Showing papers by "Virginia Commonwealth University published in 2023"

Optimization of Transspinal Stimulation Applications for Motor Recovery after Spinal Cord Injury: Scoping Review

Abstract: Spinal cord injury (SCI) is a debilitating condition that can significantly affect an individual’s life, causing paralysis, autonomic dysreflexia, and chronic pain. Transspinal stimulation (TSS) is a non-invasive form of neuromodulation that activates the underlying neural circuitries of the spinal cord. Application of TSS can be performed through multiple stimulation protocols, which may vary in the electrodes’ size or position as well as stimulation parameters, and which may influence the response of motor functions to the stimulation. Due to the novelty of TSS, it is beneficial to summarize the available evidence to identify the range of parameters that may provide the best outcomes for motor response. The PubMed and Google Scholar databases were searched for studies examining the effects of TSS on limb motor function. A literature search yielded 34 studies for analysis, in which electrode placement and stimulation parameters varied considerably. The stimulation protocols from each study and their impact on limb motor function were summarized. Electrode placement was variable based on the targeted limb. Studies for the upper limbs targeted the cervical enlargement with anatomical placement of the cathode over the cervical vertebral region. In lower-limb studies, the cathode(s) were placed over the thoracic and lumbar vertebral regions, to target the lumbar enlargement. The effects of carrier frequency were inconclusive across the studies. Multisite cathodal placements yielded favorable motor response results compared to single-site placement. This review briefly summarized the current mechanistic evidence of the effect of TSS on motor response after SCI. Our findings indicate that optimization of stimulation parameters will require future randomized controlled studies to independently assess the effects of different stimulation parameters under controlled circumstances.

Selective Inhibition of Soluble TNF using XPro1595 Improves Hippocampal Pathology to Promote Improved Neurological Recovery Following Traumatic Brain Injury in Mice

Abstract: To determine the efficacy of XPro1595 to improve pathophysiological and functional outcomes in a mouse model of traumatic brain injury (TBI).Symptoms associated with TBI can be debilitating, and treatment without off-target side effects remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of TBI.Use XPro1595 to determine whether injury-induced solTNF promotes hippocampal inflammation and dendritic plasticity, and associated functional impairments.Mild-to-moderate traumatic brain injury (CCI model) was induced in adult male C57Bl/6J WT and Thy1-YFPH mice, with XPro1595 (10 mg/kg, S.C.) or vehicle being administered in a clinically relevant window (60 minutes post-injury). The animals were assessed for differences in neurological function, and hippocampal tissue was analyzed for inflammation and glial reactivity, as well as neuronal degeneration and plasticity.We report that unilateral CCI over the right parietal cortex in mice promoted deficits in learning and memory, depressive-like behavior, and neuropathic pain. Using immunohistochemical and Western blotting techniques, we observed the cortical injury promoted a set of expected pathophysiology's within the hippocampus consistent with the observed neurological outcomes, including glial reactivity, enhanced neuronal dendritic degeneration (dendritic beading), and reduced synaptic plasticity (spine density and PSD-95 expression) within the DG and CA1 region of the hippocampus, that were prevented in mice treated with XPro1595.Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of brain-injured mice, which provides support for its use in patients with TBI.

A mixed methods exploration of the emergence of goal orientation in medical students’ individualized learning plans

Abstract: Goal orientation (GO) describes an individual's approach to different achievement situations. Understanding the motivations and approach to achieving goals of medical students is vital with the increasing emphasis on self-directed learning. The purpose of this study was to identify themes in self-improvement reflections that relate to each GO dimension (learning, performance-prove, and performance-avoid).A sequential explanatory mixed methods design was used. GO data was used to categorize students into groups aligning with the GO dimension identified in the previous stage of quantitative analysis. Individualized learning plans (ILPs) for each GO dimension group were coded inductively to identify emergent themes related to goal setting and achievement.The learning GO group was the largest of the three GOs. Five themes were identified from inductive analysis: importance of practice, identifying elements that helped, identifying structural barriers, opportunities for improvement, and acknowledging experience. While these themes occur across GO, patterns exist within their ILPs based on GO.We identified common themes for motivations of medical students, and these motivations might differ depending on their GO. Further exploration into the themes over the course of their training will provide additional insights on what factors may be involved in student motivations towards learning and achievement. Educators can use this information to individualize feedback and students can better understand their motivations towards achieving goals.

Incidence varieties in the projectivized kth Hodge bundle over curves with rational tails

Abstract: Over the moduli space of pointed smooth algebraic curves, the projectivized [Formula: see text]th Hodge bundle is the space of [Formula: see text]-canonical divisors. The incidence loci are defined by requiring the [Formula: see text]-canonical divisors to have prescribed multiplicities at the marked points. We compute the classes of the closure of the incidence loci in the projectivized [Formula: see text]th Hodge bundle over the moduli space of curves with rational tails. The classes are expressed as a linear combination of tautological classes indexed by decorated stable graphs with coefficients enumerating appropriate weightings. As a consequence, we obtain an explicit expression for some relations in tautological rings of moduli of curves with rational tails.

A pointed Prym–Petri Theorem

Abstract: We construct pointed Prym–Brill–Noether varieties parametrizing line bundles assigned to an irreducible étale double covering of a curve with a prescribed minimal vanishing at a fixed point. We realize them as degeneracy loci in type D and deduce their classes in case of expected dimension. Thus, we determine a pointed Prym–Petri map and prove a pointed version of the Prym–Petri theorem implying that the expected dimension holds in the general case. These results build on work of Welters [Ann. Sci. Ëcole Norm. Sup. (4) 18 (1985), pp. 671–683] and De Concini–Pragacz [Math. Ann. 302 (1995), pp. 687–697] on the unpointed case. Finally, we show that Prym varieties are Prym–Tyurin varieties for Prym–Brill–Noether curves of exponent enumerating standard shifted tableaux times a factor of 2 2 , extending to the Prym setting work of Ortega [Math. Ann. 356 (2013), pp. 809–817].

The homeostatic function of Regnase‐2 restricts neuroinflammation

Abstract: The precise physiological functions and mechanisms regulating RNase Regnase-2 (Reg-2/ZC3H12B/MCPIP2) activity remain enigmatic. We found that Reg-2 actively modulates neuroinflammation in nontransformed cells, including primary astrocytes. Downregulation of Reg-2 in these cells results in increased mRNA levels of proinflammatory cytokines IL-1β and IL-6. In primary astrocytes, Reg-2 also regulates the mRNA level of Regnase-1 (Reg-1/ZC3H12A/MCPIP1). Reg-2 is expressed at high levels in the healthy brain, but its expression is reduced during neuroinflammation as well as glioblastoma progression. This process is associated with the upregulation of Reg-1. Conversely, overexpression of Reg-2 is accompanied by the downregulation of Reg-1 in glioma cells in a nucleolytic NYN/PIN domain-dependent manner. Interestingly, low levels of Reg-2 and high levels of Reg-1 correlate with poor-glioblastoma patients' prognoses. While Reg-2 restricts the basal levels of proinflammatory cytokines in resting astrocytes, its expression is reduced in IL-1β-activated astrocytes. Following IL-1β exposure, Reg-2 is phosphorylated, ubiquitinated, and degraded by proteasomes. Simultaneously, the Reg-2 transcript is destabilized by tristetraprolin (TTP) and Reg-1 through the AREs elements and conservative stem-loop structure present in its 3'UTR. Thus, the peer-control loop, of Reg-1 and Reg-2 opposing each other, exists. The involvement of TTP in Reg-2 mRNA turnover is confirmed by the observation that high TTP levels correlate with the downregulation of the Reg-2 expression in high-grade human gliomas. Additionally, obtained results reveal the importance of Reg-2 in inhibiting human and mouse glioma cell proliferation. Our current studies identify Reg-2 as a critical regulator of homeostasis in the brain.

Subjective and objective burden on providers from a multicenter app-based study of patients with cirrhosis and caregivers

Abstract: App-based technologies could enhance patient and caregiver communication and provide alerts that potentially reducing readmissions. However, the burden of App alerts needs to be optimized to reduce provider burnout.The purpose of this study was to determine subjective and objective burden of using the Patient Buddy App, a health information technology (HIT) on providers in a randomized multicenter trial, who completed a semi-quantitative Likert scale survey regarding training procedures, data and privacy concerns, follow-up details, and technical support. This randomized multicenter trial recruits cirrhosis inpatients and their caregivers, and randomizes them into standard-of-care, HIT (communication only via App) and HIT+visits (App+phone calls/visits) for 30 days after discharge. The alerts are monitored by providers through a central iPad. The reason(s) and number of alerts were recorded as the objective burden. A total of 1442 messages were sent as alerts from the 103 dyads (patient + caregiver) (n=206) randomized to HIT arms. The most common messages related to Hepatic Encephalopathy (HE) (high or low bowel movement=50% or orientation tests=37%). Twelve providers completed the surveys reflecting the following themes-92% and 100%, felt adequately trained and confident about educating the patients and caregivers before roll out of App and had no concerns related to data and privacy; 70%, felt that appropriate time was spent on pursuing reason for data not being logged; 60% each, had issues with availability of adequate technical support and connectivity.The Patient Buddy App randomized multicenter trial till date shows an overall favorable rating regarding training procedures/education, privacy concerns, and ease of message follow-up, from providers. However, it is important to gauge and address subjective and objective burdens of monitoring human resources in current and future HIT studies to avoid burnout and to ensure successful study completion.

C.E. Credit. Artificial Intelligence Applications for the Radiographic Detection of Periodontal Disease: A Scoping Review

Abstract: Background Calculating radiographic bone loss (RBL) can be time-consuming, labor-intensive, and examiner dependent. Artificial intelligence (AI) models have been developed to automate the detection of RBL and the risk of developing periodontal disease and tooth loss. The aim of this scoping review was to identify and evaluate the performance of AI models in diagnosing periodontal disease by detecting RBL.Types of Studies Reviewed Medline, Embase, Web of Science, Dental and Oral Sciences Source, Cumulated Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, ClinicalTrials.gov, and MedRxiv were searched to collect evidence about AI models utilized to detect RBL and diagnosis of periodontal disease. Qualitative analysis was conducted to describe the performance and limitations of AI models for panoramic radiographs, periapical images, and cone beam computed tomography (CBCT).Results Nineteen studies met the inclusion criteria out of 322 articles identified. Mean accuracy for panoramic radiographic AI models ranged from 63% to 94%. Automated models based on periapical radiographs yielded results ranging from precision as low as 25% for detecting mild disease to a high accuracy of 99% in radiographic bone level staging performance. Periodontal bone loss sensitivity on CBCT ranged from 45% to 72%, while periodontal bone loss specificity was 81% to 83%.Practical Implications AI systems can be a helpful initial approach to screening radiographic images for periodontal disease, given that research shows these diagnostic methods might help provide a more accurate evaluation than examiner review alone. AI models developed for the diagnosis of periodontal disease using RBL require further development to accurately and reliably assess RBL and determine risk of periodontal disease independent of clinician assessment.Continuing Education Credit Available: The practice worksheet is available online in the supplemental material tab for this article.A CDA Continuing Education quiz is online for this article: https://www.cdapresents360.com/learn/catalog/view/20.

Falling Behind: The Growing Gap in Life Expectancy Between the United States and Other Countries, 1933-2021.

Abstract: Objectives. To document the evolution of the US life expectancy disadvantage and regional variation across the US states. Methods. I obtained life expectancy estimates in 2022 from the United Nations, the Human Mortality Database, and the US Mortality Database, and calculated changes in growth rates, US global position (rank), and state-level trends. Results. Increases in US life expectancy slowed from 1950 to 1954 (0.21 years/annum) and 1955 to 1973 (0.10 years/annum), accelerated from 1974 to 1982 (0.34 years/annum), and progressively deteriorated from 1983 to 2009 (0.15 years/annum), 2010 to 2019 (0.06 years/annum), and 2020 to 2021 (-0.97 years/annum). Other countries experienced faster growth in each phase except 1974 to 1982. During 1933 to 2021, 56 countries on 6 continents surpassed US life expectancy. Growth in US life expectancy was slowest in Midwest and South Central states. Conclusions. The US life expectancy disadvantage began in the 1950s and has steadily worsened over the past 4 decades. Dozens of globally diverse countries have outperformed the United States. Causal factors appear to have been concentrated in the Midwest and South. Public Health Implications. Policies that differentiate the United States from other countries and circumstances associated with the Midwest and South may have contributed. (Am J Public Health. Published online ahead of print June 1, 2023:e1-e11. https://doi.org/10.2105/AJPH.2023.307310).

Sexually Dimorphic Role for Insular Perineuronal Nets in Aversion-Resistant Ethanol Consumption

Abstract: Abstract Compulsive alcohol drinking is a key symptom of alcohol use disorder (AUD) that is particularly resistant to treatment. An understanding of the biological factors that underly compulsive drinking will allow for the development of new therapeutic targets for AUD. One animal model of compulsive alcohol drinking involves the addition of bitter-tasting quinine to an ethanol solution and measuring the willingness of the animal to consume ethanol despite the aversive taste. Previous studies have demonstrated that this type of aversion-resistant drinking is modulated in the insular cortex of male mice by specialized condensed extracellular matrix known as perineuronal nets (PNNs), which form a lattice-like structure around parvalbumin-expressing neurons in the cortex. Several laboratories have shown that female mice exhibit higher levels of aversion-resistant ethanol intake but the role of PNNs in females in this behavior has not been examined. Here we compared PNNs in the insula of male and female mice and determined if disrupting PNNs in female mice would alter aversion-resistant ethanol intake. PNNs were visualized in the insula by fluorescent labeling with Wisteria floribunda agglutinin (WFA) and disrupted in the insula by microinjecting chondroitinase ABC, an enzyme that digests the chondroitin sulfate glycosaminoglycan component of PNNs. Mice were tested for aversion-resistant ethanol consumption by the addition of sequentially increasing concentrations of quinine to the ethanol in a two-bottle choice drinking in the dark procedure. PNN staining intensity was higher in the insula of female compared to male mice, suggesting that PNNs in females might contribute to elevated aversion-resistant drinking. However, disruption of PNNs had limited effect on aversion-resistant drinking in females. In addition, activation of the insula during aversion-resistant drinking, as measured by c-fos immunohistochemistry, was lower in female mice than in males. Taken together, these results suggest that neural mechanisms underlying aversion-resistant ethanol consumption differ in males and females.

Prediction of suitable outpatient candidates following revision total knee arthroplasty using machine learning

Abstract: To identify variables independently associated with same-day discharge (SDD) of patients following revision total knee arthroplasty (rTKA) and to develop machine learning algorithms to predict suitable candidates for outpatient rTKA.Data were obtained from the American College of Surgeons National Quality Improvement Programme (ACS-NSQIP) database from the years 2018 to 2020. Patients with elective, unilateral rTKA procedures and a total hospital length of stay between zero and four days were included. Demographic, preoperative, and intraoperative variables were analyzed. A multivariable logistic regression (MLR) model and various machine learning techniques were compared using area under the curve (AUC), calibration, and decision curve analysis. Important and significant variables were identified from the models.Of the 5,600 patients included in this study, 342 (6.1%) underwent SDD. The random forest (RF) model performed the best overall, with an internally validated AUC of 0.810. The ten crucial factors favoring SDD in the RF model include operating time, anaesthesia type, age, BMI, American Society of Anesthesiologists grade, race, history of diabetes, rTKA type, sex, and smoking status. Eight of these variables were also found to be significant in the MLR model.The RF model displayed excellent accuracy and identified clinically important variables for determining candidates for SDD following rTKA. Machine learning techniques such as RF will allow clinicians to accurately risk-stratify their patients preoperatively, in order to optimize resources and improve patient outcomes.

Energy restriction or improvements in diet quality: identifying the best pathway for a longer and healthier life

Abstract: Obesity is a major risk factor for chronic non-communicable diseases (NCDs) and it has increased to epidemic proportions. Unhealthy diet represents a modifiable risk factor for both obesity and NCDs, however, there is no universal dietary intervention to improve obesity-related NCDs and particularly to reduce the risk for major adverse cardiovascular events. Energy restriction (ER) and diet quality changes, with and without ER, have been widely investigated in preclinical and clinical studies, however, the potential underlying mechanisms driving the benefits of those dietary interventions remain largely unclear. ER affects multiple metabolic, physiological, genetic, and cellular adaptation pathways associated with prolonged lifespan, particularly in preclinical models, while these benefits remain to be established in humans. Moreover, the sustainability of ER and its implementation across the different diseases remains challenging. On the other hand, diet quality with improvements, with or without ER, has been associated with more favorable long-term metabolic and cardiovascular outcomes. This narrative review will describe the role of ER and/or diet quality improvements on the risk for NCDs. It will also discuss the potential mechanisms of action underlying the potential beneficial effects of those dietary approaches.

A population-based twin study of the symptomatic diagnostic criteria for major depression that occur within versus outside of major depressive episodes

Abstract: Are genetic risk factors for current depressive symptoms good proxies for genetic risk factors for syndromal major depression (MD)?In over 9000 twins from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, the occurrence of all nine DSM symptomatic criteria for MD in the last year was assessed at personal interview and then grouped by their temporal co-occurrence. The DSM criteria which occurred outside (OUT) v. inside of (IN) MD episodes were then separated. We calculated tetrachoric correlations for OUT and IN depressive criteria in monozygotic (MZ) and dizygotic (DZ) pairs and fitted univariate and bivariate ACE twin models using OpenMx.The mean twin correlations (±95% CIs) for IN depressive criteria were substantially higher than for OUT depressive criteria in both MZ [+0.35 (0.32-0.38) v. 0.20 (0.17-0.24)] and DZ pairs [0.20 (0.17-0.24) v. 0.10 (0.04-0.16]. The mean IN-OUT cross-correlation in MZ and DZ pairs was modest [+0.15 (0.07-0.24) and +0.07 (0.03-0.12)]. The mean heritability estimates for the nine In v. Out depressive criteria was 0.31 (0.22-0.41) and 0.15 (0.08-0.21), in MZ and DZ pairs, respectively. The mean genetic correlation between the nine IN and OUT depressive criteria was +0.07 (-0.07 to 0.21).Depressive criteria occurring outside depressive episodes are less heritable than those occurring within. These two ways criteria can manifest are not closely genetically related. Current depressive symptoms - most of which are occurring outside of depressive episodes - are not, for genetic studies, good proxies for MD.

Family acculturation: Understanding the acculturation gap through the caregiver-adolescent dyad

Abstract: Family acculturation has been understood as a constellation of factors that impact caregiver-adolescent dyads. Differences in acculturation levels between caregivers and adolescents, typically referred to as acculturation gaps, often result in family conflict that leads to youth's negative mental and physical health outcomes. This chapter discusses the conceptualization and measurement of the family acculturation gap. This chapter also discusses contextualizing factors (e.g., communication and value discrepancies, family conflict, and caregiving practices) that help explain why and how family acculturation gaps are related to negative youth outcomes. Clinical, prevention, and intervention recommendations addressing bilingual and multicultural humility issues related to the family acculturation gap are also discussed. The chapter on family acculturation provides an overview of the acculturation gap through the caregiver-adolescent dyad. Cultural and contextual factors are also considered in relation to negative and positive youth outcomes. Most importantly, practical, and translational recommendations are provided in efforts to address multicultural humility related to the family acculturation gap.

Parental practices and adolescent health

Abstract: Parents play a vital role in their adolescent's health. From different practices (i.e., monitoring, communication, supervision), to family functioning, these components can influence adolescents’ overall health outcomes (i.e., safe sex practices, engaging in risky behavior, substance use, mental health). In this entry, we highlight the importance of parental practices and family functioning for adolescent health. Additionally, the section discusses the importance of examining diverse cultures and the effect of cultural values on parenting and adolescent health outcome, and the importance of parental monitoring during adolescence. We then conclude by discussing the importance of including parents in interventions targeting adolescent health, and the implications related to considering culturally tailored intervention in future studies.

Heroism and mental health

Abstract: Heroism confers obvious benefits to the recipient of the heroic act, and current research also demonstrates benefits to the heroic actor and to society as a whole. Heroic stories and mythology offer meaning, purpose, and coherence to readers and listeners. The mere act of thinking about heroes endows people with positive emotions and a sense of social connectedness. Counselors and therapists use the hero's journey to help their clients acquire resilience and achieve heroic transformation. Heroism fosters a readiness to become happy, secure, wise, and growth-oriented. Exposure to heroic acts instills people with wisdom, goals, moral role models, inspiration, healing, and emotional intelligence.

Assets and stressors on adolescent substance use: The role of religiosity

Abstract: Adolescents face many factors that can contribute to adolescent substance use. The literature highlights key biological, social-cultural, peer, and familial-factors associated with adolescent substance use. However, one of the assets is the personal and community-level aspects of religiosity, especially given that most American families still identify as religious. Given there is a significant emphasis on prevention and early intervention, these programs can be embedded into the community in spaces where families with adolescents are already in. For example, community-level religiosity within the context of positive community is essential for promoting health and resilience, despite the many stressors encountered. Therefore, religious organizations can promote health and preventing and reducing adolescent substance use.

Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes

Abstract: FSGS is a heterogeneous diagnosis with a guarded prognosis. Polymorphisms in the apolipoprotein L1 ( APOL1 ) gene are associated with developing FSGS and faster progression to kidney failure in affected patients. Better understanding the natural history of patients with FSGS and APOL1 risk alleles is essential to improve patient care and support the design and interpretation of interventional studies. The objective of this study was to evaluate the quantitative association between APOL1 and kidney disease progression and the interaction with other clinical and laboratory factors.CureGN cohort study participants with biopsy diagnosis of FSGS, regardless of self-identified race, were included. The exposure of interest was two APOL1 risk alleles (high risk) versus zero to one risk alleles (low risk). The primary outcome was eGFR slope categorized as rapid progressor (eGFR slope ≤-5 ml/min per year), intermediate progressor (slope between 0 and -5), or nonprogressor (slope ≥0). Multivariable ordinal logistic and linear regressions were used for adjusted analyses. Missing data were addressed using multiple imputation.Of 650 participants, 476 (73%) had genetic testing, among whom 87 (18%) were high risk. High-risk participants were more likely to have lower median eGFR (62 [interquartile range, 36-81] versus low-risk participants 76 ml/min per 1.73 m 2 [interquartile range, 44-106]; P <0.01). In adjusted analysis, the odds of more rapid progression of eGFR was 2.75 times higher (95% confidence interval, 1.67 to 4.53; P <0.001) in the high-risk versus low-risk groups.In patients with FSGS, high-risk APOL1 genotype is the predominant factor associated with more rapid loss of kidney function.

Dual mTORC1/2 Inhibition Synergistically Enhances AML Cell Death in Combination with the BCL2 Antagonist Venetoclax

Abstract: Abstract Purpose: Acute myelogenous leukemia (AML) is an aggressive disease with a poor outcome. We investigated mechanisms by which the anti-AML activity of ABT-199 (venetoclax) could be potentiated by dual mTORC1/TORC2 inhibition. Experimental design: Venetoclax/INK128 synergism was assessed in various AML cell lines and primary patient AML samples in vitro. AML cells overexpressing MCL-1, constitutively active AKT, BAK, and/or BAX knockout, and acquired venetoclax resistance were investigated to define mechanisms underlying interactions. The antileukemic efficacy of this regimen was also examined in xenograft and patient-derived xenograft (PDX) models. Results: Combination treatment with venetoclax and INK128 (but not the mTORC1 inhibitor rapamycin) dramatically enhanced cell death in AML cell lines. Synergism was associated with p-AKT and p-4EBP1 downregulation and dependent upon MCL-1 downregulation and BAK/BAX upregulation as MCL-1 overexpression and BAX/BAK knockout abrogated cell death. Constitutive AKT activation opposed synergism between venetoclax and PI3K or AKT inhibitors, but not INK128. Combination treatment also synergistically induced cell death in venetoclax-resistant AML cells. Similar events occurred in primary patient-derived leukemia samples but not normal CD34+ cells. Finally, venetoclax and INK128 co-treatment displayed increased antileukemia effects in in vivo xenograft and PDX models. Conclusions: The venetoclax/INK128 regimen exerts significant antileukemic activity in various preclinical models through mechanisms involving MCL-1 downregulation and BAK/BAX activation, and offers potential advantages over PI3K or AKT inhibitors in cells with constitutive AKT activation. This regimen is active against primary and venetoclax-resistant AML cells, and in in vivo AML models. Further investigation of this strategy appears warranted.