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Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.
Background: We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation model compatible with newer methylation arrays. Methods: The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. A nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection. Results: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and a retrospective cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperformed 2021 WHO grade in predicting postoperative recurrence. Dichotomizing into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (log-rank p<0.05). Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Conclusions: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. This will help improve prognostication and inform patient selection for RT.
Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
To examine the association of posttraumatic headache (PTH) type with postconcussive symptoms (PCS), pain intensity, and fluid cognitive function across recovery after pediatric concussion.
Methods:
This prospective, longitudinal study recruited children (aged 8–16.99 years) within 24 hours of sustaining a concussion or mild orthopedic injury (OI) from two pediatric hospital emergency departments. Based on parent-proxy ratings of pre- and postinjury headache, children were classified as concussion with no PTH (n = 18), new PTH (n = 43), worse PTH (n = 58), or non-worsening chronic PTH (n = 19), and children with OI with no PTH (n = 58). Children and parents rated PCS and children rated pain intensity weekly up to 6 months. Children completed computerized testing of fluid cognition 10 days, 3 months, and 6- months postinjury. Mixed effects models compared groups across time on PCS, pain intensity, and cognition, controlling for preinjury scores and covariates.
Results:
Group differences in PCS decreased over time. Cognitive and somatic PCS were higher in new, chronic, and worse PTH relative to no PTH (up to 8 weeks postinjury; d = 0.34 to 0.87 when significant) and OI (up to 5 weeks postinjury; d = 0.30 to 1.28 when significant). Pain intensity did not differ by group but declined with time postinjury. Fluid cognition was lower across time in chronic PTH versus no PTH (d = −0.76) and OI (d = −0.61) and in new PTH versus no PTH (d = −0.51).
Conclusions:
Onset of PTH was associated with worse PCS up to 8 weeks after pediatric concussion. Chronic PTH and new PTH were associated with moderately poorer fluid cognitive functioning up to 6 months postinjury. Pain declined over time regardless of PTH type.
Individuals with major depressive disorder (MDD) can experience reduced motivation and cognitive function, leading to challenges with goal-directed behavior. When selecting goals, people maximize ‘expected value’ by selecting actions that maximize potential reward while minimizing associated costs, including effort ‘costs’ and the opportunity cost of time. In MDD, differential weighing of costs and benefits are theorized mechanisms underlying changes in goal-directed cognition and may contribute to symptom heterogeneity.
Methods
We used the Effort Foraging Task to quantify cognitive and physical effort costs, and patch leaving thresholds in low effort conditions (reflecting perceived opportunity cost of time) and investigated their shared versus distinct relationships to clinical features in participants with MDD (N = 52, 43 in-episode) and comparisons (N = 27).
Results
Contrary to our predictions, none of the decision-making measures differed with MDD diagnosis. However, each of the measures was related to symptom severity, over and above effects of ability (i.e. performance). Greater anxiety symptoms were selectively associated with lower cognitive effort cost (i.e. greater willingness to exert effort). Anhedonia and behavioral apathy were associated with increased physical effort costs. Finally, greater overall depression was related to decreased patch leaving thresholds.
Conclusions
Markers of effort-based decision-making may inform understanding of MDD heterogeneity. Increased willingness to exert cognitive effort may contribute to anxiety symptoms such as worry. Decreased leaving threshold associations with symptom severity are consistent with reward rate-based accounts of reduced vigor in MDD. Future research should address subtypes of depression with or without anxiety, which may relate differentially to cognitive effort decisions.
Interpersonal psychotherapy (IPT) and antidepressant medications are both first-line interventions for adult depression, but their relative efficacy in the long term and on outcome measures other than depressive symptomatology is unknown. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses. This IPD meta-analysis compared the efficacy of IPT and antidepressants on various outcomes at post-treatment and follow-up (PROSPERO: CRD42020219891). A systematic literature search conducted May 1st, 2023 identified randomized trials comparing IPT and antidepressants in acute-phase treatment of adults with depression. Anonymized IPD were requested and analyzed using mixed-effects models. The prespecified primary outcome was post-treatment depression symptom severity. Secondary outcomes were all post-treatment and follow-up measures assessed in at least two studies. IPD were obtained from 9 of 15 studies identified (N = 1536/1948, 78.9%). No significant comparative treatment effects were found on post-treatment measures of depression (d = 0.088, p = 0.103, N = 1530) and social functioning (d = 0.026, p = 0.624, N = 1213). In smaller samples, antidepressants performed slightly better than IPT on post-treatment measures of general psychopathology (d = 0.276, p = 0.023, N = 307) and dysfunctional attitudes (d = 0.249, p = 0.029, N = 231), but not on any other secondary outcomes, nor at follow-up. This IPD meta-analysis is the first to examine the acute and longer-term efficacy of IPT v. antidepressants on a broad range of outcomes. Depression treatment trials should routinely include multiple outcome measures and follow-up assessments.
The aim of this project is to study to which extent salience alterations influence the severity of psychotic symptoms. However, rather than studying them individually, we decided to focus on their interplay with two additional variables, that is: observing their effect in a vulnerability phase (adolescence) and with another added, well-recognized risk factor (cannabis use).
The reason for this study design lies in the fact that, in our opinion, it is fundamental to observe the trajectory of psychotic symptoms over a continuum; however, rather than adopting a longitudinal approach, we decided to structure it as a cross-sectional study confronting patients from two age brackets - adolescence and adulthood.
Objectives
The primary purpose of this study was to assess a difference between THC-abusing and non-abusing patients in adolescent and adult cohorts, using the Italian version of the psychometric scale “Aberrant Salience Inventory” (ASI), and the possible correlation with more severe psychotic symptoms. The employment of several different psychometric scales and the inclusion of a variegated cohort allowed to pursue multiple secondary objectives.
Methods
We recruited 192 patients, subsequently divided into six subgroups based on age and department of recruitment (whether adolescent or adult psychiatric or neurologic units - the latter serving as controls). Each individual was administered a set of questionnaires and a socio-demographic survey; the set included: Aberrant Salience Inventory (ASI), Community Assessment of Psychic Experiences (CAPE), Positive and Negative Syndrome Scale (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale (MRS), Hamilton Anxiety Scale (HAM-A), Association for Methodology and Documentation in Psychiatry (AMDP) and Cannabis Experience Questionnaire (CEQ).
Results
The data analysis showed statistically significant (p<0.05) differences between adolescents and adults with psychotic symptoms in all of the three scales of PANSS and in MADRS. These two groups were homogenous for both cannabis use and ASI score. The intra-group comparison (either adolescent or adult) showed a hierarchical pattern in the scores of psychometric scales according to the diagnostic subgroup of allocation: patients with psychotic symptoms showed an higher level of psychopathology in all measures when compared to patients from the psychiatric unit without psychotic symptoms, which in turn scored higher than the patients from the neurologic unit.
Image:
Conclusions
The results of the present study may suggest that when salience alterations occur in adolescents with cannabis exposure, we might observe worsened positive and negative psychotic symptoms; their influence might be relevant also in other domains, especially regarding the depressive and anxiety spectrums.
The timing of tracheostomy for intensive care unit patients is controversial, with conflicting findings on early versus late tracheostomy.
Methods
Patients undergoing tracheostomy from 2001through 2012 were identified from the Medical Information Mart for Intensive Care-III database. Early tracheostomy was defined as less than the 25th percentile of time from intensive care unit admission to tracheostomy (time to tracheostomy). Statistical analysis for tracheostomy timing on intensive care unit length of stay and mortality were conducted.
Results
Of the 1,566 patients that were included, patients with early tracheostomy had shorter intensive care unit length of stay (27.32 vs 12.55 days, p < 0.001) and lower mortality (12.9 per cent vs 9.0 per cent, p = 0.039). Multivariate logistic regression analysis found an association between increasing time to tracheostomy and mortality (odds ratio: 1.029, 95 per cent confidence interval 1.007–1.051, p = 0.009).
Conclusion
Our analysis revealed that patients with early tracheostomy were more likely to have shorter intensive care unit lengths of stay and lower mortality. Our data suggest that early tracheostomy should be given strong consideration in appropriately selected patients.
Cognitive training is a non-pharmacological intervention aimed at improving cognitive function across a single or multiple domains. Although the underlying mechanisms of cognitive training and transfer effects are not well-characterized, cognitive training has been thought to facilitate neural plasticity to enhance cognitive performance. Indeed, the Scaffolding Theory of Aging and Cognition (STAC) proposes that cognitive training may enhance the ability to engage in compensatory scaffolding to meet task demands and maintain cognitive performance. We therefore evaluated the effects of cognitive training on working memory performance in older adults without dementia. This study will help begin to elucidate non-pharmacological intervention effects on compensatory scaffolding in older adults.
Participants and Methods:
48 participants were recruited for a Phase III randomized clinical trial (Augmenting Cognitive Training in Older Adults [ACT]; NIH R01AG054077) conducted at the University of Florida and University of Arizona. Participants across sites were randomly assigned to complete cognitive training (n=25) or an education training control condition (n=23). Cognitive training and the education training control condition were each completed during 60 sessions over 12 weeks for 40 hours total. The education training control condition involved viewing educational videos produced by the National Geographic Channel. Cognitive training was completed using the Posit Science Brain HQ training program, which included 8 cognitive training paradigms targeting attention/processing speed and working memory. All participants also completed demographic questionnaires, cognitive testing, and an fMRI 2-back task at baseline and at 12-weeks following cognitive training.
Results:
Repeated measures analysis of covariance (ANCOVA), adjusted for training adherence, transcranial direct current stimulation (tDCS) condition, age, sex, years of education, and Wechsler Test of Adult Reading (WTAR) raw score, revealed a significant 2-back by training group interaction (F[1,40]=6.201, p=.017, η2=.134). Examination of simple main effects revealed baseline differences in 2-back performance (F[1,40]=.568, p=.455, η2=.014). After controlling for baseline performance, training group differences in 2-back performance was no longer statistically significant (F[1,40]=1.382, p=.247, η2=.034).
Conclusions:
After adjusting for baseline performance differences, there were no significant training group differences in 2-back performance, suggesting that the randomization was not sufficient to ensure adequate distribution of participants across groups. Results may indicate that cognitive training alone is not sufficient for significant improvement in working memory performance on a near transfer task. Additional improvement may occur with the next phase of this clinical trial, such that tDCS augments the effects of cognitive training and results in enhanced compensatory scaffolding even within this high performing cohort. Limitations of the study include a highly educated sample with higher literacy levels and the small sample size was not powered for transfer effects analysis. Future analyses will include evaluation of the combined intervention effects of a cognitive training and tDCS on nback performance in a larger sample of older adults without dementia.
Cognitive training has shown promise for improving cognition in older adults. Aging involves a variety of neuroanatomical changes that may affect response to cognitive training. White matter hyperintensities (WMH) are one common age-related brain change, as evidenced by T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) MRI. WMH are associated with older age, suggestive of cerebral small vessel disease, and reflect decreased white matter integrity. Higher WMH load associates with reduced threshold for clinical expression of cognitive impairment and dementia. The effects of WMH on response to cognitive training interventions are relatively unknown. The current study assessed (a) proximal cognitive training performance following a 3-month randomized control trial and (b) the contribution of baseline whole-brain WMH load, defined as total lesion volume (TLV), on pre-post proximal training change.
Participants and Methods:
Sixty-two healthy older adults ages 65-84 completed either adaptive cognitive training (CT; n=31) or educational training control (ET; n=31) interventions. Participants assigned to CT completed 20 hours of attention/processing speed training and 20 hours of working memory training delivered through commercially-available Posit Science BrainHQ. ET participants completed 40 hours of educational videos. All participants also underwent sham or active transcranial direct current stimulation (tDCS) as an adjunctive intervention, although not a variable of interest in the current study. Multimodal MRI scans were acquired during the baseline visit. T1- and T2-weighted FLAIR images were processed using the Lesion Segmentation Tool (LST) for SPM12. The Lesion Prediction Algorithm of LST automatically segmented brain tissue and calculated lesion maps. A lesion threshold of 0.30 was applied to calculate TLV. A log transformation was applied to TLV to normalize the distribution of WMH. Repeated-measures analysis of covariance (RM-ANCOVA) assessed pre/post change in proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures in the CT group compared to their ET counterparts, controlling for age, sex, years of education and tDCS group. Linear regression assessed the effect of TLV on post-intervention proximal composite and sub-composite, controlling for baseline performance, intervention assignment, age, sex, years of education, multisite scanner differences, estimated total intracranial volume, and binarized cardiovascular disease risk.
Results:
RM-ANCOVA revealed two-way group*time interactions such that those assigned cognitive training demonstrated greater improvement on proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures compared to their ET counterparts. Multiple linear regression showed higher baseline TLV associated with lower pre-post change on Processing Speed Training sub-composite (ß = -0.19, p = 0.04) but not other composite measures.
Conclusions:
These findings demonstrate the utility of cognitive training for improving postintervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appear to be particularly sensitive to white matter hyperintensity load versus working memory training change. These data suggest that TLV may serve as an important factor for consideration when planning processing speed-based cognitive training interventions for remediation of cognitive decline in older adults.
Interventions using a cognitive training paradigm called the Useful Field of View (UFOV) task have shown to be efficacious in slowing cognitive decline. However, no studies have looked at the engagement of functional networks during UFOV task completion. The current study aimed to (a) assess if regions activated during the UFOV fMRI task were functionally connected and related to task performance (henceforth called the UFOV network), (b) compare connectivity of the UFOV network to 7 resting-state functional connectivity networks in predicting proximal (UFOV) and near-transfer (Double Decision) performance, and (c) explore the impact of network segregation between higher-order networks and UFOV performance.
Participants and Methods:
336 healthy older adults (mean age=71.6) completed the UFOV fMRI task in a Siemens 3T scanner. UFOV fMRI accuracy was calculated as the number of correct responses divided by 56 total trials. Double Decision performance was calculated as the average presentation time of correct responses in log ms, with lower scores equating to better processing speed. Structural and functional MRI images were processed using the default pre-processing pipeline within the CONN toolbox. The Artifact Rejection Toolbox was set at a motion threshold of 0.9mm and participants were excluded if more than 50% of volumes were flagged as outliers. To assess connectivity of regions associated with the UFOV task, we created 10 spherical regions of interest (ROIs) a priori using the WFU PickAtlas in SPM12. These include the bilateral pars triangularis, supplementary motor area, and inferior temporal gyri, as well as the left pars opercularis, left middle occipital gyrus, right precentral gyrus and right superior parietal lobule. We used a weighted ROI-to-ROI connectivity analysis to model task-based within-network functional connectivity of the UFOV network, and its relationship to UFOV accuracy. We then used weighted ROI-to-ROI connectivity analysis to compare the efficacy of the UFOV network versus 7 resting-state networks in predicting UFOV fMRI task performance and Double Decision performance. Finally, we calculated network segregation among higher order resting state networks to assess its relationship with UFOV accuracy. All functional connectivity analyses were corrected at a false discovery threshold (FDR) at p<0.05.
Results:
ROI-to-ROI analysis showed significant within-network functional connectivity among the 10 a priori ROIs (UFOV network) during task completion (all pFDR<.05). After controlling for covariates, greater within-network connectivity of the UFOV network associated with better UFOV fMRI performance (pFDR=.008). Regarding the 7 resting-state networks, greater within-network connectivity of the CON (pFDR<.001) and FPCN (pFDR=. 014) were associated with higher accuracy on the UFOV fMRI task. Furthermore, greater within-network connectivity of only the UFOV network associated with performance on the Double Decision task (pFDR=.034). Finally, we assessed the relationship between higher-order network segregation and UFOV accuracy. After controlling for covariates, no significant relationships between network segregation and UFOV performance remained (all p-uncorrected>0.05).
Conclusions:
To date, this is the first study to assess task-based functional connectivity during completion of the UFOV task. We observed that coherence within 10 a priori ROIs significantly predicted UFOV performance. Additionally, enhanced within-network connectivity of the UFOV network predicted better performance on the Double Decision task, while conventional resting-state networks did not. These findings provide potential targets to optimize efficacy of UFOV interventions.
Aging is associated with disruptions in functional connectivity within the default mode (DMN), frontoparietal control (FPCN), and cingulo-opercular (CON) resting-state networks. Greater within-network connectivity predicts better cognitive performance in older adults. Therefore, strengthening network connectivity, through targeted intervention strategies, may help prevent age-related cognitive decline or progression to dementia. Small studies have demonstrated synergistic effects of combining transcranial direct current stimulation (tDCS) and cognitive training (CT) on strengthening network connectivity; however, this association has yet to be rigorously tested on a large scale. The current study leverages longitudinal data from the first-ever Phase III clinical trial for tDCS to examine the efficacy of an adjunctive tDCS and CT intervention on modulating network connectivity in older adults.
Participants and Methods:
This sample included 209 older adults (mean age = 71.6) from the Augmenting Cognitive Training in Older Adults multisite trial. Participants completed 40 hours of CT over 12 weeks, which included 8 attention, processing speed, and working memory tasks. Participants were randomized into active or sham stimulation groups, and tDCS was administered during CT daily for two weeks then weekly for 10 weeks. For both stimulation groups, two electrodes in saline-soaked 5x7 cm2 sponges were placed at F3 (cathode) and F4 (anode) using the 10-20 measurement system. The active group received 2mA of current for 20 minutes. The sham group received 2mA for 30 seconds, then no current for the remaining 20 minutes.
Participants underwent resting-state fMRI at baseline and post-intervention. CONN toolbox was used to preprocess imaging data and conduct region of interest (ROI-ROI) connectivity analyses. The Artifact Detection Toolbox, using intermediate settings, identified outlier volumes. Two participants were excluded for having greater than 50% of volumes flagged as outliers. ROI-ROI analyses modeled the interaction between tDCS group (active versus sham) and occasion (baseline connectivity versus postintervention connectivity) for the DMN, FPCN, and CON controlling for age, sex, education, site, and adherence.
Results:
Compared to sham, the active group demonstrated ROI-ROI increases in functional connectivity within the DMN following intervention (left temporal to right temporal [T(202) = 2.78, pFDR < 0.05] and left temporal to right dorsal medial prefrontal cortex [T(202) = 2.74, pFDR < 0.05]. In contrast, compared to sham, the active group demonstrated ROI-ROI decreases in functional connectivity within the FPCN following intervention (left dorsal prefrontal cortex to left temporal [T(202) = -2.96, pFDR < 0.05] and left dorsal prefrontal cortex to left lateral prefrontal cortex [T(202) = -2.77, pFDR < 0.05]). There were no significant interactions detected for CON regions.
Conclusions:
These findings (a) demonstrate the feasibility of modulating network connectivity using tDCS and CT and (b) provide important information regarding the pattern of connectivity changes occurring at these intervention parameters in older adults. Importantly, the active stimulation group showed increases in connectivity within the DMN (a network particularly vulnerable to aging and implicated in Alzheimer’s disease) but decreases in connectivity between left frontal and temporal FPCN regions. Future analyses from this trial will evaluate the association between these changes in connectivity and cognitive performance post-intervention and at a one-year timepoint.
Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.
Participants and Methods:
330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.
Results:
Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.
Conclusions:
Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.
Eating disorders (ED) are serious psychiatric disorders, taking a life every 52 minutes, with high relapse. There are currently no support or effective intervention therapeutics for individuals with an ED in their everyday life. The aim of this study is to build idiographic machine learning (ML) models to evaluate the performance of physiological recordings to detect individual ED behaviors in naturalistic settings.
Methods
From an ongoing study (Final N = 120), we piloted the ability for ML to detect an individual's ED behavioral episodes (e.g. purging) from physiological data in six individuals diagnosed with an ED, all of whom endorsed purging. Participants wore an ambulatory monitor for 30 days and tapped a button to denote ED behavioral episodes. We built idiographic (N = 1) logistic regression classifiers (LRC) ML trained models to identify onset of episodes (~600 windows) v. baseline (~571 windows) physiology (Heart Rate, Electrodermal Activity, and Temperature).
Results
Using physiological data, ML LRC accurately classified on average 91% of cases, with 92% specificity and 90% sensitivity.
Conclusions
This evidence suggests the ability to build idiographic ML models that detect ED behaviors from physiological indices within everyday life with a high level of accuracy. The novel use of ML with wearable sensors to detect physiological patterns of ED behavior pre-onset can lead to just-in-time clinical interventions to disrupt problematic behaviors and promote ED recovery.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
Eating disorders (ED) are complex entities of multicausal etiology that mainly affect adolescents and young women. For this reason, EDs frequently cause medical and psychological complications that can cause potentially irreversible developmental sequelae during adolescence.
96% of Spanish youth (15-29 years old) use daily Internet. In addition, 83% use Social Networks. Internet could be a good way to spread information through social media, websites, providing material and means to achieve the body culture purpose.
As we have seen in various papers, social media can influence and trigger the development of EDs.
Objectives
The objetives of the study are to analyse the preferred social network by adolescents diagnosed with eating disorders, as well as to measure characteristic and time-use of these networks.
Methods
We decided to undergo a transversal study to analyse the use of social media. For that, we developed a survey to reflect the use of the main social networks (Instagram, Facebook, Snapchat, Twitter, YouTube and Reddit) in adolescents diagnosed with eating disorders in Spain, who are in outpatient treatment in a specialised ED unit.
Results
The total number of adolescents interviewed was 65; of these 96.9% were females and 3.1% males. The mean age was 14.8 years.
The preferred social network was Instagram (54%), followed by TikTok (34%) and YouTube (6%).
Most of the patients interviewed (68%) admitted checking Instagram daily, and 31% reflected spending between 1-3 hours/day. None of the adolescents reported using Facebook or Reddit.
The majority of adolescents (89%) admitted having ignored friend requests while 12% reflected the importance of having a high number of followers as a way of external validation, getting more ‘likes’ and getting to know more people.
Conclusions
The obtained results reinforce the need of exploring and taking into account the use of Social Media in adolescents with ED and how it may influence their pathology. There is a need for further prospective research in this field.
Although anesthesiology and endocrinology are two distinct branches of medicine, some recent breakthrough treatments have brought together both medical specialties, particularly those concerned with surgical sciences and critical care. Related to the use of various traditional surgical techniques, the lack of newer and safer drugs, the lack of monitoring tools, and the scarcity of critical care services in the past, managing patients with various endocrine disorders has always been perceived as being more difficult by practicing anesthesiologists.
Background: In meningiomas, CDKN2A/B deletions are associated with poor outcomes but are rare in most cohorts (1-5%). Large molecular datasets are therefore required to explore these deletions and their relationship to other prognostic CDKN2A alterations. Methods: We utilized multidimensional molecular data of 560 meningiomas from 5 independent cohorts to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Results: Meningiomas with either CDKN2A/B deletions (partial or homozygous loss) or an intact CDKN2A gene locus but elevated mRNA expression (CDKN2Ahigh) both had poor clinical outcomes. Increased CDKN2A mRNA expression was a poor prognostic factor independent of CDKN2A deletion. CDKN2A expression and p16 protein increased with tumor grade and more aggressive molecular and methylation groups. CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycling pathways dysregulated at different checkpoints. p16 immunohistochemistry was unreliable in differentiating between meningiomas with and without CDKN2A deletions, but increased positivity was associated with increased mRNA expression. CDKN2Ahigh meningiomas were associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. Conclusions: These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications.
This article presents reflections from 12 experts on language learners strategy (LLS) research. They were asked to offer their reflections in one of their domains of expertise, linking research into LLS with successful language learning and use practices. In essence, they were called upon to provide a review of recent scholarship by identifying areas where results of research had already led to the enhancement of learner strategy use, as well as to describe ongoing and future research efforts intended to enhance the strategy domain. The LLS areas dealt with include theory building, the dynamics of delivering strategy instruction (SI), meta-analyses of SI, learner diversity, SI for young language learners, SI for fine-tuning the comprehension and production of academic-level, grammar strategies at the macro and micro levels, lessons learned from many years of LLS research in Greece, the past and future roles of technology aimed at enhancing language learning, and applications of LLS in content instruction. This review is intended to provide the field with an updated statement as to where we have been, where we are now, and where we need to go. Ideally, it will provide ideas for future studies.