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2. The Molecular Basis of the Frank-Starling Law of the Heart: A Possible Role for PIEZO1?

Author

dos Remedios, C. G., primary, Law, K. Y. C., additional, McNamara, J. W., additional, Kraft, T., additional, Peckham, M., additional, van der Velden, J., additional, Linke, W. A., additional, Ackerman, M., additional, Sequeira, V., additional, Lal, S., additional, Cooke, R., additional, Grosser, M., additional, Campbell, K. S., additional, Martinac, B., additional, and Li, A., additional

Published
2024
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3. Visual and Refractive Efficacy of Panoptix Toric Intraocular Lens in a Clinical Setting

Author

Ackerman M, Lawless M, Levitz L, Bhatt U, Reich JA, Sutton G, Roberts TV, Tenen A, Kaur A, and Hodge C

Subjects
cataract surgery, iol, trifocal, lens extraction, visual acuity, Ophthalmology, RE1-994
Abstract

Mariska Ackerman,1 Michael Lawless,2,3 Lewis Levitz,4 Uday Bhatt,4 Joseph A Reich,4 Gerard Sutton,2,3 Timothy V Roberts,2,3 Abi Tenen,4 Amanpreet Kaur,4 Chris Hodge2,3,5,6 1Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia; 2Vision Eye Institute, Sydney, New South Wales, Australia; 3Save Sight Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; 4Vision Eye Institute, Melbourne, Victoria, Australia; 5Graduate School of Health, University of Technology Sydney, Sydney, New South Wales, Australia; 6Macquarie University, Sydney, AustraliaCorrespondence: Michael Lawless, Vision Eye Institute, Level 3 270 Victoria Avenue, Chatswood, Sydney, NSW, 2067, Australia, Tel +61 2 9424 9999, Fax +61 2 9410 3000, Email michael.lawless@vei.com.auPurpose: Trifocal Intraocular Lenses (IOLs) were developed to provide patients with effective near, intermediate and distance vision, thus minimizing spectacle dependency. Residual astigmatism has previously been shown to impact unaided visual acuity across all distances; therefore, to optimise the expected outcomes, consideration of preoperative corneal astigmatism is essential. The purpose of this study was to provide a real-world, multi-site review of visual and refractive outcomes in eyes undergoing implantation with the Panoptix Trifocal toric IOL platform.Patients and Methods: This study represents a two-fold approach. Patients who had previously undergone routine cataract removal and IOL insertion with the Panoptix Toric IOL were retrospectively analysed for routine efficacy and safety endpoints (“Retrospective Cohort”). Data was retrieved from the preoperative, surgical and postoperative visits (range 2– 6 weeks). A further subset of patients undergoing lens removal and bilateral Panoptix Toric IOL insertion were identified at surgery (“Qualitative Cohort”). These patients underwent additional testing inclusive of quality of vision questionnaire and bilateral defocus curve.Results: A total of 466 eyes of 254 patients were included in the retrospective cohort. Between 91% and 98% of eyes, respectively, were within 0.50D and 1.00D of target. Mean absolute difference from Spherical Equivalent (SE) target was 0.22 ± 0.24Ds. Following surgery, 94% of eyes demonstrated a refractive astigmatism of 0.50D or less. Further, 61% eyes achieved uncorrected distance visual acuity (UDVA) of 20/20 or better, increasing to 94% achieving 20/32 or better. Seventy percent of eyes unilaterally achieved N5 unaided and 66.0% achieved N8 or better at intermediate. In the qualitative cohort, no patient described any symptom as significant or requested explant.Conclusion: In a real-world setting, the PanOptix toric trifocal IOL continues to demonstrate refractive accuracy and good visual performance at all focal distances. This IOL also exhibited good quality of vision, with minimally bothersome visual disturbances or photic phenomena.Keywords: cataract surgery, IOL, trifocal, lens extraction, visual acuity

Published
2022

4. Therapeutic Efficacy of Mexiletine for Long QT Syndrome Type 2: Evidence from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, Transgenic Rabbits, and Patients

Author

Crotti, L, Neves, R, Dagradi, F, Musu, G, Giannetti, F, Bos, J, Barbieri, M, Cerea, P, Giovenzana, F, Torchio, M, Mura, M, Gnecchi, M, Conte, G, Auricchio, A, Sala, L, Odening, K, Ackerman, M, Schwartz, P, Crotti L., Neves R., Dagradi F., Musu G., Giannetti F., Bos J. M., Barbieri M., Cerea P., Giovenzana F. L. F., Torchio M., Mura M., Gnecchi M., Conte G., Auricchio A., Sala L., Odening K. E., Ackerman M. J., Schwartz P. J., Crotti, L, Neves, R, Dagradi, F, Musu, G, Giannetti, F, Bos, J, Barbieri, M, Cerea, P, Giovenzana, F, Torchio, M, Mura, M, Gnecchi, M, Conte, G, Auricchio, A, Sala, L, Odening, K, Ackerman, M, Schwartz, P, Crotti L., Neves R., Dagradi F., Musu G., Giannetti F., Bos J. M., Barbieri M., Cerea P., Giovenzana F. L. F., Torchio M., Mura M., Gnecchi M., Conte G., Auricchio A., Sala L., Odening K. E., Ackerman M. J., and Schwartz P. J.

Abstract

BACKGROUND: Despite major advances in the clinical management of long QT syndrome, some patients are not fully protected by beta-blocker therapy. Mexiletine is a well-known sodium channel blocker, with proven efficacy in patients with sodium channel-mediated long QT syndrome type 3. Our aim was to evaluate the efficacy of mexiletine in long QT syndrome type 2 (LQT2) using cardiomyocytes derived from patient-specific human induced pluripotent stem cells, a transgenic LQT2 rabbit model, and patients with LQT2. METHODS: Heart rate-corrected field potential duration, a surrogate for QTc, was measured in human induced pluripotent stem cells from 2 patients with LQT2 (KCNH2-p.A561V, KCNH2-p.R366X) before and after mexiletine using a multiwell multi-electrode array system. Action potential duration at 90% repolarization (APD90) was evaluated in cardiomyocytes isolated from transgenic LQT2 rabbits (KCNH2-p.G628S) at baseline and after mexiletine application. Mexiletine was given to 96 patients with LQT2. Patients were defined as responders in the presence of a QTc shortening >= 40 ms. Antiarrhythmic efficacy of mexiletine was evaluated by a Poisson regression model. RESULTS: After acute treatment with mexiletine, human induced pluripotent stem cells from both patients with LQT2 showed a significant shortening of heart rate-corrected field potential duration compared with dimethyl sulfoxide control. In cardiomyocytes isolated from LQT2 rabbits, acute mexiletine significantly shortened APD90 by 113 ms, indicating a strong mexiletine-mediated shortening across different LQT2 model systems. Mexiletine was given to 96 patients with LQT2 either chronically (n=60) or after the acute oral drug test (n=36): 65% of the patients taking mexiletine only chronically and 75% of the patients who performed the acute oral test were responders. There was a significant correlation between basal QTc and triangle QTc during the test (r= -0.8; P<0.001). The oral drug test correctly predicte

Published
2024

5. To Cluster, or Not to Cluster: An Analysis of Clusterability Methods

Author

Adolfsson, A., Ackerman, M., and Brownstein, N. C.

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning
Abstract

Clustering is an essential data mining tool that aims to discover inherent cluster structure in data. For most applications, applying clustering is only appropriate when cluster structure is present. As such, the study of clusterability, which evaluates whether data possesses such structure, is an integral part of cluster analysis. However, methods for evaluating clusterability vary radically, making it challenging to select a suitable measure. In this paper, we perform an extensive comparison of measures of clusterability and provide guidelines that clustering users can reference to select suitable measures for their applications., Comment: 30 pages, 3 figures, 10 tables

Published
2018
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6. In vivo KCNQ1-suppression-replacement gene therapy in transgenic LQT1 rabbits restores a physiological QT interval at baseline and under catecholamine infusion

Author

Giammarino, L, primary, Bains, S, additional, Louradour, J, additional, Nimani, S, additional, Alerni, N, additional, Tester, D, additional, Christoforou, N, additional, Horvath, A, additional, Beslac, O, additional, Koren, G, additional, Brunner, M, additional, Casoni, D, additional, Haeberlin, A, additional, Ackerman, M J, additional, and Odening, K E, additional

Published
2024
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7. In vivo KCNH2-suppression-replacement gene therapy attenuates the pathogenic phenotype in transgenic rabbits with short QT syndrome type 1

Author

Nimani, S, primary, Bains, S, additional, Alerni, N, additional, Giammarino, L, additional, Louradour, J, additional, Horvath, A, additional, Beslac, O, additional, Tester, D J, additional, Christoforou, N, additional, Brunner, M, additional, Casoni, D, additional, Haeberlin, A, additional, Brooks, G, additional, Ackerman, M J, additional, and Odening, K E, additional

Published
2024
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9. Early Donor Derived Cell-Free DNA Ratios Can Help Predict Future Rejection in Heart Transplant Recipients

Author

Miklin, D.J., primary, Ravi, K., additional, Qu, K., additional, Cochran, A., additional, Ackerman, M., additional, Cartus, R., additional, Fong, M., additional, Pandya, K., additional, Vaidya, A., additional, Wolfson, A., additional, Nattiv, J., additional, Stachel, M., additional, Kobulnik, J., additional, and DePasquale, E., additional

Published
2024
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10. Risk of Refractive Prediction Error After Cataract Surgery in Patients with Thyroid Eye Disease

Author

Strong Caldwell A, Patnaik JL, Ackerman M, Christopher KL, Lynch AM, and Singh JK

Subjects
thyroid eye disease, cataract surgery, refractive surprise, graves disease, Ophthalmology, RE1-994
Abstract

Anne Strong Caldwell,1 Jennifer L Patnaik,1 Melisa Ackerman,1 Karen L Christopher,1 Anne M Lynch,1 Jasleen K Singh2 1Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, USA; 2Department of Ophthalmology, Children’s Hospital of Colorado, Aurora, CO, USACorrespondence: Jasleen K SinghDepartment of Ophthalmology, Children’s Hospital of Colorado, 13123 E 16th Ave, Mailstop B430, Aurora, CO, 80045, USATel +1 706-877-0869Email Jasleen.singh@cuanschutz.eduPurpose: To investigate the risk of unexpected refractive prediction error after cataract surgery in patients with thyroid eye disease (TED) at the University of Colorado.Patients and Methods: A retrospective observational study was performed using records of patients who underwent cataract surgery (2014 to 2018) who were included in a Cataract Surgery Outcomes database. Any patient with documentation of thyroid eye disease (TED) in the medical record was classified as TED. Post-operative refraction error greater than or equal to ± 1.0 diopter from the target refraction was the main outcome of this study. Eyes with history of refractive surgery, ocular trauma, retinal detachment, non-Graves’ disease thyroid conditions or Graves’ disease without TED, and eyes without refractive error at follow-up were excluded.Results: A total of 5716 eyes from 3692 patients who underwent cataract surgery were analyzed. Sixty-five eyes of thirty-nine patients (1.1%) had TED. Former and/or current cigarette use was associated with having TED (p = 0.0504). Patients with TED had a statistically significant shorter axial length as compared to eyes without TED (p = 0.0257). Three hundred and forty-nine eyes (6.1%), including 9 eyes (13.8%) in patients with TED, had refractive prediction error greater than ± 1.0 diopter following surgery (univariate OR = 2.5, 95% CI: 1.1– 5.7, p = 0.0274). After multivariate analysis controlling for race, tobacco use, combined surgery, and axial length, TED was associated with an increased risk of our primary outcome, refractive prediction error greater than ± 1.0 diopter (OR = 2.4, 95% CI: 1.0– 5.7, p = 0.0506).Conclusion: Patients with TED are at increased risk for refractive prediction error following cataract surgery. Discussion with patients regarding their risk and possible need for glasses following surgery is important for setting realistic patient expectations.Keywords: thyroid eye disease, cataract surgery, refractive surprise, graves disease

Published
2021

11. Anomalous Dynamical Behavior of Freestanding Graphene Membranes

Author

Ackerman, M. L., Kumar, P., Neek-Amal, M., Thibado, P. M., Peeters, F. M., and Singh, S. P.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

We report subnanometer, high-bandwidth measurements of the out-of-plane (vertical) motion of atoms in freestanding graphene using scanning tunneling microscopy. By tracking the vertical position over a long time period, a 1000-fold increase in the ability to measure space-time dynamics of atomically thin membranes is achieved over the current state-of-the-art imaging technologies. We observe that the vertical motion of a graphene membrane exhibits rare long-scale excursions characterized by both anomalous mean-squared displacements and Cauchy-Lorentz power law jump distributions., Comment: 5 pages, 3 figures

Published
2016
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12. Streamlined Inexpensive Integration of a Growth Facility and Scanning Tunneling Microscope for in situ Characterization

Author

Xu, P., Qi, D., Barber, S. D., Cook, C. T., Ackerman, M. L., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Physics - Instrumentation and Detectors
Abstract

The integration of a scanning tunneling microscope chamber with a sample growth facility using non-custom, commercially available parts is described. The facility also features a newly-designed magnetic wobble stick to increase the reliability of sample transfer in a cost-effective manner., Comment: 16 pages, 6 figures

Published
2015
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13. Controlling Mn Depth Profiles in GaMnAs During High-Temperature Molecular Beam Epitaxial Growth

Author

Xu, P., Qi, D., Ackerman, M. L., Barber, S. D., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Mn-doped GaAs thin films were grown at a high substrate temperature of 580 C. During the growth process, the Mn cell temperature was ramped at different rates, resulting in a variety of different Mn concentration depth profile slopes, as measured using dynamic secondary ion mass spectrometry (SIMS). Results show that controlling the Mn deposition rate via temperature during molecular beam epitaxy (MBE) growth can mitigate the effect of Mn atoms diffusing toward the surface. Most importantly, the slope of the Mn concentration as a function of depth inside the sample can be tuned from negative to positive., Comment: 15 pages, 3 figures

Published
2015

14. Giant Surface Charge Density of Graphene Resolved From Scanning Tunneling Microscopy and First-Principles Theory

Author

Xu, P., Yang, Y., Barber, S. D., Ackerman, M. L., Schoelz, J. K., Kornev, I. A., Barraza-Lopez, S., Bellaiche, L., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

In this work, systematic constant-bias, variable-current scanning tunneling microscopy (STM) measurements and STM simulations from density-functional theory are made, yielding critical insights into the spatial structure of electrons in graphene. A foundational comparison is drawn between graphene and graphite, showing the surface charge density of graphene to be 300 percent that of graphite. Furthermore, simulated STM images reveal that high-current STM better resolves graphenes honeycomb bonding structure because of a retraction which occurs in the topmost dangling bond orbitals., Comment: 18 pages, 3 figures

Published
2015

15. Atomic Control of Strain in Freestanding Graphene

Author

Xu, P., Yang, Y., Barber, S. D., Ackerman, M. L., Schoelz, J. K., Qi, D., Kornev, I. A., Dong, L., Bellaiche, L., Barraza-Lopez, S., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

In this study, we describe a new experimental approach based on constant-current scanning tunneling spectroscopy to controllably and reversibly pull freestanding graphene membranes up to 35 nm from their equilibrium height. In addition, we present scanning tunneling microscopy (STM) images of freestanding graphene membranes with atomic resolution. Atomic-scale corrugation amplitudes 20 times larger than the STM electronic corrugation for graphene on a substrate were observed. The freestanding graphene membrane responds to a local attractive force created at the STM tip as a highly-conductive yet flexible grounding plane with an elastic restoring force. We indicate possible applications of our method in the controlled creation of pseudo-magnetic fields by strain on single-layer graphene., Comment: 16 pages, 3 figures

Published
2015

16. High-Percentage Success Method for Preparing and Pre-Evaluating Tungsten Tips for Atomic-Resolution Scanning Tunneling Microscopy

Author

Schoelz, J. K., Xu, P., Barber, S. D., Qi, D., Ackerman, M. L., Basnet, G., Cook, C. T., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

A custom double-lamella method is presented for electrochemically etching tungsten wire for use as tips in scanning tunneling microscopy (STM). For comparison, tips were also manufactured in-house using numerous conventional methods and examined using an optical microscope. Both sets of tips were used to obtain STM images of highly-oriented pyrolytic graphite, the quality of which varied. The clarity of the STM images was found to be correlated to the optically-measured cone angle of the STM tip, with larger cone angles consistently producing atomically resolved images. The custom etching procedure described allows one to create larger cone angles and consequently proved superior in reliably producing high-quality tips., Comment: 17 pages, 2 figures

Published
2015

17. A Pathway between Bernal and Rhombohedral Stacked Graphene Layers with Scanning Tunneling Microscopy

Author

Xu, P., Yang, Y., Qi, D., Barber, S. D., Ackerman, M. L., Schoelz, J. K., Bothwell, T. B., Barraza-Lopez, S., Bellaiche, L., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Condensed Matter - Materials Science
Abstract

Horizontal shifts in the top layer of highly oriented pyrolytic graphite, induced by a scanning tunneling microscope (STM) tip, are presented. Excellent agreement is found between STM images and those simulated using density functional theory. First-principle calculations identify that the low-energy barrier direction of the top layer displacement is toward a structure where none of the carbon pz orbitals overlap, while the high-energy barrier direction is toward AA stacking. Each directional shift yields a real-space surface charge density similar to graphene; however the low-energy barrier direction requires only one bond length to convert ABA (Bernal) to ABC (rhombohedral)., Comment: 12 pages, 2 figures. arXiv admin note: substantial text overlap with arXiv:1501.07827

Published
2015

18. Schottky barrier and attenuation length for hot hole injection in non-epitaxial Au on p-type GaAs

Author

Sitnitsky, I., Garramone, J. J., Abel, J. R., Xu, P., Barber, S. D., Ackerman, M. L., Schoelz, J. K., Thibado, P. M., and LaBella, V. P.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Ballistic electron emission microscopy (BEEM) was performed to obtain nanoscale current versus bias characteristics of non-epitaxial Au on p-type GaAs in order to accurately measure the local Schottky barrier height. Hole injection BEEM data was averaged from thousands of spectra for various metal film thicknesses and then used to determine the attenuation length of the energetic charge carriers as a function of tip bias. We report the marked increase in attenuation length at biases near the Schottky barrier, providing evidence for the existence of coherent BEEM currents in Schottky diodes. These results provide additional evidence against the randomization of a charge carrier's momentum at the metal-semiconductor interface., Comment: 16 pages, 4 figures

Published
2015

19. Electromechanical properties of freestanding graphene functionalized with tin oxide (SnO2) nanoparticles

Author

Dong, L., Hansen, J., Xu, P., Ackerman, M. L., Barber, S. D., Schoelz, J. K., Qi, D., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Freestanding graphene membranes were functionalized with SnO2 nanoparticles. A detailed procedure providing uniform coverage and chemical synthesis is presented. Elemental composition was determined using scanning electron microscopy combined with energy dispersive X-ray analysis. A technique called electrostatic-manipulation scanning tunneling microscopy was used to probe the electromechanical properties of functionalized freestanding graphene samples. We found ten times larger movement perpendicular to the plane compared to pristine freestanding graphene, and propose a nanoparticle encapsulation model., Comment: 14 pages, 3 figures

Published
2015
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20. Electronic transition from graphite to graphene via controlled movement of the top layer with scanning tunneling microscopy

Author

Xu, P., Yang, Y., Qi, D., Barber, S. D., Schoelz, J. K., Ackerman, M. L., Bellaiche, L., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

A series of measurements using a technique called electrostatic-manipulation scanning tunneling microscopy (EM-STM) were performed on a highly-oriented pyrolytic graphite surface. The electrostatic interaction between the STM tip and the sample can be tuned to produce both reversible and irreversible large-scale movement of the graphite surface. Under this influence, atomic-resolution STM images reveal that a continuous electronic transition from triangular symmetry, where only alternate atoms are imaged, to hexagonal symmetry can be systematically controlled. Density functional theory (DFT) calculations reveal that this transition can be related to vertical displacements of the top layer of graphite relative to the bulk. Evidence for horizontal shifts in the top layer of graphite is also presented. Excellent agreement is found between experimental STM images and those simulated using DFT., Comment: 36 pages, 8 figures

Published
2015
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21. New Scanning Tunneling Microscopy Technique Enables Systematic Study of the Unique Electronic Transition from Graphite to Graphene

Author

Xu, P., Yang, Y., Barber, S. D., Schoelz, J. K., Qi, D., Ackerman, M. L., Bellaiche, L., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

A series of measurements using a novel technique called electrostatic-manipulation scanning tunneling microscopy were performed on a highly-oriented pyrolytic graphite (HOPG) surface. The electrostatic interaction between the STM tip and the sample can be tuned to produce both reversible and irreversible large-scale vertical movement of the HOPG surface. Under this influence, atomic-resolution STM images reveal that a continuous electronic reconstruction transition from a triangular symmetry, where only alternate atoms are imaged, to a honeycomb structure can be systematically controlled. First-principles calculations reveal that this transition can be related to vertical displacements of the top layer of graphite relative to the bulk. Detailed analysis of the band structure predicts that a transition from parabolic to linear bands occurs after a 0.09 nm displacement of the top layer., Comment: 18 pages, 3 figures

Published
2015

22. Broad frequency and amplitude control of vibration in freestanding graphene via scanning tunneling microscopy with calculated dynamic pseudo-magnetic fields

Author

Xu, P., Schoelz, J. K., Barber, S. D., Ackerman, M. L., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

A technique to locally generate mechanical vibrations in freestanding graphene using scanning tunneling microscopy (STM) is presented. The frequency of the mechanical vibrations is tuned over nearly four decades and is centered around 10 Hz. The amplitude of the vibrations also changes over nearly three decades centered on 1 nm. The oscillating motion is generated in two ways: first, by scanning the STM tip on the surface and second, by scanning the bias voltage on the STM tip. The frequency and amplitude of the displaced freestanding graphene is quantitatively transformed to the frequency and strength of the locally generated pseudo-magnetic field for our specific geometry., Comment: 14 pages, 2 figures

Published
2015
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23. Graphene Manipulation on 4H-SiC(0001) Using Scanning Tunneling Microscopy

Author

Xu, P., Ackerman, M. L., Barber, S. D., Schoelz, J. K., Qi, D., Thibado, P. M., Wheeler, V. D., Nyakiti, L. O., Myers-Ward, R. L., Eddy, Jr., C. R., and Gaskill, D. K.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Atomic-scale topography of epitaxial multilayer graphene grown on 4H-SiC(0001) was investigated using scanning tunneling microscopy (STM). Bunched nano-ridges ten times smaller than previously recorded were observed throughout the surface, the morphology of which was systematically altered using a relatively new technique called electrostatic-manipulation scanning tunneling microscopy. Transformed graphene formations sometimes spontaneously returned to their original morphology, while others permanently changed. Using an electrostatic model, we calculate that a force up to ~5 nN was exerted by the STM tip, and an energy of around 10 eV was required to alter the geometry of a ~100 X 200 nm^2 area., Comment: 12 pages, 2 figures

Published
2015
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24. Atomic-Scale Movement Induced in Nano-Ridges by Scanning Tunneling Microscopy on Epitaxial Graphene Grown on 4H-SiC(0001)

Author

Xu, P., Barber, S. D., Schoelz, J. K., Ackerman, M. L., Qi, D., Thibado, P. M., Wheeler, V. D., Nyakiti, L. O., Myers-Ward, R. L., Eddy Jr., C. R., and Gaskill, D. K.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Nanoscale ridges in epitaxial multilayer graphene grown on the silicon face of 4 degree off-cut 4H-SiC (0001) were found using scanning tunneling microscopy (STM). These nano-ridges are only 0.1 nm high and 25-50 nm wide, making them much smaller than previously reported ridges. Atomic-resolution STM was performed near and on top of the nano-ridges using a dual scanning technique in which forward and reverse images are simultaneously recorded. An apparent 100% enlarged graphene lattice constant is observed along the leading edge of the image for both directions. Horizontal movement of the graphene, due to both an electrostatic attraction to the STM tip and weak bonding to the substrate, is thought to contribute to the results., Comment: 20 pages, 4 figures

Published
2015

25. Role of bias voltage and tunneling current in the perpendicular displacements of freestanding graphene via scanning tunneling microscopy

Author

Xu, P., Barber, S. D., Ackerman, M. L., Schoelz, J. K., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Systematic displacement measurements of freestanding graphene as a function of applied bias voltage and tunneling current setpoint using scanning tunneling microscopy (STM) are presented. When the bias voltage is increased the graphene approaches the STM tip, while, on the other hand, when the tunneling current is increased the graphene contracts from the STM tip. To understand the role of the bias voltage, we quantitatively model the attractive force between the tip and the sample using electrostatics. For the tunneling current, we qualitatively model the contraction of the graphene using entropic concepts. These complementary results enhance the understanding of each other and highlight peculiarities of the system., Comment: 18 pages, 3 figures

Published
2015

26. Etch-stop method for reliably fabricating sharp yet mechanically stable scanning tunneling microscope tips

Author

Basnet, G., Schoelz, J. K., Xu, P., Barber, S. D., Ackerman, M. L., and Thibado, P. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

An extension of the direct-current, double-lamella drop-off technique for electrochemically etching tungsten scanning-tunneling-microscope tips is presented. The key fabrication step introduced here is the use of an etch stop as a simple but accurate way to optimize the contact area between the etchant and the wire. By restricting the etching process, the final cone angle of the tips can be made sharp and mechanically stable without a lot of finesse from the STM tip maker.

Published
2015

27. Competing scanning tunneling microscope tip-interlayer interactions for twisted multilayer graphene on the a-plane SiC surface

Author

Xu, P., Ackerman, M. L., Barber, S. D., Schoelz, J. K., Thibado, P. M., Wheeler, V. D., Nyakiti, L. O., Myers-Ward, R. L., Eddy Jr., C. R., and Gaskill, D. K.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Condensed Matter - Materials Science
Abstract

Scanning tunneling microscopy (STM) images are obtained for the first time on few layer and twisted multilayer epitaxial graphene states synthesized on n+ 6H-SiC a-plane non-polar surface. The twisted graphene is determined to have a rotation angle of 5.4{\deg} between the top two layers, by comparing moir\'e patterns from stick and ball models of bilayer graphene to experimentally obtained images. Furthermore, the experimental moir\'e pattern shows dynamic behavior, continuously shuffling between two stable surface arrangements one bond length apart. The moir\'e pattern shifts by more than 1 nm, making it easy to observe with STM. Explanation of this dynamic behavior is attributed to electrostatic interactions between the STM tip and the graphene sample., Comment: 20 pages, 5 figures

Published
2015
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28. Thermal mirror buckling in freestanding graphene locally controlled by scanning tunneling microscopy

Author

Neek-Amal, M., Xu, P., Schoelz, J. K., Ackerman, M. L., Barber, S. D., Thibado, P. M., Sadeghi, A., and Peeters, F. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Knowledge of and control over the curvature of ripples in freestanding graphene are desirable for fabricating and designing flexible electronic devices, and recent progress in these pursuits has been achieved using several advanced techniques such as scanning tunneling microscopy. The electrostatic forces induced through a bias voltage (or gate voltage) were used to manipulate the interaction of freestanding graphene with a tip (substrate). Such forces can cause large movements and sudden changes in curvature through mirror buckling. Here we explore an alternative mechanism, thermal load, to control the curvature of graphene. We demonstrate thermal mirror buckling of graphene by scanning tunneling microscopy and large-scale molecular dynamic simulations. The negative thermal expansion coefficient of graphene is an essential ingredient in explaining the observed effects. This new control mechanism represents a fundamental advance in understanding the influence of temperature gradients on the dynamics of freestanding graphene and future applications with electro-thermal-mechanical nanodevices., Comment: 25 pages, 5 figures

Published
2014
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29. Unusual ultralow frequency fluctuations in freestanding graphene

Author

Xu, P., Neek-Amal, M., Barber, S. D., Schoelz, J. K., Ackerman, M. L., Thibado, P. M., Sadeghi, A., and Peeters, F. M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Intrinsic ripples in freestanding graphene have been exceedingly difficult to study. Individual ripple geometry was recently imaged using scanning tunneling microscopy, but these measurements are limited to static configurations. Thermally-activated flexural phonon modes should generate dynamic changes in curvature. Here we show how to track the vertical movement of a one-square-angstrom region of freestanding graphene using scanning tunneling microscopy, thereby allowing measurement of the out-of-plane time trajectory and fluctuations over long time periods. We also present a model from elasticity theory to explain the very-low-frequency oscillations. Unexpectedly, we sometimes detect a sudden colossal jump, which we interpret as due to mirror buckling. This innovative technique provides a much needed atomic-scale probe for the time-dependent behavior of intrinsic ripples. The discovery of this novel progenitor represents a fundamental advance in the use of scanning tunneling microscopy, which together with the application of a thermal load provides a low-frequency nano-resonator., Comment: 22 pages, 4 figures

Published
2014
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30. Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry

Author

Crotti, L, Spazzolini, C, Nyegaard, M, Overgaard, M, Kotta, M, Dagradi, F, Sala, L, Aiba, T, Ayers, M, Baban, A, Barc, J, Beach, C, Behr, E, Bos, J, Cerrone, M, Covi, P, Cuneo, B, Denjoy, I, Donner, B, Elbert, A, Eliasson, H, Etheridge, S, Fukuyama, M, Girolami, F, Hamilton, R, Horie, M, Iascone, M, Jaimez, J, Jensen, H, Kannankeril, P, Kaski, J, Makita, N, Muñoz-Esparza, C, Odland, H, Ohno, S, Papagiannis, J, Porretta, A, Prandstetter, C, Probst, V, Robyns, T, Rosenthal, E, Rosés-Noguer, F, Sekarski, N, Singh, A, Spentzou, G, Stute, F, Tfelt-Hansen, J, Till, J, Tobert, K, Vinocur, J, Webster, G, Wilde, A, Wolf, C, Ackerman, M, Schwartz, P, Crotti L., Spazzolini C., Nyegaard M., Overgaard M. T., Kotta M. C., Dagradi F., Sala L., Aiba T., Ayers M. D., Baban A., Barc J., Beach C. M., Behr E. R., Bos J. M., Cerrone M., Covi P., Cuneo B., Denjoy I., Donner B., Elbert A., Eliasson H., Etheridge S. P., Fukuyama M., Girolami F., Hamilton R., Horie M., Iascone M., Jaimez J. J., Jensen H. K., Kannankeril P. J., Kaski J. P., Makita N., Muñoz-Esparza C., Odland H. H., Ohno S., Papagiannis J., Porretta A. P., Prandstetter C., Probst V., Robyns T., Rosenthal E., Rosés-Noguer F., Sekarski N., Singh A., Spentzou G., Stute F., Tfelt-Hansen J., Till J., Tobert K. E., Vinocur J. M., Webster G., Wilde A. A. M., Wolf C. M., Ackerman M. J., Schwartz P. J., Crotti, L, Spazzolini, C, Nyegaard, M, Overgaard, M, Kotta, M, Dagradi, F, Sala, L, Aiba, T, Ayers, M, Baban, A, Barc, J, Beach, C, Behr, E, Bos, J, Cerrone, M, Covi, P, Cuneo, B, Denjoy, I, Donner, B, Elbert, A, Eliasson, H, Etheridge, S, Fukuyama, M, Girolami, F, Hamilton, R, Horie, M, Iascone, M, Jaimez, J, Jensen, H, Kannankeril, P, Kaski, J, Makita, N, Muñoz-Esparza, C, Odland, H, Ohno, S, Papagiannis, J, Porretta, A, Prandstetter, C, Probst, V, Robyns, T, Rosenthal, E, Rosés-Noguer, F, Sekarski, N, Singh, A, Spentzou, G, Stute, F, Tfelt-Hansen, J, Till, J, Tobert, K, Vinocur, J, Webster, G, Wilde, A, Wolf, C, Ackerman, M, Schwartz, P, Crotti L., Spazzolini C., Nyegaard M., Overgaard M. T., Kotta M. C., Dagradi F., Sala L., Aiba T., Ayers M. D., Baban A., Barc J., Beach C. M., Behr E. R., Bos J. M., Cerrone M., Covi P., Cuneo B., Denjoy I., Donner B., Elbert A., Eliasson H., Etheridge S. P., Fukuyama M., Girolami F., Hamilton R., Horie M., Iascone M., Jaimez J. J., Jensen H. K., Kannankeril P. J., Kaski J. P., Makita N., Muñoz-Esparza C., Odland H. H., Ohno S., Papagiannis J., Porretta A. P., Prandstetter C., Probst V., Robyns T., Rosenthal E., Rosés-Noguer F., Sekarski N., Singh A., Spentzou G., Stute F., Tfelt-Hansen J., Till J., Tobert K. E., Vinocur J. M., Webster G., Wilde A. A. M., Wolf C. M., Ackerman M. J., and Schwartz P. J.

Abstract

Aims: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. Methods and results: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P =. 001) and sudden death (9% vs. 27%; P =. 008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. Conclusion: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator.

Published
2023

31. Physiology and evolution of nitrate acquisition in Prochlorococcus

Author

Berube, PM, Biller, SJ, Kent, AG, Berta-Thompson, JW, Roggensack, SE, Roache-Johnson, KH, Ackerman, M, Moore, LR, Meisel, JD, Sher, D, Thompson, LR, Campbell, L, Martiny, AC, and Chisholm, SW

Subjects
Environmental Sciences, Biological Sciences, Technology, Microbiology
Abstract

Prochlorococcus is the numerically dominant phototroph in the oligotrophic subtropical ocean and carries out a significant fraction of marine primary productivity. Although field studies have provided evidence for nitrate uptake by Prochlorococcus, little is known about this trait because axenic cultures capable of growth on nitrate have not been available. Additionally, all previously sequenced genomes lacked the genes necessary for nitrate assimilation. Here we introduce three Prochlorococcus strains capable of growth on nitrate and analyze their physiology and genome architecture. We show that the growth of high-light (HL) adapted strains on nitrate is ∼17% slower than their growth on ammonium. By analyzing 41 Prochlorococcus genomes, we find that genes for nitrate assimilation have been gained multiple times during the evolution of this group, and can be found in at least three lineages. In low-light adapted strains, nitrate assimilation genes are located in the same genomic context as in marine Synechococcus. These genes are located elsewhere in HL adapted strains and may often exist as a stable genetic acquisition as suggested by the striking degree of similarity in the order, phylogeny and location of these genes in one HL adapted strain and a consensus assembly of environmental Prochlorococcus metagenome sequences. In another HL adapted strain, nitrate utilization genes may have been independently acquired as indicated by adjacent phage mobility elements; these genes are also duplicated with each copy detected in separate genomic islands. These results provide direct evidence for nitrate utilization by Prochlorococcus and illuminate the complex evolutionary history of this trait.

Published
2015

34. Cost-effectiveness analysis of genetic testing for familial long QT syndrome in symptomatic index cases

Author

Phillips, Kathryn A, Ackerman, M J, Sakowski, J, and Berul, C I

Subjects
cost-effectiveness analysis, familial long QT syndrome, genetic testing
Abstract

Background Genetic testing for long QT syndrome (LQTS) has been available in a research setting for the past decade, and a commercial test has recently become available. However, the costs and effectiveness of genetic testing have not been estimated. Objectives The purpose of this study was to conduct a cost-effectiveness analysis of genetic testing in the management of patients who have or are suspected to have familial LQTS. Methods We examined the incremental cost-effectiveness of genetic testing compared with no genetic testing for symptomatic index cases and how this varied according to changes in assumptions and data inputs. Data were obtained from the published literature and a clinical cohort. RESULTS We found that genetic testing is more cost-effective than not testing for symptomatic index cases at an estimated cost of $2,500 per year of life saved. These results were generally robust, although they were sensitive to some data inputs such as the cost of testing and the mortality rate among untreated individuals with LQTS. Conclusion A genetic test for familial LQTS is cost-effective relative to no testing, given our assumptions about the population to be tested and the relevant probabilities and costs. The primary benefit of testing is to more accurately diagnose and treat individuals based on a combination of clinical scores and test results. Future economic analyses of testing for familial LQTS should consider the potential benefits of genetic testing of broader populations, including family members.

Published
2005

35. Flecainide is associated with a reduction in arrhythmic events in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia

Author

Bergeman, A T, primary, Tanck, M W, additional, Kallas, D, additional, Sanatani, S, additional, Leenhardt, A, additional, Ackerman, M J, additional, Till, J, additional, Zorio, E, additional, Kannankeril, P J, additional, Kammeraad, J A E, additional, Aiba, T, additional, Semsarian, C, additional, Robyns, T, additional, Wilde, A A M, additional, and Van Der Werf, C, additional

Published
2023
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36. In vivo KCNQ1-suppression-replacement gene therapy in transgenic rabbits with type 1 long QT syndrome

Author

Giammarino, L, primary, Nimani, S, additional, Bains, S, additional, Alerni, N, additional, Tester, D J, additional, Christoforou, N, additional, Louradour, J, additional, Jurgensen, J, additional, Barry, M A, additional, Koren, G, additional, Zehender, M, additional, Brunner, M, additional, Brooks, G, additional, Ackerman, M J, additional, and Odening, K E, additional

Published
2023
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39. European Society of Cardiology quality indicators for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

Author

Aktaa, S, Tzeis, S, Gale, C, Ackerman, M, Arbelo, E, Behr, E, Crotti, L, D'Avila, A, de Chillou, C, Deneke, T, Figueiredo, M, Friede, T, Leclercq, C, Merino, J, Semsarian, C, Verstrael, A, Zeppenfeld, K, Tfelt-Hansen, J, Reichlin, T, Aktaa, Suleman, Tzeis, Stylianos, Gale, Chris P, Ackerman, Michael J, Arbelo, Elena, Behr, Elijah R, Crotti, Lia, d'Avila, Andre, de Chillou, Christian, Deneke, Thomas, Figueiredo, Márcio, Friede, Tim, Leclercq, Christophe, Merino, Jose L, Semsarian, Chris, Verstrael, Axel, Zeppenfeld, Katja, Tfelt-Hansen, Jacob, Reichlin, Tobias, Aktaa, S, Tzeis, S, Gale, C, Ackerman, M, Arbelo, E, Behr, E, Crotti, L, D'Avila, A, de Chillou, C, Deneke, T, Figueiredo, M, Friede, T, Leclercq, C, Merino, J, Semsarian, C, Verstrael, A, Zeppenfeld, K, Tfelt-Hansen, J, Reichlin, T, Aktaa, Suleman, Tzeis, Stylianos, Gale, Chris P, Ackerman, Michael J, Arbelo, Elena, Behr, Elijah R, Crotti, Lia, d'Avila, Andre, de Chillou, Christian, Deneke, Thomas, Figueiredo, Márcio, Friede, Tim, Leclercq, Christophe, Merino, Jose L, Semsarian, Chris, Verstrael, Axel, Zeppenfeld, Katja, Tfelt-Hansen, Jacob, and Reichlin, Tobias

Abstract

To develop a suite of quality indicators (QIs) for the management of patients with ventricular arrhythmias (VA) and the prevention of sudden cardiac death (SCD). The Working Group comprised experts in heart rhythm management including Task Force members of the 2022 European Society of Cardiology (ESC) Clinical Practice Guidelines for the management of patients with VA and the prevention of SCD, members of the European Heart Rhythm Association, international experts, and a patient representative. We followed the ESC methodology for QI development, which involves (i) the identification of the key domains of care for the management of patients with VA and the prevention of SCD by constructing a conceptual framework of care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified-Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. We identified eight domains of care for the management of patients with VA and the prevention of SCD: (i) structural framework, (ii) screening and diagnosis, (iii) risk stratification, (iv) patient education and lifestyle modification, (v) pharmacological treatment, (vi) device therapy, (vii) catheter ablation, and (viii) outcomes, which included 17 main and 4 secondary QIs across these domains. Following a standardized methodology, we developed 21 QIs for the management of patients with VA and the prevention of SCD. The implementation of these QIs will improve the care and outcomes of patients with VA and contribute to the prevention of SCD.

Published
2023

40. A Probabilistic Solution to the AX=XB Problem: Sensor Calibration without Correspondence

Author

Ackerman, M. Kendal, Chirikjian, Gregory S., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Doug, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Nielsen, Frank, editor, and Barbaresco, Frédéric, editor

Published
2013
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41. Cadherin 2-Related Arrhythmogenic Cardiomyopathy: Prevalence and Clinical Features

Author

Ghidoni, A, Elliott, P, Syrris, P, Calkins, H, James, C, Judge, D, Murray, B, Barc, J, Probst, V, Schott, J, Song, J, Hauer, R, Hoorntje, E, Van Tintelen, J, Schulze-Bahr, E, Hamilton, R, Mittal, K, Semsarian, C, Behr, E, Ackerman, M, Basso, C, Parati, G, Gentilini, D, Kotta, M, Mayosi, B, Schwartz, P, Crotti, L, Ghidoni A., Elliott P. M., Syrris P., Calkins H., James C. A., Judge D. P., Murray B., Barc J., Probst V., Schott J. J., Song J. -P., Hauer R. N. W., Hoorntje E. T., Van Tintelen J. P., Schulze-Bahr E., Hamilton R. M., Mittal K., Semsarian C., Behr E. R., Ackerman M. J., Basso C., Parati G., Gentilini D., Kotta M. -C., Mayosi B. M., Schwartz P. J., Crotti L., Ghidoni, A, Elliott, P, Syrris, P, Calkins, H, James, C, Judge, D, Murray, B, Barc, J, Probst, V, Schott, J, Song, J, Hauer, R, Hoorntje, E, Van Tintelen, J, Schulze-Bahr, E, Hamilton, R, Mittal, K, Semsarian, C, Behr, E, Ackerman, M, Basso, C, Parati, G, Gentilini, D, Kotta, M, Mayosi, B, Schwartz, P, Crotti, L, Ghidoni A., Elliott P. M., Syrris P., Calkins H., James C. A., Judge D. P., Murray B., Barc J., Probst V., Schott J. J., Song J. -P., Hauer R. N. W., Hoorntje E. T., Van Tintelen J. P., Schulze-Bahr E., Hamilton R. M., Mittal K., Semsarian C., Behr E. R., Ackerman M. J., Basso C., Parati G., Gentilini D., Kotta M. -C., Mayosi B. M., Schwartz P. J., and Crotti L.

Abstract

Background: Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by fibrofatty replacement of the right and left ventricle, often causing ventricular dysfunction and life-threatening arrhythmias. Variants in desmosomal genes account for up to 60% of cases. Our objective was to establish the prevalence and clinical features of ACM stemming from pathogenic variants in the nondesmosomal cadherin 2 (CDH2), a novel genetic substrate of ACM. Methods: A cohort of 500 unrelated patients with a definite diagnosis of ACM and no disease-causing variants in the main ACM genes was assembled. Genetic screening of CDH2 was performed through next-generation or Sanger sequencing. Whenever possible, cascade screening was initiated in the families of CDH2-positive probands, and clinical evaluation was performed. Results: Genetic screening of CDH2 led to the identification of 7 rare variants: 5, identified in 6 probands, were classified as pathogenic or likely pathogenic. The previously established p.D407N pathogenic variant was detected in 2 additional probands. Probands and family members with pathogenic/likely pathogenic variants in CDH2 were clinically evaluated, and along with previously published cases, altogether contributed to the identification of gene-specific features (13 cases from this cohort and 11 previously published, for a total of 9 probands and 15 family members). Ventricular arrhythmic events occurred in most CDH2-positive subjects (20/24, 83%), while the occurrence of heart failure was rare (2/24, 8.3%). Among probands, sustained ventricular tachycardia and sudden cardiac death occurred in 5/9 (56%). Conclusions: In this worldwide cohort of previously genotype-negative ACM patients, the prevalence of probands with CDH2 pathogenic/likely pathogenic variants was 1.2% (6/500). Our data show that this cohort of CDH2-ACM patients has a high incidence of ventricular arrhythmias, while evolution toward heart failure is rare.

Published
2021

42. Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls

Author

Walsh, R, Lahrouchi, N, Tadros, R, Kyndt, F, Glinge, C, Postema, P, Amin, A, Nannenberg, E, Ware, J, Whiffin, N, Mazzarotto, F, Skoric-Milosavljevic, D, Krijger, C, Arbelo, E, Babuty, D, Barajas-Martinez, H, Beckmann, B, Bezieau, S, Bos, J, Breckpot, J, Campuzano, O, Castelletti, S, Celen, C, Clauss, S, Corveleyn, A, Crotti, L, Dagradi, F, de Asmundis, C, Denjoy, I, Dittmann, S, Ellinor, P, Ortuno, C, Giustetto, C, Gourraud, J, Hazeki, D, Horie, M, Ishikawa, T, Itoh, H, Kaneko, Y, Kanters, J, Kimoto, H, Kotta, M, Krapels, I, Kurabayashi, M, Lazarte, J, Leenhardt, A, Loeys, B, Lundin, C, Makiyama, T, Mansourati, J, Martins, R, Mazzanti, A, Morner, S, Napolitano, C, Ohkubo, K, Papadakis, M, Rudic, B, Molina, M, Sacher, F, Sahin, H, Sarquella-Brugada, G, Sebastiano, R, Sharma, S, Sheppard, M, Shimamoto, K, Shoemaker, M, Stallmeyer, B, Steinfurt, J, Tanaka, Y, Tester, D, Usuda, K, van der Zwaag, P, Van Dooren, S, Van Laer, L, Winbo, A, Winkel, B, Yamagata, K, Zumhagen, S, Volders, P, Lubitz, S, Antzelevitch, C, Platonov, P, Odening, K, Roden, D, Roberts, J, Skinner, J, Tfelt-Hansen, J, van den Berg, M, Olesen, M, Lambiase, P, Borggrefe, M, Hayashi, K, Rydberg, A, Nakajima, T, Yoshinaga, M, Saenen, J, Kaab, S, Brugada, P, Robyns, T, Giachino, D, Ackerman, M, Brugada, R, Brugada, J, Gimeno, J, Hasdemir, C, Guicheney, P, Priori, S, Schulze-Bahr, E, Makita, N, Schwartz, P, Shimizu, W, Aiba, T, Schott, J, Redon, R, Ohno, S, Probst, V, Arnaout, A, Amelot, M, Anselme, F, Billon, O, Defaye, P, Dupuis, J, Jesel, L, Laurent, G, Maury, P, Pasquie, J, Wiart, F, Behr, E, Barc, J, Bezzina, C, Walsh R., Lahrouchi N., Tadros R., Kyndt F., Glinge C., Postema P. G., Amin A. S., Nannenberg E. A., Ware J. S., Whiffin N., Mazzarotto F., Skoric-Milosavljevic D., Krijger C., Arbelo E., Babuty D., Barajas-Martinez H., Beckmann B. M., Bezieau S., Bos J. M., Breckpot J., Campuzano O., Castelletti S., Celen C., Clauss S., Corveleyn A., Crotti L., Dagradi F., de Asmundis C., Denjoy I., Dittmann S., Ellinor P. T., Ortuno C. G., Giustetto C., Gourraud J. -B., Hazeki D., Horie M., Ishikawa T., Itoh H., Kaneko Y., Kanters J. K., Kimoto H., Kotta M. -C., Krapels I. P. C., Kurabayashi M., Lazarte J., Leenhardt A., Loeys B. L., Lundin C., Makiyama T., Mansourati J., Martins R. P., Mazzanti A., Morner S., Napolitano C., Ohkubo K., Papadakis M., Rudic B., Molina M. S., Sacher F., Sahin H., Sarquella-Brugada G., Sebastiano R., Sharma S., Sheppard M. N., Shimamoto K., Shoemaker M. B., Stallmeyer B., Steinfurt J., Tanaka Y., Tester D. J., Usuda K., van der Zwaag P. A., Van Dooren S., Van Laer L., Winbo A., Winkel B. G., Yamagata K., Zumhagen S., Volders P. G. A., Lubitz S. A., Antzelevitch C., Platonov P. G., Odening K. E., Roden D. M., Roberts J. D., Skinner J. R., Tfelt-Hansen J., van den Berg M. P., Olesen M. S., Lambiase P. D., Borggrefe M., Hayashi K., Rydberg A., Nakajima T., Yoshinaga M., Saenen J. B., Kaab S., Brugada P., Robyns T., Giachino D. F., Ackerman M. J., Brugada R., Brugada J., Gimeno J. R., Hasdemir C., Guicheney P., Priori S. G., Schulze-Bahr E., Makita N., Schwartz P. J., Shimizu W., Aiba T., Schott J. -J., Redon R., Ohno S., Probst V., Arnaout A. A., Amelot M., Anselme F., Billon O., Defaye P., Dupuis J. -M., Jesel L., Laurent G., Maury P., Pasquie J. -L., Wiart F., Behr E. R., Barc J., Bezzina C. R., Walsh, R, Lahrouchi, N, Tadros, R, Kyndt, F, Glinge, C, Postema, P, Amin, A, Nannenberg, E, Ware, J, Whiffin, N, Mazzarotto, F, Skoric-Milosavljevic, D, Krijger, C, Arbelo, E, Babuty, D, Barajas-Martinez, H, Beckmann, B, Bezieau, S, Bos, J, Breckpot, J, Campuzano, O, Castelletti, S, Celen, C, Clauss, S, Corveleyn, A, Crotti, L, Dagradi, F, de Asmundis, C, Denjoy, I, Dittmann, S, Ellinor, P, Ortuno, C, Giustetto, C, Gourraud, J, Hazeki, D, Horie, M, Ishikawa, T, Itoh, H, Kaneko, Y, Kanters, J, Kimoto, H, Kotta, M, Krapels, I, Kurabayashi, M, Lazarte, J, Leenhardt, A, Loeys, B, Lundin, C, Makiyama, T, Mansourati, J, Martins, R, Mazzanti, A, Morner, S, Napolitano, C, Ohkubo, K, Papadakis, M, Rudic, B, Molina, M, Sacher, F, Sahin, H, Sarquella-Brugada, G, Sebastiano, R, Sharma, S, Sheppard, M, Shimamoto, K, Shoemaker, M, Stallmeyer, B, Steinfurt, J, Tanaka, Y, Tester, D, Usuda, K, van der Zwaag, P, Van Dooren, S, Van Laer, L, Winbo, A, Winkel, B, Yamagata, K, Zumhagen, S, Volders, P, Lubitz, S, Antzelevitch, C, Platonov, P, Odening, K, Roden, D, Roberts, J, Skinner, J, Tfelt-Hansen, J, van den Berg, M, Olesen, M, Lambiase, P, Borggrefe, M, Hayashi, K, Rydberg, A, Nakajima, T, Yoshinaga, M, Saenen, J, Kaab, S, Brugada, P, Robyns, T, Giachino, D, Ackerman, M, Brugada, R, Brugada, J, Gimeno, J, Hasdemir, C, Guicheney, P, Priori, S, Schulze-Bahr, E, Makita, N, Schwartz, P, Shimizu, W, Aiba, T, Schott, J, Redon, R, Ohno, S, Probst, V, Arnaout, A, Amelot, M, Anselme, F, Billon, O, Defaye, P, Dupuis, J, Jesel, L, Laurent, G, Maury, P, Pasquie, J, Wiart, F, Behr, E, Barc, J, Bezzina, C, Walsh R., Lahrouchi N., Tadros R., Kyndt F., Glinge C., Postema P. G., Amin A. S., Nannenberg E. A., Ware J. S., Whiffin N., Mazzarotto F., Skoric-Milosavljevic D., Krijger C., Arbelo E., Babuty D., Barajas-Martinez H., Beckmann B. M., Bezieau S., Bos J. M., Breckpot J., Campuzano O., Castelletti S., Celen C., Clauss S., Corveleyn A., Crotti L., Dagradi F., de Asmundis C., Denjoy I., Dittmann S., Ellinor P. T., Ortuno C. G., Giustetto C., Gourraud J. -B., Hazeki D., Horie M., Ishikawa T., Itoh H., Kaneko Y., Kanters J. K., Kimoto H., Kotta M. -C., Krapels I. P. C., Kurabayashi M., Lazarte J., Leenhardt A., Loeys B. L., Lundin C., Makiyama T., Mansourati J., Martins R. P., Mazzanti A., Morner S., Napolitano C., Ohkubo K., Papadakis M., Rudic B., Molina M. S., Sacher F., Sahin H., Sarquella-Brugada G., Sebastiano R., Sharma S., Sheppard M. N., Shimamoto K., Shoemaker M. B., Stallmeyer B., Steinfurt J., Tanaka Y., Tester D. J., Usuda K., van der Zwaag P. A., Van Dooren S., Van Laer L., Winbo A., Winkel B. G., Yamagata K., Zumhagen S., Volders P. G. A., Lubitz S. A., Antzelevitch C., Platonov P. G., Odening K. E., Roden D. M., Roberts J. D., Skinner J. R., Tfelt-Hansen J., van den Berg M. P., Olesen M. S., Lambiase P. D., Borggrefe M., Hayashi K., Rydberg A., Nakajima T., Yoshinaga M., Saenen J. B., Kaab S., Brugada P., Robyns T., Giachino D. F., Ackerman M. J., Brugada R., Brugada J., Gimeno J. R., Hasdemir C., Guicheney P., Priori S. G., Schulze-Bahr E., Makita N., Schwartz P. J., Shimizu W., Aiba T., Schott J. -J., Redon R., Ohno S., Probst V., Arnaout A. A., Amelot M., Anselme F., Billon O., Defaye P., Dupuis J. -M., Jesel L., Laurent G., Maury P., Pasquie J. -L., Wiart F., Behr E. R., Barc J., and Bezzina C. R.

Abstract

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes—rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10−18) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10−13). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. Conclusion: Large case–control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.

Published
2021

43. Prevalence and Phenotypic Correlations of Calmodulinopathy-Causative CALM1-3 Variants Detected in a Multicenter Molecular Autopsy Cohort of Sudden Unexplained Death Victims

Author

Clemens, D, Gray, B, Bagnall, R, Tester, D, Giudicessi, J, Maleszewski, J, Crotti, L, Schwartz, P, Matthews, E, Semsarian, C, Behr, E, Ackerman, M, Clemens D. J., Gray B., Bagnall R. D., Tester D. J., Giudicessi J. R., Maleszewski J. J., Crotti L., Schwartz P. J., Matthews E., Semsarian C., Behr E. R., Ackerman M. J., Clemens, D, Gray, B, Bagnall, R, Tester, D, Giudicessi, J, Maleszewski, J, Crotti, L, Schwartz, P, Matthews, E, Semsarian, C, Behr, E, Ackerman, M, Clemens D. J., Gray B., Bagnall R. D., Tester D. J., Giudicessi J. R., Maleszewski J. J., Crotti L., Schwartz P. J., Matthews E., Semsarian C., Behr E. R., and Ackerman M. J.

Published
2020

44. SCN5A mutation type and a genetic risk score associate variably with brugada syndrome phenotype in SCN5A families

Author

Wijeyeratne, Y, Tanck, M, Mizusawa, Y, Batchvarov, V, Barc, J, Crotti, L, Bos, J, Tester, D, Muir, A, Veltmann, C, Ohno, S, Page, S, Galvin, J, Tadros, R, Muggenthaler, M, Raju, H, Denjoy, I, Schott, J, Gourraud, J, Skoric-Milosavljevic, D, Nannenberg, E, Redon, R, Papadakis, M, Kyndt, F, Dagradi, F, Castelletti, S, Torchio, M, Meitinger, T, Lichtner, P, Ishikawa, T, Wilde, A, Takahashi, K, Sharma, S, Roden, D, Borggrefe, M, Mckeown, P, Shimizu, W, Horie, M, Makita, N, Aiba, T, Ackerman, M, Schwartz, P, Probst, V, Bezzina, C, Behr, E, Wijeyeratne Y. D., Tanck M. W., Mizusawa Y., Batchvarov V., Barc J., Crotti L., Bos J. M., Tester D. J., Muir A., Veltmann C., Ohno S., Page S. P., Galvin J., Tadros R., Muggenthaler M., Raju H., Denjoy I., Schott J. -J., Gourraud J. -B., Skoric-Milosavljevic D., Nannenberg E. A., Redon R., Papadakis M., Kyndt F., Dagradi F., Castelletti S., Torchio M., Meitinger T., Lichtner P., Ishikawa T., Wilde A. A. M., Takahashi K., Sharma S., Roden D. M., Borggrefe M. M., McKeown P. P., Shimizu W., Horie M., Makita N., Aiba T., Ackerman M. J., Schwartz P. J., Probst V., Bezzina C. R., Behr E. R., Wijeyeratne, Y, Tanck, M, Mizusawa, Y, Batchvarov, V, Barc, J, Crotti, L, Bos, J, Tester, D, Muir, A, Veltmann, C, Ohno, S, Page, S, Galvin, J, Tadros, R, Muggenthaler, M, Raju, H, Denjoy, I, Schott, J, Gourraud, J, Skoric-Milosavljevic, D, Nannenberg, E, Redon, R, Papadakis, M, Kyndt, F, Dagradi, F, Castelletti, S, Torchio, M, Meitinger, T, Lichtner, P, Ishikawa, T, Wilde, A, Takahashi, K, Sharma, S, Roden, D, Borggrefe, M, Mckeown, P, Shimizu, W, Horie, M, Makita, N, Aiba, T, Ackerman, M, Schwartz, P, Probst, V, Bezzina, C, Behr, E, Wijeyeratne Y. D., Tanck M. W., Mizusawa Y., Batchvarov V., Barc J., Crotti L., Bos J. M., Tester D. J., Muir A., Veltmann C., Ohno S., Page S. P., Galvin J., Tadros R., Muggenthaler M., Raju H., Denjoy I., Schott J. -J., Gourraud J. -B., Skoric-Milosavljevic D., Nannenberg E. A., Redon R., Papadakis M., Kyndt F., Dagradi F., Castelletti S., Torchio M., Meitinger T., Lichtner P., Ishikawa T., Wilde A. A. M., Takahashi K., Sharma S., Roden D. M., Borggrefe M. M., McKeown P. P., Shimizu W., Horie M., Makita N., Aiba T., Ackerman M. J., Schwartz P. J., Probst V., Bezzina C. R., and Behr E. R.

Abstract

Background: Brugada syndrome (BrS) is characterized by the type 1 Brugada ECG pattern. Pathogenic rare variants in SCN5A (mutations) are identified in 20% of BrS families in whom incomplete penetrance and genotype-negative phenotype-positive individuals are observed. E1784K-SCN5A is the most common SCN5A mutation identified. We determined the association of a BrS genetic risk score (BrS-GRS) and SCN5A mutation type on BrS phenotype in BrS families with SCN5A mutations. Methods: Subjects with a spontaneous type 1 pattern or positive/negative drug challenge from cohorts harboring SCN5A mutations were recruited from 16 centers (n=312). Single nucleotide polymorphisms previously associated with BrS at genome-wide significance were studied in both cohorts: rs11708996, rs10428132, and rs9388451. An additive linear genetic model for the BrS-GRS was assumed (6 single nucleotide polymorphism risk alleles). Results: In the total population (n=312), BrS-GRS ≥4 risk alleles yielded an odds ratio of 4.15 for BrS phenotype ([95% CI, 1.45-11.85]; P=0.0078). Among SCN5A-positive individuals (n=258), BrS-GRS ≥4 risk alleles yielded an odds ratio of 2.35 ([95% CI, 0.89-6.22]; P=0.0846). In SCN5A-negative relatives (n=54), BrS-GRS ≥4 alleles yielded an odds ratio of 22.29 ([95% CI, 1.84-269.30]; P=0.0146). Among E1784K-SCN5A positive family members (n=79), hosting ≥4 risk alleles gave an odds ratio=5.12 ([95% CI, 1.93-13.62]; P=0.0011). Conclusions: Common genetic variation is associated with variable expressivity of BrS phenotype in SCN5A families, explaining in part incomplete penetrance and genotype-negative phenotype-positive individuals. SCN5A mutation genotype and a BrS-GRS associate with BrS phenotype, but the strength of association varies according to presence of a SCN5A mutation and severity of loss of function.

Published
2020

45. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases

Author

M Wilde, A, Semsarian, C, F Márquez, M, Sepehri Shamloo, A, J Ackerman, M, A Ashley, E, Sternick Eduardo, B, Barajas-Martinez, H, R Behr, E, R Bezzina, C, Breckpot, J, Charron, P, Chockalingam, P, Crotti, L, H Gollob, M, Lubitz, S, Makita, N, Ohno, S, Ortiz-Genga, M, Sacilotto, L, Schulze-Bahr, E, Shimizu, W, Sotoodehnia, N, Tadros, R, S Ware, J, S Winlaw, D, S Kaufman, E, Aiba, T, Bollmann, A, Choi, J, Dalal, A, Darrieux, F, Giudicessi, J, Guerchicoff, M, Hong, K, D Krahn, A, Mac Intyre, C, A Mackall, J, Mont, L, Napolitano, C, Ochoa Juan, P, Peichl, P, C Pereira, A, J Schwartz, P, Skinner, J, Stellbrink, C, Tfelt-Hansen, J, Deneke, T, Arthur A M Wilde, Christopher Semsarian, Manlio F Márquez, Alireza Sepehri Shamloo, Michael J Ackerman, Euan A Ashley, Back Sternick Eduardo, Héctor Barajas-Martinez, Elijah R Behr, Connie R Bezzina, Jeroen Breckpot, Philippe Charron, Priya Chockalingam, Lia Crotti, Michael H Gollob, Steven Lubitz, Naomasa Makita, Seiko Ohno, Martín Ortiz-Genga, Luciana Sacilotto, Eric Schulze-Bahr, Wataru Shimizu, Nona Sotoodehnia, Rafik Tadros, James S Ware, David S Winlaw, Elizabeth S Kaufman, Takeshi Aiba, Andreas Bollmann, Jong-Il Choi, Aarti Dalal, Francisco Darrieux, John Giudicessi, Mariana Guerchicoff, Kui Hong, Andrew D Krahn, Ciorsti Mac Intyre, Judith A Mackall, Lluís Mont, Carlo Napolitano, Pablo Ochoa Juan, Petr Peichl, Alexandre C Pereira, Peter J Schwartz, Jon Skinner, Christoph Stellbrink, Jacob Tfelt-Hansen, Thomas Deneke, M Wilde, A, Semsarian, C, F Márquez, M, Sepehri Shamloo, A, J Ackerman, M, A Ashley, E, Sternick Eduardo, B, Barajas-Martinez, H, R Behr, E, R Bezzina, C, Breckpot, J, Charron, P, Chockalingam, P, Crotti, L, H Gollob, M, Lubitz, S, Makita, N, Ohno, S, Ortiz-Genga, M, Sacilotto, L, Schulze-Bahr, E, Shimizu, W, Sotoodehnia, N, Tadros, R, S Ware, J, S Winlaw, D, S Kaufman, E, Aiba, T, Bollmann, A, Choi, J, Dalal, A, Darrieux, F, Giudicessi, J, Guerchicoff, M, Hong, K, D Krahn, A, Mac Intyre, C, A Mackall, J, Mont, L, Napolitano, C, Ochoa Juan, P, Peichl, P, C Pereira, A, J Schwartz, P, Skinner, J, Stellbrink, C, Tfelt-Hansen, J, Deneke, T, Arthur A M Wilde, Christopher Semsarian, Manlio F Márquez, Alireza Sepehri Shamloo, Michael J Ackerman, Euan A Ashley, Back Sternick Eduardo, Héctor Barajas-Martinez, Elijah R Behr, Connie R Bezzina, Jeroen Breckpot, Philippe Charron, Priya Chockalingam, Lia Crotti, Michael H Gollob, Steven Lubitz, Naomasa Makita, Seiko Ohno, Martín Ortiz-Genga, Luciana Sacilotto, Eric Schulze-Bahr, Wataru Shimizu, Nona Sotoodehnia, Rafik Tadros, James S Ware, David S Winlaw, Elizabeth S Kaufman, Takeshi Aiba, Andreas Bollmann, Jong-Il Choi, Aarti Dalal, Francisco Darrieux, John Giudicessi, Mariana Guerchicoff, Kui Hong, Andrew D Krahn, Ciorsti Mac Intyre, Judith A Mackall, Lluís Mont, Carlo Napolitano, Pablo Ochoa Juan, Petr Peichl, Alexandre C Pereira, Peter J Schwartz, Jon Skinner, Christoph Stellbrink, Jacob Tfelt-Hansen, and Thomas Deneke

Published
2022

47. Visual and Refractive Efficacy of Panoptix Toric Intraocular Lens in a Clinical Setting.

Author

Ackerman, M, Lawless, M, Levitz, L, Bhatt, U, Reich, JA, Sutton, G, Roberts, TV, Tenen, A, Kaur, A, Hodge, C, Ackerman, M, Lawless, M, Levitz, L, Bhatt, U, Reich, JA, Sutton, G, Roberts, TV, Tenen, A, Kaur, A, and Hodge, C

Abstract

PURPOSE: Trifocal Intraocular Lenses (IOLs) were developed to provide patients with effective near, intermediate and distance vision, thus minimizing spectacle dependency. Residual astigmatism has previously been shown to impact unaided visual acuity across all distances; therefore, to optimise the expected outcomes, consideration of preoperative corneal astigmatism is essential. The purpose of this study was to provide a real-world, multi-site review of visual and refractive outcomes in eyes undergoing implantation with the Panoptix Trifocal toric IOL platform. PATIENTS AND METHODS: This study represents a two-fold approach. Patients who had previously undergone routine cataract removal and IOL insertion with the Panoptix Toric IOL were retrospectively analysed for routine efficacy and safety endpoints ("Retrospective Cohort"). Data was retrieved from the preoperative, surgical and postoperative visits (range 2-6 weeks). A further subset of patients undergoing lens removal and bilateral Panoptix Toric IOL insertion were identified at surgery ("Qualitative Cohort"). These patients underwent additional testing inclusive of quality of vision questionnaire and bilateral defocus curve. RESULTS: A total of 466 eyes of 254 patients were included in the retrospective cohort. Between 91% and 98% of eyes, respectively, were within 0.50D and 1.00D of target. Mean absolute difference from Spherical Equivalent (SE) target was 0.22 ± 0.24Ds. Following surgery, 94% of eyes demonstrated a refractive astigmatism of 0.50D or less. Further, 61% eyes achieved uncorrected distance visual acuity (UDVA) of 20/20 or better, increasing to 94% achieving 20/32 or better. Seventy percent of eyes unilaterally achieved N5 unaided and 66.0% achieved N8 or better at intermediate. In the qualitative cohort, no patient described any symptom as significant or requested explant. CONCLUSION: In a real-world setting, the PanOptix toric trifocal IOL continues to demonstrate refractive accuracy and good

Published
2022

48. NP Telehealth Blood Pressure Management in Heart Transplant Patients - A Single Center Experience

Author

Jamero, G., primary, De Leon, F., additional, Ackerman, M., additional, Welton, M., additional, Kissling, N., additional, Velleca, A., additional, White, M., additional, Czer, L., additional, Nikolova, A., additional, Kransdorf, E., additional, Chang, D., additional, Kittleson, M., additional, Patel, J., additional, and Kobashigawa, J.A., additional

Published
2022
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