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ObjectiveThe present longitudinal study examines how age of alcohol initiation and regular use (weekly drinking for ≥6 months) relates to adolescent physiological development, social behaviors, psychological functioning, and substance use patterns. Method: Data are drawn from a prospective sample of 295 youth (42% female) who completed a 15-year longitudinal study. The current investigation uses data collected at 4 timepoints from ages 12-19. Results: Latent growth modeling revealed earlier age of alcohol initiation is associated with (1) a more advanced stage of pubertal development, more self-reported dating experience, and greater externalizing behaviors at ages 12-13 (study entry); (2) a slower rate of change in pubertal development; and (3) greater rate of increase in externalizing and internalizing symptoms from ages 12 to 19. These relationships were not moderated by gender. Conclusion: Early alcohol initiation appears to be associated with early onset pubertal development and dating behaviors. Over time, early alcohol use behaviors may delay pubertal development while exacerbating psychological risk behaviors (i.e. externalizing and internalizing behaviors). These findings suggest the importance of delaying alcohol initiation and may be beneficial for improving existing adolescent substance use prevention efforts.

Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatment-seeking individuals meeting DSM-IV criteria for MA abuse or dependence (n=30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of 'crave drug,' 'stimulated,' and 'would like drug access,' decreased the the post-MA administration timecourse of 'anxious' and increased ratings of 'bad drug effects,' as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA.

Background: While methamphetamine (MA) and alcohol are often used in combination, little is known about the pattern of co-use between these substances. The goal of the present study is to examine the relationship between MA use and alcohol use in a community sample of non-treatment seeking regular MA users. Methods: Participants completed a face-to-face assessment battery, which included a diagnostic interview for MA dependence and the timeline follow-back interview for both alcohol and MA use over the past 30 days. Sixty regular MA and alcohol users supplied data for 1800 person-days. Results: Compared with non-drinking days, drinking days and binge drinking days increased the odds of same day MA use by 4.22 and 4.50 times, respectively (p's.

Background: Given numerous reports implicating involvement of the precuneus in cue-reactivity paradigms, the goal of this investigation was to examine the relationship between activation of the precuneus in response to drug cues and measures of subjective craving and severity of dependence in volunteers who were comorbid for alcohol and nicotine abuse. Methods: Forty research participants, who all reported heavy drinking and daily smoking, were recruited (15 women; 70% Caucasian; mean age. = 31.2 years) for a functional magnetic resonance imaging (fMRI) session involving a cigarette video-cues task and an alcohol taste-cues task. Mean precuneus activation from both tasks during cue presentation was subjected to bivariate correlation analyses with indices of dependence severity and subjective craving. Results: Precuneus activation in the contrast of Cigarette Cues vs. Control Cues was positively correlated with scores on the Fagerström Test of Nicotine Dependence (r= 0.389, p= 0.016), and activation in the Alcohol Cues vs. Control Cues contrast was positively correlated with Alcohol Dependence Scale scores (r= 0.338, p= 0.038). No correlations with subjective craving were observed (ps. >. 0.05). Conclusions: These findings indicate that the precuneus is involved in cue reactivity for both cigarettes and alcohol, and that this involvement is moderated by severity of drug dependence. The precuneus may be a cortical locus for neuroplastic changes related to drug dependence. © 2014 Elsevier Ireland Ltd.

Background: Despite initial reports of a decline in use in the early 2000s, methamphetamine remains a significant public health concern with known neurotoxic and neurocognitive effects to the user. The goal of this review is to update the literature on methamphetamine use and addiction since its assent to peak popularity in 1990s. Methods: We first review recent epidemiological reports with a focus on methamphetamine accessibility, changes in use and disorder prevalence rates over time, and accurate estimates of the associated burden of care to the individual and society. Second, we review methamphetamine pharmacology literature with emphasis on the structural and functional neurotoxic effects associated with repeated use of the drug. Third, we briefly outline the findings on methamphetamine-related neurocognitive deficits as assessed via behavioral and neuroimaging paradigms. Lastly, we review the clinical presentation of methamphetamine addiction and the evidence supporting the available psychosocial and pharmacological treatments within the context of an addiction biology framework. Conclusion: Taken together, this review provides a broad-based update of the available literature covering methamphetamine research over the past two decades and concludes with recommendations for future research.

Rationale: Heavy-drinking smokers constitute a sizeable and hard-to-treat subgroup of smokers, for whom tailored smoking cessation therapies are not yet available.

Background: Alcohol dependence is a complex psychological disorder whose phenomenology changes as the disorder progresses. Neuroscience has provided a variety of theories and evidence for the development, maintenance, and severity of addiction; however, clinically, it has been difficult to evaluate alcohol use disorder (AUD) severity.Objective: This study seeks to evaluate and validate a data-driven approach to capturing alcohol severity in a community sample.Method: Participants were non-treatment seeking problem drinkers (n = 283). A structural equation modeling approach was used to (a) verify the latent factor structure of the indices of AUD severity; and (b) test the relationship between the AUD severity factor and measures of alcohol use, affective symptoms, and motivation to change drinking.Results: The model was found to fit well, with all chosen indices of AUD severity loading significantly and positively onto the severity factor. In addition, the paths from the alcohol use, motivation, and affective factors accounted for 68% of the variance in AUD severity. Greater AUD severity was associated with greater alcohol use, increased affective symptoms, and higher motivation to change.Conclusion: Unlike the categorical diagnostic criteria, the AUD severity factor is comprised of multiple quantitative dimensions of impairment observed across the progression of the disorder. The AUD severity factor was validated by testing it in relation to other outcomes such as alcohol use, affective symptoms, and motivation for change. Clinically, this approach to AUD severity can be used to inform treatment planning and ultimately to improve outcomes. © 2013 Moallem, Courtney, Bacio and Ray.

Background: Atrial fibrillation is the most prevalent cardiac arrhythmia, presenting symptomatic patients with diminished quality of life and worsening of heart failure. Dofetilide, a class 3 antiarrhythmic agent, is a proven and safe rhythm control medication. Initial risk of QT prolongation leading to torsade de pointes (TdP) necessitates a standard protocol mandating hospitalization for three days for initiation. Objectives: To assess safety when adhering to initiation protocol and identify traits for susceptibility to TdP in elective dofetilide admissions. Methods: We conducted a retrospective study involving patients admitted to Mayo Clinic sites across four states for elective inpatient initiation of dofetilide between 2003 and 2022. Patients’ charts underwent review, focusing on dofetilide-related TdP occurrences, baseline characteristics including QT intervals, laboratory values, comorbidities, and concomitant medications. Patients who experienced TdP were subjected to further evaluation to identify potential risk factors. Results: Of 2036 patients identified, mean age 66.4 ± 11.4 years, and 67.2 % male, 16 experienced dofetilide-related TdP (incidence rate 0.79%). Notably, 81% (13/16) of TdP cases occurred in patients who deviated from the FDA/manufacturer algorithm protocol. The concomitant use of active intravenous diuretic therapy, digoxin, and QT-prolonging drugs emerged as identifiable risk factors. Additionally, females exhibited a higher incidence of TdP (1.5%) than males (0.44%) {odd ratio [OR] 3.46; P = 0.017}. Conclusion: Overall incidence of TdP related to dofetilide initiation was low (0.79%). Adherence to protocol during elective hospital admissions appears extraordinarily safe. Patients who did not require concurrent use of intravenous diuretics, digoxin, or QT prolonging drugs exhibited lower risk of TdP.

Abstract Background The Coronavirus (COVID-19) pandemic has exacerbated the risk for poor physical and mental health outcomes among vulnerable older adults. Multicomponent interventions could potentially prevent or reduce the risk of becoming frail; however, there is limited evidence about utilizing alternative modes of delivery where access to in-person care may be challenging. This randomized feasibility trial aimed to understand how a multicomponent rehabilitation program can be delivered remotely to vulnerable older adults with frailty during the pandemic. Methods Participants were randomized to either a multimodal or socialization arm. Over a 12-week intervention period, the multimodal group received virtual care at home, which included twice-weekly exercise in small group physiotherapy-led live-streamed sessions, nutrition counselling and protein supplementation, medication consultation via a videoconference app, and once-weekly phone calls from student volunteers, while the socialization group received only once-weekly phone calls from the volunteers. The RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework was used to evaluate the feasibility of the program. The main clinical outcomes were change in the 5-times sit-to-stand test (5 × STS) and Depression, Anxiety and Stress Scale (DASS-21) scores. The feasibility outcomes were analyzed using descriptive statistics and expressed as frequencies and mean percent with corresponding confidence intervals (CI). Analysis of covariance (ANCOVA) was used for the effectiveness component. Results The program enrolled 33% (n = 72) of referrals to the study (n = 220), of whom 70 were randomized. Adoption rates from different referral sources were community self-referrals (60%), community organizations (33%), and healthcare providers (25%). At the provider level, implementation rates varied from 75 to 100% for different aspects of program delivery. Participant’s adherence levels included virtual exercise sessions 81% (95% CI: 75–88%), home-based exercise 50% (95% CI: 38–62%), protein supplements consumption 68% (95% CI: 55–80%), and medication optimization 38% (95% CI: 21–59%). Most participants (85%) were satisfied with the program. There were no significant changes in clinical outcomes between the two arms. Conclusion The GERAS virtual frailty rehabilitation study for community-dwelling older adults living with frailty was feasible in terms of reach of participants, adoption across referral settings, adherence to implementation, and participant’s intention to maintain the program. This program could be feasibly delivered to improve access to socially isolated older adults where barriers to in-person participation exist. However, trials with larger samples and longer follow-up are required to demonstrate effectiveness and sustained behavior change. Trial registration ClinicalTrials.gov NCT04500366. Registered August 5, 2020, https://clinicaltrials.gov/ct2/show/NCT04500366

Abstract Background Dance is a mind-body activity of purposeful rhythmic movement to music. There is growing interest in using dance as a form of cognitive and physical rehabilitation. This manuscript describes the development of GERAS DANcing for Cognition and Exercise (DANCE) and evaluates its feasibility in older adults with cognitive and mobility impairments. Methods The progressive dance curricula were delivered for 15 weeks (1-h class; twice weekly). Participants were eligible if they were community-dwelling older adults aged 60+ with early cognitive or mobility impairment able to follow three-step commands and move independently. Feasibility outcomes included recruitment/retention, adherence, participant satisfaction, safety, and adverse events. Results Twenty-five older adults (mean (standard deviation [SD]) age = 77.55 (6.10) years, range 68–90 years) with early cognitive (Montreal Cognitive Assessment score (SD) = 21.77 (4.05)) and mobility (92% were pre-frail/frail as indicated on the Fried Frailty Phenotype) impairments were recruited from a geriatric out-patient clinic or within the community. A total of 20/25 (80%) participants completed the study. Average class attendance was 72%, and self-reported homework adherence “most-days / every day” was 89%. A stepwise progression in the dance curricula was observed with increases in motor complexity and balance demands, and 95% of participants rated the program as a “just-right” challenge. Ninety percent of participants rated GERAS DANCE as excellent, and 100% would recommend the program to a friend or family member. Over 50% of participants connected outside of class time for a self-initiated coffee club. Adverse events of falls and fractures were reported for 2 participants, which occurred at home unrelated to the dance intervention during the study period. Pre-determined thresholds for feasibility were met for all outcomes. Discussion GERAS DANCE is a feasible and enjoyable program for older adults with early cognitive or mobility impairments. GERAS DANCE curriculum grading (duration; sequence; instructions) and motor complexity increases in agility, balance, and coordination appear appropriately tailored for this population. Future work will explore the feasibility of GERAS DANCE in new settings (i.e., virtually online, community centers, or retirement homes) and the mind-body-social benefits of dance.

Inspiring visitors to engage in conservation-related behaviour following a zoo visit is a primary objective for most zoos. Animal–visitor interactive (AVI) experiences are often central to this goal. Yet, these interactive experiences are insufficiently evaluated from both the visitors’ and captive animals’ perspectives. The current study took place at Fota Wildlife Park and involved the construction of an environmental enrichment device during an interactive visitor experience with Sumatran tigers (Panthera tigris sumatrae). It aimed to simultaneously encourage pro-conservation behaviour in visitors and promote animal welfare. Visitors (n = 51) completed a survey, observed the tigers’ behaviour and made a pledge to help tigers in the wild after completion of the AVI. Tiger behaviour was simultaneously observed by a trained researcher using occurrence or non-occurrence sampling, which found no indication that tiger welfare was compromised during the activity and was likely enhanced by engaging with the enrichment. Additionally, visitors observed a range of tigers’ behaviours. The results indicated that some visitors (8%) had continued with their pledge six weeks after the experience, and most visitors exhibited a high level of knowledge and a positive attitude towards tigers. The use of enrichment during AVIs may be a positive link between the visitor experience and animal welfare. These results can be used to guide AVIs in zoos which aim to connect people with nature and drive pro-conservation behaviour in visitors.

Inflammation is central to the mechanisms of parturition, but the lack of understanding of how it is controlled in normal parturition hampers our ability to understand how it may diverge resulting in preterm birth. Cell-free fetal DNA is found in the amniotic fluid, and it is thought to be able to activate inflammation as a danger-associated molecular pattern. Although its levels increases with gestational age, its effect has not been studied on the human fetal membranes. Thus, the aim of this study was to determine if the fetal DNA can trigger inflammation in the human fetal membranes and, thus, potentially contribute to the inflammatory load. Isolated human amniotic epithelial cells and fetal membrane explants were treated apically with fetal DNA causing the translocation of NF-KB into the nucleus of cells and throughout the cells of the explant layers with time. Fetal membrane explants were treated apically with either small or larger fragments of fetal DNA. IL-6, TNFα, and GM-CSF secretion was measured by ELISA, and pro-MMP2 and pro-MMP9 activity was measured by zymography from apical and basal media. Increased apical IL-6 secretion and basal pro-MMP2 activity was seen with small fragments of fetal DNA. When the data were disaggregated based on fetal sex, males had significant increases in IL-6 secretion and basal increased activity in pro-MMP2 and 9, whereas females had significantly increased basal secretion of TNFα. This was caused by the smaller fragments of fetal DNA, whereas the larger fragments did not cause any significant increases. Male fetal DNA had significantly lower percentages of methylation than females. Thus, when the cytokine and pro-MMP activity data were correlated with methylation percentage, IL-6 secretion significantly correlated negatively, whereas GM-CSF secretion positively correlated. These data support the role of fetal DNA as an inflammatory stimulus in the FM, as measured by increased NF-κB translocation, cytokine secretion, and increased pro-MMP activity. However, the data also suggested that the responses are different from FM tissues of male and female fetuses, and both the fragment size and methylation status of the fetal DNA can influence the magnitude and type of molecule secreted.

Background: Prior studies have reported conflicting results of persistent iatrogenic atrial septal defect (iASD) and its impact following a transcatheter edge-to-edge repair (TEER) procedure. This study aims to evaluate the incidence of iASD and its clinical and hemodynamic impact after a TEER. Methods: Consecutive patients who underwent a TEER procedure from June 2014 to September 2020 at the Mayo Clinic were identified. The presence of iASD was retrospectively identified on post-procedure transthoracic echocardiography (TTE) to group patients into an iASD+ group and an iASD− group for comparison of prognosis and cardiac function. Results: A total of 316 patients were included; the mean age was 79.1 ± 9.1 years, and 67.7% were male. Persistent iASD was diagnosed in 108 (34.2%) patients. There was no difference concerning all-cause mortality, heart failure hospitalization, and stroke/TIA between groups at follow-up (median follow-up of 9 months). Post-procedure TTE demonstrated no differences regarding right ventricle (RV) and left ventricle (LV) dimensions and function, including TAPSE (15.2 ± 4.6 vs. 15.4 ± 5.5 mm, p = 0.875), and LV ejection fraction (51.1 ± 14.0% vs. 51.3 ± 13.9%, p = 0.933). However, patients with iASD had higher RV systolic pressure (48.7 ± 14.4 vs. 45.5 ± 14.5 mmHg, p = 0.042) compared with patients without iASD. Conclusion: Notwithstanding higher RV pressures, patients with persistent iASD had no hemodynamic compromise and an equal prognosis compared with those without a residual atrial defect after a TEER procedure. These findings support the mid-term safety of procedures in which an interatrial defect needs to be created and would argue against the need for interventional closure.

In the setting of increasing restrictions to legal abortion in the United States, reports have emerged of self-induced termination of pregnancies with misoprostol, obtained without a prescription or provider. This study seeks to describe the prevalence of women seeking or employing misoprostol for self-induced abortion, and how they access information. In a cross-sectional study of women immediately following their abortion at three reproductive health clinics in the Midwestern United States, an anonymous survey queried gestational age, barriers, online investigation about self-induction and opinions concerning the availability of medical abortion. From June to September 2016, 276 women participated out of 437 presenting to the clinics during the study period. One hundred and ninety-one (74.6%) women had investigated abortion options online, and of those, 58 (30.9%) investigated misoprostol online, for home use. Women who investigated online options were less likely to have had a prior abortion than those who did not investigate online (29.3% vs. 63.1%, p

Background: The assessment of methods for analyzing over-dispersed zero inflated count outcome has received very little or no attention in stratified cluster randomized trials. In this study, we performed sensitivity analyses to empirically compare eight methods for analyzing zero inflated over-dispersed count outcome from the Vitamin D and Osteoporosis Study (ViDOS) – originally designed to assess the feasibility of a knowledge translation intervention in long-term care home setting. Method: Forty long-term care (LTC) homes were stratified and then randomized into knowledge translation (KT) intervention (19 homes) and control (21 homes) groups. The homes/clusters were stratified by home size ( = 250) and profit status (profit/non-profit). The outcome of this study was number of falls measured at 6-month post-intervention. The following methods were used to assess the effect of KT intervention on number of falls: i) standard Poisson and negative binomial regression; ii) mixed-effects method with Poisson and negative binomial distribution; iii) generalized estimating equation (GEE) with Poisson and negative binomial; iv) zero inflated Poisson and negative binomial — with the latter used as a primary approach. All these methods were compared with or without adjusting for stratification. Results: A total of 5,478 older people from 40 LTC homes were included in this study. The mean (=1) of the number of falls was smaller than the variance (=6). Also 72% and 46% of the number of falls were zero in the control and intervention groups, respectively. The direction of the estimated incidence rate ratios (IRRs) was similar for all methods. The zero inflated negative binomial yielded the lowest IRRs and narrowest 95% confidence intervals when adjusted for stratification compared to GEE and mixed-effect methods. Further, the widths of the 95% confidence intervals were narrower when the methods adjusted for stratification compared to the same method not adjusted for stratification. Conclusion: The overall conclusion from the GEE, mixed-effect and zero inflated methods were similar. However, these methods differ in terms of effect estimate and widths of the confidence interval. Trial registration: ClinicalTrials.gov: NCT01398527. Registered: 19 July 2011. Keywords: Cluster randomized trial, Stratification, Count, Zero inflated, Overdispersed, Sensitivity

Abstract Background Despite knowing better how to screen older adults, understanding how frailty progression might be modified is unclear. We explored effects of modifiable and non-modifiable factors on changes in frailty in community-dwelling adults aged 50+ years who participated in the Canadian Multicentre Osteoporosis Study (CaMos). Methods Rates of change in frailty over 10 years were examined using the 30-item CaMos Frailty Index (CFI). Incident and prevalent low-trauma fractures were categorized by fracture site into hip, clinical vertebral and non-hip-non-vertebral fractures. Multivariable generalized estimating equation models accounted for the time of frailty assessment (baseline, 5 and 10 years), sex, age, body mass index (BMI, kg/m2), physical activity, bone mineral density, antiresorptive therapy, health-related quality of life (HRQL), cognitive status, and other factors for frailty or fractures. Multiple imputation and scenario analyses addressed bias due to attrition or missing data. Results The cohort included 5566 women (mean ± standard deviation: 66.8 ± 9.3 years) and 2187 men (66.3 ± 9.5 years) with the mean baseline CFI scores of 0.15 ± 0.11 and 0.12 ± 0.10, respectively. Incident fractures and obesity most strongly predicted frailty progression in multivariable analyses. The impact of fractures differed between the sexes. With each incident hip fracture, the adjusted mean CFI accelerated per 5 years by 0.07 in women (95% confidence interval [CI]: 0.03 to 0.11) and by 0.12 in men (95% CI: 0.08 to 0.16). An incident vertebral fracture increased frailty in women (0.05, 95% CI: 0.02 to 0.08) but not in men (0.01, 95% CI: -0.07 to 0.09). Irrespective of sex and prevalent fractures, baseline obesity was associated with faster frailty progression: a 5-year increase in the adjusted mean CFI ranged from 0.01 in overweight (BMI: 25.0 to 29.9 kg/m2) to 0.10 in obese individuals (BMI: ≥ 40 kg/m2). Greater physical activity and better HRQL decreased frailty over time. The results remained robust in scenario analyses. Conclusions Older women and men with new vertebral fractures, hip fractures or obesity represent high-risk groups that should be considered for frailty interventions.

Abstract Background Cognitive impairment is characterized by problems in thinking, memory, language, and judgment that are greater than cognitive changes in normal aging. Considering the unprecedented growth of the older adult population and the projected increase in the prevalence of cognitive impairment, it is imperative to find effective strategies to improve or maintain cognitive function in older adults. The objective of this review is to summarize the effects of dance versus any other control group on cognitive function, physical function, adverse events, and quality of life in older adults. Method We will search the following databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify the randomized controlled trials (RCTs) evaluating the effects of dance on cognitive function among older adults. Also, we will search http://apps.who.int/trialsearch, clinicaltrials.gov and conference abstracts to identify ongoing and unpublished studies. There will be no restrictions on language, date, or journal of publication. Reviewers will independently and in duplicate screen for eligible studies using pre-defined criteria. Data extraction from eligible studies will be performed independently and in duplicate. The Cochrane risk of bias tool will be used to assess the risk of bias of studies. Our primary outcome of interest is cognitive function, more specifically the executive function domain. We will include other domains as well such as processing speed and reaction time. Secondary outcomes of interest are physical function. The secondary outcomes also include adverse events including falls and quality of life. We will use Review Manager (RevMan 5.3) to pool the effect of dance for each outcome where possible. Results will be presented as relative risks along with 95% confidence intervals for dichotomous outcomes and as mean differences, or standardized mean differences along with 95% confidence intervals, for continuous outcomes. We will assess the certainty of the evidence using the GRADE approach and present findings in a Summary of Findings table. Discussion This systematic review, to our best knowledge the first-ever, will synthesize the available evidence on the effects of dance on cognitive function among older people. Systematic review registration PROSPERO CRD42017057138

We examine the impact of atmospheric correction, specifically aerosol model selection, on retrieval of bio-optical properties from satellite ocean color imagery. Uncertainties in retrievals of bio-optical properties (such as chlorophyll, absorption, and backscattering coefficients) from satellite ocean color imagery are related to a variety of factors, including errors associated with sensor calibration, atmospheric correction, and the bio-optical inversion algorithms. In many cases, selection of an inappropriate or erroneous aerosol model during atmospheric correction can dominate the errors in the satellite estimation of the normalized water-leaving radiances (nLw), especially over turbid, coastal waters. These errors affect the downstream bio-optical properties. Here, we focus on the impact of aerosol model selection on the nLw radiance estimates by comparing Aerosol Robotic Network-Ocean Color (AERONET-OC) measurements of nLw and aerosol optical depth (AOD) to satellite-derived values from Moderate Resolution Imaging Spectroradiometer (MODIS) and Sea-viewing Wide Field-of-view Sensor (SeaWiFS). We also apply noise to the satellite top-of-atmosphere (TOA) radiance values in the two near-infrared (NIR) wavelengths used for atmospheric correction, to assess the effect on aerosol model selection and nLw retrievals. In general, for the data sets examined, we found that as little as 1% uncertainty (noise) in the NIR TOA radiances can lead to the selection of a different pair of bounding aerosol models, thus changing nLw retrievals. We also compare aerosol size fraction retrieved from AERONET and size fraction represented by aerosol models selected during atmospheric correction.

ObjectivesTo compare the predictive accuracy of the frailty index (FI) of deficit accumulation and the phenotypic frailty (PF) model in predicting risks of future falls, fractures and death in women aged ≥55 years.MethodsBased on the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort (n = 3,985), we compared the predictive accuracy of the FI and PF in risks of falls, fractures and death using three strategies: (1) investigated the relationship with adverse health outcomes by increasing per one-fifth (i.e., 20%) of the FI and PF; (2) trichotomized the FI based on the overlap in the density distribution of the FI by the three groups (robust, pre-frail and frail) which were defined by the PF; (3) categorized the women according to a predicted probability function of falls during the third year of follow-up predicted by the FI. Logistic regression models were used for falls and death, while survival analyses were conducted for fractures.ResultsThe FI and PF agreed with each other at a good level of consensus (correlation coefficients ≥ 0.56) in all the three strategies. Both the FI and PF approaches predicted adverse health outcomes significantly. The FI quantified the risks of future falls, fractures and death more precisely than the PF. Both the FI and PF discriminated risks of adverse outcomes in multivariable models with acceptable and comparable area under the curve (AUCs) for falls (AUCs ≥ 0.68) and death (AUCs ≥ 0.79), and c-indices for fractures (c-indices ≥ 0.69) respectively.ConclusionsThe FI is comparable with the PF in predicting risks of adverse health outcomes. These findings may indicate the flexibility in the choice of frailty model for the elderly in the population-based settings.

Introduction: There is ongoing concern about the impact of increasing use of social media and digital devices on unhealthy behaviors such as substance use in youth. Mobile phone and social media use have been associated with substance use in adolescent and young adult samples, but few studies have evaluated these relationships in younger samples., Methods: This secondary analysis of data drawn from the ABCD Study examined associations between youth-reported mobile phone ownership and social media use at age 11-12 and use of alcohol, nicotine/tobacco, and cannabis over the next 18 months., Results: Longitudinal logistic regression was used to test the hypothesis that phone ownership and social media use at age 11-12 would predict substance use over time. Phone ownership was associated with greater odds of alcohol and nicotine/tobacco use, and social media use was associated with greater odds of using nicotine/tobacco and cannabis., Conclusions: These findings suggest that pre-teen youth who own mobile phones and those who use social media may be at greater risk for substance use. Further research is needed to specify mechanisms by which this association occurs and thus inform prevention and intervention efforts., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Neal Doran, Natasha Wade, Kelly Courtney, Joanna Jacobus reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Introduction: Chronic use of nicotine and tobacco products (NTP) continues to be a leading cause of morbidity and mortality. Uptake is most common among youth and young adults but knowledge about effective prevention and intervention approaches is insufficient. The goal of the present study was to examine the impact of social cognitive factors on NTP risk over time among youth in the national ABCD cohort., Methods: Participants (n=11,880, 47.8% female) were 9-10 years old at baseline, and completed multiple assessments of NTP use and related cognitions over two years. Structural equation modeling was used to estimate concurrent and prospective associations between social cognitive factors (peer and parent NTP use and perceptions of peer approval and harms from e-cigarette use) and risk for NTP use., Results: Participant NTP use was primarily of e-cigarettes. Higher levels of parental and especially peer NTP use were significant prospective predictors of greater risk of NTP use. Lower perceived harm from and higher peer approval of e-cigarette use were significant predictors of heightened current but not future NTP risk., Conclusion: Findings suggest that youth perceptions of peer NTP use is a key predictor of the likelihood of use and a potential target for interventions designed to prevent or reduce e-cigarette and other NTP use in youth., Implications: findings indicate that perceived peer use is a more powerful predictor of nicotine and tobacco product (NTP) use than cognitive factors or parental use, even at early ages when youth NTP use is uncommon. This suggests a need for additional early intervention targeting perceptions of and responding to peer NTP use.

Introduction: Cannabis and nicotine/tobacco products (NTP) are commonly co-used in adolescence and young adulthood; however, limited research has been done on predictive health behaviors to co-use. The current study is a preliminary investigation into the relationships of modifiable health behaviors on cannabis and NTP co-use in adolescents and young adults., Method: 221 participants (ages 16-22) were characterized into cannabis use only (N = 55), NTP use only (N = 20), cannabis and NTP co-use (used cannabis and NTP; N = 96) and control (no use; N = 50) groups based on past 30-day use. Self-report measures for physical activity, sleep quality, mental health, and reward responsivity were utilized. Participants were given a comprehensive neurocognitive battery. Logistic regressions of self-report measures and fluid intelligence composite scores on substance use group status were run stratified by sex., Results: Higher approach reward sensitivity traits were associated with increased likelihood of cannabis use only (Odds Ratio (OR) = 1.15, p = .036) in female participants. Increased aerobic activity was associated with decreased likelihood of cannabis use only (OR = 0.91, p = .047) and cannabis and NTP co-use (OR = 0.88, p = .007) in female participants. Higher anxiety was associated with increased likelihood of cannabis NTP co-use (OR = 1.51, p = 0.025) in male participants., Discussion: Several health behaviors were linked with cannabis use and cannabis and NTP co-use in both females and male adolescents and young adults. Health markers differed by sex suggesting differing mechanisms of substance co-use. This study informs targetable health behaviors for prevention and intervention efforts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: With the advent of electronic nicotine delivery systems, the use of nicotine and tobacco products (NTPs) among adolescents and young adults remains high in the US. Use of e-cigarettes additionally elevates the risk of problematic use of other substances like cannabis, which is often co-used with NTPs. However, their effects on brain health, particularly the hippocampus, and cognition during this neurodevelopmental period are poorly understood., Methods: Healthy late adolescents/young adults ( N  = 223) ages 16-22 completed a structural MRI to examine right and left hippocampal volumes. Memory was assessed with the NIH Toolbox Picture Sequence Memory Test (PSMT) and Rey Auditory Verbal Learning Test (RAVLT). Cumulative 6-month NTP and cannabis episodes were assessed and modeled continuously on hippocampal volumes. Participants were then grouped based on 6-month NTP use to examine relationships with the hippocampus and memory: current users (CU) endorsed weekly or greater use; light/abstinent users (LU) endorsed less than weekly; and never users (NU)., Results: NTP use predicted larger hippocampal volumes bilaterally while cannabis use had no impact nor interacted with NTP use. For memory, larger left hippocampal volumes were positively associated with PSMT performance, RAVLT total learning, short delay and long delay recall for the NU group. In contrast, there was a negative relationship between hippocampal volumes and performances for LU and CU groups. No differences were detected between NTP-using groups., Conclusion: These results suggest that the hippocampus is sensitive to NTP exposure during late adolescence/young adulthood and may alter typical hippocampal morphometry in addition to brain-behavior relationships underlying learning and memory processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Happer, Courtney, Baca, Andrade, Thompson, Shen, Liu and Jacobus.)

Background: Incentive salience processes are important for the development and maintenance of addiction. Eye characteristics such as gaze fixation time, pupil diameter, and spontaneous eyeblink rate (EBR) are theorized to reflect incentive salience and may serve as useful biomarkers. However, conventional cue exposure paradigms have limitations that may impede accurate assessment of these markers., Objective: This study sought to evaluate the validity of these eye-tracking metrics as indicators of incentive salience within a virtual reality (VR) environment replicating real-world situations of nicotine and tobacco product (NTP) use., Methods: NTP users from the community were recruited and grouped by NTP use patterns: nondaily (n=33) and daily (n=75) use. Participants underwent the NTP cue VR paradigm and completed measures of nicotine craving, NTP use history, and VR-related assessments. Eye-gaze fixation time (attentional bias) and pupillometry in response to NTP versus control cues and EBR during the active and neutral VR scenes were recorded and analyzed using ANOVA and analysis of covariance models., Results: Greater subjective craving, as measured by the Tobacco Craving Questionnaire-Short Form, following active versus neutral scenes was observed (F1,106=47.95; P<.001). Greater mean eye-gaze fixation time (F1,106=48.34; P<.001) and pupil diameter (F1,102=5.99; P=.02) in response to NTP versus control cues were also detected. Evidence of NTP use group effects was observed in fixation time and pupillometry analyses, as well as correlations between these metrics, NTP use history, and nicotine craving. No significant associations were observed with EBR., Conclusions: This study provides additional evidence for attentional bias, as measured via eye-gaze fixation time, and pupillometry as useful biomarkers of incentive salience, and partially supports theories suggesting that incentive salience diminishes as nicotine dependence severity increases., (© Kelly Elizabeth Courtney, Weichen Liu, Gianna Andrade, Jurgen Schulze, Neal Doran. Originally published in JMIR Serious Games (https://games.jmir.org).)

Background: Young adults have historically high levels of cannabis use at a time which coincides with emotional and cognitive development. Age of regular onset of cannabis use and sex at birth are hypothesized to influence the relationship between cannabis use and cognition. Here we investigated past 6-month cannabis use in relation to emotional and executive functioning. We further considered age of onset and sex in subgroup analyses., Method: Young adults (N = 225; ages 16-22) completed a substance use interview and cognitive battery, including the Emotional Word-Emotional Face Stroop and NIH toolbox executive functioning tasks. Linear regressions examined relationships between past 6-month cannabis use episodes and performance. Subgroup analyses investigated whether age of onset or sex impacted relationships., Results: After correcting for multiple comparisons, greater past 6-month cannabis use episodes were related to poorer Emotional Stroop Congruent Accuracy (p = .0004, FDR-p = .002) and List Sorting Working Memory (p = .02, FDR-p = .10) performance. Younger age of regular use onset marginally related to lower Emotional Stroop Congruent Accuracy performance (p = .03, FDR-p = .13). There were no cannabis use by sex interactions on cognition., Conclusions: Consistent with prior findings, results suggest small reductions in cannabis-related performance in processing speed during emotional Stroop and working memory tasks. Age of onset was modestly related to Stroop performance, but not sex. Longitudinal studies which detail patterns of cannabis and other substance use are needed to better assess brain-behavior relationships and other factors (e.g., age of onset of regular use, sex) which could influence cannabis-related impairments in cognitive functioning., (© 2024. The Author(s).)

Adolescent traumatic brain injury (TBI) has long-term effects on brain functioning and behavior, impacting neural activity under cognitive load, especially in the reward network. Adolescent TBI is also linked to risk-taking behaviors including alcohol misuse. It remains unclear how TBI and neural functioning interact to predict alcohol experimentation during adolescence. Using Adolescent Brain Cognitive Development (ABCD) study data, this project examined if TBI at ages 9-10 predicts increased odds of alcohol sipping at ages 11-13 and if this association is moderated by neural activity during the Emotional EN-Back working memory task at ages 11-13. Logistic regression analyses showed that neural activity in regions of the fronto-basal ganglia network predicted increased odds of sipping alcohol by ages 11-13 (p < .05). TBI and left frontal pole activity interacted to predict alcohol sipping (OR = 0.507, 95% CI [0.303 - 0.846], p = .009) - increased activity predicted decreased odds of alcohol sipping for those with a TBI (OR = 0.516, 95% CI [0.314 - 0.850], p = .009), but not for those without (OR = 0.971, 95% CI [0.931 -1.012], p = .159). These findings suggest that for youth with a TBI, increased BOLD activity in the frontal pole, underlying working memory, may be uniquely protective against the early initiation of alcohol experimentation. Future work will examine TBI and alcohol misuse in the ABCD cohort across more time points and the impact of personality traits such as impulsivity on these associations., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest. Dr. Max provides expert testimony in cases of traumatic brain injury on an ad hoc basis for plaintiffs and defendants on a more or less equal ratio. This activity constitutes approximately 5% of his professional activities., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers., Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts., Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders., Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes., Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Introduction: Despite evidence suggesting deleterious effects of cannabis and nicotine tobacco product (NTP) use on white matter integrity, there have been limited studies examining white matter integrity among users of both cannabis and nicotine. Further, updated white matter methodology provides opportunities to investigate use patterns on neurite orientation dispersion and density (NODDI) indices and subtle tissue changes related to the intra- and extra-neurite compartment. We aimed to investigate how cannabis and NTP use among adolescents and young adults interacts to impact the white matter integrity microstructure., Materials and Methods: A total of 221 participants between the ages of 16 and 22 completed the Customary Drinking and Drug Use Record (CDDR) to measure substance use, and underwent a magnetic resonance imaging (MRI) session. Participants were divided into NTP-control and NTP groupings and cannabis-control and cannabis groupings (≥26 NTP/cannabis uses in past 6 months). Tract-Based Spatial Statistics (TBSS) and two-way between-subjects ANOVA investigated the effects of NTP use group, cannabis use group, and their interaction on fractional anisotropy (FA) and NODDI indices while controlling for age and biological sex., Results: NTP use was associated with decreased FA values and increased orientation dispersion in the left anterior capsule. There were no significant effects of cannabis use or the interaction of NTP and cannabis use on white matter outcomes., Discussion: NTP use was associated with altered white matter integrity in an adolescent and young adult sample. Findings suggest that NTP-associated alterations may be linked to altered fiber tract geometry and dispersed neurite structures versus myelination, as well as differential effects of NTP and cannabis use on white matter structure. Future work is needed to investigate how altered white matter is related to downstream behavioral effects from NTP use.

Early life substance use, including cannabis and nicotine, may result in deleterious effects on the maturation of brain tissue and gray matter cortical development. The current study employed linear regression models to investigate the main and interactive effects of past-year nicotine and cannabis use on gray matter cortical thickness estimates in 11 bilateral independent frontal cortical regions in 223 16-22-year-olds. As the frontal cortex develops throughout late adolescence and young adulthood, this period becomes crucial for studying the impact of substance use on brain structure. The distinct effects of nicotine and cannabis use status on cortical thickness were found bilaterally, as cannabis and nicotine users both had thinner cortices than non-users. Interactions between nicotine and cannabis were also observed, in which cannabis use was associated with thicker cortices for those with a history of nicotine and tobacco product (NTP) use in three left frontal regions. This study sheds light on the intricate relationship between substance use and brain structure, suggesting a potential modulation of cannabis' impact on cortical thickness by nicotine exposure, and emphasizing the need for further longitudinal research to characterize these interactions and their implications for brain health and development., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Nicotine and tobacco product (NTP) use remains prevalent in adolescence/young adulthood. The effects of NTPs on markers of brain health during this vulnerable neurodevelopmental period remain largely unknown. This report investigates associations between NTP use and gray matter cerebral blood flow (CBF) in adolescents/young adults. Adolescent/young adult (16-22 years-old) nicotine users (NTP; N = 99; 40 women) and non-users (non-NTP; N = 95; 56 women) underwent neuroimaging sessions including anatomical and optimized pseudo-continuous arterial spin labeling scans. Groups were compared on whole-brain gray matter CBF estimates and their relation to age and sex at birth. Follow-up analyses assessed correlations between identified CBF clusters and NTP recency and dependence measures. Controlling for age and sex, the NTP vs. non-NTP contrast revealed a single cluster that survived thresholding which included portions of bilateral precuneus (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05; ≥7 contiguous voxels). An interaction between NTP group contrast and age was observed in two clusters including regions of the left posterior cingulate (PCC)/lingual gyrus and right anterior cingulate cortex (ACC): non-NTP exhibited positive correlations between CBF and age in these clusters, whereas NTP exhibited negative correlations between CBF and age. Lower CBF from these three clusters correlated with urine cotinine (rs=-0.21 - - 0.16; ps < 0.04) and nicotine dependence severity (rs=-0.16 - - 0.13; ps < 0.07). This is the first investigation of gray matter CBF in adolescent/young adult users of NTPs. The results are consistent with literature on adults showing age- and nicotine-related declines in CBF and identify the precuneus/PCC and ACC as potential key regions subserving the development of nicotine dependence., (© 2023. The Author(s).)

Background: Nicotine and tobacco product (NTP) and cannabis use are common in adolescence/young adulthood and increase risk for negative psychosocial outcomes. This study investigated associations among adolescent/young adults' initial experiences with NTPs, lifetime frequency of substance use, substance-related problems, and mental health symptoms., Method: Adolescents and young adults enrolled in a study on NTP and cannabis use were asked at what age they initiated the use of NTPs and were assigned to groups based on which product or substance(s) they reported using at the earliest age. Participants who reported use of NTPs (in isolation, without cannabis) first ( N  = 78, "NTP-only"), simultaneous use of NTPs and cannabis first (e.g., blunt or bowl; N  = 25, "Simult-only"), use of both NTPs in isolation and simultaneous use at the same age ( N  = 48, "NTP + Simult"), and no NTP use ( N  = 53, "NTP-naïve") were compared on substance use, substance-related problems, and mental health symptoms., Results: Groups differed on lifetime frequency of NTP, simultaneous, and cannabis use, with NTP users reporting more substance use episodes and substance-related problems than the NTP-naïve group. The lifetime frequency of cannabis use did not differ across NTP use groups. NTP use was associated with increased anxiety and depression, with no significant differences between groups., Conclusions: Adolescents and young adults who use nicotine may be at increased risk for greater nicotine use and mental health consequences, but initiating NTP use simultaneously with cannabis may not increase the risk of negative outcomes above and beyond nicotine initiation. Prospective longitudinal research is needed to establish temporal associations between first-used NTP/cannabis products and relevant outcomes.

Objective: Eye-tracking technology is commonly used for identifying objects of visual attention. However, applying this technology to virtual reality (VR) applications is challenging. This report analyzes the performance of two gaze-to-object mapping (GTOM) algorithms applied to eye-gaze data acquired during a "real-world" VR cue-reactivity paradigm., Methods: Two groups of participants completed a VR paradigm using an HTC Vive Pro Eye. The gazed objects were determined by the reported gaze rays and one of two GTOM algorithms - naïve ray-casting (n=18) or a combination of ray-casting and Tobii's G2OM algorithm (n=18). Percent gaze duration was calculated from 1-second intervals before each object interaction to estimate gaze accuracy. The object volume of maximal divergence between algorithms was determined by maximizing the difference in Hedge's G effect sizes between small and large percent gaze duration distributions. Differences in percent gaze duration based on algorithm and target object size were tested with a mixed ANOVA., Results: The maximum Hedge's G effect sizes differentiating large and small target objects was observed at an 800cm 3 threshold. The combination algorithm performed better than the naïve ray-casting algorithm ( p =.003, η p 2 =.23), and large objects (>800cm 3 ) were associated with a higher gaze duration percentage than small objects (≤800cm 3 ; p <.001, η p 2 =.76). No significant interaction between algorithm and size was observed., Conclusions: Results demonstrated that Tobii's G2OM method outperformed naïve ray-casting in this "real-world" paradigm. As both algorithms show a clear decrease in performance for detecting objects with volumes <800cm 3 , we recommend using gaze-interactable objects >800cm 3 for future HTC Vive Pro Eye applications.

Nicotine craving typically develops shortly after last use and is conceptualized as essential to the development, maintenance, and treatment of nicotine dependence. Previous research has primarily examined the relationship between craving and use among individuals trying to quit smoking, and less is known about this relationship among active users, particularly e-cigarette users. The current study evaluated the association between craving and use by assessing both constructs twice daily over 7 days in a sample of daily (n = 80) and non-daily (n = 34) users of combustible tobacco and e-cigarette products. We used negative binomial regression modeling to analyze the relationship between nicotine craving and use in two ways. First, we evaluated a lagged model in which craving at the time of assessment predicted use during the next time period. Next, we evaluated a model in which maximum craving since the last assessment predicted use during the same time period. Maximum craving was significantly and positively associated with nicotine product use (p <.05) while craving at the time of assessment was not. These associations did not differ depending on use frequency or on specific products used. Findings provide evidence that self-report ratings of craving are associated with greater nicotine and tobacco product use for both frequent and intermittent users. Furthermore, these results may be useful in developing or modifying interventions for a wide variety of nicotine users, including those who are not yet intending to make a change to their nicotine use., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Disparities in sexual health outcomes between racial and ethnic groups throughout the state of Washington suggest the presence of systemic inequities impeding young people's experience with and access to sexual health care and education. Emerging innovations in sexual health look to center young people, particularly those who have been historically excluded, in the design and implementation of programs that aim to serve them. The Washington Youth Sexual Health Innovation and Impact Network (WYSHIIN) and 11 grant-funded partners engaged communities of youth across the state of Washington, including Two Spirit, lesbian, gay, bisexual, transgender, queer, questioning, intersex, and/or asexual (2SLGBTQIA+) and Black, Indigenous, and People of Color (BIPOC) youth, with the goal of equitably engaging participants and stakeholders to broaden services in schools and community settings. Evaluation staff from the Washington State Department of Health conducted virtual interviews with community partners for preliminary program evaluation purposes and identified 6 strategies for engaging youth. WYSHIIN partners highlighted strategies for centering youth voice and needs at all levels of program development and implementation, embracing holistic and culturally relevant approaches, and 2SLGBTQIA+ inclusion. These themes, reflective of wisdom across multiple Washington communities, offer strategies to address systemic issues that negatively impact youth access to and experience with sexual health care., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

Irritability is a prevalent, impairing transdiagnostic symptom, especially during adolescence, yet little is known about irritability's neural mechanisms. A few studies examined the integrity of white matter tracts that facilitate neural communication in irritability, but only with extreme, disorder-related symptom presentations. In this preliminary study, we used a group connectometry approach to identify white matter tracts correlated with transdiagnostic irritability in a community/clinic-based sample of 35 adolescents (mean age = 14 years, SD = 2.0). We found positive and negative associations with irritability in local white matter tract bundles including sections of the longitudinal fasciculus; frontoparietal, parolfactory, and parahippocampal cingulum; corticostriatal and thalamocortical radiations; and vertical occipital fasciculus. Our findings support functional neuroimaging studies that implicate widespread neural pathways, particularly emotion and reward networks, in irritability. Our findings of positive and negative associations reveal a complex picture of what is "good" white matter connectivity. By characterizing irritability's neural underpinnings, targeted interventions may be developed., (Copyright © 2022. Published by Elsevier B.V.)

Alcohol use confers risk for suicidal thoughts and behaviors (ideation, attempt) in early adolescents. The Research Domain Criteria provides a framework for examination of multidimensional and modifiable risk factors. We examined distinct latent profiles based on patterns of positive valence (reward responsivity) and cognitive systems (neurocognition) from the ABCD Study (age 9−10, N = 10,414) at baseline enrollment. Longitudinal associations were determined between baseline positive valence and cognitive profiles and group classification (alcohol use, suicidal thoughts and behaviors, or their co-occurrence) two-years after initial assessment (ages 11−12). Three unique profiles of positive valence, cognition, alcohol use, and suicidal thoughts and behaviors were identified. Two baseline profiles predicted alcohol use and suicidal thoughts and behaviors, two-years after initial assessment. Low positive valence with high cognition (but low impulsivity) predicted alcohol use (OR = 1.414, p< 0.001), while high positive valence with low cognition (but high impulsivity) predicted suicidal thoughts and behaviors (OR = 1.25, p = 0.038), compared to average positive valence and cognition. Unique profiles of positive valence and cognitive systems among 9−12-year-olds may be predictive of alcohol use and suicidal thoughts and behaviors over a two-year period. Findings underscore the potential for trajectory research on positive valence and cognitive profiles to enhance prevention for early-adolescents.

Nicotine and tobacco product (NTP) use has escalated, largely due to the advent of e-cigarettes. The NTP administration method (i.e., combustible cigarette, e-cigarette) may be an important differentiator. We assessed young adult substance use history, nicotine attitudes, mental health, and neurocognition by the NTP use method. Emerging adults (16-22 year olds) were divided into combustible NTP users (Combustible+ = 79, had used any combustible NTP in the last 6 months), non-combustible users (E-Cig = 43, had used non-combustible NTP, in the past 6 months), and NTP Naïve ( n = 79; had not used NTP in the past 6 months) based on past 6-month NTP use patterns. Participants completed self-report and objective neurocognition measures. Analysis of covariance assessed mental health and neurocognition by group, controlling for confounds and correcting for multiple comparisons. Nicotine groups reported more favorable attitudes toward combustible cigarette and e-cigarette use, with taste as the primary reason for e-cigarette use. Combustible+ reported more nicotine dependence and craving. Substance use differed by group, with Combustible+ using the most NTP, alcohol, and cannabis. Nicotine groups reported higher depression and stress symptoms; male Combustible+ reported higher depression symptoms than other same-gender groups. Groups did not differ on neurocognition, though cannabis use was associated with inaccurate emotional Stroop responses. Overall, research suggests that young adult combustible users are likely qualitatively different from non-combustible users. Understanding the unique characteristics related to NTP product use will help guide intervention and prevention development.

Objective: Co-use of cannabis and nicotine and tobacco products (NTPs) in adolescence/young adulthood is common and associated with worse outcomes than the use of either substance in isolation. Despite this, little is known about the unique contributions of co-use to neurostructural microstructure during this neurodevelopmentally important period. This study sought to investigate the interactive effects of nicotine and cannabis co-use on white matter fiber tract microstructure in emerging adulthood., Method: A total of 111 late adolescent (16-22 years old) nicotine (NTP; n = 55, all past-year cannabis users) and non-nicotine users (non-NTP; n = 56, 61% reporting cannabis use in the past year) completed demographic and clinical interviews and a neuroimaging session comprising anatomical and diffusion-weighted imaging scans. Group connectometry analysis identified white matter tracts significantly associated with the interaction between nicotine group and past-year cannabis use according to generalized fractional anisotropy (GFA)., Results: Nicotine Group × Cannabis Use interactions were observed in the right and left cingulum and left fornix tracts (false discovery rate = 0.053), where greater cannabis use was associated with increased GFA in the cingulum and left fornix, but only when co-used with nicotine., Conclusions: This report represents the first group connectometry analysis in late adolescent/young adult cannabis and/or NTP users. Results suggest that co-use of cannabis and NTPs results in a structurally distinct white matter phenotype as compared with cannabis use only, although to what extent this may change over time with more chronic nicotine and cannabis use remains to be examined in future work.

Cue reactivity is one of the most frequently used paradigms in functional magnetic resonance imaging (fMRI) studies of substance use disorders (SUDs). Although there have been promising results elucidating the neurocognitive mechanisms of SUDs and SUD treatments, the interpretability and reproducibility of these studies is limited by incomplete reporting of participants' characteristics, task design, craving assessment, scanning preparation and analysis decisions in fMRI drug cue reactivity (FDCR) experiments. This hampers clinical translation, not least because systematic review and meta-analysis of published work are difficult. This consensus paper and Delphi study aims to outline the important methodological aspects of FDCR research, present structured recommendations for more comprehensive methods reporting and review the FDCR literature to assess the reporting of items that are deemed important. Forty-five FDCR scientists from around the world participated in this study. First, an initial checklist of items deemed important in FDCR studies was developed by several members of the Enhanced NeuroImaging Genetics through Meta-Analyses (ENIGMA) Addiction working group on the basis of a systematic review. Using a modified Delphi consensus method, all experts were asked to comment on, revise or add items to the initial checklist, and then to rate the importance of each item in subsequent rounds. The reporting status of the items in the final checklist was investigated in 108 recently published FDCR studies identified through a systematic review. By the final round, 38 items reached the consensus threshold and were classified under seven major categories: 'Participants' Characteristics', 'General fMRI Information', 'General Task Information', 'Cue Information', 'Craving Assessment Inside Scanner', 'Craving Assessment Outside Scanner' and 'Pre- and Post-Scanning Considerations'. The review of the 108 FDCR papers revealed significant gaps in the reporting of the items considered important by the experts. For instance, whereas items in the 'General fMRI Information' category were reported in 90.5% of the reviewed papers, items in the 'Pre- and Post-Scanning Considerations' category were reported by only 44.7% of reviewed FDCR studies. Considering the notable and sometimes unexpected gaps in the reporting of items deemed to be important by experts in any FDCR study, the protocols could benefit from the adoption of reporting standards. This checklist, a living document to be updated as the field and its methods advance, can help improve experimental design, reporting and the widespread understanding of the FDCR protocols. This checklist can also provide a sample for developing consensus statements for protocols in other areas of task-based fMRI., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Craving is a clinically important phenotype for the development and maintenance of nicotine addiction. Virtual reality (VR) paradigms are successful in eliciting cue-induced subjective craving and may even elicit stronger craving than traditional picture-cue methods. However, few studies have leveraged the advances of this technology to improve the assessment of craving., Objective: This report details the development of a novel, translatable VR paradigm designed to both elicit nicotine craving and assess multiple eye-related characteristics as potential objective correlates of craving., Methods: A VR paradigm was developed, which includes three Active scenes with nicotine and tobacco product (NTP) cues present, and three Neutral scenes devoid of NTP cues. A pilot sample (N=31) of NTP users underwent the paradigm and completed subjective measures of nicotine craving, sense of presence in the VR paradigm, and VR-related sickness. Eye-gaze fixation time ("attentional bias") and pupil diameter toward Active versus Neutral cues, as well as spontaneous blink rate during the Active and Neutral scenes, were recorded., Results: The NTP Cue VR paradigm was found to elicit a moderate sense of presence (mean Igroup Presence Questionnaire score 60.05, SD 9.66) and low VR-related sickness (mean Virtual Reality Sickness Questionnaire score 16.25, SD 13.94). Scene-specific effects on attentional bias and pupil diameter were observed, with two of the three Active scenes eliciting greater NTP versus control cue attentional bias and pupil diameter (Cohen d=0.30-0.92). The spontaneous blink rate metrics did not differ across Active and Neutral scenes., Conclusions: This report outlines the development of the NTP Cue VR paradigm. Our results support the potential of this paradigm as an effective laboratory-based cue-exposure task and provide early evidence of the utility of attentional bias and pupillometry, as measured during VR, as useful markers for nicotine addiction., (©Weichen Liu, Gianna Andrade, Jurgen Schulze, Neal Doran, Kelly E Courtney. Originally published in JMIR Serious Games (https://games.jmir.org), 15.02.2022.)

Objective: Verbal memory deficits are linked to cannabis use. However, self-reported episodic use does not allow for assessment of variance from other factors (e.g., cannabis potency, route of consumption) that are important for assessing brain-behavior relationships. Further, co-occurring nicotine use may moderate the influence of cannabis on cognition. Here we utilized objective urinary measurements to assess the relationship between metabolites of cannabis, 11-nor-9-carboxy-∆9-tetrahydrocannabinol (THCCOOH), and nicotine (cotinine) on verbal memory in young adults., Method: Adolescents and young adults (n = 103) aged 16-22 completed urinary drug testing and verbal memory assessment (RAVLT). Linear regressions examined the influence of THCCOOH and cotinine quantitative concentrations, and their interaction, on RAVLT scores, controlling for demographics and alcohol. Cannabis intake frequency was also investigated. Secondary analyses examined whether past month or recency of use related to performance, while controlling for THCCOOH and cotinine concentrations., Results: THCCOOH concentration related to both poorer total learning and long delay recall. Cotinine concentration related to poorer short delay recall. Higher frequency cannabis use status was associated with poorer initial learning and poorer short delay. When comparing to self-report, THCCOOH and cotinine concentrations were negatively related to learning and memory performance, while self-report was not., Conclusions: Results confirm the negative relationship between verbal memory and cannabis use, extending findings with objective urinary THCCOOH, and cotinine concentration measurements. No moderating relationship with nicotine was found, though cotinine concentration independently associated with negative short delay performance. Findings support the use of both urinary and self-report metrics as complementary methods in substance use research.

Rationale: Co-use of cannabis and nicotine is common among adolescents/young adults and is associated with poorer psychological and physical outcomes, compared with single substance use. Little is known about the impact of co-use on the developing brain., Objectives: Preliminary investigation of the effects of nicotine on white matter (WM) cerebral blood flow (CBF) in adolescents/young adults and its potential moderation by cannabis use., Methods: Adolescent/young adult (16-22 years old) nicotine and tobacco product users (NTP; N = 37) and non-nicotine users (non-NTP; N = 26) underwent a neuroimaging session comprised of anatomical, optimized pseudo-continuous arterial spin labeling, and diffusion tensor imaging scans. Groups were compared on whole-brain WM CBF estimates and their relation to past-year cannabis use. Follow-up analyses assessed correlations between identified CBF clusters and corresponding fractional anisotropy (FA) values., Results: Group by cannabis effects were observed in five clusters (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05; ≥ 11 contiguous voxels): non-NTP exhibited positive correlations between CBF and cannabis use in all clusters, whereas no significant relationships were observed for NTP. Greater CBF extracted from one cluster (including portions of right superior longitudinal fasciculus) was associated with reduced FA for non-NTP group only., Conclusions: This is the first investigation of WM health as indexed by CBF, and its association with FA, in adolescents/young adults with nicotine and/or cannabis use. Results suggest that cannabis use by itself may be related to increased CBF in WM fiber tracts demonstrating poorer structural intergrity, yet the occurrence of even infrequent NTP use (greater than once per month) appears to diminish this relationship.

Background : Emerging evidence suggests that opioid receptor antagonists, such as naltrexone, are effective pharmacotherapies for alcohol, opioid, and possibly stimulant use disorders. It is posited that naltrexone exerts its effects, in part, by increasing functional connectivity between neural reward circuitry and frontal systems implicated in executive function. Yet no studies had examined whether executive function moderates these effects. Objectives : This study examined whether a composite measure of executive function (EF) moderates the effect of naltrexone on craving for methamphetamine and subjective responses following infusion of the drug. Methods : Individuals with methamphetamine use disorder (N = 30; 27% female) completed baseline neurocognitive assessments of premorbid and executive function, and an executive function factor was computed. Participants then underwent a randomized, double-blind, cross-over study of titration with naltrexone and placebo. Participants then received a 30-mg intravenous methamphetamine infusion and completed subjective response questionnaires at 8 times in the 120 minutes post-infusion. Results : Multilevel mixed models indicated a significant EF × medication interaction, reflecting greater effects of naltrexone to decrease "desire to access the drug", "want more of the drug", "crave the drug", "feel drug effects" and "feel high" in participants with low EF compared to those with high EF (Bs = .36-1.29, SEs = .14-.17, ps <0.01). These effects remained significant after controlling for premorbid cognitive functioning, baseline responses to methamphetamine, severity of methamphetamine use, and methamphetamine-related functional problems. Conclusion : Naltrexone may be especially effective in methamphetamine-dependent individuals with low EF. Neuropsychological assessments may also provide predictive clinical utility not captured by traditional measures of substance use severity.

Objectives: Alcohol and cannabis remain the substances most widely used by adolescents. Better understanding of the dynamic relationship between trajectories of substance use in relation to neuropsychological functioning is needed. The aim of this study was to examine the different impacts of within- and between-person changes in alcohol and cannabis use on neuropsychological functioning over multiple time points., Methods: Hierarchical linear modeling examined the effects of alcohol and cannabis use on neuropsychological functioning over the course of 14 years in a sample of 175 adolescents (aged 12-15 years at baseline)., Results: Time-specific fluctuations in alcohol use (within-person effect) predicted worse performance across time on the Wechsler Abbreviated Scale of Intelligence Block Design subtest (B = -.05, SE = .02, p = .01). Greater mean levels of percent days of cannabis use across time (between-person effect) were associated with an increased contrast score between Delis-Kaplan Executive Function System Color Word Inhibition and Color Naming conditions (B = .52, SE = .14, p < .0001) and poorer performance over time on Block Design (B = -.08, SE = .04, p = .03). Neither alcohol and/nor cannabis use over time was associated with performance in the verbal memory and processing speed domains., Conclusions: Greater cumulative cannabis use over adolescence may be linked to poorer inhibitory control and visuospatial functioning performance, whereas more proximal increases in alcohol consumption during adolescence may drive alcohol-related performance decrements in visuospatial functioning. Results from this prospective study add to the growing body of literature on the impact of alcohol and cannabis use on cognition from adolescent to young adulthood.

Background: Altered brain activation during response inhibition has been linked to a greater risk for alcohol and other substance use behaviors in late adolescence. However, the ability of neural markers of response inhibition, acquired during adolescence, to temporally predict the transition from less frequent and lower quantity alcohol use to high-risk, frequent (≥ weekly) binge drinking behavior remains unclear., Methods: Adolescents (N = 29; 9 females) were selected from a larger ongoing longitudinal study to include those who transitioned to at least weekly binge drinking (≥5/4 alcoholic drinks for males/females per occasion) over a 15-year follow-up period. Prior to the onset of weekly binge drinking (mean age = 18.0), participants underwent a functional MRI including a go/no-go task. Whole-brain activation from the no-go correct rejection versus no-go false alarm contrast was used to predict time to transition to frequent binge drinking., Results: Less no-go correct rejection versus no-go false alarm activation in a cluster including the precentral gyri, insula, and inferior frontal gyri predicted a more rapid transition into frequent binge drinking (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05, cluster threshold ≥ 18 voxels)., Conclusions: Results from this study are supported by literature suggesting that frontoinsular involvement is important for successful inhibition and cognitive control. Altered brain activation during response inhibition may thus represent neural antecedents of impulse regulation difficulties related to alcohol consumption. The magnitude of this activation provides temporal information that may be used to inform and optimize timing of interventions aimed at preventing the escalation and transition to problematic drinking for youth who have already begun to engage in drinking behaviors., (© 2020 by the Research Society on Alcoholism.)

Cannabis use during adolescence has been linked to deleterious effects on brain integrity. This article summarizes findings from two prospective investigations (3 and 6 years, on average) on adolescent cannabis use from our laboratory that utilize structural neuroimaging and neurocognitive assessment approaches. Across most studies, findings suggest recency, frequency, and age of onset of cannabis use are likely key variables in predicting poorer neural health outcomes. There is some evidence that preexisting differences in brain architecture may also contribute to vulnerability and outcome differences. Ongoing large-scale prospective studies of youth will be able to disentangle how both cannabis use as well as pre and postexposure differences play a role in divergent outcomes among youth who use cannabis., (© 2019 Wiley Periodicals, Inc.)

Objective: This article provides an overview of the scientific literature pertaining to the effects of alcohol on neural correlates of cognitive and emotional functioning, including reward processing and cue-reactivity, in adolescence and young adulthood., Method: Peer-reviewed, original research articles that included a neuroimaging assessment of alcohol effects on subsequent cognitive or emotional processing in adolescent or young adult samples were searched (through November 2018) and summarized in the review., Results: Cross-sectional studies provided early evidence of alcohol-related differences in neural processing across a number of cognitive domains. Longitudinal studies have identified neural abnormalities that predate drinking within most domains of cognitive functioning, while a few neural alterations have been observed within the domains of visual working memory, inhibitory control, reward processing, and cue-reactivity that appear to be related to the neurotoxic effect of alcohol use during adolescence. In contrast, neural correlates of emotion functioning appear to be relatively stable to the effects of alcohol., Conclusions: Larger prospective studies are greatly needed to disentangle premorbid factors from neural consequences associated with drinking, and to detect subsets of youth who may be particularly vulnerable to alcohol's effects on cognitive and emotional functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: Despite known genetic variation across races, studies examining pharmacogenetics of a single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1) on clinical response to naltrexone have been conducted in predominantly Caucasian samples. Evidence is mixed for pharmacogenetic OPRM1 and naltrexone effects on neural responses to alcohol cues. The current study tests the pharmacogenetic effects of naltrexone and OPRM1 on neural responses to alcohol taste cues in heavy drinkers of East Asian descent., Methods: Participants (N = 41) completed two double-blinded and counterbalanced functional magnetic resonance imaging (fMRI) sessions: one after taking naltrexone (50 mg/day) for four days and one after taking placebo for four days. Following titration, participants completed an fMRI alcohol taste-cues task. Analyses tested effects of naltrexone, OPRM1, and their interaction in whole-brain and region of interest (ROI) analyses of functional activation and functional connectivity in response to alcohol versus water taste cues., Results: We found no effects of naltrexone orOPRM1 on neural activation in whole-brain and ROI analyses, which included left and right ventral striatum (VS), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). Naltrexone increased functional connectivity between left VS and clusters in medial prefrontal cortex, posterior cingulate gyrus, as well as right VS and occipital cortex, compared to placebo., Conclusions: Naltrexone treatment enhanced functional connectivity in a key reinforcement-related pathway during alcohol versus water taste cues, corroborating neuroimaging work with other substances. Null medication and pharmacogenetics effects on functional activation add to a mixed naltrexone literature and may underscore the modest size of these effects in East Asians., (Copyright © 2019 Elsevier B.V. All rights reserved.)