470 results
A systematic review of the cognitive effects of the COMT inhibitor, tolcapone, in adult humans
- Emilia Kings, Konstantinos Ioannidis, Jon E. Grant, Samuel R. Chamberlain
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- CNS Spectrums , First View
- Published online by Cambridge University Press:
- 15 March 2024, pp. 1-10
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Objective
The catechol-o-methyltransferase (COMT) inhibitor tolcapone constitutes a potentially useful probe of frontal cortical dopaminergic function. The aim of this systematic review was to examine what is known of effects of tolcapone on human cognition in randomized controlled studies.
MethodsThe study protocol was preregistered on the Open Science Framework. A systematic review was conducted using PubMed to identify relevant randomized controlled trials examining the effects of tolcapone on human cognition. Identified articles were then screened against inclusion and exclusion criteria.
ResultsOf the 22 full-text papers identified, 13 randomized control trials were found to fit the pre-specified criteria. The most consistent finding was that tolcapone modulated working memory; however, the direction of effect appeared to be contingent on the COMT polymorphism (more consistent evidence of improvement in Val–Val participants). There were insufficient nature and number of studies for meta-analysis.
ConclusionThe cognitive improvements identified upon tolcapone administration, in some studies, are likely to be due to the level of dopamine in the prefrontal cortex being shifted closer to its optimum, per an inverted U model of prefrontal function. However, the results should be interpreted cautiously due to the small numbers of studies. Given the centrality of cortical dopamine to understanding human cognition, studies using tolcapone in larger samples and across a broader set of cognitive domains would be valuable. It would also be useful to explore the effects of different dosing regimens (different doses; and single versus repeated administration).
Cognition in trichotillomania: a meta-analysis
- Aliza Ali, Konstantinos Ioannidis, Jon E. Grant, Samuel R. Chamberlain
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- CNS Spectrums , First View
- Published online by Cambridge University Press:
- 13 March 2024, pp. 1-8
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Trichotillomania (TTM) is a mental health disorder characterized by repetitive urges to pull out one’s hair. Cognitive deficits have been reported in people with TTM compared to controls; however, the current literature is sparse and inconclusive about affected domains. We aimed to synthesize research on cognitive functioning in TTM and investigate which cognitive domains are impaired.
MethodsAfter preregistration on the International Prospective Register of Systematic Reviews (PROSPERO), we conducted a comprehensive literature search for papers examining cognition in people with TTM versus controls using validated tests. A total of 793 papers were screened using preestablished inclusion/exclusion criteria, yielding 15 eligible studies. Random-effects meta-analysis was conducted for 12 cognitive domains.
ResultsMeta-analysis demonstrated significant deficits in motor inhibition and extradimensional (ED) shifting in people with TTM versus controls as measured by the stop-signal task (SST) (Hedge’s g = 0.45, [CI: 0.14, 0.75], p = .004) and ED set-shift task (g = 0.38, [CI: 0.13, 0.62], p = .003), respectively. There were no significant between-group differences in the other cognitive domains tested: verbal learning, intradimensional (ID) shifting, road map spatial ability, pattern recognition, nonverbal memory, executive planning, spatial span length, Stroop inhibition, Wisconsin card sorting, and visuospatial functioning. Findings were not significantly moderated by study quality scores.
ConclusionsMotor inhibition and ED set-shifting appear impaired in TTM. However, a cautious interpretation of results is necessary as samples were relatively small and frequently included comorbidities. Treatment interventions seeking to improve inhibitory control and cognitive flexibility merit exploration for TTM.
TH-stopping in Philadelphia Puerto Rican English
- Abigail E. Patchell, Grant M. Berry
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- Journal:
- Language Variation and Change / Volume 36 / Issue 1 / March 2024
- Published online by Cambridge University Press:
- 23 February 2024, pp. 73-93
- Print publication:
- March 2024
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Analyzing data from the Puerto Rican English in Philadelphia (PREP) corpus, we investigate participation in TH-stopping, a socially stigmatized yet stable variable documented in Philadelphia. While previous studies have been impressionistic and have considered voiced and voiceless tokens to pattern together, this work validates novel, acoustically based stopping indices: mean harmonics-to-noise ratio for voiced tokens and skewness for voiceless tokens. We apply these indices to the corpus data and analyze stopping under a Bayesian framework, and we compare results from a model built from impressionistic coding of a subset of the same data. We find convergent evidence that TH-stopping is a stable variable in the Puerto Rican English data as well. Findings are compared with those of existing studies, noting future directions for research on the variable and underscoring the importance of establishing demographically representative baselines for linguistic research in diverse urban centers.
3 Quick-Reference Criteria for Identifying Clinically Significant Multivariate Change in Older Adult Cognition: A NACC Study
- Amanda M. Wisinger, Hillary F. Abel, Jeremy G. Grant, Glenn E. Smith
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 881-882
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Objective:
Accurately interpreting cognitive change is an essential aspect of clinical care for older adults. Several approaches to identifying 'true’ cognitive change in a single cognitive measure are available (e.g., reliable change methods, regression-based norms); however, neuropsychologists in clinical settings often rely on simple score differences rather than advanced statistics, especially since multiple scores compose a typical battery. This study sought to establish quick-reference normative criteria to help neuropsychologists identify how frequently significant change occurs across multiple measures in cognitively normal older adults.
Participants and Methods:Data were obtained from the National Alzheimer’s Coordinating Center (NACC). Participants were 845 older adults who were classified as cognitively normal at baseline and at 24-month follow-up. In NACC, these clinical classifications are made separately from the assessment of cognitive performance, including cognitive change. The sample was 34.9% female, 83.5% White, 13.1% Black 2.3% Asian, and 1.1% other race with a mean age of 70.7 years (SD=10.2). Of the sample, 95.5% identified as non-Hispanic. Mean education was 16.1 years (SD=2.8). The cognitive battery entailed: Craft Story Immediate and Delayed Recall, Benson Copy and Delayed Recall, Number Span (Forward & Backward), Category Fluency (Animals & Vegetables), Trails A&B, Multilingual Naming Test, and Verbal Fluency (F&L). Change scores between baseline performance and follow-up were calculated for each measure. The natural distribution of change scores was examined for each measure and cut points representing the 5th and 10th percentile were applied to each distribution to classify participants who exhibited substantial declines in performance on each measure. We then examined the multivariate frequency of statistically rare change scores for each individual.
Results:As expected in a normal sample, overall cognitive performance was generally stable between baseline and 24-month follow-up. Across cognitive measures, 81.9% of participants had at least one change score fall below the 10th percentile in the distribution of change scores, and 55.7% had at least one score below the 5th percentile, 49.3% of participants had two or more change scores that fell below the 10th percentile and 21.1% with two or more below the 5th percentile. There were 26.7% participants that had three or more change scores below the 10th percentile, and 6.4% of participants had three change scores below the 5th percentile.
Conclusions:Among cognitively normal older adults assessed twice at a 24-month interval with a battery of 13 measures, it was not uncommon for an individual to have at least one score fall below the 10th percentile (82% of the sample) or even the 5th percentile (56%) in the natural distribution of change scores. There were 27% participants that had three or more declines in test performance below the 10th percentile; in comparison, only 6% of the sample had three or more change scores at the 5th percentile. This suggests that individuals who exhibit more multivariate changes in performance than these standards are likely experiencing an abnormal rate of cognitive decline. Our findings provide a preliminary quick-reference approach to identifying clinically significant cognitive change. Future studies will explore additional batteries and examine multivariate frequencies of change in clinical populations.
29 Quick-Reference Criteria for Identifying Clinically Significant Multivariate Change in Older Adult Cognition: An ADNI Study
- Jeremy G Grant, Amanda M Wisinger, Glenn E Smith
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 342-343
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Objective:
Accurately interpreting change in cognitive functioning is an essential aspect of clinical care for older adults. Several approaches to identifying ‘true’ cognitive change in a single cognitive measure are available (e.g., reliable change methods, regression-based norms); however, neuropsychologists in clinical settings often rely on simple score differences rather than advanced analytical procedures especially since they examine multiple test performances. This study sought to establish quick-reference normative criteria to help neuropsychologists identify how frequently significant change occurs across multiple cognitive measures in cognitively normal older adults.
Participants and Methods:Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants were 401 older adults who were classified as cognitively normal at baseline and at 24-month follow-up. In ADNI, these clinical classifications are made separately from the assessment of cognitive performance, including cognitive change. The sample was 50.1% female, 93.5% non-Hispanic White, 4.0% non-Hispanic Black, 1.5% Asian American, and 1.0% other race/ethnicity, with a mean age of 76.0 years (SD = 4.9). Mean education was 16.4 years (SD = 2.7). The cognitive battery included: Boston Naming Test, Category Fluency Test, Trails A & B, Clock Drawing Test, and Auditory Verbal Learning Test, Trial 1-5 Total and Delayed Recall. Change scores between baseline performance and 24-month follow-up were calculated for each measure. The natural distribution of change scores was examined for each measure and cut points representing the 5th and 10th percentile were applied to each distribution to classify participants who exhibited substantial declines in performance on a given measure. We then examined the multivariate frequency of statistically rare change scores for each individual.
Results:As expected in a normal sample, overall cognitive performance was generally stable between baseline and 24-month followup. Across cognitive measures, 43.6% of participants had at least one change score fall below the 10th percentile in the distribution of change scores, and 21.9% had at least one score below the 5th percentile. 13.0% of participants had two or more change scores that fell below the 10th percentile, in comparison to 4.5% with two or more below the 5th percentile. 3.2% of participants had three or more change scores below the 10th percentile, versus 0.5% of participants who had three change scores below the 5th percentile.
Conclusions:Among cognitively normal older adults assessed twice at a 24-month interval with a battery of seven measures, it was not uncommon for an individual to have at least one score fall below the 10th percentile (43% of the sample) or even the 5th percentile (21%) in the natural distribution of change scores. However, only 3.2% of normals had more than two declines in test performance below the 10th percentile, and less than 1% of the sample at more than one change score at the 5th percentile. This suggests that individuals who exhibit more multivariate changes in performance than these standards are likely experiencing an abnormal rate of cognitive decline. Our findings provide a preliminary quick-reference approach to identifying clinically significant cognitive change. Future studies will explore additional batteries and examine multivariate frequencies of change in clinical populations.
3 Intensive Clinical Treatment and Rehabilitation for Veterans with Traumatic Brain Injury and Psychological Health Problems
- Charles E Gaudet, Grant L Iverson, Emily J Lubin, Lauren H Brenner, Ross Zafonte, Mary A Iaccarino
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 115-116
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Some active-duty military service members and veterans experience combinations of persistent traumatic stress, depression, suicidal ideation, anger, aggressive behavior, substance misuse, sleep disturbance, complicated grief, moral injury, headaches and migraines, chronic bodily pain, and cognitive weakness or deficits. The purpose of this study is to describe the clinical outcomes of active-duty service members and veterans who have completed the traumatic brain injury (TBI) and brain health track of a two-week intensive clinical treatment and rehabilitation program.
Participants and Methods:The sample included 141 participants, with a history of TBI, in the Intensive Clinical Program (ICP). The ICP is a multidisciplinary, two-week treatment and rehabilitation program for active duty service members and veterans with complex psychological, cognitive, and physical health concerns. The program is comprised of daily individual therapy, group psychotherapy, psychoeducation, skills-building groups, and complementary and alternative medicine treatments. Participants in the ICP completed the following measures prior to initiating treatment and immediately following completion of treatment: Neurobehavioral Symptom Inventory (NSI), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), Patient Health Questionnaire-9 (PHQ-9), Self-Efficacy for Symptom Management Scale (SE-SMS), and Patient-Reported Outcomes Measurement Information System (PROMIS)-Satisfaction with Participation in Social Roles and Activities-Short Form 8a, version 1.0 (PROMIS-S). Wilcoxon signed ranks tests were used to examine differences in scores on self-report measures from pretreatment to posttreatment for the full sample and within three subgroups stratified by age (in years: 20-34; 35-45; and 46-66). For the NSI, changes in the proportion of participants endorsing moderate or worse levels of individual symptoms from pretreatment to posttreatment were assessed using McNemar’s tests. Alpha levels were set at p<0.05 for all analyses.
Results:Participants reported statistically significant improvements across all of the administered measures (NSI, PCL-5, PHQ-9, PROMIS-S, and SE-SMS) upon conclusion of treatment. Effect sizes ranged from medium to large (d=0.34-1.04) for the full sample. Effect sizes were largely consistent across age subgroups (20-34: d=0.32-1.05; 35-45: d=0.55-0.96; 46-66: d=0.28-1.05). The magnitude of change on the SE-SMS appeared to be less with increasing age (20-34: d=1.05; 35-45: d=0.69; 46-66: d=0.28). Individual item analyses for the NSI revealed statistically significant reductions in the proportion of participants endorsing moderate or greater severity from pretreatment to posttreatment for 18 of 22 symptoms.
Conclusions:Active duty service members and veterans participating in the two-week TBI and brain health intensive clinical program reported considerable symptom reduction at the conclusion of the program. Further research is indicated to assess the durability of symptom reduction.
5 The Association of Neighborhood Socioeconomic Deprivation with Neurocognition in a Diverse Cohort of Middle- and Older-Aged Persons Living with and Without HIV
- Lily Kamalyan, Marta Jankowska, Anya Umlauf, Martha E Perez, Alonzo Mendoza, Lina Scandalis, Donald R Franklin, Matthew Allison, Igor Grant, Mariana Cherner, Maria J Marquine
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 685-687
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Due to decades of structural and institutional racism, minoritized individuals in the US are more likely to live in low socioeconomic neighborhoods, which may underlie the observed greater risk for neurocognitive impairment as they age. However, these relationships have not been examined among people aging with HIV. To investigate neurocognitive disparities among middle- and older-aged Latino and non-Latino White people living with HIV (PWH), and whether neighborhood socioeconomic deprivation may partially mediate these relationships.
Participants and Methods:Participants were 372 adults ages 40-85 living in southern California, including 186 Latinos (94 PWH, 92 without HIV) and 186 non-Latino (NL) Whites (94 PWH, 92 without HIV) age-matched to the Latino group (for the overall cohort: Age M=57.0, SD=9.1, Education: M=12.7, SD=3.9, 38% female; for the group of PWH: 66% AIDS, 88% on antiretroviral therapy [ART]; 98% undetectable plasma RNA [among those on ART]). Participants completed psychiatric and neuromedical evaluations and neuropsychological tests of verbal fluency, learning and memory in person or remotely. Neuropsychological results were converted to demographically-unadjusted global scaled scores for our primary outcome. A neighborhood socioeconomic deprivation variable (SESDep) was generated for census tracts in San Diego County using American Community Survey 2013-2017 data. Principal components analysis was used to create one measure using nine variables comprising educational (% with high school diploma), occupational (% unemployed), economic (rent to income ratio, % in poverty, (% female-headed households with dependent children, % with no car, % on public assistance), and housing (% rented housing, % crowded rooms) factors. Census tract SESDep values were averaged for a 1km radius buffer around participants’ home addresses.
Results:Univariable analyses (independent samples t-tests and Chi-square tests) indicated Latinos were more likely to be female and had fewer years of formal education than NL-Whites (ps<.05). Latino PWH had higher nadir CD4 than White PWH (p=.02). Separate multivariable regression models in the overall sample, controlling for demographics and HIV status, showed Latinos had significantly lower global scaled scores than Whites (b=-0.59; 95%CI-1.13, -0.06; p=.03) and lived in more deprived neighborhoods (b=0.62; 95%CI=0.36, 0.88; p<.001). More SES deprivation was significant associated with worse global neurocognition in an unadjusted linear regression (b=-0.55; 95%CI=-0.82, -0.28; p<.001), but similar analyses controlling for demographics and HIV status, showed SESDep was not significantly related to global scaled scores (b=-0.11; 95%CI= -0.36, 0.14; p=.40). Exploratory analyses examined primary language (i.e., English vs Spanish) as a marker of Hispanic heterogeneity and its association with neurocognition and SESDep. Controlling for demographics and HIV status, both English-speaking (b=0.33; 95%CI=0.01. 0.64; p=.04) and Spanish-speaking Latinos (b=0.88; 95%CI=0.58, 1.18; p<.001) lived in significantly greater SESDep neighborhoods than Whites, with SESDep greater for Spanish-speakers than English-speakers (p<.001). However, only English-speaking Latinos had significantly lower neurocognition than Whites (b=-0.91; 95%CI=0-1.57, -0.26; p<.01; Spanish-speakers: b=-0.27; 95%CI=-0.93, 0.38; p=.41).
Conclusions:Among our sample of diverse older adults living with and without HIV, English-speaking Latinos showed worse neurocognition than Whites. Though SES neighborhood deprivation was worse among Latinos (particularly Spanish-speakers) it was not associated with neurocognitive scores after adjusting for demographics. Further studies investigating other neighborhood characteristics and more nuanced markers of Hispanic heterogeneity (e.g., acculturation) are warranted to understand factors underlying aging and HIV-related neurocognitive disparities among diverse older adults.
72 Investigating Handedness and Cognitive Functions in People with Severe Mental Disorders
- Rune Raudeberg, Åsa Hammar, Marco Hirnstein, Charles E. Gaudet, Grant L. Iverson
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 856-857
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Our objective is to investigate whether handedness is associated with performance on verbal and visual neuropsychological tests in people with severe mental disorders. A recent study, applying a continuous scale of hand preference, reports that handedness is not associated with test performance in people with schizophrenia disorders. Conversely, in a recent large meta-analysis where handedness was applied as a dichotomous variable, right-handers had better performance in spatial ability (but not verbal ability) compared to left-handers, irrespective of gender or health status. We hypothesize that a dichotomous classification of handedness will reveal an advantage of right-handedness on tests of visuospatial functions—but not verbal functions—in people with severe mental disorders. We expect that gender will not be associated with the neuropsychological test results.
Participants and Methods:Data from a sample of 385 patients with severe mental disorders, mainly within the schizophrenia spectrum, were analyzed. All participants had Norwegian as their first language. Their mean age was 24.8 years (SD=6.2) and 153 (39.7%) were women. Handedness was evaluated by observation of preferred hand in writing and drawing during neuropsychological assessment. Chi-square tests were used to compare proportions of cases with reported frequencies of handedness in the general population and comparable clinical samples. Raw scores on Semantic Fluency and Line Orientation from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were analyzed using Mann-Whitney U tests, and possible effects of gender with two-way ANOVA. Frequencies of low scores were analyzed using frequency analyses.
Results:Overall prevalence of left-handers was 10.4% compared to 10.6% in the general population (χ2=.018, p=.893). Observed prevalence for women was 9.2% compared to expected prevalence of 9.5% (χ2=.026, p=.873) and for men 10.7% and 11.6%, respectively (χ2=.039, p=.844). There was a significant difference in Line Orientation scores (Mdright-handers=18, Mdleft-handers=17; U=5268.0, p=.013) but not Semantic Fluency scores (Mdright-handers=17, Mdleft-handers=18.5; U=7568.5, p=.315). Right-handed men had higher scores on Line Orientation but there was no handedness by gender interaction (F(1)=1.69, p=.194). For Semantic Fluency, left-handed men had higher scores and a gender by handedness interaction was found (F(1)=7.21, p=.008). Using scores corresponding to <5th percentile, 15% of left-handers and 8% of right-handers had scores <5th percentile on Line Orientation, as opposed to 15% and 14% on Semantic Fluency.
Conclusions:Right-handers had significantly better performance on a test measuring visuospatial function, irrespective of gender. Left-handers had about twice the number of scores in the impaired range (i.e., <5th percentile) compared to right-handers. Left-handed men had better performance on a test of verbal functions, which was unexpected. A recent study reported no right-hand associated advantage on visuospatial tests in people with schizophrenia disorders when measuring handedness on a continuous scale. This suggests that the classification of handedness as either a dichotomous or as a continuous variable is important in studies of handedness and cognitive functions.
4 Methamphetamine, cannabis, HIV, and their combined effects on neurocognition
- Jeffrey M Rogers, Igor Grant, Maria Cecilia Marcondes, Erin E Morgan, Mariana Cherner, Ronald J Ellis, Scott L Letendre, Robert K Heaton, Jennifer E Iudicello
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 797-798
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Objective:
Methamphetamine and cannabis are two widely used substances with possibly opposing effects on aspects of central nervous system functioning. Use of these substances is prevalent among people with HIV (PWH), though their combined effects on HIV-associated neurocognitive impairment (NCI) are unknown. Adverse effects of methamphetamine use on cognition are well documented. Cannabis may disturb cognition acutely, though its longer-term effects in PWH are not well understood. Our prior analysis of people without HIV (PWoH) found that cotemporaneous cannabis use was associated with better neurocognitive outcomes among methamphetamine users. The aim of this study was to assess how lifetime cannabis and methamphetamine use disorder relate to neurocognitive outcomes in PWH.
Participants and Methods:HIV-positive participants (n=472) were on average 45.6±11.5 years of age, male (86.4%), White (60.6%), and educated 13.9±2.5 years. Most participants were on ART (81.9%) and virally suppressed (70%). Participants were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n=187), M-C+ (n=68), M+C-, (n=82) and M+C+ (n=135) and completed a comprehensive neurobehavioral assessment. Demographically corrected T-scores and deficit scores were used for analyses. Group differences in global and domain NC performances (i.e., T-scores) were examined using multiple linear regression, holding constant covariates that were associated with study groups and/or cognition. Specifically, M+ participants displayed higher rates of Hepatitis C infection (p=.004), higher current depressive symptom scores (p<.001), and higher rates of detectable plasma HIV RNA (p=.014). Multiple logistic regression was used to test for group differences in probability of neurocognitive impairment (i.e., deficit scores>0.5), including the same covariates. Pooling data with a sample of HIV-negative participants (n=423), we used generalized linear mixed effect models to examine how neurocognitive performance and impairment profiles varied by methamphetamine and/or cannabis use group, HIV disease characteristics, and their interactions.
Results:Compared to M+C+, M+C- performed worse on measures of executive functions (ß=-3.17), learning (ß=-3.95), memory (ß=-5.58), and working memory (ß=-4.05) and were more likely to be classified as impaired in the learning (OR=2.93), memory (OR=5.24), and working memory (OR=2.48) domains. M-C- performed better than M+C+ on measures of learning (ß=3.46) and memory (ß=5.19), but worse than M-C+ on measures of executive functions (ß=-3.90), learning (ß=-3.32), memory (ß=-3.38), and working memory (ß=-3.38). Generalized linear mixed effect models indicate that detectable plasma HIV RNA (ß=-1.85) and low nadir CD4 T-cell counts (nadir CD4<200; ß=-1.07) were associated with worse neurocognitive performance, and these effects did not differ in size or direction by substance use group.
Conclusions:In PWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. Cannabis use disorder does not appear to exacerbate methamphetamine-related deficits in PWH. Instead, results are consistent with findings from preclinical studies that cannabis use may protect against methamphetamine’s deleterious effects. Profile analysis models showed that participants with a history of cannabis use disorder display better overall neurocognitive performance than comparison (M-C-) participants. Mechanisms underlying a potential protective effect of cannabis may be elucidated by examining the temporal relationship between cannabis and methamphetamine consumption and neurocognitive performance.
19 Preseason Neurocognitive Test Performance and Symptom Reporting Among Student Athletes with Autism Spectrum Disorders
- Nathan E. Cook, Ila A. Iverson, Bruce Maxwell, Ross Zafonte, Paul D. Berkner, Grant L. Iverson
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 628-629
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Participation in sports likely confers multiple benefits for children and adolescents with autism spectrum disorder (ASD). Adolescent student athletes often undergo preseason testing as part of a broader concussion management program for schools. This study compares preseason neurocognitive functioning and symptom reporting between high school athletes with and without ASD.
Participants and Methods:Participants were derived from a database of 60,751 adolescent student athletes from Maine (aged 13-18) who completed preseason testing between 2009 and 2019 and did not have missing data on the history question relating to ASD. There were 425 students (0.7%) who self-reported having been diagnosed with ASD in their health history. Cognitive functioning was measured by ImPACT, and the Post-Concussion Symptom Scale (PCSS) was used to obtain symptom ratings. Group differences between the ASD and the population control group on the five ImPACT cognitive test composite raw scores and the total symptom score from the PCSS were examined using Mann-Whitney U tests.
Results:Compared to the population control sample, those with ASD reported much greater rates of comorbid conditions: attention deficit/hyperactivity disorder (50.1% vs. 10.3%), special education (39.2% vs. 4.4%), learning disabilities (43.8% vs. 4.4%), and prior treatment for a psychiatric condition (23.4% vs. 7.5%). Groups differed significantly across all neurocognitive composites (p values <.002). However, all differences were negligible in terms of the magnitude of the effects (r values range from 0.01-0.03). The groups also differed significantly on the PCSS total symptom score (p<.001), but the magnitude of the difference was negligible (r=.031). Among boys, the ASD group endorsed 21 of the 22 symptoms at a greater rate. Among girls, the ASD group endorsed 11 of the 22 individual baseline symptoms at a greater rate than the control group. Examples of symptoms that were endorsed at a higher rate among both boys and girls with ASD: sensitivity to noise (girls: odds ratio, OR=4.38; boys: OR=4.99), numbness or tingling (girls: OR=3.67; boys: OR=3.25), difficulty remembering (girls: OR=2.01; boys: OR=2.49), difficulty concentrating (girls: OR=1.82; boys: OR=2.40), sleeping more than usual (girls: OR=1.94; boys: OR=1.97), sensitivity to light (girls: OR=1.82; boys: OR=1.76), sadness (girls: OR=1.72; boys: OR=2.56), nervousness (girls: OR=1.80; boys: OR=2.27), and feeling more emotional (girls: OR=1.79; boys: OR=2.84).
Conclusions:Students with ASD participating in organized sports are likely high functioning, on average. There were small differences in their cognitive test scores compared to the population control sample. They endorsed more symptoms, however, during baseline preseason testing. If they sustain a concussion, their clinical management should be more intensive to maximize the likelihood of swift and favorable recovery.
3 The Relationship Between Apolipoprotein-E4 Genotype, Memory, and the Medial Temporal Lobe and How These Relationships Vary by Race in Middle-Aged Persons with HIV
- Laura M Campbell, Maulika Kohli, Erin E Sundermann, Christine Fennema-Notestine, Averi Barrett, Cinnamon Bloss, Mark W Bondi, David B Clifford, Ronald J Ellis, Donald Franklin, Benjamin Gelman, Igor Grant, Robert K Heaton, Scott Letendre, Payal B Patel, David J Moore, Susan Morgello, Raeanne C Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 683-684
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Objective:
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
GWAS of Dizygotic Twinning in an Enlarged Australian Sample of Mothers of DZ Twins
- Scott D. Gordon, David L. Duffy, David C. Whiteman, Catherine M. Olsen, Kerrie McAloney, Jessica M. Adsett, Natalie A. Garden, Simone M. Cross, Susan E. List-Armitage, Joy Brown, Jeffrey J. Beck, Hamdi Mbarek, Sarah E. Medland, Grant W. Montgomery, Nicholas G. Martin
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- Journal:
- Twin Research and Human Genetics / Volume 26 / Issue 6 / December 2023
- Published online by Cambridge University Press:
- 23 November 2023, pp. 327-338
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Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).
RADIOCARBON ANALYSIS OF SOIL MICROBIAL BIOMASS VIA DIRECT CHLOROFORM EXTRACTION
- Kari M Finstad, Erin E Nuccio, Katherine E Grant, Taylor A B Broek, Jennifer Pett-Ridge, Karis J McFarlane
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- Radiocarbon , First View
- Published online by Cambridge University Press:
- 02 October 2023, pp. 1-9
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Microbial processing of soil organic matter is a significant driver of C cycling, yet we lack an understanding of what shapes the turnover of this large terrestrial pool. In part, this is due to limited options for accurately identifying the source of C assimilated by microbial communities. Laboratory incubations are the most common method for this; however, they can introduce artifacts due to sample disruption and processing and can take months to produce sufficient CO2 for analysis. We present a biomass extraction method which allows for the direct 14C analysis of microbial biomolecules and compare the results to laboratory incubations. In the upper 50 cm soil depths, the Δ14C from incubations was indistinguishable from that of extracted microbial biomass. Below 50 cm, the Δ14C of the biomass was more depleted than that of the incubations, either due to the stimulation of labile C decomposition in the incubations, the inclusion of biomolecules from non-living cells in the biomass extractions, or differences in C used for assimilation versus respiration. Our results suggest that measurement of Δ14C of microbial biomass extracts can be a useful alternative to soil incubations.
Duration of untreated illness in gambling disorder
- Jon E. Grant, Samuel R. Chamberlain
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- Journal:
- CNS Spectrums / Volume 29 / Issue 1 / February 2024
- Published online by Cambridge University Press:
- 11 September 2023, pp. 54-59
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Objective
Gambling disorder is common, affects 0.5–2% of the population, and is under-treated. Duration of untreated illness (DUI) has emerged as a clinically important concept in the context of other mental disorders, but DUI in gambling disorder, has received little research scrutiny.
MethodsData were aggregated from previous clinical trials in gambling disorder with people who had never previously received any treatment. DUI was quantified, and clinical characteristics were compared as a function of DUI status.
ResultsA total of 298 individuals were included, and the mean DUI (standard deviation) was 8.9 (8.4) years, and the median DUI was 6 years. Longer DUI was significantly associated with male gender, older age, earlier age when the person first started to gamble, and family history of alcohol use disorder. Longer DUI was not significantly associated with racial-ethnic status, gambling symptom severity, current depressive or anxiety severity, comorbidities, or disability/functioning. The two groups did not differ in their propensity to drop out of the clinical trials, nor in overall symptom improvement associated with participation in those trials.
ConclusionsThese data suggest that gambling disorder has a relatively long DUI and highlight the need to raise awareness and foster early intervention for affected and at-risk individuals. Because earlier age at first gambling in any form was strongly linked to longer DUI, this highlights the need for more rigorous legislation and education to reduce exposure of younger people to gambling.
The effect of a prospective intervention program with automated monitoring of hand hygiene performance in long-term and acute-care units at a Veterans Affairs medical center
- W. Grant Starrett, James W. Arbogast, Albert E. Parker, Pamela T. Wagner, Susan E. Mahrer, Vanessa Christian, Barbara L. Lane, V. Lorraine Cheek, Gregory A. Robbins, John M. Boyce, Hari Polenakovik
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 45 / Issue 2 / February 2024
- Published online by Cambridge University Press:
- 31 August 2023, pp. 207-214
- Print publication:
- February 2024
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Objective:
To measure the impact of an automated hand hygiene monitoring system (AHHMS) and an intervention program of complementary strategies on hand hygiene (HH) performance in both acute-care and long-term care (LTC) units.
Design:Prospective, nonrandomized, before-and-after intervention study.
Setting:Single Veterans Affairs Medical Center (VAMC), with 2 acute-care units and 6 LTC units.
Methods:An AHHMS that provides group HH performance rates was implemented on 8 units at a VAMC from March 2021 through April 2022. After a 4-week baseline period and 2.5-week washout period, the 52-week intervention period included multiple evidence-based components designed to improve HH compliance. Unit HH performance rates were expressed as the number of dispenses (events) divided by the number of patient room entries and exits (opportunities) × 100. Statistical analysis was performed with a Poisson general additive mixed model.
Results:During the 4-week baseline period, the median HH performance rate was 18.6 (95% CI, 16.5–21.0) for all 8 units. During the intervention period, the median HH rate increased to 21.6 (95% CI, 19.1–24.4; P < .0001), and during the last 4 weeks of the intervention period (exactly 1 year after baseline), the 8 units exhibited a median HH rate of 25.1 (95% CI, 22.2–28.4; P < .0001). The median HH rate increased from 17.5 to 20.0 (P < .0001) in LTC units and from 22.9 to 27.2 (P < .0001) in acute-care units.
Conclusions:The intervention was associated with increased HH performance rates for all units. The performance of acute-care units was consistently higher than LTC units, which have more visitors and more mobile veterans.
Cannabis use may attenuate neurocognitive performance deficits resulting from methamphetamine use disorder
- Jeffrey M. Rogers, Igor Grant, Maria Cecilia G. Marcondes, Erin E. Morgan, Mariana Cherner, Ronald J. Ellis, Scott L. Letendre, Robert K. Heaton, Jennifer E. Iudicello
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- Journal of the International Neuropsychological Society / Volume 30 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 09 August 2023, pp. 84-93
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Objective:
Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders.
Method:423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M−/M+) and/or cannabis (C−/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition.
Results:Globally, M+C+ performed worse than M−C− but better than M+C−. M+C+ outperformed M+C− on measures of verbal fluency, information processing speed, learning, memory, and working memory. M−C+ did not display lower performance than M−C− globally or on any domain measures, and M−C+ even performed better than M−C− on measures of learning, memory, and working memory.
Conclusions:Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.
Impaired cognitive flexibility across psychiatric disorders
- Jon E. Grant, Samuel R. Chamberlain
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- Journal:
- CNS Spectrums / Volume 28 / Issue 6 / December 2023
- Published online by Cambridge University Press:
- 28 April 2023, pp. 688-692
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Objective
Problems with cognitive flexibility have been associated with multiple psychiatric disorders, but there has been little understanding of how cognitive flexibility compares across these disorders. This study examined problems of cognitive flexibility in young adults across a range of psychiatric disorders using a validated computerized trans-diagnostic flexibility paradigm. We hypothesized that obsessive-compulsive spectrum disorders (eg, obsessive-compulsive disorder, trichotillomania, and skin-picking disorder) would be associated with pronounced flexibility problems as they are most often associated with irrational or purposeless repetitive behaviors.
MethodsA total of 576 nontreatment seeking participants (aged 18-29 years) were enrolled from general community settings, provided demographic information, and underwent structured clinical assessments. Each participant undertook the intra-extra-dimensional task, a validated computerized test measuring set-shifting ability. The specific measures of interest were total errors on the task and performance on the extra-dimensional (ED) shift, which reflects the ability to inhibit and shift attention away from one stimulus dimension to another.
ResultsParticipants with depression and PTSD had elevated total errors on the task with moderate effect sizes; and those with the following had deficits of small effect size: generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), antisocial personality disorder, and binge-eating disorder. For ED errors, participants with PTSD, GAD, and binge-eating disorder exhibited deficits with medium effect sizes; those with the following had small effect size deficits: depression, social anxiety disorder, OCD, substance dependence, antisocial personality disorder, and gambling disorder.
ConclusionsThese data indicate cognitive flexibility deficits occur across a range of mental disorders. Future work should explore whether these deficits can be ameliorated with novel treatment interventions.
Associations between acute and chronic lifetime stressors and psychosis-risk symptoms in individuals with 22q11.2 copy number variants
- Jasmine Modasi, Vahe Khachadourian, Kathleen O'Hora, Leila Kushan, George M. Slavich, Grant S. Shields, Eva Velthorst, Carrie E. Bearden
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- Journal:
- Psychological Medicine / Volume 53 / Issue 15 / November 2023
- Published online by Cambridge University Press:
- 20 April 2023, pp. 7222-7231
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Background
The 22q11.2 deletion (22q11Del) is among the strongest known genetic risk factors for psychosis. Stress, a known risk factor for psychosis in the general population, has seldom been studied in 22q11Del. We investigated how lifetime stressors related to symptomatic outcomes in patients with 22q11Del. We also explored this association in individuals with 22q11.2 duplications (22q11Dup), which may be potentially protective against psychosis.
MethodOne hundred individuals (46 with 22q11Del, 30 with 22q11Dup, and 24 healthy controls; Mage = 17.30 years±10.15) were included. Logistic models were used to examine cross-sectional associations between lifetime acute and chronic stressors (severity and count) and the presence (score ⩾3) of positive, negative, and general symptoms, assessed via the Structured Interview for Psychosis-risk Syndromes (SIPS).
ResultsThe 22q11Dup group reported the greatest number and severity of acute lifetime stressors, but did not differ from 22q11Del in chronic stressor count or severity. Lifetime chronic and acute stressors were uniquely associated with positive symptoms in 22q11Del (chronic count: odds ratio [OR] = 2.35, p = 0.02; chronic severity: OR = 1.88, p = 0.03; acute count: OR = 1.78, p = 0.03), but not with negative or general symptoms (ps > 0.05).
ConclusionFindings suggest that stress may play a role in psychotic symptoms in 22q1Del, while the 22q11Dup CNV appears protective against psychotic symptoms despite higher rates of stressors. Interventions that mitigate effects of stressors in 22qDel may reduce the odds of psychosis in this group. Prospective longitudinal research is needed to replicate these findings.
Cognition in adults with borderline personality disorder
- Ibrahim H. Aslan, Jon E. Grant, Samuel R. Chamberlain
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- Journal:
- CNS Spectrums / Volume 28 / Issue 6 / December 2023
- Published online by Cambridge University Press:
- 16 March 2023, pp. 674-679
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Objective
Borderline personality disorder (BPD) is a common and disabling mental health disorder and has detrimental effects on affected individuals across multiple domains. We aimed to investigate whether individuals with BPD differ from control subjects in terms of cognitive functions, and to see if there is a relationship between cognitive functions, impulsivity, and BPD symptom severity.
MethodsBPD individuals (n = 26; mean age = 26.7; 69.2% female) and controls (n = 58; mean age = 25.3; 51.7% female) were enrolled. Intra/Extra-Dimensional Set Shift (IED) and One Touch Stockings of Cambridge (OTS) tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess cognitive functions. Barratt Impulsivity Scale-version 11 (BIS−11) was administered to measure impulsivity and both the Zanarini Scale for Borderline Personality Disorder self-report and the clinician-administered versions were used to assess BPD symptom severity.
ResultsBPD group showed significantly impaired cognitive performance on the IED task versus controls, but there was not a significant difference in the OTS task. BPD symptom severity was positively correlated with trait (BIS-11) impulsivity and no correlation was found between BPD symptom severity and cognitive functions.
ConclusionsThis study suggests people with BPD experience impaired cognitive flexibility and heightened impulsivity. Only impulsivity appeared to be directly related to symptom severity, perhaps indicating that cognitive inflexibility could be a vulnerability marker. Future research should focus on a longitudinal approach to extend clinical and theoretical knowledge in this area.
Contents
- Jon E. Grant, University of Chicago, Samuel R. Chamberlain, University of Southampton
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- Impulse
- Published online:
- 09 February 2023
- Print publication:
- 09 February 2023, pp v-vi
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