and morbidity in AF patients in India. Copyright © 2016. Published by Elsevier B.V.

Successful Repeat Catheter Ablation of Recurrent Longstanding Persistent Atrial Fibrillation With Rotor Elimination as the Procedural Endpoint: A Case Series.

PubMed

Sommer, Philipp; Kircher, Simon; Rolf, Sascha; John, Silke; Arya, Arash; Dinov, Borislav; Richter, Sergio; Bollmann, Andreas; Hindricks, Gerhard

2016-03-01

There remains a lack of consensus regarding the ideal ablation strategy for atrial fibrillation (AF), particularly in patients with persistent or longstanding persistent AF. Given increasing evidence from clinical imaging studies that rotors sustain AF, rotor elimination may be a desirable procedural endpoint. However, there is no description to date of the clinical outcomes using rotor elimination during ablation as the procedural endpoint. Moreover, a series of studies question whether procedural AF termination is a desirable endpoint for ablation after many forms of AF ablation. We report a single-center experience of rotor elimination during AF ablation using Focal Impulse and Rotor Mapping (FIRM), describing 20 consecutive patients with case descriptions of 3 patients with recurrent longstanding persistent AF after prior ablation. In all cases, endocardial mapping using a 64-electrode basket catheter was performed to identify rotors, which were eliminated using radiofrequency catheter ablation. After it was verified that all identified rotors were eliminated, standard ablation consisting of PV isolation was performed. Notably, persistent AF terminated in only 1/20 (5%) patients. However, after a follow-up of 6 months, single-procedure freedom from AF was 80% (16/20 patients) with only 1 patient on antiarrhythmic drugs. All three patients in the highlighted series are AF free despite the lack of acute procedural AF termination. Patients with persistent AF including those with unsuccessful prior ablation can be treated successfully by rotor targeted ablation, using the elimination of all rotors rather than acute AF termination as the procedural endpoint. © 2015 Wiley Periodicals, Inc.

A structured reading algorithm improves telemetric detection of atrial fibrillation after acute ischemic stroke.

PubMed

Kallmünzer, Bernd; Breuer, Lorenz; Hering, Christiane; Raaz-Schrauder, Dorette; Kollmar, Rainer; Huttner, Hagen B; Schwab, Stefan; Köhrmann, Martin

2012-04-01

Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter (AF). However, the condition remains underdiagnosed, because paroxysmal AF may be missed by diagnostic tests in the acute phase. In this study, the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data (SEA-AF). Three hundred forty-six consecutive patients with acute ischemic stroke were prospectively included and subjected to standard telemetric monitoring. In addition, telemetric data were separately analyzed following SEA-AF, consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration. Serial electrocardiograms were conducted in 24-hour intervals. Median effective telemetry monitoring time was 75.5 hours (interquartile range 64-86 hours). Overall, AF was diagnosed in 119 of 346 patients (34.4%). The structured reading algorithm was the most sensitive method to detected AF. Conventional telemetry and serial electrocardiographic assessments were less effective. However, only 35% of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring. Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessments and standard telemetry without structured reading. The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessments. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

A systematic review of the health benefits of exercise rehabilitation in persons living with atrial fibrillation.

PubMed

Giacomantonio, Nicholas B; Bredin, Shannon S D; Foulds, Heather J A; Warburton, Darren E R

2013-04-01

This systematic review sought to evaluate critically the health benefits of physical activity among persons with atrial fibrillation (AF). AF is increasing in Western society. While health benefits of physical activity are well established, benefits of physical activity among individuals with AF are not clearly identified. Literature was retrieved systematically through searching electronic databases (MEDLINE, EMBASE, Cochrane), cross-referencing, and drawing on the authors' knowledge. Identified original research articles evaluated health benefits of physical activity among persons with AF or effects of physical activity on AF incidence. From 1056 individual citations, 36 eligible articles were identified. Moderate-intensity physical activity was found to improve exercise capacity, quality of life, and the ability to carry out activities of daily living among persons with AF (n = 6). Increased incidence of AF was not associated with physical activity among the general population (n = 2), although long-term vigorous endurance exercise may be associated with increased incidence of AF (n = 7), and greater risks may be associated with high-intensity physical activity among those with AF (n = 2). Moderate-intensity physical activity among individuals with AF does not adversely alter training outcomes, functional capacity, morbidity, or mortality compared with those in sinus rhythm (n = 12). Physical activity may improve management and treatment of AF (n = 6) and, among at-risk populations, may reduce incidence of AF (n = 3). In conclusion, moderate-intensity physical activity should be encouraged among persons with or at risk of AF. Further research is needed. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions

PubMed Central

Pellman, Jason; Sheikh, Farah

2017-01-01

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting 1% to 2% of the general population. It is characterized by rapid and disorganized atrial activation leading to impaired atrial function, which can be diagnosed on an EKG by lack of a P-wave and irregular QRS complexes. AF is associated with increased morbidity and mortality and is a risk factor for embolic stroke and worsening heart failure. Current research on AF support and explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria, either specifically as in lone AF or secondary to other heart disease as in heart failure-associated AF. Remodeling in AF can be grouped into three categories that include: (i) electrical remodeling, which includes modulation of L-type Ca2+ current, various K+ currents and gap junction function; (ii) structural remodeling, which includes changes in tissues properties, size, and ultrastructure; and (iii) autonomic remodeling, including altered sympathovagal activity and hyperinnervation. Electrical, structural, and autonomic remodeling all contribute to creating an AF-prone substrate which is able to produce AF-associated electrical phenomena including a rapidly firing focus, complex multiple reentrant circuit or rotors. Although various remodeling events occur in AF, current AF therapies focus on ventricular rate and rhythm control strategies using pharmacotherapy and surgical interventions. Recent progress in the field has started to focus on the underlying substrate that drives and maintains AF (termed upstream therapies); however, much work is needed in this area. Here, we review current knowledge of AF mechanisms, therapies, and new areas of investigation. PMID:25880508

Lone atrial fibrillation: where are we now?

PubMed

Potpara, Tatjana S; Lip, Gregory Y

2011-10-01

There is a growing pandemic of atrial fibrillation (AF), affecting nearly 2% of the general adult population. Atrial fibrillation is commonly associated with structural heart disease, and AF itself causes a sequence of complex processes of electrical, contractile, and structural remodeling of the atrial myocardium, which facilitate further AF progression. Nonetheless, AF may also affect individuals aged ≤ 65 years who have no evidence of associated cardiopulmonary or other disease, including hypertension; this is otherwise referred to as "lone" AF and is considered to have a generally favorable prognosis. The true prevalence of lone AF is unknown. Growing insights into the diversity of numerous mechanisms involved in the pathogenesis of AF, including acute atrial stretch, structural and electrophysiological alterations, systemic inflammation, oxidative stress, autonomic imbalance, genetic predisposition, and many others, and increasing recognition of novel risk factors for AF, including obesity, metabolic syndrome, subclinical atherosclerosis, sleep apnea, alcohol consumption, and endurance sports, suggest that apparently lone AF might not be so "lone" in many patients, which could have important prognostic and therapeutic implications. In this article, we summarize the current knowledge of epidemiology, etiopathogenesis, and pathophysiology of so-called lone AF and discuss the issues of long-term prognosis and management of patients who have an apparently lone AF.

AF-6 is a positive modulator of the PINK1/parkin pathway and is deficient in Parkinson's disease

PubMed Central

Haskin, Joseph; Szargel, Raymonde; Shani, Vered; Mekies, Lucy N.; Rott, Ruth; Lim, Grace G. Y.; Lim, Kah-Leong; Bandopadhyay, Rina; Wolosker, Herman; Engelender, Simone

2013-01-01

Parkin E3 ubiquitin-ligase activity and its role in mitochondria homeostasis are thought to play a role in Parkinson's disease (PD). We now report that AF-6 is a novel parkin interacting protein that modulates parkin ubiquitin-ligase activity and mitochondrial roles. Parkin interacts with the AF-6 PDZ region through its C-terminus. This leads to ubiquitination of cytosolic AF-6 and its degradation by the proteasome. On the other hand, endogenous AF-6 robustly increases parkin translocation and ubiquitin-ligase activity at the mitochondria. Mitochondrial AF-6 is not a parkin substrate, but rather co-localizes with parkin and enhances mitochondria degradation through PINK1/parkin-mediated mitophagy. On the other hand, several parkin and PINK1 juvenile disease-mutants are insensitive to AF-6 effects. AF-6 is present in Lewy bodies and its soluble levels are strikingly decreased in the caudate/putamen and substantia nigra of sporadic PD patients, suggesting that decreased AF-6 levels may contribute to the accumulation of dysfunctional mitochondria in the disease. The identification of AF-6 as a positive modulator of parkin translocation to the mitochondria sheds light on the mechanisms involved in PD and underscores AF-6 as a novel target for future therapeutics. PMID:23393160

Rhythm-based heartbeat duration normalization for atrial fibrillation detection.

PubMed

Islam, Md Saiful; Ammour, Nassim; Alajlan, Naif; Aboalsamh, Hatim

2016-05-01

Screening of atrial fibrillation (AF) for high-risk patients including all patients aged 65 years and older is important for prevention of risk of stroke. Different technologies such as modified blood pressure monitor, single lead ECG-based finger-probe, and smart phone using plethysmogram signal have been emerging for this purpose. All these technologies use irregularity of heartbeat duration as a feature for AF detection. We have investigated a normalization method of heartbeat duration for improved AF detection. AF is an arrhythmia in which heartbeat duration generally becomes irregularly irregular. From a window of heartbeat duration, we estimate the possible rhythm of the majority of heartbeats and normalize duration of all heartbeats in the window based on the rhythm so that we can measure the irregularity of heartbeats for both AF and non-AF rhythms in the same scale. Irregularity is measured by the entropy of distribution of the normalized duration. Then we classify a window of heartbeats as AF or non-AF by thresholding the measured irregularity. The effect of this normalization is evaluated by comparing AF detection performances using duration with the normalization, without normalization, and with other existing normalizations. Sensitivity and specificity of AF detection using normalized heartbeat duration were tested on two landmark databases available online and compared with results of other methods (with/without normalization) by receiver operating characteristic (ROC) curves. ROC analysis showed that the normalization was able to improve the performance of AF detection and it was consistent for a wide range of sensitivity and specificity for use of different thresholds. Detection accuracy was also computed for equal rates of sensitivity and specificity for different methods. Using normalized heartbeat duration, we obtained 96.38% accuracy which is more than 4% improvement compared to AF detection without normalization. The proposed normalization method was found useful for improving performance and robustness of AF detection. Incorporation of this method in a screening device could be crucial to reduce the risk of AF-related stroke. In general, the incorporation of the rhythm-based normalization in an AF detection method seems important for developing a robust AF screening device. Copyright © 2016 Elsevier Ltd. All rights reserved.

Advancing the literature on designing audit and feedback interventions: identifying theory-informed hypotheses.

PubMed

Colquhoun, Heather L; Carroll, Kelly; Eva, Kevin W; Grimshaw, Jeremy M; Ivers, Noah; Michie, Susan; Sales, Anne; Brehaut, Jamie C

2017-09-29

Audit and feedback (A&F) is a common strategy for helping health providers to implement evidence into practice. Despite being extensively studied, health care A&F interventions remain variably effective, with overall effect sizes that have not improved since 2003. Contributing to this stagnation is the fact that most health care A&F interventions have largely been designed without being informed by theoretical understanding from the behavioral and social sciences. To determine if the trend can be improved, the objective of this study was to develop a list of testable, theory-informed hypotheses about how to design more effective A&F interventions. Using purposive sampling, semi-structured 60-90-min telephone interviews were conducted with experts in theories related to A&F from a range of fields (e.g., cognitive, health and organizational psychology, medical decision-making, economics). Guided by detailed descriptions of A&F interventions from the health care literature, interviewees described how they would approach the problem of designing improved A&F interventions. Specific, theory-informed hypotheses about the conditions for effective design and delivery of A&F interventions were elicited from the interviews. The resulting hypotheses were assigned by three coders working independently into themes, and categories of themes, in an iterative process. We conducted 28 interviews and identified 313 theory-informed hypotheses, which were placed into 30 themes. The 30 themes included hypotheses related to the following five categories: A&F recipient (seven themes), content of the A&F (ten themes), process of delivery of the A&F (six themes), behavior that was the focus of the A&F (three themes), and other (four themes). We have identified a set of testable, theory-informed hypotheses from a broad range of behavioral and social science that suggest conditions for more effective A&F interventions. This work demonstrates the breadth of perspectives about A&F from non-healthcare-specific disciplines in a way that yields testable hypotheses for healthcare A&F interventions. These results will serve as the foundation for further work seeking to set research priorities among the A&F research community.

Rabbit notochordal cells modulate the expression of inflammatory mediators by human annulus fibrosus cells cocultured with activated macrophage-like THP-1 cells.

PubMed

Kim, Joo Han; Moon, Hong Joo; Lee, Jin Hoon; Kim, Jong Hyun; Kwon, Taek Hyun; Park, Youn Kwan

2012-10-15

We evaluated the influence of rabbit notochordal cells on the expression of inflammatory mediators by human annulus fibrosus (AF) cells cocultured with macrophage-like cells. To identify the protective effect of rabbit notochordal cells on AF during in vitro inflammation. Discogenic pain, which is an important cause of intractable lower back pain, is associated with macrophage-mediated inflammation in the AF. Although rabbit notochordal cells prevent intervertebral disc degeneration, their effects on human AF inflammation remain unknown. Human AF pellets were cocultured for 48 hours with notochordal cell clusters from adult New Zealand White rabbits and phorbol myristate acetate (PMA)-stimulated human macrophage-like THP-1 cells. Conditioned media (CM) from the cocultures were assayed by enzyme-linked immunosorbent assay. The expression of inflammatory mediators in the AF pellets was evaluated by real-time reverse-transcription polymerase chain reaction. The levels of mRNA for interleukin (IL)-6, IL-8, and inducible nitric oxide synthase (iNOS) in the AF pellets cocultured with notochordal cells and macrophages (hAF[rNC-M]) were significantly lower than those in the AF pellets cultured with macrophages alone (hAF[M]) (P < 0.05). The levels of IL-6 and IL-8 proteins in the CM of hAF(rNC-M) were significantly lower than those in the CM of hAF(M) (P < 0.05). Coculturing with notochordal cells significantly decreased the levels of mRNA for IL-6, IL-8, and iNOS in the macrophage-exposed AF pellets (P < 0.05). After 1 ng/mL IL-1β stimulation, the levels of IL-6 and IL-8 mRNA and the level of IL-8 protein production were significantly decreased in the AF pellets with notochordal cells compared with naïve AF pellets (P < 0.05). In an in vitro coculture system, rabbit notochordal cells reduced the levels of main inflammatory mediators and gene expression in the human AF during inflammation. Therefore, rabbit notochordal cells may constitute an important protective tool against symptomatic disc development.

Catalytic soman scavenging by Y337A/F338A acetylcholinesterase mutant assisted with novel site-directed aldoximes

PubMed Central

Kovarik, Zrinka; Hrvat, Nikolina Maček; Katalinić, Maja; Sit, Rakesh K.; Paradyse, Alexander; Žunec, Suzana; Musilek, Kamil; Fokin, Valery V.; Taylor, Palmer; Radić, Zoran

2016-01-01

Exposure to the nerve agent soman is difficult to treat due to the rapid dealkylation of soman-acetylcholinesterase (AChE) conjugate known as aging. Oxime antidotes commonly used to reactivate organophosphate inhibited AChE are ineffective against soman, while the efficacy of the recommended nerve agent bioscavenger butyrylcholinesterase is limited by strictly stoichiometric scavenging. To overcome this limitation, we tested ex vivo, in human blood, and in vivo, in soman exposed mice, the capacity of aging-resistant human AChE mutant Y337A/F338A in combination with oxime HI-6 to act as a catalytic bioscavenger of soman. HI-6 was previously shown in vitro to efficiently reactivate this mutant upon soman, as well as VX, cyclosarin, sarin and paraoxon inhibition. We here demonstrate that ex vivo, in whole human blood, 1 μM soman was detoxified within 30 minutes when supplemented with 0.5 μM Y337A/F338A AChE and 100 μM HI-6. This combination was further tested in vivo. Catalytic scavenging of soman in mice improved the therapeutic outcome and resulted in the delayed onset of toxicity symptoms. Furthermore, in a preliminary in vitro screen we identified an even more efficacious oxime than HI-6, in a series of forty-two pyridinium aldoximes, and five imidazole 2-aldoxime N-propyl pyridinium derivatives. One of the later imidazole aldoximes, RS-170B, was a 2–3 –fold more effective reactivator of Y337A/F338A AChE than HI-6 due to the smaller imidazole ring, as indicated by computational molecular models, that affords a more productive angle of nucleophilic attack. PMID:25835984

Effect of Simultaneous Inoculation with Yeast and Bacteria on Fermentation Kinetics and Key Wine Parameters of Cool-Climate Chardonnay

PubMed Central

Jussier, Delphine; Dubé Morneau, Amélie; Mira de Orduña, Ramón

2006-01-01

Inoculating grape musts with wine yeast and lactic acid bacteria (LAB) concurrently in order to induce simultaneous alcoholic fermentation (AF) and malolactic fermentation (MLF) can be an efficient alternative to overcome potential inhibition of LAB in wines because of high ethanol concentrations and reduced nutrient content. In this study, the simultaneous inoculation of yeast and LAB into must was compared with a traditional vinification protocol, where MLF was induced after completion of AF. For this, two suitable commercial yeast-bacterium combinations were tested in cool-climate Chardonnay must. The time courses of glucose and fructose, acetaldehyde, several organic acids, and nitrogenous compounds were measured along with the final values of other key wine parameters. Sensory evaluation was done after 12 months of storage. The current study could not confirm a negative impact of simultaneous AF/MLF on fermentation success and kinetics or on final wine parameters. While acetic acid concentrations were slightly increased in wines after simultaneous AF/MLF, the differences were of neither practical nor legal significance. No statistically significant differences were found with regard to the final values of pH or total acidity and the concentrations of ethanol, acetaldehyde, glycerol, citric and lactic acids, and the nitrogen compounds arginine, ammonia, urea, citrulline, and ornithine. Sensory evaluation by a semiexpert panel confirmed the similarity of the wines. However, simultaneous inoculation led to considerable reductions in overall fermentation durations. Furthermore, differences of physiological and microbiological relevance were found. Specifically, we report the vinification of “super-dry” wines devoid of glucose and fructose after simultaneous inoculation of yeast and bacteria. PMID:16391046

Impact of dronedarone in atrial fibrillation and flutter on stroke reduction.

PubMed

Christiansen, Christine Benn; Torp-Pedersen, Christian; Køber, Lars

2010-04-07

Dronedarone has been developed for treatment of atrial fibrillation (AF) or atrial flutter (AFL). It is an amiodarone analogue but noniodinized and without the same adverse effects as amiodarone. This is a review of 7 studies (DAFNE, ADONIS, EURIDIS, ATHENA, ANDROMEDA, ERATO and DIONYSOS) on dronedarone focusing on efficacy, safety and prevention of stroke. There was a dose-finding study (DAFNE), 3 studies focusing on maintenance of sinus rhythm (ADONIS, EURIDIS and DIONYSOS), 1 study focusing on rate control (ERATO) and 2 studies investigating mortality and morbidity (ANDROMEDA and ATHENA). The target dose for dronedarone was established in the DAFNE study to be 400 mg twice daily. Both EURIDIS and ADONIS studies demonstrated that dronedarone was superior to placebo for maintaining sinus rhythm. However, DIONYSOS found that dronedarone is less efficient at maintaining sinus rhythm than amiodarone. ERATO concluded that dronedarone reduces ventricular rate in patients with chronic AF. The ANDROMEDA study in patients with severe heart failure was discontinued because of increased mortality in dronedarone group. Dronedarone reduced cardiovascular hospitalizations and mortality in patients with AF or AFL in the ATHENA trial. Secondly, according to a post hoc analysis a significant reduction in stroke was observed (annual rate 1.2% on dronedarone vs 1.8% on placebo, respectively [hazard ratio 0.66, confidence interval 0.46 to 0.96, P = 0.027]). In total, 54 cases of stroke occurred in 3439 patients (crude rate 1.6%) receiving dronedarone compared to 76 strokes in 3048 patients on placebo (crude rate 2.5%), respectively. Dronedarone can be used for maintenance of sinus rhythm and can reduce stroke in patients with AF who receive usual care, which includes antithrombotic therapy and heart rate control.

Breakthrough curves for toluene adsorption on different types of activated carbon fibers: application in respiratory protection.

PubMed

Balanay, Jo Anne G; Floyd, Evan L; Lungu, Claudiu T

2015-05-01

Activated carbon fibers (ACF) are considered viable alternative adsorbent materials in respirators because of their larger surface area, lighter weight, and fabric form. The purpose of this study was to characterize the breakthrough curves of toluene for different types of commercially available ACFs to understand their potential service lives in respirators. Two forms of ACF, cloth (AC) and felt (AF), with three surface areas each were tested. ACFs were challenged with six toluene concentrations (50-500 p.p.m.) at constant air temperature (23°C), relative humidity (50%), and air flow (16 l min-1) at different bed depths. Breakthrough data were obtained using continuous monitoring by gas chromatography using a gas sampling valve. The ACF specific surface areas were measured by an automatic physisorption analyzer. Results showed unique shapes of breakthrough curves for each ACF form: AC demonstrated a gradual increase in breakthrough concentration, whereas AF showed abrupt increase in concentration from the breakpoint, which was attributed to the difference in fiber density between the forms. AF has steeper breakthrough curves compared with AC with similar specific surface area. AC exhibits higher 10% breakthrough times for a given bed depth due to higher mass per bed depth compared with AF, indicating more adsorption per bed depth with AC. ACF in respirators may be appropriate for use as protection in environments with toluene concentration at the Occupational Safety and Health Administration Permissible Exposure Limit, or during emergency escape for higher toluene concentrations. ACF has shown great potential for application in respiratory protection against toluene and in the development of thinner, lighter, and more efficient respirators. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Characterization of cationic polymers by asymmetric flow field-flow fractionation and multi-angle light scattering-A comparison with traditional techniques.

PubMed

Wagner, Michael; Pietsch, Christian; Tauhardt, Lutz; Schallon, Anja; Schubert, Ulrich S

2014-01-17

In the field of nanomedicine, cationic polymers are the subject of intensive research and represent promising carriers for genetic material. The detailed characterization of these carriers is essential since the efficiency of gene delivery strongly depends on the properties of the used polymer. Common characterization methods such as size exclusion chromatography (SEC) or mass spectrometry (MS) suffer from problems, e.g. missing standards, or even failed for cationic polymers. As an alternative, asymmetrical flow field-flow fractionation (AF4) was investigated. Additionally, analytical ultracentrifugation (AUC) and (1)H NMR spectroscopy, as well-established techniques, were applied to evaluate the results obtained by AF4. In this study, different polymers of molar masses between 10 and 120kgmol(-1) with varying amine functionalities in the side chain or in the polymer backbone were investigated. To this end, some of the most successful gene delivery agents, namely linear poly(ethylene imine) (LPEI) (only secondary amines in the backbone), branched poly(ethylene imine) (B-PEI) (secondary and tertiary amino groups in the backbone, primary amine end groups), and poly(l-lysine) (amide backbone and primary amine side chains), were characterized. Moreover, poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA), poly(2-(amino)ethyl methacrylate) (PAEMA), and poly(2-(tert-butylamino)ethyl methacrylate) (PtBAEMA) as polymers with primary, secondary, and tertiary amines in the side chain, have been investigated. Reliable results were obtained for all investigated polymers by AF4. In addition, important factors for all methods were evaluated, e.g. the influence of different elution buffers and AF4 membranes. Besides this, the correct determination of the partial specific volume and the suppression of the polyelectrolyte effect are the most critical issues for AUC investigations. Copyright © 2013 Elsevier B.V. All rights reserved.

In vivo and in vitro antiarrhythmic effects of SSR149744C in animal models of atrial fibrillation and ventricular arrhythmias.

PubMed

Gautier, Patrick; Serre, Martine; Cosnier-Pucheu, Sylvie; Djandjighian, Laurent; Roccon, Alain; Herbert, Jean-Marc; Nisato, Dino

2005-02-01

SSR149744C (2-butyl-3-{4-[3-(dibutylamino)propyl]benzoyl}-1-benzofuran-5-carboxylate isopropyl fumarate) is a new noniodinated benzofuran derivative structurally related to amiodarone and dronedarone that is currently undergoing clinical trials as an antiarrhythmic agent. As SSR149744C exhibits electrophysiological and hemodynamic properties of class I, II, III, and IV antiarrhythmic agents, the aim of this study was to evaluate its acute intravenous (IV) or oral (PO) antiarrhythmic activities in in vitro and in vivo animal models of atrial and ventricular arrhythmias. In vagally induced atrial fibrillation (AF) in anesthetized dogs, SSR149744C (3 and 10 mg/kg IV) terminated AF in all 7 dogs and prevented reinduction in 4 out of 7 dogs; effective refractory periods of right atrium were dose-dependently and frequency-independently lengthened. In low-K+ medium-induced AF models, SSR149744C (0.1 to 1 microM) prevented AF in isolated guinea pig hearts in a concentration-dependent manner. At the ventricular level, SSR149744C (0.1 to 10 mg/kg IV and 3 to 90 mg/kg PO) prevented reperfusion-induced arrhythmias in anesthetized rats with a dose-effect relationship, and, at doses of 30 to 90 mg/kg PO, it reduced early (0-24 hours) mortality following permanent left coronary artery ligature in conscious rats. The present results show that SSR149744C is an effective antiarrhythmic agent in atrial fibrillation and in ventricular arrhythmias. Like amiodarone and dronedarone, its efficiency in these animal models of arrhythmias is likely be related to its multifactorial mechanism of action.

Joint terminals and relay optimization for two-way power line information exchange systems with QoS constraints

NASA Astrophysics Data System (ADS)

Wu, Xiaolin; Rong, Yue

2015-12-01

The quality-of-service (QoS) criteria (measured in terms of the minimum capacity requirement in this paper) are very important to practical indoor power line communication (PLC) applications as they greatly affect the user experience. With a two-way multicarrier relay configuration, in this paper we investigate the joint terminals and relay power optimization for the indoor broadband PLC environment, where the relay node works in the amplify-and-forward (AF) mode. As the QoS-constrained power allocation problem is highly non-convex, the globally optimal solution is computationally intractable to obtain. To overcome this challenge, we propose an alternating optimization (AO) method to decompose this problem into three convex/quasi-convex sub-problems. Simulation results demonstrate the fast convergence of the proposed algorithm under practical PLC channel conditions. Compared with the conventional bidirectional direct transmission (BDT) system, the relay-assisted two-way information exchange (R2WX) scheme can meet the same QoS requirement with less total power consumption.

Adaptive and predictive control of a simulated robot arm.

PubMed

Tolu, Silvia; Vanegas, Mauricio; Garrido, Jesús A; Luque, Niceto R; Ros, Eduardo

2013-06-01

In this work, a basic cerebellar neural layer and a machine learning engine are embedded in a recurrent loop which avoids dealing with the motor error or distal error problem. The presented approach learns the motor control based on available sensor error estimates (position, velocity, and acceleration) without explicitly knowing the motor errors. The paper focuses on how to decompose the input into different components in order to facilitate the learning process using an automatic incremental learning model (locally weighted projection regression (LWPR) algorithm). LWPR incrementally learns the forward model of the robot arm and provides the cerebellar module with optimal pre-processed signals. We present a recurrent adaptive control architecture in which an adaptive feedback (AF) controller guarantees a precise, compliant, and stable control during the manipulation of objects. Therefore, this approach efficiently integrates a bio-inspired module (cerebellar circuitry) with a machine learning component (LWPR). The cerebellar-LWPR synergy makes the robot adaptable to changing conditions. We evaluate how this scheme scales for robot-arms of a high number of degrees of freedom (DOFs) using a simulated model of a robot arm of the new generation of light weight robots (LWRs).

Improved reference standards for femtosecond three-photon excitation of fluorescence in the wavelength range 950 - 1750 nm

NASA Astrophysics Data System (ADS)

Rebane, Aleksander; Mikhaylov, Alexander

2018-02-01

Fluorescence excited by instantaneous three-photon absorption (3PA) in organic fluorophores is gaining importance as a versatile modality for deep-tissue microscopy and imaging. However, due to technical difficulty of quantifying the higher-order nonlinear absorption cross-section, reliable 3PA cross section values, σ3PA, covering a broad spectral range have been so far not available. This lack of experimental data hinders us from gaining quantitative understanding of relevant structure-property relationships as well as impedes progress towards developing 3-photon fluorophores optimized for various applications. We report on measurement of the absolute 3PA cross section spectra in the 950 - 1750 nm range in a series of common organic fluorophores in various solvents: (a) Rhodamine 6G in deuterated methanol, (b) Coumarin 153 in DMSO and toluene, (c) Prodan in DMSO and toluene, (d) Fluorescein in pH11 buffer, (e) AF455 in toluene, (f) BDPAS in deuterated methylene chloride. In these experiments, we employ femtosecond wavelength-tunable optical parametric amplifier to excite fluorescence signal that has cubic dependence on the incident photon flux. Absolute values of σ3PA are determined using two complementary methods: (i) calibrating the fluorescence signal relative to one-photon (linear) excitation combined with accurate measurement of the pulse temporal- and spatial profile to determine the excitation photon flux and (ii) calibration of the cubic fluorescence signal relative to quadratic florescence excited in fluorophores with known two-photon absorption cross section. Depending on the method utilized, the peak σ3PA values have estimated accuracy 50% and vary in the range, σ3PA = 10-81 - 10-79 cm6 s2 photon-2 , depending on the system studied, with AF455 showing the most enhanced 3PA efficiency. The 3PA spectral shapes have estimated accuracy of 20% and show some unexpected deviations from corresponding one-photon spectral profiles.

Porous silicon photoluminescence biosensor for rapid and sensitive detection of toxins

NASA Astrophysics Data System (ADS)

Melnyk, Yulia; Pavlova, Karyna; Myndrul, Valerii; Viter, Roman; Smyntyna, Valentyn; Iatsunskyi, Igor

2017-08-01

A rapid and low cost photoluminescence (PL) immunosensor for the determination of low concentrations of Ochratoxin A(OTA) and Aflatoxine B1 (AfB1) has been developed. This biosensor was based on porous silicon (PSi) fabricated by metal-assisted chemical etching (MACE) and modified by antibodies against OTA/AfB1 (anti-OTA/anti-AfB1). Biofunctionalization method of the PSi surface by anti-OTA/ anti-AfB1 was developed. The changes of the PL intensity after interaction of the immobilized anti-OTA/anti-AfB1with OTA/AfB1 antigens were used as biosensor signal, allowing sensitive and selective detection of OTA/AfB1 antigens in BSA solution. The sensitivity of the reported optical biosensor towards OTA/AfB1 antigens is in the range from 10-3 to 102 ng/ml.

Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48

PubMed Central

Gupta, Deepak K.; Shah, Amil M.; Giugliano, Robert P.; Ruff, Christian T.; Antman, Elliott M.; Grip, Laura T.; Deenadayalu, Naveen; Hoffman, Elaine; Patel, Indravadan; Shi, Minggao; Mercuri, Michele; Mitrovic, Veselin; Braunwald, Eugene; Solomon, Scott D.

2014-01-01

Aims The complex relationship between left atrial (LA) structure and function, electrical burden of atrial fibrillation (AF) and stroke risk is not well understood. We aimed to describe LA structure and function in AF. Methods and results Left atrial structure and function was assessed in 971 subjects enrolled in the echocardiographic substudy of ENGAGE AF-TIMI 48. Left atrial size, emptying fraction (LAEF), and contractile function were compared across AF types (paroxysmal, persistent, or permanent) and CHADS2 scores as an estimate of stroke risk. The majority of AF patients (55%) had both LA enlargement and reduced LAEF, with an inverse relationship between LA size and LAEF (R = −0.57, P < 0.001). With an increasing electrical burden of AF and higher CHADS2 scores, LA size increased and LAEF declined. Moreover, 19% of AF subjects had impaired LAEF despite normal LA size, and LA contractile dysfunction was present even among the subset of AF subjects in sinus rhythm at the time of echocardiography. Conclusions In a contemporary AF population, LA structure and function were increasingly abnormal with a greater electrical burden of AF and higher stroke risk estimated by the CHADS2 score. Moreover, LA dysfunction was present despite normal LA size and sinus rhythm, suggesting that the assessment of LA function may add important incremental information in the evaluation of AF patients. Clinical Trial Registration: http://www.clinicaltrials.gov; ID = NCT00781391. PMID:24302269

DEMONSTRATION AND TESTING OF AN EER OPTIMIZER SYSTEM FOR DX AIR-CONDITIONERS

DTIC Science & Technology

2017-10-07

Performance-Based Maintenance PCS Power Current Sensor PLC Programmable Logic Controller ppm Parts Per Million PSIG Pounds per Square Inch Gauge PVS Power...all utilities and facilities at Patrick AFB, Cape Canaveral AFS, Jonathan Dickinson Military Tracking Annex, Malabar Annex, Ramey Solar Observatory...Cost 8,057 0 Annual O&M Cost 453 1191 Annual FD&D Monitoring 880 ‐ BLCC LIFE CYCLE RESULTS Energy Savings $12,317 O&M Net Savings $493 PV  Life Cycle

Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival

PubMed Central

Fei, Dennis Liang; Motowski, Hayley; Chatrikhi, Rakesh; Gao, Shaojian; Kielkopf, Clara L.; Varmus, Harold

2016-01-01

We have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so that U2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analyzing published data on human lung adenocarcinomas, we show that S34F-associated changes in alternative splicing are proportional to the ratio of S34F:wild-type gene products and not to absolute levels of either the mutant or wild-type factor. Preferential recognition of specific 3′ splice sites in S34F-expressing cells is largely explained by differential in vitro RNA-binding affinities of mutant versus wild-type U2AF1 for those same 3′ splice sites. Finally, we show that lung adenocarcinoma cell lines bearing U2AF1 mutations do not require the mutant protein for growth in vitro or in vivo. In contrast, wild-type U2AF1 is required for survival, regardless of whether cells carry the U2AF1S34F allele. Our results provide mechanistic explanations of the magnitude of splicing changes observed in U2AF1-mutant cells and why tumors harboring U2AF1 mutations always retain an expressed copy of the wild-type allele. PMID:27776121

Gibberellic Acid, Synthetic Auxins, and Ethylene Differentially Modulate α-l-Arabinofuranosidase Activities in Antisense 1-Aminocyclopropane-1-Carboxylic Acid Synthase Tomato Pericarp Discs1

PubMed Central

Sozzi, Gabriel O.; Greve, L. Carl; Prody, Gerry A.; Labavitch, John M.

2002-01-01

α-l-Arabinofuranosidases (α-Afs) are plant enzymes capable of releasing terminal arabinofuranosyl residues from cell wall matrix polymers, as well as from different glycoconjugates. Three different α-Af isoforms were distinguished by size exclusion chromatography of protein extracts from control tomatoes (Lycopersicon esculentum) and an ethylene synthesis-suppressed (ESS) line expressing an antisense 1-aminocyclopropane-1-carboxylic synthase transgene. α-Af I and II are active throughout fruit ontogeny. α-Af I is the first Zn-dependent cell wall enzyme isolated from tomato pericarp tissues, thus suggesting the involvement of zinc in fruit cell wall metabolism. This isoform is inhibited by 1,10-phenanthroline, but remains stable in the presence of NaCl and sucrose. α-Af II activity accounts for over 80% of the total α-Af activity in 10-d-old fruit, but activity drops during ripening. In contrast, α-Af III is ethylene dependent and specifically active during ripening. α-Af I released monosaccharide arabinose from KOH-soluble polysaccharides from tomato cell walls, whereas α-Af II and III acted on Na2CO3-soluble pectins. Different α-Af isoform responses to gibberellic acid, synthetic auxins, and ethylene were followed by using a novel ESS mature-green tomato pericarp disc system. α-Af I and II activity increased when gibberellic acid or 2,4-dichlorophenoxyacetic acid was applied, whereas ethylene treatment enhanced only α-Af III activity. Results suggest that tomato α-Afs are encoded by a gene family under differential hormonal controls, and probably have different in vivo functions. The ESS pericarp explant system allows comprehensive studies involving effects of physiological levels of different growth regulators on gene expression and enzyme activity with negligible wound-induced ethylene production. PMID:12114586

Incidence of atrial fibrillation in whites and African-Americans: the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Alonso, Alvaro; Agarwal, Sunil K; Soliman, Elsayed Z; Ambrose, Marietta; Chamberlain, Alanna M; Prineas, Ronald J; Folsom, Aaron R

2009-07-01

To define the incidence and cumulative risk of atrial fibrillation (AF) in a population-based cohort of whites and African Americans. African-Americans reportedly have a lower risk of AF than whites despite their higher exposure to AF risk factors. However, precise estimates of AF incidence in African Americans have not been previously published. We studied the incidence of AF in the Atherosclerosis Risk in Communities (ARIC) study, which has followed up 15,792 men and women 45 to 65 years of age at baseline from 4 communities in the United States since 1987. Atrial fibrillation cases were identified from electrocardiograms conducted at baseline and 3 follow-up visits, and from hospitalizations and death certificates through the end of 2004. During follow-up, 1,085 new cases of AF were identified (196 in African Americans, 889 in whites). Crude incidence rates of AF were 6.7, 4.0, 3.9, and 3.0 per 1,000 persons per year in white men, white women, African-American men, and African-American women, respectively. Increasing age was exponentially associated with an elevated risk of AF. Compared to whites, African-Americans had a 41% (95% CI: 8%-62%) lower age- and sex-adjusted risk of being diagnosed with AF. The cumulative risk of AF at 80 years of age was 21% in white men, 17% in white women, and 11% in African-American men and women. In this population-based cohort, African Americans presented a lower risk of AF than whites. Still, the burden of AF among the former is substantial, with 1 in 9 receiving a diagnosis of AF before 80 years of age.

An epidemiological study on the prevalence of atrial fibrillation in the Chinese population of mainland China.

PubMed

Zhou, Ziqiang; Hu, Dayi

2008-01-01

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Since only limited data on the Chinese population, which is the largest in the world, is available, we conducted an epidemiological study on the prevalence and risk factors of AF in mainland China. This population-based study conducted by cluster sampling comprised 29079 participants forming 14 cohorts from 13 provinces across China, where the population was nearly 1 billion. Every participant underwent electrocardiogram and physical examinations and responded to the interviewer-led questionnaire(s). Univariate and multiple statistical analyses were conducted to explore the relationship between AF prevalence and risk factors. The age-standardized prevalence of AF in China (>or=30 y) was 0.65%, and it increased with age. Men showed a higher prevalence of AF than women (0.91% [age-standardized, 0.66%] vs. 0.65% [0.63%], P = 0.013); several significant risk factors (age, hyperthyroidism, coronary heart disease, and rheumatic heart disease) were identified for AF in the general population. Stroke prevalence was much higher in AF patients than in non-AF people (12.95% vs. 2.28%, P < 0.001). AF was confirmed to be a significant independent risk factor for stroke prevalence in the studied population (OR = 2.776, [1.814, 4.248], P < 0.001). We found that AF patients received poor treatment (2.7%, warfarin; 39.7%, aspirin). This study conducted on a large sample size demonstrates that AF prevalence in mainland China is slightly lower than that in Western countries and similar to that in Asian areas, and confirms that AF is a serious public health problem in China. We identified several potential risk factors, but their associations with AF still need to be further studied.

Aspergillus sensitization or carriage in cystic fibrosis patients.

PubMed

Fillaux, Judith; Brémont, François; Murris, Marlène; Cassaing, Sophie; Tétu, Laurent; Segonds, Christine; Pipy, Bernard; Magnaval, Jean-François

2014-07-01

Aspergillus fumigatus (Af) sensitization and persistent carriage are deleterious to lung function, but no consensus has been reached defining these medical entities. This work aimed to identify possible predictive factors for patients who become sensitized to Af, compared with a control group of non-sensitized Af carriers. Between 1995 and 2007, 117 pediatric patients were evaluated. Demographic data, CFTR gene mutations, body mass index and FEV1 were recorded. The presence of Af in sputum, the levels of Af-precipitin, total IgE (t-IgE) and specific IgE to Af (Af-IgE) were determined. Patients were divided into 2 groups: (1) "sensitization": level of Af-IgE > 0.35 IU/mL with t-IgE level < 500 IU/mL and (2) "persistent or transient carriage": Af-IgE level ≤ 0.35 IU/mL with either an Af transient or persistent positive culture. A survival analysis was performed with the appearance of Af-IgE in serum as an outcome variable. Severe mutation (hazard ratio = 3.2), FEV1 baseline over 70% of theoretical value (hazard ratio = 4.9), absence of Pa colonization, catalase activity and previous azithromycin administration (hazard ratio = 9.8, 4.1 and 1.9, respectively) were predictive factors for sensitization. We propose a timeline of the biological events and a tree diagram for risk calculation. Two profiles of cystic fibrosis patients can be envisaged: (1) patients with nonsevere mutation but low FEV1 baselines are becoming colonized with Af or (2) patients with high FEV1 baselines who present with severe mutation are more susceptible to the Af sensitization and then to the presentation of an allergic bronchopulmonary aspergillosis event.

Predictors of Long-term Success After Concomitant Surgical Ablation for Atrial Fibrillation.

PubMed

Pecha, Simon; Ghandili, Susanne; Hakmi, Samer; Willems, Stephan; Reichenspurner, Hermann; Wagner, Florian Mathias

2017-01-01

According to guidelines, atrial fibrillation (AF) ablation success should be measured by 24-hour Holter electrocardiogram (ECG). However, information on long-term success, especially obtained by 24-hour Holter ECG, is rare. We therefore analyzed rhythm course and long-term outcomes of our patients undergoing concomitant surgical AF ablation. Between January 2003 and April 2011, 486 patients underwent concomitant surgical AF ablation in our institution. Patients with 24-hour Holter ECG rhythm status available between 5 and 10 years postoperatively were included in this retrospective data analysis (n = 155). Ablation lesions were limited to either a pulmonary vein isolation (n = 31, 20%), a more complex left atrial lesion set (n = 89, 57%), or biatrial lesions (n = 35, 23%). Primary end point of the study was freedom from AF during long-term follow-up. Mean patient age was 68.1 ± 8.4 years; 57.4% were male. Mean follow-up time was 5.9 years. Surgical AF ablation provided freedom from AF rate of 56.6% during long-term follow-up, with significantly better results in patients with paroxysmal than in those with persistent AF (67.2% vs 51.8% P = 0.03). A stable rhythm course was observed during follow-up, without statistically significant differences between 12 months and latest follow-up (63.2% vs 56.6%; P = 0.25). In multivariate analysis, preoperative paroxysmal AF, duration of AF, and left atrial diameter were predictors of long-term ablation success. Surgical AF ablation provided freedom from AF rate of 56.6% during long-term follow-up. Statistically significant predictors of ablation success at latest follow-up were preoperative paroxysmal AF, duration of AF, and a preoperative smaller left atrial diameter. Copyright © 2017. Published by Elsevier Inc.

Comparison of treatment outcomes between convergent procedure and catheter ablation for paroxysmal atrial fibrillation evaluated with implantable loop recorder monitoring.

PubMed

Jan, Matevž; Žižek, David; Geršak, Živa Miriam; Geršak, Borut

2018-05-03

While catheter ablation (CA) is an established treatment for symptomatic paroxysmal atrial fibrillation (AF), convergent epicardial and endocardial ablation procedure (CVP) has been primarily used to treat persistent AF. The aim of this single-center, prospective, randomized study was to compare treatment efficacy of CA and CVP in paroxysmal AF patients by monitoring AF, atrial tachycardia (AT), and atrial flutter (AFL) recurrence with Implantable Loop Recorder (ILR). Fifty patients (74% male) with history of paroxysmal AF were randomized between CA and CVP. Outcomes were determined by ILRs; every episode of AF/AT/AFL lasting 6 minutes or more was defined as a recurrence. AF burden (AFB) and required AF reinterventions (cardioversions and repeat ablations) were quantified after a 3-month blanking period. Total procedural (266 ± 44 vs. 242 ± 39 minutes) and ablation duration (52 ± 10 vs. 48 ± 12 minutes) was similar in both groups. Recurrence of AF/AT/AFL was more likely in the CA group compared to the CVP group (OR 3.78 (95% CI (1.17, 12.19), P  =  0.048)). During the follow-up period (mean 30.5 ± 6.9 months), higher AF burden and more reinterventions for recurrent AF were recorded in the CA group. There were more periprocedural complications in the CVP group (12.5%) compared to the CA group (0%). Treatment of paroxysmal AF with CVP showed less arrhythmia recurrence compared to CA. In addition, patients after CVP had fewer reinterventions and lower AF burden, but more periprocedural complications. © 2018 Wiley Periodicals, Inc.

Atrial Fibrillation and Colonic Neoplasia in African Americans.

PubMed

Nouraie, Mehdi; Kansal, Vandana; Belfonte, Cassius; Ghazvini, Mohammad; Haidari, Tahmineh; Shahnazi, Anahita; Brim, Hassan; Soliman, Elsayed Z; Ashktorab, Hassan

2015-01-01

Colorectal cancer (CRC) and atrial fibrillation/flutter (AF) share several risk factors including increasing age and obesity. However, the association between CRC and AF has not been thoroughly examined, especially in African Americans. In this study we aimed to assess the prevalence of AF and its risk factors in colorectal neoplasia in an African American. We reviewed records of 527 African American patients diagnosed with CRC and 1008 patients diagnosed with benign colonic lesions at Howard University Hospital from January 2000 to December 2012. A control group of 731 hospitalized patients without any cancer or colonic lesion were randomly selected from the same time and age range, excluding patients who had diagnosis of both CRC and/or adenoma. The presence or absence of AF was based upon ICD-9 code documentation. The prevalence of AF in these three groups was compared by multivariate logistic regression. The prevalence of AF was highest among CRC patients (10%) followed by adenoma patients (7.2%) then the control group (5.4%, P for trend = 0.002). In the three groups of participants, older age (P<0.008) and heart failure (P<0.001) were significantly associated with higher risk of AF. After adjusting for these risk factors, CRC (OR: 1.4(95%CI):0.9-2.2, P = 0.2) and adenoma (OR: 1.1(95%CI):0.7-1.6, P = 0.7) were not significantly associated AF compared to control group. AF is highly prevalent among CRC patients; 1 in 10 patients had AF in our study. The predictors of AF in CRC was similar to that in adenoma and other patients after adjustment for potential confounders suggesting that the increased AF risk in CRC is explained by higher prevalence of AF risk factors.

Multi-modulus algorithm based on global artificial fish swarm intelligent optimization of DNA encoding sequences.

PubMed

Guo, Y C; Wang, H; Wu, H P; Zhang, M Q

2015-12-21

Aimed to address the defects of the large mean square error (MSE), and the slow convergence speed in equalizing the multi-modulus signals of the constant modulus algorithm (CMA), a multi-modulus algorithm (MMA) based on global artificial fish swarm (GAFS) intelligent optimization of DNA encoding sequences (GAFS-DNA-MMA) was proposed. To improve the convergence rate and reduce the MSE, this proposed algorithm adopted an encoding method based on DNA nucleotide chains to provide a possible solution to the problem. Furthermore, the GAFS algorithm, with its fast convergence and global search ability, was used to find the best sequence. The real and imaginary parts of the initial optimal weight vector of MMA were obtained through DNA coding of the best sequence. The simulation results show that the proposed algorithm has a faster convergence speed and smaller MSE in comparison with the CMA, the MMA, and the AFS-DNA-MMA.

Atrioventricular node functional remodeling induced by atrial fibrillation.

PubMed

Zhang, Youhua; Mazgalev, Todor N

2012-09-01

The atrioventricular node (AVN) plays a vital role in determining the ventricular rate during atrial fibrillation (AF). AF results in profound electrophysiological and structural remodeling in the atria as well as the sinus node. However, it is unknown whether AVN undergoes remodeling during AF. To determine whether AVN undergoes functional remodeling during AF. AVN conduction properties were studied in vitro in 9 rabbits with AF and 10 normal controls. A previously validated index of AVN dual-pathway electrophysiology, His-electrogram alternans, was used to monitor fast-pathway or slow-pathway (SP) AVN conduction in these experiments. AVN conduction properties were further studied in vivo in 7 dogs with chronic AF and 8 controls. Compared with the control rabbits, the rabbits with AF had a longer AVN conduction time (83 ± 16 ms vs 68 ± 7 ms; P <.01), longer AVN effective refractory period (141 ± 27 ms vs 100 ± 9 ms; P <.01), an earlier transition from fast-pathway to SP conduction (at a longer prematurity, 249 ± 60 ms vs 171 ± 24 ms; P <.01), and a slower ventricular rate during simulated AF (RR interval 249 ± 42 ms vs 202 ± 12 ms; P <.01). Notably, a larger proportion of conducted beats utilized the SP in AF preparations (92% ± 12% vs 63% ± 32%; P <.05). Long-term AF in dogs resulted in a longer atrioventricular conduction time and AVN effective refractory period and a slower ventricular rate during AF compared with the controls. Pronounced AVN functional electrophysiological remodeling occurs after long-term AF, which could lead to a spontaneous slowing of the ventricular rate. Furthermore, the SP dominance during AF underscores the effectiveness of its modification by ablation for ventricular rate control during AF. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Central serous chorioretinopathy fundus autofluorescence comparison with two different confocal scanning laser ophthalmoscopes.

PubMed

Nam, Ki Tae; Yun, Cheol Min; Kim, Jee Taek; Yang, Kyung-Sook; Kim, Hyun Joo; Kim, Seong-Woo; Oh, Jaeryung; Huh, Kuhl

2015-12-01

To compare the lesion characteristics of two different types of confocal scanning laser ophthalmoscopy (cSLO) autofluorescence (AF) images in central serous chorioretinopathy (CSC). The study included 63 eyes of 61 patients; 63 pairs of fundus autofluorescence (FAF) images were compared before CSC resolution in 63 eyes, FAF images of 31 eyes were also compared after CSC resolution. The lesion characteristics (brightness and composite pattern) were compared between Heidelberg Retina Angiograph 2 (HRA2; Heidelberg Engineering, Germany) and Optomap Tx (Optomap; Optos, Scotland) FAF images. The lesion composite pattern was categorized as diffuse or granular. Diffuse AF was defined as homogenously increased or decreased AF, and granular AF was defined as dot-like, coarse changes in AF. The mean disease duration and subretinal fluid (SRF) height in the spectral domain optical coherence tomography were compared according to the FAF image characteristics. Lesion brightness before CSC resolution was hypo-AF in 48 eyes (76.2 %), hyper-AF in three (4.8 %), and mixed-AF in 12 (19.0 %) in HRA2 FAF images. In comparison, nine (14.3 %) images were hypo-AF, 44 (69.8 %) were hyper-AF, and 10 (15.9 %) were mixed-AF in Optomap FAF images (P < 0.0001). There was no significant difference in lesion composite pattern between the two FAF image wavelengths. Patients with lesions that were hyper-AF in Optomap FAF and hypo-AF in HRA2 FAF had a shorter disease duration and greater SRF height (1 month, 281 um) than those who were hyper-AF in both Optomap and HRA2 images (26 months, 153 um; P = 0.004, 0.001). The two types of FAF images of CSC showed different lesion brightness before and after CSC resolution but demonstrated similar lesion composite patterns.

Study protocol for Smartphone Monitoring for Atrial fibrillation in Real-Time in India (SMART-India): a community-based screening and referral programme

PubMed Central

Karna, Sunil; Patel, Harshil; Fahey, Nisha; Raithatha, Shyamsundar; Handorf, Anna; Bostrom, John; Bashar, Syed; Talati, Kandarp; Shah, Ravi; Goldberg, Robert J; Thanvi, Sunil; Allison, Jeroan J; Chon, Ki; Nimbalkar, Somashekhar Marutirao; McManus, David D

2017-01-01

Introduction Atrial fibrillation (AF), the world’s most common arrhythmia, often goes undetected and untreated in low-resource communities, including India, where AF epidemiology is undefined. AF is an important risk factor for stroke, which plagues an estimated 1.6 million Indians annually. As such, early detection of AF and management of high-risk patients is critically important to decrease stroke burden in individuals with AF. This study aims to describe the epidemiology of AF in Anand District, Gujarat, India, characterise the clinical profile of individuals who are diagnosed with AF and determine the performance of two mobile technologies for community-based AF screening. Methods This observational study builds on findings from a previous feasibility study and leverages two novel technologies as well as an existing community health programme to perform door-to-door AF screening for 2000 people from 60 villages of Anand District, Gujarat, India using local health workers. A single-lead ECG and a pulse-based application is used to screen each individual for AF three times over a period of 5 days. Participants with suspected arrhythmias are followed up by study cardiologist who makes final diagnoses. Participants diagnosed with AF are initiated on treatment based on current anticoagulation guidelines and clinical reasoning. Analytical plan Age-stratified and sex-stratified prevalence of AF in the Anand District will be calculated for sample and estimated for Anand distribution using survey design weights. Sociodemographic and clinical factors associated with AF will be evaluated using multivariable regression methods. Performance of each mobile technology in detecting AF will be evaluated using a 12-lead ECG interpretation as the gold standard. Ethics and dissemination This protocol was approved separately by the Institutional Review Board of University of Massachusetts Medical School and the Human Research Ethics Committee at Charutar Arogya Mandal. The findings of this study will be disseminated through peer-reviewed journals and scientific conferences. PMID:29247089

Treatment of Atrial Fibrillation By The Ablation Of Localized Sources

PubMed Central

Narayan, Sanjiv M.; Krummen, David E.; Shivkumar, Kalyanam; Clopton, Paul; Rappel, Wouter-Jan; Miller, John M.

2012-01-01

Objectives We hypothesized that human atrial fibrillation (AF) may be sustained by localized sources (electrical rotors and focal impulses), whose elimination (Focal Impulse and Rotor Modulation, FIRM) may improve outcome from AF ablation. Background Catheter ablation for AF is a promising therapy, whose success is limited in part by uncertainty in the mechanisms that sustain AF. We developed a computational approach to map whether AF is sustained by several meandering waves (the prevailing hypothesis) or localized sources, then prospectively tested whether targeting patient-specific mechanisms revealed by mapping would improve AF ablation outcome. Methods We recruited 92 individuals during 107 consecutive ablation procedures for paroxysmal or persistent (72%) AF. Cases were prospectively treated, in a 2-arm 1:2 design, by ablation at sources (FIRM-Guided) followed by conventional ablation (n=36), or conventional ablation alone (n=71; FIRM-Blinded). Results Localized rotors or focal impulses were detected in 98 (97%) of 101 cases with sustained AF, each exhibiting 2.1±1.0 sources. The acute endpoint (AF termination or consistent slowing) was achieved in 86% of FIRM-guided versus 20% of FIRM-Blinded cases (p<0.001). FIRM ablation alone at the primary source terminated AF in 2.5 minutes (median; IQR 1.0–3.1). Total ablation time did not differ between groups (57.8±22.8 versus 52.1±17.8 minutes, p=0.16). During 273 days (median; IQR 132–681 days) after a single procedure, FIRM-Guided cases had higher freedom from AF (82.4% versus 44.9%; p<0.001) after a single procedure than FIRM-blinded cases with rigorous, often implanted, ECG monitoring. Adverse events did not differ between groups. CONCLUSIONS Localized electrical rotors and focal impulse sources are prevalent sustaining-mechanisms for human AF. FIRM ablation at patient-specific sources acutely terminated or slowed AF, and improved outcome. These results offer a novel mechanistic framework and treatment paradigm for AF. (ClinicalTrials.gov number, NCT01008722) PMID:22818076

Recognition of the 3′ splice site RNA by the U2AF heterodimer involves a dynamic population shift

PubMed Central

Voith von Voithenberg, Lena; Sánchez-Rico, Carolina; Kang, Hyun-Seo; Madl, Tobias; Zanier, Katia; Barth, Anders; Warner, Lisa R.; Sattler, Michael; Lamb, Don C.

2016-01-01

An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3′ splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands. To investigate the molecular mechanism and dynamics of 3′ splice site recognition by U2AF65 and the role of U2AF35 in the U2AF heterodimer, we have combined single-pair FRET and NMR experiments. In the absence of RNA, the RRM1,2 domain arrangement is highly dynamic on a submillisecond time scale, switching between closed and open conformations. The addition of Py-tract RNA ligands with increasing binding affinity (strength) gradually shifts the equilibrium toward an open conformation. Notably, the protein–RNA complex is rigid in the presence of a strong Py-tract but exhibits internal motion with weak Py-tracts. Surprisingly, the presence of U2AF35, whose UHM domain interacts with U2AF65 RRM1, increases the population of the open arrangement of U2AF65 RRM1,2 in the absence and presence of a weak Py-tract. These data indicate that the U2AF heterodimer promotes spliceosome assembly by a dynamic population shift toward the open conformation of U2AF65 to facilitate the recognition of weak Py-tracts at the 3′ splice site. The structure and RNA binding of the heterodimer was unaffected by cancer-linked myelodysplastic syndrome mutants. PMID:27799531

Effectiveness of atrial fibrillation rotor ablation is dependent on conduction velocity: An in-silico 3-dimensional modeling study

PubMed Central

Lim, Byounghyun; Hwang, Minki; Song, Jun-Seop; Ryu, Ah-Jin; Joung, Boyoung; Shim, Eun Bo; Ryu, Hyungon

2017-01-01

Background We previously reported that stable rotors are observed in in-silico human atrial fibrillation (AF) models, and are well represented by a dominant frequency (DF). In the current study, we hypothesized that the outcome of DF ablation is affected by conduction velocity (CV) conditions and examined this hypothesis using in-silico 3D-AF modeling. Methods We integrated 3D CT images of left atrium obtained from 10 patients with persistent AF (80% male, 61.8±13.5 years old) into in-silico AF model. We compared AF maintenance durations (max 300s), spatiotemporal stabilities of DF, phase singularity (PS) number, life-span of PS, and AF termination or defragmentation rates after virtual DF ablation with 5 different CV conditions (0.2, 0.3, 0.4, 0.5, and 0.6m/s). Results 1. AF maintenance duration (p<0.001), spatiotemporal mean variance of DF (p<0.001), and the number of PS (p = 0.023) showed CV dependent bimodal patterns (highest at CV0.4m/s and lowest at CV0.6m/s) consistently. 2. After 10% highest DF ablation, AF defragmentation rates were the lowest at CV0.4m/s (37.8%), but highest at CV0.5 and 0.6m/s (all 100%, p<0.001). 3. In the episodes with AF termination or defragmentation followed by 10% highest DF ablation, baseline AF maintenance duration was shorter (p<0.001), spatiotemporal mean variance of DF was lower (p = 0.014), and the number of PS was lower (p = 0.004) than those with failed AF defragmentation after DF ablation. Conclusion Virtual ablation of DF, which may indicate AF driver, was more likely to terminate or defragment AF with spatiotemporally stable DF, but not likely to do so in long-lasting and sustained AF conditions, depending on CV. PMID:29287119

Circulating miRNAs in acute new-onset atrial fibrillation and their target mRNA network.

PubMed

da Silva, Ananília Medeiros Gomes; de Araújo, Jéssica Nayara Góes; de Oliveira, Katiene Macêdo; Novaes, Ana Eloísa Melo; Lopes, Mariana Borges; de Sousa, Júlio César Vieira; Filho, Antônio Amorim de Araújo; Luchessi, André Ducati; de Rezende, Adriana Augusto; Hirata, Mário Hiroyuki; Silbiger, Vivian Nogueira

2018-04-20

MicroRNAs (miRNAs) are involved in the pathogenesis of atrial fibrillation (AF), acting on development and progression. Our pilot study investigated the expression of six miRNAs and their miRNA-mRNA interactions in patients with acute new-onset AF, well-controlled AF, and normal sinus rhythm (controls). Plasma of acute new-onset AF patients (n = 5) was collected in the emergency room when patients presented with irregular and fast-atrial fibrillation rhythm. Samples from well-controlled AF (n = 16) and control (n =  15) patients were collected during medical appointments following an ECG. Expression of miR-21, miR-133a, miR-133b, miR-150, miR-328, and miR-499 was analyzed by real-time PCR. Ingenuity Pathway Analysis and the TargetScan database identified the top 30 mRNA targets of these miRNA, seeking the miRNA-mRNA interactions in cardiovascular process. Increased expression of miR-133b (1.4-fold), miR-328 (2.0-fold), and miR-499 (2.3-fold) was observed in patients with acute new-onset AF, compared with well-controlled AF and control patients. Decreased expression of miR-21 was seen in patients with well-controlled AF compared to those with acute new-onset AF and controls (0.6-fold). The miRNA-mRNA interaction demonstrated that SMAD7 and FASLG genes were the targets of miR-21, miR-133b, and miR-499 and were directly related to AF, being involved in apoptosis and fibrosis. The miRNAs had different expression profiles dependent on the AF condition, with higher expression in the acute new-onset AF than well-controlled AF. Clinically, this may contribute to an effective assessment for patients, leading to early detection of AF and monitoring to reduce the risk of other serious cardiovascular events. © 2018 Wiley Periodicals, Inc.

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial.

PubMed

Steinberg, Benjamin A; Hellkamp, Anne S; Lokhnygina, Yuliya; Patel, Manesh R; Breithardt, Günter; Hankey, Graeme J; Becker, Richard C; Singer, Daniel E; Halperin, Jonathan L; Hacke, Werner; Nessel, Christopher C; Berkowitz, Scott D; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Piccini, Jonathan P

2015-02-01

Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

Multimodal Imaging of Disease-Associated Pigmentary Changes in Retinitis Pigmentosa

PubMed Central

Schuerch, Kaspar; Marsiglia, Marcela; Lee, Winston; Tsang, Stephen H.; Sparrow, Janet R.

2016-01-01

Purpose Using multiple imaging modalities we evaluated the changes in photoreceptor cells and RPE that are associated with bone spicule-shaped melanin pigmentation in retinitis pigmentosa (RP). Methods In a cohort of 60 RP patients, short-wavelength autofluorescence (SW-AF), near-infrared (NIR)-AF, NIR-reflectance (NIR-R), spectral domain optical coherence tomography (SD-OCT) and color fundus images were studied. Results Central AF rings were visible in both SW-AF and NIR-AF images. Bone spicule pigmentation was non-reflective in NIR-R, hypoautofluorescent with SW-AF and NIR-AF imaging and presented as intraretinal hyperreflective foci in SD-OCT images. In areas beyond the AF ring outer border, the photoreceptor ellipsoid zone (EZ) band was absent in SD-OCT scans and the visibility of choroidal vessels in SW-AF, NIR-AF and NIR-R images was indicative of reduced RPE pigmentation. Choroidal visibility was most pronounced in the zone approaching peripheral areas of bone spicule pigmentation; here RPE/Bruch’s membrane thinning became apparent in SD-OCT scans. Conclusions These findings are consistent with a process by which RPE cells vacate their monolayer and migrate into inner retina in response to photoreceptor cell degeneration. The remaining RPE spread, undergo thinning and consequently become less pigmented. An explanation for the absence of NIR-AF melanin signal in relation to bone spicule pigmentation is not forthcoming. PMID:28005673

Screening for Atrial Fibrillation in Patients ≥65 Years Using an Automatic Blood Pressure Monitor in a Skilled Nursing Facility.

PubMed

Wiesel, Joseph; Salomone, Thomas J

2017-10-15

Early detection of asymptomatic atrial fibrillation (AF) provides an opportunity to treat patients to reduce their risk of stroke. Long-term residents of skilled nursing facilities frequently have multiple risk factors for strokes due to AF and may benefit from screening for AF. Patients in a skilled nursing facility 65 years and older, without a history of AF and without a pacemaker or defibrillator, were evaluated using a Microlife WatchBP Home A automatic blood pressure monitor that can detect AF when set to a triple reading mode. Those with readings positive for AF were evaluated with a standard 12-lead electrocardiogram (ECG) or a 30-second single-channel ECG to confirm the presence of AF. A total of 101 patients were screened with an average age of 78 years, and 48 (48%) were female. Nine automatic blood pressure monitor readings were positive for possible AF. Of those, 7 (6.9%, 95% confidence intervals 3.0% to 14.2%) had AF confirmed with ECG. Only 2 (2%, 95% confidence interval 0.3% to 7.7%) were false-positive readings. One-time screening for AF using an automatic blood pressure monitor in a skilled nursing facility resulted in a high number of patients with newly diagnosed AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative performance evaluation of full-scale anaerobic and aerobic wastewater treatment processes in Brazil.

PubMed

von Sperling, M; Oliveira, S C

2009-01-01

This article evaluates and compares the actual behavior of 166 full-scale anaerobic and aerobic wastewater treatment plants in operation in Brazil, providing information on the performance of the processes in terms of the quality of the generated effluent and the removal efficiency achieved. The observed results of effluent concentrations and removal efficiencies of the constituents BOD, COD, TSS (total suspended solids), TN (total nitrogen), TP (total phosphorus) and FC (faecal or thermotolerant coliforms) have been compared with the typical expected performance reported in the literature. The treatment technologies selected for study were: (a) predominantly anaerobic: (i) septic tank + anaerobic filter (ST + AF), (ii) UASB reactor without post-treatment (UASB) and (iii) UASB reactor followed by several post-treatment processes (UASB + POST); (b) predominantly aerobic: (iv) facultative pond (FP), (v) anaerobic pond followed by facultative pond (AP + FP) and (vi) activated sludge (AS). The results, confirmed by statistical tests, showed that, in general, the best performance was achieved by AS, but closely followed by UASB reactor, when operating with any kind of post-treatment. The effluent quality of the anaerobic processes ST + AF and UASB reactor without post-treatment was very similar to the one presented by facultative pond, a simpler aerobic process, regarding organic matter.

New-onset atrial fibrillation in bacteremia is not associated with C-reactive protein, but is an indicator of increased mortality during hospitalization.

PubMed

Kindem, Ingvild A; Reindal, Eva K; Wester, Astrid L; Blaasaas, Karl G; Atar, Dan

2008-01-01

Several studies have associated elevated C-reactive protein (CRP) levels to the occurrence of atrial fibrillation (AF). We sought to estimate the frequency and prognostic impact of AF in patients with bacteremia, and to study the possible association between AF and CRP as well as between AF and mortality in this population. We retrospectively evaluated patient charts of patients with bacteremia with Escherichia coli or Streptococcus pneumoniae admitted to the Aker University Hospital in Oslo between 1994 and 2004. Known cardiac risk factors for AF, signs and mode of conversion of AF, and, if applicable, date of death were registered, as were characteristics of infection, such as systemic inflammatory response syndrome and white blood cell count. Initial CRP values were categorized into 4 strata. Odds ratios of the 3 highest CRP categories compared with the lowest were obtained from logistic models adjusting for known cardiac risk factors for AF as well as possible factors that may have had an impact on the odds ratios for the different CRP levels. Cox regression analysis was used to compare new-onset AF and death during the first 2 weeks after hospitalization. A total of 672 patient charts were studied; 104 patients (15.4%) had new-onset AF. Peak incidence of new-onset AF occurred on the day of admission. Peak CRP values were reached during the following 2 days. High CRP level at admission did not predict the occurrence of AF. The observed mortality was higher among patients with new-onset AF (p = 0.001) during the first 2 weeks after hospitalization, but this effect disappears when adjusted for relevant factors. The frequency of new-onset AF in bacteremia is substantial. Initial CRP levels or white blood cell count do not seem to predict new-onset AF, as opposed to systemic inflammatory response syndrome. On the other hand, in patients with bacteremia, new-onset AF should be viewed as an indicator of increased mortality and morbidity. Copyright 2008 S. Karger AG, Basel.

Attitudes toward Catheter Ablation for Atrial Fibrillation: A Nationwide Survey among Danish Cardiologists.

PubMed

Vadmann, Henrik; Pedersen, Susanne S; Nielsen, Jens Cosedis; Rodrigo-Domingo, Maria; Pehrson, Steen; Johannessen, Arne; Hansen, Peter Steen; Johansen, Jens Brock; Riahi, Sam

2015-10-01

Catheter ablation for atrial fibrillation (AF) is an important but expensive procedure that is the subject of some debate. Physicians' attitudes toward catheter ablation may influence promotion and patient acceptance. This is the first study to examine the attitudes of Danish cardiologists toward catheter ablation for AF, using a nationwide survey. We developed a purpose-designed questionnaire to evaluate attitudes toward catheter ablation for AF that was sent to all Danish cardiologists (n = 401; response n = 272 (67.8%)). There was no association between attitudes toward ablation and the experience or age of the cardiologist with respect to patients with recurrent AF episodes with a duration of <48 hours or >7 days and/or need for cardioversion. The majority (69%) expected a recurrence of AF after catheter ablation in more than 30% of the cases. For patients with persistent longstanding AF with a duration of >1 year, the attitude toward ablation for longstanding AF was more likely to be positive with increasing age (P < 0.01) and years of experience of the cardiologist (P = 0.002). Danish cardiologists generally have a positive attitude toward catheter ablation for AF, maintain up-to-date knowledge of the procedure, and are aware what information on ablation treatment should be given to patients with AF. The cardiologists had a positive attitude toward ablation for AF in patients with AF episodes <48 hours and patients with episodes >7 days, or those who needed medical/electrical conversion, but a more negative attitude toward treating longstanding AF patients. © 2015 Wiley Periodicals, Inc.

Debris extrusion and foraminal deformation produced by reciprocating instruments made of thermally treated NiTi wires.

PubMed

Frota, Myrna Maria Arcanjo; Bernardes, Ricardo Affonso; Vivan, Rodrigo Ricci; Vivacqua-Gomes, Nilton; Duarte, Marco Antonio Hungaro; Vasconcelos, Bruno Carvalho de

2018-01-18

To evaluate the amount of apically extruded debris, percentage of foraminal enlargement and apical foramen (AF) deformation that occurred during root canal preparation with different reciprocation systems: Reciproc, WaveOne (M-Wire), and ProDesign R (Shape Memory Technology Wire) at two different working lengths (WLs): 0.0 and 1.0 mm beyond the AF. The AF of 120 root canals in 60 mesial roots of mandibular molars were photographed with stereomicroscope and randomly assigned into four groups: manual, Reciproc (REC), WaveOne (WO), and ProDesign R (PDR); subsequently, they were further subdivided according to the WL (n=15). Teeth were instrumented, coupled to a dual collecting chamber, and then another photograph of each AF was captured. Extrusion was analysed by determining the weight of extruded debris. Each AF diameter was measured in pre- and post-instrumentation images to determine deformation, which was analysed, and afterwards the final format of AFs was classified (circular/oval/deformed). We found no significant differences when analysing each system at different WLs. When considering each WL, REC and WO showed highest extrusion values (P<.05); for AF enlargement, differences were observed only for WO, when it was used beyond the AF; differences were observed among M-Wire groups beyond the AF (P<.05). AF deformation was observed in all groups; PDR showed the lowest AF deformation values at both WLs; M-Wire groups showed 50% strain beyond the AF. Authors concluded that beyond the apical limit, the alloy and taper are important aspects when considering extrusion and deformation.

The incidence and distribution characteristics of MLL rearrangements in Chinese acute myeloid leukemia patients by multiplex nested RT-PCR.

PubMed

Yang, Hua; Cao, Tingting; Gao, Li; Wang, Lili; Zhu, Chengying; Xu, Yuanyuan; Jing, Yu; Zhu, Haiyan; Lv, Na; Yu, Li

2017-07-20

Occurrence of MLL (Mixed Lineage Leukemia) gene rearrangements indicates poor prognosis in acute myeloid leukemia (AML) patients. This is the first study to report the positive rate and distribution characteristics of MLL rearrangements in AML patients in north China. We used multiplex nested real time PCR (RT-PCR) to screen for incidence of 11 MLL rearrangements in 433 AML patients. Eleven MLL rearrangements included (MLL-PTD, MLL-AF9, MLL-ELL, MLL-AF10, MLL-AF17, MLL-AF6, MLL-ENL, MLL-AF1Q, MLL-CBP, MLL-AF1P, MLL-AFX1). There were 68 AML patients with MLL rearrangements, and the positive rate was 15.7%. MLL-PTD (4.84%) was detected in 21 patients, MLL-AF9 in 15, (3.46%), MLL-ELL in 10 (2.31%), MLL-AF10 in 8 (1.85%), MLL-AF1Q in 2 (0.46%), 3 cases each of MLL-AF17, MLL-AF6, MLL-ENL (0.69% each), a and single case each of MLL-CBP, MLL-AF1P, and MLL-AFX1 (0.23% each). The highest rate of MLL rearrangements was found in 24 patients with M5 subtype AML, occurring in 24 cases (35.3%). MLL rearrangements occurred in 21 patients with M2 subtype AML (30.9%), and in 10 patients with M4 subtype AML (14.7%). Screening fusion genes by multiplex nested RT-PCR is a convenient, fast, economical, and accurate method for diagnosis and predicting prognosis of AML.

Incidence, predictive factors, management, and survival impact of atrial fibrillation in non-Hodgkin lymphoma.

PubMed

Sorigue, Marc; Gual-Capllonch, Francisco; Garcia, Olga; Sarrate, Edurne; Franch-Sarto, Mireia; Ibarra, Gladys; Grau, Javier; Orna, Elisa; Ribera, Josep-Maria; Sancho, Juan-Manuel

2018-05-04

Atrial fibrillation (AF) and cancer are common disorders in the general population but there are few studies in patients with both diseases. More specifically, there are scarce data on AF in patients with non-Hodgkin lymphoma (NHL). We assessed the incidence, predictive factors, management, and survival impact of AF in a cohort of patients with NHL from a single institution between 2002 and 2016 (n = 747). Twenty-three patients were diagnosed with AF before and 40 after the diagnosis of NHL (of the later, 16 were secondary to an extracardiac comorbidity and 24 unrelated to any triggering event [primary AF]). The 5-year cumulative incidence of new-onset AF was 4% (95% confidence interval [CI] 3-6%). Age and hypertension were the only predictive factors for the development of AF. Management of AF was heterogeneous, primarily with anti-vitamin K agents but also antiplatelet therapy in a significant proportion of patients. Among the 63 patients, there were six episodes of ischemic stroke/transient ischemic attack and four venous thromboembolic events, with four major bleeding episodes. Overall survival (OS) was inferior in patients with AF (HR 0.1, 95% CI 0.01-0.7, p = 0.02), largely due to secondary AF. We conclude that the incidence of new-onset AF in NHL patients seemed somewhat higher than in the general population, although with similar predictive factors. The management was heterogeneous, and the risk of ischemic and hemorrhagic events did not seem higher than in cancer-free patients. Survival was particularly poor for patients with secondary AF.

Recurrence quantification analysis applied to spatiotemporal pattern analysis in high-density mapping of human atrial fibrillation.

PubMed

Zeemering, Stef; Bonizzi, Pietro; Maesen, Bart; Peeters, Ralf; Schotten, Ulrich

2015-01-01

Spatiotemporal complexity of atrial fibrillation (AF) patterns is often quantified by annotated intracardiac contact mapping. We introduce a new approach that applies recurrence plot (RP) construction followed by recurrence quantification analysis (RQA) to epicardial atrial electrograms, recorded with a high-density grid of electrodes. In 32 patients with no history of AF (aAF, n=11), paroxysmal AF (PAF, n=12) and persistent AF (persAF, n=9), RPs were constructed using a phase space electrogram embedding dimension equal to the estimated AF cycle length. Spatial information was incorporated by 1) averaging the recurrence over all electrodes, and 2) by applying principal component analysis (PCA) to the matrix of embedded electrograms and selecting the first principal component as a representation of spatial diversity. Standard RQA parameters were computed on the constructed RPs and correlated to the number of fibrillation waves per AF cycle (NW). Averaged RP RQA parameters showed no correlation with NW. Correlations improved when applying PCA, with maximum correlation achieved between RP threshold and NW (RR1%, r=0.68, p <; 0.001) and RP determinism (DET, r=-0.64, p <; 0.001). All studied RQA parameters based on the PCA RP were able to discriminate between persAF and aAF/PAF (DET persAF 0.40 ± 0.11 vs. 0.59 ± 0.14/0.62 ± 0.16, p <; 0.01). RP construction and RQA combined with PCA provide a quick and reliable tool to visualize dynamical behaviour and to assess the complexity of contact mapping patterns in AF.

Influence of atrial substrate on local capture induced by rapid pacing of atrial fibrillation.

PubMed

Rusu, Alexandru; Jacquemet, Vincent; Vesin, Jean-Marc; Virag, Nathalie

2014-05-01

Preliminary studies showed that the septum area was the only location allowing local capture of both the atria during rapid pacing of atrial fibrillation (AF) from a single site. The present model-based study investigated the influence of atrial substrate on the ability to capture AF when pacing the septum. Three biophysical models of AF with an identical anatomy from human atria but with different AF substrates were used: (i) AF based on multiple wavelets, (ii) AF based on heterogeneities in vagal activation, (iii) AF based on heterogeneities in repolarization. A fourth anatomical model without Bachmann's bundle (BB) was also implemented. Rapid pacing was applied from the septum at pacing cycle lengths in the range of 50-100% of AF cycle length. Local capture was automatically assessed with 24 pairs of electrodes evenly distributed on the atrial surface. The results were averaged over 16 AF simulations. In the homogeneous substrate, AF capture could reach 80% of the atrial surface. Heterogeneities degraded the ability to capture during AF. In the vagal substrate, the capture tended to be more regular and the degradation of the capture was not directly related to the spatial extent of the heterogeneities. In the third substrate, heterogeneities induced wave anchorings and wavebreaks even in areas close to the pacing site, with a more dramatic effect on AF capture. Finally, BB did not significantly affect the ability to capture. Atrial fibrillation substrate had a significant effect on rapid pacing outcomes. The response to therapeutic pacing may therefore be specific to each patient.

Remodeling of Kv1.5 channel in right atria from Han Chinese patients with atrial fibrillation.

PubMed

Ou, Xian-hong; Li, Miao-ling; Liu, Rui; Fan, Xin-rong; Mao, Liang; Fan, Xue-hui; Yang, Yan; Zeng, Xiao-rong

2015-04-28

The incidence of atrial fibrillation (AF) in rheumatic heart diseases (RHD) is very high and increases with age. Occurrence and maintenance of AF are very complicated process accompanied by many different mechanisms. Ion-channel remodeling, including the voltage-gated potassium channel Kv1.5, plays an important role in the pathophysiology of AF. However, the changes of Kv1.5 channel expression in Han Chinese patients with RHD and AF remain poorly understood. The aim of the present study was to investigate whether the Kv1.5 channels of the right atria may be altered with RHD, age, and sex to contribute to AF. Right atrial appendages were obtained from 20 patients with normal cardiac functions who had undergone surgery, and 26 patients with AF. Subjects were picked from 4 groups: adult and aged patients in normal sinus rhythm (SR) and AF. Patients were divided into non-RHD and RHD groups or men and women groups in normal SR and AF, respectively. The expression of Kv1.5 protein and messenger RNA (mRNA) were measured using Western blotting and polymerase chain reaction (PCR) method, respectively. Compared with the SR group, the expression of Kv1.5 protein decreased significantly in the AF group. However, neither Kv1.5 protein nor KCNA5 mRNA had significant differences in adult and aged groups, non-RHD and RHD group, and men and women group of AF. The expression of Kv1.5 channel protein changes with AF but not with age, RHD, and sex in AF.

Impact of atrial fibrillation on stroke-related healthcare costs.

PubMed

Sussman, Matthew; Menzin, Joseph; Lin, Iris; Kwong, Winghan J; Munsell, Michael; Friedman, Mark; Selim, Magdy

2013-11-25

Limited data exist on the economic implications of stroke among patients with atrial fibrillation (AF). This study assesses the impact of AF on healthcare costs associated with ischemic stroke (IS), hemorrhagic stroke (HS), or transient ischemic attack (TIA). A retrospective analysis of MarketScan claims data (2005-2011) for AF patients ≥18 years old with ≥1 inpatient claim for stroke, or ≥1 ED or inpatient claim for TIA as identified by ICD-9-CM codes who had ≥12 months continuous enrollment prior to initial stroke. Initial event- and stroke-related costs 12 months post-index were compared among patients with AF and without AF. Adjusted costs were estimated, controlling for demographics, comorbidities, anticoagulant use, and baseline resource use. Data from 23,807 AF patients and 136,649 patients without AF were analyzed. Unadjusted mean cost of the index event was $20,933 for IS, $59,054 for HS, $8616 for TIA hospitalization, and $3395 for TIA ED visit. After controlling for potential confounders, adjusted mean incremental costs (index plus 12-month post-index) for AF patients were higher than those for non-AF patients by: $4726, $7824, and $1890 for index IS, HS, TIA (identified by hospitalization), respectively, and $1700 for TIA (identified by ED) (all P<0.01). In multivariate regression analysis, AF was associated with a 20% (IS), 13% (HS), and 18% (TIA) increase in total stroke-related costs. Stroke-related care for IS, HS, and TIA is costly, especially among individuals with AF. Reducing the risk of AF-related stroke is important from both clinical and economic standpoints.

Catheter ablation in patients with persistent atrial fibrillation

PubMed Central

Kirchhof, Paulus; Calkins, Hugh

2017-01-01

Catheter ablation is increasingly offered to patients who suffer from symptoms due to atrial fibrillation (AF), based on a growing body of evidence illustrating its efficacy compared with antiarrhythmic drug therapy. Approximately one-third of AF ablation procedures are currently performed in patients with persistent or long-standing persistent AF. Here, we review the available information to guide catheter ablation in these more chronic forms of AF. We identify the following principles: Our clinical ability to discriminate paroxysmal and persistent AF is limited. Pulmonary vein isolation is a reasonable and effective first approach for catheter ablation of persistent AF. Other ablation strategies are being developed and need to be properly evaluated in controlled, multicentre trials. Treatment of concomitant conditions promoting recurrent AF by life style interventions and medical therapy should be a routine adjunct to catheter ablation of persistent AF. Early rhythm control therapy has a biological rationale and trials evaluating its value are underway. There is a clear need to generate more evidence for the best approach to ablation of persistent AF beyond pulmonary vein isolation in the form of adequately powered controlled multi-centre trials. PMID:27389907

[Structural and functional changes of myocardium in Chernobyl disaster clean-up workers with atrial fibrillation].

PubMed

Khomaziuk, I M; Habulavichene, Zh M; Khomaziuk, V A

2011-01-01

Particularities and clinical importance of the structural and functional changes of myocardium were estimated in Chernobyl disaster clean-up workers with atrial fibrillation (AF). We examined 122 men with AF, which was associated with ischemic heart disease and arterial hypertension. Paroxysmal AF was diagnosed in 42 patients, 80 patients had permanent AE Control group comprised 80 men without AF. Echocardiography and Doppler studies were performed using ultrasound scanner Aloka SSD-630 (Japan). Significant structural and functional changes of the heart were revealed already in paroxysmal AF and became more pronounced in permanent AF. Increased left atrial size, its ratio to left ventricular end diastolic diameter, diastolic dysfunction were important echocardiographic predictors of AF. Heart walls thickening was accompanied by disorders of myocardial relaxation, increase in myocardial mass led to ischemia, and together they promoted overload, dysfunction of atrium and development of AF. Obligatory echocardiographic examination of the Chernobyl disaster clean-up workers with ischemic heart disease and arterial hypertension is necessary for predicting AF early, ordering adequate therapy in proper time and improving prognosis.

Favorable outcome in non-infant children with MLL-AF4-positive acute lymphoblastic leukemia: a report from the Tokyo Children's Cancer Study Group.

PubMed

Tomizawa, Daisuke; Kato, Motohiro; Takahashi, Hiroyuki; Fujimura, Junya; Inukai, Takeshi; Fukushima, Takashi; Kiyokawa, Nobutaka; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira

2015-11-01

Unlike acute lymphoblastic leukemia (ALL) in infants, MLL gene rearrangement (MLL-r) is rare in ALL children (≥1 year old). The outcome and optimal treatment options for MLL-r ALL remain controversial. Among the 1827 children enrolled in the Tokyo Children's Cancer Study Group ALL studies L95-14, L99-15, L99-1502, L04-16, and L07-1602 (1995-2009), 25 MLL-r ALL patients (1.3 %) were identified. Their median age and leukocyte count at diagnosis was 2 years old (range 1-15 years) and 27,690/μL (range 1800-1,113,000/μL), respectively. All but one patient achieved complete remission (CR) after induction therapy, and 19 underwent allogeneic hematopoietic stem cell transplantation (HSCT) in first CR according to the protocol. The 5-year event-free survival (EFS) and overall survival (OS) rate were 60.0 % [standard error (SE), 9.7 %] and 64.0 % (SE 9.6 %), respectively. Notably, 9/12 cases with MLL-AF4-positive ALL are alive in continuous CR with a 75.0 % (SE 12.5 %) EFS rate. The causes of treatment failure were as follows: one induction failure, five relapses, and five transplant-related deaths. With intensive chemotherapy and allogeneic HSCT, favorable outcome of children (≥1 year old) with MLL-AF4-positive ALL was observed. However, considering the risk of acute and late toxicities associated with HSCT, its indication should be restricted.

Medication therapy disease management: Geisinger's approach to population health management.

PubMed

Jones, Laney K; Greskovic, Gerard; Grassi, Dante M; Graham, Jove; Sun, Haiyan; Gionfriddo, Michael R; Murray, Michael F; Manickam, Kandamurugu; Nathanson, Douglas C; Wright, Eric A; Evans, Michael A

2017-09-15

Pharmacists' involvement in a population health initiative focused on chronic disease management is described. Geisinger Health System has cultivated a culture of innovation in population health management, as highlighted by its ambulatory care pharmacy program, the Medication Therapy Disease Management (MTDM) program. Initiated in 1996, the MTDM program leverages pharmacists' pharmacotherapy expertise to optimize care and improve outcomes. MTDM program pharmacists are trained and credentialed to manage over 16 conditions, including atrial fibrillation (AF) and multiple sclerosis (MS). Over a 15-year period, Geisinger Health Plan (GHP)-insured patients with AF whose warfarin therapy was managed by the MTDM program had, on average, 18% fewer emergency department (ED) visits and 18% fewer hospitalizations per year than GHP enrollees with AF who did not receive MTDM services, with 23% lower annual total care costs. Over a 2-year period, GHP-insured patients with MS whose pharmacotherapy was managed by pharmacists averaged 28% fewer annual ED visits than non-pharmacist-managed patients; however, the mean annual total care cost was 21% higher among MTDM clinic patients. The Geisinger MTDM program has evolved over 20 years from a single pharmacist-run anticoagulation clinic into a large program focused on managing the health of an ever-growing population. Initial challenges in integrating pharmacists into the Geisinger patient care framework as clinical experts were overcome by demonstrating the MTDM program's positive impact on patient outcomes. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Characterization of branched ultrahigh molar mass polymers by asymmetrical flow field-flow fractionation and size exclusion chromatography.

PubMed

Otte, T; Pasch, H; Macko, T; Brüll, R; Stadler, F J; Kaschta, J; Becker, F; Buback, M

2011-07-08

The molar mass distribution (MMD) of synthetic polymers is frequently analyzed by size exclusion chromatography (SEC) coupled to multi angle light scattering (MALS) detection. For ultrahigh molar mass (UHM) or branched polymers this method is not sufficient, because shear degradation and abnormal elution effects falsify the calculated molar mass distribution and information on branching. High temperatures above 130 °C have to be applied for dissolution and separation of semi-crystalline materials like polyolefins which requires special hardware setups. Asymmetrical flow field-flow fractionation (AF4) offers the possibility to overcome some of the main problems of SEC due to the absence of an obstructing porous stationary phase. The SEC-separation mainly depends on the pore size distribution of the used column set. The analyte molecules can enter the pores of the stationary phase in dependence on their hydrodynamic volume. The archived separation is a result of the retention time of the analyte species inside SEC-column which depends on the accessibility of the pores, the residence time inside the pores and the diffusion ability of the analyte molecules. The elution order in SEC is typically from low to high hydrodynamic volume. On the contrary AF4 separates according to the diffusion coefficient of the analyte molecules as long as the chosen conditions support the normal FFF-separation mechanism. The separation takes place in an empty channel and is caused by a cross-flow field perpendicular to the solvent flow. The analyte molecules will arrange in different channel heights depending on the diffusion coefficients. The parabolic-shaped flow profile inside the channel leads to different elution velocities. The species with low hydrodynamic volume will elute first while the species with high hydrodynamic volume elute later. The AF4 can be performed at ambient or high temperature (AT-/HT-AF4). We have analyzed one low molar mass polyethylene sample and a number of narrow distributed polystyrene standards as reference materials with known structure by AT/HT-SEC and AT/HT-AF4. Low density polyethylenes as well as polypropylene and polybutadiene, containing high degrees of branching and high molar masses, have been analyzed with both methods. As in SEC the relationship between the radius of gyration (R(g)) or the molar mass and the elution volume is curved up towards high elution volumes, a correct calculation of the MMD and the molar mass average or branching ratio is not possible using the data from the SEC measurements. In contrast to SEC, AF4 allows the precise determination of the MMD, the molar mass averages as well as the degree of branching because the molar mass vs. elution volume curve and the conformation plot is not falsified in this technique. In addition, higher molar masses can be detected using HT-AF4 due to the absence of significant shear degradation in the channel. As a result the average molar masses obtained from AF4 are higher compared to SEC. The analysis time in AF4 is comparable to that of SEC but the adjustable cross-flow program allows the user to influence the separation efficiency which is not possible in SEC without a costly change of the whole column combination. Copyright © 2011 Elsevier B.V. All rights reserved.

Predisposing factors for atrial fibrillation in the elderly

PubMed Central

Wasmer, Kristina; Eckardt, Lars; Breithardt, Günter

2017-01-01

Atrial fibrillation (AF) in the elderly occurs as a consequence of cardiovascular aging and an age related increase of comorbidity. Several predisposing factors for AF have been identified for the overall AF population. Most of them, cardiovascular disease in particular, play a role in younger and older patients. The longer time period during which these risk factors can cause structural changes that ultimately lead to AF may, at least in part, explain the association between age and AF. In addition, less well defined age-related changes in cellular electrophysiologic properties and structure predispose to AF in the elderly. PMID:28592961

A Prospective Randomized Trial of Apixaban Dosing During Atrial Fibrillation Ablation: The AEIOU Trial.

PubMed

Reynolds, Matthew R; Allison, J Scott; Natale, Andrea; Weisberg, Ian L; Ellenbogen, Kenneth A; Richards, Mark; Hsieh, Wen-Hua; Sutherland, Julie; Cannon, Christopher P

2018-05-01

This study sought to determine whether uninterrupted apixaban would have similar rates of bleeding and thromboembolic events as does minimally interrupted apixaban at the time of atrial fibrillation (AF) ablation and to compare those results with rates in historical patients treated with uninterrupted warfarin. The safety, efficacy, and optimal dosing regimen for apixaban at the time of AF ablation are uncertain. This prospective, multicenter clinical trial enrolled 306 patients undergoing catheter ablation for nonvalvular AF and randomized 300 to uninterrupted versus minimally interrupted (holding 1 dose) periprocedural apixaban. A retrospective cohort of patients treated with uninterrupted warfarin at the same centers was matched to the apixaban-treated subjects for comparison. Endpoints included clinically significant bleeding, major bleeding, and nonhemorrhagic stroke or systemic embolism (SE) from the time of ablation through 30 days. There were no stroke or SE events. Clinically significant bleeding occurred in 11.3% of 150 evaluable patients on uninterrupted apixaban and 9.7% of 145 evaluable patients on interrupted apixaban (risk difference: 1.7% [95% confidence interval: -5.5% to 8.8%]; p = NS). Rates of major bleeding were 1.3% with uninterrupted apixaban, and 2.1% with interrupted (risk difference: -0.7%; p = NS). The rates of clinically significant and major bleeding were similar for all apixaban patients combined (10.5% and 1.7%), compared with the matched warfarin group (9.8% and 1.4%). Both uninterrupted and minimally interrupted apixaban at the time of AF ablation were associated with a very low rate of thromboembolic events, and rates of both major (<2%) and clinically significant bleeding were similar to uninterrupted warfarin. (Apixaban Evaluation of Interrupted Or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation [AEIOU]; NCT02608099). Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Simultaneous multi-mycotoxin determination in nutmeg by ultrasound-assisted solid-liquid extraction and immunoaffinity column clean-up coupled with liquid chromatography and on-line post-column photochemical derivatization-fluorescence detection.

PubMed

Kong, Wei-Jun; Liu, Shu-Yu; Qiu, Feng; Xiao, Xiao-He; Yang, Mei-Hua

2013-05-07

A simple and sensitive analytical method based on ultrasound-assisted solid-liquid extraction and immunoaffinity column clean-up coupled with high performance liquid chromatography and on-line post-column photochemical derivatization-fluorescence detection (USLE-IAC-HPLC-PCD-FLD) has been developed for simultaneous multi-mycotoxin determination of aflatoxins B1, B2, G1, G2 (AFB1, AFB2, AFG1, AFG2) and ochratoxin A (OTA) in 13 edible and medicinal nutmeg samples marketed in China. AFs and OTA were extracted from nutmeg samples by ultrasonication using a methanol : water (80 : 20, v/v) solution, followed by an IAC clean-up step. Different USL extraction conditions, pre-processing ways for nutmeg sample and clean-up columns for mycotoxins, as well as HPLC-PCD-FLD parameters (mobile phase, column temperature, elution procedure, excitation and emission wavelengths) were optimized. This method, which was appraised for analyzing nutmeg samples, showed satisfactory results with reference to limits of detection (LODs) (from 0.02 to 0.25 μg kg(-1)), limits of quantification (LOQs) (from 0.06 to 0.8 μg kg(-1)), linear ranges (up to 30 ng mL(-1) for AFB1, AFG1 and OTA and 9 ng mL(-1) for AFB2 and AFG2), intra- and inter-day variability (all <2%) and average recoveries (from 79.6 to 90.8% for AFs and from 93.6 to 97.3% for OTA, respectively). The results of the application of developed method in nutmeg samples have elucidated that four samples were detected with contamination of AFs and one with OTA. AFB1 was the most frequently found mycotoxin in 30.8% of nutmeg samples at contamination levels of 0.73-16.31 μg kg(-1). At least two different mycotoxins were co-occurred in three samples, and three AFs were simultaneously detected in one sample.

Optimizing the use of oral anticoagulant therapy for atrial fibrilation in primary care: a pharmacist-led intervention.

PubMed

Virdee, Mandeep S; Stewart, Derek

2017-02-01

Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA 2 DS 2 -VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA 2 DS 2 -VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist-led intervention re-aligned oral anticoagulant therapy to the latest evidence based guidelines for stroke prophylaxis, whilst simultaneously correcting the over-utilisation of antiplatelet therapy.

Randomised clinical trial of cryoballoon versus irrigated radio frequency catheter ablation for atrial fibrillation-the effect of double short versus standard exposure cryoablation duration during pulmonary vein isolation (CIRCA-DOSE): methods and rationale.

PubMed

Andrade, Jason G; Deyell, Marc W; Badra, Mariano; Champagne, Jean; Dubuc, Marc; Leong-Sit, Peter; Macle, Laurent; Novak, Paul; Roux, Jean-Francois; Sapp, John; Tang, Anthony; Verma, Atul; Wells, George A; Khairy, Paul

2017-10-05

Pulmonary vein isolation (PVI) is an effective therapy for paroxysmal atrial fibrillation (AF), but it has limitations. The two most significant recent advances have centred on the integration of real-time quantitative assessment of catheter contact force into focal radio frequency (RF) ablation catheters and the development of dedicated ablation tools capable of achieving PVI with a single ablation lesion (Arctic Front cryoballoon, Medtronic, Minneapolis, MN, USA). Although each of these holds promise for improving the clinical success of catheter ablation of AF, there has not been a rigorous comparison of these advanced ablation technologies. Moreover, the optimal duration of cryoablation (freezing time) has not been determined. Patients undergoing an initial PVI procedure for paroxysmal AF will be recruited. Patients will be randomised 1:1:1 between contact-force irrigated RF ablation, short duration cryoballoon ablation (2 min applications) and standard duration cryoballoon ablation (4 min applications). The primary outcome is time to first documented AF recurrence on implantable loop recorder. With a sample size of 111 per group and a two-sided 0.025 significance level (to account for the two main comparisons), the study will have 80% power (using a log-rank test) to detect a difference of 20% between contact force RF catheter ablation and either of the two cryoballoon ablation groups. Factoring in a 4% loss to follow-up, 116 patients per group should be randomised and followed for a year (total study population of 348). The study was approved by the University of British Columbia Office of Research (Services) Ethics Clinical Research Ethics Board. Results of the study will be submitted for publication in a peer-reviewed journal. NCT01913522; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Characterization of a novel antibacterial glycopeptide produced by Penicillium sp. M03.

PubMed

Yang, W H; Zhang, W C; Lu, X M; Jiang, G S; Gao, P J

2009-04-01

To isolate a novel antibiotic termed AF from fermentation broth of Penicillium sp. M03 and to examine its antimicrobial activity, biological properties and structure characteristics. Sephadex LH-20 and HPLC were used to purify AF from fermentation broth of Penicillium sp. M03. The antimicrobial activity of AF was evaluated with the agar diffusion test. Amino acid and monosaccharide composition of AF was analysed by a HITACHI 835 detector and HPLC assay, respectively. Matrix-assisted laser desorption time of flight mass spectrometry, FT-IR and (1)H nuclear magnetic resonance spectra analyses were performed to examine the initial structure of AF. Eighty milligrams of AF was isolated as white powder from 1-l Penicillium sp. M03 fermentation broth. It consists of five amino acid and two monosaccharide residues and the molecular weight of it was 1017, and it was stable to beta-lactamase, heat, acid and alkali. AF showed inhibitory activity to a wide range of bacteria, particularly to multidrug-resistant Staphylococcus aureus. AF was a novel antibacterial glycopeptide with a broad inhibitory spectrum to pathogenic bacteria including multidrug-resistant agents. Furthermore, it is difficult to generate bacteria resistant to AF. Characterization of AF made it a potential antibiotic to fight against antibiotic-resistant bacterial pathogens.

A new predictor of atrial fibrillation after coronary artery bypass graft surgery: HATCH score.

PubMed

Selvi, Mithat; Gungor, Hasan; Zencir, Cemil; Gulasti, Sevil; Eryilmaz, Ufuk; Akgullu, Cagdas; Durmaz, Selim

2018-03-01

The aim of this study was to investigate the association between HATCH score and atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery. 369 patients (103 patients with AF and 266 patients without AF) undergoing isolated CABG surgery were analyzed. Complete medical records were retrospectively collected to investigate HATCH score. The median age of patients with AF was significantly higher than the median age of non-AF group (60.8±10.0 years vs 67.8±9.5 years, P<0.001). HATCH score was significantly higher in patients who developed AF after CABG surgery than the non-AF group (P=0.017). Multivariate logistic regression analysis showed that HATCH score (OR 1.334; 95% CI 1.022 to 1.741, P=0.034) was an independent predictor of AF after CABG surgery. Receiver operating characteristic curve analysis showed that the cut-off point of HATCH score related to predict AF was >1 (two or more), with a sensitivity of 42% and specificity of 70%. Patients with elevated preoperative HATCH score may have higher risk for AF after CABG surgery. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Critical Role for CRM1 in Regulating HOXA Gene Transcription in CALM-AF10 Leukemias

PubMed Central

Conway, Amanda E.; Haldeman, Jonathan M.; Wechsler, Daniel S.; Lavau, Catherine P.

2014-01-01

The leukemogenic CALM-AF10 fusion protein is found in patients with immature acute myeloid and T-lymphoid malignancies. CALM-AF10 leukemias display abnormal H3K79 methylation and increased HOXA cluster gene transcription. Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear. We previously determined that CALM contains a CRM1-dependent nuclear export signal (NES), which is both necessary and sufficient for CALM-AF10-mediated leukemogenesis. Here, we find that interaction of CALM-AF10 with the nuclear export receptor CRM1 is necessary for activating HOXA gene expression. We show that CRM1 localizes to HOXA loci where it recruits CALM-AF10, leading to transcriptional and epigenetic activation of HOXA genes. Genetic and pharmacological inhibition of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin, resulting in immediate loss of transcription. These results provide a comprehensive mechanism by which the CALM-AF10 translocation activates the critical HOXA cluster genes. Furthermore, this report identifies a novel function of CRM1: the ability to bind chromatin and recruit the NES-containing CALM-AF10 transcription factor. PMID:25027513

Atrial Fibrillation in Eight New World Camelids.

PubMed

Bozorgmanesh, R; Magdesian, K G; Estell, K E; Stern, J A; Swain, E A; Griffiths, L G

2016-01-01

There is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC). Describe clinical signs and outcome of AF in NWC. Eight New World Camelids admitted with AF. A retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG). All animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8). Atrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Quantitative fundus autofluorescence in healthy eyes.

PubMed

Greenberg, Jonathan P; Duncker, Tobias; Woods, Russell L; Smith, R Theodore; Sparrow, Janet R; Delori, François C

2013-08-21

Fundus autofluorescence was quantified (qAF) in subjects with healthy retinae using a standardized approach. The objective was to establish normative data and identify factors that influence the accumulation of RPE lipofuscin and/or modulate the observed AF signal in fundus images. AF images were acquired from 277 healthy subjects (age range: 5-60 years) by employing a Spectralis confocal scanning laser ophthalmoscope (cSLO; 488-nm excitation; 30°) equipped with an internal fluorescent reference. For each image, mean gray level was calculated as the average of eight preset regions, and was calibrated to the reference, zero-laser light, magnification, and optical media density from normative data on lens transmission spectra. Relationships between qAF and age, sex, race/ethnicity, eye color, refraction/axial length, and smoking status were evaluated as was measurement repeatability and the qAF spatial distribution. qAF levels exhibited a significant increase with age. qAF increased with increasing eccentricity up to 10° to 15° from the fovea and was highest superotemporally. qAF values were significantly greater in females, and, compared with Hispanics, qAF was significantly higher in whites and lower in blacks and Asians. No associations with axial length and smoking were observed. For two operators, between-session repeatability was ± 9% and ± 12%. Agreement between the operators was ± 13%. Normative qAF data are a reference tool essential to the interpretation of qAF measurements in ocular disease.

Clinical, Electrocardiographic, and Echocardiographic Parameter Combination Predicts the Onset of Atrial Fibrillation.

PubMed

Soeki, Takeshi; Matsuura, Tomomi; Tobiume, Takeshi; Bando, Sachiko; Matsumoto, Kazuhisa; Nagano, Hiromi; Uematsu, Etsuko; Kusunose, Kenya; Ise, Takayuki; Yamaguchi, Koji; Yagi, Shusuke; Fukuda, Daiju; Yamada, Hirotsugu; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Sata, Masataka

2018-05-30

The ability to identify risk markers for new-onset atrial fibrillation (AF) is critical to the development of preventive strategies, but it remains unknown whether a combination of clinical, electrocardiographic, and echocardiographic parameters predicts the onset of AF. In the present study, we evaluated the predictive value of a combined score that includes these parameters.Methods and Results:We retrospectively studied 1,040 patients without AF who underwent both echocardiography and 24-h Holter electrocardiography between May 2005 and December 2010. During a median follow-up period of 68.4 months (IQR, 49.9-93.3 months), we investigated the incidence of new-onset AF. Of the 1,040 patients, 103 (9.9%) developed AF. Patients who developed AF were older than patients who did not. Total heart beats, premature atrial contraction (PAC) count, maximum RR interval, and frequency of sinus pause quantified on 24-h electrocardiography were associated with new-onset AF. LA diameter (LAD) on echocardiography was also associated with the development of AF. On multivariate Cox analysis, age ≥58 years, PAC count ≥80 beats/day, maximum RR interval ≥1.64 s, and LAD ≥4.5 cm were independently associated with the development of AF. The incidence rate of new-onset AF significantly increased as the combined score (i.e., the sum of the risk score determined using hazard ratios) increased. A combined score that includes age, PAC count, maximum RR interval, and LAD could help characterize the risk of new-onset AF.

Statin and Atrial Fibrilation: When does it work?

PubMed

Fauchier, Laurent; Clementy, Nicolas; Pierre, Bertrand; Babuty, Dominique

2012-01-01

In the recent years, some clinical and experimental studies have suggested that the use of statins may protect against atrial fibrillation (AF). A relation between inflammation and the development of AF has been described, and the potent anti-inflammatory and antioxidant properties of statins may make them effective in preventing the development of AF. A global analysis of the literature suggests that the use of statins is associated with a decreased risk of incidence or recurrence of AF in some cases. However, this beneficial effect is not seen for all types of AF in all the patients. The use of statins seems associated 1) with a lack of benefit in primary prevention of AF, 2) with a significant but heterogeneous decreased risk of recurrence of AF in secondary prevention, and 3) with a very significant and homogeneous reduction for the risk of post operative AF. An intensive lipid lowering statin regimen does not provide greater protection against AF. Patients with coronary heart disease are curr ently treated with statins in most cases, and this may not have an impact on their treatment. In contrast, it remains to determine more accurately if statins may bring a significant benefit for some AF patients without any type of established atherosclerotic disease or with a low risk of atherogenesis. Since it remains uncertain whether the suppression of AF in these patients is beyond doubt beneficial, prescribing statins for this purpose alone should not be recommended at the present time.

The Impact of Transforming Growth Factor-β1 Level on Outcome After Catheter Ablation in Patients With Atrial Fibrillation.

PubMed

Kishima, Hideyuki; Mine, Takanao; Takahashi, Satoshi; Ashida, Kenki; Ishihara, Masaharu; Masuyama, Tohru

2017-04-01

Transforming growth factor-β 1 (TGF-β 1 ) is an important factor that induces atrial fibrosis and atrial fibrillation (AF). The purpose of this study was to evaluate the association between TGF-β 1 level and clinical factors before catheter ablation (CA), and to investigate the impact of TGF-β 1 level on the outcome after CA for AF. This prospective study included 151 patients (persistent AF group: n = 59, paroxysmal AF [PAF] group: n = 54, and control group: n = 38). All patients who underwent CA for AF were followed up for 12 months. The PAF group had the highest TGF-β 1 levels in all patients. An early recurrence of AF (ERAF: defined as episodes of atrial tachyarrhythmia within a 3-month blanking period) was detected in 60 patients (53%). Recurrent AF after the blanking period was detected in 36 patients (32%). On multivariate analysis, low TGF-β 1 level was the only independent factor associated with recurrent AF. Moreover, the AF recurrence ratio was higher in the low TGF-β 1 group (< 12.56 ng/mL) than in the high TGF-β 1 group (16 of 29 patients, 55% vs. 20 of 84 patients, 24%, P = 0.002 by log-rank test). PAF was associated with a higher TGF-β 1 level. Moreover, lower TGF-β 1 level in AF patients could be a cause of recurrent AF after CA. © 2017 Wiley Periodicals, Inc.

AF4 and AF4N protein complexes: recruitment of P-TEFb kinase, their interactome and potential functions

PubMed Central

Scholz, Bastian; Kowarz, Eric; Rössler, Tanja; Ahmad, Khalil; Steinhilber, Dieter; Marschalek, Rolf

2015-01-01

AF4/AFF1 and AF5/AFF4 are the molecular backbone to assemble “super-elongation complexes” (SECs) that have two main functions: (1) control of transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb = CyclinT1/CDK9) that is usually stored in inhibitory 7SK RNPs; (2) binding of different histone methyltransferases, like DOT1L, NSD1 and CARM1. This way, transcribed genes obtain specific histone signatures (e.g. H3K79me2/3, H3K36me2) to generate a transcriptional memory system. Here we addressed several questions: how is P-TEFb recruited into SEC, how is the AF4 interactome composed, and what is the function of the naturally occuring AF4N protein variant which exhibits only the first 360 amino acids of the AF4 full-length protein. Noteworthy, shorter protein variants are a specific feature of all AFF protein family members. Here, we demonstrate that full-length AF4 and AF4N are both catalyzing the transition of P-TEFb from 7SK RNP to their N-terminal domain. We have also mapped the protein-protein interaction network within both complexes. In addition, we have first evidence that the AF4N protein also recruits TFIIH and the tumor suppressor MEN1. This indicate that AF4N may have additional functions in transcriptional initiation and in MEN1-dependend transcriptional processes. PMID:26171280

The lateralized arcuate fasciculus in developmental pitch disorders among mandarin amusics: left for speech and right for music.

PubMed

Chen, Xizhuo; Zhao, Yanxin; Zhong, Suyu; Cui, Zaixu; Li, Jiaqi; Gong, Gaolang; Dong, Qi; Nan, Yun

2018-05-01

The arcuate fasciculus (AF) is a neural fiber tract that is critical to speech and music development. Although the predominant role of the left AF in speech development is relatively clear, how the AF engages in music development is not understood. Congenital amusia is a special neurodevelopmental condition, which not only affects musical pitch but also speech tone processing. Using diffusion tensor tractography, we aimed at understanding the role of AF in music and speech processing by examining the neural connectivity characteristics of the bilateral AF among thirty Mandarin amusics. Compared to age- and intelligence quotient (IQ)-matched controls, amusics demonstrated increased connectivity as reflected by the increased fractional anisotropy in the right posterior AF but decreased connectivity as reflected by the decreased volume in the right anterior AF. Moreover, greater fractional anisotropy in the left direct AF was correlated with worse performance in speech tone perception among amusics. This study is the first to examine the neural connectivity of AF in the neurodevelopmental condition of amusia as a result of disrupted music pitch and speech tone processing. We found abnormal white matter structural connectivity in the right AF for the amusic individuals. Moreover, we demonstrated that the white matter microstructural properties of the left direct AF is modulated by lexical tone deficits among the amusic individuals. These data support the notion of distinctive pitch processing systems between music and speech.

Expression of TGFbeta1 in pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs.

PubMed

Li, Shufeng; Li, Hongli; Mingyan, E; Yu, Bo

2009-02-01

The development of pulmonary vein stenosis has recently been described after radiofrequency ablation (RF) to treat atrial fibrillation (AF). The purpose of this study was to examine expression of TGFbeta1 in pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs. About 28 mongrel dogs were randomly assigned to the sham-operated group (n = 7), the AF group (n = 7), AF + RF group (n = 7), and RF group (n = 7). In AF or AF + RF groups, dogs underwent chronic pulmonary vein (PV) pacing to induce sustained AF. RF application was applied around the PVs until electrical activity was eliminated. Histological assessment of pulmonary veins was performed using hematoxylin and eosin staining; TGFbeta1 gene expression in pulmonary veins was examined by RT-PCR analysis; expression of TGFbeta1 protein in pulmonary veins was assessed by Western blot analysis. Rapid pacing from the left superior pulmonary vein (LSPV) induced sustained AF in AF group and AF + RF group. Pulmonary vein ablation terminated the chronic atrial fibrillation in dogs. Histological examination revealed necrotic tissues in various stages of collagen replacement, intimal thickening, and cartilaginous metaplasia with chondroblasts and chondroclasts. Compared with sham-operated and AF group, TGFbeta1 gene and protein expressions was increased in AF + RF or RF groups. It was concluded that TGFbeta1 might be associated with pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs.

A solution quality assessment method for swarm intelligence optimization algorithms.

PubMed

Zhang, Zhaojun; Wang, Gai-Ge; Zou, Kuansheng; Zhang, Jianhua

2014-01-01

Nowadays, swarm intelligence optimization has become an important optimization tool and wildly used in many fields of application. In contrast to many successful applications, the theoretical foundation is rather weak. Therefore, there are still many problems to be solved. One problem is how to quantify the performance of algorithm in finite time, that is, how to evaluate the solution quality got by algorithm for practical problems. It greatly limits the application in practical problems. A solution quality assessment method for intelligent optimization is proposed in this paper. It is an experimental analysis method based on the analysis of search space and characteristic of algorithm itself. Instead of "value performance," the "ordinal performance" is used as evaluation criteria in this method. The feasible solutions were clustered according to distance to divide solution samples into several parts. Then, solution space and "good enough" set can be decomposed based on the clustering results. Last, using relative knowledge of statistics, the evaluation result can be got. To validate the proposed method, some intelligent algorithms such as ant colony optimization (ACO), particle swarm optimization (PSO), and artificial fish swarm algorithm (AFS) were taken to solve traveling salesman problem. Computational results indicate the feasibility of proposed method.

Correction of autofluorescence intensity for epithelial scattering by optical coherence tomography: a phantom study

NASA Astrophysics Data System (ADS)

Pahlevaninezhad, H.; Lee, A. M. D.; Hyun, C.; Lam, S.; MacAulay, C.; Lane, P. M.

2013-03-01

In this paper, we conduct a phantom study for modeling the autofluorescence (AF) properties of tissue. A combined optical coherence tomography (OCT) and AF imaging system is proposed to measure the strength of the AF signal in terms of the scattering layer thickness and concentration. The combined AF-OCT system is capable of estimating the AF loss due to scattering in the epithelium using the thickness and scattering concentration calculated from the co-registered OCT images. We define a correction factor to account for scattering losses in the epithelium and calculate a scatteringcorrected AF signal. We believe the scattering-corrected AF will reduce the diagnostic false-positives rate in the early detection of airway lesions due to confounding factors such as increased epithelial thickness and inflammations.

Increased Susceptibility to Atrial Fibrillation Secondary to Atrial Fibrosis in Transgenic Goats Expressing Transforming Growth Factor-β1

PubMed Central

Davies, Christopher J.; Regouski, Misha; Hall, Justin; Olsen, Aaron L.; Meng, Qinggang; Rutigliano, Heloisa M.; Dosdall, Derek J.; Angel, Nathan A.; Sachse, Frank B.; Seidel, Thomas; Thomas, Aaron J.; Stott, Rusty; Panter, Kip E.; Lee, Pamela M.; Van Wettere, Arnaud J.; Stevens, John R.; Wang, Zhongde; MacLeod, Rob S.; Marrouche, Nassir F.; White, Kenneth L.

2016-01-01

Introduction Large animal models of progressive atrial fibrosis would provide an attractive platform to study relationship between structural and electrical remodeling in atrial fibrillation (AF). Here we established a new transgenic goat model of AF with cardiac specific overexpression of TGF-β1 and investigated the changes in the cardiac structure and function leading to AF. Methods and Results Transgenic goats with cardiac specific overexpression of constitutively active TGF-β1 were generated by somatic cell nuclear transfer. We examined myocardial tissue, ECGs, echocardiographic data, and AF susceptibility in transgenic and wild-type control goats. Transgenic goats exhibited significant increase in fibrosis and myocyte diameters in the atria compared to controls, but not in the ventricles. P-wave duration was significantly greater in transgenic animals starting at 12-month of age, but no significant chamber enlargement was detected, suggesting conduction slowing in the atria. Furthermore, this transgenic goat model exhibited a significant increase in AF vulnerability. Six of 8 transgenic goats (75%) were susceptible to AF induction and exhibited sustained AF (>2 minutes), whereas, none of 6 controls displayed sustained AF (P<0.01). Length of induced AF episodes was also significantly greater in the transgenic group compared to controls (687±212.02 vs. 2.50±0.88 seconds, P<0.0001), but no persistent or permanent AF was observed. Conclusion A novel transgenic goat model with a substrate for AF was generated. In this model, cardiac overexpression of TGF-β1 led to an increase in fibrosis and myocyte size in the atria, and to progressive P-wave prolongation. We suggest that these factors underlie increased AF susceptibility. PMID:27447370

Association between Heat Shock Protein-60 and Development of Atrial Fibrillation: Results from the Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Maan, Abhishek; Jorgensen, Neal W; Mansour, Moussa; Dudley, Samuel; Jenny, Nancy S; Defilippi, Christopher; Szklo, Moyses; Alonso, Alvaro; Refaat, Marwan M; Ruskin, Jeremy; Heckbert, Susan R; Heist, E Kevin

2016-12-01

During atrial fibrillation (AF), a high rate of myocyte activation causes cellular stress and initiates the process of atrial remodeling, which further promotes persistence of AF. Although heat shock proteins (HSPs) have been shown to prevent atrial remodeling and suppress the occurrence of AF in cellular and animal experimental models, increased levels of HSP-60 have been observed in patients with postoperative AF, likely reflecting a response to cellular stress. To better understand the role of HSP-60 in relation to AF, we examined the association of HSP-60 levels in relation to the future development of AF in the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a cohort study that recruited 6,814 participants aged 45-84 years and free of known cardiovascular disease at baseline (2000-2002) from six field centers. We investigated 983 participants, selected at random from the total cohort, who had HSP-60 measured and were free of AF at baseline. We tested the association of HSP-60 levels with the incidence of AF using multivariate Cox models after adjustment for demographics, clinical characteristics, and biomarkers. During an average of 10.6 years of follow-up, 77 participants developed AF. We did not observe a significant association between the log-transformed HSP-60 levels and development of AF on either unadjusted or multivariate analysis (adjusted hazard ratio: 1.02 per unit difference on natural log scale, 95% confidence interval: 0.77-1.34 ln (ng/mL). Contrary to the findings from the preclinical studies, which demonstrated an important role of HSP-60 in the pathogenesis of AF, we did not observe a significant association between HSP-60 and occurrence of AF. © 2016 Wiley Periodicals, Inc.

Quality of life, activity impairment, and healthcare resource utilization associated with atrial fibrillation in the US National Health and Wellness Survey.

PubMed

Goren, Amir; Liu, Xianchen; Gupta, Shaloo; Simon, Teresa A; Phatak, Hemant

2013-01-01

This study builds upon current studies of atrial fibrillation (AF) and health outcomes by examining more comprehensively the humanistic burden of illness (quality of life, activity impairment, and healthcare resource utilization) among adult patients with AF, using a large, nationally representative sample and matched controls. Data were analyzed from the Internet-based 2009 US National Health and Wellness Survey. Outcomes were Mental and Physical Component Summary (MCS and PCS) and health utility scores from the SF-12, activity impairment, hospitalizations, and healthcare provider and emergency room (ER) visits. Patients with self-reported diagnosis of AF were matched randomly on age and gender with an equal number of respondents without AF. Generalized linear models examined outcomes as a function of AF vs. non-AF status, controlling for CHADS2 score, comorbidity counts, demographics, and clinical variables. Exploratory structural equation modeling assessed the above in an integrated model of humanistic burden. Mean age of AF patients (1,296 from a total sample of 75,000) was 64.9 years and 65.1% were male. Adjusting for covariates, compared with non-AF patients, AF patients had lower MCS, PCS, and utility scores, greater activity impairment (rate ratio = 1.26), more traditional provider visits (rate ratio = 1.43), and increased odds of ER visits (OR = 2.53) and hospitalizations (OR = 2.71). Exploratory structural equation modeling analyses revealed that persons with AF experienced a significantly higher overall humanistic burden. This study highlights and clarifies the substantial burden of AF and its implications for preparing efficacious AF management plans to address the imminent rise in prevalence.

Pulmonary Vein Isolation Alone Versus Additional Linear Ablation in Patients With Persistent Atrial Fibrillation Converted to Paroxysmal Type With Antiarrhythmic Drug Therapy: A Multicenter, Prospective, Randomized Study.

PubMed

Yu, Hee Tae; Shim, Jaemin; Park, Junbeom; Kim, In-Soo; Kim, Tae-Hoon; Uhm, Jae-Sun; Joung, Boyoung; Lee, Moon-Hyoung; Kim, Young-Hoon; Pak, Hui-Nam

2017-06-01

Atrial fibrillation (AF) type can vary depending on condition and timing, and some patients who initially present with persistent AF may be changed to paroxysmal AF after antiarrhythmic drug medication and cardioversion. We investigated whether circumferential pulmonary vein isolation (CPVI) alone is an effective rhythm control strategy in patients with persistent AF to paroxysmal AF. We enrolled 113 patients with persistent AF to paroxysmal AF (male 75%, 60.4±10.1 years old) who underwent catheter ablation for nonvalvular AF at 3 tertiary hospitals. The participants were randomly assigned to 2 groups: CPVI alone (n=59) or CPVI plus linear ablation (CPVI+Line; posterior box+anterior line, n=54). Compared with the CPVI+Line, CPVI alone required shorter procedure (187.2±58.0 versus 211.2±63.9 min; P =0.043) and ablation times (4922.1±1110.5 versus 6205.7±1425.2 s; P <0.001) without difference in procedure-related major complication (3% versus 2%; P =0.611). Antiarrhythmic drug utility rates after ablation were not different between the 2 groups (22% versus 30%; P =0.356). Overall, AF-free survival (log-rank; P =0.206) and AF and antiarrhythmic drug-free survival (log-rank; P =0.321) were not different between groups. CPVI alone is an effective rhythm control strategy with a shorter procedure time in persistent AF patients converted to paroxysmal AF compared with CPVI with linear ablation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02176616. © 2017 American Heart Association, Inc.

Association of Proteinuria and Incident Atrial Fibrillation in Patients With Intact and Reduced Kidney Function.

PubMed

Molnar, Amber O; Eddeen, Anan Bader; Ducharme, Robin; Garg, Amit X; Harel, Ziv; McCallum, Megan K; Perl, Jeffrey; Wald, Ron; Zimmerman, Deborah; Sood, Manish M

2017-07-06

Early evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function. Retrospective cohort study using administrative healthcare databases in Ontario, Canada (2002-2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin-to-creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow-up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow-up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF ( P <0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P <0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0-5.1] and 2.6 [95% CI, 2.4-2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses. Proteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified

PubMed Central

Movérare-Skrtic, Sofia; Börjesson, Anna E.; Farman, Helen H.; Sjögren, Klara; Windahl, Sara H.; Lagerquist, Marie K.; Andersson, Annica; Stubelius, Alexandra; Carlsten, Hans; Gustafsson, Jan-Åke; Ohlsson, Claes

2014-01-01

The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-20) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-20 mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-20 mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. In conclusion, ICI uses ERα AF-1 in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist. PMID:24395795

The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified.

PubMed

Movérare-Skrtic, Sofia; Börjesson, Anna E; Farman, Helen H; Sjögren, Klara; Windahl, Sara H; Lagerquist, Marie K; Andersson, Annica; Stubelius, Alexandra; Carlsten, Hans; Gustafsson, Jan-Åke; Ohlsson, Claes

2014-01-21

The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-2(0)) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-2(0) mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-2(0) mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. In conclusion, ICI uses ERα AF-1 in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist.

Debris extrusion and foraminal deformation produced by reciprocating instruments made of thermally treated NiTi wires

PubMed Central

Frota, Myrna Maria Arcanjo; Bernardes, Ricardo Affonso; Vivan, Rodrigo Ricci; Vivacqua-Gomes, Nilton; Duarte, Marco Antonio Hungaro; de Vasconcelos, Bruno Carvalho

2018-01-01

Abstract Objective To evaluate the amount of apically extruded debris, percentage of foraminal enlargement and apical foramen (AF) deformation that occurred during root canal preparation with different reciprocation systems: Reciproc, WaveOne (M-Wire), and ProDesign R (Shape Memory Technology Wire) at two different working lengths (WLs): 0.0 and 1.0 mm beyond the AF. Material and methods The AF of 120 root canals in 60 mesial roots of mandibular molars were photographed with stereomicroscope and randomly assigned into four groups: manual, Reciproc (REC), WaveOne (WO), and ProDesign R (PDR); subsequently, they were further subdivided according to the WL (n=15). Teeth were instrumented, coupled to a dual collecting chamber, and then another photograph of each AF was captured. Extrusion was analysed by determining the weight of extruded debris. Each AF diameter was measured in pre- and post-instrumentation images to determine deformation, which was analysed, and afterwards the final format of AFs was classified (circular/oval/deformed). Results We found no significant differences when analysing each system at different WLs. When considering each WL, REC and WO showed highest extrusion values (P<.05); for AF enlargement, differences were observed only for WO, when it was used beyond the AF; differences were observed among M-Wire groups beyond the AF (P<.05). AF deformation was observed in all groups; PDR showed the lowest AF deformation values at both WLs; M-Wire groups showed 50% strain beyond the AF. Conclusion Authors concluded that beyond the apical limit, the alloy and taper are important aspects when considering extrusion and deformation. PMID:29364346

Incident Atrial Fibrillation and Risk of End-Stage Renal Disease in Adults with Chronic Kidney Disease

PubMed Central

Bansal, Nisha; Fan, Dongjie; Hsu, Chi-yuan; Ordonez, Juan D.; Marcus, Gregory M.; Go, Alan S.

2013-01-01

Background Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD). However, the long-term impact of development of AF on the risk of adverse renal outcomes in patients with CKD is unknown. In this study, we determined the association between incident AF and risk of end-stage renal disease (ESRD) among adults with CKD. Methods and Results We studied adults with CKD (defined as persistent glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 by the CKD-EPI equation) enrolled in Kaiser Permanente Northern California who were identified between 2002–2010 and who did not have prior ESRD or previously documented AF. Incident AF was identified using primary hospital discharge diagnoses and/or two or more outpatient visits for AF. Incident ESRD was ascertained from a comprehensive health plan registry for dialysis and renal transplant. Among 206,229 adults with CKD, 16,463 developed incident AF. During a mean follow-up of 5.1± 2.5 years, there were 345 cases of ESRD that occurred after development of incident AF (74 per 1000 person-years) compared with 6505 cases of ESRD during periods without AF (64 per 1000 person-years, P<0.001). After adjustment for potential confounders, incident AF was associated with a 67% increase in rate of ESRD (hazard ratio 1.67, 95% confidence interval: 1.46–1.91). Conclusions Incident AF is independently associated with increased risk of developing ESRD in adults with CKD. Further study is needed to identify potentially modifiable pathways through which AF leads to a higher risk of progression to ESRD. PMID:23275377

Temporal trends in the occurrence and outcomes of atrial fibrillation in patients with acute myocardial infarction (from the Atherosclerosis Risk in Communities Surveillance Study).

PubMed

Bengtson, Lindsay G S; Chen, Lin Y; Chamberlain, Alanna M; Michos, Erin D; Whitsel, Eric A; Lutsey, Pamela L; Duval, Sue; Rosamond, Wayne D; Alonso, Alvaro

2014-09-01

Atrial fibrillation (AF) frequently coexists in the setting of myocardial infarction (MI), being associated with increased mortality. Nonetheless, temporal trends in the occurrence of AF complicating MI and in the prognosis of these patients are not well described. We examined temporal trends in prevalence of AF in the setting of MI and the effect of AF on prognosis in the community. We studied a population-based sample of 20,049 validated first-incident nonfatal hospitalized MIs among 35- to 74-year old residents of 4 communities in the Atherosclerosis Risk in Communities (ARIC) Study from 1987 through 2009. Prevalence of AF in the setting of MI increased from 11% to 15% during the 23-year study period. The multivariable adjusted odds ratio for prevalent AF, per 5-year increment, was 1.11 (95% confidence interval 1.04 to 1.19). Overall, in patients with MI, AF was associated with increased 1-year case fatality (odds ratio 1.47, 95% confidence interval 1.07 to 2.01) compared with those without AF. However, there was no evidence that the impact of AF on MI survival changed over time or differed over time by sex, race, or MI classification (all p values >0.10). In conclusion, co-occurrence of AF in MI slightly increased between 1987 and 2009. The adverse impact of AF on survival in the setting of MI was consistent throughout. In the setting of MI, co-occurrence of AF should be viewed as a critical clinical event, and treatment needs unique to this population should be explored further. Copyright © 2014 Elsevier Inc. All rights reserved.

Dominant frequency increase rate predicts transition from paroxysmal to long-term persistent atrial fibrillation.

PubMed

Martins, Raphael P; Kaur, Kuljeet; Hwang, Elliot; Ramirez, Rafael J; Willis, B Cicero; Filgueiras-Rama, David; Ennis, Steven R; Takemoto, Yoshio; Ponce-Balbuena, Daniela; Zarzoso, Manuel; O'Connell, Ryan P; Musa, Hassan; Guerrero-Serna, Guadalupe; Avula, Uma Mahesh R; Swartz, Michael F; Bhushal, Sandesh; Deo, Makarand; Pandit, Sandeep V; Berenfeld, Omer; Jalife, José

2014-04-08

Little is known about the mechanisms underlying the transition from paroxysmal to persistent atrial fibrillation (AF). In an ovine model of long-standing persistent AF we tested the hypothesis that the rate of electric and structural remodeling, assessed by dominant frequency (DF) changes, determines the time at which AF becomes persistent. Self-sustained AF was induced by atrial tachypacing. Seven sheep were euthanized 11.5±2.3 days after the transition to persistent AF and without reversal to sinus rhythm; 7 sheep were euthanized after 341.3±16.7 days of long-standing persistent AF. Seven sham-operated animals were in sinus rhythm for 1 year. DF was monitored continuously in each group. Real-time polymerase chain reaction, Western blotting, patch clamping, and histological analyses were used to determine the changes in functional ion channel expression and structural remodeling. Atrial dilatation, mitral valve regurgitation, myocyte hypertrophy, and atrial fibrosis occurred progressively and became statistically significant after the transition to persistent AF, with no evidence for left ventricular dysfunction. DF increased progressively during the paroxysmal-to-persistent AF transition and stabilized when AF became persistent. Importantly, the rate of DF increase correlated strongly with the time to persistent AF. Significant action potential duration abbreviation, secondary to functional ion channel protein expression changes (CaV1.2, NaV1.5, and KV4.2 decrease; Kir2.3 increase), was already present at the transition and persisted for 1 year of follow up. In the sheep model of long-standing persistent AF, the rate of DF increase predicts the time at which AF stabilizes and becomes persistent, reflecting changes in action potential duration and densities of sodium, L-type calcium, and inward rectifier currents.

Socioeconomic status and the development of atrial fibrillation in Hispanics, African Americans and non-Hispanic whites.

PubMed

Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Ferrick, Kevin J; Krumerman, Andrew

2017-09-01

Atrial fibrillation (AF) is the most common arrhythmia and is associated with significant morbidity and mortality. Despite having a higher burden of traditional AF risk factors, African American and Hispanic minorities have a lower incidence of AF when compared to non-Hispanic whites, referred to as the "racial paradox." Lower SES among Hispanics and African Americans may help to explain the lower incidence rates of AF compared to non-Hispanic whites. An electrocardiogram/electronic medical records database in New York State was interrogated for individuals free of AF for development of subsequent AF from 2000 to 2013. SES was assessed per zip code via a composite of 6 measures Z-scored to the New York State average. SES was reclassified into decile groups. Cox regression analysis controlling for all baseline differences was used to estimate the independent predictive ability of SES for AF. We identified 48 631 persons (43% Hispanic, 37% African Americans, and 20% non-Hispanic white; mean age 59 years; mean follow-up of 3.2 years) of which 4556 AF cases occurred. Hispanics and African Americans had lower AF risk than whites in all SES deciles (P < 0.001 by log-rank test). Higher SES was borderline associated with lower AF risk (hazard ratio: 0.990, 95% confidence interval: 0.980-1.001, P = 0.061). P trend analysis was not significant by any race/ethnic group by SES deciles for AF. Our study suggests that non-Hispanic whites were at higher risk for AF compared to nonwhites, and this was independent of SES. © 2017 Wiley Periodicals, Inc.

Increased Susceptibility to Atrial Fibrillation Secondary to Atrial Fibrosis in Transgenic Goats Expressing Transforming Growth Factor-β1.

PubMed

Polejaeva, Irina A; Ranjan, Ravi; Davies, Christopher J; Regouski, Misha; Hall, Justin; Olsen, Aaron L; Meng, Qinggang; Rutigliano, Heloisa M; Dosdall, Derek J; Angel, Nathan A; Sachse, Frank B; Seidel, Thomas; Thomas, Aaron J; Stott, Rusty; Panter, Kip E; Lee, Pamela M; Van Wettere, Arnaud J; Stevens, John R; Wang, Zhongde; MacLeod, Rob S; Marrouche, Nassir F; White, Kenneth L

2016-10-01

Large animal models of progressive atrial fibrosis would provide an attractive platform to study relationship between structural and electrical remodeling in atrial fibrillation (AF). Here we established a new transgenic goat model of AF with cardiac specific overexpression of TGF-β1 and investigated the changes in the cardiac structure and function leading to AF. Transgenic goats with cardiac specific overexpression of constitutively active TGF-β1 were generated by somatic cell nuclear transfer. We examined myocardial tissue, ECGs, echocardiographic data, and AF susceptibility in transgenic and wild-type control goats. Transgenic goats exhibited significant increase in fibrosis and myocyte diameters in the atria compared to controls, but not in the ventricles. P-wave duration was significantly greater in transgenic animals starting at 12 months of age, but no significant chamber enlargement was detected, suggesting conduction slowing in the atria. Furthermore, this transgenic goat model exhibited a significant increase in AF vulnerability. Six of 8 transgenic goats (75%) were susceptible to AF induction and exhibited sustained AF (>2 minutes), whereas none of 6 controls displayed sustained AF (P < 0.01). Length of induced AF episodes was also significantly greater in the transgenic group compared to controls (687 ± 212.02 seconds vs. 2.50 ± 0.88 seconds, P < 0.0001), but no persistent or permanent AF was observed. A novel transgenic goat model with a substrate for AF was generated. In this model, cardiac overexpression of TGF-β1 led to an increase in fibrosis and myocyte size in the atria, and to progressive P-wave prolongation. We suggest that these factors underlie increased AF susceptibility. © 2016 Wiley Periodicals, Inc.

Atrial fibrillation is associated with the fibrotic remodelling of adipose tissue in the subepicardium of human and sheep atria.

PubMed

Haemers, Peter; Hamdi, Hadhami; Guedj, Kevin; Suffee, Nadine; Farahmand, Patrick; Popovic, Natasa; Claus, Piet; LePrince, Pascal; Nicoletti, Antonino; Jalife, Jose; Wolke, Carmen; Lendeckel, Uwe; Jaïs, Pierre; Willems, Rik; Hatem, Stéphane N

2017-01-01

Accumulation of atrial adipose tissue is associated with atrial fibrillation (AF). However, the underlying mechanisms remain poorly understood. We examined the relationship between the characteristics of fatty infiltrates of the atrial myocardium and the history of AF. Atrial samples, collected in 92 patients during cardiac surgery and in a sheep model of persistent AF, were subjected to a detailed histological analysis. In sections of human right atrial samples, subepicardial fatty infiltrations were commonly observed in the majority of patients. A clear difference in the appearance and fibrotic content of these fatty infiltrations was observed. Fibro-fatty infiltrates predominated in patients with permanent AF (no AF: 37 ± 24% vs. paroxysmal AF: 50 ± 21% vs. permanent AF: 64 ± 23%, P < 0.001). An inverse correlation between fibrotic remodelling and the amount of subepicardial adipose tissue suggested the progressive fibrosis of fatty infiltrates with permanent AF. This hypothesis was tested in a sheep model of AF. In AF sheep, an increased accumulation of peri-atrial fat depot was observed on cardiac magnetic resonance imaging and dense fibro-fatty infiltrations predominated in the left atria of AF sheep. Cellular inflammation, mainly consisting of functional cytotoxic T lymphocytes, was observed together with adipocyte cell death in human atria. Atrial fibrillation is associated with the fibrosis of subepicardial fatty infiltrates, a process in which cytotoxic lymphocytes might be involved. This remodelling of the atrial subepicardium could contribute to structural remodelling forming a substrate for AF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Loss of atrial contractility is primary cause of atrial dilatation during first days of atrial fibrillation.

PubMed

Schotten, Ulrich; de Haan, Sunniva; Neuberger, Hans-Ruprecht; Eijsbouts, Sabine; Blaauw, Yuri; Tieleman, Robert; Allessie, Maurits

2004-11-01

Atrial fibrillation (AF) induces a progressive dilatation of the atria which in turn might promote the arrhythmia. The mechanism of atrial dilatation during AF is not known. To test the hypothesis that loss of atrial contractile function is a primary cause of atrial dilatation during the first days of AF, eight goats were chronically instrumented with epicardial electrodes, a pressure transducer in the right atrium, and piezoelectric crystals to measure right atrial diameter. AF was induced with the use of repetitive burst pacing. Atrial contractility was assessed during sinus rhythm, atrial pacing (160-, 300-, and 400-ms cycle length), and electrically induced AF. The compliance of the fibrillating right atrium was measured during unloading the atria with diuretics and loading with 1 liter of saline. All measurements were repeated after 6, 12, and 24 h of AF and then once a day during the first 5 days of AF. Recovery of the observed changes after spontaneous cardioversion was also studied. After 5 days of AF, atrial contractility during sinus rhythm or slow atrial pacing was greatly reduced. During rapid pacing (160 ms) or AF, the amplitude of the atrial pressure waves had declined to 20% of control. The compliance of the fibrillating atria increased twofold, whereas the right atrial pressure was unchanged. As a result, the mean right atrial diameter increased by approximately 12%. All changes were reversible within 3 days of sinus rhythm. We conclude that atrial dilatation during the first days of AF is due to an increase in atrial compliance caused by loss of atrial contractility during AF. Atrial compliance and size are restored when atrial contractility recovers after cardioversion of AF.

Examining rare and low-frequency genetic variants previously associated with lone or familial forms of atrial fibrillation in an electronic medical record system: a cautionary note.

PubMed

Weeke, Peter; Denny, Joshua C; Basterache, Lisa; Shaffer, Christian; Bowton, Erica; Ingram, Christie; Darbar, Dawood; Roden, Dan M

2015-02-01

Studies in individuals or small kindreds have implicated rare variants in 25 different genes in lone and familial atrial fibrillation (AF) using linkage and segregation analysis, functional characterization, and rarity in public databases. Here, we used a cohort of 20 204 patients of European or African ancestry with electronic medical records and exome chip data to compare the frequency of AF among carriers and noncarriers of these rare variants. The exome chip included 19 of 115 rare variants, in 9 genes, previously associated with lone or familial AF. Using validated algorithms querying a combination of clinical notes, structured billing codes, ECG reports, and procedure codes, we identified 1056 AF cases (>18 years) and 19 148 non-AF controls (>50 years) with available genotype data on the Illumina HumanExome BeadChip v.1.0 in the Vanderbilt electronic medical record-linked DNA repository, BioVU. Known correlations between AF and common variants at 4q25 were replicated. None of the 19 variants previously associated with AF were over-represented among AF cases (P>0.1 for all), and the frequency of variant carriers among non-AF controls was >0.1% for 14 of 19. Repeat analyses using non-AF controls aged >60 (n=14 904), >70 (n=9670), and >80 (n=4729) years did not influence these findings. Rare variants previously implicated in lone or familial forms of AF present on the exome chip are detected at low frequencies in a general population but are not associated with AF. These findings emphasize the need for caution when ascribing variants as pathogenic or causative. © 2014 American Heart Association, Inc.

The Long and Short Term Impact of Elevated Body Mass Index on Risk of New Atrial Fibrillation in the Women’s Health Study

PubMed Central

Tedrow, Usha B; Conen, David; Ridker, Paul M; Cook, Nancy R; Koplan, Bruce A; Manson, JoAnn E; Buring, Julie E; Albert, Christine M

2010-01-01

Objectives To characterize the relationship between changes in body mass index (BMI) and incident atrial fibrillation (AF) in a large cohort of women. Background Obesity and AF are increasing public health problems. The importance of dynamic obesity-associated AF risk is uncertain, and mediators are not well characterized. Methods Cases of AF were confirmed by medical record review in 34,309 participants in the Women’s Health Study. Baseline and updated measures of BMI were obtained from periodic questionnaires. Results Over 12.9 +/− 1.9 years of follow-up, 834 AF events were confirmed. BMI was linearly associated with AF risk, with a 4.7% (95% CI 3.4, 6.1, p<0.0001) increase in risk with each kg/m2. Adjustment for inflammatory markers minimally attenuated this risk. When updated measures of BMI were utilized to estimate dynamic risk, overweight (HR 1.22 95%CI 1.02, 1.45, p=0.03) and obesity (HR 1.65 95%CI 1.36, 2.00, p<0.0001) were associated with adjusted short term elevations in AF risk. Participants becoming obese during the first 60 months had a 41% adjusted increase in risk of developing AF (p=0.02) compared to those maintaining BMI <30 kg/m2. The prevalence of overweight and obesity increased over time. The adjusted proportion of incident AF attributable to short term elevations in BMI was substantial (18.3%). Conclusions In this population of apparently healthy women, BMI was associated with short and long term elevations in AF risk, accounting for a large proportion of incident AF independent of traditional risk factors. A strategy of weight control may reduce the increasing incidence of AF. PMID:20488302

The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation.

PubMed

Kawabata, Mihoko; Goya, Masahiko; Takagi, Takamitsu; Yamashita, Shu; Iwai, Shinsuke; Suzuki, Masahito; Takamiya, Tomomasa; Nakamura, Tomofumi; Hayashi, Tatsuya; Yagishita, Atsuhiko; Sasaki, Takeshi; Takahashi, Yoshihide; Ono, Yuhichi; Hachiya, Hitoshi; Yamauchi, Yasuteru; Otomo, Kenichiro; Nitta, Junichi; Okishige, Kaoru; Nishizaki, Mitsuhiro; Iesaka, Yoshito; Isobe, Mitsuaki; Hirao, Kenzo

2016-12-01

Atrial fibrillation (AF) often coexists with Wolff-Parkinson-White (WPW) syndrome. We compared the efficacy of Kent bundle ablation alone and additional AF ablation on accompanying AF, and examined which patients would still have a risk of AF after successful Kent bundle ablation. This retrospective multicenter study included 96 patients (56±15 years, 72 male) with WPW syndrome and AF undergoing Kent bundle ablation. Some patients underwent simultaneous pulmonary vein isolation (PVI) for AF. The incidence of post-procedural AF was examined. Sixty-four patients underwent only Kent bundle ablation (Kent-only group) and 32 also underwent PVI (+PVI group). There was no significant difference in the basic patient characteristics between the groups. Additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p=0.53). In the Kent-only group, AF episodes remained in 25.0% during the follow-up (709 days). A univariate analysis showed that age ≥60 years, left atrial dimension ≥38mm, B-type natriuretic peptide (BNP) ≥40pg/ml, and concomitant hypertension were predictive factors for residual AF. However, in the multivariate analysis, only BNP ≥40pg/ml remained as an independent predictive factor (HR=17.1 and CI: 2.3-128.2; p=0.006). Among patients with WPW syndrome and AF, Kent bundle ablation alone may have a sufficient clinical impact of preventing recurrence of AF in select patients. Screening the BNP level would help decide the strategy to manage those patients. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Type III interferon is a critical regulator of innate antifungal immunity.

PubMed

Espinosa, Vanessa; Dutta, Orchi; McElrath, Constance; Du, Peicheng; Chang, Yun-Juan; Cicciarelli, Bryan; Pitler, Amy; Whitehead, Ian; Obar, Joshua J; Durbin, Joan E; Kotenko, Sergei V; Rivera, Amariliz

2017-10-06

Type III interferons (IFN-λs) are the most recently found members of the IFN cytokine family and engage IFNLR1 and IL10R2 receptor subunits to activate innate responses against viruses. We have identified IFN-λs as critical instructors of antifungal neutrophil responses. Using Aspergillus fumigatus ( Af ) as a model to study antifungal immune responses, we found that depletion of CCR2 + monocytes compromised the ability of neutrophils to control invasive fungal growth. Using an unbiased approach, we identified type I and III IFNs as critical regulators of the interplay between monocytes and neutrophils responding to Af We found that CCR2 + monocytes are an important early source of type I IFNs that prime optimal expression of IFN-λ. Type III IFNs act directly on neutrophils to activate their antifungal response, and mice with neutrophil-specific deletion of IFNLR1 succumb to invasive aspergillosis. Dysfunctional neutrophil responses in CCR2-depleted mice were rescued by adoptive transfer of pulmonary CCR2 + monocytes or by exogenous administration of IFN-α and IFN-λ. Thus, CCR2 + monocytes promote optimal activation of antifungal neutrophils by initiating a coordinated IFN response. We have identified type III IFNs as critical regulators of neutrophil activation and type I IFNs as early stimulators of IFN-λ expression. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Translation of an engineered nanofibrous disc-like angle-ply structure for intervertebral disc replacement in a small animal model.

PubMed

Martin, John T; Milby, Andrew H; Chiaro, Joseph A; Kim, Dong Hwa; Hebela, Nader M; Smith, Lachlan J; Elliott, Dawn M; Mauck, Robert L

2014-06-01

Intervertebral disc degeneration has been implicated in the etiology of low back pain; however, the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF) and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(ε-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, can achieve functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle-ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilized the motion segment via external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the peri-implant space and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Comparing the economic burden of ischemic stroke patients with and without atrial fibrillation: a retrospective study in Beijing, China.

PubMed

Wen, Liankui; Wu, Jingjing; Feng, Lin; Yang, Li; Qian, Feng

2017-10-01

Little is known about the economic burden for ischemic stroke (IS) patients with atrial fibrillation (AF) in China. We aimed to compare the economic burden of treatment-related costs in IS patients with AF vs. without AF in China. This retrospective analysis used economic burden data from the Beijing urban health insurance database. Using a random sampling method, 10% of the patients diagnosed with IS from 1 January through 31 December 2012 were enrolled. First hospitalization was considered as the index event and hospital utilization after the index event was followed up until September 2013. Overall healthcare cost during the study period was analyzed. In 4061 patients with IS (mean ± SD age, 68.45 ± 13.95 years; AF: 992; without AF: 3069), the AF group had a higher percentage of patients with co-morbidities at baseline. Compared with the non-AF group, the AF group had significantly greater hospitalization at the index event (p < .001). Overall inpatient cost per patient during the observational period (Renminbi (RMB) 141,875.9 ± 121,071.8 vs. RMB 53,834.03 ± 63,535.72, in 2012 terms), total healthcare cost per patient (RMB 163,550.4 ± 131,103.5 vs. RMB 64,735.41 ± 67,584.95), total healthcare cost covered by health insurance, and annualized total healthcare cost per patient were higher in the AF group than in the non-AF group (p < .001). Treatment costs were significantly associated with old age, male gender, AF, and frequency of outpatient visits and hospitalization. AF increased the use of healthcare resources, treatment cost, and economic burden in patients with IS. Therefore, prevention of cardio-embolic events in patients with AF by anticoagulants may decrease the economic burden in patients with IS.

Inflammation as a Mediator of the Association Between Race and Atrial Fibrillation: Results from the Health, Aging, and Body Composition Study

PubMed Central

Dewland, Thomas A.; Vittinghoff, Eric; Harris, Tamara B.; Magnani, Jared W.; Liu, Yongmei; Hsu, Fang-Chi; Satterfield, Suzanne; Wassel, Christina; Marcus, Gregory M.

2015-01-01

Background Despite a lower prevalence of established atrial fibrillation (AF) risk factors, Whites exhibit substantially higher rates of this arrhythmia compared to Blacks. The mechanism underlying this observation is not known. Both inflammation and obesity are risk factors for AF, and adipose tissue is a known contributor to systemic inflammation. Objectives We sought to determine the degree to which racial differences in AF risk are explained by differences in inflammation and adiposity. Methods Baseline serum inflammatory biomarker concentrations and abdominal adiposity (assessed by computed tomography) were quantified in a subset of Black and White participants without prevalent AF in the Health, Aging, and Body Composition (Health ABC) Study. Participants were prospectively followed for the diagnosis of AF using study ECGs and Medicare claims data. Cox proportional hazards models were used to determine the adjusted relative hazard of incident AF between races before and after biomarker adjustment. Results Among 2,768 participants (43% Black), 721 developed incident AF over a median follow up of 10.9 years. White race was associated with a heightened adjusted risk of incident AF (HR 1.55, 95% CI 1.30 to 1.84, p < 0.001). Abdominal adiposity was not associated with AF when added to the adjusted model. Among the studied biomarkers, adiponectin, TNF-α, TNF-α SR I, and TNF-α SR II concentrations were each higher among Whites and independently associated with a greater risk of incident AF. Together, these inflammatory cytokines mediated 42% (95% CI 15 to 119%, p = 0.004) of the adjusted race-AF association. Conclusions Systemic inflammatory pathways significantly mediate the heightened risk of AF among Whites. The higher level of systemic inflammation and concomitant increased AF risk in Whites is not explained by racial differences in abdominal adiposity or the presence of other pro-inflammatory cardiovascular comorbidities. PMID:26501131

Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study.

PubMed

Lowres, Nicole; Neubeck, Lis; Salkeld, Glenn; Krass, Ines; McLachlan, Andrew J; Redfern, Julie; Bennett, Alexandra A; Briffa, Tom; Bauman, Adrian; Martinez, Carlos; Wallenhorst, Christopher; Lau, Jerrett K; Brieger, David B; Sy, Raymond W; Freedman, S Ben

2014-06-01

Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ≥65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ≥2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be $AUD5,988 (€3,142; $USD4,066) per Quality Adjusted Life Year gained and $AUD30,481 (€15,993; $USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered.

Origin and ablation of the adenosine triphosphate induced atrial fibrillation after circumferential pulmonary vein isolation: effects on procedural success rate.

PubMed

Zhang, Jinlin; Tang, Cheng; Zhang, Yonghua; Su, X I

2014-04-01

Adenosine triphosphate (ATP) has been used to provoke dormant pulmonary vein (PV) conduction after circumferential PV isolation (CPVI). However, there have been no systematic studies examining the incidence and the mechanism of ATP-induced atrial fibrillation (AF) following CPVI in paroxysmal AF. In this study, we explore the mechanism of ATP-induced AF and assess the feasibility of eliminating this response by additional radiofrequency (RF) ablation. A total of 300 consecutive patients with paroxysmal AF underwent CPVI. After all PVs were isolated, intravenous ATP (40 mg) was administered during an intravenous isoproterenol (ISP) infusion (5 μg/min). AF was reproducibly induced by ATP in 39 patients. Non-PV foci were confirmed and located in 29 of these patients at the onset of AF, including 27 foci in the superior vena cava (SVC), 1 focus in the crista terminalis, and 1 focus near the antrum of the PV. In all these cases, ATP-induced AF was eliminated after the non-PV foci were successfully ablated. For the other 10 patients, the foci triggering AF could not be confirmed or located due to the transient effect of ATP, thus no further ablation was performed. After a mean follow-up period of 18.7 ± 6.4 (8-24) months, the success rate in the ATP-induced AF group was not significantly different compared with the conventional treatment group who did not exhibit ATP-induced AF (76.9% vs 67.3%; P = 0.25). But in the subgroup of which the ATP-induced AF could be eliminated by additional RF ablation, the success rate was significantly higher than the non-ATP inducible group (86.2% vs 67.3%; P = 0.04). A large proportion of the ATP-induced AF post CPVI were initiated by rapid firing in the SVC. Eliminating this response by additional ablation may have an influence on clinical results of paroxysmal AF ablation. © 2014 Wiley Periodicals, Inc.

Atrial fibrillation incrementally increases dementia risk across all CHADS2 and CHA2DS2VASc strata in patients receiving long-term warfarin.

PubMed

Graves, Kevin G; May, Heidi T; Jacobs, Victoria; Bair, Tami L; Stevens, Scott M; Woller, Scott C; Crandall, Brian G; Cutler, Michael J; Day, John D; Mallender, Charles; Osborn, Jeffrey S; Peter Weiss, J; Jared Bunch, T

2017-06-01

Patients with atrial fibrillation (AF) are at higher risk for developing dementia. Warfarin is a common therapy for the prevention of thromboembolism in AF, valve replacement, and thrombosis patients. The extent to which AF itself increases dementia risk remains unknown. A total 6030 patients with no history of dementia and chronically anticoagulated with warfarin were studied. Warfarin management was provided through a Clinical Pharmacy Anticoagulation Service. Patients were stratified by warfarin indication of AF (n=3015) and non-AF (n=3015) and matched by propensity score (±0.01). Patients were stratified by the congestive heart failure, hypertension, age >75 years, diabetes, stroke (CHADS 2 ) score calculated at the time of warfarin initiation and followed for incident dementia. The average age of the AF cohort was 69.3±11.2 years, and 52.7% were male; average age of non-AF cohort was 69.3±10.9 years, and 51.5% were male. Increasing CHADS 2 score was associated with increased dementia incidence, P trend=.004. When stratified by warfarin indication, AF patients had an increased risk of dementia incidence. After multivariable adjustment, AF patients continued to display a significantly increased risk of dementia when compared with non-AF patients across all CHADS 2 scores strata. In patients receiving long-term warfarin therapy, dementia risk increased with increasing CHADS 2 scores. However, the presence of AF was associated with higher rates of dementia across all CHADS 2 score strata. These data suggest that AF contributes to the risk of dementia and that this risk is not solely attributable to anticoagulant use. Dementia may be an end manifestation of a systemic disease state, and AF likely contributes to its progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Macular autofluorescence in eyes with cystoid macula edema, detected with 488 nm-excitation but not with 580 nm-excitation.

PubMed

Bessho, Kenichiro; Gomi, Fumi; Harino, Seiyo; Sawa, Miki; Sayanagi, Kaori; Tsujikawa, Motokazu; Tano, Yasuo

2009-06-01

Fundus autofluorescence (AF) derives from lipofuscin in the retinal pigment epithelium (RPE). Because lipofuscin is a by-product of phagocytosis of photoreceptors by RPE, AF imaging is expected to describe some functional aspect of the retina. In this study we report distribution of AF in patients showing macular edema. Three eyes with diabetic macular edema (DME) and 11 with retinal vein occlusion (RVO), associated with macular edema (ME) were examined. ME was determined by standard fundus examination, fluorescein angiography (FA) and optical coherence tomography (OCT). AF was recorded using a Heidelberg confocal scanning laser ophthalmoscope (cSLO) with 488 nm laser exciter (488 nm-AF), and a conventional Topcon fundus camera with halogen lamp exciter and 580 nm band-pass filter (580 nm-AF). Color fundus picture, FA image and these two AF images were analyzed by superimposing all images. All subjects presented cystoid macular edema (CME) with petaloid pattern hyperfluorescence in FA. In 488 nm-AF, all eyes (100%) showed macular autofluorescence of a similar shape to that of the CME in FA. In contrast, in 580 nm-AF only one eye (7%) presented this corresponding petaloid-shaped autofluorescence. In all cases, peripheral retinal edemas did not show autofluorescence corresponding to the leakage in FA. In eyes with CME, analogous hyperautofluorescence to the CME was always observed in 488 nm-AF, while it was rarely observed in 580 nm-AF. Moreover, this CME hyperautofluorescence was only seen in the macular area. We hypothesize that autofluorescence from CME may be considered as a "pseudo" or "relative" autofluorescence, due to macular stretching following CME that may result in lateral displacement of macular pigments (MPs) and subsequent reduction of MPs density, as MPs block 488 nm-AF more intensely than 580 nm-AF. Although this phenomenon may not directly indicate change of RPE function, it may be used as a method to assess or track CME non-invasively.

Wholly Patient-tailored Ablation of Atrial Fibrillation Guided by Spatio-Temporal Dispersion of Electrograms in the Absence of Pulmonary Veins Isolation

PubMed Central

Seitz, Julien; Bars, Clément; Théodore, Guillaume; Beurtheret, Sylvain; Lellouche, Nicolas; Bremondy, Michel; Ferracci, Ange; Faure, Jacques; Penaranda, Guillaume; Yamazaki, Masatoshi; Avula, Uma Mahesh R.; Curel, Laurence; Siame, Sabrina; Berenfeld, Omer; Pisapia, André; Kalifa, Jérôme

2017-01-01

Background The use of intra-cardiac electrograms to guide atrial fibrillation (AF) ablation has yielded conflicting results. We evaluated an electrogram marker of AF drivers: the clustering of electrograms exhibiting spatio-temporal dispersion — regardless of whether such electrograms were fractionated or not. Objective To evaluate the usefulness of spatio-temporal dispersion, a visually recognizable electric footprint of AF drivers, for the ablation of all forms of AF. Methods We prospectively enrolled 105 patients admitted for AF ablation. AF was sequentially mapped in both atria with a 20-pole PentaRay catheter. We tagged and ablated only regions displaying electrogram dispersion during AF. Results were compared to a validation set in which a conventional ablation approach was used (pulmonary vein isolation/stepwise approach). To establish the mechanism underlying spatio-temporal dispersion of AF electrograms, we conducted realistic numerical simulations of AF drivers in a 2-dimensional model and optical mapping of ovine atrial scar-related AF. Results Ablation at dispersion areas terminated AF in 95%. After ablation of 17±10% of the left atrial surface and 18 months of follow-up, the atrial arrhythmia recurrence rate was 15% after 1.4±0.5 procedure/patient vs 41% in the validation set after 1.5±0.5 procedure/patient (arrhythmia free-survival rates: 85% vs 59%, log rank P<0.001). In comparison with the validation set, radiofrequency times (49 ± 21 minutes vs 85 ± 34.5 minutes, p=0.001) and procedure times (168 ± 42 minutes vs. 230 ± 67 minutes, p<.0001) were shorter. In simulations and optical mapping experiments, virtual PentaRay recordings demonstrated that electrogram dispersion is mostly recorded in the vicinity of a driver. Conclusions The clustering of intra-cardiac electrograms exhibiting spatio-temporal dispersion is indicative of AF drivers. Their ablation allows for a non-extensive and patient-tailored approach to AF ablation. Clinical trial.gov number: NCT02093949 PMID:28104073

Atrial fibrillation in patients with Wolff-Parkinson-White syndrome: role of pulmonary veins.

PubMed

Derejko, Paweł; Szumowski, Lukasz Jan; Sanders, Prashanthan; Krupa, Wojciech; Bodalski, Robert; Orczykowski, Michał; Urbanek, Piotr; Zakrzewska, Joanna; Lim, Han S; Lau, Dennis H; Kuśnierz, Jacek; Walczak, Franciszek

2012-03-01

We aimed to characterize electrophysiological properties of pulmonary veins (PVs) in patients with Wolff-Parkinson-White (WPW) syndrome and atrial fibrillation (AF), and to compare them to those in patients with WPW without AF. A total of 31 patients (mean age 40 ± 15 years, 23 males) with WPW were recruited: 16 patients with (AF group) and 15 without (controls) a history of AF. The basic electrophysiological (EPS) and echocardiographic data were not different between the 2 groups. Effective refractory periods (ERPs) of PVs were significantly shorter in the AF group compared to controls: left superior (LS) PV ERP 185±29 versus 230 ± 24 ms, P = 0.001; left inferior PV ERP 198 ± 25 versus 219 ± 26 ms, P = 0.04; right superior (RS) PV ERP 207 ± 25 versus 236 ± 19 ms, P = 0.001; right inferior PV ERP 208 ± 30 versus 240 ± 19 ms, P = 0.003. Maximal veno-atrial conduction delay (i.e., the maximal prolongation of interval from stimulus delivered at PV ostia to proximal coronary sinus after extrastimulus compared to the basic drive cycle) was longer in the AF group when pacing from LSPV (69.3 ± 37.9 vs 32.6 ± 16.1 ms, P = 0.01) and RSPV (74.1 ± 25.9 vs 50.2 ± 26.5 ms, P = 0.04). During EPS, AF was induced more often in the AF group (n = 7) compared to controls (n = 1; P = 0.04). Follow-up revealed that AF recurred in 3 patients in the AF group and none of the controls. Patients with WPW syndrome and AF have shorter ERPs of PVs and greater maximal veno-atrial conduction delay compared to patients with WPW without AF. These findings suggest a potential role of PVs in the development of AF in patients with WPW. © 2011 Wiley Periodicals, Inc.

Baseline Demographics, Safety, and Patient Acceptance of an Insertable Cardiac Monitor for Atrial Fibrillation Screening: The REVEAL-AF Study.

PubMed

Conti, Sergio; Reiffel, James A; Gersh, Bernard J; Kowey, Peter R; Wachter, Rolf; Halperin, Jonathan L; Kaplon, Rachelle E; Pouliot, Erika; Verma, Atul

2017-01-01

Given the high prevalence and risk of stroke associated with atrial fibrillation (AF), detection strategies have important public health implications. The ongoing prospective, single-arm, open-label, multicenter REVEAL AF trial is evaluating the incidence of previously undetected AF using an insertable cardiac monitor (ICM) in patients without prior AF or device implantation, but who could be at risk for AF due to their demographic characteristics, +/- non-specific but compatible symptoms. Enrollment required an elevated AF risk profile defined as CHADS2≥3 or CHADS 2 =2 plus one or more of the following: coronary artery disease, renal impairment, sleep apnea or chronic obstructive pulmonary disease. Exclusions included stroke or transient ischemic attack occurring in the previous year. Of 450 subjects screened, 399 underwent a device insertion attempt, and 395 were included in the final analysis (Reveal XT: n=122; Reveal LINQ: n=273; excluded: n=4). Participants were primarily identified by demographic characteristics and the presence of nonspecific symptoms, but without prior documentation of "overt" AF. The most common symptoms were palpitations (51%), dizziness/lightheadedness/pre-syncope (36%), and shortness of breath (36%). Over 100 subjects were enrolled in each pre-defined CHADS2 subgroup (2, 3 and ≥4). AF risk factors not included in the CHADS2 score were well represented (prevalence≥15%). Procedure and/or device related serious adverse events were low, with the miniaturized Reveal LINQ ICM having a more favorable safety profile than the predicate Reveal XT (all: n=13 [3.3%]; LINQ: n=6 [2.2%]; XT: n=7 [5.7%]). These data demonstrate that REVEAL AF was successful in enrolling its target population, high risk patients were willing to undergo ICM monitoring for AF screening, and ICM use in this group is becoming increasingly safe with advancements in technology. A clinically meaningful incidence of device detected AF in this study will inform clinical decisions regarding ICM use for AF screening in patients at risk.

Cloning and characterization of two duplicated interleukin-17A/F2 genes in common carp (Cyprinus carpio L.): Transcripts expression and bioactivity of recombinant IL-17A/F2.

PubMed

Li, Hongxia; Yu, Juhua; Li, Jianlin; Tang, Yongkai; Yu, Fan; Zhou, Jie; Yu, Wenjuan

2016-04-01

Interleukin-17 (IL-17) plays an important role in inflammation and host defense in mammals. In this study, we identified two duplicated IL-17A/F2 genes in the common carp (Cyprinus carpio) (ccIL-17A/F2a and ccIL-17A/F2b), putative encoded proteins contain 140 amino acids (aa) with conserved IL-17 family motifs. Expression analysis revealed high constitutive expression of ccIL-17A/F2s in mucosal tissues, including gill, skin and intestine, their expression could be induced by Aeromonas hydrophila, suggesting a potential role in mucosal immunity. Recombinant ccIL-17A/F2a protein (rccIL-17A/F2a) produced in Escherichia coli could induce the expression of proinflammatory cytokines (IL-1β) and the antimicrobial peptides S100A1, S100A10a and S100A10b in the primary kidney in a dose- and time-dependent manner. Above findings suggest that ccIL-17A/F2 plays an important role in both proinflammatory and innate immunity. Two duplicated ccIL-17A/F2s showed different expression level with ccIL-17A/F2a higher than b, comparison of two 5' regulatory regions indicated the length from anticipated promoter to transcriptional start site (TSS) and putative transcription factor binding site (TFBS) were different. Promoter activity of ccIL-17A/F2a was 2.5 times of ccIL-17A/F2b which consistent with expression results of two genes. These suggest mutations in 5'regulatory region contributed to the differentiation of duplicated genes. To our knowledge, this is the first report to analyze 5'regulatory region of piscine IL-17 family genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hybrid Rigid-Deformable Model for Prediction of Neighboring Intervertebral Disk Loads During Flexion Movement After Lumbar Interbody Fusion at L3-4 Level.

PubMed

Tuan Dao, Tien

2017-03-01

Knowledge of spinal loads in neighboring disks after interbody fusion plays an important role in the clinical decision of this treatment as well as in the elucidation of its effect. However, controversial findings are still noted in the literature. Moreover, there are no existing models for efficient prediction of intervertebral disk stresses within annulus fibrosus (AF) and nucleus pulposus (NP) regions. In this present study, a new hybrid rigid-deformable modeling workflow was established to quantify the mechanical stress behaviors within AF and NP regions of the L1-2, L2-3, and L4-5 disks after interbody fusion at L3-4 level. The changes in spinal loads were compared with results of the intact model without interbody fusion. The fusion outcomes revealed maximal stress changes (10%) in AF region of L1-2 disk and in NP region of L2-3 disk. The minimal stress change (1%) is noted at the NP region of the L1-2 disk. The validation of simulation outcomes of fused and intact lumbar spine models against those of other computational models and in vivo measurements showed good agreements. Thus, this present study may be used as a novel design guideline for a specific implant and surgical scenario of the lumbar spine disorders.

Microbial species delineation using whole genome sequences.

PubMed

Varghese, Neha J; Mukherjee, Supratim; Ivanova, Natalia; Konstantinidis, Konstantinos T; Mavrommatis, Kostas; Kyrpides, Nikos C; Pati, Amrita

2015-08-18

Increased sequencing of microbial genomes has revealed that prevailing prokaryotic species assignments can be inconsistent with whole genome information for a significant number of species. The long-standing need for a systematic and scalable species assignment technique can be met by the genome-wide Average Nucleotide Identity (gANI) metric, which is widely acknowledged as a robust measure of genomic relatedness. In this work, we demonstrate that the combination of gANI and the alignment fraction (AF) between two genomes accurately reflects their genomic relatedness. We introduce an efficient implementation of AF,gANI and discuss its successful application to 86.5M genome pairs between 13,151 prokaryotic genomes assigned to 3032 species. Subsequently, by comparing the genome clusters obtained from complete linkage clustering of these pairs to existing taxonomy, we observed that nearly 18% of all prokaryotic species suffer from anomalies in species definition. Our results can be used to explore central questions such as whether microorganisms form a continuum of genetic diversity or distinct species represented by distinct genetic signatures. We propose that this precise and objective AF,gANI-based species definition: the MiSI (Microbial Species Identifier) method, be used to address previous inconsistencies in species classification and as the primary guide for new taxonomic species assignment, supplemented by the traditional polyphasic approach, as required. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Systems Biology Graphical Notation: Activity Flow language Level 1 Version 1.2.

PubMed

Mi, Huaiyu; Schreiber, Falk; Moodie, Stuart; Czauderna, Tobias; Demir, Emek; Haw, Robin; Luna, Augustin; Le Novère, Nicolas; Sorokin, Anatoly; Villéger, Alice

2015-09-04

The Systems Biological Graphical Notation (SBGN) is an international community effort for standardized graphical representations of biological pathways and networks. The goal of SBGN is to provide unambiguous pathway and network maps for readers with different scientific backgrounds as well as to support efficient and accurate exchange of biological knowledge between different research communities, industry, and other players in systems biology. Three SBGN languages, Process Description (PD), Entity Relationship (ER) and Activity Flow (AF), allow for the representation of different aspects of biological and biochemical systems at different levels of detail. The SBGN Activity Flow language represents the influences of activities among various entities within a network. Unlike SBGN PD and ER that focus on the entities and their relationships with others, SBGN AF puts the emphasis on the functions (or activities) performed by the entities, and their effects to the functions of the same or other entities. The nodes (elements) describe the biological activities of the entities, such as protein kinase activity, binding activity or receptor activity, which can be easily mapped to Gene Ontology molecular function terms. The edges (connections) provide descriptions of relationships (or influences) between the activities, e.g., positive influence and negative influence. Among all three languages of SBGN, AF is the closest to signaling pathways in biological literature and textbooks, but its well-defined semantics offer a superior precision in expressing biological knowledge.

Mini-review: Inhibition of biofouling by marine microorganisms.

PubMed

Dobretsov, Sergey; Abed, Raeid M M; Teplitski, Max

2013-01-01

Any natural or artificial substratum exposed to seawater is quickly fouled by marine microorganisms and later by macrofouling species. Microfouling organisms on the surface of a substratum form heterogenic biofilms, which are composed of multiple species of heterotrophic bacteria, cyanobacteria, diatoms, protozoa and fungi. Biofilms on artificial structures create serious problems for industries worldwide, with effects including an increase in drag force and metal corrosion as well as a reduction in heat transfer efficiency. Additionally, microorganisms produce chemical compounds that may induce or inhibit settlement and growth of other fouling organisms. Since the last review by the first author on inhibition of biofouling by marine microbes in 2006, significant progress has been made in the field. Several antimicrobial, antialgal and antilarval compounds have been isolated from heterotrophic marine bacteria, cyanobacteria and fungi. Some of these compounds have multiple bioactivities. Microorganisms are able to disrupt biofilms by inhibition of bacterial signalling and production of enzymes that degrade bacterial signals and polymers. Epibiotic microorganisms associated with marine algae and invertebrates have a high antifouling (AF) potential, which can be used to solve biofouling problems in industry. However, more information about the production of AF compounds by marine microorganisms in situ and their mechanisms of action needs to be obtained. This review focuses on the AF activity of marine heterotrophic bacteria, cyanobacteria and fungi and covers publications from 2006 up to the end of 2012.

Plasma Heating inside ICMEs by Alfvenic Fluctuations Dissipation

NASA Astrophysics Data System (ADS)

Li, H.; Wang, C.; He, J.; Zhang, L.; Richardson, J. D.; Belcher, J. W.; Tu, C.

2017-12-01

Nonlinear cascade of low-frequency Alfvenic fluctuations (AFs) is regarded as one of the candidate energy sources that heat plasma during the non-adiabatic expansion of interplanetary coronal mass ejections (ICMEs). However, AFs inside ICMEs were seldom reported in the literature. In this study, we investigate AFs inside ICMEs using observations from Voyager 2 between 1 and 6 au. It has been found that AFs with a high degree of Alfvenicity frequently occurred inside ICMEs for almost all of the identified ICMEs (30 out of 33 ICMEs) and for 12.6% of the ICME time interval. As ICMEs expand and move outward, the percentage of AF duration decays linearly in general. The occurrence rate of AFs inside ICMEs is much less than that in ambient solar wind, especially within 4.75 au. AFs inside ICMEs are more frequently presented in the center and at the boundaries of ICMEs. In addition, the proton temperature inside ICME has a similar "W"-shaped distribution. These findings suggest significant contribution of AFs on local plasma heating inside ICMEs.

Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options—a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference

PubMed Central

Kirchhof, Paulus; Lip, Gregory Y.H.; Van Gelder, Isabelle C.; Bax, Jeroen; Hylek, Elaine; Kaab, Stefan; Schotten, Ulrich; Wegscheider, Karl; Boriani, Giuseppe; Brandes, Axel; Ezekowitz, Michael; Diener, Hans; Haegeli, Laurent; Heidbuchel, Hein; Lane, Deirdre; Mont, Luis; Willems, Stephan; Dorian, Paul; Aunes-Jansson, Maria; Blomstrom-Lundqvist, Carina; Borentain, Maria; Breitenstein, Stefanie; Brueckmann, Martina; Cater, Nilo; Clemens, Andreas; Dobrev, Dobromir; Dubner, Sergio; Edvardsson, Nils G.; Friberg, Leif; Goette, Andreas; Gulizia, Michele; Hatala, Robert; Horwood, Jenny; Szumowski, Lukas; Kappenberger, Lukas; Kautzner, Josef; Leute, Angelika; Lobban, Trudie; Meyer, Ralf; Millerhagen, Jay; Morgan, John; Muenzel, Felix; Nabauer, Michael; Baertels, Christoph; Oeff, Michael; Paar, Dieter; Polifka, Juergen; Ravens, Ursula; Rosin, Ludger; Stegink, W.; Steinbeck, Gerhard; Vardas, Panos; Vincent, Alphons; Walter, Maureen; Breithardt, Günter; Camm, A. John

2012-01-01

While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. PMID:21791573

Presence and transcriptional activity of anaerobic fungi in agricultural biogas plants.

PubMed

Dollhofer, Veronika; Callaghan, Tony M; Griffith, Gareth W; Lebuhn, Michael; Bauer, Johann

2017-07-01

Bioaugmentation with anaerobic fungi (AF) is promising for improved biogas generation from lignocelluloses-rich substrates. However, before implementing AF into biogas processes it is necessary to investigate their natural occurrence, community structure and transcriptional activity in agricultural biogas plants. Thus, AF were detected with three specific PCR based methods: (i) Copies of their 18S genes were found in 7 of 10 biogas plants. (ii) Transcripts of a GH5 endoglucanase gene were present at low level in two digesters, indicating transcriptional cellulolytic activity of AF. (iii) Phylogeny of the AF-community was inferred with the 28S gene. A new Piromyces species was isolated from a PCR-positive digester. Evidence for AF was only found in biogas plants operated with high proportions of animal feces. Thus, AF were most likely transferred into digesters with animal derived substrates. Additionally, high process temperatures in combination with long retention times seemed to impede AF survival and activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Stressors and Coping Strategies of Older Adults With Persistent Atrial Fibrillation Prior to and Following Direct Current Cardioversion.

PubMed

Rush, Kathy L; Hatt, Linda; Shay, Matt; Gorman, Nicole; Laberge, Carol G; Reid, R Colin; Wilson, Ryan

2017-09-01

The purpose of this study was to explore the stressors and coping strategies of older adults with persistent atrial fibrillation (AF) before and after direct current cardioversion. The study used a qualitative descriptive design. Sixteen patients were recruited through an AF clinic to participate in individual interviews prior to the cardioversion and at 6 and 12 weeks post procedure. Pre-cardioversion, older adults experienced symptom and health care-related stressors superimposed on existing non-AF stressors. They used a range of emotion and problem-focused coping. Non-AF stressors increased post procedure at the same time that participants perceived less need for coping strategies with a return to regular rhythm. There was a shift from AF to non-AF related stressors following the cardioversion but a decrease in coping strategies. Older adults with AF should be encouraged to maintain use of coping strategies to manage ongoing stress and reduce the risk of AF recurrence.

Associations of Lipoprotein(a) Levels With Incident Atrial Fibrillation and Ischemic Stroke: The ARIC (Atherosclerosis Risk in Communities) Study.

PubMed

Aronis, Konstantinos N; Zhao, Di; Hoogeveen, Ron C; Alonso, Alvaro; Ballantyne, Christie M; Guallar, Eliseo; Jones, Steven R; Martin, Seth S; Nazarian, Saman; Steffen, Brian T; Virani, Salim S; Michos, Erin D

2017-12-15

Lipoprotein(a) (Lp[a]) is proatherosclerotic and prothrombotic, causally related to coronary disease, and associated with other cardiovascular diseases. The association of Lp(a) with incident atrial fibrillation (AF) and with ischemic stroke among individuals with AF remains to be elucidated. In the community-based ARIC (Atherosclerosis Risk in Communities) study cohort, Lp(a) levels were measured by a Denka Seiken assay at visit 4 (1996-1998). We used multivariable-adjusted Cox models to compare AF and ischemic stroke risk across Lp(a) levels. First, we evaluated incident AF in 9908 participants free of AF at baseline. AF was ascertained by electrocardiography at study visits, hospital International Statistical Classification of Diseases, 9th Revision ( ICD-9 ) codes, and death certificates. We then evaluated incident ischemic stroke in 10 127 participants free of stroke at baseline. Stroke was identified by annual phone calls, hospital ICD-9 Revision codes, and death certificates. The baseline age was 62.7±5.6 years. Median Lp(a) levels were 13.3 mg/dL (interquartile range, 5.2-39.7 mg/dL). Median follow-up was 13.9 and 15.8 years for AF and stroke, respectively. Lp(a) was not associated with incident AF (hazard ratio, 0.98; 95% confidence interval, 0.82-1.17), comparing those with Lp(a) ≥50 with those with Lp(a) <10 mg/dL. High Lp(a) was associated with a 42% relative increase in stroke risk among participants without AF (hazard ratio, 1.42; 95% confidence interval, 1.07-1.90) but not in those with AF (hazard ratio, 1.06; 95% confidence interval, 0.70-1.61 [ P interaction for AF=0.25]). There were no interactions by race or sex. No association was found for cardioembolic stroke subtype. High Lp(a) levels were not associated with incident AF. Lp(a) levels were associated with increased ischemic stroke risk, primarily among individuals without AF but not in those with AF. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Study protocol for Smartphone Monitoring for Atrial fibrillation in Real-Time in India (SMART-India): a community-based screening and referral programme.

PubMed

Soni, Apurv; Karna, Sunil; Patel, Harshil; Fahey, Nisha; Raithatha, Shyamsundar; Handorf, Anna; Bostrom, John; Bashar, Syed; Talati, Kandarp; Shah, Ravi; Goldberg, Robert J; Thanvi, Sunil; Phatak, Ajay Gajanan; Allison, Jeroan J; Chon, Ki; Nimbalkar, Somashekhar Marutirao; McManus, David D

2017-12-14

Atrial fibrillation (AF), the world's most common arrhythmia, often goes undetected and untreated in low-resource communities, including India, where AF epidemiology is undefined. AF is an important risk factor for stroke, which plagues an estimated 1.6 million Indians annually. As such, early detection of AF and management of high-risk patients is critically important to decrease stroke burden in individuals with AF. This study aims to describe the epidemiology of AF in Anand District, Gujarat, India, characterise the clinical profile of individuals who are diagnosed with AF and determine the performance of two mobile technologies for community-based AF screening. This observational study builds on findings from a previous feasibility study and leverages two novel technologies as well as an existing community health programme to perform door-to-door AF screening for 2000 people from 60 villages of Anand District, Gujarat, India using local health workers. A single-lead ECG and a pulse-based application is used to screen each individual for AF three times over a period of 5 days. Participants with suspected arrhythmias are followed up by study cardiologist who makes final diagnoses. Participants diagnosed with AF are initiated on treatment based on current anticoagulation guidelines and clinical reasoning. Age-stratified and sex-stratified prevalence of AF in the Anand District will be calculated for sample and estimated for Anand distribution using survey design weights. Sociodemographic and clinical factors associated with AF will be evaluated using multivariable regression methods. Performance of each mobile technology in detecting AF will be evaluated using a 12-lead ECG interpretation as the gold standard. This protocol was approved separately by the Institutional Review Board of University of Massachusetts Medical School and the Human Research Ethics Committee at Charutar Arogya Mandal. The findings of this study will be disseminated through peer-reviewed journals and scientific conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Comparison of resource utilization of pulmonary vein isolation: cryoablation versus RF ablation with three-dimensional mapping in the Value PVI Study.

PubMed

DeVille, J Brian; Svinarich, J Thomas; Dan, Dan; Wickliffe, Andrew; Kantipudi, Charan; Lim, Hae W; Plummer, Lisa; Baker, James; Kowalski, Marcin; Baydoun, Hassan; Jenkins, Mark; Chang-Sing, Peter

2014-06-01

Point-to-point focal radiofrequency (RF) catheter ablation for aberrant pulmonary vein triggers that manifest into atrial fibrillation (AF) is the traditional method for treating symptomatic drug-resistant paroxysmal AF (PAF) when an ablation procedure is warranted. More recently, pulmonary vein isolation (PVI) using the cryoballoon has been demonstrated to be safe and effective (STOP AF clinical trial). Currently, two small studies have reviewed the procedural efficiency when comparing cryoballoon to focal RF catheter ablation procedures; however, no multicenter study has yet reported on this comparison of the two types of ablation catheters. A multicenter retrospective chart extraction and evaluation was conducted at seven geographically mixed cardiac care centers. The study examined procedural variables during ablation for PVI in PAF patients. In several procedural measurements, the two modalities were comparable in efficiencies, including: acute PVI >96%; length of hospital stay at approximately 27 hours; and about 30% usage of adenosine after procedural testing. However, when compared to RF catheters, the cryoballoon procedure demonstrated a 13% reduction in laboratory occupancy time (247 min vs 283 min), a 13% reduction in procedure time (174 min vs 200 min), and a 21% reduction in fluoroscopy time (33 min vs 42 min). Additionally, when comparing the material usage of both cryoballoon and RF catheters, the cryoballoon used more radiopaque contrast agent (78 cc vs 29 cc) while using less intraprocedural saline (1234 cc vs 2386 cc), intracardiac echocardiography (88% vs 99%), three-dimensional electroanatomic mapping (30% vs 87%), and fewer transseptal punctures (1.5 vs 1.9). This study is the first United States multicenter examination to report the procedural comparisons between the cryoballoon and focal RF catheters when used for the treatment of PAF patients. In this hospital chart review study, potential advantages were found when operating the cryoballoon with regard to hospital resource allocation. There was no statistical difference between cryoballoon and RF catheters for acute PVI success during the ablation procedure.

Perturbation of Chromatin Structure Globally Affects Localization and Recruitment of Splicing Factors

PubMed Central

Risso, Guillermo J.; Pawellek, Andrea; Ule, Jernej; Lamond, Angus I.; Kornblihtt, Alberto R.

2012-01-01

Chromatin structure is an important factor in the functional coupling between transcription and mRNA processing, not only by regulating alternative splicing events, but also by contributing to exon recognition during constitutive splicing. We observed that depolarization of neuroblastoma cell membrane potential, which triggers general histone acetylation and regulates alternative splicing, causes a concentration of SR proteins in nuclear speckles. This prompted us to analyze the effect of chromatin structure on splicing factor distribution and dynamics. Here, we show that induction of histone hyper-acetylation results in the accumulation in speckles of multiple splicing factors in different cell types. In addition, a similar effect is observed after depletion of the heterochromatic protein HP1α, associated with repressive chromatin. We used advanced imaging approaches to analyze in detail both the structural organization of the speckle compartment and nuclear distribution of splicing factors, as well as studying direct interactions between splicing factors and their association with chromatin in vivo. The results support a model where perturbation of normal chromatin structure decreases the recruitment efficiency of splicing factors to nascent RNAs, thus causing their accumulation in speckles, which buffer the amount of free molecules in the nucleoplasm. To test this, we analyzed the recruitment of the general splicing factor U2AF65 to nascent RNAs by iCLIP technique, as a way to monitor early spliceosome assembly. We demonstrate that indeed histone hyper-acetylation decreases recruitment of U2AF65 to bulk 3′ splice sites, coincident with the change in its localization. In addition, prior to the maximum accumulation in speckles, ∼20% of genes already show a tendency to decreased binding, while U2AF65 seems to increase its binding to the speckle-located ncRNA MALAT1. All together, the combined imaging and biochemical approaches support a model where chromatin structure is essential for efficient co-transcriptional recruitment of general and regulatory splicing factors to pre-mRNA. PMID:23152763

Comprehensive Mutation Scanning of LMNA in 268 Patients With Lone Atrial Fibrillation

PubMed Central

Brauch, Katharine M.; Chen, Lin Y.; Olson, Timothy M.

2009-01-01

Atrial fibrillation (AF) is a heritable, genetically heterogeneous disorder. To identify gene defects that cause or confer susceptibility to AF, a cohort of 268 unrelated patients with idiopathic forms of familial and sporadic AF was recruited. LMNA, encoding the nuclear membrane proteins, lamin A/C, was selected as a candidate gene for lone AF based on its established association with a syndrome of dilated cardiomyopathy, conduction system disease, and AF. Comprehensive mutation scanning identified only 1 potentially pathogenic mutation. In conclusion, LMNA mutations rarely cause lone AF and routine genetic testing of LMNA in these patients does not appear warranted. PMID:19427440

Oxidized CaMKII Triggers Atrial Fibrillation

PubMed Central

Purohit, Anil; Rokita, Adam G.; Guan, Xiaoqun; Chen, Biyi; Koval, Olha M.; Voigt, Niels; Neef, Stefan; Sowa, Thomas; Gao, Zhan; Luczak, Elizabeth D.; Stefansdottir, Hrafnhildur; Behunin, Andrew C.; Li, Na; El-Accaoui, Ramzi N.; Yang, Baoli; Swaminathan, Paari Dominic; Weiss, Robert M.; Wehrens, Xander H.T.; Song, Long-Sheng; Dobrev, Dobromir; Maier, Lars S.; Anderson, Mark E.

2013-01-01

Background Atrial fibrillation is a growing public health problem without adequate therapies. Angiotensin II (Ang II) and reactive oxygen species (ROS) are validated risk factors for atrial fibrillation (AF) in patients, but the molecular pathway(s) connecting ROS and AF is unknown. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) has recently emerged as a ROS activated proarrhythmic signal, so we hypothesized that oxidized CaMKIIδ(ox-CaMKII) could contribute to AF. Methods and Results We found ox-CaMKII was increased in atria from AF patients compared to patients in sinus rhythm and from mice infused with Ang II compared with saline. Ang II treated mice had increased susceptibility to AF compared to saline treated WT mice, establishing Ang II as a risk factor for AF in mice. Knock in mice lacking critical oxidation sites in CaMKIIδ (MM-VV) and mice with myocardial-restricted transgenic over-expression of methionine sulfoxide reductase A (MsrA TG), an enzyme that reduces ox-CaMKII, were resistant to AF induction after Ang II infusion. Conclusions Our studies suggest that CaMKII is a molecular signal that couples increased ROS with AF and that therapeutic strategies to decrease ox-CaMKII may prevent or reduce AF. PMID:24030498

Health Literacy and Atrial Fibrillation: Relevance and Future Directions for Patient-centred Care.

PubMed

Aronis, Konstantinos N; Edgar, Brittany; Lin, Wendy; Martins, Maria Auxiliadora Parreiras; Paasche-Orlow, Michael K; Magnani, Jared W

2017-01-01

Atrial fibrillation (AF) is a common cardiac arrhythmia with significant clinical outcomes, and is associated with high medical and social costs. AF is complicated for patients because of its specialised terminology, long-term adherence, symptom monitoring, referral to specialty care, array of potential interventions and potential for adversity. Health literacy is a frequently under-recognised, yet fundamental, component towards successful care in AF. Health literacy is defined as the capacity to obtain, process and understand health information, and has had markedly limited study in AF. However, health literacy could contribute to how patients interpret symptoms, navigate care, and participate in treatment evaluation and decision-making. This review aims to summarise the clinical importance and essential relevance of health literacy in AF. We focus here on central aspects of AF care that are most related to self-care, including understanding the symptoms of AF, shared decision-making, adherence and anticoagulation for stroke prevention. We discuss opportunities to enhance AF care based on findings from the literature on health literacy, and identify important gaps. Our overall objective is to articulate the importance and relevance of integrating health literacy in the care of individuals with AF.

Origin and Evolution of the Sponge Aggregation Factor Gene Family

PubMed Central

Grice, Laura F.; Gauthier, Marie E.A.; Roper, Kathrein E.; Fernàndez-Busquets, Xavier; Degnan, Sandie M.

2017-01-01

Although discriminating self from nonself is a cardinal animal trait, metazoan allorecognition genes do not appear to be homologous. Here, we characterize the Aggregation Factor (AF) gene family, which encodes putative allorecognition factors in the demosponge Amphimedon queenslandica, and trace its evolution across 24 sponge (Porifera) species. The AF locus in Amphimedon is comprised of a cluster of five similar genes that encode Calx-beta and Von Willebrand domains and a newly defined Wreath domain, and are highly polymorphic. Further AF variance appears to be generated through individualistic patterns of RNA editing. The AF gene family varies between poriferans, with protein sequences and domains diagnostic of the AF family being present in Amphimedon and other demosponges, but absent from other sponge classes. Within the demosponges, AFs vary widely with no two species having the same AF repertoire or domain organization. The evolution of AFs suggests that their diversification occurs via high allelism, and the continual and rapid gain, loss and shuffling of domains over evolutionary time. Given the marked differences in metazoan allorecognition genes, we propose the rapid evolution of AFs in sponges provides a model for understanding the extensive diversification of self–nonself recognition systems in the animal kingdom. PMID:28104746

Thromboembolic event rate in paroxysmal and persistent atrial fibrillation: Data from the GISSI-AF trial

PubMed Central

2013-01-01

Background Few data on the thromboembolic (TE) risk of paroxysmal and persistent atrial fibrillation (AF) are available. This study aimed to assess the incidence of TE events in paroxysmal and persistent AF. Methods We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter, prospective, randomized, double-blind, placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences – where the choice of antithrombotic treatment was left to the judgment of the referring physician. TE and major outcome events were centrally validated. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions. Results Eighty-five percent of patients had a history of hypertension, and the 7.7% had heart failure, left ventricular dysfunction, or both. The mean CHADS2 score was 1.41±0.84. TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up (0.97% and 0.81%, respectively). The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE, major bleeding events or mortality in paroxysmal and persistent AF patients. TE events were more common among women than men (p=0.02). The follow-up examination showed under- or overtreatment with warfarin in many patients, according to guideline suggestions. Warfarin was more frequently prescribed to patients with persistent AF (p<0.0001) and patients with AF recurrences (p<0.0001). AF recurrences were noninvasively detected in 632 (51.2%) patients. In patients without AF recurrences, the TE event rate was 0.5% versus 1.74%, 1.28%, and 1.18% for those with only symptomatic, only asymptomatic or both symptomatic and asymptomatic AF recurrences, respectively, but the difference was not statistically significant, even after adjusting for warfarin treatment and the CHADS2 score (HR 2.93; CI 95%; 0.8-10.9; p=0.11). Conclusions TE and major bleeding events showed a very low incidence in the GISSI-AF trial population, despite under- or overtreatment with warfarin in many patients. TE events had a similar rate in paroxysmal and persistent AF. Trial registration Trial registration number: NCT00376272 PMID:23586654

Increased liver uptake of liposomes and improved targeting efficacy by labeling with asialofetuin in rodents.

PubMed

Wu, J; Liu, P; Zhu, J L; Maddukuri, S; Zern, M A

1998-03-01

To improve liposome-directed therapy of liver disease and gene delivery, it would be beneficial to selectively target hepatocytes. For this purpose, conventional liposomes (CL) were labeled with asialofetuin (AF), an asialoglycoprotein. The biodistribution of AF-labeled liposomes (AF-L) in mice and their incorporation into rat hepatocytes, and their potential use in acute liver injury, were investigated. AF-L displayed a quicker plasma clearance than CL, and 25.4%, 2.7%, and 1.2% of the injected dose remained in the plasma versus 47.0%, 26.1%, and 9.5% of CL, respectively at 2, 4, and 20 hours after the injection. Total liver uptake of AF-L (73%+/-3.9%) was markedly higher (P < .005) than CL (16.5%+/-1.8%) 4 hours after the injection. Liposomal radioactivity (cpm/mg) was greatly enhanced in the liver (11-fold) during the first 4 hours after the administration of 14C-AF-L, and was much higher than in 14C-CL-injected mice (1.5-fold). In vitro incubation of isolated rat hepatocytes with 14C-AF-L or intravenous injection of 14C-AF-L in rats resulted in higher hepatocyte-bound radioactivity compared with 14C-CL (P < .01-.005). AF-L-associated 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) fluorescent signals were not only located in Kupffer cells, but also in hepatocytes, in which bile canaliculus networks were imaged. Intravenous administration of vitamin E (VE)-associated CL (VE-CL, 1 mg/mouse) significantly lowered alanine transaminase (ALT) levels in CCl4-treated mice (196+/-79 vs. 2,107+/-235 U/mL; P < .01). The ALT level in CCl4 + VE-AF-L group was decreased to 38+/-16 units/mL, which was significantly lower than the CC14 + VE-CL group (P < .05). In conclusion, labeling liposomes with AF led to a shortened liposome plasma half-life and greatly enhanced uptake of AF-L liposome by the liver. The enhanced uptake resulted from an increased incorporation of hepatocytes with AF-L liposomes. VE-associated AF liposomes further improved the protective effect of VE liposomes on CC14-induced acute liver injury in mice. Preferential hepatocyte incorporation of AF-L liposomes suggests a useful hepatocyte-targeting approach for drug delivery and gene transfection.

A computer-aided differential diagnosis between UIP and NSIP using automated assessment of the extent and distribution of regional disease patterns at HRCT: comparison with the radiologist's decision

NASA Astrophysics Data System (ADS)

Kim, Namkug; Seo, Joon Beom; Park, Sang Ok; Lee, Youngjoo; Lee, Jeongjin

2009-02-01

To evaluate the accuracy of computer aided differential diagnosis (CADD) between usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP) at HRCT in comparison with that of a radiologist's decision. A computerized classification for six local disease patterns (normal, NL; ground-glass opacity, GGO; reticular opacity, RO; honeycombing, HC; emphysema, EM; and consolidation, CON) using texture/shape analyses and a SVM classifier at HRCT was used for pixel-by-pixel labeling on the whole lung area. The mode filter was applied on the results to reduce noise. Area fraction (AF) of each pattern, directional probabilistic density function (pdf) (dPDF: mean, SD, skewness of pdf /3 directions: superior-inferior, anterior-posterior, central-peripheral), regional cluster distribution pattern (RCDP: number, mean, SD of clusters, mean, SD of centroid of clusters) were automatically evaluated. Spatially normalized left and right lungs were evaluated separately. Disease division index (DDI) on every combination of AFs and asymmetric index (AI) between left and right lung ((left-right)/left) were also evaluated. To assess the accuracy of the system, fifty-four HRCT data sets in patients with pathologically diagnosed UIP (n=26) and NSIP (n=28) were used. For a classification procedure, a CADD-SVM classifier with internal parameter optimization, and sequential forward floating feature selection (SFFS) were employed. The accuracy was assessed by a 5-folding cross validation with 20- times repetition. For comparison, two thoracic radiologists reviewed the whole HRCT images without clinical information and diagnose each case either as UIP or NSIP. The accuracies of radiologists' decision were 0.75 and 0.87, respectively. The accuracies of the CADD system using the features of AF, dPDF, AI of dPDF, RDP, AI of RDP, DDI were 0.70, 0.79, 0.77, 0.80, 0.78, 0.81, respectively. The accuracy of optimized CADD using all features after SFFS was 0.91. We developed the CADD system to differentiate between UIP and NSIP using automated assessment of the extent and distribution of regional disease patterns at HRCT.

Development and Translation of a Tissue-Engineered Disc in a Preclinical Rodent Model

DTIC Science & Technology

2012-10-01

DAPS AF constructs, fabricated complete DAPS comprised of a PCL nanofiber AF and a hyaluronic acid hydrogel NP, and designed and commencement of...of a PCL nanofiber AF and a hyaluronic acid hydrogel NP, and design and commencement of construction of a novel multi-axis bioreactor that will be... nanofiber AF and a hyaluronic acid hydrogel NP We have commenced fabrication and in vitro pre-culture of composite DAPS constructs. An AF region