Received: 14 September 2020 | Revised: 17 November 2020 | Accepted: 30 November 2020

DOI: 10.1111/jce.14857

ORIGINAL ARTICLES

Surface unipolar electrogram characteristics to predict site

of origin of outflow tract arrhythmias using noninvasive
mapping

Kristie M. Coleman RN | Moussa Saleh MD | Parth Makker MD |

Aditi S. Vaishnav MBBS | Gourg Atteya MD | Jamie Shein PA‐C |
Amarbir Bhullar MD | Nicholas T. Skipitaris MD | Stavros E. Mountantonakis MD

Department of Cardiac Electrophysiology,

Northwell Health‐Lenox Hill Heart and Lung,
New York, New York, USA
Correspondence
Kristie M. Coleman, RN, 100 East 77th
St, 2 Lachman, New York, NY 10075, USA.
Email: kcoleman1@northwell.edu
Disclosures: Dr Mountantonakis Speakers
Honoraria. Dr Skipitaris, Medtronic Advisory
Board. The remaining authors have nothing to
disclose.
Funding information
Medtronic
Abstract
Background: Noninvasive electroanatomic mapping (NIEAM) demonstrate patterns
of depolarization that are useful in identifying the chamber of origin (COO) in
outflow tract ventricular arrhythmias (OTVA). However, its use in predicting exact
site of origin (SOO) has not yet been validated.
Methods: NIEAMs (CardioInsight, Medtronic) from 40 patients (age 62.5 ± 2.6) un-
dergoing ablation for OTVA were reviewed for diagnostic accuracy in predicting the
SOO. Earliest arrhythmia breakout and directionality of earliest instantaneous unipolar
electrograms (uEGMs) on NIEAMs were evaluated subjectively by two observers for
quality and amplitude. Sites with most negative earliest uEGMs on right and left ven-
tricular outflow tracts, as well as epicardial surface were manually identified. Using
NIEAM‐based activation timing of the lateral mitral annulus and basal septum COO
was identified for each OTVA. Predictions of SOO using NIEAMs was compared
with true SOO from invasive study. NIEAMs SOO predictions were compared with
subjective 12 lead electrocardiogram (ECG) review by two observers.
Results: Review of arrhythmia breakout and signal directionality had poor diagnostic
value in predicting SOO in OTVA (50.6% and 49.4%, 56.6% and 43.4%, respectively)
and underperformed compared with ECG interpretation (59.1% and 80.5%). After
excluding uEGMs with poor characteristics, the uEGM with most negative amplitude at
the COO was predictive of the true SOO with 96.4% sensitivity and specificity.
Conclusion: We propose a stepwise approach when interpreting NIEAMs for OTVA
where patterns of activation are evaluated first to determine the COO, followed by
identification of the site with most negative amplitude instantaneous uEGM to
determine SOO.

KEYWORDS
body surface mapping, catheter ablation, noninvasive electroanatomic mapping, premature
ventricular contraction, ventricular arrhythmia

Abbreviations: LVOT, left ventricular outflow tract; LVS, left ventricular summit; NIEAM, noninvasive electroanatomic mapping; OTVA, outflow tract ventricular arrhythmias; RVOT, right
ventricular outflow tract; uEGMs, unipolar electrograms.

J Cardiovasc Electrophysiol. 2021;32:391–399. wileyonlinelibrary.com/journal/jce © 2020 Wiley Periodicals LLC | 391


392 | COLEMAN
1 | INTRODUCTION
Elucidating the site of origin (SOO) of ventricular arrhythmias
(OTVAs) arising from the outflow tracts namely the right ventricular
outflow tract (RVOT), the left ventricular outflow tract (LVOT), and
the left ventricular summit can often be challenging.1–3 Distin-
guishing between these neighboring sites can aid in procedural
planning, avoid unnecessary access, mapping, and ablation.4–8 The
use of noninvasive electroanatomic mapping (NIEAM) to predict
the chamber of origin of OTVA has been investigated by prior
9–11
studies. We have shown that current signal processing result in
noninvasive electroanatomical maps that lack the spatial and tem-
poral resolution to reliably differentiate between the neighboring
structures of the outflow tracts when using the earliest arrhythmia
breakout. Using NIEAM‐based activation timing of the lateral mitral
annulus and basal septum, we have previously proposed a two‐step
algorithm that differentiates between RVOT, LVOT, and the epi-
cardial origin with a 100% diagnostic accuracy.12 This algorithm is
proven to be superior to the 12‐lead electrocardiogram (ECG) and
has been shown to obviate unnecessary vascular access and elim-
inate unnecessary mapping and ablation.13 Although the two‐step
algorithm allows operators to identify the chamber of origin, it
provides no insight on the specific SOO. With this study, we sought
to identify the SOO of OTVAs by manual analysis of the earliest
recorded surface unipolar electrograms collected by the available
NIEAM system (CardioInsight, Medtronic Inc.).
2 | METHODS
2.1 | Study population
We reviewed consecutive patients who underwent both invasive
(IEAM) and NIEAM during ablation of symptomatic OTVAs between
January 2019 and June 2020 and analyzed only patients with OTVA
origin from the RVOT, LVOT or distal great cardiac vein (dGCV).
Patients with history of prior ablation were excluded. OTVA true site of
origin was determined retrospectively after the ablation based on ar-
rhythmia elimination with a single radiofrequency application, site of
earliest activation at least 35 ms pre‐QRS and/or more than or equal to
95% pace‐map match. OTVAs with presumed intramural origin were
excluded from our cohort. We also excluded patients where ablation
was not successful in eliminating the clinical OTVA and patients who
had recurrence of the clinical arrhythmia within 3 months. The presence
of scar was ruled out by cardiac magnetic resonance imaging in
patients with depressed left ventricular ejection fraction. The study was
approved by the Institutional Review Board.
2.2 | Analysis of 12‐lead ECGs
Site of origin based on ECGs recorded for each patient were sub-
jectively evaluated by two observers that were blinded to the
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ET AL.
NIEAMs and results of the electrophysiology study. In case of dis-
agreement a third observer would make the final determination
between the two interpretations.
2.3 | NIEAM acquisition and analysis
Patients underwent NIEAM (CardioInsight, Medtronic Inc.) the day
of the procedure as previously described.12 Briefly the patients were
fitted with a multielectrode vest (CardioInsight, Medtronic) at the
holding area followed by a noncontrast computed tomography (CT)
of chest and abdomen. The vest records unipolar electrograms from
surface electrodes and projects them to the ventricular epicardium
using the inverse equation. Recordings of the OTVAs was initiated at
the holding area and continued during the electrophysiology study.
We evaluated the two types of maps provided by the current
system (CardioInsight, Medtronic Inc.). The potential maps display
unipolar electrograms overtime and assign a white color to the site
that has the most negative recordings at a particular point of time.
Areas with most negative unipolar electrograms at a specific time
(instantaneous unipolar electrograms) indicate cardiac depolariza-
tion at this particular point of time. The area that generates negative
unipolar electrograms the earliest coincides with presumed site of
origin (arrhythmia breakout; Figures 1A–3A).
The second type of NIEAMs are directional activation maps and are
based on timing of the maximum dV/dT on unipolar electrograms (de-
noting the steepest negative slope). The myocardium with earliest
maximum dV/dT correlates with earliest activation and is shown in red
marking. The rest of the heart is color coded based on timing of max-
imum dV/dT relative to the earliest area (Figures 1B–3B). Activation
maps also provide information about the directionality of unipolar
electrograms. The system displays arrows that suggest electrical
propagation over the entire duration of ventricular complex
(Figures 1C–3C). We used this feature to determine the presumed SOO
as the site surrounded by most efferent unipolar electrograms.
Potential and directional activation maps were presented to two
electrophysiologists blinded to the results of the invasive electro-
physiology study who independently predicted the origin of the
OTVAs. In case of disagreement, consensus had to be reached be-
tween the two observers for the final prediction of origin. Inter-
observer variability was calculated.
In addition to the information above provided by the system
(CardioInsight, Medtronic Inc.), we manually adjudicated in-
stantaneous unipolar electrograms (uEGMs) to identify the signal
with the earliest most negative amplitude and the following char-
acteristics (Figure 4):
1. Absence of an initial r wave.
2. Sharp downward electrogram with no notches in the downward
slope.
3. Single component electrogram.
We focused our manual adjudication of signals in the following sites:
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COLEMAN ET AL.
| 393

F I G U R E 1 RVOT. (A) Potential NIEAM: Earliest arrhythmia breakout depicted by a relatively wide white area that ovelaps between
anteroseptal RVOT, LCC and epicardial space. Reviewers prediction were split between septal RVOT and LCC origin. The most negative unipolar
signal was seen in the septal RVOT area and is tagged with a red point. (B) Directionality of Unipolar Signals on Activation Map: Red arrows
depicting propogation of unipolar electrograms. Site with the most efferent uEGMs is shown with a yellow arrow. Reviewers prediction were split
between septal RVOT or epicardial space (LVS). (C) Earliest activation site based on dV/dT, also covers an expansive area between RVOT and
LVOT depicted by red coloration. Activation timing to the mitral annulus was 72msec and to the basal septum 37ms suggesting that the chamber
of origin is the right ventricular outflow tract. The most negative uEGM within the RVOT shown with a yellow point depicting anterior septal
RVOT site of origin. (D) IEAM merged with non‐contrast CT: Site of earliest activation (white region) showing anterior septal RVOT site of origin.
(E) ECG: Premature Ventricular Depolarization originating from RVOT. ECG, electrocardiogram; LVOT, left ventricular outflow tract;
LVS, left ventricular summit; NIEAM, noninvasive electroanatomic mapping; RVOT, right ventricular outflow tract; uEGM, unipolar electrograms

1. Area of earliest arrhythmia breakout based on potential NIEAMs
(white area on Figures 1A and 2A).
2. Area of earliest activation based on activation NIEAMs (red area
on Figures 1B and 2B).
3. Chamber of VPD origin. This was based on previously published
algorithm that uses activation timing of the tricuspid and mitral
annulus and the superior basal septum.12 More specifically, late
depolarization of the lateral mitral annulus ( > 60.5 ms) suggest
RVOT origin and early depolarization of the basal septum
(<22.5 ms) suggest LVOT origin. Depolarization of the lateral
mitral annulus in < 60.5 ms and of the basal septum of >22.5 ms
suggest epicardial origin.
The site with most negative instantaneous unipolar signals and
aforementioned quality characteristics were identified and tagged on
the different types of NIEAMs.
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394 | COLEMAN ET AL.

F I G U R E 2 Epicardial. (A) Potential NIEAM: Earliest arrhythmia breakout on NIEAM potential maps depicted by white coloring in area
encompassing portions of RVOT, LVOT, and epicardium. Red dot represents most negative unipolar signal thought to be on the epicardial space
between the outflow tracts (LVS). (B) Directionality of unipolar signals on activation map: Red arrows depicting propogation of unipolar
electrograms. Site with the most efferent uEGMs is indicated by a yellow arrow and thought to be on the LVS. (C) Activation NIEAM: Earliest
activation site based on dV/dT, red coloration in epicardial space as well as LCC and anterior septal RVOT. Activation timing to the mitral
annulus was 24 ms and to the basal septum was 27 ms suggesting epicardial origin. The most negative uEGM on the epicardium is shown with a
yellow point depicting LVS site of origin. (D) IEAM merged with noncontrast CT: Site of earliest activation (white region) showing epicardial site
of origin. (E) ECG: Premature ventricular depolarization originating from LVS. CT, computed tomography; ECG, electrocardiogram; LVOT, left
ventricular outflow tract; LVS, left ventricular summit; NIEAM, noninvasive electroanatomic mapping; RVOT, right ventricular outflow
tract; uEGM, unipolar electrograms

2.4 | IEAM acquisition and analysis 2.5 | Comparison between IEAM and NIEAM

A detailed focus invasive electroanatomic map (IEAM) was For objective comparison between the prediction sites and the SOO
performed during the EP study and ablation and the SOO was the outflow tracts were divided in the following seven segments
tagged on the IEAM. For more accurate comparison between (Figure 5).
the IEAM and NIEAM, we merged the IEAM with the non‐contrast
CT images performed the same day for the needs of NIEAM 1. Anterior RVOT.
(Figures 1D–3D). 2. Mid‐Septal RVOT.
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COLEMAN ET AL.
| 395

F I G U R E 3 LVOT. (A) Potential NIEAM: Earliest arrhythmia breakout on NIEAM potential maps depicted by white coloring in area
encompassing portions of LVOT and epicardium. Red point represents most negative uEGM on the left coronary cusp (LCC). (B) Directionality
of unipolar signals on activation map: Red arrows depicting propogation of unipolar electrograms. The site with the most efferent uEGMs
illustrated with a yellow arrow. One observer concluded LCC origin as opposed to the second that predicted epicardial origin. (C) Activation
NIEAM: Earliest activation site based on dV/dT, red coloration in epicardial space as well as LCC and anterior septal RVOT. Activation timing to
the mitral annulus was 33 ms and to the basal septum was 14 ms suggesting LVOT origin. The most negative uEGM within the presumed
chamber of origin is shown with a yellow point and. coincides with LCC origin. (D) IEAM merged with non‐contrast CT: Site of earliest activation
(white region) showing LCC site of origin. (E) ECG: Premature ventricular depolarization originating from SoV. CT, computed tomography; ECG,
electrocardiogram; LVOT, left ventricular outflow tract; LVS, left ventricular summit; NIEAM, noninvasive electroanatomic mapping; RVOT,
right ventricular outflow tract; uEGM, unipolar electrograms

3. Posterior RVOT. and compared using analysis of variance or the nonparametric

4. Free Wall RVOT. test of Whitney U‐Test for two variables and the Kruskal–Wallis
5. Left coronary cusp (LCC). test for more than two variables, as appropriate. Categorical
6. Right coronary cusp (RCC). variables are presented as absolute and relative frequencies and
7. Left ventricular summit (LVS). compared using the Pearson's χ2 test. Sensitivity and specificity
were calculated for each modality used to predict VPD SOO.
Sensitivity and specificity were calculated for the different
2.6 | Statistical analysis methods of prediction using NIEAM and true SOO. Interobserver
variability was calculated using Cohen's kappa. All statistical
Continuous variables are presented as mean ± SD or median ± analyses were performed using SPSS Statistics version 25.0
SEM for parametric and nonparametric variables respectively, (IBM Corp.).

396 | COLEMAN
F I G U R E 4 Criteria for manual adjudication of unipolar electrograms when manually adjudicating unipolar electrograms, we excluded signals
containing an initial r wave (A), changed polarity especially during the initial negative deflection (B), and that were multicomponent especially
during the downward slope (C). Surface electrograms with sharp downward deflection were selected for amplitude measurement (D)
F I G U R E 5 In our review the outflow tracts were divided in the
following seven segments for objective comparison between the
prediction sites and the site of origin: (A) anterior RVOT,
(B) mid‐septal RVOT, (C) posterior RVOT, (D) free wall RVOT,
(E) left coronary cusp (LCC), (F) right coronary cusp (RCC), and
(G) left ventricular summit (LVS)
3 | RESULTS
We reviewed 50 patients undergoing EP study for symptomatic
OTVAs between January 2019 and June 2020. Of those, we ex-
cluded six patients whose site of origin was undetermined during the
invasive electrophysiology study and four patients whose arrhythmia
recurred within 3 months post procedure. Our cohort for this study
included 40 patients (14 female) with a mean age of 62.5 ± 2.6 years.
The cohort had an average ejection fraction of 50.1 ± 14.2% and
22.8% had a diagnosis of nonischemic cardiomyopathy. The average
burden amongst patients with frequent ventricular premature de-
polarizations was 24.6 ± 12.3%. Based on IEAM, the site of origin was
classified as RVOT for 18 (45.0%) patients, LVOT for 10 (25.0%)
patients, and epicardial for 12 (30.0%) patients.
Subjective review of the arrhythmia breakout on potential
NIEAMs by the two blinded reviewers, yielded a sensitivity and a
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ET AL.
specificity of 56.6% and 43.4%, respectively. Interobserver varia-
bility for using potential maps was 0.573. Similarly, using the di-
rectionality of unipolar signals on activation NIEAMs yielded a
sensitivity and specificity of 50.6% and 49.4%, respectively. Using
the above information alone, NIEAM underperformed compared
to 12‐lead ECGs interpretation that yielded a sensitivity of 59.1%
and a specificity of 80.5%.
Early instantaneous uEGMs were adjudicated for quality as
previously described (Figure 4). When comparing the amplitude of
arrhythmia breakout between chambers of origin, epicardial had
the highest amplitude (21.2 ± 10.0 mV) followed by LVOT
(15.8 ± 5.7 mV) with RVOT having the lowest uEGM negative
amplitude (9.5 ± 5.0 mV, p < .000).
Identifying the site with uEGM with most negative amplitude in
either area of arrhythmia breakout (potential maps) or area of ear-
liest activation yield a low sensitivity and specificity (Table 1) in
predicting the SOO as this was most frequently located on the epi-
cardial site. On the contrary, identifying the site of the most negative
early instantaneous uEGM in the chamber of presumed origin using
our algorithm yielded a sensitivity and specificity of 96.4% in iden-
tifying the true SOO. The two cases that were misclassified utilizing
the algorithm were septal RVOT, where posterior origin was mis-
classified as anterior, and vice versa in the second case.
4 | DISCUSS ION
Identifying OTVA site of origin before catheter ablation has been
well established to aid in procedural planning, procedural risk
assessment and ablation strategy.13 The 12‐lead ECG has been the
main diagnostic modality for that purpose, however given the
anatomical complexity of outflow tract region, proposed ECG al-
gorithms are often cumbersome and lack specificity.14–17 Prior
studies have shown that NIEAM can reliably identify chamber of
origin for OTVAs and can prevent unnecessary access and
mapping, therefore reducing overall procedure time.10–12,18,19

COLEMAN ET AL.
Method Sensitivity (%)
Subjective review electrocardiogram 59.1
Earliest arrhythmia breakout (potential maps) 56.6
Directionality of unipolar signals (activation maps) 50.6
Most negative uEGM within the arrhythmia breakout area 55.6
(potential maps)
Most negative uEGM within the area of earliest activation 24.4
(activation maps)
Most negative uEGM within the chamber of origin 96.4
Abbreviations: NIEAM, noninvasive electroanatomic mapping; OTVA, outflow tract ventricular
arrhythmias; SOO; site of origin; uEGM, unipolar electrograms.
These studies have relied on general patterns of activation and
while they provide insight on the chamber that is activated first,
they cannot predict the exact SOO.
In this review, we demonstrate that earliest arrhythmia break-
out, as well as directionality of unipolar electrograms as depicted by
current NIEAM technology have low sensitivity and specificity in
identifying SOO. The current system creates maps based on sum-
mation of all recorded unipolar signals without the ability for signal
quality screening. In addition, the system projects all recordings
uniformly to the epicardial, “outside” surface of the segmented heart,
even to nonexcitable areas including areas of fat or scar, valves, and
cavities. This makes its use problematic in the outflow tracts, an area
characterized by multiple anatomical borders, nonexcitable struc-
tures and cavities that cover a large proportion of the segmented
outflow tract area. The majority of those signals were of poor quality,
and due to their large number made a significant contribution to how
the system determined the earliest arrhythmia breakout. For those
signals, the onset, as well as sharpest dV/dT picked by the computer
was highly inaccurate. When focusing only on electrograms that
were assigned to the walls of the RVOT below the pulmonic valve,
periphery of LVOT at the level of the cusps and the epicardial space
between the two, we encountered signals of high quality in the vast
majority of the cases. The current system does not allow us to
reconstruct the NIEAM after excluding signals, so it is impossible for
us to know how the diagnostic accuracy of NIEAM would have
improved should the system have excluded the poor quality signals
from the beginning.
Finally, since the available system records signals from the
epicardial surface, it is expected that epicardial activation occurs
much later than onset of focal activation on the endocardium.
Due to the above factors, arrhythmia breakout site on potential
maps is typically broad, does not follow anatomical borders and
spans over neighboring chambers (Figures 1A–3A). This explains
the high interobserver variability in identifying the SOO at the
outflow tracts.
Prior studies have sought to validate NIEAM through com-
parison with IEAM. Duchateau et al.20 attempted to compare
epicardial activation between NIEAM and IEAM and showed that
correlation was poor. The authors highlight the need for
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| 397
T A B L E 1 Diagnostic accuracy of
Specificity (%)
NIEAM data methods to predict SOO
80.5 in OTVA
43.4
49.4
50.0
50.0
96.4
postprocessing to improve the clinical application of NIEAMs. We
agree with the above statement, however, we have shown that
while the imaging of electrical propagation with NIEAM is poor for
the entire cycle length, one can deduct conclusions on the general
patterns of activation and determine the order of depolarization
of cardiac segments that are anatomically distant. This technique
has allowed us to determine the chamber of origin of OTVA based
on activation timing of lateral mitral annulus versus basal septum
versus lateral tricuspid annulus.12 Given limitations in spatial and
temporal resolution of the current system, we believe that de-
termination of chamber of origin is important first step before
attempting to predict the SOO for OTVAs.
During this analysis we used the areas of arrhythmia break out
and earliest activation to review and adjudicate surface unipolar
signals. Characteristics like sharp negative deflection, the absence
of initial r wave and the absence of multiple or “rounded” com-
ponents in a signal were taken into consideration during signal
adjudication. In addition, signal amplitude was measured for all
uEGMs that met the above criteria. Amplitude of a unipolar
electrogram at a specific time correlates not only with the onset of
depolarization relative to the time of recording but also to the
mass of myocardium that is depolarized, similarly to the en-
docardial signals. This is supported by our analysis that showed
higher amplitude of unipolar signals on the muscular epicardial
space as opposed to the much thinner layer RVOT. The premise of
manual adjudication of unipolar signals has been previously ex-
plored by Cheniti et al.,21 noting that manual review of signals for
the presence of a QS pattern can be done before automatic pro-
cessing of NIEAM maps. Before standardizing our protocol eva-
luation of each NIEAM took several hours. However, once refined
the protocol takes approximately 10 min. First determining the
chamber of origin based on activation of lateral tricuspid annulus,
lateral mitral annulus and basal septum takes 2–3 min. Subse-
quently, once the chamber of origin is determined, review of
electrograms on the wall of the chamber of origin to locate the
electrogram with the highest amplitude takes 5 min.
With our report we suggest that this adjudication could also be
performed after automatic signal processing and NIEAM creation.
Future upgrades could incorporate the algorithm into the current

398 | COLEMAN
system to identify the chamber of origin. Furthermore, the system
should allow the operator to exclude nonexcitable areas from
analysis (valves, cavities, and areas of scar) and offer automating
the identification of the site with the most negative unipolar elec-
trograms. The above improvements would streamline the process of
predicting the exact origin of outflow tract VPDs.
In conclusion, with this report we show that the amplitude of
quality instantaneous surface unipolar electrograms recorded at
the chamber of origin are highly predictive of SOO for OTVAs. We
therefore propose a stepwise approach when interpreting NIEAMs
for OTVAs where activation timing of the mitral annulus and
basal septum is evaluated first to determine the chamber of origin
followed by manual review of the surface electrograms at the
presumed chamber of origin to identify the exact SOO.
5 | STUDY L IMITATIONS
The results of this analysis could be applied only for outflow tract
ventricular arrhythmias. Since available technology does not allow
for both NIEAM and IEAM to be merged, matching between the SOO
identified by the two modalities might not be exact. However, using
the same cardiac CT to create both maps makes them comparable
and allows for a subjective localization of SOO without the need of
fluoroscopic images or objective origin determination by the op-
erator. The segmentation of outflow tract into seven areas was
arbitrary and was created to allow comparisons between the two
modalities. In addition, it does not provide information on the level of
SOO on the vertical axis (superior vs inferior) for the RVOT cases.
We acknowledge the cost of using NIEAM is higher than the tradi-
tional 12‐lead ECG, however, if the information gained from NIEAM
contributes to procedural success and freedom from future PVCs,
the use of it can be justified. While the application of the NIEAM vest
and preprocedural CT can be seen as an extra step, previous studies
have shown NIEAM saves both mapping and ablation time.13 Further
studies are needed to determine if this improved method further
shortens procedural time.
A C K N O W L E D GM E N T
Medtronic grant awarded to Dr Mountantonakis.
DATA AV AILA BILITY STATEMENT
The data that supports the findings of this study are available from
the corresponding author, KC, upon reasonable request.
ORCID
Kristie M. Coleman http://orcid.org/0000-0001-6616-8234
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