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Prehospital Emergency Care

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ipec20

Prehospital Electroencephalography to Detect


Traumatic Brain Injury during Helicopter
Transport: A Pilot Observational Cohort Study

David J. Barton, Patrick J. Coppler, Nadine N. Talia, Alexi Charalambides,


Brian Stancil, Ava M. Puccio, David O. Okonkwo, Clifton W. Callaway, Francis
X. Guyette & Jonathan Elmer

To cite this article: David J. Barton, Patrick J. Coppler, Nadine N. Talia, Alexi Charalambides,
Brian Stancil, Ava M. Puccio, David O. Okonkwo, Clifton W. Callaway, Francis X. Guyette &
Jonathan Elmer (2023): Prehospital Electroencephalography to Detect Traumatic Brain Injury
during Helicopter Transport: A Pilot Observational Cohort Study, Prehospital Emergency Care,
DOI: 10.1080/10903127.2023.2185333

To link to this article: https://doi.org/10.1080/10903127.2023.2185333

View supplementary material Published online: 13 Mar 2023.

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PREHOSPITAL EMERGENCY CARE
https://doi.org/10.1080/10903127.2023.2185333

Prehospital Electroencephalography to Detect Traumatic Brain Injury during


Helicopter Transport: A Pilot Observational Cohort Study
David J. Bartona , Patrick J. Copplera , Nadine N. Taliaa, Alexi Charalambidesb, Brian Stancilb,
Ava M. Puccioc, David O. Okonkwoc, Clifton W. Callawaya , Francis X. Guyettea , and Jonathan Elmera
a
Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; bLifeware Labs, LLC, Pittsburgh, Pennsylvania;
c
Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania

ABSTRACT ARTICLE HISTORY


Objective: Early recognition of traumatic brain injury (TBI) is important to facilitate time-sensitive Received 21 November 2022
care. Electroencephalography (EEG) can identify TBI, but feasibility of EEG has not been evaluated Revised 9 January 2023
in prehospital settings. We tested the feasibility of obtaining single-channel EEG during air medical Accepted 21 February 2023
transport after trauma. We measured association between quantitative EEG features, early blood
biomarkers, and abnormalities on head computerized tomography (CT).
Methods: We performed a pilot prospective, observational study enrolling consecutive patients
transported by critical care air ambulance from the scene of trauma to a Level I trauma center.
During transport, prehospital clinicians placed a sensor on the patient’s forehead to record EEG.
We reviewed EEG waveforms and selected 90 seconds of recording for quantitative analysis. EEG
data processing included fast Fourier transform to summarize component frequency power in the
delta (0-4 Hz), theta (4-8 Hz), and alpha (8-13 Hz) ranges. We collected blood samples on day 1 and
day 3 post-injury and measured plasma levels of two brain injury biomarkers (ubiquitin C-terminal
hydrolase L1 [UCH-L1] and glial fibrillary acidic protein [GFAP]). We compared predictors between
individuals with and without CT-positive TBI findings.
Results: Forty subjects were enrolled, with EEG recordings successfully obtained in 34 (85%).
Reasons for failure included uncharged battery (n ¼ 5) and user error (n ¼ 1). Data were lost in
three cases. Of 31 subjects with data, interpretable EEG signal was recorded in 26 (84%). Mean age
was 48 (SD 16) years, 79% were male, and 50% suffered motor vehicle crashes. Eight subjects
(24%) had CT-positive TBI. Subjects with and without CT-positive TBI had similar median delta
power, alpha power, and theta power. UCH-L1 and GFAP plasma levels did not differ across groups.
Delta power inversely correlated with UCH-L1 day 1 plasma concentration (r ¼ -0.60, p ¼ 0.03).
Conclusions: Prehospital EEG acquisition is feasible during air transport after trauma.

Introduction severe thoracoabdominal injuries, and is insensitive for


detection of axonal injury (3). Point-of-care strategies to
Traumatic brain injury (TBI) is a leading cause of death in
screen for mass lesions in TBI are urgently needed. Prior
children and young adults (1). Rapid identification of TBI by
studies have explored vital signs (4, 5), clinical examination
medical personnel is important to appropriately triage these
patients and guide time-sensitive therapeutic interventions. (6), full or multi-channel clinical electroencephalography
Simultaneously, the ability to rule out clinically significant (EEG) (7, 8), and blood-based biomarkers (9) as indicators
TBI allows focused treatment of other known or suspected of TBI. These studies have mostly focused on patients with
injuries and enables improved transport destination decisions. mild injuries and used diagnostics acquired after hospital
Prehospital identification of TBI is difficult; a systematic arrival. These modalities require further study in major
review of eight studies evaluating prehospital triage accuracy trauma patients and in the prehospital setting.
demonstrated low sensitivity (19.8% to 87.9%) and specifi- Prehospital care offers a window of opportunity for early
city (41.4% to 94.4%) of various methods to identify TBI resuscitation and appropriate triage of TBI patients. We
(2). Computerized tomographic (CT) brain imaging is the tested the feasibility of using a wearable digital device to col-
current standard for diagnosing and detecting surgical path- lect single-channel EEG data in the prehospital setting.
ology in patients with acute TBI. Unfortunately, CT is not Secondarily, we explored associations between prehospital
available in prehospital or resource-limited settings, is unsafe EEG, blood-based biomarkers sampled on hospital arrival,
in hemodynamically unstable patients with concomitant and TBI on CT imaging.

CONTACT David J. Barton bartond2@upmc.edu


Supplemental data for this article is available online at https://doi.org/10.1080/10903127.2023.2185333
ß 2023 National Association of EMS Physicians
2 D. J. BARTON ET AL.

Methods with subdermal electrodes and visually confirmed equivalent


signals recognizable as EEG were acquired.
Study Design
We performed a prospective, observational study to test the
Study Procedures
feasibility of collecting physiological data including EEG
using a novel biosensor device (Apollo, Lifeware Labs, LLC, Prior to study initiation, EMS personnel completed a 5-
Pittsburgh, PA, USA) during prehospital patient care and minute introductory training to the research study back-
transport. We included all trauma patients 18 years of age ground, study design, and impact, in addition to the EEG
(or who appeared post-pubescent if age was initially device via a PowerPoint presentation and brief quiz. After
unknown) treated and transported directly from the scene of 80% of EMS personnel in the service completed the training
injury to a single Level I trauma center via helicopter by a and quiz, we started study enrollment.
regional critical care transport service (STAT MedEvac) in Flight crews enrolled patients meeting inclusion/exclusion
western Pennsylvania. We excluded patients known to be criteria and being transported to our Level I trauma center.
prisoners and/or pregnant. Three Apollo devices were used, Patients were enrolled by treating air medical clinicians dur-
and we distributed one device each to three air ambulance ing prehospital transport. We defined enrollment as place-
bases that carried the devices continuously. Patients from ment of the electrodes on the patient. After initial patient
these three bases were eligible. We targeted a sample size of resuscitation and stabilization, flight crews were instructed
40 patients with the goal of allowing each base to use these to place the device while enroute to prevent delay to defini-
devices at least 10 times each to ensure the ability of person- tive care. Crewmembers placed the biosensor device onto
nel to learn and appropriately use the device. Patients were the patient’s right forehead using two standard ECG electro-
enrolled consecutively from January to June 2021. des placed on the temporal region and the forehead. The
The University of Pittsburgh Human Research Protection device takes <1 minute to apply. The device was paired via
Office approved this research (STUDY20080103), and Bluetooth technology to a Google Pixel 3XL cell phone car-
granted a waiver of the requirement for obtaining informed ried by the crew to allow waveform visualization and
consent given this was a minimal risk study, and a consent recording. Crewmembers were instructed to only apply the
process would not be practical in the time frame needed device and initiate phone application recording, and not to
under emergency conditions necessitating EMS transport. monitor any device data. Upon arrival at the emergency
Funders had no role in study design, data analysis, or deci- department, the Apollo device was removed and cleaned for
sion to publish. re-use. Investigators transferred recording data from the cell
phone to cloud-based storage.
Investigators received prehospital trauma alert pages con-
Biosensor Device for EEG Recording
currently with the ED trauma team, and one of two investi-
The Apollo device (Figure 1) measures photoplethysmogra- gators (DJB or NNT) responded to the ED to initiate study
phy and electrocardiography (ECG) at 200 Hz each procedures after patient arrival.
(MAX86150, Maxim Integrated), and motion at 100 Hz Investigators collected demographic and clinical data via
(LSM6DS3, ST Microelectronics). The raw data is transmit- medical chart abstraction, and all data were recorded using
ted via Bluetooth Low Energy to an Android app. Although REDCap (10, 11). Neuroradiologists interpreted and reported
the sensor is intended for ECG, the frequency range of EEG all head CT scans. We reviewed written CT reports for the
(0.5 Hz to 30 Hz) is similar to that of ECG (0.5 Hz to presence of TBI findings, including subarachnoid hemorrhage,
150 Hz), and so we placed electrodes on the scalp (one subdural hemorrhage, epidural hemorrhage, intracerebral
frontal, one temporal) aiming primarily to collect EEG. To hemorrhage, intraventricular hemorrhage, and contusion. We
validate this use prior to field deployment, we tested the categorized subjects with any of these findings as CT-positive
device against a standard clinical EEG amplifier (CNS-210) TBI. Isolated skull or facial fractures were not included. We

Figure 1. EEG device (Lifeware Labs).


PREHOSPITAL EMERGENCY CARE 3

determined Rotterdam CT scores on all patients with available in the delta (0–4 Hz), theta (4–8 Hz), and alpha (8–13 Hz)
data. Injury Severity Scores (ISS) and Abbreviated Injury Scale ranges, as well as the ratio of alpha/delta power.
(AIS) scores were later obtained from the UPMC Trauma We performed statistical analyses with Stata SE 17.0,
Registry. including descriptive statistics and bivariate analyses. We
tested categorical variables for between-group differences
using Pearson exact tests due to low expected cell counts.
Blood Collection and Biomarker Assays
We assessed continuous variables for normal distribution
Study personnel collected venous blood samples from patients using Shapiro-Wilk tests; variables with significant test val-
in the emergency department immediately upon arrival using ues were reported as medians (interquartile range [IQR])
tri-potassium ethylenediaminetetraacetic acid coated tubes. and analyzed using non-parametric tests (e.g., Mann-
We obtained second blood samples at approximately 72 hours Whitney tests and Spearman correlation coefficients). All p-
post-injury in patients who were still hospitalized. Blood sam- values were considered significant at <0.05.
ples were obtained at the time of clinical blood draws or
from existing intravenous catheters to avoid excessive veni-
Results
punctures. We kept samples at room temperature for 30–
60 minutes (five samples were placed on ice for up to several Cohort Information
hours when logistically required due to investigator availabil-
ity), then centrifuged samples for 10 minutes at 1500x relative A flow diagram of patients eligible during the study period is
centrifugal force. Plasma supernatants were aliquoted and in Figure 2. Four of six missed enrollments came within the
immediately frozen at 80 C for batch analysis. first 2 months of study initiation, and the rate of missed
Samples were sent for commercial measurement to Abbott enrollments decreased over time. One missed enrollment was
Laboratories on dry ice. Plasma levels of glial fibrillary acidic due to crewmembers not having time to do so because the
protein (GFAP) and ubiquitin C-terminal hydrolase L1 patient required continuous resuscitation. Otherwise, no spe-
(UCHL1) were measured using the Abbot Alinity immuno- cific injuries precluded placement or use of the device. All
assay platform. Both assays have <10% coefficients of vari- patients tolerated the device, and there were no observed
ation. The laboratory was blinded to clinical data, and cases of patients removing the leads, requiring additional sed-
biomarker data were analyzed by the authors. ation, or harm. Device battery failure occurred in five cases;
this was addressed by providing EMS flight crews with in-
helicopter charging cords to keep the EEG device constantly
Data Analysis charged. After this intervention, no battery failures occurred.
All data, including EEG, were analyzed post-hoc and not Overall, we included 34 subjects in whom EEG and/or
during patient care. An investigator experienced at EEG blood was collected. Clinical characteristics of the cohort are
interpretation visually inspected EEG waveform recordings summarized in Table 1. Subjects were mostly male (79%),
to determine if interpretable EEG was recorded. For each had a mean age of 48 y (range 17–79 y), and were most fre-
interpretable recording, we visually selected one 90-second quently injured due to falls (38%). Median (IQR) ISS was 9
period of the most artifact-free data for quantitative analysis. (2–17). Twelve subjects had AIS head region scores > 0,
In this pilot study, we focused on frequency decompositions and the median (IQR) of these 12 subjects was 2 (1–3).
of the EEG signal, since this has been used successfully in Eight subjects (24%) had initial CT imaging with evidence
past research to identify brain hypoperfusion (1), preclinical of TBI; six of these individuals had presenting Glasgow
signs of concussion (2), and risk of traumatic encephalop- Coma Scale (GCS) scores of 15 (Table 2). One individual
athy (2), and can be used to grade TBI severity in both the with CT-positive TBI developed delayed low-pressure hydro-
acute and chronic phases (3). We used the eegkit package cephalus and coma requiring placement of an external ven-
(12) and R version 4.0.4 (13) to conduct Fast Fourier trans- tricular drain and ventriculoperitoneal shunt.
form for frequency decomposition. A Fourier transform
decomposes a complex waveform into its component fre- EEG Measures
quencies (i.e., the original waveform is treated as a sum of
multiple sinusoidal functions). Each of these functions has Mean (standard deviation) electrographic recording time was
an amplitude and frequency. The signal decomposition we 9.5 (7.4) minutes. Twenty-six of 31 individuals (84%) had
performed uses this approach to approximate the sum of the 90 second periods of interpretable EEG for quantitative ana-
total power with specific clinically relevant frequency bands. lysis. Five subjects (16%) had uninterpretable recordings, all
We applied a bandpass filter from 0.1 to 30 Hz, and then of whom were enrolled in the first half of the study. The five
used a notch-filter (using the signal package (14)) to exclude subjects with uninterpretable EEG recordings were older than
non-physiological electromechanical interference attributable those with interpretable EEG (median age 64 vs 44 years;
to harmonics of the helicopter rotor blades or other invariant, p ¼ 0.02 by Mann-Whitney test), but there was no difference
high-amplitude, non-physiological spikes occurring at fixed in subjects’ sex, race, mechanisms of injury, endotracheal
frequencies. We summarized results of the frequency decom- intubation, presence of intoxication, or presence of TBI on
position by considering total band-pass filtered spectral power CT (p > 0.05 for all comparisons via Fisher exact tests).
4 D. J. BARTON ET AL.

Figure 2. Study sample flow diagram.

Table 1. Patient characteristics. Comparisons between subjects with and without CT-posi-
Patient characteristic Total N ¼ 34 tive TBI (Figure 3) demonstrated no significant differences
Age – y, mean (SD) 48 (16) between median values of alpha-power (63.0 vs. 72.1 mV;
Male sex, n (%) 27 (79)
Race, n (%)
p ¼ 0.74), theta-power (97.5 vs. 88.8 mV; p ¼ 0.41), delta-
White 30 (88) power (458.4 vs. 353.6 mV; p ¼ 0.79), or alpha-delta ratios
African-American/Black 4 (12) (0.19 vs. 0.20; p ¼ 0.41).
Mechanism of Injury, n (%)
Fall 13 (38)
Motor vehicle crash 9 (26)
Motorcycle crash 6 (18) Blood Biomarker Analysis
Pedestrian struck by vehicle 2 (6)
Gunshot wound 2 (6) We collected blood upon ED arrival (day 1; n ¼ 19) and
Amputation 1 (3) 72 hours after admission (day 3; n ¼ 17) and analyzed plasma
Hanging 1 (3)
Systolic blood pressure – mmHg, mean (SD) 138 (29)
levels of UCH-L1 and GFAP (Figure 4). Median (IQR) level of
Diastolic blood pressure – mmHg, mean (SD) 92 (25) UCH-L1 was 2242 (353.3-4624.1) pg/mL on day 1 and 123.7
Heart rate – min-1, mean (SD) 92 (20) (87.4-209.6) pg/mL on day 3 among all individuals. Median
Respiratory rate – min-1, mean (SD) 19 (4)
Prehospital intubation, n (%) 5 (15) (IQR) level of GFAP was 29.4 (19.2-77.6) pg/mL on day 1 and
Traumatic brain injury on CT scan 8 (24) 96.7 (28.4-330.8) pg/mL on day 3 among all individuals. Two
Clinical seizures within 3 days 1 (3) individuals with CT-positive TBI had blood available on day 1,
Clinical seizures within 30 days 4 (17)a
Length of hospital stay – days, median (IQR) 5 (2–10) and four had blood available on day 3. No significant differen-
Mortality at 30 days 0 (0)a ces in UCH-L1 or GFAP levels were noted between CT-posi-
a
29 patients had follow-up information available via medical record review. tive TBI vs. CT-negative groups at either time point (p > 0.05
PREHOSPITAL EMERGENCY CARE 5

Table 2. Characteristics of patients with CT-positive TBI. be as low as 26 of 40 (65%) if considering the entire enrolled
TBI, n ¼ 8 population as the denominator (Figure 2). Trauma victims
Glasgow coma scale score, median (IQR) 15 (12.5-15) comprise a sizable proportion of patients treated by helicopter
CT injury types
Subarachnoid hemorrhage 7 (88)
EMS. Identifying TBI can facilitate triage, trigger time-sensi-
Subdural hemorrhage 2 (25) tive interventions, and reduce secondary injury. Recent guid-
Intraventricular hemorrhage 2 (25) ance from the Excellence in Prehospital Injury Care-TBI
Contusion 1 (12.5)
Diffuse axonal injury 1 (12.5)
study reinforces the importance of evidence-based prehospital
Epidural hemorrhage 0 (0) medical care for improving TBI-related outcomes (15).
Intraparenchymal hemorrhage 0 (0) Limited prior work has assessed EEG in prehospital set-
Rotterdam CT score, median (IQR) 2 (1-2)
Neurosurgical intervention within 3 days 0 (0) tings. Jakab et al. first reported on design and testing of a
Neurosurgical intervention within 30 days 1 (12.5) six-channel EEG system intended for rapid deployment;
they tested two healthy volunteers in an ambulance and
reported sufficient diagnostic recordings (16). In a small
military study of soldiers with closed head injury, authors
demonstrated the BrainScope One device (which uses EEG
as one component) may be a useful tool for identifying and
ruling out structural brain lesions in the battlefield; however
this study included only 13 subjects, and only three subjects
received CT scans (17). Most recently, a dry electrode EEG
system has been reported to have modest utility in prehospi-
tal detection of stroke with large vessel occlusion (18). There
remains interest in applying simplified, point-of-care EEG in
emergency and prehospital settings to screen for stroke
(19, 20) and non-convulsive status epilepticus (21–23),
which is frequently missed in prehospital settings (24). Such
applications could be helpful in guiding prehospital treat-
ments and determination of transport destination. However,
further work is needed to demonstrate feasibility and trans-
lation to the prehospital setting with its associated challenges
to implementation such as patient movement, electrode
placement, external bleeding, cranial trauma, intoxication,
combativeness, and helicopter motion. Our work adds to the
literature by demonstrating satisfactory EEG is possible des-
pite these operational barriers.
Prior literature demonstrates acute quantitative EEG
changes in mild TBI include reduction in alpha power and
increase in theta and delta power (25). In our exploratory
analyses, we did not detect significant differences in quanti-
Figure 3. Quantitative EEG measures in non-TBI vs. TBI groups based on CT
imaging. tative EEG measures, with the significant limitation of our
small sample size, although our median values agree with
for all comparisons), although we had a low sample size for this relationship directionality in TBI vs. non-TBI. Thus, it
this exploratory comparison (Supplemental Figure 1). remains our hypothesis that these quantitative EEG meas-
We calculated correlation coefficients between quantita- ures are associated with presence of TBI. Alternatively, it is
tive EEG measures and day 1 biomarker levels (generally possible that effect sizes are too small to show clinical effect
in the early post-trauma time course of prehospital care.
collected < 1 hour after EEG recordings). Delta power was
Larger studies are needed to better answer this question.
inversely correlated with UCH-L1 levels upon ED arrival
We provide novel data of UCH-L1 and GFAP relation-
(Spearman’s r ¼ 0.60; p ¼ 0.03), but other measures did not
ships with quantitative EEG measures, independent of radio-
have significant relationships (Figure 4).
graphic TBI. Delta power was inversely correlated with
UCH-L1 levels. While this analysis is unadjusted and
Discussion remains small in sample size, this exploratory finding is
interesting because of the proximate time between the EEG
In this prospective observational cohort, we report on our recording and blood collection and the role of UCH-L1 in
experience with single-channel EEG in trauma patients in the maintaining neuron axonal integrity (26) and synaptic struc-
prehospital helicopter ambulance setting. We find that EMS ture (27). Blood biomarkers of TBI remain an active area of
clinicians can successfully acquire limited frontal EEG in the investigation. Currently, the FDA-approved assay for these
prehospital (air medical) setting. Alternative calculations biomarkers is only available for plasma, not whole blood,
could yield the success rate of obtaining interpretable EEG to which would be necessary for prehospital use.
6 D. J. BARTON ET AL.

Figure 4. Scatter plots of quantitative EEG measures and plasma UCH-L1 and GFAP levels.

Our work has associated limitations. First, we used a sin- improve spatial coverage would affect either signal quality
gle channel, two-electrode EEG device to simplify the moni- or feasibility. Second, we used CT-positive findings to desig-
toring as much as possible for EMS clinicians who used it as nate TBI comparison groups for logistical practicality. TBI is
a new tool. It is unknown if adding additional channels to not solely defined by CT findings, and symptom-based
PREHOSPITAL EMERGENCY CARE 7

measures may help better stratify groups. Nonetheless, CT- 3. Figueira Rodrigues Vieira G, Guedes Correa JF. Early computed
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Acknowledgments 1111/acem.13175.
9. Bazarian JJ, Biberthaler P, Welch RD, Lewis LM, Barzo P,
This work was presented at the Society of Academic Emergency Bogner-Flatz V, Gunnar Brolinson P, B€ uki A, Chen JY,
Medicine Annual Meeting on May 13, 2022 in New Orleans, LA. Christenson RH, et al. Serum GFAP and UCH-L1 for prediction
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Disclosure Statement 789. doi:10.1016/S1474-4422(18)30231-X.
10. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG.
AC and BS are co-founders of Lifeware Labs, LLC which produced the
Research electronic data capture (REDCap)–a metadata-driven
EEG devices used in this study.
methodology and workflow process for providing translational
research informatics support. J Biomed Inform. 2009;42(2):377–
381. doi:10.1016/j.jbi.2008.08.010.
Funding 11. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal
This study was supported by the National Institutes of Health under L, McLeod L, Delacqua G, Delacqua F, Kirby J, REDCap
grant numbers T32HL134615, K23NS091629, and UL1TR001857 Consortium, et al. The REDCap consortium: building an inter-
through the Clinical and Translational Sciences Institute at the national community of software platform partners. J Biomed
University of Pittsburgh. Biomarker measurements were provided as Inform. 2019;95:103208. doi:10.1016/j.jbi.2019.103208.
gift-in-kind by Abbott Laboratories (Chicago, IL, USA). 12. Helwig NE. eegkit: toolkit for electroencephalography data
[Internet]; 2018. https://CRAN.R-project.org/package=eegkit.
13. R Core Team. R: a language and environment for statistical com-
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ORCID
Computing; 2021. https://www.R-project.org
David J. Barton http://orcid.org/0000-0003-0976-0383 14. fsignalg: Signal processing [Internet]. 2014. http://r-forge.r-pro-
Patrick J. Coppler http://orcid.org/0000-0002-0731-7989 ject.org/projects/signal/.
Clifton W. Callaway http://orcid.org/0000-0002-3309-1573 15. Spaite DW, Bobrow BJ, Keim SM, Barnhart B, Chikani V,
Francis X. Guyette http://orcid.org/0000-0002-9151-4896 Gaither JB, Sherrill D, Denninghoff KR, Mullins T, Adelson PD,
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