Inter- and intravisit repeatability of free-breathing MRI in pediatric cystic fibrosis lung disease.

PURPOSE: The purpose of this study is to assess the intra- and interscan repeatability of free-breathing phase-resolved functional lung (PREFUL) MRI in stable pediatric cystic fibrosis (CF) lung disease in comparison to static breath-hold hyperpolarized 129-xenon MRI (Xe-MRI) and pulmonary function tests. METHODS: Free-breathing 1-hydrogen MRI and Xe-MRI were acquired from 15 stable pediatric CF patients and seven healthy age-matched participants on two visits, 1 month apart. Same-visit MRI scans were also performed on a subgroup of the CF patients. Following the PREFUL algorithm, regional ventilation (RVent) and regional flow volume loop cross-correlation maps were determined from the free-breathing data. Ventilation defect percentage (VDP) was determined from RVent maps (VDPRVent ), regional flow volume loop cross-correlation maps (VDPCC ), VDPRVent ∪ VDPCC , and multi-slice Xe-MRI. Repeatability was evaluated using Bland-Altman analysis, coefficient of repeatability (CR), and intraclass correlation. RESULTS: Minimal bias and no significant differences were reported for all PREFUL MRI and Xe-MRI VDP parameters between intra- and intervisits (all P > 0.05). Repeatability of VDPRVent , VDPCC , VDPRVent ∪ VDPCC , and multi-slice Xe-MRI were lower between the two-visit scans (CR = 14.81%, 15.36%, 16.19%, and 9.32%, respectively) in comparison to the same-day scans (CR = 3.38%, 2.90%, 1.90%, and 3.92%, respectively). pulmonary function tests showed high interscan repeatability relative to PREFUL MRI and Xe-MRI. CONCLUSION: PREFUL MRI, similar to Xe-MRI, showed high intravisit repeatability but moderate intervisit repeatability in CF, which may be due to inherent disease instability, even in stable patients. Thus, PREFUL MRI may be considered a suitable outcome measure for future treatment response studies.

The benefits of simultaneous tDCS and working memory training on transfer outcomes: A systematic review and meta-analysis.

BACKGROUND: Transcranial direct current stimulation (tDCS) has shown potential as an effective aid to facilitate learning. A popular application of this technology has been in combination with working memory training (WMT) in order to enhance transfer effects to other cognitive measures after training. OBJECTIVE: This meta-analytic review aims to synthesize the existing literature on tDCS-enhanced WMT to quantify the extent to which tDCS can improve performance on transfer tasks after training. Furthermore, we were interested to evaluate the moderating effects of assessment time point (immediate post-test vs. follow-up) and transfer distance, i.e., the degree of similarity between transfer and training tasks. METHODS: Using robust variance estimation, we performed a systematic meta-analysis of all studies to date that compared WMT with tDCS to WMT with sham in healthy adults. All procedures conformed to PRISMA guidelines. RESULTS: Across 265 transfer measures in 18 studies, we found a small positive net effect of tDCS on improving overall performance on transfer measures after WMT. These effects were sustained at follow-up, which ranged from 1 week to one year after training, with a median of 1 month. Additionally, although there were no significant differences as a function of transfer distance, effects were most pronounced for non-trained working memory tasks. CONCLUSIONS: This review provides evidence that tDCS can be effective in promoting learning over and above WMT alone, and can durably improve performance on trained and untrained measures for weeks to months after the initial training and stimulation period. In particular, boosting performance on dissimilar working memory tasks may present the most promising target for tDCS-augmented WMT.

Higher vaccination rates predict reduction in SARS-CoV-2 transmission across the United States.

PURPOSE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began proliferating widely throughout the world in late 2019/early 2020, creating a global pandemic and health crisis. Although vaccines became available to the public approximately 1 year after the onset of the pandemic, there still remains much hesitancy surrounding vaccination. One key concern comes from reports of breakthrough infections among the vaccinated that show comparable levels of peak viral load as the unvaccinated, calling into question the ability of vaccines to prevent transmission. Therefore young, healthy individuals who are at low risk of serious complications themselves have little incentive to receive a vaccine that they are not convinced will protect others around them. To address this important concern, this study aimed to evaluate the extent to which vaccination rates are associated with reduced SARS-CoV-2 transmission among the unvaccinated population. METHODS: An observational study was conducted in the United States of America throughout the months of June through September, 2021. Vaccination rate and incidence of coronavirus disease 2019 (COVID-19) were obtained for each state, along with a number of important control variables. Panel data regression was used to predict incidence among the unvaccinated based on each state's vaccination rate. RESULTS: States with a higher proportion of fully vaccinated individuals reported fewer new cases among the remaining unvaccinated population. CONCLUSION: These data add to accumulating evidence that COVID-19 vaccinations can indeed slow the spread of SARS-CoV-2, and are an important tool in society's arsenal to put this pandemic behind us.

Effects of Multisession Prefrontal Transcranial Direct Current Stimulation on Long-term Memory and Working Memory in Older Adults.

Transcranial direct current stimulation (tDCS) is a noninvasive form of electrical brain stimulation popularly used to augment the effects of working memory (WM) training. Although success has been mixed, some studies report enhancements in WM performance persisting days, weeks, or even months that are actually more reminiscent of consolidation effects typically observed in the long-term memory (LTM) domain, rather than WM improvements per se. Although tDCS has been often reported to enhance both WM and LTM, these effects have never been directly compared within the same study. However, given their considerable neural and behavioral overlap, this is a timely comparison to make. This study reports results from a multisession intervention in older adults comparing active and sham tDCS over the left dorsolateral pFC during training on both an n-back WM task and a word learning LTM task. We found strong and robust effects on LTM, but mixed effects on WM that only emerged for those with lower baseline ability. Importantly, mediation analyses showed an indirect effect of tDCS on WM that was mediated by improvements in consolidation. We conclude that tDCS over the left dorsolateral pFC can be used as an effective intervention to foster long-term learning and memory consolidation in aging, which can manifest in performance improvements across multiple memory domains.

Outcomes of Cystic Fibrosis Screening-Positive Infants With Inconclusive Diagnosis at School Age.

BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF) screen-positive infants with an inconclusive diagnosis (CFSPID) are infants in whom sweat testing and genetic analysis does not resolve a CF diagnosis. Lack of knowledge about the health outcome of these children who require clinical follow-up challenges effective consultation. Early predictive biomarkers to delineate the CF risk would allow a more targeted approach to these children. METHODS: Prospective, longitudinal, multicenter, Canada-wide cohort study of CF positive-screened newborns with 1 to 2 cystic fibrosis transmembrane conductance regulator gene variants, of which at least 1 is not known to be CF-causing and/or a sweat chloride between 30 and 59 mmol/L. These were monitored for conversion to a CF diagnosis, pulmonary, and nutritional outcomes. RESULTS: The mean observation period was 7.7 (95% confidence interval 7.1 to 8.4) years. A CF diagnosis was established for 24 of the 115 children with CFSPID (21%) either because of reinterpretation of the cystic fibrosis transmembrane conductance regulator genotype or because of increase in sweat chloride concentration ≥60 mmol/L. An initial sweat chloride of ≥40 mmol/l predicted conversion to CF on the basis of sweat testing. The 91 remaining children with CFSPID were pancreatic sufficient and showed normal growth until school age. Pulmonary function as well as lung clearance index in a subgroup of children with CFSPID were similar to that of healthy controls. CONCLUSIONS: Children with CFSPID have good nutritional and pulmonary outcomes at school age, but rates of reclassifying the diagnosis are high. The initial sweat chloride test can be used as a biomarker to predict the risk for CF in CFSPID.

Higher Vaccination Rate Predicts Reduction in SARS-CoV-2 Transmission across the United States.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began proliferating widely throughout the world in late 2019/early 2020, creating a global pandemic and health crisis. Although vaccines became available to the public approximately one year after the onset of the pandemic, there still remains much hesitancy surrounding vaccination even two years into the pandemic. One key concern comes from reports of breakthrough infections among the vaccinated that show comparable levels of peak viral load as the unvaccinated, calling into question the ability of vaccines to slow or prevent transmission. Therefore young, healthy individuals who are at low risk of serious complications themselves have little incentive to receive a vaccine that they are not convinced will protect others around them. To address this important concern, this article analyzes COVID-19 incidence in the United States as a function of each state's vaccination rate. Results show that states with higher percentages of fully vaccinated individuals report fewer new cases among the remaining unvaccinated population. These data add to accumulating evidence that COVID-19 vaccinations can indeed slow the spread of SARS-CoV-2, and are an important tool in society's arsenal to put this pandemic behind us.

Post-training stimulation of the right dorsolateral prefrontal cortex impairs working memory training performance.

Research investigating transcranial direct current stimulation (tDCS) to enhance cognitive training augments both our understanding of its long-term effects on cognitive plasticity as well as potential applications to strengthen cognitive interventions. Previous work has demonstrated enhancement of working memory training while applying concurrent tDCS to the dorsolateral prefrontal cortex (DLPFC). However, the optimal stimulation parameters are still unknown. For example, the timing of tDCS delivery has been shown to be an influential variable that can interact with task learning. In the present study, we used tDCS to target the right DLPFC while participants trained on a visuospatial working memory task. We sought to compare the relative efficacy of online stimulation delivered during training to offline stimulation delivered either immediately before or afterwards. We were unable to replicate previously demonstrated benefits of online stimulation; however, we did find evidence that offline stimulation delivered after training can actually be detrimental to training performance relative to sham. We interpret our results in light of evidence suggesting a role of the right DLPFC in promoting memory interference, and conclude that while tDCS may be a promising tool to influence the results of cognitive training, more research and an abundance of caution are needed before fully endorsing its use for cognitive enhancement. This work suggests that effects can vary substantially in magnitude and direction between studies, and may be heavily dependent on a variety of intervention protocol parameters such as the timing and location of stimulation delivery, about which our understanding is still nascent.

Quantifying the Difference between Active and Passive Control Groups in Cognitive Interventions Using two Meta-Analytical Approaches.

Despite promising reports of broad cognitive benefit in studies of cognitive training, it has been argued that the reliance of many studies on no-intervention control groups (passive controls) make these reports difficult to interpret because placebo effects cannot be ruled out. Although researchers have recently been trying to incorporate more active controls, in which participants engage in an alternate intervention, previous work has been contentious as to whether this actually yields meaningfully different results. To better understand the influence of passive and active control groups on cognitive interventions, we conducted two meta-analyses to estimate their relative effect sizes. While the first one broadly surveyed the literature by compiling data from 34 meta-analyses, the second one synthesized data from 42 empirical studies that simultaneously employed both types of controls. Both analyses showed no meaningful performance difference between passive and active controls, suggesting that current active control placebo paradigms might not be appropriately designed to reliably capture these non-specific effects or that these effects are minimal in this literature.

Growth of Pulmonary Arteriovenous Malformations in Pediatric Patients with Hereditary Hemorrhagic Telangiectasia.

The evolution of pulmonary arteriovenous malformations (PAVMs) over time in children with hereditary hemorrhagic telangiectasia (HHT) is not well-defined. Herein we demonstrate that, although new PAVMs did not evolve in children with HHT, existing PAVMs exhibit quantitative growth over time highlighting the need for ongoing follow-up throughout childhood.

Does the multiple-breath washout test need to be measured before spirometry?

Spirometry does not have a short-term effect on multiple-breath washout outcomes, thus allowing greater flexibility for implementation into clinical practice http://ow.ly/2Tg330ngXk4.

Effects of non-symbolic arithmetic training on symbolic arithmetic and the approximate number system.

The approximate number system (ANS) is an innate cognitive template that allows for the mental representation of approximate magnitude, and has been controversially linked to symbolic number knowledge and math ability. A series of recent studies found that an approximate arithmetic training (AAT) task that draws upon the ANS can improve math skills, which not only supports the existence of this link, but suggests it may be causal. However, no direct transfer effects to any measure of the ANS have yet been reported, calling into question the mechanisms by which math improvements may emerge. The present study investigated the effects of a 7-day AAT and successfully replicated previously reported transfer effects to math. Furthermore, our exploratory analyses provide preliminary evidence that certain ANS-related skills may also be susceptible to training. We conclude that AAT has reproducible effects on math performance, and provide avenues for future studies to further explore underlying mechanisms - specifically, the link between improvements in math and improvements in ANS skills.

Is Inquiry Science Instruction Effective for English Language Learners? A Meta-Analytic Review.

Despite being among the fastest growing segments of the student population, English Language Learners (ELLs) have yet to attain the same academic success as their English-proficient peers, particularly in science. In an effort to support the pedagogical needs of this group, educators have been urged to adopt inquiry approaches to science instruction. Whereas inquiry instruction has been shown to improve science outcomes for non-ELLs, systematic evidence in support of its effectiveness with ELLs has yet to be established. The current meta-analysis summarizes the effect of inquiry instruction on the science achievement of ELLs in elementary school. Although an analysis of 26 articles confirmed that inquiry instruction produced significantly greater impacts on measures of science achievement for ELLs compared to direct instruction, there was still a differential learning effect suggesting greater efficacy for non-ELLs compared to ELLs. Contextual factors that moderate these effects are identified and discussed.

Cerebellar transcranial direct current stimulation improves adaptive postural control.

OBJECTIVE: Rehabilitation interventions contribute to recovery of impaired postural control, but it remains a priority to optimize their effectiveness. A promising strategy may involve transcranial direct current stimulation (tDCS) of brain areas involved in fine-tuning of motor adaptation. This study explored the effects of cerebellar tDCS (ctDCS) on postural recovery from disturbance by Achilles tendon vibration. METHODS: Twenty-eight healthy volunteers participated in this sham-ctDCS controlled study. Standing blindfolded on a force platform, four trials were completed: 60 s quiet standing followed by 20 min active (anodal-tDCS, 1 mA, 20 min, N = 14) or sham-ctDCS (40 s, N = 14) tDCS; three quiet standing trials with 15 s of Achilles tendon vibration and 25 s of postural recovery. Postural steadiness was quantified as displacement, standard deviation and path derived from the center of pressure (COP). RESULTS: Baseline demographics and quiet standing postural steadiness, and backwards displacement during vibration were comparable between groups. However, active-tDCS significantly improved postural steadiness during vibration and reduced forward displacement and variability in COP derivatives during recovery. CONCLUSIONS: We demonstrate that ctDCS results in short-term improvement of postural adaptation in healthy individuals. SIGNIFICANCE: Future studies need to investigate if multisession ctDCS combined with training or rehabilitation interventions can induce prolonged improvement of postural balance.

The relationship between chronotype and depressive symptoms: A meta-analysis.

BACKGROUND: Expanding our understanding of the factors that influence depression is crucial for prognosis and treatment. In light of increasing evidence of an association between disrupted circadian rhythms and affective symptoms, a meta-analysis was used to examine the relationship between an eveningness chronotype and depression. METHODS: Electronic searches of the PsycINFO, Medline, Scopus, and Google Scholar databases were conducted in February 2016. Relevant reviews, related journals, and reference lists were manually searched. Statistical data were reported or transformed to a Fisher's z correlational coefficient for effect size analysis. RESULTS: Data from 36 studies (n =15734) met the inclusion criteria and were analysed under a random effects model. Nearly all included studies utilised the Composite Scale of Morningness (CSM) or the Morningness-Eveningness Questionnaire (MEQ) as a measure of chronotype. Overall effect size from 58 effect sizes was small (z=-.20; 95% CI: -.18 to -.23). Effect sizes based on the CSM were significantly larger than those based on the MEQ. There was no evidence of publication bias. LIMITATIONS: The number of studies comparing different mood disorders or the potential moderating effects of gender and age were too few to draw conclusions regarding their respective effect sizes. Future research should utilise longitudinal designs to draw causal inferences on the directionality of this relationship. CONCLUSIONS: Findings from this meta-analysis indicate an eveningness orientation is somewhat associated with more severe mood symptoms. Chronobiological approaches may contribute to the prevention and treatment of depressive disorders.

Individual Differences and Long-term Consequences of tDCS-augmented Cognitive Training.

A great deal of interest surrounds the use of transcranial direct current stimulation (tDCS) to augment cognitive training. However, effects are inconsistent across studies, and meta-analytic evidence is mixed, especially for healthy, young adults. One major source of this inconsistency is individual differences among the participants, but these differences are rarely examined in the context of combined training/stimulation studies. In addition, it is unclear how long the effects of stimulation last, even in successful interventions. Some studies make use of follow-up assessments, but very few have measured performance more than a few months after an intervention. Here, we utilized data from a previous study of tDCS and cognitive training [Au, J., Katz, B., Buschkuehl, M., Bunarjo, K., Senger, T., Zabel, C., et al. Enhancing working memory training with transcranial direct current stimulation. Journal of Cognitive Neuroscience, 28, 1419-1432, 2016] in which participants trained on a working memory task over 7 days while receiving active or sham tDCS. A new, longer-term follow-up to assess later performance was conducted, and additional participants were added so that the sham condition was better powered. We assessed baseline cognitive ability, gender, training site, and motivation level and found significant interactions between both baseline ability and motivation with condition (active or sham) in models predicting training gain. In addition, the improvements in the active condition versus sham condition appear to be stable even as long as a year after the original intervention.

The Benefits and Challenges of Implementing Motivational Features to Boost Cognitive Training Outcome.

In the current literature, there are a number of cognitive training studies that use N-back tasks as their training vehicle; however, the interventions are often bland, and many studies suffer from considerable attrition rates. An increasingly common approach to increase participant engagement has been the implementation of motivational features in training tasks; yet, the effects of such "gamification" on learning have been inconsistent. To shed more light on those issues, here, we report the results of a training study conducted at two Universities in Southern California. A total of 115 participants completed 4 weeks (20 sessions) of N-back training in the laboratory. We varied the amount of "gamification" and the motivational features that might make the training more engaging and, potentially, more effective. Thus, 47 participants trained on a basic color/identity N-back version with no motivational features, whereas 68 participants trained on a gamified version that translated the basic mechanics of the N-back task into an engaging 3D space-themed "collection" game (Deveau et al. Frontiers in Systems Neuroscience, 8, 243, 2015). Both versions used similar adaptive algorithms to increase the difficulty level as participants became more proficient. Participants' self-reports indicated that the group who trained on the gamified version enjoyed the intervention more than the group who trained on the non-gamified version. Furthermore, the participants who trained on the gamified version exerted more effort and also improved more during training. However, despite the differential training effects, there were no significant group differences in any of the outcome measures at post-test, suggesting that the inclusion of motivational features neither substantially benefited nor hurt broader learning. Overall, our findings provide guidelines for task implementation to optimally target participants' interest and engagement to promote learning, which may lead to broader adoption and adherence of cognitive training.

Enhancing Working Memory Training with Transcranial Direct Current Stimulation.

Working memory (WM) is a fundamental cognitive ability that supports complex thought but is limited in capacity. Thus, WM training interventions have become very popular as a means of potentially improving WM-related skills. Another promising intervention that has gained increasing traction in recent years is transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation that can modulate cortical excitability and temporarily increase brain plasticity. As such, it has the potential to boost learning and enhance performance on cognitive tasks. This study assessed the efficacy of tDCS to supplement WM training. Sixty-two participants were randomized to receive either right prefrontal, left prefrontal, or sham stimulation with concurrent visuospatial WM training over the course of seven training sessions. Results showed that tDCS enhanced training performance, which was strikingly preserved several months after training completion. Furthermore, we observed stronger effects when tDCS was spaced over a weekend break relative to consecutive daily training, and we also demonstrated selective transfer in the right prefrontal group to nontrained tasks of visual and spatial WM. These findings shed light on how tDCS may be leveraged as a tool to enhance performance on WM-intensive learning tasks.

There is no convincing evidence that working memory training is NOT effective: A reply to Melby-Lervåg and Hulme (2015).

Our recent meta-analysis concluded that training on working memory can improve performance on tests of fluid intelligence (Au et al., Psychon Bull Rev, 22(2), 366-377, 2015). Melby-Lervåg and Hulme (Psychon Bull Rev, doi: 10.3758/s13423-015-0862-z ) challenge this conclusion on the grounds that it did not take into consideration baseline differences on a by-study level and that the effects were primarily driven by purportedly less rigorous studies that did not include active control groups. Their re-analysis shows that accounting for baseline differences produces a statistically significant, but considerably smaller, overall effect size (g = 0.13 vs g = 0.24 in Au et al.), which loses significance after excluding studies without active controls. The present report demonstrates that evidence of impact variation by the active/passive nature of control groups is ambiguous and also reveals important discrepancies between Melby-Lervåg and Hulme's analysis and our original meta-analysis in terms of the coding and organization of data that account for the discrepant effect sizes. We demonstrate that there is in fact no evidence that the type of control group per se moderates the effects of working memory training on measures of fluid intelligence and reaffirm the original conclusions in Au et al., which are robust to multiple methods of calculating effect size, including the one proposed by Melby-Lervåg and Hulme.

Improving fluid intelligence with training on working memory: a meta-analysis.

Working memory (WM), the ability to store and manipulate information for short periods of time, is an important predictor of scholastic aptitude and a critical bottleneck underlying higher-order cognitive processes, including controlled attention and reasoning. Recent interventions targeting WM have suggested plasticity of the WM system by demonstrating improvements in both trained and untrained WM tasks. However, evidence on transfer of improved WM into more general cognitive domains such as fluid intelligence (Gf) has been more equivocal. Therefore, we conducted a meta-analysis focusing on one specific training program, n-back. We searched PubMed and Google Scholar for all n-back training studies with Gf outcome measures, a control group, and healthy participants between 18 and 50 years of age. In total, we included 20 studies in our analyses that met our criteria and found a small but significant positive effect of n-back training on improving Gf. Several factors that moderate this transfer are identified and discussed. We conclude that short-term cognitive training on the order of weeks can result in beneficial effects in important cognitive functions as measured by laboratory tests.

A feasibility trial of Cogmed working memory training in fragile X syndrome.

Individuals with fragile X syndrome (FXS) often present with an array of neurocognitive deficits, particularly in working memory (WM) and other executive functions. Evidence is accumulating that WM training can be effective in certain clinical populations in improving WM abilities and decreasing attention deficit hyperactivity disorder symptoms. We report preliminary findings evaluating the feasibility of Cogmed JM program, a computer-based WM intervention, within the FXS population. Twenty-five participants were evaluated for training. Seventeen were deemed eligible, of whom eight enrolled in the 5-wk training. Baseline characteristics were analyzed, as well as training progress and parental impressions. We conclude that Cogmed JM is a feasible intervention in FXS, though a certain baseline level of ability is required, and urge future controlled trials to determine efficacy.