Dr. A.J. Rogers is a Cardiovascular Medicine Fellow and Postdoctoral Research Scholar at Stanford University. He has over 10 years of medical device experience ranging from basic and translational research to device development and entrepreneurship. His undergraduate coursework in Biomedical Engineering at Duke University focused on neurobiology, signal processing, and computer modeling while his research investigated piezoelectric arrays for intracardiac ultrasound and computer vision of 3D ultrasound images for automated surgical robot tasks (Stephen Smith Laboratory). He earned his medical degree from the University of North Carolina and graduated in the inaugural class for the combined MBA degree program from the Kenan-Flagler Business School at UNC (focus in Healthcare Entrepreneurship). While working toward these degrees, A.J. participated in epidemiologic and translational research in the academic setting and worked as a clinical engineer for a start-up medical device company in the field of heart failure. He completed training in Internal Medicine and Cardiovascular Medicine at Stanford University. He joined Dr. Sanjiv Narayan’s Computational Arrhythmia Research Laboratory to explore mechanisms of cardiac fibrillation using techniques of signal processing, machine learning, and in silico modeling. Outside of his research and clinical pursuits, A.J. enjoys athletics of all kinds (especially sand volleyball), travelling, and live music events.
- Cardiovascular Medicine
- Cardiac Arrhythmia
M.D., University of North Carolina, Medicine (2014)
M.B.A., UNC Kenan-Flagler Business School, Healthcare Entrepreneurship (2014)
B.S.E., Duke University, Biomedical Engineering, Chemistry, Medicine (2009)
LARGER ORGANIZED AREAS IN PERSISTENT ATRIAL FIBRILLATION PREDICTS TERMINATION DURING ABLATION
ELSEVIER SCIENCE INC. 2020: 279
View details for Web of Science ID 000522979100273
PREDICTING SUDDEN CARDIAC DEATH BY MACHINE LEARNING OF VENTRICULAR ACTION POTENTIALS
ELSEVIER SCIENCE INC. 2020: 427
View details for Web of Science ID 000522979100416
- The interconnected atrium: Acute impact of pulmonary vein isolation on remote atrial tissue. Journal of cardiovascular electrophysiology 2020
Continuous Ablation Improves Lesion Maturation Compared with Intermittent Ablation Strategies.
Journal of cardiovascular electrophysiology
Interrupted ablation is increasingly proposed as part of high-power short duration radiofrequency ablation (RFA) strategies and may also result from loss of contact from respiratory patterns or cardiac motion.To study the extent that ablation interruption affects lesions.In ex vivo and in vivo experiments, lesion characteristics and tissue temperatures were compared between continuous (Group 1) and interrupted (Groups 2,3) RFA with equal total ablation duration and contact force. Extended duration ablation lesions were also characterized from 1 to 5 minutes.In the ex vivo study, continuous RFA (Group 1) produced larger total lesion volumes compared with each interrupted ablation lesion group (273.8±36.5 mm3 vs. 205.1±34.2 and vs. 174.3±32.3, all p<0.001). Peak temperatures for Group 1 were higher at 3mm and 5mm than Groups 2 and 3. In vivo, continuous ablation resulted in larger lesions, greater lesion depths, and higher tissue temperatures. Longer ablation durations created larger lesion volumes and increased lesion depths. However, after 3 min of ablation, the rate of lesion volume and depth formation decreased.Continuous RFA delivery resulted in larger and deeper lesions with higher tissue temperatures compared to interrupted ablation. This work may have implications for high-power short duration ablation strategies, motivates strategies to reduce variations in ablation delivery, and provides an upper limit for ablation duration beyond which power delivery has diminishing returns. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/jce.14510
View details for PubMedID 32323395
Non-Invasive Assessment of Complexity of Atrial Fibrillation: Correlation with Contact Mapping and Impact of Ablation.
Circulation. Arrhythmia and electrophysiology
Background - It is difficult to non-invasively phenotype atrial fibrillation (AF) in a way that reflects clinical endpoints such as response to therapy. We set out to map electrical patterns of disorganization and regions of reentrant activity in AF from the body surface using electrocardiographic imaging (ECGI), calibrated to panoramic intracardiac recordings and referenced to AF termination by ablation. Methods - Bi-atrial intracardiac electrograms of 47 AF patients at ablation (30 persistent, 29 male, 63±9 years) were recorded with 64-pole basket catheters and simultaneous 57-lead body surface ECGs. Atrial epicardial electrical activity was reconstructed and organized sites were invasively and non-invasively tracked in 3D using phase singularity (PS). In a subset of 17 patients, sites of AF organization were targeted for ablation. Results - Body surface mapping showed greater AF organization near intracardially-detected drivers than elsewhere, both in PS density (2.3±2.1 vs 1.9±1.6, p=0.02) and number of drivers (3.2±2.3 vs 2.7±1.7, p=0.02). Complexity, defined as the number of stable AF reentrant sites, was concordant between non-invasive and invasive methods (r2 =0.5, CC=0.71). In the subset receiving targeted ablation, AF complexity showed lower values in those in whom AF terminated than those in whom AF did not terminate (p<0.01). Conclusions - AF complexity tracked non-invasively correlates well with organized and disorganized regions detected by panoramic intracardiac mapping, and correlates with the acute outcome by ablation. This approach may assist in bedside monitoring of therapy or in improving the efficacy of ongoing ablation procedures.
View details for DOI 10.1161/CIRCEP.119.007700
View details for PubMedID 32078374
- Letter in reply: Continuous radiofrequency ablation in scar-based arrhythmia substrate. Journal of cardiovascular electrophysiology 2020
Termination of persistent atrial fibrillation by ablating sites that control large atrial areas.
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology
Persistent atrial fibrillation (AF) has been explained by multiple mechanisms which, while they conflict, all agree that more disorganized AF is more difficult to treat than organized AF. We hypothesized that persistent AF consists of interacting organized areas which may enlarge, shrink or coalesce, and that patients whose AF areas enlarge by ablation are more likely to respond to therapy.We mapped vectorial propagation in persistent AF using wavefront fields (WFF), constructed from raw unipolar electrograms at 64-pole basket catheters, during ablation until termination (Group 1, N = 20 patients) or cardioversion (Group 2, N = 20 patients). Wavefront field mapping of patients (age 61.1 ± 13.2 years, left atrium 47.1 ± 6.9 mm) at baseline showed 4.6 ± 1.0 organized areas, each separated by disorganization. Ablation of sites that led to termination controlled larger organized area than competing sites (44.1 ± 11.1% vs. 22.4 ± 7.0%, P < 0.001). In Group 1, ablation progressively enlarged unablated areas (rising from 32.2 ± 15.7% to 44.1 ± 11.1% of mapped atrium, P < 0.0001). In Group 2, organized areas did not enlarge but contracted during ablation (23.6 ± 6.3% to 15.2 ± 5.6%, P < 0.0001).Mapping wavefront vectors in persistent AF revealed competing organized areas. Ablation that progressively enlarged remaining areas was acutely successful, and sites where ablation terminated AF were surrounded by large organized areas. Patients in whom large organized areas did not emerge during ablation did not exhibit AF termination. Further studies should define how fibrillatory activity is organized within such areas and whether this approach can guide ablation.
View details for DOI 10.1093/europace/euaa018
View details for PubMedID 32243508
Electrographic flow mapping in persistent atrial fibrillation
WILEY. 2019: 1745–46
View details for Web of Science ID 000485280500073
Wavefront Field Mapping Reveals a Physiologic Network Between Drivers Where Ablation Terminates Atrial Fibrillation.
Circulation. Arrhythmia and electrophysiology
2019; 12 (8): e006835
BACKGROUND: Localized drivers are proposed mechanisms for persistent atrial fibrillation (AF) from optical mapping of human atria and clinical studies of AF, yet are controversial because drivers fluctuate and ablating them may not terminate AF. We used wavefront field mapping to test the hypothesis that AF drivers, if concurrent, may interact to produce fluctuating areas of control to explain their appearance/disappearance and acute impact of ablation.METHODS: We recruited 54 patients from an international registry in whom persistent AF terminated by targeted ablation. Unipolar AF electrograms were analyzed from 64-pole baskets to reconstruct activation times, map propagation vectors each 20 ms, and create nonproprietary phase maps.RESULTS: Each patient (63.6±8.5 years, 29.6% women) showed 4.0±2.1 spatially anchored rotational or focal sites in AF in 3 patterns. First, a single (type I; n=7) or, second, paired chiral-antichiral (type II; n=5) rotational drivers controlled most of the atrial area. Ablation of 1 to 2 large drivers terminated all cases of types I or II AF. Third, interaction of 3 to 5 drivers (type III; n=42) with changing areas of control. Targeted ablation at driver centers terminated AF and required more ablation in types III versus I (P=0.02 in left atrium).CONCLUSIONS: Wavefront field mapping of persistent AF reveals a pathophysiologic network of a small number of spatially anchored rotational and focal sites, which interact, fluctuate, and control varying areas. Future work should define whether AF drivers that control larger atrial areas are attractive targets for ablation.
View details for DOI 10.1161/CIRCEP.118.006835
View details for PubMedID 31352796
- Propagation velocity at atrial fibrillation sources: Go with the flow INTERNATIONAL JOURNAL OF CARDIOLOGY 2019; 286: 76–77
- Editorial: High density mapping of atrial fibrillation sources JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY 2019; 30 (6): 964–65
- Comparing phase and electrographic flow mapping for persistent atrial fibrillation PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY 2019; 42 (5): 499–507
- Predictability in complex atrial arrhythmias: The N/N-1 algorithm to guide ablation of atrial tachycardias HEART RHYTHM 2019; 16 (4): 562–63
SITES THAT CONTROL LARGER AREAS DURING ATRIAL FIBRILLATION MAY DETERMINE TERMINATION DURING ABLATION
ELSEVIER SCIENCE INC. 2019: 400
View details for Web of Science ID 000460565900400
INTRACLASS CORRELATIONS OF VOLTAGE, FRACTIONATED ELECTROGRAMS, AND DOMINANT FREQUENCY IN PATIENTS WHERE LOCALIZED ABLATION TERMINATED PERSISTENT ATRIAL FIBRILLATION
ELSEVIER SCIENCE INC. 2019: 521
View details for Web of Science ID 000460565900521
MACHINE LEARNING IDENTIFIES SITES WHERE ABLATION TERMINATES PERSISTENT ATRIAL FIBRILLATION
ELSEVIER SCIENCE INC. 2019: 301
View details for Web of Science ID 000460565900301
- Structurally-based electrical predictors of atrial arrhythmias INTERNATIONAL JOURNAL OF CARDIOLOGY 2019; 278: 151–52
- Integrating blockchain technology with artificial intelligence for cardiovascular medicine. Nature reviews. Cardiology 2019
Large-Scale Assessment of a Smartwatch to Identify Atrial Fibrillation.
The New England journal of medicine
2019; 381 (20): 1909–17
BACKGROUND: Optical sensors on wearable devices can detect irregular pulses. The ability of a smartwatch application (app) to identify atrial fibrillation during typical use is unknown.METHODS: Participants without atrial fibrillation (as reported by the participants themselves) used a smartphone (Apple iPhone) app to consent to monitoring. If a smartwatch-based irregular pulse notification algorithm identified possible atrial fibrillation, a telemedicine visit was initiated and an electrocardiography (ECG) patch was mailed to the participant, to be worn for up to 7 days. Surveys were administered 90 days after notification of the irregular pulse and at the end of the study. The main objectives were to estimate the proportion of notified participants with atrial fibrillation shown on an ECG patch and the positive predictive value of irregular pulse intervals with a targeted confidence interval width of 0.10.RESULTS: We recruited 419,297 participants over 8 months. Over a median of 117 days of monitoring, 2161 participants (0.52%) received notifications of irregular pulse. Among the 450 participants who returned ECG patches containing data that could be analyzed - which had been applied, on average, 13 days after notification - atrial fibrillation was present in 34% (97.5% confidence interval [CI], 29 to 39) overall and in 35% (97.5% CI, 27 to 43) of participants 65 years of age or older. Among participants who were notified of an irregular pulse, the positive predictive value was 0.84 (95% CI, 0.76 to 0.92) for observing atrial fibrillation on the ECG simultaneously with a subsequent irregular pulse notification and 0.71 (97.5% CI, 0.69 to 0.74) for observing atrial fibrillation on the ECG simultaneously with a subsequent irregular tachogram. Of 1376 notified participants who returned a 90-day survey, 57% contacted health care providers outside the study. There were no reports of serious app-related adverse events.CONCLUSIONS: The probability of receiving an irregular pulse notification was low. Among participants who received notification of an irregular pulse, 34% had atrial fibrillation on subsequent ECG patch readings and 84% of notifications were concordant with atrial fibrillation. This siteless (no on-site visits were required for the participants), pragmatic study design provides a foundation for large-scale pragmatic studies in which outcomes or adherence can be reliably assessed with user-owned devices. (Funded by Apple; Apple Heart Study ClinicalTrials.gov number, NCT03335800.).
View details for DOI 10.1056/NEJMoa1901183
View details for PubMedID 31722151
Editorial: High density mapping of atrial fibrillation sources.
Journal of cardiovascular electrophysiology
View details for PubMedID 31056801
Online webinar training to analyse complex atrial fibrillation maps: A randomized trial.
2019; 14 (7): e0217988
Specific tools have been recently developed to map atrial fibrillation (AF) and help guide ablation. However, when used in clinical practice, panoramic AF maps generated from multipolar intracardiac electrograms have yielded conflicting results between centers, likely due to their complexity and steep learning curve, thus limiting the proper assessment of its clinical impact.The main purpose of this trial was to assess the impact of online training on the identification of AF driver sites where ablation terminated persistent AF, through a standardized training program. Extending this concept to mobile health was defined as a secondary objective.An online database of panoramic AF movies was generated from a multicenter registry of patients in whom targeted ablation terminated non-paroxysmal AF, using a freely available method (Kuklik et al-method A) and a commercial one (RhythmView-method B). Cardiology Fellows naive to AF mapping were enrolled and randomized to training vs no training (control). All participants evaluated an initial set of movies to identify sites of AF termination. Participants randomized to training evaluated a second set of movies in which they received feedback on their answers. Both groups re-evaluated the initial set to assess the impact of training. This concept was then migrated to a smartphone application (App).12 individuals (median age of 30 years (IQR 28-32), 6 females) read 480 AF maps. Baseline identification of AF termination sites by ablation was poor (40%±12% vs 42%±11%, P = 0.78), but similar for both mapping methods (P = 0.68). Training improved accuracy for both methods A (P = 0.001) and B (p = 0.012); whereas controls showed no change in accuracy (P = NS). The Smartphone App accessed AF maps from multiple systems on the cloud to recreate this training environment.Digital online training improved interpretation of panoramic AF maps in previously inexperienced clinicians. Combining online clinical data, smartphone apps and other digital resources provides a powerful, scalable approach for training in novel techniques in electrophysiology.
View details for DOI 10.1371/journal.pone.0217988
View details for PubMedID 31269029
- Dielectric-Based Imaging And Navigation Of The Heart. Heart rhythm 2019
Structurally-based electrical predictors of atrial arrhythmias.
International journal of cardiology
View details for PubMedID 30528625
Predictability in Complex Atrial Arrhythmias: the N/N-1 Algorithm to Guide Ablation of Atrial Tachycardias.
View details for PubMedID 30465903
- Integrating mapping methods for atrial fibrillation. Pacing and clinical electrophysiology : PACE 2018
Interaction of Localized Drivers and Disorganized Activation in Persistent Atrial Fibrillation: Reconciling Putative Mechanisms Using Multiple Mapping Techniques
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
2018; 11 (6): e005846
Mechanisms for persistent atrial fibrillation (AF) are unclear. We hypothesized that putative AF drivers and disorganized zones may interact dynamically over short time scales. We studied this interaction over prolonged durations, focusing on regions where ablation terminates persistent AF using 2 mapping methods.We recruited 55 patients with persistent AF in whom ablation terminated AF prior to pulmonary vein isolation from a multicenter registry. AF was mapped globally using electrograms for 360±45 cycles using (1) a published phase method and (2) a commercial activation/phase method.Patients were 62.2±9.7 years, 76% male. Sites of AF termination showed rotational/focal patterns by methods 1 and 2 (51/55 vs 55/55; P=0.13) in spatially conserved regions, yet fluctuated over time. Time points with no AF driver showed competing drivers elsewhere or disordered waves. Organized regions were detected for 61.6±23.9% and 70.6±20.6% of 1 minute per method (P=nonsignificant), confirmed by automatic phase tracking (P<0.05). To detect AF drivers with >90% sensitivity, 8 to 32 s of AF recordings were required depending on driver definition.Sites at which persistent AF terminated by ablation show organized activation that fluctuate over time, because of collision from concurrent organized zones or fibrillatory waves, yet recur in conserved spatial regions. Results were similar by 2 mapping methods. This network of competing mechanisms should be reconciled with existing disorganized or driver mechanisms for AF, to improve clinical mapping and ablation of persistent AF.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02997254.
View details for PubMedID 29884620
- Clinical Implications of Ablation of Drivers for Atrial Fibrillation A Systematic Review and Meta-Analysis CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY 2018; 11 (5)
- Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY 2018; 29 (5): 687–95
- CAVOTRICUSPID ISTHMUS ABLATION FOR TREATMENT OF RECURRENT ATRIAL TACHYARRHYTHMIA IN PATIENT WITH DRUG-INDUCED TORSADE DE POINTES AND SEVERE SYSTOLIC HEART FAILURE ELSEVIER SCIENCE INC. 2018: 2565
Independent mapping methods reveal rotational activation near pulmonary veins where atrial fibrillation terminates before pulmonary vein isolation.
Journal of cardiovascular electrophysiology
OBJECTIVE: To investigate mechanisms by which atrial fibrillation (AF) may terminate during ablation near the pulmonary veins before the veins are isolated (PVI).INTRODUCTION: It remains unstudied how AF may terminate during ablation before PVs are isolated, or how patients with PV reconnection can be arrhythmia-free. We studied patients in whom PV antral ablation terminated AF before PVI, using two independent mapping methods.METHODS: We studied patients with AF referred for ablation, in whom biatrial contact basket electrograms were studied by both an activation/phase mapping method and by a second validated mapping method reported not to create false rotational activity.RESULTS: In 22 patients (age 60.1 ± 10.4, 36% persistent AF), ablation at sites near the PVs terminated AF (77% to sinus rhythm) prior to PVI. AF propagation revealed rotational (n=20) and focal (n=2) patterns at sites of termination by mapping method 1 and method 2. Both methods showed organized sites that were spatially concordant (P<0.001) with similar stability (P<0.001). Vagal slowing was not observed at sites of AF termination.DISCUSSION: PV antral regions where ablation terminated AF before PVI exhibited rotational and focal activation by two independent mapping methods. These data provide an alternative mechanism for the success of PVI, and may explain AF termination before PVI or lack of arrhythmias despite PV reconnection. Mapping such sites may enable targeted PV lesion sets and improved freedom from AF.
View details for PubMedID 29377478
Clinical Implications of Ablation of Drivers for Atrial Fibrillation: A Systematic Review and Meta-Analysis.
Circulation. Arrhythmia and electrophysiology
2018; 11 (5): e006119
The outcomes from pulmonary vein isolation (PVI) for atrial fibrillation (AF) are suboptimal, but the benefits of additional lesion sets remain unproven. Recent studies propose ablation of AF drivers improves outcomes over PVI, yet with conflicting reports in the literature. We undertook a systematic literature review and meta-analysis to determine outcomes from ablation of AF drivers in addition to PVI or as a stand-alone procedure.Database search was done using the terms atrial fibrillation and ablation or catheter ablation and driver or rotor or focal impulse or FIRM (Focal Impulse and Rotor Modulation). We pooled data using random effects model and assessed heterogeneity with I2 statistic.Seventeen studies met inclusion criteria, in a cohort size of 3294 patients. Adding AF driver ablation to PVI reported freedom from AF of 72.5% (confidence interval [CI], 62.1%-81.8%; P<0.01) and from all arrhythmias of 57.8% (CI, 47.5%-67.7%; P<0.01). AF driver ablation when added to PVI or as stand-alone procedure compared with controls produced an odds ratio of 3.1 (CI, 1.3-7.7; P=0.02) for freedom from AF and an odds ratio of 1.8 (CI, 1.2-2.7; P<0.01) for freedom from all arrhythmias in 4 controlled studies. AF termination rate was 40.5% (CI, 30.6%-50.9%) and predicted favorable outcome from ablation(P<0.05).In controlled studies, the addition of AF driver ablation to PVI supports the possible benefit of a combined approach of AF driver ablation and PVI in improving single-procedure freedom from all arrhythmias. However, most studies are uncontrolled and are limited by substantial heterogeneity in outcomes. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to PVI.
View details for PubMedID 29743170
Minimizing Radiation in the Modern Electrophysiology Laboratory
The Journal of Innovations in Cardiac Rhythm Management
2018; 2018 (9): 3265-3270
View details for DOI 10.19102/icrm.2018.090805
Rotational Drivers in Atrial Fibrillation: Are Multiple Techniques Circling Similar Mechanisms?
Circulation. Arrhythmia and electrophysiology
2017; 10 (12)
View details for PubMedID 29254949
- Rotational Drivers in Atrial Fibrillation Are Multiple Techniques Circling Similar Mechanisms? CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY 2017; 10 (12)
Drivers of persistent atrial fibrillation: do focal or rotational regions differ in their stability over time?
OXFORD UNIV PRESS. 2017: 638
View details for Web of Science ID 000440509302454
Drivers of Persistent Atrial Fibrillation: Are Focal and Rotational Sites Transient or Stable Over Time?
WILEY. 2017: 606–7
View details for Web of Science ID 000403296100062
Editorial commentary: What can lung transplantation teach us about the mechanisms of atrial arrhythmias?
Trends in cardiovascular medicine
View details for PubMedID 28893519
Spatial relationship of sites for atrial fibrillation drivers and atrial tachycardia in patients with both arrhythmias.
International journal of cardiology
2017; 248: 188–95
Atrial fibrillation (AF) often converts to and from atrial tachycardia (AT), but it is undefined if these rhythms are mechanistically related in such patients. We tested the hypothesis that critical sites for AT may be related to regional AF sources in patients with both rhythms, by mapping their locations and response to ablation on transitions to and from AF.From 219 patients undergoing spatial mapping of AF prior to ablation at 3 centers, we enrolled 26 patients in whom AF converted to AT by ablation (n=19) or spontaneously (n=7; left atrial size 42±6cm, 38% persistent AF). Both atria were mapped in both rhythms by 64-electrode baskets, traditional activation maps and entrainment.Each patient had a single mapped AT (17 reentrant, 9 focal) and 3.7±1.7 AF sources. The mapped AT spatially overlapped one AF source in 88% (23/26) of patients, in left (15/23) or right (8/23) atria. AF transitioned to AT by 3 mechanisms: (a) ablation anchoring AF rotor to AT (n=13); (b) residual, unablated AF source producing AT (n=6); (c) spontaneous slowing of AF rotor leaving reentrant AT at this site without any ablation (n=7). Electrogram analysis revealed a lower peak-to-peak voltage at overlapping sites (0.36±0.2mV vs 0.49±0.2mV p=0.03).Mechanisms responsible for AT and AF may arise in overlapping atrial regions. This mechanistic inter-relationship may reflect structural and/or functional properties in either atrium. Future work should delineate how acceleration of an organized AT may produce AF, and whether such regions can be targeted a priori to prevent AT recurrence post AF ablation.
View details for PubMedID 28733070
FMN fluorescence in inducible NOS constructs reveals a series of conformational states involved in the reductase catalytic cycle
2012; 279 (7): 1306-1317
Nitric oxide synthases (NOSs) produce NO as a molecular signal in the nervous and cardiovascular systems and as a cytotoxin in the immune response. NO production in the constitutive isoforms is controlled by calmodulin regulation of electron transfer. In the tethered shuttle model for NOS reductase function, the FMN domain moves between NADPH dehydrogenase and oxygenase catalytic centers. Crystal structures of neuronal NOS reductase domain and homologs correspond to an 'input state', with FMN in close contact with FAD. We recently produced two domain 'output state' (oxyFMN) constructs showing calmodulin dependent FMN domain association with the oxygenase domain. FMN fluorescence is sensitive to enzyme conformation and calmodulin binding. The inducible NOS (iNOS) oxyFMN construct is more fluorescent than iNOS holoenzyme. The difference in steady state fluorescence is rationalized by the observation of a series of characteristic states in the two constructs, which we assign to FMN in different environments. OxyFMN and holoenzyme share open conformations with an average lifetime of ~4.3 ns. The majority state in holoenzyme has a short lifetime of ~90 ps, probably because of FAD-FMN interactions. In oxyFMN about 25-30% of the FMN is in a state with a lifetime of 0.9 ns, which we attribute to quenching by heme in the output state. Occupancy of the output state together with our previous kinetic results yields a heme edge to FMN distance estimate of 12-15 Å. These results indicate that FMN fluorescence is a valuable tool to study conformational states involved in the NOS reductase catalytic cycle.
View details for DOI 10.1111/j.1742-4658.2012.08525.x
View details for Web of Science ID 000301571800015
View details for PubMedID 22325715
A High-Fiber Diet Does Not Protect Against Asymptomatic Diverticulosis
2012; 142 (2): 266-U158
The complications of diverticulosis cause considerable morbidity in the United States; health care expenditures for this disorder are estimated to be $2.5 billion per year. Many physicians and patients believe that a high-fiber diet and frequent bowel movements prevent the development of diverticulosis. Evidence for these associations is poor. We sought to determine whether low-fiber or high-fat diets, diets that include large quantities of red meat, constipation, or physical inactivity increase risk for asymptomatic diverticulosis.We performed a cross-sectional study of 2104 participants, 30-80 years old, who underwent outpatient colonoscopy from 1998 to 2010. Diet and physical activity were assessed in interviews using validated instruments.The prevalence of diverticulosis increased with age, as expected. High intake of fiber did not reduce the prevalence of diverticulosis. Instead, the quartile with the highest fiber intake had a greater prevalence of diverticulosis than the lowest (prevalence ratio = 1.30; 95% confidence interval, 1.13-1.50). Risk increased when calculated based on intake of total fiber, fiber from grains, soluble fiber, and insoluble fiber. Constipation was not a risk factor. Compared to individuals with <7 bowel movements per week, individuals with >15 bowel movements per week had a 70% greater risk for diverticulosis (prevalence ratio = 1.70; 95% confidence interval, 1.24-2.34). Neither physical inactivity nor intake of fat or red meat was associated with diverticulosis.A high-fiber diet and increased frequency of bowel movements are associated with greater, rather than lower, prevalence of diverticulosis. Hypotheses regarding risk factors for asymptomatic diverticulosis should be reconsidered.
View details for DOI 10.1053/j.gastro.2011.10.035
View details for Web of Science ID 000299540000033
View details for PubMedID 22062360
Simulation of Autonomous Robotic Multiple-Core Biopsy by 3D Ultrasound Guidance
2010; 32 (2): 118-127
An autonomous multiple-core biopsy system guided by real-time 3D ultrasound and operated by a robotic arm with 6+1 degrees of freedom has been developed. Using a specimen of turkey breast as a tissue phantom, our system was able to first autonomously locate the phantom in the image volume and then perform needle sticks in each of eight sectors in the phantom in a single session, with no human intervention required. Based on the fraction of eight sectors successfully sampled in an experiment of five trials, a success rate of 93% was recorded. This system could have relevance in clinical procedures that involve multiple needle-core sampling such as prostate or breast biopsy.
View details for Web of Science ID 000280155300005
View details for PubMedID 20687279
THREE-DIMENSIONAL ULTRASOUND GUIDANCE OF AUTONOMOUS ROBOTIC BREAST BIOPSY: FEASIBILITY STUDY
ULTRASOUND IN MEDICINE AND BIOLOGY
2010; 36 (1): 173-177
Feasibility studies of autonomous robot biopsies in tissue have been conducted using real-time three-dimensional (3-D) ultrasound combined with simple thresholding algorithms. The robot first autonomously processed 3-D image volumes received from the ultrasound scanner to locate a metal rod target embedded in turkey breast tissue simulating a calcification, and in a separate experiment, the center of a water-filled void in the breast tissue simulating a cyst. In both experiments the robot then directed a needle to the desired target, with no user input required. Separate needle-touch experiments performed by the image-guided robot in a water tank yielded an rms error of 1.15 mm. (E-mail: email@example.com).
View details for DOI 10.1016/j.ultrasmedbio.2009.08.014
View details for Web of Science ID 000278012200019
View details for PubMedID 19900753
3-D Ultrasound Guidance of Autonomous Robot for Location of Ferrous Shrapnel
IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL
2009; 56 (7): 1301-1303
Vibrations can be induced in ferromagnetic shrapnel by a variable electromagnet. Real time 3-D color Doppler ultrasound located the induced motion in a needle fragment and determined its 3-D position in the scanner coordinates. This information was used to guide a robot which moved a probe to touch the shrapnel fragment.
View details for DOI 10.1109/TUFFC.2009.1185
View details for Web of Science ID 000267222400006
View details for PubMedID 19574140