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1. Comparison of the impact of skull density ratio with alternative skull metrics on magnetic resonance–guided focused ultrasound thalamotomy for tremor

Author

Jason, Yuen, Abhinav, Goyal, Timothy J, Kaufmann, Lauren M, Jackson, Kai J, Miller, Bryan T, Klassen, Neha, Dhawan, Kendall H, Lee, and Vance T, Lehman

Subjects
General Medicine
Abstract

OBJECTIVE One of the key metrics that is used to predict the likelihood of success of MR-guided focused ultrasound (MRgFUS) thalamotomy is the overall calvarial skull density ratio (SDR). However, this measure does not fully predict the sonication parameters that would be required or the technical success rates. The authors aimed to assess other skull characteristics that may also contribute to technical success. METHODS The authors retrospectively studied consecutive patients with essential tremor who were treated by MRgFUS at their center between 2017 and 2021. They evaluated the correlation between the different treatment parameters, particularly maximum power and energy delivered, with a range of patients’ skull metrics and demographics. Machine learning algorithms were applied to investigate whether sonication parameters could be predicted from skull density metrics alone and whether including combined local transducer SDRs with overall calvarial SDR would increase model accuracy. RESULTS A total of 62 patients were included in the study. The mean age was 77.1 (SD 9.2) years, and 78% of treatments (49/63) were performed in males. The mean SDR was 0.51 (SD 0.10). Among the evaluated metrics, SDR had the highest correlation with the maximum power used in treatment (ρ = −0.626, p < 0.001; proportion of local SDR values ≤ 0.8 group also had ρ = +0.626, p < 0.001) and maximum energy delivered (ρ = −0.680, p < 0.001). Machine learning algorithms achieved a moderate ability to predict maximum power and energy required from the local and overall SDRs (accuracy of approximately 80% for maximum power and approximately 55% for maximum energy), and high ability to predict average maximum temperature reached from the local and overall SDRs (approximately 95% accuracy). CONCLUSIONS The authors compared a number of skull metrics against SDR and showed that SDR was one of the best indicators of treatment parameters when used alone. In addition, a number of other machine learning algorithms are proposed that may be explored to improve its accuracy when additional data are obtained. Additional metrics related to eventual sonication parameters should also be identified and explored.

Published
2023

2. SAFETY MONITORING OF COVID-19 VACCINE: IN A TERTIARY CARE HOSPITAL IN HARYANA

Author

ARVIND NARWAT, MITALI DUA, and ABHINAV GOYAL

Subjects
Pharmacology, Pharmaceutical Science
Abstract

Objective: The present study aimed to ensure the safety and related potential adverse effects following ChAdOx1 nCoV-19 vaccination (AZD1222) in a scenario when numerous vaccines have been approved on an emergency basis by the WHO and other regulatory agencies to prevent the widespread of COVID-19 infection and to decrease the associated mortality and morbidity. Methods: This study was an open, non-comparative, non-interventional, observational study conducted on healthcare workers of BPS Govt. medical college for women and elderly people who received the first dose of COVID-19 vaccinationChAdOx1 nCoV-19 vaccine (AZD1222) by conducting their interviews and recording the data Results: Between January and March 2021, a total of 1907 participants were enrolled in this study. Out of 1907 recipients, 70 recipients reports adverse drug events following vaccination. Myalgia (0.629%), headache (1.31%), fever (≥ 37.5 °C, 0.839%) and fever with chills (≥ 37.5 °C, 1.048) were the most common adverse events after the first dose of vaccination of ChAdOx1 nCoV-19 vaccine (AZD1222. Throat irritation (0.209 %) and Generalised itching (0.262) were the least common adverse events. Conclusion: ChAdOx1 nCoV-19 (Astrazeneca) has an acceptable safety profile as observed in this study. To our knowledge, very few studies are done that review the safety of COVID-19 vaccines. Further safety data from a larger sample size and of longer duration are warranted to establish safety

Published
2023

3. A COMPARISON OF EFFECTS OF DEXMEDETOMIDINE VERSUS MIDAZOLAM-FENTANYL ON POST-OPERATIVE RECOVERY, SEDATION, ANALGESIA AND HEMODYNAMIC PARAMETERS IN PATIENTS UNDERGOING MIDDLE EAR SURGERY UNDER LOCAL ANESTHESIA

Author

Abhinav Goyal, Garima Bhutani, Meena Singh, Naveen Sharma, Seema Rani, Rahul Saini, and Mohd Fazal Ahmed Makki

Subjects
Pharmacology, Pharmaceutical Science, Pharmacology (medical)
Abstract

Objective: The objective of the study was to compare the effects of dexmedetomidine versus midazolam-fentanyl on post-operative recovery, sedation, analgesia, and hemodynamic parameters in patients undergoing middle ear surgery under local anesthesia. Methods: Seventy-two patients were randomly divided into two equal groups - Group D (dexmedetomidine) and Group MF (midazolam and fentanyl). Intra operative heart rate, mean blood pressure, respiratory rate (RR), and SPO2 were recorded every 15 min for the 1st 30 min and then at every 30 min interval till the end of the surgery. In post-operative period, hemodynamic parameters, Aldrete score and pain were assessed at every 30 min till the patient was discharged from post anesthesia care unit (PACU). Post-operative sedation of the patient was checked at 1 h, 2 h, 4 h, and 8 h. Observations: Midazolam and fentanyl combination caused more fall in Aldrete scores as compared to dexmedetomidine initially, but readiness to discharge from PACU was similar in both the groups. Patients of MF group had significantly higher sedation scores at post op 2 h, but overall duration of sedation was similar in both the groups. Post-op pain was significantly more in MF group patients, as compared to dexmedetomidine patients at 1.5 h. More number of patients of MF group demanded rescue analgesia in PACU. Both group of drugs caused similar changes in hemodynamic parameters during surgery but in post-operative period, dexmedetomidine produced less decline in RR and oxygen saturation as compared to midazolam and fentanyl combination. Conclusion: The present study concluded that dexmedetomidine seems to be a better alternative to the combination of midazolam plus fentanyl sedation for patients undergoing middle ear surgeries done under local anesthesia due to better analgesia and lesser derangement of hemodynamic parameters in post-operative period.

Published
2022

5. Preexisting frailty and outcomes in older patients with acute myocardial infarction

Author

Jacob A. Udell, Di Lu, Akshay Bagai, John A. Dodson, Nihar R. Desai, Gregg C. Fonarow, Abhinav Goyal, Kirk N. Garratt, Joseph Lucas, William S. Weintraub, Daniel E. Forman, Matthew T. Roe, and Karen P. Alexander

Subjects
Canada, Frailty, Frail Elderly, Myocardial Infarction, Humans, Female, Hospital Mortality, Registries, Cardiology and Cardiovascular Medicine, Aged
Abstract

Little is known about the prevalence and prognostic impact of preexisting frailty on acute care and in-hospital outcomes in older adults in the setting of acute myocardial infarction (AMI).Preexisting frailty was assessed at baseline in consecutive AMI patients ≥65 years of age treated at 778 hospitals participating in the NCDR ACTION Registry between January 1, 2015 to December 31, 2016. Three domains of preexisting frailty (cognition, ambulation, and functional independence) were abstracted from chart review and summed in 2 ways: an ACTION Frailty Scale based on responses to 6 groups adapted from the Canadian Study of Health and Aging Clinical Frailty Scale and an ACTION Frailty Score derived by summing a rank score of 0-2 assigned for each grade (total ranged between 0 to 6). Multivariable logistic regression examined the association between assigned frailty by score or scale and in-hospital mortality.Among 143,722 older AMI patients, 108,059 (75.2%) were fit and/or well and 6,484 (4.5%) were vulnerable to frailty, while 7,527 (5.2%) had mild, 3,913 (2.7%) had moderate, 2,715 had (1.9%) severe, and 632 (0.4%) had very severe frailty according to the ACTION Frailty Scale, while 14,392 (10.0%) could not be categorized due to incomplete ascertainment. Frail patients were older, more frequently female, of non-white race and/or ethnicity, and less likely to be treated with guideline-recommended therapies. Increasing severity of frailty by this scale was associated with a step-wise higher risk for in-hospital mortality (P-trend.001). Patient categories of the ACTION Frailty Score provided similar results. After adjustment, each 1-unit increase in Frailty Score was associated with a 12% higher mortality risk (OR 1.12, 95% CI 1.10-1.15).Among older patients with acute myocardial infarction, frailty is common and independently associated with in-hospital mortality. These findings show the importance of pragmatic evaluation of frailty in hospital-level quality scores, guideline recommendations, and incorporation into other registry data collection efforts.

Published
2022

6. Democracy and the pricing of initial public offerings around the world

Author

Huu Nhan Duong, Abhinav Goyal, Madhu Veeraraghavan, and Vasileios Kallinterakis

Subjects
Economics and Econometrics, Corporate governance, Information asymmetry, Strategy and Management, media_common.quotation_subject, Audit, Monetary economics, Venture capital, Democracy, Shareholder, Accounting, Agency (sociology), IPO underpricing, Business, Initial public offering, Finance, media_common
Abstract

We find a negative relation between democracy and initial public offering (IPO) underpricing for a sample of 23,050 IPOs across 45 countries. The effect of democracy on underpricing is weaker for IPOs audited by Big 4 auditing firms, backed by venture capital firms, and with better disclosure specificity of use of proceeds. Democracy exerts a larger influence on underpricing for firms with higher agency problems, in countries with weaker institutional quality or shareholder protection, and during periods of high investor sentiment or economic policy uncertainty. Overall, our results highlight the importance of democracy in reducing IPO underpricing around the world.

Published
2022

7. Risk Factors Associated With New-Onset Myocardial Perfusion Abnormalities in Kidney Transplant Candidates

Author

Lehman, Godwin, Ziduo, Zheng, Suprateek, Kundu, Ryan, Cousins, Billy Joe, Mullinax, Yi-An, Ko, Kendra, Little, Andrew, Smith, Arshed, Quyyumi, Abhinav, Goyal, Thomas, Pearson, Valeria, Moncayo, and Adam J, Mitchell

Subjects
Male, Perfusion, Tomography, Emission-Computed, Single-Photon, Peripheral Arterial Disease, Risk Factors, Myocardial Infarction, Myocardial Ischemia, Myocardial Perfusion Imaging, Humans, Female, Coronary Artery Disease, Cardiology and Cardiovascular Medicine, Kidney Transplantation
Abstract

The optimal coronary artery disease surveillance strategy for end-stage renal disease patients being evaluated for kidney transplantation is unknown. It is unclear what risk factors are associated with the development of new-onset perfusion abnormalities on serial myocardial perfusion imaging. Potential kidney transplant recipients who underwent 2 myocardial perfusion imaging studies at Emory University Hospital between January 2010 and December 2019 were identified. We assessed the frequency of development of any new perfusion defect and development of moderate to severe ischemia (reversible perfusion defect10%) on serial imaging. Finally, we identified the clinical and imaging factors associated with new perfusion defects and explored the association between new perfusion defects and all-cause mortality. History of myocardial infarction (MI) and peripheral artery disease was associated with an increased risk of developing a new perfusion defect. History of MI was also associated with the risk of developing moderate-severe ischemia. Female patients were less likely to develop new perfusion defects or moderate-severe ischemia. There was no association between either outcome and all-cause mortality. In conclusion, a history of MI, peripheral artery disease, and male gender are risk factors for developing new perfusion defects, although only the history of MI and male gender predict moderate to severe ischemia. Interval development of any abnormal perfusion is not associated with increased mortality.

Published
2022

8. Micromagnetic Stimulation (μMS) Controls Dopamine Release: An in vivo Study Using WINCS Harmoni

Author

Renata Saha, Abhinav Goyal, Jason Yuen, Yoonbae Oh, Robert P. Bloom, Onri J. Benally, Kai Wu, Theoden I. Netoff, Walter C. Low, Kevin E. Bennet, Kendall H. Lee, Hojin Shin, and Jian-Ping Wang

Subjects
Article
Abstract

ObjectiveResearch into the role of neurotransmitters in regulating normal and pathologic brain functions has made significant progress. Yet, clinical trials that aim to improve therapeutic interventions do not take advantage of thein vivochanges in the neurochemistry that occur in real time during disease progression, drug interactions or response to pharmacological, cognitive, behavioral, and neuromodulation therapies. In this work, we used the WINCSHarmonitool to study the real timein vivochanges in dopamine release in rodent brains for the micromagnetic neuromodulation therapy.ApproachAlthough still in its infancy, micromagnetic stimulation (μMS) using micro-meter sized coils or microcoils (μcoils) has shown incredible promise in spatially selective, galvanic contact free and highly focal neuromodulation. These μcoils are powered by a time-varying current which generates a magnetic field. As per Faraday’s Laws of Electromagnetic Induction, this magnetic field induces an electric field in a conducting medium (here, the brain tissues). We used a solenoidal-shaped μcoil to stimulate the medial forebrain bundle (MFB) of the rodent brainin vivo. The evokedin vivodopamine releases in the striatum were tracked in real time by carbon fiber microelectrodes (CFM) using fast scan cyclic voltammetry (FSCV).ResultsOur experiments report that μcoils can successfully activate the MFB in rodent brains, triggering dopamine releasein vivo. We further show that the successful release of dopamine upon micromagnetic stimulation is dependent on the orientation of the μcoil. Furthermore, varied intensities of μMS can control the concentration of dopamine releases in the striatum.SignificanceThis work helps us better understand the brain and its conditions arising from a new therapeutic intervention, like μMS, at the level of neurotransmitter release. Despite its early stage, this study potentially paves the path for μMS to enter the clinical world as a precisely controlled and optimized neuromodulation therapy.

Published
2023

9. Deep brain stimulation alleviates tics in Tourette syndrome via striatal dopamine transmission

Author

Aaron E Rusheen, Juan Rojas-Cabrera, Abhinav Goyal, Hojin Shin, Jason Yuen, Dong-Pyo Jang, Keven E Bennet, Charles D Blaha, Kendall H Lee, and Yoonbae Oh

Subjects
Neurology (clinical)
Abstract

Tourette syndrome is a childhood-onset neuropsychiatric disorder characterized by intrusive motor and vocal tics that can lead to self-injury and deleterious mental health complications. While dysfunction in striatal dopamine neurotransmission has been proposed to underlie tic behavior, evidence is scarce and inconclusive. Deep brain stimulation (DBS) of the thalamic centromedian parafascicular complex (CMPf), an approved surgical interventive treatment for medical refractory Tourette syndrome, may reduce tics by affecting striatal dopamine release. Here, we use electrophysiology, electrochemistry, optogenetics, pharmacological treatments, and behavioral measurements to mechanistically examine how thalamic DBS modulates synaptic and tonic dopamine activity in the dorsomedial striatum. Previous studies demonstrated focal disruption of GABAergic transmission in the dorsolateral striatum of rats led to repetitive motor tics recapitulating the major symptom of Tourette Syndrome. We employed this model under light anesthesia and found CMPf DBS evoked synaptic dopamine release and elevated tonic dopamine levels via striatal cholinergic interneurons while concomitantly reducing motor tic behavior. The improvement in tic behavior was found to be mediated by D2 receptor activation as blocking this receptor prevented the therapeutic response. Our results demonstrate that release of striatal dopamine mediates the therapeutic effects of CMPf DBS, and points to striatal dopamine dysfunction as a driver for motor tics in the pathoneurophysiology of Tourette syndrome.

Published
2023

11. Cocaine increases stimulation-evoked serotonin efflux in the nucleus accumbens

Author

Jason Yuen, Abhinav Goyal, Aaron E. Rusheen, Abbas Z. Kouzani, Michael Berk, Jee Hyun Kim, Susannah J. Tye, Charles D. Blaha, Kevin E. Bennet, Kendall H. Lee, Yoonbae Oh, and Hojin Shin

Subjects
Male, Rats, Sprague-Dawley, Serotonin, Cocaine, Physiology, Dopamine, General Neuroscience, Animals, Electric Stimulation, Nucleus Accumbens, Research Article, Rats
Abstract

Although dopamine is the most implicated neurotransmitter in the mediation of the pathophysiology of addiction, animal studies show serotonin also plays a vital role. Cocaine is one of the most common illicit drugs globally, but the role of serotonin in its mechanism of action is insufficiently characterized. Consequently, we investigated the acute effects of the psychomotor stimulant cocaine on electrical stimulation-evoked serotonin (phasic) release in the nucleus accumbens core (NAcc) of urethane-anesthetized (1.5 g/kg ip) male Sprague–Dawley rats using N-shaped fast-scan cyclic voltammetry (N-FSCV). A single carbon fiber microelectrode was first implanted in the NAcc. Stimulation was applied to the medial forebrain bundle using 60 Hz, 2 ms, 0.2 mA, 2-s biphasic pulses before and after cocaine (2 mg/kg iv) was administered. Stimulation-evoked serotonin release significantly increased 5 min after cocaine injection compared with baseline (153 ± 21 nM vs. 257 ± 12 nM; P = 0.0042; n = 5) but was unaffected by saline injection (1 mL/kg iv; n = 5). N-FSCV’s selective measurement of serotonin release in vivo was confirmed pharmacologically via administration of the selective serotonin reuptake inhibitor escitalopram (10 mg/kg ip) that effectively increased the signal in a separate group of rats (n = 5). Selectivity to serotonin was further confirmed in vitro in which dopamine was minimally detected by N-FSCV with a serotonin to dopamine response ratio of 1:0.04 (200 nM of serotonin:1 µM dopamine ratio; P = 0.0048; n = 5 electrodes). This study demonstrates a noteworthy influence of cocaine on serotonin dynamics, and confirms that N-FSCV can effectively and selectively measure phasic serotonin release in the NAcc. NEW & NOTEWORTHY Serotonin plays a vital role in drug addiction. Here, using N-shaped fast-scan cyclic voltammetry, we demonstrated the effect of cocaine on the phasic release of serotonin at the nucleus accumbens core. To the best of our knowledge, this has not previously been elucidated. Our results not only reinforce the role of serotonin in the mechanism of action of cocaine but also help to fill a gap in our knowledge and provide a baseline for future studies in cocaine addiction.

Published
2022

12. Abstract WP80: The Heart-brain Connection: Implementing Strategies To Reduce The Rate Of Perioperative Stroke For Patients Undergoing Coronary Artery Bypass Graft Surgery

Author

Deborah Westover, Wendy Wright, Iman Aziz, Abhinav Goyal, W B Keeling, Kendra J Grubb, Gaetano Paone, Julie Shoffstall, Antasia Giebler, Robert Groff, Dee Lacey, Karima Benameur, Sylvia Yaw, and Fadi B Nahab

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Background: Stroke is a known complication of cardiac surgery. The objective of this study was to implement a systemwide strategy to reduce perioperative stroke after isolated coronary artery bypass graft (CABG) surgery utilizing best practices from cardiothoracic surgery and neurology expertise. Methods: A prospective, quality improvement study of all isolated CABG patients at three hospitals within a multicenter academic healthcare system, in a large metropolitan area, was completed from January 1, 2021 to June 30, 2022. Utilizing Lean methodology, a multidisciplinary team of cardiothoracic surgeons, neurologists, anesthesiologists, certified stroke nurses, and process improvement specialists conducted a gap analysis to identify interventions to decrease the observed to expected (O/E) ratio of risk-adjusted perioperative strokes. The team developed a pre-operative evaluation process for patients with a history of stroke, formalized the utilization of intra-operative epiaortic ultrasound, and deployed education on BE-FAST symptoms and the purpose of stroke alerts to providers, nurses, and ancillary staff caring for the patient population. Results: During the study period, 1175 patients underwent isolated CABG. Risk adjusted perioperative stroke rates in the first 6 months of 2021 compared to 2022 declined from an O/E ratio of 1.32 to 0.78. Among patients with new post-operative stroke symptoms, the time frame from last known well to symptom recognition decreased from 704 to 486 minutes. Following the implementation of the protocol, one site saw the utilization of inpatient stroke alerts after CABG increase from 81.3% to 100% for patients with new BE-FAST symptoms. Conclusion: Multidisciplinary implementation of best practices was associated with lower risk adjusted perioperative stroke rates, reductions in time to new symptom recognition, and increased utilization of inpatient stroke alert processes. Further study is needed to monitor the effects of the pre-operative evaluation process and the standardization of epiaortic ultrasound. Future goals are to standardize the methods and assess the benefit to other types of cardiac surgery.

Published
2023

14. Enhanced Dopamine Sensitivity Using Steered Fast-Scan Cyclic Voltammetry

Author

Cheonho Park, Sangmun Hwang, Kendall H. Lee, Kevin E. Bennet, Hojin Shin, Dong Pyo Jang, Jinsick Park, Hyun U. Cho, Abhinav Goyal, Yumin Kang, and Yoonbae Oh

Subjects
Millisecond, Materials science, musculoskeletal, neural, and ocular physiology, General Chemical Engineering, Analytical chemistry, Fast-scan cyclic voltammetry, General Chemistry, Article, Chemistry, Dopamine, Temporal resolution, medicine, Sensitivity (control systems), Cyclic voltammetry, QD1-999, medicine.drug
Abstract

Fast-scan cyclic voltammetry (FSCV) is a technique for measuring phasic release of neurotransmitters with millisecond temporal resolution. The current data are captured by carbon fiber microelectrodes, and non-Faradaic current is subtracted from the background current to extract the Faradaic redox current through a background subtraction algorithm. FSCV is able to measure neurotransmitter concentrations in vivo down to the nanomolar scale, making it a very robust and useful technique for probing neurotransmitter release dynamics and communication across neural networks. In this study, we describe a technique that can further lower the limit of detection of FSCV. By taking advantage of a “waveform steering” technique and by amplifying only the oxidation peak of dopamine to reduce noise fluctuations, we demonstrate the ability to measure dopamine concentrations down to 0.17 nM. Waveform steering is a technique to dynamically alter the input waveform to ensure that the background current remains stable over time. Specifically, the region of the input waveform in the vicinity of the dopamine oxidation potential (∼0.6 V) is kept flat. Thus, amplification of the input waveform will amplify only the Faradaic current, lowering the existing limit of detection for dopamine from 5.48 to 0.17 nM, a 32-fold reduction, and for serotonin, it lowers the limit of detection from 57.3 to 1.46 nM, a 39-fold reduction compared to conventional FSCV. Finally, the applicability of steered FSCV to in vivo dopamine detection was also demonstrated in this study. In conclusion, steered FSCV might be used as a neurochemical monitoring tool for enhancing detection sensitivity.

Published
2021

15. Development and Evaluation of a Core Genome Multilocus Sequencing Typing (cgMLST) Scheme for Serratia marcescens Molecular Surveillance and Outbreak Investigations

Author

Stefanie Kampmeier, Karola Prior, Scott A. Cunningham, Abhinav Goyal, Dag Harmsen, Robin Patel, and Alexander Mellmann

Subjects
Microbiology (medical), Whole Genome Sequencing, Epidemiology, Humans, Serratia marcescens, Genome, Bacterial, Multilocus Sequence Typing, Disease Outbreaks
Abstract

Serratia marcescens can cause a range of severe infections and contributes to nosocomial outbreaks. Although whole-genome sequencing (WGS)-based typing is the standard method for molecular surveillance and outbreak investigation, there is no standardized analytic scheme for S. marcescens core genome multilocus sequence typing (cgMLST). Here, the development and evaluation of a S. marcescens cgMLST scheme is reported with the goal of enabling a standardized methodology and typing nomenclature. Four hundred ninety-one high-quality S. marcescens WGS data sets were extracted from public databases and-using the genomic sequence of NCBI reference strain S. marcescens Db11 (NZ_HG326223.1) as a starting point-all Db11 genes present in ≥97% data sets used to create a cgMLST scheme. The novel scheme was evaluated using WGS data from 24 outbreak investigations (in/i= 175 isolates) distributed over three continents. Analysis of Db11 genes within the 491 data sets identified 2,692 target genes present in ≥97% of genomes (mean, 99.1%; median, 99.9%). These genes formed the novel cgMLST scheme, covering 47.8% of nucleotides in the Db11 genome. Analyzing 175 isolates from 24 outbreaks using the novel scheme gave comparable results to previous typing efforts for both general groupings and allelic distances within clusters. In summary, a novel cgMLST scheme for S. marcescens was developed and evaluated. The scheme and its associated nomenclature will improve standardization of typing efforts for molecular surveillance and outbreak investigation, allowing better understanding of S. marcescens genomic epidemiology and facilitating interlaboratory comparisons.

Published
2022

16. Emergency Interhospital Transfer of Patients With ST‐Segment–Elevation Myocardial Infarction: Call 9‐1‐1—The American Heart Association Mission: Lifeline Program

Author

William J. French, Mic Gunderson, David Travis, Mark Bieniarz, Jessica Zegre‐Hemsey, Abhinav Goyal, and Alice K. Jacobs

Subjects
Cardiology and Cardiovascular Medicine
Abstract

The American Heart Association Mission: Lifeline program objectives are to improve the quality of care and outcomes for patients with ST‐segment–elevation myocardial infarction. Every minute of delay in treatment adversely affects 1‐year mortality. Transfer of patients safely and timely to hospitals with primary percutaneous coronary intervention capability is needed to improve outcomes. But treatment times continue to show delays, especially during interhospital transfers. A simple 3‐step process of an interhospital “Call 9‐1‐1” protocol may expedite this process. This STAT TRANSFER process uses a systems approach that considers diverse ways in which patients access care, how EMS responds and determines destinations, how referring hospital transfers are performed, urban and rural differences, and how receiving hospitals prepare for an incoming patient with ST‐segment–elevation myocardial infarction. This initiative suggests a strategy to reduce variability in interhospital transfer times using a STAT TRANSFER and a Call 9‐1‐1 process in a system of care that involves all stakeholders.

Published
2022

17. Software for near-real-time voltammetric tracking of tonic neurotransmitter levels in vivo

Author

Abhinav, Goyal, Sangmun, Hwang, Aaron E, Rusheen, Charles D, Blaha, Kevin E, Bennet, Kendall H, Lee, Dong Pyo, Jang, Yoonbae, Oh, and Hojin, Shin

Subjects
General Neuroscience
Abstract

Tonic extracellular neurotransmitter concentrations are important modulators of central network homeostasis. Disruptions in these tonic levels are thought to play a role in neurologic and psychiatric disease. Therefore, ways to improve their quantification are actively being investigated. Previously published voltammetric software packages have implemented FSCV, which is not capable of measuring tonic concentrations of neurotransmitters in vivo. In this paper, custom software was developed for near-real-time tracking (scans every 10 s) of neurotransmitters’ tonic concentrations with high sensitivity and spatiotemporal resolution both in vitro and in vivo using cyclic voltammetry combined with dynamic background subtraction (M-CSWV and FSCAV). This software was designed with flexibility, speed, and user-friendliness in mind. This software enables near-real-time measurement by reducing data analysis time through an optimized modeling algorithm, and efficient memory handling makes long-term measurement possible. The software permits customization of the cyclic voltammetric waveform shape, enabling experiments to detect a specific analyte of interest. Finally, flexibility considerations allow the user to alter the fitting parameters, filtering characteristics, and size and shape of the analyte kernel, based on data obtained live during the experiment to obtain accurate measurements as experimental conditions change. Herein, the design and advantages of this near-real-time voltammetric software are described, and its use is demonstrated in in vivo experiments.

Published
2022
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18. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author

Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara 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Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits

Subjects
Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Published
2020

19. A PROSPECTIVE RANDOMIZED SINGLE-BLIND STUDY COMPARING ALPRAZOLAM VERSUS CLONIDINE AND PREGABALIN AS PREANAESTHETIC MEDICATION IN PATIENTS UNDERGOING ELECTIVE LOWER LIMB SURGERIES

Author

MOHD FAZAL AHMED MAKKI, SEEMA RANI, SANJEEV KUMAR, PRANAV BANSAL, RAHUL SAINI, and ABHINAV GOYAL

Subjects
Pharmacology, Pharmaceutical Science, Pharmacology (medical)
Abstract

Objective: The objective of the study was to study comparison of alprazolam versus clonidine and pregabalin as pre-anesthetic medication in patients undergoing elective lower limb surgeries. Methods: The present study was undertaken to compare the effects of alprazolam 0.5 mg, clonidine 100 μg, and pregabalin 75 mg as premedicant drugs for the reduction of pre-operative anxiety. 90 patients of ASA Grades I and II, between 18 and 60 years, of either sex, undergoing elective lower limb surgery were divided into three groups of 30 patients each. Baseline anxiety level and level after 2 h of the drug were assessed. Side effects due to drugs were noted before going to OT (Post drug, i.e., 2 h after drug administration), after the completion of the surgery, and at 24 h. Results: There is a significant post-drug reduction in s-STAI score, t-STAI score, and CGI score when compared to baseline values in all the Group’s A, C, and P. Side effects were mild and there were no serious adverse effects observed in all three groups. In Group A, 10% of patients complained of fatigue while in Group C, 13.3% of patients complained of dryness of mouth, and 10% of patients complained of headache 2 h post drug administration but in Group P, no side effect was noted. Conclusion: Premedication with 0.5 mg alprazolam, 100 μg clonidine, and 75 mg pregabalin for control of pre-operative anxiety was comparable though pregabalin offered a significant advantage in terms of less side effects.

Published
2022

20. County-Level Social Vulnerability is Associated With In-Hospital Death and Major Adverse Cardiovascular Events in Patients Hospitalized With COVID-19: An Analysis of the American Heart Association COVID-19 Cardiovascular Disease Registry

Author

Shabatun J. Islam, Gargya Malla, Robert W. Yeh, Arshed A. Quyyumi, Dhruv S. Kazi, Wei Tian, Yang Song, Aditi Nayak, Anurag Mehta, Yi-An Ko, James A. de Lemos, Fatima Rodriguez, Abhinav Goyal, and Rishi K. Wadhera

Subjects
Adult, Social Vulnerability, COVID-19, American Heart Association, Middle Aged, United States, Cardiovascular Diseases, Ethnicity, Humans, Hospital Mortality, Registries, Cardiology and Cardiovascular Medicine, Pandemics, Minority Groups
Abstract

Background: The COVID-19 pandemic has disproportionately affected low-income and racial/ethnic minority populations in the United States. However, it is unknown whether hospitalized patients with COVID-19 from socially vulnerable communities experience higher rates of death and/or major adverse cardiovascular events (MACEs). Thus, we evaluated the association between county-level social vulnerability and in-hospital mortality and MACE in a national cohort of hospitalized COVID-19 patients. Methods: Our study population included patients with COVID-19 in the American Heart Association COVID-19 Cardiovascular Disease Registry across 107 US hospitals between January 14, 2020 to November 30, 2020. The Social Vulnerability Index (SVI), a composite measure of community vulnerability developed by Centers for Disease Control and Prevention, was used to classify the county-level social vulnerability of patients’ place of residence. We fit a hierarchical logistic regression model with hospital-level random intercepts to evaluate the association of SVI with in-hospital mortality and MACE. Results: Among 16 939 hospitalized COVID-19 patients in the registry, 5065 (29.9%) resided in the most vulnerable communities (highest national quartile of SVI). Compared with those in the lowest quartile of SVI, patients in the highest quartile were younger (age 60.2 versus 62.3 years) and more likely to be Black adults (36.7% versus 12.2%) and Medicaid-insured (31.1% versus 23.0%). After adjustment for demographics (age, sex, race/ethnicity) and insurance status, the highest quartile of SVI (compared with the lowest) was associated with higher likelihood of in-hospital mortality (OR, 1.25 [1.03–1.53]; P =0.03) and MACE (OR, 1.26 [95% CI, 1.05–1.50]; P =0.01). These findings were not attenuated after accounting for clinical comorbidities and acuity of illness on admission. Conclusions: Patients hospitalized with COVID-19 residing in more socially vulnerable communities experienced higher rates of in-hospital mortality and MACE, independent of race, ethnicity, and several clinical factors. Clinical and health system strategies are needed to improve health outcomes for socially vulnerable patients.

Published
2022

21. Use of primary bariatric surgery among patients with obesity and diabetes. Insights from the Diabetes Collaborative Registry

Author

Priya, Jain, Vittal, Hejjaji, Merrill B, Thomas, Raul Angel, Garcia, Kevin F, Kennedy, Abhinav, Goyal, Laurence, Sperling, Sandeep R, Das, Samar, Hafida, Jonathan R, Enriquez, and Suzanne V, Arnold

Subjects
Male, Diabetes Mellitus, Type 2, Weight Loss, Diabetes Mellitus, Humans, Bariatric Surgery, Female, Obesity, Registries, Obesity, Morbid, Retrospective Studies
Abstract

Despite its cardiometabolic benefits, bariatric surgery has historically been underused in patients with obesity and diabetes, but contemporary data are lacking. Among 1,520,182 patients evaluated from 2013 to 2019 within a multicenter, longitudinal, US registry of outpatients with diabetes, we found that 462,033 (30%) met eligibility for bariatric surgery. After a median follow-up of 854 days, 6310/384,859 patients (1.6%) underwent primary bariatric surgery, with a slight increase over time (0.38% per year [2013] to 0.68% per year [2018]). Patients who underwent bariatric surgery were more likely to be female (63% vs. 56%), white (87% vs. 82%), have higher body mass indices (42.1 ± 6.9 vs. 40.6 ± 5.9 kg/m

Published
2022

22. Corporate governance, life cycle, and payout precommitment: An emerging market study

Author

Thomas Flavin, Abhinav Goyal, and Thomas O’Connor

Subjects
040101 forestry, 050208 finance, media_common.quotation_subject, Corporate governance, 05 social sciences, 04 agricultural and veterinary sciences, Monetary economics, Good governance, Shareholder, Accounting, Debt, 0502 economics and business, 0401 agriculture, forestry, and fisheries, Dividend, Precommitment, Endogeneity, Business, Emerging markets, Finance, media_common
Abstract

We analyze the role of firm-level corporate governance in determining the precommitment payout policy of emerging market firms and investigate if there is a precommitment lifecycle effect. Unlike previous studies for the U.S. firms, we only find evidence of precommitment among relatively well-governed firms, who combine good governance with large dividend payouts to shareholders and large debt-related repayments to creditors. We also document a strong precommitment lifecycle effect. Firms in the growth and mature stages of their lifecycle tend to use both debt and dividends to precommit to investors, with an increasing proportion of dividends in total payout measures. Our results are robust to an array of control variables, alternate payout proxies and market setting, firm-level corporate governance and addresses any potential endogeneity concerns in the sample.

Published
2021

23. Automatic and Reliable Quantification of Tonic Dopamine Concentrations In Vivo Using a Novel Probabilistic Inference Method

Author

Abhijeet S. Barath, Kendall H. Lee, Yoonbae Oh, Jason Yuen, Aaron E. Rusheen, J. Blair Price, Juan M. Rojas Cabrera, Danielle E. Jondal, Abhinav Goyal, Jaekyung Kim, Charles D. Blaha, Hojin Shin, and Dong Pyo Jang

Subjects
Signal processing, Computer science, General Chemical Engineering, Inference, Statistical model, General Chemistry, Signal, Article, Chemistry, In vivo, Log-normal distribution, Tonic (music), Sensitivity (control systems), Biological system, QD1-999
Abstract

Dysregulation of the neurotransmitter dopamine (DA) is implicated in several neuropsychiatric conditions. Multiple-cyclic square-wave voltammetry (MCSWV) is a state-of-the-art technique for measuring tonic DA levels with high sensitivity (

Published
2021

24. Mapping internal strain fields of fused filament fabrication metal filled polylactic acid structure using digital volume correlation

Author

Abhinav Goyal, Cristofaro S Timpano, and Garrett W Melenka

Subjects
Mechanics of Materials, Mechanical Engineering, Materials Chemistry, Ceramics and Composites
Abstract

With the advancement in Fused Filament Fabrication (FFF), its application is increasing widely across different industries such as aeronautical, biomedical, robotics, etc. The internal structure is becoming more complex and intricate with varying materials of reinforcement which are used to improve mechanical properties. Current measurement techniques like Digital Image Correlation (DIC) are non-destructive testing methods that do not provide enough information on the behaviour of internal microstructure for anisotropic FFF materials. Digital Volume Correlation (DVC) is non-destructive testing technique which provides full field internal 3D deformation and strain fields. Copper particle filled PLA samples manufactured using FFF method with 20, 40, 60 and 80 infill percentages were loaded in tension inside Micro-CT. X-rays were passed through the sample to get a volumetric dataset for different loadings. Using DVC method on the dataset, internal displacement and strain fields were generated for 20, 40, 60 and 80 infill percentage FFF sample.

Published
2023

25. Advances in neurochemical measurements: A review of biomarkers and devices for the development of closed-loop deep brain stimulation systems

Author

Yoonbae Oh, Kevin E. Bennet, Su Youne Chang, Hojin Shin, J. Blair Price, Kendall H. Lee, Danielle E. Jondal, Abhijeet S. Barath, Charles D. Blaha, Abhinav Goyal, Aaron E. Rusheen, and Juan M. Rojas Cabrera

Subjects
Deep brain stimulation, medicine.medical_treatment, Disease, Tourette syndrome, Article, Analytical Chemistry, 03 medical and health sciences, 0302 clinical medicine, Neurochemical, Dopamine, medicine, QD1-999, 030304 developmental biology, 0303 health sciences, closed-loop, voltammetry, business.industry, medicine.disease, electrophysiology, Neuromodulation (medicine), deep brain stimulation, Chemistry, Electrophysiology, electrochemistry, neuromodulation, business, Neuroscience, Closed loop, 030217 neurology & neurosurgery, medicine.drug
Abstract

Neurochemical recording techniques have expanded our understanding of the pathophysiology of neurological disorders, as well as the mechanisms of action of treatment modalities like deep brain stimulation (DBS). DBS is used to treat diseases such as Parkinson’s disease, Tourette syndrome, and obsessive-compulsive disorder, among others. Although DBS is effective at alleviating symptoms related to these diseases and improving the quality of life of these patients, the mechanism of action of DBS is currently not fully understood. A leading hypothesis is that DBS modulates the electrical field potential by modifying neuronal firing frequencies to non-pathological rates thus providing therapeutic relief. To address this gap in knowledge, recent advances in electrochemical sensing techniques have given insight into the importance of neurotransmitters, such as dopamine, serotonin, glutamate, and adenosine, in disease pathophysiology. These studies have also highlighted their potential use in tandem with electrophysiology to serve as biomarkers in disease diagnosis and progression monitoring, as well as characterize response to treatment. Here, we provide an overview of disease-relevant neurotransmitters and their roles and implications as biomarkers, as well as innovations to the biosensors used to record these biomarkers. Furthermore, we discuss currently available neurochemical and electrophysiological recording devices, and discuss their viability to be implemented into the development of a closed-loop DBS system.

Published
2020

26. Quality of Care Among Patients with Diabetes and Cerebrovascular Disease. Insights from The Diabetes Collaborative Registry

Author

Justin B. Echouffo-Tcheugui, Alexander Turchin, Robert S. Rosenson, Gregg C. Fonarow, Abhinav Goyal, James A. de Lemos, and Suzanne V. Arnold

Subjects
Glycated Hemoglobin, General Medicine, Coronary Artery Disease, Glucagon-Like Peptide-1 Receptor, Cerebrovascular Disorders, Glucose, Diabetes Mellitus, Type 2, Fibrinolytic Agents, Cardiovascular Diseases, Humans, Hypoglycemic Agents, Thiazolidinediones, Registries, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Sodium-Glucose Transporter 2 Inhibitors
Abstract

Although secondary cardiovascular prevention is a focus among patients with type 2 diabetes (T2D) and coronary artery disease (CAD) or peripheral artery disease (PAD), the application of guideline-recommended therapy in T2D patients and isolated cerebrovascular disease (CeVD) remains unknown.In a US outpatient registry, T2D patients with established cardiovascular disease from 2014-2018 were categorized as: isolated CeVD, CeVD plus CAD or PAD, or isolated CAD/PAD. In each group, we determined the proportion with optimal secondary prevention (hemoglobin [Hb]AOur study included 727,467 T2D outpatients with cardiovascular disease (isolated CeVD [n = 99,777], CeVD plus CAD/PAD [n = 158,361], isolated CAD/PAD [n = 469,329]). Compared with isolated CAD/PAD patients, isolated CeVD patients more often had an HbAAmong T2D patients, those with isolated CeVD had the lowest rates of secondary cardiovascular prevention goals attainment. More focus is needed on secondary prevention in patients with CeVD.

Published
2022

27. Impact of Palliative Care Utilization for Surgical Patients Receiving Prolonged Mechanical Ventilation: National Trends (2009–2013)

Author

Abhinav Goyal, Howard L. Corwin, Kevin W. Sexton, Kshitij Chatterjee, Sarah E. Harrington, and Ronald D. Robertson

Subjects
Adult, medicine.medical_specialty, Palliative care, Leadership and Management, medicine.medical_treatment, Length of hospitalization, 03 medical and health sciences, High morbidity, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, National trends, Aged, Retrospective Studies, Mechanical ventilation, business.industry, 030503 health policy & services, Palliative Care, Length of Stay, Respiration, Artificial, Long-term care, Cross-Sectional Studies, Emergency medicine, 0305 other medical science, business, Surgical patients
Abstract

Patients requiring mechanical ventilation (MV) have high morbidity and mortality. Providing palliative care has been suggested as a way to improve comprehensive management. The objective of this retrospective cross-sectional study was to identify predictors for palliative care utilization and the association with hospital length of stay (LOS) among surgical patients requiring prolonged MV (≥ 96 consecutive hours).National Inpatient Sample (NIS) data 2009-2013 was used to identify adults (age ≥ 18) who had a surgical procedure and required prolonged MV (≥ 96 consecutive hours), as well as patients who also had a palliative care encounter. Outcomes were palliative care utilization and association with hospital LOS.Utilization of palliative care among surgical patients with prolonged MV increased yearly, from 5.7% in 2009 to 11.0% in 2013 (p0.001). For prolonged MV surgical patients who died, palliative care increased from 15.8% in 2009 to 33.2% in 2013 (p0.001). Median hospital LOS for patients with and without palliative care was 16 and 18 days, respectively (p0.001). Patients discharged to either short or long term care facilities had a shorter LOS if palliative care was provided (20 vs. 24 days, p0.001). Factors associated with palliative care utilization included older age, malignancy, and teaching hospitals. Non-Caucasian race was associated with less palliative care utilization.Among surgical patients receiving prolonged MV, palliative care utilization is increasing, although it remains low. Palliative care is associated with shorter hospital LOS for patients discharged to short or long term care facilities.

Published
2020

28. Temporary Emergency Guidance to STEMI Systems of Care During the COVID-19 Pandemic

Author

Timothy D. Henry, Hani Jneid, Abhinav Goyal, Christopher B. Granger, Venu Menon, Michael Redlener, Mark Bieniarz, James G. Jollis, Jason N. Katz, Patricia J.M. Best, Alice K. Jacobs, General Cardiology, Gregg C. Fonarow, Murtuza J. Ali, Lori Hollowell, Jessica K. Zègre-Hemsey, Jacqueline E. Tamis-Holland, William J. French, Mauricio G. Cohen, and Peter J. Mason

Subjects
Consensus, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Pneumonia, Viral, Cardiology, Risk Assessment, STEMI, Betacoronavirus, Risk Factors, Physiology (medical), Pandemic, medicine, Humans, Pandemics, Occupational Health, Host Microbial Interactions, SARS-CoV-2, business.industry, percutaneous coronary intervention, COVID-19, Percutaneous coronary intervention, Frame of Reference, American Heart Association, Prognosis, medicine.disease, United States, Perspective, ST Elevation Myocardial Infarction, Cardiology Service, Hospital, Patient Safety, Medical emergency, Coronavirus Infections, Emergency Service, Hospital, Cardiology and Cardiovascular Medicine, business, Delivery of Health Care
Published
2020

29. Functionally distinct high and low theta oscillations in the human hippocampus

Author

Sameer A. Sheth, Ashwini Sharan, Joel M. Stein, Jonathan P. Miller, Chengyuan Wu, Michael R. Sperling, Bradley C. Lega, Salman E. Qasim, Catherine A. Schevon, Cory S. Inman, Honghui Zhang, Andrew J. Watrous, Jon T. Willie, Abhinav Goyal, Elliot H. Smith, Jui Jui Lin, Joshua J. Jacobs, Robert E. Gross, and Guy M. McKhann

Subjects
Adult, Male, 0301 basic medicine, Science, General Physics and Astronomy, Hippocampus, Hippocampal formation, Spatial memory, Article, General Biochemistry, Genetics and Molecular Biology, Learning and memory, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Rhythm, Task Performance and Analysis, Humans, Theta Rhythm, lcsh:Science, Electrodes, Episodic memory, Spatial Memory, Physics, Multidisciplinary, Oscillation, Cognition, General Chemistry, Middle Aged, Electrophysiology, 030104 developmental biology, Female, lcsh:Q, Neuroscience, 030217 neurology & neurosurgery
Abstract

Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4–10 Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta’s function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior–posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3 Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes., We show that the human hippocampus exhibits two distinct theta oscillations during spatial navigation with the faster oscillation in posterior regions showing movement modulation. This result suggests a distinct feature of the human hippocampus compared to rodents, which generally show a single 8 Hz rhythm.

Published
2020

33. Tonic Serotonin Measurements In Vivo Using N-Shaped Multiple Cyclic Square Wave Voltammetry

Author

Rohan Jha, J. Hudson Barnett, Kendall H. Lee, Yumin Kang, Aaron E. Rusheen, Sang Mun Hwang, Michael L. Heien, Charles D. Blaha, Abhinav Goyal, Cheonho Park, Hojin Shin, Dong Pyo Jang, Kevin E. Bennet, Yoonbae Oh, Jason Yuen, and Hyun-U Cho

Subjects
Brain Chemistry, Serotonin, Chemistry, Dopamine, Dopaminergic, Ascorbic acid, Serotonergic, Article, Analytical Chemistry, Rats, Rats, Sprague-Dawley, In vivo, medicine, Biophysics, Tonic (music), Animals, Reuptake inhibitor, Microelectrodes, medicine.drug
Abstract

Here, we present the development of a novel voltammetric technique, N-shaped multiple cyclic square wave voltammetry (N-MCSWV) and its application in vivo. It allows quantitative measurements of tonic extracellular levels of serotonin in vivo with mitigated fouling effects. N-MCSWV enriches the electrochemical information by generating high dimensional voltammograms, which enables high sensitivity and selectivity against 5-hydroindoleacetic acid (5-HIAA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), histamine, ascorbic acid, norepinephrine, adenosine, and pH. Using N-MCSWV, in combination with PEDOT:Nafion-coated carbon fiber microelectrodes, a tonic serotonin concentration of 52 ± 5.8 nM (n = 20 rats, ±SEM) was determined in the substantia nigra pars reticulata of urethane-anesthetized rats. Pharmacological challenges with dopaminergic, noradrenergic, and serotonergic synaptic reuptake inhibitors supported the ability of N-MCSWV to selectively detect tonic serotonin levels in vivo. Overall, N-MCSWV is a novel voltammetric technique for analytical quantification of serotonin. It offers continuous monitoring of changes in tonic serotonin concentrations in the brain to further our understanding of the role of serotonin in normal behaviors and psychiatric disorders.

Published
2021

35. Abstract 12208: Ecological Analysis of the Temporal Trends in the Association of Social Vulnerability and Race/Ethnicity With County-Level COVID-19 Incidence and Outcomes in the United States

Author

Shabatun Islam, Aditi Nayak, Yingtian Hu, Anurag Mehta, Katherine Dieppa, Zakaria Almuwaqqat, Yi-An Ko, Shivani Patel, Abhinav Goyal, Samaah Sullivan, Tene Lewis, Viola Vaccarino, Alanna A Morris, and Arshed A Quyyumi

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: The COVID-19 pandemic adversely affected socially vulnerable and minority communities in the US initially, but the temporal trends during the year-long pandemic remain unknown. Objective: We examined temporal association between county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in US in the year starting in March 2020. Methods: Counties (n=3091) with > 50 COVID-19 cases by March 6th, 2021 were included. Associations between SVI (and its subcomponents) and county level racial composition with incidence and death per capita were assessed using a negative-binomial mixed-effects model. This model was used to examine potential time varying associations between weekly number of cases/deaths and SVI or racial composition. Data was adjusted for percentage of population aged ≥65 years, state level testing rate, county-level comorbidities, and environmental factors. Results: Higher SVI, indicative of greater social vulnerability, was independently associated with higher COVID-19 incidence (adjusted incidence rate ratio [IRR] per-10 percentile increase:1.02, (95% CI 1.02, 1.03, p Conclusion: Except for winter “third wave” when majority White communities had highest incidence of cases, counties with greater social vulnerability and higher minority populations, experienced worse COVID-19 outcomes.

Published
2021

36. Abstract 11078: Neighborhood Social Vulnerability is Associated with Major Adverse Cardiovascular Events and Deaths Among Patients Hospitalized with Covid-19: An Analysis of the Aha Covid-19 Cardiovascular Disease Registry

Author

Shabatun Islam, Gargya Malla, Wei Tian, Yang Song, Dhruv S Kazi, Aditi Nayak, Anurag Mehta, Yi-An Ko, Arshed A Quyyumi, Robert W Yeh, Abhinav Goyal, and Rishi Wadhera

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: The COVID-19 pandemic has disproportionately affected low-income and racial/ethnic minority populations in the US. However, it remains unclear whether hospitalized COVID-19 patients who live in socially vulnerable neighborhoods are more likely to experience major adverse cardiovascular events and/or death. We evaluated the association between neighborhood social vulnerability and in-hospital outcomes in a national cohort of hospitalized COVID-19 patients. Hypothesis: Among patients hospitalized with COVID-19, residence in socially vulnerable neighborhoods is associated with worse in-hospital outcomes. Methods: The American Heart Association COVID-19 Cardiovascular Disease Registry includes patients hospitalized with COVID-19 across 107 hospitals in the US between January 14, 2020 to November 30, 2020. The Social Vulnerability Index (SVI), a composite measure of community vulnerability developed by Center for Disease Control was used to classify the social vulnerability of patients’ place of residence defined by zip codes. We fit multivariable logistic regression models to evaluate the association between patient’s SVI and in-hospital death or major adverse cardiovascular events (MACE, defined as composite of all-cause death, MI, stroke, new onset heart failure, or cardiogenic shock). Results: Among 20,925 hospitalized COVID-19 patients in the registry, 6083 (29.1%) resided in the most vulnerable communities (highest national quartile of SVI). Compared with those in lowest quartile of SVI, patients in the highest quartile were younger (mean age 59.8±17.7 versus 62.0±17.9), more likely to be women (47.1% vs. 43.2%), Black patients (36.1% vs. 13.3%), and less likely to have private insurance (29.0% vs. 39.1%). After adjusting for demographics (age, sex, race/ethnicity), insurance status, and comorbidities, the highest quartile of SVI (compared to lowest) was associated with higher likelihood of in-hospital MACE (OR [95% CI] 1.28 [1.12, 1.46], p Conclusion: Hospitalized patients with COVID-19 who reside in more socially vulnerable neighborhoods experience higher rates of in-hospital MACE and death, independent of race and ethnicity.

Published
2021

37. Do Investors Feedback Trade in the Bitcoin—And Why?

Author

Skander Slim, John W. Goodell, Rabaa Karaa, Abhinav Goyal, and Vasileios Kallinterakis

Subjects
Cryptocurrency, Series (mathematics), Volume, Economics, Econometrics and Finance (miscellaneous), Feedback trading, Asset allocation, Monetary economics, Market liquidity, Sentiment, Extant taxon, Liquidity, Economics, Futures contract, Bitcoin, Volume (compression), Positive feedback
Abstract

We empirically examine whether feedback traders are active in the Bitcoin and the extent to which their presence is affected by a series of noise-related factors (sentiment; volume; liquidity) at three different frequencies (hourly; daily; weekly) for the April 2013–July 2019 period based on Bitstamp data. Our findings suggest that positive feedback trading grows stronger for higher (hourly; daily) frequencies, with its presence manifesting itself mainly during periods of high/improving sentiment and high/rising volume/liquidity. Additional tests reveal that the significance of hourly feedback trading is identified during hours corresponding to the trading hours of major European/North American markets. Overall, our results confirm extant literature evidence on the prevalence of noise trading in cryptocurrencies, while further showcasing that the factors motivating feedback trading in other asset classes (equities; ETFs; futures) exhibit similar effects over the presence of feedback traders in the cryptocurrency market.

Published
2021

42. Societal secrecy and IPO underpricing

Author

Yangyang Chen, Andy C.W. Chui, Abhinav Goyal, and Madhu Veeraraghavan

Subjects
Economics and Econometrics, Strategy and Management, Business and International Management, Finance
Published
2022

43. Polypharmacy and mortality association by chronic kidney disease status: The RE asons for G eographic A nd R acial D ifferences in S troke Study

Author

Michael Goodman, Abhinav Goyal, George Howard, Winn Cashion, William M. McClellan, Valerie Prince, David G. Kleinbaum, Paul Muntner, and Suzanne E. Judd

Subjects
Polypharmacy, medicine.medical_specialty, Proportional hazards model, business.industry, Hazard ratio, medicine.disease, Confidence interval, Neurology, Internal medicine, Cohort, Epidemiology, medicine, General Pharmacology, Toxicology and Pharmaceutics, business, Stroke, Kidney disease
Abstract

Many Americans take multiple medications simultaneously (polypharmacy). Polypharmacy's effects on mortality are uncertain. We endeavored to assess the association between polypharmacy and mortality in a large U.S. cohort and examine potential effect modification by chronic kidney disease (CKD) status. The REasons for Geographic And Racial Differences in Stroke cohort data (n = 29 627, comprised of U.S. black and white adults) were used. During a baseline home visit, pill bottle inspections ascertained medications used in the previous 2 weeks. Polypharmacy status (major [≥8 ingredients], minor [6-7 ingredients], and none [0-5 ingredients]) was determined by counting the total number of generic ingredients. Cox models (time-on-study and age-time-scale methods) assessed the association between polypharmacy and mortality. Alternative models examined confounding by indication and possible effect modification by CKD. Over 4.9 years median follow-up, 2538 deaths were observed. Major polypharmacy was associated with increased mortality in all models, with hazard ratios and 95% confidence intervals ranging from 1.22 (1.07-1.40) to 2.35 (2.15-2.56), with weaker associations in more adjusted models. Minor polypharmacy was associated with mortality in some, but not all, models. The polypharmacy-mortality association did not differ by CKD status. While residual confounding by indication cannot be excluded, in this large American cohort, major polypharmacy was consistently associated with mortality.

Published
2021

44. Cocaine-Induced Changes in Tonic Dopamine Concentrations Measured Using Multiple-Cyclic Square Wave Voltammetry in vivo

Author

Jason Yuen, Abhinav Goyal, Aaron E. Rusheen, Abbas Z. Kouzani, Michael Berk, Jee Hyun Kim, Susannah J. Tye, Charles D. Blaha, Kevin E. Bennet, Dong-Pyo Jang, Kendall H. Lee, Hojin Shin, and Yoonbae Oh

Subjects
Microdialysis, tonic dopamine, nucleus accumbens, medicine.medical_treatment, cocaine, RM1-950, Pharmacology, Nucleus accumbens, Tonic (physiology), neuroscience, 03 medical and health sciences, 0302 clinical medicine, Neurochemical, In vivo, Dopamine, medicine, Pharmacology (medical), Medial forebrain bundle, Saline, 030304 developmental biology, Original Research, 0303 health sciences, voltammetry, Chemistry, psychiatry, mental disorders, Therapeutics. Pharmacology, addiction, 030217 neurology & neurosurgery, medicine.drug
Abstract

For over 40 years, in vivo microdialysis techniques have been at the forefront in measuring the effects of illicit substances on brain tonic extracellular levels of dopamine that underlie many aspects of drug addiction. However, the size of microdialysis probes and sampling rate may limit this technique’s ability to provide an accurate assessment of drug effects in microneural environments. A novel electrochemical method known as multiple-cyclic square wave voltammetry (M-CSWV), was recently developed to measure second-to-second changes in tonic dopamine levels at microelectrodes, providing spatiotemporal resolution superior to microdialysis. Here, we utilized M-CSWV and fast-scan cyclic voltammetry (FSCV) to measure changes in tonic or phasic dopamine release in the nucleus accumbens core (NAcc) after acute cocaine administration. Carbon-fiber microelectrodes (CFM) and stimulating electrodes were implanted into the NAcc and medial forebrain bundle (MFB) of urethane anesthetized (1.5 g/kg i.p.) Sprague-Dawley rats, respectively. Using FSCV, depths of each electrode were optimized by determining maximal MFB electrical stimulation-evoked phasic dopamine release. Changes in phasic responses were measured after a single dose of intravenous saline or cocaine hydrochloride (3 mg/kg; n = 4). In a separate group, changes in tonic dopamine levels were measured using M-CSWV after intravenous saline and after cocaine hydrochloride (3 mg/kg; n = 5). Both the phasic and tonic dopamine responses in the NAcc were augmented by the injection of cocaine compared to saline control. The phasic and tonic levels changed by approximately x2.4 and x1.9, respectively. These increases were largely consistent with previous studies using FSCV and microdialysis. However, the minimal disruption/disturbance of neuronal tissue by the CFM may explain why the baseline tonic dopamine values (134 ± 32 nM) measured by M-CSWV were found to be 10-fold higher when compared to conventional microdialysis. In this study, we demonstrated phasic dopamine dynamics in the NAcc with acute cocaine administration. M-CSWV was able to record rapid changes in tonic levels of dopamine, which cannot be achieved with other current voltammetric techniques. Taken together, M-CSWV has the potential to provide an unprecedented level of physiologic insight into dopamine signaling, both in vitro and in vivo, which will significantly enhance our understanding of neurochemical mechanisms underlying psychiatric conditions.

Published
2021

45. In times of crisis does ownership matter? Liquidity extraction through dividends during the 2007-2009 financial crisis

Author

John W. Goodell, Wei Huang, and Abhinav Goyal

Subjects
Economics and Econometrics, Dividends, Agency cost, Institutional investor, Monetary economics, Foreign direct investment, Financial crises, Chinese capital markets, Market liquidity, Shareholder, Financial crisis, Economics, Dividend, Financial liquidity, Foreign equity ownership, Capital market, Finance
Abstract

Liquidity flow between regions with different levels of temporary financial constraints has received insufficient attention. This study takes advantage of a natural opportunity: Chinese capital markets clearly distinguish between foreign direct investment firms and firms with foreign institutional investment. Using the distinctive categorization of institutional holding structures in China, we find that foreign controlled enterprises were associated with an extraordinary increase in dividend payouts during the Global Financial Crisis, with concomitant underinvestment. Our results suggest that foreign-controlling shareholders extracted liquidity through dividends, highlighting a previously ignored channel for global transference of liquidity, with concomitant agency costs.

Published
2021

46. DeepNavNet: Automated Landmark Localization for Neuronavigation

Author

Christine A. Edwards, Abhinav Goyal, Aaron E. Rusheen, Abbas Z. Kouzani, and Kendall H. Lee

Subjects
Neuronavigation, Computer science, neurosurgery planning, Neurosciences. Biological psychiatry. Neuropsychiatry, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Posterior commissure, Neuroimaging, medicine, Computer vision, Image resolution, Original Research, Ground truth, neuroimaging, Landmark, neuronavigation, medicine.diagnostic_test, business.industry, General Neuroscience, Brain atlas, deep learning, Magnetic resonance imaging, deep brain stimulation, landmark localization, Artificial intelligence, human-machine teaming, business, 030217 neurology & neurosurgery, Neuroscience, RC321-571
Abstract

Functional neurosurgery requires neuroimaging technologies that enable precise navigation to targeted structures. Insufficient image resolution of deep brain structures necessitates alignment to a brain atlas to indirectly locate targets within preoperative magnetic resonance imaging (MRI) scans. Indirect targeting through atlas-image registration is innately imprecise, increases preoperative planning time, and requires manual identification of anterior and posterior commissure (AC and PC) reference landmarks which is subject to human error. As such, we created a deep learning-based pipeline that consistently and automatically locates, with submillimeter accuracy, the AC and PC anatomical landmarks within MRI volumes without the need for an atlas. Our novel deep learning pipeline (DeepNavNet) regresses from MRI scans to heatmap volumes centered on AC and PC anatomical landmarks to extract their three-dimensional coordinates with submillimeter accuracy. We collated and manually labeled the location of AC and PC points in 1128 publicly available MRI volumes used for training, validation, and inference experiments. Instantiations of our DeepNavNet architecture, as well as a baseline model for reference, were evaluated based on the average 3D localization errors for the AC and PC points across 311 MRI volumes. Our DeepNavNet model significantly outperformed a baseline and achieved a mean 3D localization error of 0.79 ± 0.33 mm and 0.78 ± 0.33 mm between the ground truth and the detected AC and PC points, respectively. In conclusion, the DeepNavNet model pipeline provides submillimeter accuracy for localizing AC and PC anatomical landmarks in MRI volumes, enabling improved surgical efficiency and accuracy.

Published
2021

47. Ecological Analysis of the Temporal Trends in the Association of Social Vulnerability and Race/Ethnicity with County-Level COVID-19 Incidence and Outcomes in the United States

Author

Katherine Dieppa, Samaah Sullivan, Anurag Mehta, Shivani A. Patel, Aditi Nayak, Zakaria Almuwaqqat, Viola Vaccarino, Alanna A. Morris, Shabatun J. Islam, Abhinav Goyal, Yi-An Ko, Yingtian Hu, Tené T. Lewis, and Arshed A. Quyyumi

Subjects
medicine.medical_specialty, Equity (economics), Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, Incidence (epidemiology), Incidence, COVID-19, Health Status Disparities, Article, United States, Epidemiology, Pandemic, medicine, Ethnicity, Humans, Ecological analysis, business, Association (psychology), Social vulnerability, Pandemics, Demography
Abstract

BackgroundThe COVID-19 pandemic adversely affected the socially vulnerable and minority communities in the U.S. initially, but the temporal trends during the year-long pandemic remain unknown.ObjectiveWe examined the temporal association between the county-level Social Vulnerability Index (SVI), a percentile-based measure of social vulnerability to disasters, its subcomponents and race/ethnic composition with COVID-19 incidence and mortality in the U.S. in the year starting in March 2020.MethodsCounties (n=3091) with ≥ 50 COVID-19 cases by March 6th, 2021 were included in the study. Associations between SVI (and its subcomponents) and county level racial composition with the incidence and death per capita were assessed by fitting a negative-binomial mixed-effects model. This model was also used to examine potential time varying associations between weekly number of cases/deaths and SVI or racial composition. Data was adjusted for percentage of population aged ≥65 years, state level testing rate, comorbidities using the average Hierarchical Condition Category (HCC) score, and environmental factors including average fine particulate matter (PM2.5), temperature and precipitation.ResultsHigher SVI, indicative of greater social vulnerability, was independently associated with higher COVID-19 incidence (adjusted incidence rate ratio [IRR] per-10 percentile increase:1.02, (95% CI 1.02, 1.03, pConclusionExcept for the winter “third wave” when majority White communities had the highest incidence of cases, counties with greater social vulnerability and proportionately higher minority populations, experienced worse COVID-19 outcomes.Article Summary/Strengths & LimitationsExamined full 12 months of county-level data in the US delineating the temporal trends in the association between social vulnerability index and COVID-19 outcomesInvestigated COVID-19 outcomes in predominantly Black and Hispanic communities in comparison to White communities in the USAnalysis is ecological, descriptive, and on the county-level rather than on an individual levelAnalysis adjusted for confounders including county level age ≥ 65, comorbidities, and environmental factorsAnalysis limited to the US

Published
2021

48. Case Report: Heparin-induced thrombocytopenia in a patient with COVID-19 [version 2; peer review: 2 approved]

Author

Ragia Aly, Sachin Gupta, Sorab Gupta, Balraj Singh, Abhinav Goyal, and Sheila Kalathil

Subjects
Science, Medicine
Abstract

With the spread of the novel coronavirus disease of 2019 (COVID-19) worldwide and associated high incidence of thromboembolic complications, the use of heparin is on the rise. It therefore is crucial to identify patients with contraindications for heparin. Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of exposure to heparin. We report a 66-year-old woman, who was admitted to the hospital with COVID-19 infection. Her course was complicated by pulmonary embolism and dialysis catheter thrombosis. Our patient had a known history of HIT. Treatment of this patient with heparin would have been catastrophic. The COVID-19 pandemic has overwhelmed healthcare systems and is causing a global health crisis. Nevertheless, this case serves as a reminder of the importance of making every effort to obtain thorough history and review of records of every patient.

Published
2021

49. Primary Gastric Adenosquamous Carcinoma: A Case Report

Author

Balraj Singh, Navroop Nagra, Abhinav Goyal, Sorab Gupta, Ragia Aly, and Sachin Gupta

Subjects
0301 basic medicine, medicine.medical_specialty, Gastric Adenosquamous Carcinoma, Adenosquamous carcinoma, Stomach cancer, Case Report, Pembrolizumab, Adenocarcinoma, Gastroenterology, 03 medical and health sciences, Gastric adenocarcinoma, 0302 clinical medicine, Internal medicine, medicine, business.industry, Stomach, digestive, oral, and skin physiology, Cancer, medicine.disease, digestive system diseases, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, business, Gastric cancer
Abstract

Gastric adenosquamous carcinoma (GASC) is a rare variant of gastric cancer; the limited data available suggest that these tumors are more aggressive and have a worse outcome in comparison to gastric adenocarcinoma. Currently, the management of GASC is similar to adenocarcinoma. We report a case of GASC that progressed rapidly despite treatment.

Published
2020

50. Invariant patterns of clonal succession determine specific clinical features of myelodysplastic syndromes

Author

Mohammad Fahad B Asad, Tomas Radivoyevitch, Yuichi Shiraishi, Satoru Miyano, Jaroslaw P. Maciejewski, Hassan Awada, Abhinav Goyal, Hiroko Tanaka, Kenichi Yoshida, Torsten Haferlach, Hiromichi Suzuki, Sudipto Mukherjee, Aziz Nazha, Kenichi Chiba, Bartlomiej P Przychodzen, Yasunobu Nagata, Thomas LaFramboise, Hideki Makishima, Seishi Ogawa, Mikkael A. Sekeres, Mai Aly, Teodora Kuzmanovic, Tetsuichi Yoshizato, and Cassandra M Kerr

Subjects
Male, 0301 basic medicine, Myeloid, Somatic cell, Science, General Physics and Astronomy, Biology, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Exome Sequencing, Cancer genomics, medicine, Humans, lcsh:Science, Exome sequencing, Aged, Genetics, Multidisciplinary, Myelodysplastic syndromes, Clonal architecture, General Chemistry, Phosphoproteins, Splicing Factor U2AF, medicine.disease, Phenotype, Hematopoiesis, Leukemia, Myeloid, Acute, Leukemia, Treatment Outcome, 030104 developmental biology, medicine.anatomical_structure, Primary Myelofibrosis, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Mutation, Female, lcsh:Q, RNA Splicing Factors, KRAS, Tumor Suppressor Protein p53, Myelodysplastic syndrome
Abstract

Myelodysplastic syndromes (MDS) arise in older adults through stepwise acquisitions of multiple somatic mutations. Here, analyzing 1809 MDS patients, we infer clonal architecture by using a stringent, the single-cell sequencing validated PyClone bioanalytic pipeline, and assess the position of the mutations within the clonal architecture. All 3,971 mutations are grouped based on their rank in the deduced clonal hierarchy (dominant and secondary). We evaluated how they affect the resultant morphology, progression, survival and response to therapies. Mutations of SF3B1, U2AF1, and TP53 are more likely to be dominant, those of ASXL1, CBL, and KRAS are secondary. Among distinct combinations of dominant/secondary mutations we identified 37 significant relationships, of which 12 affect clinical phenotypes, 5 cooperatively associate with poor prognosis. They also predict response to hypomethylating therapies. The clonal hierarchy has distinct ranking and the resultant invariant combinations of dominant/secondary mutations yield novel insights into the specific clinical phenotype of MDS., Stepwise acquisition of mutations gives rise to myelodysplastic syndrome (MDS) in older adults. Here, the authors infer the clonal hierarchy of 1809 MDS patients, revealing insights into the evolution of dominant/secondary mutations and how these impact clinical phenotypes like leukemic progression and therapy response.

Published
2019

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