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The impact of social-environmental factors on IQ in syndromic intellectual developmental disabilities
- Walker S. McKinney, Desireé N. Williford, Leonard Abbeduto, Lauren M. Schmitt
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 05 April 2024, e59
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Despite having the same underlying genetic etiology, individuals with the same syndromic form of intellectual developmental disability (IDD) show a large degree of interindividual differences in cognition and IQ. Research indicates that up to 80% of the variation in IQ scores among individuals with syndromic IDDs is attributable to nongenetic effects, including social-environmental factors. In this narrative review, we summarize evidence of the influence that factors related to economic stability (focused on due to its prevalence in existing literature) have on IQ in individuals with syndromic IDDs. We also highlight the pathways through which economic stability is hypothesized to impact cognitive development and drive individual differences in IQ among individuals with syndromic IDDs. We also identify broader social-environmental factors (e.g., social determinants of health) that warrant consideration in future research, but that have not yet been explored in syndromic IDDs. We conclude by making recommendations to address the urgent need for further research into other salient factors associated with heterogeneity in IQ. These recommendations ultimately may shape individual- and community-level interventions and may inform systems-level public policy efforts to promote the cognitive development of and improve the lived experiences of individuals with syndromic IDDs.
316 Machine Learning to Predict Fluid Responsiveness in Hypotensive Children
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- Sarah B. Walker, Kyle S. Honegger, Michael S. Carroll, Debra E. Weese-Mayer, L. Nelson Sanchez-Pinto
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 97
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OBJECTIVES/GOALS: Fluid boluses are administered to hypotensive, critically ill children but may not reverse hypotension, leading to delay of vasoactive infusion, end-organ damage, and mortality. We hypothesize that a machine learning-based model will predict which children will have sustained response to fluid bolus. METHODS/STUDY POPULATION: We will conduct a single-center retrospective observational cohort study of hypotensive critically ill children who received intravenous isotonic fluid of at least 10 ml/kg within 72 hours of pediatric intensive care unit admission between 2013 and 2023. We will extract physiologic variables from stored bedside monitors data and clinical variables from the EHR. Fluid responsive (FR) will be defined as a MAP increase by 310%. We will construct elastic net, random forest, and a long short-term memory models to predict FR. We will compare complicated course (multiple organ dysfunction on day 7 or death by day 28) between: 1) FRs and non-FRs, 2) predicted FRs and non-FRs, 3), FRs and non-FRs stratified by race/ethnicity, and 4) FRs and non-FRs stratified by sex as a biologic variable. RESULTS/ANTICIPATED RESULTS: We anticipate approximately 800 critically ill children will receive 2,000 intravenous isotonic fluid boluses, with a 60% rate of FR. We anticipate being able to complete all three models. We hypothesize that the model with the best performance will be the long short-term memory model and the easiest to interpret will be the tree-based random forest model. We hypothesize non-FRs will have a higher complicated course than FRs and that predicted non-FRs will have a higher rate of complicated course than FRs. Based on previous adult studies, we hypothesize that there will be a higher rate of complicated course in patients of black race and/or Hispanic ethnicity when compared to non-Hispanic white patients. We also hypothesize that there will be no difference in complicated course when comparing sex as a biologic variable. DISCUSSION/SIGNIFICANCE: We have a critical need for easily-deployed, real-time prediction of fluid response to personalize and improve resuscitation for children in shock. We anticipate the clinical application of such a model will decrease time with hypotension for critically ill children, leading to decreased morbidity and mortality.
Developmental perspectives on the origins of psychotic disorders: The need for a transdiagnostic approach
- Elaine F. Walker, Katrina Aberizk, Emerald Yuan, Zarina Bilgrami, Benson S. Ku, Ryan M. Guest
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- Development and Psychopathology , First View
- Published online by Cambridge University Press:
- 26 February 2024, pp. 1-11
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Research on serious mental disorders, particularly psychosis, has revealed highly variable symptom profiles and developmental trajectories prior to illness-onset. As Dante Cicchetti pointed out decades before the term “transdiagnostic” was widely used, the pathways to psychopathology emerge in a system involving equifinality and multifinality. Like most other psychological disorders, psychosis is associated with multiple domains of risk factors, both genetic and environmental, and there are many transdiagnostic developmental pathways that can lead to psychotic syndromes. In this article, we discuss our current understanding of heterogeneity in the etiology of psychosis and its implications for approaches to conceptualizing etiology and research. We highlight the need for examining risk factors at multiple levels and to increase the emphasis on transdiagnostic developmental trajectories as a key variable associated with etiologic subtypes. This will be increasingly feasible now that large, longitudinal datasets are becoming available and researchers have access to more sophisticated analytic tools, such as machine learning, which can identify more homogenous subtypes with the ultimate goal of enhancing options for treatment and preventive intervention.
The association between neighborhood-level social fragmentation and distressing psychotic-like experiences in early adolescence: the moderating role of close friends
- Benson S. Ku, Jiyuan Ren, Michael T. Compton, Benjamin G. Druss, Shuyi Guo, Elaine F. Walker
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 16 February 2024, pp. 1-9
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Background
Early exposure to neighborhood social fragmentation has been shown to be associated with schizophrenia. The impact of social fragmentation and friendships on distressing psychotic-like experiences (PLE) remains unknown. We investigate the relationships between neighborhood social fragmentation, number of friends, and distressing PLE among early adolescents.
MethodsData were collected from the Adolescent Brain Cognitive Development Study. Generalized linear mixed models tested associations between social fragmentation and distressing PLE, as well as the moderating role of the number of total and close friends.
ResultsParticipants included 11 133 adolescents aged 9 to 10, with 52.3% being males. Greater neighborhood social fragmentation was associated with higher levels of distressing PLE (adjusted β = 0.05; 95% CI: 0.01–0.09). The number of close but not total friends significantly interacted with social fragmentation to predict distressing PLE (adjusted β = −0.02; 95% CI: −0.04 to <−0.01). Among those with fewer close friends, the association between neighborhood social fragmentation and distressing PLE was significant (adjusted β = 0.07; 95% CI: 0.03–0.11). However, among those with more close friends, the association was non-significant (adjusted β = 0.03; 95% CI: −0.01 to 0.07).
ConclusionsGreater neighborhood social fragmentation is associated with higher levels of distressing PLE, particularly among those with fewer close friends. Further research is needed to disentangle aspects of the interaction between neighborhood characteristics and the quality of social interactions that may contribute to psychosis, which would have implications for developing effective interventions at the individual and community levels.
FC30: The relationships between neuroticism, social connection and cognition
- Jennifer Bethell, Melissa K. Andrew, Paul Mick, Debra Morgan, Megan E. O’Connell, Natalie A. Phillips, Steven Stewart, Jennifer D. Walker, Walter Wittich, Katherine S. McGilton
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- Journal:
- International Psychogeriatrics / Volume 35 / Issue S1 / December 2023
- Published online by Cambridge University Press:
- 02 February 2024, pp. 92-94
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Background:
Social connection is associated with better health, including reduced risk of dementia. Personality traits are also linked to cognitive outcomes; neuroticism is associated with increased risk of dementia. Personality traits and social connection are also associated with each other. Taken together, evidence suggests the potential impacts of neuroticism and social connection on cognitive outcomes may be linked. However, very few studies have simultaneously examined the relationships between personality, social connection and health.
Research objective:We tested the association between neuroticism and cognitive measures while exploring the potential mediating roles of aspects of social connection (loneliness and social isolation).
Method:We conducted a cross-sectional study with a secondary analysis of the Canadian Longitudinal Study on Aging (CLSA) Comprehensive Cohort, a sample of Canadians aged 45 to 85 years at baseline. We used only self-reported data collected at the first follow-up, between 2015 and 2018 (n= 27,765). We used structural equation modelling to assess the association between neuroticism (exposure) and six cognitive measures (Rey Auditory Verbal Learning Test immediate recall and delayed recall, Animal Fluency Test, Mental Alternation Test, Controlled Oral Word Association Test and Stroop Test interference ratio), with direct and indirect effects (through social isolation and loneliness). We included age, education and hearing in the models and stratified all analyses by sex, females (n= 14,133) and males (n=13,632).
Preliminary results of the ongoing study:We found positive, statistically significant associations between neuroticism and social isolation (p<0.05) and loneliness (p<0.05), for both males and females. We also found inverse, statistically significant associations between neuroticism and all cognitive measures (p<0.05), except the Stroop Test interference ratio. In these models, there was consistent evidence of indirect effects (through social isolation and loneliness) and, in some cases, evidence of direct effects. We found sex differences in the model results.
Conclusion:Our findings suggest that the association between neuroticism and cognitive outcomes may be mediated by aspects of social connection and differ by sex. Understanding if and how modifiable risk factors mediate the association between personality and cognitive outcomes would help develop and target intervention strategies that improve social connection and brain health.
2 Cognitive Heterogeneity and Risk of Progression in Data-Driven Subtle Cognitive Decline Phenotypes
- Kelsey R Thomas, Katherine J Bangen, Alexandra J Weigand, Gema Ortiz, Kayla S Walker, David P Salmon, Mark W Bondi, Emily C Edmonds
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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. 103-104
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Objective:
There is increasing recognition of cognitive and pathological heterogeneity in early-stage Alzheimer’s disease and other dementias. Data-driven approaches have demonstrated cognitive heterogeneity in those with mild cognitive impairment (MCI), but few studies have examined this heterogeneity and its association with progression to MCI/dementia in cognitively unimpaired (CU) older adults. We identified cluster-derived subgroups of CU participants based on comprehensive neuropsychological data and compared baseline characteristics and rates of progression to MCI/dementia or a Dementia Rating Scale (DRS) of <129 across subgroups.
Participants and Methods:A hierarchical cluster analysis was conducted using 11 baseline neuropsychological test scores from 365 CU participants in the UCSD Shiley-Marcos Alzheimer’s Disease Research Center (age M=71.93 years, SD=7.51; 55.9% women; 15.6% Hispanic/Latino/a/x/e). A discriminate function analysis was then conducted to test whether the individual neuropsychological scores predicted cluster-group membership. Cox regressions examined the risk of progression to consensus diagnosis of MCI or dementia, or to DRS score <129, by cluster group.
Results:Cluster analysis identified 5 groups: All-Average (n=139), Low-Visuospatial (n=46), Low-Executive (n=51), Low-Memory/Language (n=83), and Low-All Domains (n=46). The discriminant function analysis using the neuropsychological measures to predict group membership into these 5 clusters correctly classified 85.2% of the participants. Subgroups had unique demographic and clinical characteristics. Relative to the All-Average group, the Low-Visuospatial (hazard ratio [HR] 2.39, 95% CI [1.03, 5.56], p=.044), Low-Memory/Language (HR 4.37, 95% CI [2.24, 8.51], p<.001), and Low-All Domains (HR 7.21, 95% CI [3.59, 14.48], p<.001) groups had greater risk of progression to MCI/dementia. The Low-Executive group was also twice as likely to progress to MCI/dementia compared to the AllAverage group, but did not statistically differ (HR 2.03, 95% CI [0.88,4.70], p=.096). A similar pattern of results was found for progression to DRS score <129, with the Low-Executive (HR 2.82, 95% CI [1.26, 6.29], p=.012), Low-Memory/Language (HR 3.70, 95% CI [1.80, 7.56], p<.001) and Low-All Domains (HR 5.79, 95% CI [2.74, 12.27], p<.001) groups at greater risk of progression to a DRS score <129 than the All-Average group. The Low-Visuospatial group was also twice as likely to progress to DRS <129 compared to the All-Average group, but did not statistically differ (HR 2.02, 95% CI [0.80, 5.06], p=.135).
Conclusions:Our results add to a growing literature documenting heterogeneity in the earliest cognitive and pathological presentations associated with Alzheimer’s disease and related disorders. Participants with subtle memory/language, executive, and visuospatial weaknesses all declined at faster rates than the All-Average group, suggesting that there are multiple pathways and/or unique subtle cognitive decline profiles that ultimately lead to a diagnosis of MCI/dementia. These results have important implications for early identification of individuals at risk for MCI/dementia. Given that the same classification approach may not be optimal for everyone, determining profiles of subtle cognitive difficulties in CU individuals and implementing neuropsychological test batteries that assess multiple cognitive domains may be a key step towards an individualized approach to early detection and fewer missed opportunities for early intervention.
50 BSI-18 as a Measure of Psychological Distress Across Different Domains in TMS Patients
- Bruno N. Gamboa, Kathleen Hodges, Stephanie C. Gee, Michelle R. Madore, Noah S. Philip, F. Andrew Kozel, Nicole C. Walker
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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. 836-837
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Objective:
Transcranial magnetic stimulation (TMS) is an effective treatment for individuals with pharmacoresistant major depressive disorder (MDD), yet identifying which patients best respond remains an important area of inquiry. The Brief Symptom Inventory (BSI-18) serves as a screen for psychological distress, providing measures across three separate domains (e.g., somatization, depression, and anxiety) and one composite score (i.e., global severity index). The psychometric properties of the BSI-18 have been validated across multiple studies; however, it has sparsely been used to track changes in patient symptoms in response to intervention. Assessing patient symptom severity across these domains is imperative since these symptoms can negatively influence cognitive functioning. Accordingly, the current study utilized the BSI-18 to measure psychological distress across these different domains in patients receiving TMS treatment. We hypothesized that all domains of the BSI-18 would see a significant decrease after treatment, that elevated scores in specific domains would predict a less favorable response to treatment, and that measurement of depressive symptoms will be consistent across measures of similar scope.
Participants and Methods:Veterans (n=94) with MDD and met standard clinical TMS criteria were administered the BSI-18 before and after receiving an adequate dose of treatment (e.g., 30 sessions). Paired Samples T-test were used to compare the pre-treatment and post-treatment scores across domains.
Results:The results of paired sample t-tests indicated a statistically significant reduction in measures of global psychological distress (t(93) = 7.99, p < .001, Cohen's d =.82), as well as depressive (t(93) = 8.34, p < .001, d = .86), anxious (t(93) = 7.64, p < .001, d = .79), and somatic symptoms (t(92) = 5.29, p < .001, d = .55) after receiving treatment. Individuals with elevated levels of anxiety (e.g., BSI-A>63) saw a significant reduction in depressive (t(62) = 8.15, p < .001, d = 1.03), anxious (t(62) = 8.34, p < .001, d = 1.05) and somatic (t(61) = 4.94, p < .001, d = .63) symptoms. Lastly, two measures of depressive symptoms, the BSI-D and PHQ-9, had a statistically significant strong, positive relationship before (r=.66) and after (r=.88) treatment (all n=65 and p<.001).
Conclusions:The BSI-18 can detect changes in different domains of psychological distress as a function of TMS treatment. Unexpectedly, TMS patients with elevated levels of anxiety responded well to treatment despite comorbid anxiety often being associated with less favorable outcomes in treatment trials. The positive relationship of the BSI-D and PHQ-9 before and after treatment suggests the use of the BSI as a valid, additional measure of depressive symptoms.
73 Sleep Onset Latency and Duration in rTMS Treatment in Veterans with Treatment-Resistant Major Depressive Disorder
- Sonia S Rehman, Zachary D Zuschlag, Michael Norred, Laurie Chin, Nicole C Walker, Noah S Philip, F. Andrew Kozel, Michelle R Madore
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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. 478-479
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Objective:
This study builds on the work by Rehman et al (2022) who argued that transcranial magnetic stimulation (TMS) treatment not only helps treat depression but also decreases sleep problems such as difficulty falling asleep,staying asleep, and waking too early. The present study further explores differences in sleep onset latency, meaning the time it takes to fall asleep, and duration of sleep per night in the pre and post treatment phases of rTMS. The information regarding major attributes of sleep is critical because recent research shows that about 90% of patients with major depressive disorder (MDD) also struggle with sleep disorders (Li et al., 2022), and sleeping for less than seven hours may eventually lead to sleep deprivation (Hirshkowitz et al., 2015), with increased risk of physical and mental health problems (Sheehan et al, 2019). Sleep onset latency estimates vary from individual to individual but typical sleep latency is considered between 10 to 20 minutes (Jung et al, 2013). As it has been shown that overall sleep problems improve with rTMS, we hypothesized that self-reported sleep onset latency will decrease, and sleep duration will increase.
Participants and Methods:All participants met inclusion criteria for MDD diagnosis and completed a full course of TMS treatment (N=470; Mean age=53.45, SD=13.73). The sample was mostly male (81%) and ethnically diverse: 77.7% non-Hispanic White, 13.3% Black Americans, 1.9% Asian, 0.2 % Asian Indian, and 1.9% other ethnicities. Sleep problems were assessed using the following questions at the pre and post treatment stages: the number of minutes it takes to fall asleep and duration of sleep each night.
Results:A Wilcoxon matched-pairs signed-rank test was conducted to determine whether there was a difference in sleep onset latency and hours of sleep per night between pre and post intervention. The results indicated a significant difference in time to fall asleep between pre and post treatment (pre-treatment M = 1.19, SD = 0.99, post-treatment M = 0.93, SD = 0.91; z = -5.01, p < .001. In addition, there was a significant increase in the minutes of sleep per night in pre (M = 6.11, SD = 2.07) compared to the post treatment (M = 6.32, SD = 1.77), z = -2.56, p = .010.
Conclusions:Reduced sleep is known to negatively impact mood, cognitive ability, work performance, and immune function (Besedovsky et al., 2012; Killgore, 2010; Massar et al, 2019; Vandekerckhove & Wang, 2018). Similarly, longer sleep onset latency can cause an individual to enter the first sleep stage later than expected and complete fewer sleep cycles. The results of the present study show the effectiveness of rTMS in decreasing sleep onset latency and increasing the duration of sleep. Given the comorbidity and bidirectionality between sleep disturbances and mood disorders (Fang et al., 2019; Palagini et al., 2019), further researching treatments such as rTMS to improve sleep as a means to also improve mood is crucial. We propose acquiring knowledge about sleep attributes as an essential part of clinicians’ work early on in the rTMS treatment in order to monitor an individual’s global functioning level in light of improved sleep.
73 Identification of 24-Month Cognitive Trajectories Among Clinical High Risk for Psychosis (CHR-P) Using Latent Class Mixture Modeling
- Ryan M. Guest, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Barbara A. Cornblatt, Daniel H. Mathalon, Diana O. Perkins, Ming T. Tsuang, Scott W. Woods, Tyrone D. Cannon, Matcheri S. Keshavan, William S. Stone, Elaine F. Walker
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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. 857-858
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Objective:
Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.
Participants and Methods:Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).
Results:A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).
Conclusions:Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.
3 Type 2 Diabetes Moderates the Association between Amyloid PET and Attention/Executive Functioning in Older Veterans
- Rachel Membreno Almendares, Katherine J Bangen, Monica T Ly, Kayla S Walker, Sunder Mudaliar, Kelsey R Thomas
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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. 104-105
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Objective:
Type 2 diabetes (T2D) is a risk factor for cognitive impairment/dementia and has been shown to modify the impact of Alzheimer’s disease (AD) biomarkers on cognition and everyday functioning. Studies examining amyloid-ß (Aß), one of the hallmark AD pathologies, have shown mixed results regarding associations of Aß biomarkers with cross-sectional cognition as well as T2D, though Aß is generally associated with future cognitive declines. The purpose of the present study is to examine whether T2D impacts the associations between amyloid positron emission tomography (PET) and cognition in older Veterans.
Participants and Methods:The current study included 202 mostly male Vietnam-Era Veterans from the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DOD ADNI) study (age M=69.38 years, SD=4.37; 40% with self-reported T2D) who completed neuropsychological testing and florbetapir PET imaging. The Aß PET standardized uptake variable ratio (SUVR) was measured using a previously-validated summary SUVR calculated by dividing the mean uptake across 4 AD-vulnerable cortical regions by whole cerebellar uptake. General linear models examined whether T2D moderated the relationship of Aß PET with memory, attention/executive functioning, and language composite scores. Models adjusted for age, education, apolipoprotein E e4 carrier status, vascular risk burden, depressive symptoms, post-traumatic stress disorder (PTSD) symptom severity, and history of traumatic brain injury (TBI).
Results:There was no main effect of diabetes on memory, attention/executive functioning, or language performance, and higher Aß PET SUVR was only associated with worse attention/executive functioning performance (ß=-.146, 95% CI [-.261, -.031], p=.013). The Aß PET x T2D interaction was significant for attention/executive functioning such that higher Aß PET SUVR was associated with lower attention/executive functioning scores, but only in those with T2D (ß=-.116, [-.225, -.006], p=.038). This interaction was not significant for language or memory.
Conclusions:The results show that Aß may negatively impact attention/executive functioning, but this effect was only found in Veterans with T2D. Prior work has suggested that T2D may be more associated with tau biomarkers than markers of Aß, so it is possible that the current results are due to a compounding effect of Aß pathology plus microvascular and/or tau pathology. Notably, the sample was relatively young, a relatively large proportion had elevated PTSD symptoms and/or a TBI history (which have both been shown to relate to attention/executive function), and the measures that made up the attention/executive composite (Trail Making Test A and B) have been shown to be particularly sensitive - all of which may have contributed to the domain-specific effects. Future research is needed to investigate the role that tau and vascular pathology may play in cognition among individuals with T2D. Longitudinal studies are also needed to better understand the timing and progression of these relationships.
54 Cognitive Profiles of Older Adults with Depression in Psychotherapy Trials: A Scoping Review
- Matthew S. Schurr, Ting Tong, Teresa J. Walker, Rakshitha Mohankumar, Brenna N. Renn
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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, p. 840
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Objective:
Cognitive impairment is often comorbid with depression and anxiety, and the cognitive status of older adult patients can drastically impact depression treatment outcomes. The cognitive status of these patients invariably changes psychological treatment approaches that otherwise are viable and feasible in older adults. For example, although cognitive behavioral therapy is effective in treating cognitively intact patients with depression, it often relies on executive function (such as flexible thinking and problem solving) and other cognitive abilities that are impaired in patients with comorbid cognitive impairment. Practically, this results in unstandardized modifications to psychotherapy that may impact the fidelity—and thus effectiveness—of treatment. It is important to assess and classify cognitive dysfunction in depression treatment-seeking older adults in trials. This can help generalize research findings and identify potential barriers in transferring psychotherapeutic approaches for older adults with depression from treatment trials to practical clinical use, particularly in hard-to-treat populations with comorbid cognitive impairment.
Participants and Methods:A systematic literature search was conducted in PubMed for the period 2000-2022. Study inclusion criteria was operationalised as follows: participants were identified as older adults (55 years and older), their primary psychiatric diagnosis was depression, and the study was a trial for depression treatment. Key search terms included: depression, treatment, psychotherapy, therapy, counseling, intervention, older adult, senior, late-life, elder, aged, clinical trial, and randomized controlled trial.
Results:An initial search of the key terms returned 3,972 articles. 178 of these articles were subject to full text review. Of those, 45 articles met inclusion criteria. Overall study quality was acceptable. A portion of treatment trials did not assess for cognitive functioning. A majority of the articles excluded patients with cognitive impairment, with no further elaboration on the potential impact of cognitive functioning on treatment outcomes. A smaller portion of studies were more inclusive of the cognitive range of patient participants; however, they did not comment on the cognitive heterogeneity of their samples. Only three studies used a more extensive neuropsychological battery to examine cognitive profiles of patient participants. However, two of these studies also excluded individuals that fell below the cognitively intact range based on brief cognitive screening measures. Of the few studies that examined depression treatment in cognitively impaired and dementia patient populations, two trials examined cognitive functioning as a predictor or moderator of depression treatment outcome.
Conclusions:Given that cognitive status can significantly impact depression treatment outcomes for older adults, there is a shocking dearth of inclusion of cognitively impaired patients in depression treatment clinical trials. Moreover, the limited studies that examined depression treatment in cognitively impaired populations, there is a lack of comprehensive cognitive assessment, and lack of exploration on how different types of cognitive dysfunction may contribute to variable depression treatment response. Future depression treatment trials in older adults should expand to include a variety of cognitive functioning ranges, as well as a more detailed assessment of how specific cognitive domains may impact treatment outcomes.
56 TBI Severity Moderates the Association between Subjective and Objective Attention in Older Veterans
- Peter P Rantins, Monica Ly, Alexandra L Clark, Alexandra J Weigand, Kayla S Walker, Victoria C Merritt, Katherine J Bangen, Kelsey R Thomas
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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. 363-364
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Objective:
Prior work on associations between self-reported cognition and objective cognitive performance in Veterans has yielded mixed findings, with some evidence indicating that mild traumatic brain injury (TBI) may not impact the associations between subjective and objective cognition. However, few studies have examined these relationships in both mild and moderate-to-severe TBI, in older Veterans, and within specific cognitive domains. Therefore, we assessed the moderating effect of TBI severity on subjective and objective cognition across multiple cognitive domains.
Participants and Methods:This study included 246 predominately male Vietnam-Era Veterans (age M=69.61, SD=4.18, Range = 60.87 – 85.16) who completed neuropsychological testing and symptom questionnaires as part of the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI). Participants were classified as having history of no TBI (n=81), mild TBI (n=80), or moderate-tosevere TBI (n=85). Neuropsychological composite scores in the domains of memory, attention/executive functioning, and language were included as the outcome variables. The Everyday Cognition (ECog) measure was used to capture subjective cognition and, specifically, the ECog domain scores of memory, divided attention, and language were chosen as independent variables to mirror the objective cognitive domains. General linear models, adjusting for age, education, apolipoprotein E ε4 carrier status, pulse pressure, depressive symptom severity, and PTSD symptom severity, tested whether TBI severity moderated the associations of domain-specific subjective and objective cognition.
Results:Across the sample, subjective memory was associated with objective memory (β=-.205, 95% CI [-.332, -.078], p=.002) and subjective language was associated with objective language (β=-.267, 95% CI [-.399, -.134], p<.001). However, the main effect of subjective divided attention was not associated with objective attention/executive functioning (p=.124). The main effect of TBI severity was not associated with any of the objective cognitive domain scores after adjusting for the other variables in the model. The TBI severity x subjective cognition interaction was significant for attention/executive functioning [F(2,234)=5.18, p=.006]. Specifically, relative to Veterans without a TBI, participants with mild TBI (β=-.311, 95% CI [-.620, -.002], p=.048) and moderate-to-severe TBI (β=-.499, 95% CI [-.806, -.193], p=.002) showed stronger negative associations between subjective divided attention and objective attention/executive functioning. TBI severity did not moderate the associations between subjective and objective cognition for memory or language domains. The pattern of results did not change when the total number of TBIs was included in the models.
Conclusions:In this DoD-ADNI sample, stronger associations between subjective and objective attention were evident among individuals with mild and moderate-to-severe TBI compared to Veterans without a TBI history. Attention/executive functioning measures (Trails A and B) may be particularly sensitive to detecting subtle cognitive difficulties related to TBI and/or comorbid psychiatric symptoms, which may contribute to these attention-specific findings. The strongest associations were among those with moderate-to-severe TBI, potentially because the extent to which their attention difficulties are affecting their daily lives are more apparent despite no significant differences in objective attention performance by TBI group. This study highlights the importance of assessing both subjective and objective cognition in older Veterans and the particular relevance of the attention domain within the context of TBI.
71 Treatment with TMS Improves Aspects of Attention in Depression: A Pilot Study
- Nicole C Walker, Nathan Ramirez, Laurie Chin, Sonia S Rehman, Stephanie C Gee, Kathleen Hodges, Leanne M Williams, Robert Hickson, L. Chauncey Green, Talaya Patton, Hanaa Aldasouqi, Noah S Philip, F. Andrew Kozel, Jerome A Yesavage, Michelle R Madore
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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. 476-477
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Objective:
Repetitive transcranial magnetic stimulation (TMS) is an evidenced based treatment for adults with treatment resistant depression (TRD). The standard clinical protocol for TMS is to stimulate the left dorsolateral prefrontal cortex (DLPFC). Although the DLPFC is a defining region in the cognitive control network of the brain and implicated in executive functions such as attention and working memory, we lack knowledge about whether TMS improves cognitive function independent of depression symptoms. This exploratory analysis sought to address this gap in knowledge by assessing changes in attention before and after completion of a standard treatment with TMS in Veterans with TRD.
Participants and Methods:Participants consisted of 7 Veterans (14.3% female; age M = 46.14, SD = 7.15; years education M = 16.86, SD = 3.02) who completed a full 30-session course of TMS treatment and had significant depressive symptoms at baseline (Patient Health Questionnaire-9; PHQ-9 score >5). Participants were given neurocognitive assessments measuring aspects of attention [Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV) subtests: Digits Forward, Digits Backward, and Number Sequencing) at baseline and again after completion of TMS treatment. The relationship between pre and post scores were examined using paired-samples t-test for continuous variables and a linear regression to covary for depression and posttraumatic stress disorder (PTSD), which is often comorbid with depression in Veteran populations.
Results:There was a significant improvement in Digit Span Forward (p=.01, d=-.53), but not Digit Span Backward (p=.06) and Number Sequencing (p=.54) post-TMS treatment. Depression severity was not a significant predictor of performance on Digit Span Forward (f(1,5)=.29, p=.61) after TMS treatment. PTSD severity was also not a significant predictor of performance on Digit Span Forward (f(1,5)=1.31, p=.32).
Conclusions:Findings suggested that a standard course of TMS improves less demanding measures of working memory after a full course of TMS, but possibly not the more demanding aspects of working memory. This improvement in cognitive function was independent of improvements in depression and PTSD symptoms. Further investigation in a larger sample and with direct neuroimaging measures of cognitive function is warranted.
Improving prediction of psychosis in youth at clinical high-risk: pre-baseline symptom duration and cortical thinning as moderators of the NAPLS2 risk calculator
- Michelle A. Worthington, Meghan A. Collins, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Barbara A. Cornblatt, Matcheri Keshavan, Daniel H. Mathalon, Diana O. Perkins, William S. Stone, Elaine F. Walker, Scott W. Woods, Tyrone D. Cannon
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- Journal:
- Psychological Medicine / Volume 54 / Issue 3 / February 2024
- Published online by Cambridge University Press:
- 29 August 2023, pp. 611-619
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Background
Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models.
MethodsParticipants from both the NAPLS2 and NAPLS3 samples were classified as either ‘long’ or ‘short’ symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis.
ResultsThe risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78).
ConclusionsThese results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes.
Early detection and intervention of psychosis in children and adolescents in Zurich, Switzerland: Clinical Data from 2017-2022
- M. Franscini, N. Traber-Walker, F. Probst, M. Gerstenberg, S. Walitza
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S1075-S1076
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Introduction
The construct of a clinical high-risk (CHR) state of psychosis has been established to describe potentially prodromal symptoms which typically appear during adolescence and young adulthood. This is a very sensitive developmental period and the clinical high risk (CHR) is associated with increased functional impairment. To address the specialities in the care for this patient population a specialized outpatient care unit for early intervention in psychosis at the Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital, of the University Zürich (CAPS) is established. The interdisciplinary team (psychiatrists and psychologists) supports children and adolescents with psychotic disorders or at clinical high risk for developing psychosis. The early intervention service offers specialized assessment, treatment and case management for minors with a first psychosis or CHR-state in an outpatient or inpatient setting as well as by day clinic care.
ObjectivesThe evaluation main objective was to get a better understanding about this vulnerable patient group. Therefore we analysed the clinical data about CHR-state, comorbid diagnosis, treatment, medication and hospitalisation of the patients who entered the service for early intervention in psychosis.
MethodsParticipants who entered the service for early intervention in psychosis were followed up in the years 2017-2021 and descriptive analysis was used to summarize the data. For the evaluation of the risk construct the participants have been classified in “no increased risk”, “CHR” or “early onset psychosis” (EOP). Additionally, ICD diagnosis, demographics and treatment (medication, psychotherapy, treatment setting) were assessed. Therapy was either psychotherapy and/or group training called DBT2P (Dialectical behavioral group training for adolescents, to prevent psychiatric disorders). Additionally, the use of a smartphone application “Robin Z”(add-on treatment tool to support the patients between the sessions) was assessed.
ResultsIn the last five years we saw 300 patients (112 female, mean age 15.7) who sought the care unit for early intervention. The evaluation of the risk showed that 44 patients had no increased risk, 205 were classified with a CHR and 51 fulfilled the criteria of an early onset psychosis (18.5%). Most of the patients showed comorbid diagnosis, mainly depressive disorders (42%). The data about the treatment will be analyzed for the congress.
ConclusionsDespite clinical implications, there is little data about early detection and early intervention in psychosis for children and adolescent. Therefore, the evaluation of the clinical data of the CAPS is of clinical importance and expected to add essential information in the fields of prevention and early intervention in psychosis.
Disclosure of InterestNone Declared
Clinical implementation of the smartphone app Robin Z as an additional treatment tool to support adolescents with psychiatric symptoms
- N. Traber-Walker, E. Voets, C. Bühlmann, M. Gerstenberg, F. Probst, M. Franscini, S. Walitza
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S858-S859
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Introduction
Interest in the development of innovative technologies in the health sector has increased due to their potential to improve accessibility, efficacy, quality, and cost-effectiveness of treatment. Based on these considerations, we developed the app Robin Z to support adolescents in psychiatric treatment. Robin Z is intended as an add on therapy-tool. It aims to assess symptoms in real time, offer help in coping with symptoms and everyday life and to support medication adherence. Despite initial encouraging research findings supporting the use of smartphone technology in psychotherapy, it remains unclear whether the consistent use of smartphone technology in outpatient clinics is practical outside of research projects. Thus, it is uncertain whether patients will engage with this technology over an extended period of time and whether clinicians will be willing to integrate this new technology into their routine. In view of these factors, it is crucial to evaluate the use of smartphone apps for their applicability, effectiveness, and efficiency in clinical routine. In our investigation, we want to address these questions and fill the gap between research and clinical practice.
ObjectivesThe aim of our evaluation is to identify barriers in clinical implementation plus to assess the usability and applicability of the Robin Z app in clinical practice.
MethodsWe started the clinical implementation of Robin Z in four community-based outpatient services. We collected data of 27 adolescent patients and their caregivers (N=15) over a six-week period. They all completed questionnaires on user-friendliness and satisfaction. Further, user data about mood logs, symptom trajectories, achieved weekly goals and entries for positive reinforcement were gathered to examine the clinical impact of using the app.
ResultsThe clinical implementation and evaluation will provide data on feasibility, user-friendliness, clinical implication and satisfaction of patients and therapists with the smartphone app Robin Z.
ConclusionsAlthough many apps are available for young people with mental health problems, most of these have not been developed by professionals, and their effectiveness has not been evaluated. To the best of our knowledge, Robin Z is one of the first apps of its kind to be specifically developed by clinical experts as an additional tool to support psychotherapy for adolescent patients. The results of this evaluation are of clinical importance to the field of eMental Health. They will provide preliminary evidence of the clinical utility of the app. In addition, the results will improve our understanding of potential barriers and facilitators to using Robin Z for both patients and therapists.
Disclosure of InterestNone Declared
Treatment effects on adolescents at increased risk for psychosis: evaluation of a treatment approach combining a standardized manual with a smartphone app
- N. Traber-Walker, F. Probst, M. Gerstenberg, C. Bertossa, S. Walitza, M. Franscini
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S633
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Introduction
The goal of psychotic disorders has led researchers to focus on early identification of individuals at clinical high risk (CHR) for psychosis and treatment of CHR symptoms. CHR symptoms typically occur in adolescence and young adulthood. This is a very sensitive developmental period, and CHR-state is associated with increased functional impairment. Age-appropriate treatment approaches that address youth-specific interests, complex symptomatology, associated distress, and functional impairment are needed. However, there is a lack of research on treatment strategies for this vulnerable age group. To address this gap, we developed the combined treatment program “Robin” (standardized manual and smartphone app). The treatment program targets CHR symptoms, comorbid symptoms, and improvement of quality of life and daily functioning. The smartphone app “Robin Z” is an add-on treatment tool to support patients between their sessions. While a number of studies using smartphone apps in therapy have shown promising effects with adult psychosis patients, little is known about their use in therapy with minor patients. “Robin Z” is one of the first smartphone apps targeting adolescent patients with CHR or full-blown psychotic symptoms.
ObjectivesThe investigation of efficacy of this specific intervention versus treatment as usual
MethodsOur study was designed as a naturalistic clinical intervention study with a matched controlled design (treatment as usual). A total of 40 help-seeking adolescents (67% female) with CHR symptoms aged 13-18 years (mean age 15.86) were recruited to the intervention condition between September 2017 and May 2022. For the control group, data from 62 patients from a previous study are available and will be matched for age and gender. CHR symptoms, comorbid symptoms, functioning, self-efficacy, and quality of life will be monitored at six time points (baseline, during the treatment phase, immediately after the intervention, and 6, 12, and 24 months later).
ResultsAll participants have now completed the intervention phase. In Paris, the first results on treatment effects will be presented at the symposium. This will include baseline data for the intervention group and their intraindividual changes in symptomatology, well-being, and level of functioning during and immediately after treatment. In addition, the results of the first follow up examinations compared to the control group will be presented.
ConclusionsTo our knowledge, this is the first controlled trial to evaluate the effectiveness of a specific treatment for adolescents with early psychosis combined with a smartphone app. The results of our evaluation are of clinical importance and should provide essential information for both the field of eMental Health and the topic of early intervention in psychosis.
Disclosure of InterestNone Declared
The Southern-sky MWA Rapid Two-metre (SMART) pulsar survey—II. Survey status, pulsar census, and first pulsar discoveries – ADDENDUM
- N. D. R. Bhat, N. A. Swainston, S. J. McSweeney, M. Xue, B.W. Meyers, S. Kudale, S. Dai, S. E. Tremblay, W. van Straten, R. M. Shannon, K. R. Smith, M. Sokolowski, S. M. Ord, G. Sleap, A. Williams, P. J. Hancock, R. Lange, J. Tocknell, M. Johnston-Hollitt, D. L. Kaplan, S. J. Tingay, M. Walker
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- Publications of the Astronomical Society of Australia / Volume 40 / 2023
- Published online by Cambridge University Press:
- 18 July 2023, e031
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6 - The Mean-Field Approach
- James S. Walker, Washington State University (emeritus)
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- A Student's Guide to the Ising Model
- Published online:
- 11 May 2023
- Print publication:
- 25 May 2023, pp 150-173
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Summary
Exact solutions for infinite Ising systems are rare, specific in terms of the interactions allowed, and limited to one and two dimensions. To study a wider range of models we must resort to various approximation techniques. One of the simplest and most comprehensive of these is the mean-field approximation, the subject of this chapter. Some versions of this approximation rely on a self-consistent requirement, and in this respect the mean-field method for the Ising model is similar to a number of other self-consistent approximation methods in physics, including the Hartree–Fock approximation for atomic and molecular orbitals, the BCS theory of superconductivity, and the relaxation method for determining electric potentials. We will also introduce a somewhat different mean-field approach, the Landau–Ginzburg approximation, which is based on a series expansion of the free energy. One of the drawbacks of all of the mean-field theories, however, is that they predict the same mean-field critical exponents, which, unfortunately, are at odds with the results of exact solutions and experiments.
About This Book
- James S. Walker, Washington State University (emeritus)
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- Book:
- A Student's Guide to the Ising Model
- Published online:
- 11 May 2023
- Print publication:
- 25 May 2023, pp vii-viii
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