Designing Virtual, Moderated Studies of Early Childhood Development.

With increased public access to the Internet and digital tools, web-based research has gained prevalence over the past decades. However, digital adaptations for developmental research involving children have received relatively little attention. In 2020, as the COVID-19 pandemic led to reduced social contact, causing many developmental university research laboratories to close, the scientific community began to investigate online research methods that would allow continued work. Limited resources and documentation of factors that are essential for developmental research (e.g., caregiver involvement, informed assent, controlling environmental distractions at home for children) make the transition from in-person to online research especially difficult for developmental scientists. Recognizing this, we aim to contribute to the field by describing three separate moderated virtual behavioral assessments in children ranging from 4 to 13years of age that were highly successful. The three studies encompass speech production, speech perception, and reading fluency. However varied the domains we chose, the different age groups targeted by each study and different methodological approaches, the success of our virtual adaptations shared certain commonalities with regard to how to achieve informed consent, how to plan parental involvement, how to design studies that attract and hold children's attention and valid data collection procedures. Our combined work suggests principles for future facilitation of online developmental work. Considerations derived from these studies can serve as documented points of departure that inform and encourage additional virtual adaptations in this field.

Rapid online assessment of reading ability.

An accurate model of the factors that contribute to individual differences in reading ability depends on data collection in large, diverse and representative samples of research participants. However, that is rarely feasible due to the constraints imposed by standardized measures of reading ability which require test administration by trained clinicians or researchers. Here we explore whether a simple, two-alternative forced choice, time limited lexical decision task (LDT), self-delivered through the web-browser, can serve as an accurate and reliable measure of reading ability. We found that performance on the LDT is highly correlated with scores on standardized measures of reading ability such as the Woodcock-Johnson Letter Word Identification test (r = 0.91, disattenuated r = 0.94). Importantly, the LDT reading ability measure is highly reliable (r = 0.97). After optimizing the list of words and pseudowords based on item response theory, we found that a short experiment with 76 trials (2-3 min) provides a reliable (r = 0.95) measure of reading ability. Thus, the self-administered, Rapid Online Assessment of Reading ability (ROAR) developed here overcomes the constraints of resource-intensive, in-person reading assessment, and provides an efficient and automated tool for effective online research into the mechanisms of reading (dis)ability.

Annotating digital text with phonemic cues to support decoding in struggling readers.

An advantage of digital media is the flexibility to personalize the presentation of text to an individual's needs and embed tools that support pedagogy. The goal of this study was to develop a tablet-based reading tool, grounded in the principles of phonics-based instruction, and determine whether struggling readers could leverage this technology to decode challenging words. The tool presents a small icon below each vowel to represent its sound. Forty struggling child readers were randomly assigned to an intervention or control group to test the efficacy of the phonemic cues. We found that struggling readers could leverage the cues to improve pseudoword decoding: after two weeks of practice, the intervention group showed greater improvement than controls. This study demonstrates the potential of a text annotation, grounded in intervention research, to help children decode novel words. These results highlight the opportunity for educational technologies to support and supplement classroom instruction.

Intensive Summer Intervention Drives Linear Growth of Reading Skill in Struggling Readers.

A major achievement of reading research has been the development of effective intervention programs for struggling readers. Most intervention studies employ a pre-post design, to examine efficacy, but this precludes the study of growth curves over the course of the intervention program. Determining the time-course of improvement is essential for cost-effective, evidence-based decisions on the optimal intervention dosage. The goal of this study was to analyze reading growth curves during an intensive summer intervention program. A cohort of 31 children (6-12 years) with reading difficulties (N = 21 with dyslexia diagnosis) were enrolled in 160 h of intervention occurring over 8 weeks of summer vacation. We collected behavioral measures over 4 sessions assessing decoding, oral reading fluency, and comprehension. Mixed-effects modeling of longitudinal measurements revealed a linear dose-response relationship between hours of intervention and improvement in reading ability; there was significant linear growth on every measure of reading skill and none of the measures showed non-linear growth trajectories. Decoding skills showed substantial growth [Cohen's d = 0.85 (WJ Basic Reading Skills)], with fluency and comprehension growing more gradually [d = 0.41 (WJ Reading Fluency)]. These results highlight the opportunity to improve reading skills over an intensive, short-term summer intervention program, and the linear dose-response relationship between duration and gains enables educators to set reading level goals and design a treatment plan to achieve them.

Rapid and widespread white matter plasticity during an intensive reading intervention.

White matter tissue properties are known to correlate with performance across domains ranging from reading to math, to executive function. Here, we use a longitudinal intervention design to examine experience-dependent growth in reading skills and white matter in grade school-aged, struggling readers. Diffusion MRI data were collected at regular intervals during an 8-week, intensive reading intervention. These measurements reveal large-scale changes throughout a collection of white matter tracts, in concert with growth in reading skill. Additionally, we identify tracts whose properties predict reading skill but remain fixed throughout the intervention, suggesting that some anatomical properties stably predict the ease with which a child learns to read, while others dynamically reflect the effects of experience. These results underscore the importance of considering recent experience when interpreting cross-sectional anatomy-behavior correlations. Widespread changes throughout the white matter may be a hallmark of rapid plasticity associated with an intensive learning experience.

A functionally personalized boundary condition model to improve estimates of fractional flow reserve with CT (CT-FFR).

PURPOSE: The purpose of this study is to develop and evaluate a functionally personalized boundary condition (BC) model for estimating the fractional flow reserve (FFR) from coronary computed tomography angiography (CCTA) using flow simulation (CT-FFR). MATERIALS AND METHODS: The CCTA data of 90 subjects with subsequent invasive FFR in 123 lesions within 21 days (range: 0-83) were retrospectively collected. We developed a functionally personalized BC model accounting specifically for the coronary microvascular resistance dependency on the coronary outlets pressure suggested by several physiological studies. We used the proposed model to estimate the hemodynamic significance of coronary lesions with an open-loop physics-based flow simulation. We generated three-dimensional (3D) coronary tree geometries using automatic software and corrected manually where required. We evaluated the improvement in CT-FFR estimates achieved using a functionally personalized BC model over anatomically personalized BC model using k-fold cross-validation. RESULTS: The functionally personalized BC model slightly improved CT-FFR specificity in determining hemodynamic significance of lesions with intermediate diameter stenosis (30%-70%, N = 72), compared to the anatomically personalized model lesions with invasive FFR measurements as the reference (sensitivity/specificity: 0.882/0.79 vs 0.882/0.763). For the entire set of 123 coronary lesions, the functionally personalized BC model improved only the area under the curve (AUC) but not the sensitivity/specificity in determining the hemodynamic significance of lesions, compared to the anatomically personalized model (AUC: 0.884 vs 0.875, sensitivity/specificity: 0.848/0.805). CONCLUSION: The functionally personalized BC model has the potential to improve the quality of CT-FFR estimates compared to an anatomically personalized BC model.

Experience With an On-Site Coronary Computed Tomography-Derived Fractional Flow Reserve Algorithm for the Assessment of Intermediate Coronary Stenoses.

Fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) is a new technique for the diagnosis of ischemic coronary artery stenoses. The aim of this prospective study was to evaluate the diagnostic performance of a novel on-site computed tomography-based fractional flow reserve algorithm (CT-FFR) compared with invasive FFR as the gold standard, and to determine whether its diagnostic performance is affected by interobserver variations in lumen segmentation. We enrolled 44 consecutive patients (64.6 ± 8.9 years, 34% female) with 60 coronary atherosclerotic lesions who underwent coronary CTA and invasive coronary angiography in 2 centers. An FFR value ≤0.8 was considered significant. Coronary CTA scans were evaluated by 2 expert readers, who manually adjusted the semiautomated coronary lumen segmentations for effective diameter stenosis (EDS) assessment and on-site CT-FFR simulation. The mean CT-FFR value was 0.77 ± 0.15, whereas the mean EDS was 43.6 ± 16.9%. The sensitivity, specificity, positive predictive value, and negative predictive value of CT-FFR versus EDS with a cutoff of 50% were the following: 91%, 72%, 63%, and 93% versus 52%, 87%, 69%, and 77%, respectively. The on-site CT-FFR demonstrated significantly better diagnostic performance compared with EDS (area under the curve 0.89 vs 0.74, respectively, p <0.001). The CT-FFR areas under the curve of the 2 readers did not show any significant difference (0.89 vs 0.88, p = 0.74). In conclusion, on-site CT-FFR simulation is feasible and has better diagnostic performance than anatomic stenosis assessment. Furthermore, the diagnostic performance of the on-site CT-FFR simulation algorithm does not depend on the readers' semiautomated lumen segmentation adjustments.

The causal relationship between dyslexia and motion perception reconsidered.

It is well established that visual sensitivity to motion is correlated with reading skills. Yet, the causal relationship between motion sensitivity and reading skills has been debated for more than thirty years. One hypothesis posits that dyslexia is caused by deficits in the motion processing pathway. An alternative hypothesis explains the motion processing deficit observed in dyslexia as the consequence of a lack, or poor quality, of reading experience. Here we used an intensive reading intervention program to test the causal relationship between learning to read and motion processing in children. Our data show that, while the reading intervention enhanced reading abilities, learning to read did not affect motion sensitivity. Motion sensitivity remained stable over the course of the intervention. Furthermore, the motion sensitivity deficit did not negatively impact the learning process. Children with poor motion sensitivity showed the same improvement in reading skills as children with typical motion sensitivity. Our findings call into question the view that motion processing deficits are due to poor reading experience. We propose that the correlation between the two measures arises from other common mechanisms, or that motion processing deficits are among a collection of correlated risk factors for reading difficulties.

Serum- and HDL3-serum amyloid A and HDL3-LCAT activity are influenced by increased CVD-burden.

BACKGROUND: High density lipoproteins (HDL) protect against cardiovascular disease (CVD). However, increased serum amyloid-A (SAA) related inflammation may negate this property. This study investigated if SAA was related to CVD-burden. METHODS: Subjects referred to the rapid chest pain clinic (n = 240) had atherosclerotic burden assessed by cardiac computerised tomography angiography. Subjects were classified as: no-CVD (n = 106), non-obstructive-CVD, stenosis<50% (n = 58) or moderate/significant-CVD, stenosis ≥50% (n = 76). HDL was subfractionated into HDL2 and HDL3 by rapid-ultracentrifugation. SAA-concentration was measured by ELISA and lecithin cholesterol acyltransferase (LCAT) activity measured by a fluorimetric assay. RESULTS: We illustrated that serum-SAA and HDL3-SAA-concentration were higher and HDL3-LCAT-activity lower in the moderate/significant-CVD-group, compared to the no-CVD and non-obstructive-CVD-groups (percent differences: serum-SAA, +33% & +30%: HDL3-SAA, +65% and +39%: HDL3-LCAT, -6% & -3%; p < 0.05 for all comparisons). We also identified a positive correlation between serum-SAA and HDL3-SAA (r = 0.698; p < 0.001) and a negative correlation between HDL3-SAA and HDL3-LCAT-activity (r = -0.295; p = 0.003), while CVD-burden positively correlated with serum-SAA (r = 0.150; p < 0.05) and HDL3-SAA (r = 0.252; p < 0.001) and negatively correlated with HDL3-LCAT-activity (r = -0.182; p = 0.006). Additionally, multivariate regression analysis adjusted for age, gender, CRP and serum-SAA illustrated that HDL3-SAA was significantly associated with modifying CVD-risk of moderate/significant CVD-risk (p < 0.05). CONCLUSION: This study has demonstrated increased SAA-related inflammation in subjects with moderate/significant CVD-burden, which appeared to impact on the antiatherogenic potential of HDL. We suggest that SAA may be a useful biomarker to illustrate increased CVD-burden, although this requires further investigation.

The Essentials of Cardiac Computerized Tomography.

Cardiac computerized tomography (CT) has evolved from a research tool to an important diagnostic investigation in cardiology, and is now recommended in European, US, and UK guidelines. This review is designed to give the reader an overview of the current state of cardiac CT. The role of cardiac CT is multifaceted, and includes risk stratification, disease detection, coronary plaque quantification, defining congenital heart disease, planning for structural intervention, and, more recently, assessment of ischemia. This paper addresses basic principles as well as newer evidence.

Carotid-access transcatheter aortic valve replacement in a patient with a previous mitral valve replacement.

We describe a case of transcatheter aortic valve replacement (TAVR) using carotid artery access and regional anesthesia in a patient with rheumatic heart disease, previous mitral valve replacement, and multiple co-morbidities. It highlights the role of the multidisciplinary Heart Team and multimodality imaging in reaching and implementing an appropriate management plan in this complex patient group.

A comparison of Diamond Forrester and coronary calcium scores as gatekeepers for investigations of stable chest pain.

To determine if calcium scores (CS) could act as a more effective gatekeeper than Diamond Forrester (DF) in the assessment of patients with suspected coronary artery disease (CAD). A sub-study of the Cardiac CT for the Assessment of Chest Pain and Plaque (CAPP) study, a randomised control trial evaluating the cost-effectiveness of cardiac CT in symptomatic patients with stable chest pain. Stable pain was defined as troponin negative pain without symptoms of unstable angina. 250 patients undergoing cardiac CT had both DF scores and CS calculated, with the accuracy of both evaluated against CT coronary angiogram. Criteria given in UK national guidelines were compared. Of the 250 patients, 4 withdrew. 140 (57 %) patients were male. The mean DF was 47.8 and mean CS 172.5. Of the 144 patients with non-anginal pain 19.4 % had significant disease (>50 % stenosis). In general the DF over estimated the presence of CAD whereas the CS reclassified patients to lower risk groups, with 91 in the high risk DF category compared to 26 in the CS. Both receiver operating curve and McNemar Bowker test analysis suggested the DF was less accurate in the prediction of CAD compared to CS [Formula: see text] Projected downstream investigations were also calculated, with the cost per number of significant stenoses identified cheaper with the CS criteria. Patients with suspected stable CAD are more accurately risk stratified by CS compared to the traditional DF. CS was more successful in the prediction of significant stenosis and appears to be more effective at targeting clinical resources to those patients that are in need of them.