Search

Objective: The ability to assess cognitive skills remotely is increasing with the widespread use and availability of smartphones. The Mobile Toolbox (MTB) is a measurement system that includes Sequences, a new measure of working memory designed specifically for smartphones. This study describes the development of Sequences and presents the studies conducted to evaluate its psychometric properties. Methods: We developed a new measure of working memory that can be self-administered remotely using an iOS or Android smartphone. In Sequences, a series of numbers and letters are shown on the screen one at a time, and the participant must first tap the letters they see in alphabetical order, followed by tapping the numbers in ascending numerical order. The Sequences measure was evaluated for usability and feasibility across two pilot studies and then assessed in this validation study (which included a total sample size of N = 1,246). Psychometric properties of the new measure were evaluated in three studies involving participants aged 18–90 years. In Study 1 (N = 92), participants completed MTB measures in a laboratory setting. They were also administered both an equivalent NIH Toolbox (NIHTB) measure along with external measures of similar constructs. In Study 2 (N = 1,007), participants were administered NIHTB measures in the laboratory and then completed MTB measures remotely on their own devices. In Study 3 (N = 147), participants completed MTB measures twice, remotely on their own devices, with a 2–week interval between sessions. Results: Sequences exhibited moderately high correlations with a comparable NIHTB test and external measures of a similar construct, while exhibiting a lower correlation with an unrelated test, as hypothesized. Internal consistency was high, but test-retest reliability was moderate. When controlling for age, phone operating system (iOS vs. Android) and sex assigned at birth did not significantly impact performance; however, there was a significant difference between individuals who completed college and those with a high school education or lower. Conclusion: The results support the validity of Sequences as a measure of working memory for remote self-administered use. The internal consistency was strong, with moderate test-retest reliability that is likely a function of the test's unproctored self-administration method. The findings suggest that Sequences is appropriate for use with adults aged 18–90 years in remote self-administered designs that focus on group results. [ABSTRACT FROM AUTHOR]

Introduction: The National Institutes of Health (NIH) Toolbox Near Visual Acuity Test is a novel digitized measure designed to provide an assessment of near vision in a time-and cost-effective manner. This study is the first to report the psychometric properties of the NIH Toolbox Near Visual Acuity Test in a sample of community-dwelling middle-aged and older adults. Methods: Ninety-eight adults (ages 40–81) completed the tablet-based near vision test and the gold standard chart-based near vision test. Performance on the tablet-and chart-based near vision tests was expressed in logarithmic units. Chart-and tablet-based administration order was counterbalanced. To assess test–retest reliability, the NIH Toolbox Near Visual Acuity Test was administered twice within the same day. Additionally, two equivalent versions of the chart-based test were randomly assigned to participants. Results: Analyses revealed that test–retest reliability of the NIH Toolbox Near Visual Acuity Test was good (intraclass correlation = 0.87, p < 0.001). Concurrence between the NIH Toolbox Near Visual Acuity Test and gold standard chart-based test was also good (r = 0.79, p < 0.001). Discussion: Findings provide support for the reliability and validity of the NIH Toolbox Near Visual Acuity Test as a near vision assessment for middle-aged to older adult populations. With further research, the integration of this test within the widely used NIH Toolbox may provide a more efficient means to understanding how near visual acuity influences neurocognitive test performance and brain function in middle-aged to older adult populations. [ABSTRACT FROM AUTHOR]

Background: Exposure to repetitive head impacts (RHI) is associated with the neurodegenerative tauopathy chronic traumatic encephalopathy (CTE). There is substantial heterogeneity in the clinical presentation of CTE. Younger age of first exposure (AFE) to American football has not been associated with odds or severity of CTE. Yet, it has been associated with earlier onset and severity of symptoms, potentially by decreasing resilience to RHI‐related neuropathologies. We examined the association between AFE to football and clinical and neurobehavioral outcomes in deceased football players across the age continuum. Methods: The sample included 677 male football players who donated their brains to the UNITE Brain Bank. Informants of brain donors completed modified scales assessing donor cognitive function (Cognitive Difficulties Scale [CDS], BRIEF‐A Metacognition Index [MI]), daily function (Functional Activities Questionnaire [FAQ]), mood (Geriatric Depression Scale‐15 [GDS‐15], Beck Anxiety Inventory [BAI] Apathy Evaluation Scale [AES]), and neurobehavioral dysregulation (Barratt Impulsiveness Scale [BIS‐11], BRIEF‐A Behavioral Regulation Index [BRI], Brown‐Goodwin Aggression Scale Adult Sum). Dementia was adjudicated through consensus conferences. Neuropathologists were blinded to clinical history. Global p‐tau burden was calculated by summing semi‐quantitative ratings of p‐tau severity across nine brain regions. Regressions tested the association between AFE and each scale, dementia status, and CTE status. Analyses were performed stratified by age 60 to isolate the effect of neurodegenerative disease resilience adjusting for age, global p‐tau burden, and duration of football play. Results: Sample characteristics are in Tables 1‐2. Most donors played football in college and/or professionally (n = 509, 76%). CTE was the most common neuropathological diagnosis (n = 471, 70%). AFE was not associated with CTE neuropathology. Global tau and age were consistent predictors of the clinical scales (Table 3). There were significant associations between AFE and the clinical scales among those older but not younger than age 60. Among those over age 60, younger AFE to football was associated with higher CDS (p = 0.02), BRIEF‐A MI (p = 0.02), and BIS‐11 (p = 0.03) scores. Conclusions: Younger AFE was associated with worse informant‐reported clinical outcomes in older but not younger deceased football players, independent of tau. Youth exposure to RHI from football might decrease resilience to cope with neuropathologies later in life. [ABSTRACT FROM AUTHOR]

Although no dataset at the nanoscale for the entire human brain has yet been acquired and neither a nanoscale human whole brain atlas has been constructed, tremendous progress in neuroimaging and high-performance computing makes them feasible in the non-distant future. To construct the human whole brain nanoscale atlas, there are several challenges, and here, we address two, i.e., the morphology modeling of the brain at the nanoscale and designing of a nanoscale brain atlas. A new nanoscale neuronal format is introduced to describe data necessary and sufficient to model the entire human brain at the nanoscale, enabling calculations of the synaptome and connectome. The design of the nanoscale brain atlas covers design principles, content, architecture, navigation, functionality, and user interface. Three novel design principles are introduced supporting navigation, exploration, and calculations, namely, a gross neuroanatomy-guided navigation of micro/nanoscale neuroanatomy; a movable and zoomable sampling volume of interest for navigation and exploration; and a nanoscale data processing in a parallel-pipeline mode exploiting parallelism resulting from the decomposition of gross neuroanatomy parcellated into structures and regions as well as nano neuroanatomy decomposed into neurons and synapses, enabling the distributed construction and continual enhancement of the nanoscale atlas. Numerous applications of this atlas can be contemplated ranging from proofreading and continual multi-site extension to exploration, morphometric and network-related analyses, and knowledge discovery. To my best knowledge, this is the first proposed neuronal morphology nanoscale model and the first attempt to design a human whole brain atlas at the nanoscale.

Malonyl-CoA-acyl carrier protein transacylase (MCAT) is an enzyme involved in mitochondrial fatty acid synthesis (mtFAS) and catalyzes the transfer of the malonyl moiety of malonyl-CoA to the mitochondrial acyl carrier protein (ACP). Previously, we showed that loss-of-function of mtFAS genes, including Mcat, is associated with severe loss of electron transport chain (ETC) complexes in mouse immortalized skeletal myoblasts (Nowinski et al., 2020). Here, we report a proband presenting with hypotonia, failure to thrive, nystagmus, and abnormal brain MRI findings. Using whole exome sequencing, we identified biallelic variants in MCAT. Protein levels for NDUFB8 and COXII, subunits of complex I and IV respectively, were markedly reduced in lymphoblasts and fibroblasts, as well as SDHB for complex II in fibroblasts. ETC enzyme activities were decreased in parallel. Re-expression of wild-type MCAT rescued the phenotype in patient fibroblasts. This is the first report of a patient with MCAT pathogenic variants and combined oxidative phosphorylation deficiency.

Abstract Background Chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy, cannot currently be diagnosed during life. Atrophy patterns on magnetic resonance imaging could be an effective in vivo biomarker of CTE, but have not been characterized. Mechanisms of neurodegeneration in CTE are unknown. Here, we characterized macrostructural magnetic resonance imaging features of brain donors with autopsy-confirmed CTE. The association between hyperphosphorylated tau (p-tau) and atrophy on magnetic resonance imaging was examined. Methods Magnetic resonance imaging scans were obtained by medical record requests for 55 deceased symptomatic men with autopsy-confirmed CTE and 31 men (n = 11 deceased) with normal cognition at the time of the scan, all >60 years Three neuroradiologists visually rated regional atrophy and microvascular disease (0 [none]–4 [severe]), microbleeds, and cavum septum pellucidum presence. Neuropathologists rated tau severity and atrophy at autopsy using semi-quantitative scales. Results Compared to unimpaired males, donors with CTE (45/55=stage III/IV) had greater atrophy of the orbital-frontal (mean diff.=1.29), dorsolateral frontal (mean diff.=1.31), superior frontal (mean diff.=1.05), anterior temporal (mean diff.=1.57), and medial temporal lobes (mean diff.=1.60), and larger lateral (mean diff.=1.72) and third (mean diff.=0.80) ventricles, controlling for age at scan (ps

BackgroundAnnual cognitive screening in adults aged >65 years can improve early detection of cognitive impairment, yet less than half of all cases are identified in primary care. Time constraints in primary care settings present a major barrier to routine screening. A remote cognitive screener completed on a patient’s own smartphone before a visit has the potential to save primary care clinics time, encourage broader screening practices, and increase early detection of cognitive decline. ObjectiveWe described the iterative design and proposed the implementation of a remote cognitive screening app, MyCog Mobile, to be completed on a patient’s smartphone before an annual wellness visit. The research questions were as follows: What would motivate primary care clinicians and clinic administrators to implement a remote cognitive screening process? How might we design a remote cognitive screener to fit well with existing primary care workflows? What would motivate an older adult patient to complete a cognitive screener on a smartphone before a primary care visit? How might we optimize the user experience of completing a remote cognitive screener on a smartphone for older adults? MethodsTo address research questions 1 and 2, we conducted individual interviews with clinicians (n=5) and clinic administrators (n=3). We also collaborated with clinic administrators to create user journey maps of their existing and proposed MyCog Mobile workflows. To address research questions 3 and 4, we conducted individual semistructured interviews with cognitively healthy older adults (n=5) and solicited feedback from a community stakeholder panel (n=11). We also tested and refined high-fidelity prototypes of the MyCog Mobile app with the older adult interview participants, who rated the usability on the Simplified System Usability Scale and After-Scenario Questionnaire. ResultsClinicians and clinic administrators were motivated to adopt a remote cognitive screening process if it saved time in their workflows. Findings from interviews and user journey mapping informed the proposed implementation and core functionality of MyCog Mobile. Older adult participants were motivated to complete cognitive screeners to ensure that they were cognitively healthy and saw additional benefits to remote screening, such as saving time during their visit and privacy. Older adults also identified potential challenges to remote smartphone screening, which informed the user experience design of the MyCog Mobile app. The average rating across prototype versions was 91 (SD 5.18) on the Simplified System Usability Scale and 6.13 (SD 8.40) on the After-Scenario Questionnaire, indicating above-average usability. ConclusionsThrough an iterative, human-centered design process, we developed a viable remote cognitive screening app and proposed an implementation strategy for primary care settings that was optimized for multiple stakeholders. The next steps include validating the cognitive screener in clinical and healthy populations and piloting the finalized app in a community primary care clinic.

Research highlights the increasing overlap of autism spectrum disorder and substance use disorders in young people. However, no behavioral treatments exist addressing this comorbidity despite great need. A team of clinicians developed an integrated behavioral protocol addressing substance use in youth with autism spectrum disorder. The multidisciplinary team developed 12 youth, 7 parent, and 3 joint modules based on established evidence-based therapies shown to have effectiveness separately addressing autism spectrum and substance use. Two cases are discussed to illuminate this integrated intervention. Adaptations to the protocol were made during feedback from patients and their parents. Further research is needed to determine the effectiveness of this preliminary protocol.

ABSTRACT Assigning taxonomy remains a challenging topic in microbiome studies, due largely to ambiguity of reads which overlap multiple reference genomes. With the Web of Life (WoL) reference database hosting 10,575 reference genomes and growing, the percentage of ambiguous reads will only increase. The resulting artifacts create both the illusion of co-occurrence and a long tail end of extraneous reference hits that confound interpretation. We introduce genome cover, the fraction of reference genome overlapped by reads, to distinguish these artifacts. We show how to dynamically predict genome cover by read count and examine our model in Staphylococcus aureus monoculture. Our modeling cleanly separates both S. aureus and true contaminants from the false artifacts of reference overlap. We next introduce saturated genome cover, the true fraction of a reference genome overlapped by sample contents. Genome cover may not saturate for low abundance or low prevalence bacteria. We assuage this worry with examination of a large human fecal data set. By compositing the metric across like samples, genome cover saturates even for rare species. We note that it is a threshold on saturated genome cover, not genome cover itself, which indicates a spurious reference hit or distant relative. We present Zebra, a method to compute and threshold the genome cover metric across like samples, a recurrence to estimate genome cover and confirm saturation, and provide guidance for choosing cover thresholds in real world scenarios. Standalone genome cover and integration into Woltka are available: https://github.com/biocore/zebra_filter, https://github.com/qiyunzhu/woltka. IMPORTANCE Taxonomic assignment, assigning sequences to specific taxonomic units, is a crucial processing step in microbiome analyses. Issues in taxonomic assignment affect interpretation of what microbes are present in each sample and may be associated with specific environmental or clinical conditions. Assigning importance to a particular taxon relies strongly on independence of assigned counts. The false inclusion of thousands of correlated taxa makes interpretation ambiguous, leading to underconstrained results which cannot be reproduced. The importance sometimes attached to implausible artifacts such as anthrax or bubonic plague is especially problematic. We show that the Zebra filter retrieves only the nearest relatives of sample contents enabling more reproducible and biologically plausible interpretation of metagenomic data.

A challenge for longitudinal studies is combining individual assessments into visits that are scientifically logical, not burdensome for participants, well-choreographed, and operationally feasible. The visits then need to be sequenced and spaced to address the scientific goals and generate a data archive that is sufficiently robust and well-documented to support subsequent analyses. This paper summarizes comprehensive multi-disciplinary activities that were coordinated to design the content, format, and structure of the National Children's Study and concurrently serve as a model and resource for other studies.

The gastrointestinal (GI) impact of fibers including resistant starch (RS) consumption depends on various types and amounts of fibers, the initial microbiome states, and accurate intake measurements. A randomized clinical trial evaluated the GI impact of varying doses of a novel resistant starch blend (RSB) with smart cap monitoring. RSB contained at least 50% RS and was a proprietary mixture of a potato starch, green banana flour, and apple fiber powder (a source of apple pectin, not resistant starch). The study design randomized participants to one of four arms: 10 g/day of potato starch (0 RSB), 10 g/day of RSB, 10 to 20 to 20 g/day of RSB or 10 to 20 to 30 g/day RSB for two-week intervals over 6 weeks. Results confirmed that while resistant starch of approximately 5 g per day improves GI symptoms at 2, 4, and 6 weeks, it did not demonstrate a detectable effect on short chain fatty acids. Increasing doses of the blend (RSB) led to a decrease in the diarrhea score. Using an estimate of total consumption of RSB based on smart cap recordings of container openings and protocol-specified doses of RSB, a reduction in the sleep disturbance score was associated with higher RSB dose. The exploratory microbiome evaluation demonstrated that among the 16S rRNA gene sequences most associated with the consumption of the novel blend RSB, two belong to taxa of notable interest to human health: Faecalibacterium and Akkermansia.

Abstract Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term “response to bacterium” was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term “response to stress” was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.

Objectives: To help promote early detection of cognitive impairment in primary care, MyCog Mobile was designed as a cognitive screener that can be self-administered remotely on a personal smartphone. We explore the potential utility of MyCog Mobile in primary care by comparing MyCog Mobile to a commonly used screener, Mini-Cog. Methods: A sample of 200 older adults 65+ years (mean age = 72.56 years), completed the Mini-Cog and MyCog Mobile, which includes 2 memory measures and 2 executive functioning measures. A logistic regression model was conducted to predict failing Mini-Cog scores (≤2) based on MyCog Mobile measures. Results: A total of 20 participants earned a Mini-Cog score ≤2. MyCog Mobile demonstrated an AUC of 0.83 (95% bootstrap CI [0.75, 0.95]), sensitivity of 0.76 (95% bootstrap CI [0.63, 0.97]), and specificity of.88 (95% bootstrap CI [0.63, 0.10]). The subtest Name Matching from MyFaces and MySorting were the only significant predictors of failed Mini-Cogs. Conclusions: MyCog Mobile demonstrated sensitivity and specificity to identify participants who failed the Mini-Cog, and may show promise as a screening tool for cognitive impairment in older adults. Further research is necessary to establish the clinical utility of MyCog Mobile in a larger sample using documented clinical diagnoses. [ABSTRACT FROM AUTHOR]

Background/Objectives: Diagnosing concussions is problematic, in part due to the invisible nature of concussion symptoms, in addition to personal and interpersonal factors that influence symptom reporting. As a result, observable signs of concussion can ensure concussions are identified and appropriately treated. Here, we define a potential novel sign, the spontaneous headshake after a kinematic event (SHAAKE) and evaluate its utility in the diagnosis of concussion. Methods: A cross-sectional survey study of 347 athletes (age 27, IQR: 25–29; 47.6% female; highest level of play: college—46.1%, high school—41.2%) identified whether SHAAKE occurred, the reasons underlying SHAAKEs, and its utility for self-reported concussion. Sensitivity and positive predictive value were calculated across all sports and these parameters, as well as estimates for specificity and negative predictive value leveraging published helmet sensor data, were calculated for football players. Results: The median number of times participants reported SHAAKE was 5 (IQR: 3–10), with 4 (IQR: 2–7) associated with a self-reported concussion. Overall, 84.9% of participants reported concussion symptoms as the most common reason for their SHAAKEs. Across all sports, SHAAKE had a sensitivity of 49.6% and positive predictive value 72.4% for diagnosing concussion. In football players, SHAAKE had a sensitivity of 52.3%, estimated specificity of 99.9%, positive predictive value of 91.9%, and estimated negative predictive value of 99.5% for diagnosing self-reported concussion. Conclusions: These results demonstrate that nearly three-quarters of athletes reported a SHAAKE associated with a self-reported concussion, which supports the potential for SHAAKE to be used as a concussion screening tool. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy more frequently found in deceased former football players. CTE has heterogeneous clinical presentations with multifactorial causes. Previous literature has shown substance use (alcohol/drug) can contribute to Alzheimer's disease and related tauopathies pathologically and clinically. Objective: To examine the association between substance use and clinical and neuropathological endpoints of CTE. Methods: Our sample included 429 deceased male football players. CTE was neuropathologically diagnosed. Informant interviews assessed features of substance use and history of treatment for substance use to define indicators: history of substance use treatment (yes vs no, primary variable), alcohol severity, and drug severity. Outcomes included scales that were completed by informants to assess cognition (Cognitive Difficulties Scale, BRIEF-A Metacognition Index), mood (Geriatric Depression Scale-15), behavioral regulation (BRIEF-A Behavioral Regulation Index, Barratt Impulsiveness Scale-11), functional ability (Functional Activities Questionnaire), as well as CTE status and cumulative p-tau burden. Regression models tested associations between substance use indicators and outcomes. Results: Of the 429 football players (mean age = 62.07), 313 (73%) had autopsy confirmed CTE and 100 (23%) had substance use treatment history. Substance use treatment and alcohol/drug severity were associated with measures of behavioral regulation (FDR-p-values<0.05, ΔR2 = 0.04–0.18) and depression (FDR-p-values<0.05, ΔR2 = 0.02–0.05). Substance use indicators had minimal associations with cognitive scales, whereas p-tau burden was associated with all cognitive scales (p-values <0.05). Substance use treatment had no associations with neuropathological endpoints (FDR-p-values>0.05). Conclusions: Among deceased football players, substance use was common and associated with clinical symptoms. [ABSTRACT FROM AUTHOR]

The presentation of cortical arteries is challenging, as most of their course is hidden in the depth of the sulci. Despite that, demonstrating the arteries on the cortical surface is a standard way of their presentation. To keep advantages of surface presentation while lessening its limitation, we propose a novel context-related method of cerebrovasculature presentation by cortical openings consisting in the removal of a selected region from the cortical mantle and exposing underlying structures. We also introduce a reverse than standard vessel-to-context mapping from a gyrus/lobule to vessels supplying it. The method has the following steps: define a cortical opening, develop a tool to perform them, create cortical openings for gyri and lobules with underlying white matter and intracranial arteries, generate labeled and parcellated images for the created openings, and integrate the cortical opening images with the NOW in BRAIN public repository of 8600 3D neuroimages. The cortical openings are created for 64 gyri and six lobules for the left and right cerebral hemispheres resulting in 210 images arranged in triples as spatially corresponding non-parcellated and unlabeled, parcellated by color and unlabeled, and parcellated and labeled images. The cortical opening approach, generally, increases vessel exposure in a higher number of depicted branches, revealing arteries otherwise hidden deep in sulci, a more complete vessel course, and a lower number of required views. The gyrus/lobule-to-arteries mapping facilitates exploration of a studied region, encapsulates all local arteries, and reduces vascular complexity by decomposing the entire vascular system into smaller sets involved in the studied region. [ABSTRACT FROM AUTHOR]

One of the key challenges in neuroscience is to generate the human nanoscale connectome which requires comprehensive knowledge of synaptome forming the neural microcircuits. The synaptic architecture determines limits of individual mental capacity and provides the framework for understanding neurologic disorders. Here, I address morphology modeling and storage estimation for the human synaptome at the nanoscale. A synapse is defined as a pair of pairs [(presynaptic_neuron),(presynaptic_axonal_terminal);(postsynaptic_neuron),(postsynaptic_dendritic_terminal)]. Center coordinates, radius, and identifier characterize a dendritic or axonal terminal. A synapse comprises topology with the paired neuron and terminal identifiers, location with terminal coordinates, and geometry with terminal radii. The storage required for the synaptome depends on the number of synapses and storage necessary for a single synapse determined by a synaptic model. I introduce three synaptic models: topologic with topology, point with topology and location, and geometric with topology, location, and geometry. To accommodate for a wide range of variations in the numbers of neurons and synapses reported in the literature, four cases of neurons (30;86;100;138 billion) and three cases of synapses per neuron (1,000;10,000;30,000) are considered with three full and simplified (to reduce storage) synaptic models resulting in total 72 cases of storage estimation. The full(simplified) synaptic model of the entire human brain requires from 0.21(0.14) petabytes (PB) to 28.98(18.63) PB for the topologic model, from 0.57(0.32) PB to 78.66(43.47) PB for the point model, and from 0.69(0.38) PB to 95.22(51.75) PB for the geometric model. The full(simplified) synaptic model of the cortex needs from 86.80(55.80) TB to 2.60(1.67) PB for the topologic model, from 235.60(130.02) TB to 7.07(3.91) PB for the point model, and from 285.20(155.00) TB to 8.56(4.65) PB for the geometric model. The topologic model is sufficient to compute the connectome's topology, but it is still too big to be stored on today's top supercomputers related to neuroscience. Frontier, the world's most powerful supercomputer for 86 billion neurons can handle the nanoscale synaptome in the range of 1,000–10,000 synapses per neuron. To my best knowledge, this is the first big data work attempting to provide storage estimation for the human nanoscale synaptome. [ABSTRACT FROM AUTHOR]

Objective We describe the development of a new computer adaptive vocabulary test, Mobile Toolbox (MTB) Word Meaning, and validity evidence from 3 studies. Method Word Meaning was designed to be a multiple-choice synonym test optimized for self-administration on a personal smartphone. The items were first calibrated online in a sample of 7,525 participants to create the computer-adaptive test algorithm for the Word Meaning measure within the MTB app. In Study 1, 92 participants self-administered Word Meaning on study-provided smartphones in the lab and were administered external measures by trained examiners. In Study 2, 1,021 participants completed the external measures in the lab and Word Meaning was self-administered remotely on their personal smartphones. In Study 3, 141 participants self-administered Word Meaning remotely twice with a 2-week delay on personal iPhones. Results The final bank included 1363 items. Internal consistency was adequate to good across samples (ρxx = 0.78 to 0.81, p  < .001). Test–retest reliability was good (ICC = 0.65, p  < .001), and the mean theta score was not significantly different upon the second administration. Correlations were moderate to large with measures of similar constructs (ρ = 0.67–0.75, p  < .001) and non-significant with measures of dissimilar constructs. Scores demonstrated small to moderate correlations with age (ρ = 0.35 to 0.45, p  < .001) and education (ρ = 0.26, p  < .001). Conclusion The MTB Word Meaning measure demonstrated evidence of reliability and validity in three samples. Further validation studies in clinical samples are necessary. [ABSTRACT FROM AUTHOR]

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with a history of repetitive head impacts (RHI). CTE was described in boxers as early as the 1920s and by the 1950s it was widely accepted that hits to the head caused some boxers to become “punch drunk.” However, the recent discovery of CTE in American and Australian-rules football, soccer, rugby, ice hockey, and other sports has resulted in renewed debate on whether the relationship between RHI and CTE is causal. Identifying the strength of the evidential relationship between CTE and RHI has implications for public health and medico-legal issues. From a public health perspective, environmentally caused diseases can be mitigated or prevented. Medico-legally, millions of children are exposed to RHI through sports participation; this demographic is too young to legally consent to any potential long-term risks associated with this exposure. To better understand the strength of evidence underlying the possible causal relationship between RHI and CTE, we examined the medical literature through the Bradford Hill criteria for causation. The Bradford Hill criteria, first proposed in 1965 by Sir Austin Bradford Hill, provide a framework to determine if one can justifiably move from an observed association to a verdict of causation. The Bradford Hill criteria include nine viewpoints by which to evaluate human epidemiologic evidence to determine if causation can be deduced: strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy. We explored the question of causation by evaluating studies on CTE as it relates to RHI exposure. Through this lens, we found convincing evidence of a causal relationship between RHI and CTE, as well as an absence of evidence-based alternative explanations. By organizing the CTE literature through this framework, we hope to advance the global conversation on CTE mitigation efforts.