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Introduction Premenopausal women with intermediate-high risk HR+ breast cancer often receive near-complete estrogen deprivation with ovarian function suppression concurrent with an AI. Hypoestrogenemia is associated with cardiotoxicity, but the cardiovascular impact of this newer breast cancer treatment is largely unknown. With increases in survival rates and younger women being diagnosed, methods to monitor and predict cardiac damage due to OFS+AI therapy are needed. Left ventricle (LV) ejection fraction is currently used for monitoring cancer treatment-related cardiovascular degradation, and can detect major heart defects, but is insensitive to subclinical left ventricle function. Emerging methods include T1 mapping and estimation of myocardial strain to indicate fibrosis. We propose an extension of these methods by estimating cardiac tissue elasticity using LV wall deformation to drive a biomechanical model. Elasticity is a more functional and direct measurement of tissue response based on structural mechanics driven by patient-specific cardiac magnetic resonance imaging (CMR) data. Elasticity measurements may serve as a predictive biomarker of early AI-induced cardiac changes.MethodsThis study is a retrospective initial proof-of-concept correlative imaging study to an existing clinical study for the use of CMR to detect cardiovascular damage (ESPRIT). Two cohorts of premenopausal breast cancer patients either: (1) undergoing OFS+AI for HR+ breast cancer or (2) triple negative breast cancer (TNBC) patients that have already received chemotherapy, were imaged twice, 3-6 months apart using CINE CMR. TNBC patients serve as the control, with no expectation of further cancer treatment-related cardiac damage. Time steps during passive ventricular diastole were visually selected from CINE CMRs. Each slice was non-rigidly registered to estimate LV deformation during passive filling. Deformation was simulated on a finite element mesh of the LV based on linear elastic transverse isotropic mechanical equilibrium. Using an inverse problem formulation, simulated deformation was compared to model-calculated deformation to estimate the spatial tissue longitudinal and transverse elasticity. Elasticity maps of the LV at initial and final points are compared to determine regional stiffening of the LV wall, to be used as early biomarkers for LV fibrosis. ResultsIn this initial investigation, elasticity maps were analyzed for four patients (n=2 from each cohort). Passive LV tissue stiffening was observed in each AI patient, with 100% and 25% relative increases observed for longitudinal elasticity and 50% increases for transverse elasticity in the basal inferior region, and mid anterior region of the LV in each patient, respectively. No increases in stiffness of the LV were observed for TNBC patients. Ejection fraction remained consistent for all patients. ConclusionIn this proof-of-concept study, we demonstrate that elasticity maps indicate local stiffening of the LV using a biomechanical model-based elasticity imaging method that could be used to indicate cardiac dysfunction in breast cancer patients receiving AIs. Spatial elasticity mapping allows direct observation of structural mechanics to reveal specific areas of LV stiffening. Moving beyond traditional strain imaging, our method yields a functional measure of tissue stiffness to directly indicate cardiac fibrosis. This study demonstrates the use of biomechanical models to interpret CMR and provides potential for use of more advanced constitutive models. Our non-invasive biomechanical model-based elasticity imaging method shows significant promise to indicate early cardiac function deterioration, critical for premenopausal women undergoing extended cancer therapies. Citation Format: Caroline Elizabeth Miller, Jennifer Jordan, Alexandra Thomas, Jared Weis. Predicting cardiac dysfunction in breast cancer patients undergoing aromatase inhibitor treatment using biomechanical model-based elasticity imaging [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-21.

Hyperactivity is a core ADHD symptom that has been both positively and negatively associated with cognition and functional outcomes. The reason for these conflicting findings is unclear but may relate to subjective assessments that conflate excess physical movement (hyperactivity) with verbally intrusive/impulsive behaviors. The current study adopted a model-driven, rational-empirical approach to distinguish excess physical movement symptoms from other, auditorily perceived behaviors assessed under the "hyperactivity/impulsivity" umbrella. We then tested this alternative conceptualization's fit, reliability, replicability, convergent/divergent validity via actigraphy, and generalizability across informants (parents, teachers) in a well-characterized, clinically evaluated sample of 132 children ages 8-13 years (M = 10.34, SD = 1.51; 47 girls; 67% White/non-Hispanic). The current DSM hyperactivity/impulsivity item pool can be reliably reclassified by knowledgeable judges into items reflecting excess physical movement (visual hyperactivity) and auditory interruptions (verbal intrusion). This bifactor structure showed evidence for multidimensionality and superior model fit relative to traditional hyperactivity/impulsivity models. The resultant visual hyperactivity factor was reliable, replicable, and showed strong convergent validity evidence via associations with objectively assessed hyperactivity. The verbal intrusion factor also showed evidence for reliability and explained a substantive portion of reliable variance, but demonstrated lower estimated replicability. These findings provide preliminary support for conceptualizing ADHD symptoms from the perspective of their cognitive-perceptual impact on others, as well as differentiating excess physical movement (hyperactivity) from other behaviors assessed under the hyperactivity/impulsivity umbrella. "Verbal intrusion" appears to provide a better explanation than "impulsivity" for the reliable, non-hyperactivity variance assessed by these items, but the current item set appears insufficient for replicable measurement of this construct. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Purpose: Assessing cardiotoxicity as a result of breast cancer therapeutics is increasingly important as breast cancer diagnoses are trending younger and overall survival is increasing. With evidence showing that prevention of cardiotoxicity plays a significant role in increasing overall survival, there is an unmet need for accurate non-invasive methods to assess cardiac injury due to cancer therapies. Current clinical methods are too coarse and emerging research methods have not yet achieved clinical implementation. Approach: As a proof of concept, we examine myocardial elasticity imaging in the setting of premenopausal women diagnosed with hormone receptor positive (HR-positive) breast cancer undergoing severe estrogen depletion, as cardiovascular injury from early estrogen depletion is well-established. We evaluate the ability of our model-based cardiac elasticity imaging analysis method to indicate subclinical cancer therapy-related cardiac decline by examining differences in the change in cardiac elasticity over time in two cohorts of premenopausal women either undergoing severe estrogen depletion for HR-positive breast cancer or triple negative breast cancer patients as comparators. Results: Our method was capable of producing functional mechanical elasticity maps of the left ventricle (LV). Using these elasticity maps, we show significant differences in cardiac mechanical elasticity in the HR-positive breast cancer cohort compared to the comparator cohort. Conclusions: We present our methodology to assess the mechanical stiffness of the LV by interrogating cardiac magnetic resonance images within a computational biomechanical model. Our preliminary study suggests the potential of this method for examining cardiac tissue mechanical stiffness properties as an early indicator of cardiac decline.

Most children with ADHD have impaired working memory abilities. These working memory deficits predict impairments in activities of daily living (ADLs) for adults with ADHD. However, our understanding of the relation between pediatric ADHD and ADLs is limited. Thus, this study aimed to examine (1) the extent to which pediatric ADHD is associated with ADL difficulties; and if so (2) the extent to which these difficulties are related to their well-documented working memory difficulties and/or core ADHD inattentive and hyperactive/impulsive symptom domains. A well-characterized, clinically evaluated sample of 141 children ages 8–13 years (M=10.36, SD=1.46; 51 girls; 70% White/non-Hispanic) were administered a battery of well-validated working memory tests and assessed for ADHD symptoms (teacher-ratings) and ADL difficulties (parent-ratings); cross-informant reports were used to control for mono-informant bias. Children with ADHD exhibited medium magnitude difficulties with ADLs (d=0.61, p

Objective Executive function deficits are well-established in ADHD. Unfortunately, replicated evidence indicates that executive function training for ADHD has been largely unsuccessful. We hypothesized that this may reflect insufficient targeting, such that extant protocols do not sufficiently and specifically target the neurocognitive systems associated with phenotypic ADHD behaviors/impairments. Method Children with ADHD ages 8-12 (M = 10.41, SD = 1.46; 12 girls; 74% Caucasian/Non-Hispanic) were randomized with allocation concealment to either central executive training (CET; n = 25) or newly developed inhibitory control training (ICT; n = 29). Detailed data analytic plans were preregistered. Results Both treatments were feasible/acceptable based on training duration, child-reported ease of use, and parent-reported high satisfaction. CET was superior to ICT for improving its primary intervention targets: phonological and visuospatial working memory (d = 0.70-0.84). CET was also superior to ICT for improving go/no-go (d = 0.84) but not stop-signal inhibition. Mechanisms of change analyses indicated that CET-related working memory improvements produced significant reductions in the primary clinical endpoints (objectively assessed hyperactivity) during working memory and inhibition testing (indirect effects: β ≥ -.11; 95% CIs exclude 0.0). CET was also superior to ICT on 3 of 4 secondary clinical endpoints (blinded teacher-rated ADHD symptoms; d = 0.46-0.70 vs. 0.16-0.42) and 2 of 4 feasibility/acceptability clinical endpoints (parent-reported ADHD symptoms; d = 0.96-1.42 vs. 0.45-0.65). CET-related gains were maintained at 2-4 month follow-up; ICT-related gains were maintained for attention problems but not hyperactivity/impulsivity per parent report. Conclusions Results support the use of CET for treating executive function deficits and targeting ADHD behavioral symptoms in children with ADHD. Findings for ICT were mixed at best and indicate the need for continued development/study. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objective: Attention-deficit/hyperactivity disorder (ADHD) has been associated with large magnitude impairments in working memory, whereas short-term memory deficits, when detected, tend to be less pronounced. However, confidence in these findings is limited due to task impurity combined with methodological and statistical limitations of the current evidence base. Method: A well-characterized, clinically evaluated sample of 172 children ages 8-13 years (M = 10.30, SD = 1.42; 72 girls; 64% White/non-Hispanic) were administered multiple, counterbalanced working memory tests. Bifactor-(s-1) modeling was used to characterize the presence and magnitude of central executive working memory, phonological short-term memory, and visuospatial short-term memory deficits in pediatric ADHD. Results: ADHD status was associated with very large magnitude impairments in central executive working memory that are present in most pediatric cases (d = 1.63-2.03; 75%-81% impaired), and these deficits covaried with ADHD inattentive and hyperactive/impulsive symptom severity based on both parent and teacher report. There was also evidence for a unique, albeit significantly smaller, impairment in visuospatial short-term memory (d = 0.60; 38% impaired); however, visuospatial short-term memory abilities did not covary with ADHD symptom severity. There was no evidence linking ADHD with phonological short-term memory deficits across either the dimensional or categorical analyses. Conclusion: These findings provide strong evidence that ADHD is associated with marked central executive working memory deficits that covary with their behavioral symptom presentation across settings. In contrast, visuospatial short-term memory deficits, when present, are likely epiphenomenal, and the most parsimonious conclusion appears to be that phonological short-term memory is intact in pediatric ADHD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objective Sluggish cognitive tempo refers to a constellation of symptoms that include slowed behavior/thinking, reduced alertness, and getting lost in one's thoughts. Despite the moniker "sluggish cognitive tempo," the evidence is mixed regarding the extent to which it is associated globally with slowed (sluggish) mental (cognitive) information processing speed (tempo). Method A well-characterized clinical sample of 132 children ages 8-13 years (M = 10.34, SD = 1.51; 47 girls; 67% White/non-Hispanic) were administered multiple, counterbalanced neurocognitive tests and assessed for sluggish cognitive tempo symptoms via multiple-informant reports. Results Bayesian linear regressions revealed significant evidence against associations between sluggish cognitive tempo and computationally modeled processing speed (BF01 > 3.70), and significant evidence for associations with slower working memory manipulation speed. These findings were consistent across parent and teacher models, with and without control for attention-deficit/hyperactivity disorder inattentive symptoms and IQ. There was also significant evidence linking faster inhibition speed with higher parent-reported sluggish cognitive tempo symptoms. Conclusions These findings provide strong evidence against characterizing children with sluggish cognitive tempo symptoms as possessing a globally sluggish cognitive tempo. Instead, these symptoms appear to be related, to a significant extent, to executive dysfunction characterized by working memory systems that are too slow and inhibition systems that are too fast. Behaviorally, these findings suggest that requiring extra time to rearrange the active contents of working memory delays responding, whereas an overactive inhibition system likely terminates thoughts too quickly and therefore prevents intended behaviors from starting or completing, thereby giving the appearance that children are absent-minded or failing to act when expected. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Meat from oxidative skeletal muscle has a higher postmortem ultimate pH, which was originally thought to be a result from decreased antemortem glycogen stores. Therefore, we hypothesized that excess glycogen may not resolve the high ultimate pH of meat from oxidative muscles in ruminants and poultry. To test this hypothesis, an in vitro muscle glycolytic buffer system containing excess glycogen was used to compare glycolysis and pH decline of glycolytic and oxidative muscle from beef, lamb, chicken, and turkey. Glycogen concentration of both glycolytic and oxidative muscle homogenates was similar at 0 min and decreased significantly with time in all species tested. All homogenates contained residual glycogen at 1440 min, indicating glycogen was provided in excess. The ultimate pH of the oxidative muscle homogenates was significantly increased compared to the glycolytic muscle. The oxidative muscle also contained decreased lactate and decreased glucose 6-phosphate in all the species tested at 1440 min. Combined these data suggest that glycolysis and pH decline of oxidative muscles terminate prematurely at higher ultimate pH even in the presence of excess glycogen across livestock species. Additionally, the data indicated that the in vitro glycolytic buffer system can be used to study species specific meat quality problems in beef, lamb, chicken, and turkey.

PURPOSE: To ascertain which patients are most likely to benefit from a phase II cardiac rehabilitation (CR) program. METHODS: A retrospective chart review was conducted on 425 patients who completed a 6-minute walk test (6MWT), body weight (BW), and the Medical Outcomes Short Form Health Survey physical (PCS) and mental (MCS) component scores before and after CR. These variables were compared between patients who attended 24 or less and 25 or more sessions and between tertiles on the basis of initial 6MWT and the relative change in 6MWT. RESULTS: The entire cohort of patients improved their 6MWT 20.1 +/- 16.3% with CR (P < .001). On average, patients experienced a modest reduction in BW (P = .03) and had higher PCS and MCS scores (P < .001 for both) after CR. The improvement in 6MWT was inversely related to initial walk distance (r = -0.465, P < .001). Patients in the lowest initial 6MWT tertile exhibited greater improvement in the 6MWT than those in the highest tertile (28 +/- 20 vs 13 +/- 10%, P < .001). Patients who attended 25 or more sessions demonstrated greater 6MWT (20 +/- 18 vs 18 +/- 14%, P = .012) and reductions in BW (-1.3 +/- 2.8 vs -0.5 +/- 2.5 kg, P = .003) than those attending 24 or fewer sessions. Patients exhibiting greater than 23% improvement in 6MWT lost more BW (-1.4 +/- 2.9 vs -0.6 +/- 2.5 kg, P = .006) and exhibited greater PCS (10.2 +/- 9.8 vs 6.3 +/- 9.4, P = .004) than those exhibiting