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1.
Kathleen?S. McDowell Fijoy Vadakkumpadan Robert Blake Joshua Blauer Gernot Plank Rob?S. MacLeod Natalia?A. Trayanova 《Biophysical journal》2013,104(12):2764-2773
Atrial fibrillation (AF), the most common arrhythmia in humans, is initiated when triggered activity from the pulmonary veins propagates into atrial tissue and degrades into reentrant activity. Although experimental and clinical findings show a correlation between atrial fibrosis and AF, the causal relationship between the two remains elusive. This study used an array of 3D computational models with different representations of fibrosis based on a patient-specific atrial geometry with accurate fibrotic distribution to determine the mechanisms by which fibrosis underlies the degradation of a pulmonary vein ectopic beat into AF. Fibrotic lesions in models were represented with combinations of: gap junction remodeling; collagen deposition; and myofibroblast proliferation with electrotonic or paracrine effects on neighboring myocytes. The study found that the occurrence of gap junction remodeling and the subsequent conduction slowing in the fibrotic lesions was a necessary but not sufficient condition for AF development, whereas myofibroblast proliferation and the subsequent electrophysiological effect on neighboring myocytes within the fibrotic lesions was the sufficient condition necessary for reentry formation. Collagen did not alter the arrhythmogenic outcome resulting from the other fibrosis components. Reentrant circuits formed throughout the noncontiguous fibrotic lesions, without anchoring to a specific fibrotic lesion. 相似文献
2.
Kathleen S. McDowell Fijoy Vadakkumpadan Robert Blake Joshua Blauer Gernot Plank Rob S. MacLeod Natalia A. Trayanova 《Biophysical journal》2013
Atrial fibrillation (AF), the most common arrhythmia in humans, is initiated when triggered activity from the pulmonary veins propagates into atrial tissue and degrades into reentrant activity. Although experimental and clinical findings show a correlation between atrial fibrosis and AF, the causal relationship between the two remains elusive. This study used an array of 3D computational models with different representations of fibrosis based on a patient-specific atrial geometry with accurate fibrotic distribution to determine the mechanisms by which fibrosis underlies the degradation of a pulmonary vein ectopic beat into AF. Fibrotic lesions in models were represented with combinations of: gap junction remodeling; collagen deposition; and myofibroblast proliferation with electrotonic or paracrine effects on neighboring myocytes. The study found that the occurrence of gap junction remodeling and the subsequent conduction slowing in the fibrotic lesions was a necessary but not sufficient condition for AF development, whereas myofibroblast proliferation and the subsequent electrophysiological effect on neighboring myocytes within the fibrotic lesions was the sufficient condition necessary for reentry formation. Collagen did not alter the arrhythmogenic outcome resulting from the other fibrosis components. Reentrant circuits formed throughout the noncontiguous fibrotic lesions, without anchoring to a specific fibrotic lesion. 相似文献
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Background
Postoperative atrial fibrillation (POAF) remains the most common complication after cardiac surgery. Current guidelines recommend β-blockers to prevent POAF. Carvedilol is a non-selective β-adrenergic blocker with anti-inflammatory, antioxidant, and multiple cationic channel blocking properties. These unique properties of carvedilol have generated interest in its use as a prophylaxis for POAF.Objective
To investigate the efficacy of carvedilol in preventing POAF.Methods
PubMed from the inception to September 2013 was searched for studies assessing the effect of carvedilol on POAF occurrence. Pooled relative risk (RR) with 95% confidence interval (CI) was calculated using random- or fixed-effect models when appropriate. Six comparative trials (three randomized controlled trials and three nonrandomized controlled trials) including 765 participants met the inclusion criteria.Results
Carvedilol was associated with a significant reduction in POAF (relative risk [RR] 0.49, 95% confidence interval [CI] 0.37 to 0.64, p<0.001). Subgroup analyses yielded similar results. In a subgroup analysis, carvedilol appeared to be superior to metoprolol for the prevention of POAF (RR 0.51, 95% CI 0.37 to 0.70, p<0.001). No evidence of heterogeneity was observed.Conclusions
In conclusion, carvedilol may effectively reduce the incidence of POAF in patients undergoing cardiac surgery. It appeared to be superior to metoprolol. A large-scale, well-designed randomized controlled trial is needed to conclusively answer the question regarding the utility of carvedilol in the prevention of POAF. 相似文献5.
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Sven M?bius-Winkler Marcus Sandri Norman Mangner Phillip Lurz Ingo D?hnert Gerhard Schuler 《Journal of visualized experiments : JoVE》2012,(60)
Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an estimated 6 million people in the United States 1. Since AF affects primarily elderly people, its prevalence increases parallel with age. As such, it is expected that 15.9 million Americans will be affected by the year 2050 2. Ischemic stroke occurs in 5% of non-anticoagulated AF patients each year. Current treatments for AF include rate control, rhythm control and prevention of stroke 3.The American College of Cardiology, American Heart Association, and European Society of Cardiology currently recommended rate control as the first course of therapy for AF 3. Rate control is achieved by administration of pharmacological agents, such as β-blockers, that lower the heart rate until it reaches a less symptomatic state 3. Rhythm control aims to return the heart to its normal sinus rhythm and is typically achieved through administration of antiarrhythmic drugs such as amiodarone, electrical cardioversion or ablation therapy. Rhythm control methods, however, have not been demonstrated to be superior to rate-control methods 4-6. In fact, certain antiarrhythmic drugs have been shown to be associated with higher hospitalization rates, serious adverse effects 3, or even increases in mortality in patients with structural heart defects 7. Thus, treatment with antiarrhythmics is more often used when rate-control drugs are ineffective or contraindicated. Rate-control and antiarrhythmic agents relieve the symptoms of AF, including palpitations, shortness of breath, and fatigue 8, but don''t reliably prevent thromboembolic events 6.Treatment with the anticoagulant drug warfarin significantly reduces the rate of stroke or embolism 9,10. However, because of problems associated with its use, fewer than 50% of patients are treated with it. The therapeutic dose is affected by drug, dietary, and metabolic interactions, and thus requires detailed monitoring. In addition, warfarin has the potential to cause severe, sometimes lethal, bleeding 2. As an alternative, aspirin is commonly prescribed. While aspirin is typically well tolerated, it is far less effective at preventing stroke 10. Other alternatives to warfarin, such as dabigatran 11 or rivaroxaban 12 demonstrate non-inferiority to warfarin with respect to thromboembolic events (in fact, dabigatran given as a high dose of 150 mg twice a day has shown superiority). While these drugs have the advantage of eliminating dietary concerns and eliminating the need for regular blood monitoring, major bleeding and associated complications, while somewhat less so than with warfarin, remain an issue 13-15.Since 90% of AF-associated strokes result from emboli that arise from the left atrial appendage (LAA) 2, one alternative approach to warfarin therapy has been to exclude the LAA using an implanted device to trap blood clots before they exit. Here, we demonstrate a procedure for implanting the WATCHMAN Left Atrial Appendage Closure Device. A transseptal cannula is inserted through the femoral vein, and under fluoroscopic guidance, inter-atrial septum is crossed. Once access to the left atrium has been achieved, a guidewire is placed in the upper pulmonary vein and the WATCHMAN Access Sheath and dilator are advanced over the wire into the left atrium. The guidewire is removed, and the access sheath is carefully advanced into the distal portion of the LAA over a pigtail catheter. The WATCHMAN Delivery System is prepped, inserted into the access sheath, and slowly advanced. The WATCHMAN device is then deployed into the LAA. The device release criteria are confirmed via fluoroscopy and transesophageal echocardiography (TEE) and the device is released. 相似文献
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Chin-Chou Huang Wan-Leong Chan Jiing-Chyuan Luo Yu-Chun Chen Tzeng-Ji Chen Chia-Min Chung Po-Hsun Huang Shing-Jong Lin Jaw-Wen Chen Hsin-Bang Leu 《PloS one》2012,7(10)
Objectives
Precise mechanisms of atrial fibrillation (AF) are uncertain, but their association with esophageal disorders has been recently proposed. The association between gastroesophageal reflux disease (GERD), the most common gastroesophageal disorder, and AF remains undetermined. We therefore aimed to investigate the association between GERD and later development of AF.Methods and Results
Patients with GERD were identified from the 1,000,000-person cohort dataset sampled from the Taiwan National Health Insurance database. The study cohort comprised 29,688 newly diagnosed adult GERD patients; 29,597 randomly selected age-, gender-, comobidity-matched subjects comprised the comparison cohort. Cox proportional hazard regressions were performed as a means of comparing the AF-free survival rate for the two cohorts. During a maximum three years of follow-up, a total of 351 patients experienced AF, including 184 (0.62%) patients in the GERD cohort and 167 (0.56%) in the control group. The log-rank test showed that patients with GERD had significantly higher incidence of AF than those without GERD (p = 0.024). After Cox proportional hazard regression model analysis, GERD was independently associated with the increased risk of AF (hazard ratio, 1.31; 95% confidence interval, 1.06–1.61, p = 0.013).Conclusion
GERD was independently associated with an increased risk of future AF in a nationwide population-based cohort. 相似文献9.
Cheng DC Ad N Martin J Berglin EE Chang BC Doukas G Gammie JS Nitta T Wolf RK Puskas JD 《Innovations (Philadelphia, Pa.)》2010,5(2):84-96
OBJECTIVES:: This meta-analysis sought to determine whether surgical ablation improves clinical outcomes and resource utilization compared with no ablation in adult patients with persistent and permanent atrial fibrillation (AF) undergoing cardiac surgery. METHODS:: A comprehensive search was undertaken to identify all randomized (RCT) and nonrandomized (non-RCT) controlled trials of surgical ablation versus no ablation in patients with AF undergoing cardiac surgery up to April 2009. The primary outcome was sinus rhythm. Secondary outcomes included survival and any other reported clinically relevant outcome or indicator of resource utilization. Odds ratios (OR) and weighted mean differences (WMD) and their 95% confidence intervals (95% CI) were analyzed as appropriate using the random effects model. Heterogeneity was measured using the I statistic. Meta-regression was performed to explore the relationship between the benefit from surgical AF and duration of follow-up. RESULTS:: Thirty-three studies met the inclusion criteria (10 RCTs and 23 non-RCTs) for a total of 4647 patients. The number of patients in sinus rhythm was significantly improved at discharge in the surgical AF ablation group versus (68.6%) the surgery alone group (23.0%) in RCTs (OR 10.1, 95% CI 4.5-22.5) and non-RCTs (OR 7.15, 95% CI 3.42-14.95). This effect on sinus rhythm (74.6% vs. 18.4%) remained at follow-up of 1 to 5 years (OR 6.7, 95% CI 2.8-15.7 for RCT, and OR 15.5, 95% CI 6.6-36.7 for non-RCT). The risk of all-cause mortality at 30 days was not different between the groups in RCT (OR 1.20, 95% CI 0.52-3.16) or non-RCT studies (OR 0.99, 95% CI 0.52-1.87). In studies reporting all-cause mortality at 1 year or more (up to 5 years), mortality did not differ in RCT studies (OR 1.21, 95% CI 0.59-2.51) but was significantly reduced in non-RCT studies (OR 0.54, 95% CI 0.31-0.96). Stroke incidence was not reduced significantly; however, in meta-regression, the risk of stroke decreased significantly with longer follow-up. Other clinical outcomes were similar between groups. Operation time was significantly increased with surgical AF ablation; however, overall impact on length of stay was variable. CONCLUSIONS:: In patients with persistent or permanent AF who present for cardiac surgery, the addition of surgical AF ablation led to a significantly higher rate of sinus rhythm in RCT and non-RCT studies compared with cardiac surgery alone, and this effect remains robust over the longer term (1-5 years). Although non-RCT studies suggest the possibility of reduced risk of stroke and death, this remains to be proven in prospective RCTs with adequate power and follow-up. 相似文献
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Objective
To evaluate the evidence for the effectiveness and safety of Shensongyangxin Capsules (SSYX) for treating paroxysmal atrial fibrillation (PAF).Methods
We searched for randomized clinical trials for SSYX in PAF up to June 2015. The Cochrane risk of bias tool was used to assess the methodological quality. RevMan 5.3 was used to synthesize the results.Results
We included 22 trials involving 2,347 PAF patients. The quality of the included studies was generally poor. The results of the meta-analysis showed that SSYX plus routine treatment was more effective at improving P-wave dispersion (Pwd) and the frequency of PAF attacks compared with routine treatment alone. The results from the included trials that compared SSYX plus routine treatment and arrhythmic drugs plus routine treatment were inconsistent. Trials reported on Pwd, quality of life, frequency of PAF attacks or maintenance rate of sinus rhythm and found that SSYX combined with anti-arrhythmic drugs plus routine treatment was more effective than anti-arrhythmic drugs plus routine treatment. Four of the trials reported adverse events, indicating that SSYX was potentially safer than anti-arrhythmic drugs.Conclusions
There appears to be some benefit from the use of SSYX. However, due to poor methodological quality, we could not draw confirmative conclusions regarding the beneficial effect of using SSYX. 相似文献11.
Martin J. Swaans Arash Alipour Benno J.W.M. Rensing Martijn C. Post Lucas V.A. Boersma 《Journal of visualized experiments : JoVE》2013,(72)
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope 4, 5. Patients with AF have a five-fold higher risk of stroke 6.Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64% 7. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range 8-11. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug 8.The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF 12,13, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers 4. CA is a well-established treatment for AF symptoms 14, 15, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy 16.Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation 17, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes) 18. This device received the Conformité Européenne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy 19.Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding 20 or other warfarin-associated problems.The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1 21. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted. 相似文献
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Catheter ablation provides an important treatment option for patients with both paroxysmal and persistent atrial fibrillation. It mainly involves pulmonary vein isolation and additional ablations in the left atrium in persistent cases. There have been significant advancements in this procedure to enhance the safety and effectiveness. One of them is the evolution of various imaging modalities to facilitate better visualization of the complex left atrial anatomy and the pulmonary veins in order to deliver the lesions accurately. In this article, we review the electroanatomic mapping systems including the magnetic-based and impedence-based systems. Each of these mapping systems has its own advantages and disadvantages. In addition, we also discuss the role of intracardiac echocardiography and three dimensional rotational angiography in atrial fibrillation ablation. 相似文献
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We report a case of sarcoidosis presenting initially as atrial fibrillation(AF). His response to anti-arrhythmic treatment strategy was suboptimal. On initiation of immunosuppressive therapy, AF was better controlled. This interesting case highlights a likely link between inflammation and pathogenesis of atrial fibrillation. 相似文献
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Na Wu Shifei Tong Ying Xiang Long Wu Bin Xu Yao Zhang Xiangyu Ma Yafei Li Zhiyuan Song Li Zhong 《PloS one》2015,10(4)
Background
There is growing evidence that indicates the presence of a prothrombotic state in atrial fibrillation (AF). However, the role of hemostatic markers in AF remains inconclusive.Methods
We conducted a meta-analysis of observational studies to evaluate the association between hemostatic markers and AF. A meta-regression was performed to explore potential sources of heterogeneity.Results
A total of 59 studies met our inclusion criteria for the meta-analysis. For platelet activation, increased circulating platelet factor-4, β-thromboglobulin (BTG) and P-selectin were significantly higher in AF cases compared with controls (standardized mean difference [SMD][95% confidence interval (CI)]: 1.72[0.96–2.49], 1.61[1.03–2.19] and 0.50[0.23–0.77], respectively). For coagulation activation, increased levels of plasma D-dimer, fibrinogen, thrombin-antithrombin, prothrombin fragment 1+2, and antithrombin-III were significantly associated with AF (SMD[95% CI]: 1.82[1.38–2.26], 0.72[0.55–0.89], 0.42[0.13–0.72], 1.00 [0.00–1.99] and 1.38[0.16–2.60], respectively). For fibrinolytic function, tissue-type plasminogen activator and plasminogen activator inhibitor-1 were significantly increased in AF cases compared with controls (SMD[95% CI]: 0.86[0.04–1.67] and 0.87[0.28–1.47], respectively) but the associations became nonsignificant after performing subgroup analysis by anticoagulants treatment status. For endothelial function, increased von Willebrand factor was significantly associated with AF (SMD, 0.79; 95% CI, 0.60–0.99); however, no association was observed for soluble thrombomodulin (SMD, 0.60; 95% CI, -0.13–1.33).Conclusions
Increased circulating hemostatic factors (PF-4, BTG, P-selectin, D-dimer, fibrinogen, TAT, F1+2, AT- III, and vWf) are significantly associated with AF. Future research is necessary to elucidate the precise mechanism of the prothrombotic state and how hemostatic markers promote thromboembolism in AF. 相似文献16.
Objective
To conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF).Patients and Methods
We searched Medline, Embase, NHSEED and HTA databases and the Tuft’s Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation) models of newer agents for SPAF.Results
Eighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%), European (39%) and Canadian (17%) perspectives. Models typically assumed patients between 65–73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110 mg (n = 4)/150 mg (n = 2); rivaroxaban (n = 1)) vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547–$86,000 for dabigatran 150 mg, $20,713–$150,000 for dabigatran 110 mg, $4,084–$21,466 for sequentially-dosed dabigatran and $23,065–$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400–$25,059) vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results.Conclusions
Cost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent. 相似文献17.
Atrial fibrillation is a common arrhythmia with considerable morbidity and mortality. Limitations in studying both the mechanisms and therapy of atrial fibrillation arise due to the paucity of models that yield sufficiently high-quality data, are not costly, and in which atrial fibrillation is sustained long enough to make the necessary observations. The canine model we present is based on the hypothesis that atrial fibrillation requires heterogeneity of repolarization, that distribution of vagal fibers is heterogeneous in the atria, and that atrial fibrillation will persist after reflex stimulation of vagal efferents by increased systemic arterial pressure. Dogs were anesthetized with morphine–chloralose because this combination maintains nearly intact autonomic control. Systemic arterial pressure was elevated approximately 75 mm Hg during infusion of phenylephrine (2 μg/kg · min−1). The right atrium was paced for 20 min at 40 Hz. Atrial fibrillation was sustained after cessation of atrial pacing in dogs receiving phenylephrine, but terminated within seconds in normotensive animals. In conclusion, atrial fibrillation can be maintained for at least 40 min after cessation of rapid atrial pacing in dogs with phenylephrine-induced hypertension.Atrial fibrillation is a common arrhythmia that affects more than 2 million persons in the United States.1 This condition is characterized by chaotic asynchronous activation and contraction of hundreds of regions of the atria, resulting in both absence of active atrial transport of blood and a rapid ventricular response. With chronic atrial fibrillation, patients can develop thromboembolism and stroke;22 and 15% of strokes in the United States occur in patients with atrial fibrillation.1 Despite prodigious efforts to understand the mechanism of this condition and to prevent and remediate it, atrial fibrillation leads to enormous morbidity and mortality.3 One factor hindering studies of atrial fibrillation is the absence of a model in which fibrillation can be sustained for more than several seconds, although the arrhythmia can be sustained nearly permanently after weeks of rapid atrial pacing in animals with either heart failure or physical injury to the left atrium.8Rapid atrial pacing decreases the atrial effective refractory period, slows atrial conduction, and increases electrophysiologic heterogeneity.10,11,20 Recently, phenylephrine was shown to increase the difference between left and right atrial and intraatrial refractory periods, thus creating heterogeneity of atrial refractoriness.16 We therefore postulated that rapid atrial pacing together with phenylephrine infusion would induce relatively sustained atrial fibrillation for at least 40 min in dogs—a duration likely to be sufficient for testing of agents with potential to convert atrial fibrillation. This report describes a simple canine model using rapid atrial pacing in which atrial fibrillation was sustained for at least 40 min. 相似文献
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Renate B. Schnabel Matthias Michal Sandra Wilde J?rg Wiltink Philipp S. Wild Christoph R. Sinning Edith Lubos Francisco M. Ojeda Tanja Zeller Thomas Munzel Stefan Blankenberg Manfred E. Beutel 《PloS one》2013,8(12)