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Levofloxacin prophylaxis for pediatric leukemia patients: monitoring of outcomes for sustained benefit and consequences
- Andrea L. Davis, Alexandra M. Stevens, Julienne Brackett, Lucila Marquez, Catherine E. Foster, Adriana Sarmiento Clemente, Hannah E. Sauer, Grant T. Stimes, Judith R. Campbell
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- Journal:
- Antimicrobial Stewardship & Healthcare Epidemiology / Volume 4 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 22 May 2024, e90
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Levofloxacin prophylaxis reduces bloodstream infections in neutropenic patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. A retrospective, longitudinal cohort study compares incidence of bacteremia, multidrug-resistant organisms (MDRO), and Clostridioides difficile (CDI) between time periods of levofloxacin prophylaxis implementation. Benefits were sustained without increasing MDRO or CDI.
Non-suicidal self-injury in trichotillomania and skin picking disorder
- Jon E. Grant, Madison Collins
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- CNS Spectrums , First View
- Published online by Cambridge University Press:
- 17 May 2024, pp. 1-5
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Background
Trichotillomania and skin picking disorder have been characterized as body-focused repetitive behavior (BFRB) disorders (i.e., repetitive self-grooming behaviors that involve biting, pulling, picking, or scraping one’s own hair, skin, lips, cheeks, or nails). Trichotillomania and skin picking disorder have also historically been classified, by some, as types of compulsive self-injury as they involve repetitive hair pulling and skin picking, respectively. The question of the relationship of these disorders to more conventional forms of self-injury such as cutting or self-burning remains incompletely investigated. The objective of this study was to examine the relationship of these two disorders with non-suicidal self-injury (NSSI).
MethodsAdults with trichotillomania (n = 93) and skin picking (n = 105) or both (n = 82) were recruited from the general population using advertisements and online support groups and completed an online survey. Participants completed self-report instruments to characterize clinical profiles and associated characteristics. In addition, each participant completed a mental health history questionnaire.
ResultsOf the 280 adults with BFRB disorders, 141 (50.1%) reported a history of self-injury independent of hair pulling and skin picking. Participants with a history of self-injury reported significantly worse pulling and picking symptoms (p < .001) and were significantly more likely to have co-occurring alcohol problems (p < .001), borderline personality disorder (p < .001), buying disorder (p < .001), gambling disorder (p < .001), compulsive sex behavior (p < 001), and binge eating disorder (p = .041).
ConclusionsNSSI appears common in trichotillomania and skin picking disorder and may be part of a larger constellation of behaviors associated with impulse control or reward-related dysfunction.
Lifetime alcohol use disorder and gambling disorder: clinical profile and treatment response
- Samuel R. Chamberlain, Konstantinos Ioannidis, Jon E. Grant
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- Journal:
- CNS Spectrums , First View
- Published online by Cambridge University Press:
- 17 May 2024, pp. 1-6
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Objectives
Gambling disorder affects 0.5–2.4% of the population and shows strong associations with lifetime alcohol use disorder. Very little is known regarding whether lifetime alcohol use disorder can impact the clinical presentation or outcome trajectory of gambling disorder.
MethodsData were pooled from previous clinical trials conducted on people with gambling disorder, none of whom had current alcohol use disorder. Demographic and clinical variables were compared between those who did versus did not have lifetime alcohol use disorder.
ResultsOf the 621 participants in the clinical trials, 103 (16.6%) had a lifetime history of alcohol use disorder. History of alcohol use disorder was significantly associated with male gender (relative risk [RR] = 1.42), greater body weight (Cohen’s D = 0.27), family history of alcohol use disorder in first-degree relative(s) (RR = 1.46), occurrence of previous hospitalization due to psychiatric illness (RR = 2.68), and higher gambling-related legal problems (RR = 1.50). History of alcohol use disorder was not significantly associated with other variables that were examined, such as severity of gambling disorder or extent of functional disability. Lifetime alcohol use disorder was not significantly associated with the extent of clinical improvement in gambling disorder symptoms during the subsequent clinical trials.
ConclusionsThese data highlight that lifetime alcohol use disorder is an important clinical variable to be considered when assessing gambling disorder because it is associated with several untoward features (especially gambling-related legal problems and prior psychiatric hospitalization). The study design enabled these associations to be disambiguated from current or recent alcohol use disorder.
Examining the unique relationships between problematic use of the internet and impulsive and compulsive tendencies: network approach
- Chang Liu, Kristian Rotaru, Lei Ren, Samuel R. Chamberlain, Erynn Christensen, Mary-Ellen Brierley, Karyn Richardson, Rico S. C. Lee, Rebecca Segrave, Jon E. Grant, Edouard Kayayan, Sam Hughes, Leonardo F. Fontenelle, Amelia Lowe, Chao Suo, René Freichel, Reinout W. Wiers, Murat Yücel, Lucy Albertella
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- Journal:
- BJPsych Open / Volume 10 / Issue 3 / May 2024
- Published online by Cambridge University Press:
- 09 May 2024, e104
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Background
Both impulsivity and compulsivity have been identified as risk factors for problematic use of the internet (PUI). Yet little is known about the relationship between impulsivity, compulsivity and individual PUI symptoms, limiting a more precise understanding of mechanisms underlying PUI.
AimsThe current study is the first to use network analysis to (a) examine the unique association among impulsivity, compulsivity and PUI symptoms, and (b) identify the most influential drivers in relation to the PUI symptom community.
MethodWe estimated a Gaussian graphical model consisting of five facets of impulsivity, compulsivity and individual PUI symptoms among 370 Australian adults (51.1% female, mean age = 29.8, s.d. = 11.1). Network structure and bridge expected influence were examined to elucidate differential associations among impulsivity, compulsivity and PUI symptoms, as well as identify influential nodes bridging impulsivity, compulsivity and PUI symptoms.
ResultsResults revealed that four facets of impulsivity (i.e. negative urgency, positive urgency, lack of premeditation and lack of perseverance) and compulsivity were related to different PUI symptoms. Further, compulsivity and negative urgency were the most influential nodes in relation to the PUI symptom community due to their highest bridge expected influence.
ConclusionsThe current findings delineate distinct relationships across impulsivity, compulsivity and PUI, which offer insights into potential mechanistic pathways and targets for future interventions in this space. To realise this potential, future studies are needed to replicate the identified network structure in different populations and determine the directionality of the relationships among impulsivity, compulsivity and PUI symptoms.
Emotion regulation across psychiatric disorders
- Ibrahim H. Aslan, Lucy Dorey, Jon E. Grant, Samuel R. Chamberlain
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- Journal:
- CNS Spectrums / Volume 29 / Issue 3 / June 2024
- Published online by Cambridge University Press:
- 02 May 2024, pp. 215-220
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Objective
Difficulties with emotion regulation have been associated with multiple psychiatric conditions. In this study, we aimed to investigate emotional regulation difficulties in young adults who gamble at least occasionally (ie, an enriched sample), and diagnosed with a range of psychiatric disorders using the validated Difficulties in Emotion Regulation Scale (DERS).
MethodsA total of 543 non-treatment-seeking individuals who had engaged in gambling activities on at least 5 occasions within the previous year, aged 18–29 were recruited from general community settings. Diagnostic assessments included the Mini International Neuropsychiatric Inventory, Minnesota Impulsive Disorders Interview, attention-deficit/hyperactivity disorder World Health Organization Screening Tool Part A, and the Structured Clinical Interview for Gambling Disorder. Emotional dysregulation was evaluated using DERS. The profile of emotional dysregulation across disorders was characterized using Z-scores (those with the index disorder vs. those without the index disorder).
ResultsIndividuals with probable ADHD displayed the highest level of difficulties in emotional regulation, followed by intermittent explosive disorder, social phobia, and generalized anxiety disorder. In contrast, participants diagnosed with obsessive-compulsive disorder showed relatively lower levels of difficulties with emotional regulation.
ConclusionsThis study highlights the importance of recognizing emotional dysregulation as a trans-diagnostic phenomenon across psychiatric disorders. The results also reveal differing levels of emotional dysregulation across diagnoses, with potential implications for tailored treatment approaches. Despite limitations such as small sample sizes for certain disorders and limited age range, this study contributes to a broader understanding of emotional regulation’s role in psychiatric conditions.
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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- Journal:
- CNS Spectrums / Volume 29 / Issue 3 / June 2024
- Published online by Cambridge University Press:
- 15 March 2024, pp. 166-175
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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).
Head and Neck Cancer: United Kingdom National Multidisciplinary Guidelines, Sixth Edition
- Jarrod J Homer, Stuart C Winter, Elizabeth C Abbey, Hiba Aga, Reshma Agrawal, Derfel ap Dafydd, Takhar Arunjit, Patrick Axon, Eleanor Aynsley, Izhar N Bagwan, Arun Batra, Donna Begg, Jonathan M Bernstein, Guy Betts, Colin Bicknell, Brian Bisase, Grainne C Brady, Peter Brennan, Aina Brunet, Val Bryant, Linda Cantwell, Ashish Chandra, Preetha Chengot, Melvin L K Chua, Peter Clarke, Gemma Clunie, Margaret Coffey, Clare Conlon, David I Conway, Florence Cook, Matthew R Cooper, Declan Costello, Ben Cosway, Neil J A Cozens, Grant Creaney, Daljit K Gahir, Stephen Damato, Joe Davies, Katharine S Davies, Alina D Dragan, Yong Du, Mark R D Edmond, Stefano Fedele, Harriet Finze, Jason C Fleming, Bernadette H Foran, Beth Fordham, Mohammed M A S Foridi, Lesley Freeman, Katherine E Frew, Pallavi Gaitonde, Victoria Gallyer, Fraser W Gibb, Sinclair M Gore, Mark Gormley, Roganie Govender, J Greedy, Teresa Guerrero Urbano, Dorothy Gujral, David W Hamilton, John C Hardman, Kevin Harrington, Samantha Holmes, Jarrod J Homer, Deborah Howland, Gerald Humphris, Keith D Hunter, Kate Ingarfield, Richard Irving, Kristina Isand, Yatin Jain, Sachin Jauhar, Sarra Jawad, Glyndwr W Jenkins, Anastasios Kanatas, Stephen Keohane, Cyrus J Kerawala, William Keys, Emma V King, Anthony Kong, Fiona Lalloo, Kirsten Laws, Samuel C Leong, Shane Lester, Miles Levy, Ken Lingley, Gitta Madani, Navin Mani, Paolo L Matteucci, Catriona R Mayland, James McCaul, Lorna K McCaul, Pádraig McDonnell, Andrew McPartlin, Valeria Mercadante, Zoe Merchant, Radu Mihai, Mufaddal T Moonim, John Moore, Paul Nankivell, Sonali Natu, A Nelson, Pablo Nenclares, Kate Newbold, Carrie Newland, Ailsa J Nicol, Iain J Nixon, Rupert Obholzer, James T O'Hara, S Orr, Vinidh Paleri, James Palmer, Rachel S Parry, Claire Paterson, Gillian Patterson, Joanne M Patterson, Miranda Payne, L Pearson, David N Poller, Jonathan Pollock, Stephen Ross Porter, Matthew Potter, Robin J D Prestwich, Ruth Price, Mani Ragbir, Meena S Ranka, Max Robinson, Justin W G Roe, Tom Roques, Aleix Rovira, Sajid Sainuddin, I J Salmon, Ann Sandison, Andy Scarsbrook, Andrew G Schache, A Scott, Diane Sellstrom, Cherith J Semple, Jagrit Shah, Praveen Sharma, Richard J Shaw, Somiah Siddiq, Priyamal Silva, Ricard Simo, Rabin P Singh, Maria Smith, Rebekah Smith, Toby Oliver Smith, Sanjai Sood, Francis W Stafford, Neil Steven, Kay Stewart, Lisa Stoner, Steve Sweeney, Andrew Sykes, Carly L Taylor, Selvam Thavaraj, David J Thomson, Jane Thornton, Neil S Tolley, Nancy Turnbull, Sriram Vaidyanathan, Leandros Vassiliou, John Waas, Kelly Wade-McBane, Donna Wakefield, Amy Ward, Laura Warner, Laura-Jayne Watson, H Watts, Christina Wilson, Stuart C Winter, Winson Wong, Chui-Yan Yip, Kent Yip
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- Journal:
- The Journal of Laryngology & Otology / Volume 138 / Issue S1 / April 2024
- Published online by Cambridge University Press:
- 14 March 2024, pp. S1-S224
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- April 2024
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Cognition in trichotillomania: a meta-analysis
- Aliza Ali, Konstantinos Ioannidis, Jon E. Grant, Samuel R. Chamberlain
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- CNS Spectrums / Volume 29 / Issue 3 / June 2024
- Published online by Cambridge University Press:
- 13 March 2024, pp. 158-165
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Objective
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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Objective:
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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Objective:
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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Objective:
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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Objective:
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.