Background/Objectives: Strabismus, or eye misalignment, has not been well-described in U.S. military Veterans. This study was undertaken to characterize Veterans with a strabismus diagnosis as well as those who underwent strabismus surgery. Methods: A retrospective analysis of electronic health records (EHR) from the Veterans Health Administration (VHA) was conducted using patient data from 2000 to 2022. VHA-enrolled Veterans ≥ 18 years with strabismus-related International Classification of Diseases (ICD) codes and/or Current Procedural Terminology (CPT) codes were identified. Total and demographic (age group, sex, race, and ethnicity) stratified prevalence and incidence rates were calculated, as well as sex-stratified residual lifetime risk. Results: A total of 321,639 patients had a strabismus diagnosis, with most (320,107) identified by ICD code (CPT code only = 1532). The peak prevalence was 2.29% in the 2022 VHA fiscal year (1 October 2021 to 30 September 2022) with a median annual age-adjusted incidence rate of 168.9/100 000 enrollees. Age-adjusted lifetime risk was 10.19% for males and 11.03% for females. Significant differences by age group, sex, race, and ethnicity were identified for strabismus prevalence (p < 0.001), strabismus diagnosis types (p < 0.001), and between patients with strabismus who either did or did not have surgery (sex p < 0.05, all others p < 0.001). Compared with other U.S. adult populations, VHA Veterans have similar or higher prevalence, annual incidence rates, and lifetime risk of a strabismus diagnosis, with demographic factors significantly affecting the rates and types of strabismus. Notably, despite lower prevalence and incidence than other racial groups, a higher percentage of African American patients with strabismus underwent surgery, contrasting with published Medicare data. Inconsistencies between ICD and CPT codes highlight potential miscoding and/or missing codes, with reliance on ICD code diagnoses potentially underestimating strabismus prevalence. Conclusions: Further characterization of factors affecting strabismus risk among these patients may help improve strabismus diagnosis and management for many US Veterans. This foundational study serves as a platform for detailed predictive analyses in determining risk outcomes for individuals. This includes better identification of at-risk individuals, informing effective resource allocation for treatment.

Background: Quantitative susceptibility mapping (QSM) of the brain is an advanced MRI technique for assessing tissue characteristics based on magnetic susceptibility, which varies with the composition of the tissue, such as iron, calcium, and myelin levels. QSM consists of multiple processing steps, with various choices for each step. Despite its increasing application in detecting and monitoring neurodegenerative diseases, the impact of algorithmic choices in QSM's workflow on clinical outcomes has not been thoroughly quantified. Objective: This study aimed to evaluate how choices in background field removal (BFR), dipole inversion algorithms, and anatomical referencing impact the sensitivity and reproducibility error of QSM in detecting group-level and longitudinal changes in deep gray matter susceptibility in a clinical setting. Methods: We compared 378 different QSM pipelines using a 10-year follow-up dataset of healthy adults. We analyzed the sensitivity of pipelines to detect known aging-related susceptibility changes in the DGM over time. Results: We found high variability in the sensitivity of QSM pipelines to detect susceptibility changes. The study highlighted that while most pipelines could detect changes reliably, the choice of BFR algorithm and the referencing strategy substantially influenced the outcome reproducibility error and sensitivity. Notably, pipelines using RESHARP with AMP-PE, HEIDI or LSQR inversion showed the highest overall sensitivity. Conclusions: The findings underscore the critical influence of algorithmic choices in QSM processing on the accuracy and reliability of detecting physiological changes in the brain. This has profound implications for clinical research and trials where QSM is used as a biomarker for disease progression, highlighting that careful consideration should be given to pipeline configuration to optimize clinical outcomes.

BACKGROUND:Oral mucosal immunotherapy (OMIT) involves the use of a specifically formulated toothpaste to deliver allergenic proteins to immunologically active areas of the oral cavity. This represents a novel delivery mechanism with several features designed to improve food allergy desensitization. OMIT has advantages over other approaches to allergy immunotherapy due to its targeted delivery and simplified administration. OBJECTIVE:To determine the safety, tolerability, and adherence to OMIT with INT301 in adults with peanut allergy. METHODS:The Oral Mucosal Escalation Goal Assessment study enrolled 32 adults, aged 18 to 55 years, with peanut allergy in a 3:1 ratio to receive either an escalating dose of INT301 or a placebo. Entry criteria included a positive skin prick test result with a wheal diameter greater than or equal to 3 mm than control and/or peanut-specific IgE level greater than or equal to 0.35 kU/L. Subjects were required to fail an oral food challenge less than or equal to 100 mg dose of peanut protein. Safety and tolerability were monitored in the 48-week trial period. RESULTS:All active subjects (100%) tolerated the prespecified protocol at the highest dose. No moderate or severe systemic reactions were observed in the active participants. Nonsystemic adverse reactions were mostly local (oral and nasal cavities), mild and transient. Active subjects adhered to the treatment for 97% of the days in the study, with no withdrawals due to study medication. CONCLUSION:In the Oral Mucosal Escalation Goal Assessment trial, INT301 met all primary and secondary end points of safety, tolerability, and adherence. Thus, OMIT seems to be a safe and convenient option for individuals with food allergies. These results support the need for further evaluation in the pediatric population. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04603300.

BACKGROUND:While brief behavioral therapy for insomnia (BBTI) has shown promising results in improving sleep outcomes, its effects on health-related quality of life (HRQOL) and mental health among cancer survivors have been understudied. PURPOSE:To evaluate the effect of BBTI on HRQOL and mental health outcomes among cancer survivors, relative to an attention control group receiving a healthy eating program (HEP), over periods from baseline to 12 months and from 3 to 12 months. METHODS:A sample of 132 cancer survivors with insomnia symptoms (Mage: 63.7 ± 10 years; 55.3% female) was assessed at baseline, with the final analytical sample of 121 (BBTI = 62, HEP = 59). Self-reported HRQOL, mood disturbance, depression, and anxiety at baseline, 3 months, and 12 months were examined. A multivariate linear model using least squares means evaluated within- and between-group differences. RESULTS:No significant differences in outcome variables were found between the randomized groups at any time point. Both groups showed significant improvements in total HRQOL, mood disturbance, and anxiety symptoms from baseline to 12 months. Only the BBTI group demonstrated a significant reduction in depressive symptoms within the group, an effect not observed in the HEP group. The most noticeable changes occurred within the first 3 months, with no statistically significant differences from 3 to 12 months within or between groups. CONCLUSION:While both randomized groups showed improvements in total HRQOL, mood, and anxiety symptoms, only BBTI produced significant within-group improvements in depressive symptoms over 12 months. CLINICAL TRIAL REGISTRATION:https://ClinicalTrials.gov, NCT03810365.

OBJECTIVE:Negative affect and affect variability figure prominently in models of addictive behaviors but are not without controversy. Negative affect variability may better capture a mechanism of behavior change in alcohol use disorder (AUD) treatment because it contains information about affect regulation, a common clinical target. The aims of this study are to examine the change in: (a) trajectory of negative affect variability, (b) association of negative affect variability and abstinence, and (c) association of negative affect variability and heavy drinking during AUD treatment. METHOD:This article is a secondary analysis of data drawn from a randomized clinical trial. N = 181 participants diagnosed with Diagnostic and Statistical Manual of Mental Disorders, fifth edition AUD (Mage = 50.8, SDage = 10.6; 51.4% female) received 12 sessions of Cognitive Behavioral Coping Skills Therapy for AUD. Participants completed one daily diary prompt per day for 84 consecutive days. Each day, participants reported on negative affect and number of alcoholic drinks consumed the previous day. Time-varying effect models examined changes in negative affect variability and its associations with abstinence and heavy drinking. RESULTS:Negative affect variability decreased throughout treatment. The positive association between negative affect variability and heavy drinking became nonsignificant (decoupled) midway through treatment. The inverse association between negative affect variability and daily abstinence became nonsignificant (decoupled) at approximately day 75 of 84. When mean levels of NA were added as a covariate, the effects were in the same direction but no longer statistically significant. CONCLUSION:Reductions in negative affect variability may capture an important change mechanism of behavioral treatments for AUD because it contains information about affect regulation as compared with mean levels of negative affect. Negative affect variability warrants further consideration as a mechanism of behavior change. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: To better understand the timing and unique contribution of four potential mechanisms of behavior change (MOBC) during alcohol use disorder (AUD) treatment (negative affect, positive affect, alcohol craving, and adaptive alcohol coping), we used a time-varying effect modeling analytic approach to examine the change trajectories of alcohol abstinence, heavy drinking, the hypothesized MOBCs, and the time-varying associations between the MOBCs and alcohol outcomes. Method: Participants (N = 181; M-age = 50.8 years, SD = 10.6; 51% women; 93.5% Caucasian) were enrolled in a 12-week randomized clinical trial of cognitive behavioral outpatient treatment program for AUD. For 84 consecutive days, participants provided self-reports of positive and negative affect, craving, alcohol use, and adaptive alcohol coping strategies employed. Results: Throughout the 84-day treatment window, higher daily average craving levels were associated with both decreased likelihood of alcohol abstinence and increased odds of heavy drinking, whereas higher adaptive alcohol coping was associated with increased odds of abstinence and decreased odds of heavy drinking. Higher negative affect was associated with decreased odds of abstinence in the first 10 days of treatment and increased odds of heavy drinking before Day 4 or Day 5. Higher positive affect was associated with decreased odds of heavy drinking during the first 4 or 5 days. Conclusions: The differential time-varying associations between negative affect, positive affect, alcohol craving, adaptive alcohol coping, and alcohol use provide insights into how and when each of the MOBCs is active during AUD treatment. These findings can help optimize the efficacy of future AUD treatments.

Neglect remains understudied compared to other forms of maltreatment. While studies have shown that neglect has negative effects on mental health in adolescence, yet unresolved is whether these impacts result from critical period or cumulative effects. In the present article, we use a novel approach to compare these two hypotheses from the impact of two types of neglect, failure to provide (FTP) and lack of supervision (LOS), on adolescent depression and internalizing symptoms. Data derive from the LONGSCAN consortium, a diverse, multi-site, prospective study of children from approximately age 2-16. Despite our hypothesis that the critical period of early childhood would have the greatest impact on adolescent internalizing mental health, exposure to neglect during the critical period of adolescence (ages 12-16) was the best-fitting model for the effects of FTP neglect on depression, and the effects of LOS neglect on both depression and internalizing symptoms. The cumulative model (exposure across all time periods) best explained the effects of FTP neglect on internalizing symptoms. Results were robust to the addition of control variables, including other forms of maltreatment. These findings demonstrate that responding to neglect into adolescence must be considered as urgent for child welfare systems.

OBJECTIVES:To explore and characterize predisposing, precipitating, and perpetuating factors of subthreshold, moderate, and severe insomnia in cancer survivors. SAMPLE & SETTING:135 cancer survivors who self-reported symptom severity on the Insomnia Severity Index during the baseline phase of a randomized clinical trial on insomnia treatment. METHODS & VARIABLES:Participants completed measures assessing predisposing factors (age, sex, race and ethnicity, body mass index), precipitating factors (number of years since cancer diagnosis, depression and anxiety symptoms, health-related quality of life), and perpetuating factors (frequency of consuming alcoholic and caffeinated beverages, napping behavior, dysfunctional beliefs about sleep). RESULTS:In the multivariate model, being female was protective against insomnia, and being a person of color, having higher anxiety, having more depression symptoms, and having stronger dysfunctional beliefs about sleep were significantly associated with greater insomnia severity. IMPLICATIONS FOR NURSING:By fostering interprofessional collaboration and implementing evidence-based interventions, nurses can contribute to the well-being of cancer survivors and address their sleep-related challenges. This study underscores the importance of regular insomnia screenings for cancer survivors, with nurses as essential facilitators.

To determine the efficacy of nurse-delivered brief behavioral treatment for insomnia (BBTI) compared to an attention control, in a heterogeneous sample of cancer survivors to reduce insomnia symptom severity. We recruited 132 participants from cancer care clinics, who had an Insomnia Severity Index (ISI) score ≥ 8. Participants were randomized into two groups: an experimental BBTI group and a healthy eating attention control group. Demographics survey at baseline, and sleep-related questionnaires, self-reported sleep diaries, and wrist-worn actigraphy at baseline, 1, 3, and 12 months were collected. Statistical analyses used analysis of covariance (ANCOVA) models with two-sided 0.05 nominal significance level for treatment effect for primary outcome of insomnia severity at 1 month. Participants were cancer survivors with a mean age of 63.7 years, 55 http://ClinicalTrials.gov , NCT03810365. Implementing BBTI in survivorship settings can effectively address and manage insomnia symptoms, thus bridging a crucial gap in care for cancer survivors.

With the increasing burden of professional burnout in physicians, attention is being paid to optimizing sleep health, starting in training. The multiple dimensions of physicians’ sleep are not well described due to obstacles to easily and reliably measuring sleep. This pilot study tested the feasibility of using commercial wearable devices and completing manual sleep logs to describe sleep patterns of medical students and residents. Prospective pilot study of 50 resident physicians and medical students during a single year of training. Participants completed a manual sleep log while concurrently wearing the Fitbit Inspire device for 14-consecutive days over three clinical rotations of varying work schedules: light, medium, and heavy clinical rotations. Study completion was achieved in 24/50 (48%) participants. Overall correlation coefficients between the sleep log and Fitbit were statistically low; however, the discrepancies were acceptable, i.e., Fitbit underestimated time in bed and total sleep time by 4.3 and 2.7 minutes, respectively. Sleep onset time and waketime were within 8 minutes, with good agreement. Treatment of sleep episodes during the day led to variance in the data. Average missingness of collected data did not vary between medical students or residents or by rotation type. When comparing the light to heavy rotations, hours slept went from 7.7 (±0.64) to 6.7 (±0.88), quality-of-life and sleep health decreased and stress, burnout, and medical errors increased. Burnout was significantly associated with worse sleep health, hours worked, and quality-of-life. Prospective data collection of sleep patterns using both sleep logs and commercial wearable devices is burdensome for physicians-in-training. Using commercial wearable devices may increase study success as long as attention is paid to daytime sleep. In future studies investigating the sleep of physicians, the timing of data collection should account for rotation type.

SummaryExisting evidence linking insomnia to all‐cause mortality in older individuals remains inconclusive. We conducted a retrospective study of a large cohort of veterans aged 65–80 years old identified from the Corporate Data Warehouse, a large data repository derived from the Veterans Health Administration integrated medical records. Veterans' enrollees with and without International Classification of Diseases, Ninth and Tenth Revision, codes corresponding to insomnia diagnosis between 1 January 2010 and 30 March 2019 were assessed for eligibility. The primary outcome was all‐cause mortality. A total of 36,269 veterans, 9584 with insomnia and 26,685 without insomnia, were included in the analysis. Baseline mean (SD) age was 72.6 (4.2) years. During a mean follow‐up of 6.0 (2.9) years of the propensity score matched sample, the mortality rate was 34.8 [95% confidence interval: 33.2–36.6] deaths per 1000 person‐years among patients with insomnia compared with 27.8 [95% confidence interval: 26.6–29.1] among patients without insomnia. In a Cox proportional hazards model, insomnia was significantly associated with higher mortality (hazard ratio: 1.39; [95% confidence interval: 1.27–1.52]). Patients with insomnia also had a higher risk of non‐fatal cardiovascular events (hazard ratio: 1.21; [95% confidence interval: 1.06–1.37]). Secondary stratified analyses by sex, race, ethnicity and hypertension showed no evidence of effect modification. A higher risk of mortality (hazard ratio: 1.51; [95% confidence interval: 1.33–1.71]) was observed when depression was present compared with absent (hazard ratio: 1.26; [95% confidence interval: 1.12–1.44]; p = 0.02). In this cohort study, insomnia was associated with increased risk‐adjusted mortality and non‐fatal cardiovascular events in older individuals.

Abstract Introduction Insomnia is prevalent in more than 50% of cancer survivors, occurring during and after their treatment trajectory, potentially leading to subsequent insomnia disorder. Brief Behavioral Treatment for Insomnia (BBTI) aims to assist cancer survivors to self-manage their behaviors to improve their sleep to reduce insomnia symptom burden. This study determined efficacy of BBTI versus a healthy eating program attention control on insomnia severity index (ISI) and sleep quality measures overtime, in a heterogeneous sample of cancer survivors. Methods A sample of 132 eligible cancer survivors were recruited and randomized into BBTI (experimental) and control groups. All participants completed baseline demographics and sleep-related surveys (e.g., ISI, Pittsburgh Sleep Quality Index [PSQI]) at: baseline, 1-month, 3-month, and 12-month post intervention. Statistical analysis of ISI and sleep quality at each time point proceeded using fitted ANCOVA models with independent variables including randomized treatment assignment, participant cancer type, the interaction between treatment assignment and cancer type, and baseline outcome level. Tests for treatment effect were performed using an exact permutation testing approach with a two-sided 0.05 nominal significance level. Results Statistically significant group differences (p-values < 0.05) were observed at all time points for both ISI and sleep quality. Mean differences (95% CI) in ISI (BBTI minus control) were estimated to be -2.2(-4.1, 0.4), -2.1(-4.2, 0.1), and -2.3(-4.4, 0.1) at 1-, 3-, and 12-months, respectively. For sleep quality, the estimated mean differences were -1.4(-2.6, 0.2), -1.8(-3.0, 0.5), and -1.8(-3.3, 0.3), respectively. When adjusting for covariates known to be predictive of outcome, ISI results were robust, with treatment group difference remaining statistically significant except for when adjusting for treatment related surgery where results became borderline non-significant. Conclusion BBTI was significantly effective in reducing insomnia severity and improving sleep quality overtime compared to control among cancer survivors with insomnia symptoms. Use of BBTI in cancer survivors can help bridge the gap in addressing insomnia symptoms in survivorship settings. Support (if any) NIH/NINR R01NR018215 (Dean/Dickerson), ClinicalTrials-NCT03810365

BackgroundHuman restricted genes contribute to human specific traits in the immune system. CHRFAM7A, a uniquely human fusion gene, is a negative regulator of the α7 nicotinic acetylcholine receptor (α7 nAChR), the highest Ca2+ conductor of the ACh receptors implicated in innate immunity. Understanding the mechanism of how CHRFAM7A affects the immune system remains unexplored.MethodsTwo model systems are used, human induced pluripotent stem cells (iPSC) and human primary monocytes, to characterize α7 nAChR function, Ca2+ dynamics and decoders to elucidate the pathway from receptor to phenotype.FindingsCHRFAM7A/α7 nAChR is identified as a hypomorphic receptor with mitigated Ca2+ influx and prolonged channel closed state. This shifts the Ca2+ reservoir from the extracellular space to the endoplasmic reticulum (ER) leading to Ca2+ dynamic changes. Ca2+ decoder small GTPase Rac1 is then activated, reorganizing the actin cytoskeleton. Observed actin mediated phenotypes include cellular adhesion, motility, phagocytosis and tissue mechanosensation.InterpretationCHRFAM7A introduces an additional, human specific, layer to Ca2+ regulation leading to an innate immune gain of function. Through the actin cytoskeleton it drives adaptation to the mechanical properties of the tissue environment leading to an ability to invade previously immune restricted niches. Human genetic diversity predicts profound translational significance as its understanding builds the foundation for successful treatments for infectious diseases, sepsis, and cancer metastasis.FundingThis work is supported in part by the Community Foundation for Greater Buffalo (Kinga Szigeti) and in part by NIH grant R01HL163168 (Yongho Bae).

STUDY OBJECTIVES Reduced sleep duration and work hour variability contribute to medical error and physician burnout. This study assesses the relationships between physician performance, burnout and the dimensions of sleep beyond hours slept. METHODS This was an ancillary analysis of 3 years of data from the international prospective cohort study: the Intern Health Study. Actigraphy data from 3,654 intern physicians capturing sleep timing, regularity, efficiency, and duration were used individually and combined as a composite sleep health index to measure the association of multi-dimensional sleep patterns on self-reported medical errors and burnout. RESULTS From 2017 to 2019, Interns' work hours decreased by 4 hours per week while total sleep time also decreased (6.7 to 5.99 hours) and sleep efficiency, timing and regularity all worsened  (all p<0.05).  In the 21.2% of participants who committed an error, there was no difference in sleep duration, timing or regularity.  Lower sleep efficiency was associated with higher odds of committing an error (p=0.003) and higher burnout scores (p<0.001).  While overall sleep quality was poor in the entire cohort, Interns in the lowest quintile of sleep duration, regularity and efficiency had higher burnout scores than those in the best quintile. CONCLUSIONS Sleep efficiency, not duration, was associated with increased self-reported medical errors and burnout in Intern physicians. Overall sleep quality and duration worsened despite fewer hours worked.  Future studies on physician burnout should measure all aspects of sleep health.

The National Institute on Alcohol Abuse and Alcoholism's (NIAAA) definition of alcohol use disorder (AUD) recovery stipulates two criteria: remission from DSM-5 AUD and cessation of heavy drinking. Importantly, these criteria allow for consideration of nonabstinent alcohol treatment outcomes. However, researchers have yet to assess potential predictors of the NIAAA recovery outcome. The current study examined associations between mental health and coping predictors of NIAAA recovery status in an AUD treatment sample. At baseline (BL) and end-of-treatment (EOT) research interviews in a clinical trial, participants (N = 118) completed questionnaires assessing alcohol dependence, mental health, and confidence levels in reducing heavy drinking, as well as alcohol use and DSM-5 AUD symptom endorsement. Logistic regression models tested the associations between chosen predictors and the odds of achieving NIAAA recovery. Twenty-four percent of individuals (n = 28) met both criteria for NIAAA recovery at EOT. Higher levels of BL state anxiety and anxiety sensitivity predicted lower odds of achieving NIAAA recovery, while greater confidence to reduce heavy drinking predicted increased odds of NIAAA recovery. Social workers are encouraged to continue assessing and addressing mental health in AUD treatment to help individuals with alcohol problems achieve their AUD recovery goals.

BACKGROUND AND OBJECTIVES:Recent technological advances have enabled visualizing in vivo a subset of chronic active brain lesions in persons with multiple sclerosis (pwMS), referred to as "paramagnetic rim lesions" (PRLs), with iron-sensitive MRI. PRLs predict future clinical disease progression, making them a promising clinical and translational imaging marker. However, it is unknown how disease progression is modified by PRL evolution (PRL disappearance, new PRL appearance). This is key to understanding MS pathophysiology and may help inform selection of sensitive endpoints for clinical trials targeting chronic active inflammation. To this end, we assessed the longitudinal associations between PRL disappearance and new PRL appearance and clinical disability progression and brain atrophy. METHODS:PwMS and healthy controls (HCs) were included from a larger prospective, longitudinal cohort study at the University at Buffalo if they had available 3T MRI and clinical visits at baseline and follow-up timepoints. PwMS with sufficient clinical data for confirmed disability progression (CDP) analysis were included in a Disability Progression Cohort, and pwMS and HCs with brain volumetry data at baseline and follow-up were included in MS and HC Brain Atrophy cohorts. PRLs were assessed at baseline and follow-up and assigned as disappearing, newly appearing, or persisting at follow-up. Linear models were fit to compare annualized PRL disappearance rates or new PRL appearance (yes/no) with annualized rates of CDP and progression independent of relapse activity (PIRA) or with annualized rates of brain atrophy, adjusting for covariates including baseline PRL number and follow-up time. Statistical analyses were corrected for false discovery rate (FDR; i.e., q-value). RESULTS:In total, 160 pwMS (73.8% female; mean baseline age 46.6 ± 11.4 years; mean baseline disease duration 13.8 ± 10.6 years; median follow-up time 5.6 [interquartile range 5.2-7.8] years; 26.9% progressive MS) and 27 HCs (74.1% female; mean baseline age 43.9 ± 13.6 years; median follow-up time 5.4 [5.2-5.6] years) were enrolled. Greater PRL disappearance rates were associated with reduced rates of CDP (β mean = -0.262, 95% CI -0.475 to -0.049, q = 0.028) and PIRA (β mean = -0.283, 95% CI -0.492 to -0.073, q = 0.036), and new PRL appearance was associated with increased rates of PIRA (β mean = 0.223, 95% CI 0.049-0.398, q = 0.036). By contrast, no associations between new PRL appearance or PRL disappearance and brain volume changes survived FDR correction (q > 0.05). DISCUSSION:Our results show that resolution of existing PRLs and lack of new PRLs are associated with improved clinical outcomes. These findings further motivate the need for novel therapies targeting microglia-mediated brain inflammation and adoption of clinical strategies to prevent appearance of new PRL.

Background: The National Institute of Alcohol Abuse and Alcoholism (NIAAA) recently released a new definition of recovery from alcohol use disorder (AUD). A patient is considered recovered if they are remitted from DSM-5 AUD and report cessation of heavy drinking. The NIAAA has also recently proposed the Addictions Neuroclinical Assessment (ANA) to guide treatment research. Negative emotionality is one of three domains of the ANA and theory proposes that AUD is maintained by negative reinforcement via the relief of negative affect. The purpose of the current study was to examine: (1) the relationship of end-of-treatment negative emotionality and NIAAA recovery, and (2) the ability of NIAAA recovery at the end of treatment to predict three- and six-month drinking outcomes. Method: At baseline and end-of-treatment, women and men (n = 181) in treatment for AUD completed measures of negative emotionality, drinking, and were assessed for DSM-5 AUD diagnostic criteria. At three- and sixmonths post-treatment, drinking was re-assessed. Results: 22.5% (n = 24) of participants met full criteria for NIAAA recovery at end-of-treatment. Lower levels of end of treatment negative emotionality were associated with increased odds of achieving NIAAA recovery. Meeting NIAAA recovery predicted greater percent days abstinent (PDA) and lower percent heavy drinking days (PHDD) at 3-months, but not at 6-months post-treatment. Conclusions: This study is among the first to report a relationship between the negative emotionality domain of the ANA and NIAAA recovery. Results underscore the importance of addressing negative emotionality in treatment. Findings also suggest that NIAAA recovery predicts positive short term drinking outcomes.

PURPOSE:Lexical characteristics of speech stimuli can significantly impact intelligibility. However, lexical characteristics of the widely used Speech Intelligibility Test (SIT) are unknown. We aimed to (a) define variation in neighborhood density, word frequency, grammatical word class, and type-token ratio across a large corpus of SIT sentences and tests and (b) determine the relationship of lexical characteristics to speech intelligibility in speakers with multiple sclerosis (MS), Parkinson's disease (PD), and neurologically healthy controls. METHOD:Using an extant database of 92 speakers (32 controls, 30 speakers with MS, and 30 speakers with PD), percent correct intelligibility scores were obtained for the SIT. Neighborhood density, word frequency, word class, and type-token ratio were calculated and summed for each of the 11 sentences of each SIT test. The distribution of each characteristic across SIT sentences and tests was examined. Linear mixed-effects models were performed to assess the relationship between intelligibility and the lexical characteristics. RESULTS:There was large variability in the distribution of lexical characteristics across this large corpus of SIT sentences and tests. Modeling revealed a relationship between intelligibility and the lexical characteristics, with word frequency and word class significantly contributing to the model. CONCLUSIONS:Three primary findings emerged: (a) There was considerable variability in lexical characteristics both within and across the large corpus of SIT tests; (b) there was not a robust association between intelligibility and the lexical characteristics; and (c) findings from a study demonstrating an effect of neighborhood density and word frequency on intelligibility were replicated. Clinical and research implications of the findings are discussed, and three exemplar SIT tests systematically controlling for neighborhood density and word frequency are provided.