Cardiopulmonary exercise testing on adaptive equipment in children and adults with Friedreich ataxia.

INTRODUCTION/AIMS: Traditional exercise is often difficult for individuals with Friedreich ataxia (FRDA), and evidence is limited regarding how to measure exercise performance in this population. We evaluated the feasibility, reliability, and natural history of adaptive cardiopulmonary exercise test (CPET) performance in children and adults with FRDA. METHODS: Participants underwent CPET on either an arm cycle ergometer (ACE) or recumbent leg cycle ergometer (RLCE) at up to four visits (baseline, 2 weeks, 4 weeks, and 1 year). Maximum work, oxygen consumption (peak VO2), oxygen (O2) pulse, and anaerobic threshold (AT) were measured in those who reached maximal volition. Test-retest reliability was assessed with intraclass coefficients, and longitudinal change was assessed using regression analysis. RESULTS: In our cohort (N = 23), median age was 18 years (interquartile range [IQR], 14-23), median age of FRDA onset was 8 years (IQR 6-13), median Friedreich Ataxia Rating Scale score was 58 (IQR 54-62), and GAA repeat length on the shorter FXN allele (GAA1) was 766 (IQR, 650-900). Twenty-one (91%) completed a maximal CPET (n = 8, ACE and n = 13, RLCE). Age, sex, and GAA1 repeat length were each associated with peak VO2. Preliminary estimates demonstrated reasonable agreement between visits 2 and 3 for peak work by both ACE and RLCE, and for peak VO2, O2 pulse, and AT by RLCE. We did not detect significant performance changes over 1 year. DISCUSSION: Adaptive CPET is feasible in FRDA, a relevant clinical trial outcome for interventions that impact exercise performance and will increase access to participation as well as generalizability of findings.

Enhancing the health knowledge and health literacy of recently resettled refugees through classroom-based instructional methods.

Health education can elevate health literacy, which is associated with health knowledge, health-seeking behaviors and overall improved health outcomes. Refugees are particularly vulnerable to the effects of low health knowledge and literacy, which can exacerbate already poor health stemming from their displacement experience. Traditional learning methods including classroom-based instruction are typically how health-related information is presented to refugees. Through a series of interactive classes focused on specific health topics relevant to the resettled refugee population, this study evaluated the effectiveness of a classroom-based health education model in enhancing the health knowledge of recently resettled refugees. We used the Wilcoxon signed-rank test to evaluate differences in pre- and post-class knowledge through test performance. We found a significant improvement in health knowledge in two refugee groups: females and those who were employed. Culturally and socially sensitive considerations including language inclusiveness, class timing, transportation and childcare provisions are important when creating an educational program for individuals with refugee backgrounds. Developing focused approaches to instruction that enhance health knowledge could lead to better health literacy and ultimately improve health-related behaviors and outcomes in the refugee population.

A Path FORWARD: Development of a Comprehensive Multidisciplinary Clinic to Create Health and Wellness for the Child and Adolescent with a Fontan Circulation.

Today, it is anticipated most individuals diagnosed with single-ventricle malformation will survive surgical reconstruction through a successful Fontan operation. As greater numbers of patients survive, so has the recognition that individuals with Fontan circulation face a variety of challenges. The goal of a normal quality and duration of life will not be reached by all. The hurdles fall into a variety of domains. From a cardiovascular perspective, the Fontan circulation is fundamentally flawed by its inherent nature of creating a state of chronically elevated venous pressure and congestion, accompanied by a relatively low cardiac output. Ventricular dysfunction, atrioventricular valve regurgitation, and arrhythmia may directly impact cardiac performance and can progress with time. Problems are not limited to the cardiovascular system. Fontan circulatory physiology impacts a multitude of biological processes and health parameters outside the heart. The lymphatic circulation is under strain manifesting as variable degrees of protein-rich lymph loss and immune system dysregulation. Organ system dysfunction develops through altered perfusion profiles. Liver fibrosis is ubiquitous, and a process of systemic fibrogenesis in response to circulatory stressors may affect other organs as well. Somatic growth and development can be delayed. Behavioral and mental health problems are common, presenting as clinically important levels of anxiety and depression. Most striking is the high variability in prevalence and magnitude of these complications within the population, indicating the likelihood of additional factors enhancing or mitigating their emergence. We propose that optimal care for the individual with single ventricle and a Fontan circulation is ideally offered in a comprehensive multidisciplinary manner, with attention to elements that are beyond cardiac management alone. In this report, we share the concepts, our experiences, and perspectives on development of a clinic model-the "Fontan rehabilitation, wellness and resilience development" or FORWARD program. We provide insights into the mechanics of our multidisciplinary model of care and the benefits offered serving our growing population of individuals with a Fontan circulation and their families.

Normative Values for Cardiopulmonary Exercise Stress Testing Using Ramp Cycle Ergometry in Children and Adolescents.

OBJECTIVES: To provide sex, age, and race specific reference values for ramp cycle ergometer cardiopulmonary exercise test (CPET) in children in the US. STUDY DESIGN: Retrospective review was conducted of all cardiopulmonary CPET data from our Exercise Physiology Laboratory on healthy children and adolescents (6-18 years) with body mass index between the 5th and 95th percentiles and structurally normal hearts who performed a ramp cycle ergometry stress test between 1999 and 2015. Twenty-eight exercise variables were included: peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, peak work rate, resting and peak heart rate and blood pressure, resting pulmonary function testing, and ventilatory responses to progressive exercise using breath-by-breath gas exchange. Owing to the nonlinear association between CPET results and age, fractional polynomials were used in the mixed-effects regression models to describe the sex- and age-specific normative values with 95% CIs, after adjusting for race and body mass index. RESULTS: We analyzed data on 1829 children (average age, 13.6 ± 2.6 years; 52% male). After 12 years of age, males generally had higher peak values for aerobic capacity and work rate. There were progressive increases with age for both sexes in resting pulmonary function and ventilatory response to exercise, peak aerobic and work rate, and oxygen pulse. Notably, there was an age-related decrease in ventilatory equivalents of oxygen and carbon dioxide at the ventilatory anaerobic threshold. CONCLUSIONS: Future research using prospective, inclusive, and statistically planned cohorts with standardized laboratory approaches and confirmed interoperability should be considered as a focus for validating normative pediatric CPET values in the future.

Velocity influences the relative contributions of visual and vestibular cues to self-acceleration.

Self-motion perception is based on the integration of visual (optic flow) and vestibular (inertial) sensory information. Previous research has shown that the relative contribution of visual and vestibular cues can change in real time based on the reliability of that information. The present study assessed whether initial velocity and acceleration magnitude influence the relative contribution of these cues to the detection of self-acceleration. Participants performed a simple response time task with visual and vestibular self-acceleration cues as targets. Visual optic flow was presented at three possible initial velocities of 3, 9, or 15 m/s, and accelerated to result in three possible final velocities of 21, 27, or 33 m/s. Corresponding vestibular cues were presented at magnitudes between 0.01 and 0.04 g. The self-acceleration cues were presented at three possible stimulus onset asynchronies (SOAs): visual-first (by 100 ms), in-sync, and vestibular-first (by 100 ms). We found that presenting the cues in-sync resulted in the fastest responses across all velocities and acceleration magnitudes. Interestingly, presenting the visual cue first resulted in a relative advantage over vestibular-first at the slowest initial velocity of 3 m/s, and vice versa for the fastest initial velocity of 15 m/s. The fastest overall responses for visual-first and in-sync were observed at 9 m/s. The present results support the hypothesis that velocity of optic flow can alter the relative contribution of visual and vestibular cues to the detection of self-acceleration.

Attention modulates event-related spectral power in multisensory self-motion perception.

Humans integrate visual and physical (vestibular and proprioceptive) cues to motion during self-motion perception. Theta and alpha-band oscillations have been associated with the processing of visual motion (e.g. optic flow). Alpha and beta-band oscillations have been shown to be associated with sensory-motor processing (e.g. walking). The present study examined modulation of theta, alpha, and beta oscillations while participants made heading direction judgments during a passive self-motion task which required selective attention to one of the simultaneously presented visual or physical motion stimuli. Attention to physical (while ignoring visual) motion produced a different time course of changes in spectral power compared to attention to visual (while ignoring physical) motion. We observed weaker theta event-related synchronization (ERS), as well as stronger beta and later onset of alpha event-related desynchronization (ERD) in the attend-physical condition compared to the attend-visual condition. We observed individual differences in terms of ability to perform the task. Specifically, some participants were not able to ignore or discount the visual input when visual and physical heading direction was incongruent; this was reflected by similar event-related spectral power for both conditions. The results demonstrated a possible electrophysiological signature of the time course of 1) cue conflict (congruency effects), 2) attention to specific motion cues, and 3) individual differences in perceptual weighting of motion stimuli (high-vs. low-accuracy effects).

The Effectiveness of Simulator Motion in the Transfer of Performance on a Tracking Task Is Influenced by Vision and Motion Disturbance Cues.

OBJECTIVE: To examine the importance of platform motion to the transfer of performance in motion simulators. BACKGROUND: The importance of platform motion in simulators for pilot training is strongly debated. We hypothesized that the type of motion (e.g., disturbance) contributes significantly to performance differences. METHODS: Participants used a joystick to perform a target tracking task in a pod on top of a MOOG Stewart motion platform. Five conditions compared training without motion, with correlated motion, with disturbance motion, with disturbance motion isolated to the visual display, and with both correlated and disturbance motion. The test condition involved the full motion model with both correlated and disturbance motion. We analyzed speed and accuracy across training and test as well as strategic differences in joystick control. RESULTS: Training with disturbance cues produced critical behavioral differences compared to training without disturbance; motion itself was less important. CONCLUSION: Incorporation of disturbance cues is a potentially important source of variance between studies that do or do not show a benefit of motion platforms in the transfer of performance in simulators. APPLICATION: Potential applications of this research include the assessment of the importance of motion platforms in flight simulators, with a focus on the efficacy of incorporating disturbance cues during training.

A Quantitative Examination of Undergraduate Neuroscience Majors Applying and Matriculating to Osteopathic Medical School.

Undergraduates choose to become neuroscience majors for a number of reasons including future career goals. Faculty and administration of undergraduate neuroscience programs understand that many neuroscience majors have aspirations of applying and matriculating to medical school (Prichard, 2015); however a quantitative understanding of this particular student population remains unknown, especially in the context of the national growth in undergraduate neuroscience education (Ramos et al., 2011). In the present report, we use medical school application data to establish a novel quantitative understanding of the number of neuroscience majors that apply and matriculate to osteopathic medical school. Our data indicate that a substantial number of neuroscience majors do indeed apply and matriculate to medical school compared to other majors in the life sciences, math and physical sciences, and humanities. These data are relevant to faculty and administration of undergraduate neuroscience programs and suggest that when programmatic, curricular, and training decisions are made, they should be made in the context of the diverse motivations and professional goals of neuroscience majors including careers in medicine. Finally, our novel quantitative approach of determining student motivation and professional goals based on application/matriculation data, can complement traditional methods such as surveys and questionnaires and can be used to determine the extent to which neuroscience majors apply to other professional and graduate degree programs.

Undergraduate Neuroscience Education in the U.S.: Quantitative Comparisons of Programs and Graduates in the Broader Context of Undergraduate Life Sciences Education.

The impact of undergraduate neuroscience programs on the broader landscape of life sciences education has not been described. Using data from the National Center for Education Statistics, we found that the number of undergraduate neuroscience programs in the U.S. continues to grow. Within any given institution, neuroscience programs exist alongside a small number of other life sciences undergraduate programs, suggesting that neuroscience is one of few major options from which students can choose from at many institutions. Neuroscience majors constitute a substantial proportion of all life sciences graduates at many institutions, and in several cases, neuroscience majors were the majority of life sciences graduates. Thus, neuroscience programs contribute substantially to life sciences education, and neuroscience is a highly attractive major among undergraduate students where these programs are available. These data have implications for institutions with existing neuroscience programs as well as for institutions seeking to establish a new program.

Creating a digital approach for promoting physical activity in pediatric pulmonary hypertension: A framework for future interventions.

Children with pulmonary hypertension (PH) often demonstrate limited exercise capacity. Data support exercise as an effective nonpharmacologic intervention among adults with PH. However, data on exercise training in children and adolescents are limited, and characteristics of the optimal exercise program in pediatric PH have not been identified. Exercise programs may have multiple targets, including muscle deficits which are associated with exercise limitations in both adult and pediatric PH. Wearable accelerometer sensors measure physical activity volume and intensity in the naturalistic setting and can facilitate near continuous data transfer and bidirectional communication between patients and the study team when paired with informatics tools during exercise interventions. To address the knowledge gaps in exercise training in pediatric PH, we designed a prospective, single arm, nonrandomized pilot study to determine feasibility and preliminary estimates of efficacy of a 16-week home exercise intervention, targeting lower extremity muscle mass and enriched by wearable mobile health technology. The exercIse Training in pulmONary hypertEnsion (iTONE) trial includes (1) semistructured exercise prescriptions tailored to the participant's baseline level of activity and access to resources; (2) interval goal setting fostering self-efficacy; (3) real time monitoring of activity via wearable devices; (4) a digital platform enabling communication and feedback between participant and study team; (5) multiple avenues to assess participant safety. This pilot intervention will provide information on the digital infrastructure needed to conduct home-based exercise interventions in PH and will generate important preliminary data on the effect of exercise interventions in youth with chronic cardiorespiratory conditions to power larger studies in the future.

Child safety assessments during a caregiver's evaluation in emergency departments after intimate partner violence.

BACKGROUND: Physical abuse of children is reported to occur in 30%-60% of homes with intimate partner violence (IPV). IPV in adult victims presenting to emergency departments (EDs) represents a critical opportunity to evaluate for child safety. OBJECTIVES: The primary objective was to determine the frequency of child safety assessments (CSAs), defined as any documented inquiry about the presence of children in the household, when adults presented to EDs for IPV. The secondary aims were to assess (1) the impact of demographic factors, ED type, and social work (SW) involvement on the likelihood of CSAs; (2) the nature of children's exposure; and (3) the frequency of child protective services (CPS) reports. METHODS: We performed a chart review of encounters with ICD-10-CM codes for patients aged 18-60 with IPV presenting to three EDs in Connecticut from 2017 through 2019. RESULTS: CSAs were completed in 179/277 encounters (78.9%) and were more likely to be completed in encounters with SW involvement than without (162/171 [94.7%] vs. 17/56 [30.3%], p < 0.001). A total of 143 children lived in the home at the time of the incident; of the 107 children for whom the nature of exposure was known, 10 (9.3%) were physically involved and 26 (24.2%) were direct witnesses to the violence. CPS reports were made in 52.4% of the encounters in which children lived in the home. CONCLUSIONS: CSAs were omitted in one-fifth of encounters for IPV. Given the high prevalence of children involved in IPV episodes, ED encounters for IPV represent an opportunity to improve the safety of children.

Perspectives and recommendations of opioid overdose survivors experiencing unsheltered homelessness on housing, overdose, and substance use treatment in Boston, MA.

INTRODUCTION: Opioid overdose causes one in four deaths among people experiencing homelessness in Boston, MA. To reduce overdose risks, the experience and perspectives of people experiencing homelessness should be incorporated into housing, overdose prevention, and substance use treatment efforts. METHODS: In 2021, we conducted qualitative interviews with 59 opioid overdose survivors to inform equitable access to treatment services. In response to policy debate surrounding a public drug scene near a key recruitment site, we conducted a targeted thematic analysis of transcribed interview data from a subset of participants experiencing unsheltered homelessness (n=29) to explore their perspectives and recommendations on housing, overdose prevention, and substance use treatment. RESULTS: Among 29 participants who identified as non-Hispanic Black (n=10), Hispanic/Latinx (n=10), or as non-Hispanic White (n=9), the median number of self-reported opioid overdoses in the past three months was 2.0 (SD 3.7). Three themes emerged from this targeted analysis: (1) Participants described inadequate housing resources and unwelcoming shelter environments. (2) Participants near a large public drug scene explained how unsheltered homelessness was chaotic, dangerous, and disruptive to recovery goals. (3) Participants provided recommendations for improving housing and addiction treatment systems and including their perspectives in the development of solutions to the intersecting housing and opioid overdose crises. CONCLUSIONS: The overdose prevention, housing and substance use treatment systems must address the needs of opioid overdose survivors experiencing unsheltered homelessness. Overdose survivors experiencing unsheltered homelessness described a chaotic public drug scene but resorted to residing in nearby encampments because the existing shelter, housing, and addiction treatment systems were unwelcoming, difficult to navigate, or unaffordable. Despite efforts to provide low-threshold housing in Boston, additional low-barrier housing services (i.e., including harm reduction resources and without "sobriety" requirements) could promote the health and safety of people who use drugs and are experiencing homelessness.

Reading aloud and the question of intent.

Must readers intend to process a word to activate various levels of representation, or is such processing simply triggered by the presentation of a word (i.e., is it "automatic")? This issue was addressed via the use of Besner and Care's Task Set paradigm. On each trial a cue, which indicated which of two tasks to perform appeared either before the target, or at the same time as the target. If subjects can process the target while preparing a task set, then the effect of a manipulated psycholinguistic factor should be absorbed into the time taken to process the cue. Despite robust main effects of SOA and word frequency there was no interaction between these factors when the task was to read aloud. This result implies that target processing is delayed until the subject knows what task to perform, and therefore that intention plays an important role when reading words aloud.

Cardiopulmonary Exercise Testing in Pediatric Patients With Hypertrophic Cardiomyopathy.

Background: Exercise stress testing (EST) in pediatric hypertrophic cardiomyopathy (HCM) patients has not well described in a large heterogenous cohort. Objectives: The objective of the study was to determine the clinical utility of EST in pediatric HCM. Methods: This was a retrospective single-center analysis of HCM patients younger than 21 years who had EST between January 1, 2000, and January 1, 2019. Clinical, demographic characteristics, and EST data were analyzed, using the last EST during the study or prior to the event in subjects with a primary outcome. The primary composite endpoint included cardiac death, transplant, or arrhythmia requiring implantable cardioverter-defibrillator placement. Outcome analysis was performed using Cox proportional hazard modeling. Results: The study cohort included 140 patients, 52% with a recognized genetic variant. There were 2 tests aborted due to safety concerns (ST-segment changes, ventricular ectopy). The median age at first EST was 13.6 years. Ninety percent of patients were tested using cycle ergometry, and 44% were on a beta-blocker. The median peak oxygen consumption was 37.1 mL/kg/min (IQR: 12.5 mL/kg/min) or 81.2% predicted, the mean anaerobic threshold was 21.8 Ml (IQR: 8.3 mL), and the median peak power was 2.6 ± 1.1 W/kg or 73.7% predicted. Ectopy during EST was seen in 44% of patients, and 8% had an abnormal blood pressure response to exercise. The endpoint was reached in 12 patients. The presence of any degree of ectopy was a predictor of the composite endpoint (hazard ratio: 5.8; 95% CI: 1.3-26.7). Conclusions: EST is clinically useful in select pediatric patients with HCM. Ectopy on EST is a risk factor for cardiac death, cardiac transplant, and arrhythmias requiring implantable cardioverter-defibrillator.

On the strength of connections between localist mental modules as a source of frequency-of-occurrence effects.

Frequency-of-occurrence effects (e.g., effects of word frequency or familiarity) are widely thought to arise through differences in resting levels of activation in localist input-output modules. A different account posits that these effects at least partially reflect the strength of connections between various localist modules. Given that Arabic numerals appear more frequently than their alphabetic counterparts, we contrasted reaction times to stimuli in both formats in a naming/reading-aloud task and a parity-judgment task. The script effect (the difference between reaction times to Arabic and to alphabetic formats) was large in the parity-judgment task but absent in the naming/reading-aloud task. This script-by-task interaction follows naturally from the idea that at least part of the effect of frequency of occurrence of a printed word or digit (and other instances of familiarity) resides in the strength of connections between specialized localist input-output modules and a localist semantic module. This conclusion is likely applicable across a variety of domains.

Lexical processing while deciding what task to perform: reading aloud in the context of the task set paradigm.

The results of two experiments provide the first direct demonstration that subjects can process a word lexically despite concurrently being engaged in decoding a task cue telling them which of two tasks to perform. These results, taken together with others, point to qualitative differences between the mind's ability to engage in lexical versus sublexical processing during the time they are engaged with other tasks. The emerging picture is one in which some form of resource(s) plays little role during lexical processing whereas the need for some form of resource(s) during sublexical processing serves to bottleneck performance.

On the role of set when reading aloud: a dissociation between prelexical and lexical processing.

Two experiments investigated the role that mental set plays in reading aloud using the task choice procedure developed by Besner and Care [Besner, D., & Care, S. (2003). A paradigm for exploring what the mind does while deciding what it should do. Canadian Journal of Experimental Psychology, 57, 311-320]. Subjects were presented with a word, and asked to either read it aloud or decide whether it appeared in upper/lower case. Task information, in the form of a brief auditory cue, appeared 750ms before the word, or at the same time as the word. Experiment 1 yielded evidence consistent with the claim that at least some pre-lexical processing can be carried out in parallel with decoding the task cue (the 0 SOA condition yielded a smaller contrast effect than the long SOA condition). Experiment 2 provided evidence that such processing is restricted to pre-lexical levels (the word frequency effect was equivalent at the 0 SOA and the long SOA). These data suggest that a task set is a necessary preliminary to lexical processing when reading aloud.

Reading aloud: qualitative differences in the relation between stimulus quality and word frequency as a function of context.

Virtually all theories of visual word recognition assume (typically implicitly) that when a pathway is used, processing within that pathway always unfolds in the same way. This view is challenged by the observation that simple variations in list composition are associated with qualitative changes in performance. The present experiments demonstrate that when reading aloud, the joint effects of stimulus quality and word frequency on response time are driven by the presence/absence of nonwords in the list. Interacting effects of these factors are seen when only words appear in the experiment, whereas additive effects are seen when words and nonwords are randomly intermixed. One way to explain these and other data appeals to the distinction between cascaded processing (or interactive activation) on the one hand versus a thresholded mode of processing on the other, with contextual factors determining which mode of processing dominates.

Reading aloud: spelling-sound translation uses central attention.

Contrary to the received view that reading aloud reflects processes that are "automatic," recent evidence suggests that some of these processes require a form of attention. This issue was investigated further by examining the effect of a prior presentation of exception words (words whose spelling-sound translation are atypical, such as pint as compared with mint, hint, or lint) and pseudohomophones (nonwords that sound identical to words, such as brane from brain) on reading aloud in the context of the psychological refractory period paradigm. For exception words, the joint effects of repetition and stimulus onset asynchrony (SOA) yielded an underadditive interaction on the time to read aloud, replicating previous work -- a short SOA between Task 1 and Task 2 increased reaction time (RT) and reduced the magnitude of the repetition effect relative to the long SOA. For pseudohomophones, in contrast, the joint effects of repetition and SOA were additive on RT. These results provide converging evidence for the conclusion that (a) processing up to and including the orthographic input lexicon does not require central attention when reading aloud, whereas (b) translating lexical and sublexical spelling to sound requires the use of central attention.