Piezo1-induced durotaxis of pancreatic stellate cells depends on TRPC1 and TRPV4 channels.

Pancreatic stellate cells (PSCs) are primarily responsible for producing the stiff tumor tissue in pancreatic ductal adenocarcinoma (PDAC). Thereby, PSCs generate a stiffness gradient between the healthy pancreas and the tumor. This gradient induces durotaxis, a form of directional cell migration driven by differential stiffness. The molecular sensors behind durotaxis are still unclear. To investigate the role of mechanosensitive ion channels in PSC durotaxis, we established a two-dimensional stiffness gradient mimicking PDAC. Using pharmacological and genetic methods, we investigated the role of the ion channels Piezo1, TRPC1, and TRPV4 in PSC durotaxis. We found that PSC migration towards a stiffer substrate is diminished by altering Piezo1 activity. Moreover, disrupting TRPC1 along with TRPV4 abolishes PSC durotaxis even when Piezo1 is functional. Hence, PSC durotaxis is optimal with an intermediary level of mechanosensitive channel activity, which we simulated using a numerically discretized mathematical model. Our findings suggest that mechanosensitive ion channels, particularly Piezo1, detect the mechanical microenvironment to guide PSC migration.

The STOP COVID 2 Study: Fluvoxamine vs Placebo for Outpatients With Symptomatic COVID-19, a Fully Remote Randomized Controlled Trial.

Background: Prior randomized clinical trials have reported benefit of fluvoxamine ≥200 mg/d vs placebo for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This randomized, double-blind, placebo-controlled, fully remote multisite clinical trial evaluated whether fluvoxamine prevents clinical deterioration in higher-risk outpatients with acute coronavirus disease 2019 (COVID-19). Between December 2020 and May 2021, nonhospitalized US and Canadian participants with confirmed symptomatic infection received fluvoxamine (50 mg on day 1, 100 mg twice daily thereafter) or placebo for 15 days. The primary modified intent-to-treat (mITT) population included participants who started the intervention within 7 days of symptom onset with a baseline oxygen saturation ≥92%. The primary outcome was clinical deterioration within 15 days of randomization, defined as having both (1) shortness of breath (severity ≥4 on a 0-10 scale or requiring hospitalization) and (2) oxygen saturation <92% on room air or need for supplemental oxygen. Results: A total of 547 participants were randomized and met mITT criteria (n = 272 fluvoxamine, n = 275 placebo). The Data Safety Monitoring Board recommended stopping early for futility related to lower-than-predicted event rates and declining accrual concurrent with vaccine availability in the United States and Canada. Clinical deterioration occurred in 13 (4.8%) participants in the fluvoxamine group and 15 (5.5%) participants in the placebo group (absolute difference at day 15, 0.68%; 95% CI, -3.0% to 4.4%; log-rank P = .91). Conclusions: This trial did not find fluvoxamine efficacious in preventing clinical deterioration in unvaccinated outpatients with symptomatic COVID-19. It was stopped early and underpowered due to low primary outcome rates. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT04668950.

Cannabis demand and use among veterans: A prospective examination.

OBJECTIVE: Cannabis demand (i.e., relative value), assessed cross-sectionally via a hypothetical marijuana purchase task (MPT), has been associated with use, problems, and dependence symptoms, among others. However, limited work exists on the prospective stability of the MPT. Furthermore, cannabis demand among veterans endorsing cannabis use, and the prospective cyclical relationship between demand and use over time, have yet to be investigated. METHOD: Two waves of data from a veteran sample (N = 133) reporting current (past 6-month) cannabis use were analyzed to assess stability in cannabis demand over 6 months. Autoregressive cross-lagged panel models (CLPMs) assessed the longitudinal associations between demand indices (i.e., intensity, Omax, Pmax, breakpoint) and cannabis use. RESULTS: Baseline cannabis use predicted greater intensity (ß = .32, p < .001), Omax (ß = .37, p < .001), breakpoint (ß = .28, p < .001), and Pmax (ß = .21, p = .017) at 6 months. Conversely, baseline intensity (ß = .14, p = .028), breakpoint (ß = .12, p = .038), and Pmax (ß = .12, p = .043), but not Omax, predicted greater use at 6 months. Only intensity demonstrated acceptable prospective reliability. CONCLUSIONS: Cannabis demand demonstrated stability over 6 months in CLPM models, varying along with natural changes in cannabis use. Importantly, intensity, Pmax, and breakpoint displayed bidirectional predictive associations with cannabis use, and the prospective pathway from use to demand was consistently stronger. Test-retest reliability ranged from good to poor across indices. Findings highlight the value of assessing cannabis demand longitudinally, particularly among clinical samples, to determine how demand fluctuates in response to experimental manipulation, intervention, and treatment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Prospective Associations Between Anxiety Sensitivity, Distress Intolerance, Depressive Symptoms, and Indices of Alcohol and Cannabis Use Among Veterans.

OBJECTIVE: There is substantial evidence linking anxiety sensitivity and distress intolerance to depressive symptoms, and further evidence linking depressive symptoms to alcohol and cannabis use. However, the prospective indirect associations of anxiety sensitivity and distress intolerance with alcohol and cannabis use through depressive symptoms remain uncertain. Thus, the current study examined whether depressive symptoms mediated the associations between anxiety sensitivity and distress intolerance with alcohol and cannabis use frequency, quantity, and problems in a longitudinal sample of veterans. METHOD: Participants (N = 361; 93% male; 80% White) were military veterans with lifetime cannabis use recruited from a Veterans Health Administration in the Northeastern United States. Eligible veterans completed three semi-annual assessments. Prospective mediation models were used to test for the effects of baseline anxiety sensitivity and distress intolerance on alcohol and cannabis use quantity, frequency and problems at 12 months via depressive symptoms at 6 months. RESULTS: Baseline anxiety sensitivity was positively associated with 12-month alcohol problems. Baseline distress intolerance was positively associated with 12-month cannabis use frequency and quantity. Baseline anxiety sensitivity and distress intolerance significantly predicted increased alcohol problems and cannabis use frequency at 12 months through depressive symptoms at 6 months. There were no significant indirect effects of anxiety sensitivity and distress intolerance on alcohol use frequency or quantity, cannabis use quantity, or cannabis problems. CONCLUSIONS: Anxiety sensitivity and distress intolerance share a common pathway to alcohol problems and cannabis use frequency through depressive symptoms. Interventions focused on modulating negative affectivity may reduce cannabis use frequency and alcohol problems.

Acute Consequences Associated With Co-use of Alcohol and Cannabis: A Daily Survey Analysis.

OBJECTIVE: Co-use of alcohol and cannabis has been associated with more total negative consequences than single-substance use, but results have been mixed depending on whether the single substance was alcohol or cannabis. The present study used within-person analyses to examine whether co-use increased the risk for experiencing specific acute negative consequences. METHOD: College students who were co-users of alcohol and cannabis (N = 341; M age = 19.8 years; 51.3% female; 74.8% White) completed 56 days of five daily surveys across two bursts. We used generalized linear mixed effects models to examine the effects of type of substance use day on specific negative consequences, controlling for consumption and covariates. RESULTS: Relative to both alcohol-only and co-use days, cannabis-only days were associated with decreased likelihood of experiencing hangover, blackout, nausea/vomiting, injury, rude/aggressive behavior, and unwanted sex. Relative to alcohol-only days, cannabis-only and co-use days were associated with an increased likelihood of driving high/drunk. Finally, there was an increased likelihood of hangovers on alcohol-only days compared with co-use days. CONCLUSIONS: Days with different types of substance use differed in specific consequences. Most of the negative co-use consequences investigated here appear to be driven by alcohol consumption rather than cannabis use. The results also indicated that these young adults were more likely to endorse driving under the influence of cannabis than alcohol. Interventions for co-use should target alcohol consumption to reduce negative consequences such as blackout, injury, rude/aggressive behavior, and unwanted sex and highlight the dangers of driving under the influence of cannabis.

A free boundary problem-in time-for the spread of Covid-19.

In this paper we deal with two aspects of the Covid epidemic. The first is a phase change during the epidemic. The empirical observation is that once a certain threshold of active infections is reached, the rate of infection is increasing significantly. This threshold depends, among others, also on the season. We model this phenomenon as a jump in the coefficient of the virus exposition, giving the force of infection. In a chemical mass action law this coefficient corresponds to the reaction rate. We get a free boundary problem in time, which exhibits deterministic 'metastability'. In a population which is in a state of herd immunity, still, if the number of imported infections is large enough, an epidemic wave can start. The second aspect is the two scale nature of the infection network. On one hand side, there is always a finite number of reoccuring-deterministic-contacts, and on the other hand there is a large number of possible random contacts. We present a simple example, where the group size of deterministic contacts is two, and the graph of random contacts is complete.

Combined Cognitive Training and Vortioxetine Mitigates Age-Related Declines in Functional Brain Network Integrity.

OBJECTIVE: Age-related cognitive decline is common and potentially modifiable with cognitive training. Combining cognitive training with pro-cognitive medication offers an opportunity to modify brain networks to mitigate age-related cognitive decline. We tested the hypothesis that the efficacy of cognitive training could be amplified by combining it with vortioxetine, a pro-cognitive and pro-neuroplastic multimodal antidepressant. METHODS: We evaluated the effects of 6 months of computerized cognitive training plus vortioxetine (versus placebo) on resting state functional connectivity in older adults (age 65+) with age-related cognitive decline. We first evaluated the association of functional connectivity with age and cognitive performance (N = 66). Then we compared the effects of vortioxetine plus cognitive training versus placebo plus cognitive training on connectivity changes over the training period (n = 20). RESULTS: At baseline, greater age was significantly associated with lower within-network strength and network segregation, and poorer cognitive function. Cognitive training plus vortioxetine over 6 months positively impacted the relationship between age to mean network segregation. These effects were not observed in the placebo group. In contrast, vortioxetine did not modify the relationship of age to change in mean within-network strength. Exploratory analyses identified the cingulo-opercular network as the network most affected by cognitive training plus vortioxetine. CONCLUSION: This preliminary study provides evidence that combining cognitive training with pro-cognitive medication may modulate the effects of aging on functional brain networks. Results indicate that for older adults experiencing age-related cognitive decline, vortioxetine has a potentially beneficial effect on the correspondence between aging and functional brain network segregation. These results await replication in a larger sample.

Real-time and next-morning correlates of subjective alcohol consequence evaluations.

OBJECTIVE: There is considerable variation in how college student drinkers evaluate alcohol-related consequences across time and consequence type. Previous qualitative work suggested that students perceive consequences less negatively under certain circumstances (i.e., higher intoxication, when less time has passed, positive mood, after discussing with friends). The present study sought to confirm these patterns, using ecological momentary assessment (EMA) during drinking episodes paired with retrospective next-day assessments. METHOD: For 28 days, heavy-drinking college students (n = 90, 50% female) completed self-reports during drinking episodes and the next morning. Measures included alcohol use, subjective intoxication, mood, negative consequences (e.g., being aggressive) and positive consequences (e.g., new friend), and consequence-specific evaluations. RESULTS: Consistent with hypotheses, multilevel models revealed that during drinking events compared to the next morning, average evaluations of negative and positive consequences were less negative and more positive, respectively. During drinking events, neither subjective intoxication nor estimated blood alcohol concentration (eBAC) was associated with positive or negative evaluations. In morning reports, more positive mood was associated with less negative evaluations of negative consequences and more positive evaluations of positive consequences. Next-day discussion with friends was not significantly associated with consequence evaluations. CONCLUSIONS: This study is the first to assess subjective consequence evaluations in real time as well as retrospectively, for the same events. Findings continue to support the role of context (timing, mood) on subjective consequence evaluations, and suggest that ecological momentary interventions targeting alcohol consequences and related cognitions might best be delivered the morning after drinking, to capitalize on relatively more negative perceptions of one's drinking experiences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The role of alcohol and cannabis co-use in drinking rate and its impact on consequences.

BACKGROUND: The impact of alcohol and cannabis co-use on college student drinking and related outcomes is complex. Specific characteristics or patterns of co-use events beyond drinking quantity may be important to the experience of consequences. The present study used repeated daily surveys to examine the association between co-use (versus use of alcohol only) and drinking rate on negative consequences. METHODS: The sample included 318 college students (Mage  = 19.8, 47% female, 76% non-Hispanic White) who were co-users of alcohol and cannabis, recruited from three U.S. college campuses. Participants completed 56 days of data collection (number of drinking days ranged from 1 to 38). Two measures of drinking rate were examined: (1) daily rate (number of drinks divided by number of hours spent drinking per day); and (2) peak hour rate (maximum number of drinks consumed in a single hour) to account for anomalous drinking days of long duration. Generalized linear mixed models examined: (1) associations of co-use with peak hour rate (model 1a) and daily rate (model 1b); (2) associations of peak hour rate (model 2a) and daily rate (model 2b) with experiencing any negative consequence; and (3) interactions of co-use with peak hour rate (model 3a) and daily rate (model 3b) on experiencing a consequence. RESULTS: Co-use was positively associated with peak hour rate but not daily rate. Both peak hour and daily rate positively predicted likelihood of experiencing a negative consequence. The interaction of both peak hour and daily rate by co-use was significant such that the association of rate with experiencing a consequence was stronger on alcohol-only days compared to co-use days. CONCLUSIONS: Daily drinking rate and peak hour drinking rate are unique and should be considered when discussing drinking patterns. Both predict negative consequences and may be important aspects of interventions for negative drinking-related outcomes among college students.

Event-level contextual predictors of high-intensity drinking events among young adults.

BACKGROUND: Drinking events are characterized by social and physical contexts that are associated with level of alcohol consumption. Ecologically valid data is needed to delineate aspects of the drinking context that are most likely to precipitate excessive alcohol consumption. METHODS: We utilized event-level data from a longitudinal study that included repeated daily surveys administered in two 28-day bursts. Data from 341 college student past-month alcohol and cannabis users (Mage=19.79; 53 % women; 74 % White) produced a total of 4107 alcohol use days. Generalized linear mixed effects models were used to predict drinking level (moderate: 1-3/1-4 for women/men; heavy-episodic drinking (HED): 4-7/5-9; high-intensity drinking (HID), 8+/10+) by social (e.g., with friends) and physical (e.g., at a party) contexts. We conducted analyses for the first and last drink reported, controlling demographic and study characteristics. RESULTS: Being at a party, friend's house, or with strangers at the last drink reported were associated with HID compared to HED, while being at home, alone, or with family were protective for HID. No first drink contexts were associated with HID relative to HED. Witnessing others who were intoxicated was consistently associated with HID. CONCLUSIONS: Social settings such as parties and those with intoxicated persons were associated with risk for HID. The context of drinks at the end of an event are salient signals of level of alcohol consumption. Preventive interventions, particularly those that deliver strategies in real time, should consider accounting for contextual risk factors to reduce harms associated with excessive alcohol consumption.

Longitudinal associations between impulsivity and alcohol and cannabis use frequency, quantity, and problems among military veterans.

OBJECTIVE: Impulsivity is an established etiological risk factor for alcohol- and cannabis-related outcomes. However, limited work has focused on longitudinal associations between multiple trait impulsivity facets and indices of alcohol and cannabis use among military veterans-a contextually distinct population that evidence unique impulsive personality traits and substance use patterns. METHOD: A structural equation model (SEM) examined longitudinal associations between five UPPS-P impulsivity facets measured at baseline and six indices of alcohol and cannabis use (i.e., frequency, quantity, and problems) measured at 1-year follow-up among 361 returning Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND) veterans. RESULTS: Findings indicated baseline sensation seeking was significantly positively associated with 1-year alcohol use frequency (ß = .18); baseline negative urgency was positively associated with alcohol use problems (ß = .31); and baseline lack of perseverance (ß = .25) and sensation seeking (ß = .21) were positively associated with 1-year cannabis use problems. None of the baseline impulsivity facets were associated with 1-year alcohol use quantity, cannabis use frequency, or cannabis use quantity. CONCLUSIONS: Results provide preliminary support that impulsivity may play a unique role in understanding alcohol- and cannabis-related problems over time among veterans. Further, results suggest that specific impulsivity facets are prospectively associated with cannabis problems (i.e., lack of perseverance and sensation seeking) and alcohol problems (i.e., negative urgency). Findings reinforce the importance of differentially evaluating impulsivity-substance use associations within contextually distinct populations (e.g., adolescent, veteran), and highlight potentially meaningful intervention targets among veterans. However, replication is needed with stronger temporal controls and more diverse veteran subsamples. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Unplanned versus planned simultaneous alcohol and cannabis use in the daily lives of a predominantly white college student sample: What are the motives, contexts, and outcomes?

OBJECTIVE: Simultaneous alcohol and cannabis use is common among college students and associated with more consumption and consequences compared to single-substance use. This study examined occasions of simultaneous use and compared planned occasions to unplanned occasions with respect to motives, contexts, consumption, and consequences. METHOD: College student simultaneous users (N = 341; 53% women; 74% White) completed five daily surveys for 54 days. Mixed-effects models examined motives and contexts of simultaneous use occasions as a function of whether alcohol and cannabis use were (a) both planned versus (b) unplanned, no use planned, or (c) unplanned, single-substance use planned and whether alcohol and cannabis consumption and negative simultaneous use-related consequences varied across planned versus unplanned occasions. RESULTS: Social and enhancement motives were related to planned simultaneous use; offered and coping motives were associated with planned single-substance use that became simultaneous use (vs. planned simultaneous use). Compared to unplanned use, planned simultaneous use was negatively associated with using at home or alone, and positively associated with using with others, more intoxicated people, and more people using cannabis. Planned simultaneous use was associated with more alcohol and cannabis consumption. No significant differences were found for negative consequences. CONCLUSIONS: Planned simultaneous use was motivated by social and enhancement reasons, whereas planned single-substance use that became simultaneous use was more likely motivated by offers or for coping. Planned simultaneous use resulted in greater consumption, but not negative consequences. Results provide specific motives and contexts associated with unplanned and planned simultaneous use to be incorporated into real-time interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Changes in Cannabis Consumption Among College Students During COVID-19.

OBJECTIVE: College campuses closed in March 2020 because of the COVID-19 pandemic, disrupting the lives of students. The goal of the present study was to examine whether cannabis use changed from before campus departures prompted by COVID-19 to after campus departures and after the semester ended--and if living situation explained observed changes. We also examined changes in specific formulations of cannabis and self-reported reasons for perceived changes in use frequency. METHOD: A sample of 223 college student cannabis users (61% female) from three universities completed two online surveys (one in May 2020 assessing cannabis use pre-campus closure [pre-closure] and since campus closed [post-closure-1], and another in September 2020 assessing cannabis use since remote classes ended [post-closure-2]). RESULTS: Any use of cannabis and use of each specific formulation (leaf, edibles, concentrates) declined from pre-closure to post-closure-1, whereas the frequency of use did not change. Any cannabis use declined for those who stayed living dependently or moved to dependent living. Leaf use declined for all groups, concentrate use declined only for those who moved from independent to dependent living, and edible use declined only for those who stayed living dependently or moved to dependent living. Cannabis use did not change between post-closure-1 and post-closure-2, regardless of living situation stability or transition. CONCLUSIONS: Overall, among a sample of cannabis-using college students, the prevalence of any cannabis use, but not frequency of use, was reduced during the pandemic. Living with parents appears to be protective against frequent cannabis use.

Cannabis use and posttraumatic stress disorder: prospective evidence from a longitudinal study of veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) is the most highly co-occurring psychiatric disorder among veterans with cannabis use disorder (CUD). Despite some evidence that cannabis use prospectively exacerbates the course of PTSD, which in turn increases the risk for CUD, the causal nature of the relationship between cannabis and psychiatric comorbidity is debated. The longitudinal relationship between PTSD diagnosis and traumatic intrusion symptoms with cannabis use and CUD was examined using cross-lagged panel model (CLPM) analysis. METHODS: Prospective data from a longitudinal observational study of 361 veterans deployed post-9/11/2001 included PTSD and CUD diagnoses, cannabis use, and PTSD-related traumatic intrusion symptoms from the Inventory of Depression and Anxiety Symptoms. RESULTS: A random intercept CLPM analysis that leveraged three waves (baseline, 6 months and 12 months) of cannabis use and PTSD-related intrusion symptoms to account for between-person differences found that baseline cannabis use was significantly positively associated with 6-month intrusion symptoms; the converse association was significant but reduced in magnitude (baseline use to 6-month intrusions: ß = 0.46, 95% CI 0.155-0.765; baseline intrusions to 6-month use: ß = 0.22, 95% CI -0.003 to 0.444). Results from the two-wave CLPM reveal a significant effect from baseline PTSD to 12-month CUD (ß = 0.15, 95% CI 0.028-0.272) but not from baseline CUD to 12-month PTSD (ß = 0.12, 95% CI -0.022 to 0.262). CONCLUSIONS: Strong prospective associations capturing within-person changes suggest that cannabis use is linked with greater severity of trauma-related intrusion symptoms over time. A strong person-level directional association between PTSD and CUD was evident. Findings have significant clinical implications for the long-term effects of cannabis use among individuals with PTSD.

A qualitative examination of intentions and willingness for heavy drinking among young adult high-intensity drinkers.

OBJECTIVE: Heavy episodic drinking (HED) and high-intensity drinking (HID) are common in young adulthood but pose unique risks. Quantitative studies have used the Theory of Planned Behavior (TPB) and the Prototype-Willingness Model (PWM) to understand decision-making processes underlying alcohol misuse. However, our understanding of intentions (plans) and willingness (openness) for HED/HID is in its nascent stages. This study represents the first qualitative examination of relationships between intentions and willingness to engage in HED/HID. METHOD: We conducted individual interviews among 28 young adult high-intensity drinkers (12 male, 15 female, 1 trans male; M age = 23 years). Interviews focused on HED/HID events with open-ended questions examining: (a) variability in intentions/willingness by occasion and within a drinking event; (b) formation of intentions for consumption and/or intoxication; and (c) interplay of willingness and intentions on heavy drinking nights. Verbatim transcripts were coded within NVivo software and content was analyzed using applied thematic analysis. RESULTS: Participants described intentions and willingness as varying by occasion and perceived their shifting across a drinking event. Intentions for heavy drinking reflected a desired level of intoxication, rather than a specific number of drinks. Willingness, rather than intentions, to engage in heavy drinking/HID was more evident. CONCLUSIONS: Findings have significant implications for future measurement work in this area. There may be value in assessing intentions and willingness multiple times per day and during the drinking event itself. We also recommend that intentions for both consumption and intoxication levels be assessed, particularly in studies aiming to examine impaired control. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Nuanced relations between simultaneous alcohol and cannabis use motives and negative consequences among college students: The role of multiple product use.

Simultaneous alcohol and marijuana (SAM) use is common, but it exacerbates negative consequences. Individuals use alcohol and cannabis products in different ways and have distinct reasons for use. The present study examines day-level effects of motives on consequences on SAM-use days, accounting for consumption, and tests whether using multiple alcohol (e.g., beer + liquor) and/or cannabis (e.g., concentrate + leaf) products on the same day mediates these relations. College students engaging in SAM use at least once in the past month (N = 281; Mage = 20.17) completed two bursts of 28 consecutive days of data collection. We examined within-person effects of motives (effect-enhancement, social, offered [it was offered], coping) on number of negative consequences and on experiencing hangover, nausea, or blackout; and indirect effects via two concurrent mediators: using multiple alcohol products and multiple cannabis products. Total effect models showed effect-enhancement motives were related to nausea, social motives to number of total consequences and hangover, and coping motives to blackout. Effect-enhancement, social, and offered motives evinced significant indirect effects on consequence outcomes via multiple alcohol, but not cannabis, product use. Coping motives did not exhibit significant indirect effects, and were related to multiple cannabis, but not alcohol, product use, although all other motives were related to both mediators. Findings support recent work demonstrating within-person relations between social motives and negative consequences on SAM-use days. Limiting the number of alcohol products consumed on SAM-use days may be beneficial, particularly for young adults using to enhance intoxication or for social reasons. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Comprehensive measurement invariance of alcohol outcome expectancies among adolescents using regularized moderated nonlinear factor analysis.

Alcohol outcomes expectancies (AOEs) are robust predictors of alcohol initiation and escalation of drinking behavior among adolescents. Although measurement invariance is a prerequisite for inferring valid comparisons of AOEs across groups (e.g., age), empirical evidence is lacking. In a secondary data analysis study, we employed regularized moderated nonlinear factor analysis (MNLFA) to simultaneously test differential item functioning (DIF) across age, sex, race, ethnicity, socioeconomic status (SES), and alcohol initiation for a 22-item, two-factor measure of positive and negative AOEs among adolescents (analytic n = 936 drawn from a parent study of 1023 adolescents). Evidence of DIF was minimal, with no DIF for the negative AOE factor and DIF for only two items of the positive AOE factor. The item "feel grown up" exhibited DIF by age, and the item "feel romantic" exhibited DIF by SES. After accounting for DIF, the positive AOE latent factor mean differed by SES, age, and alcohol initiation, and exhibited lower variability by alcohol initiation. The negative AOE latent factor mean differed by sex and SES, with greater variability by SES and age and lower variability by alcohol initiation. Group-differences findings for age and alcohol initiation are consistent with prior work, and differences by sex and SES are a new contribution to the literature that should prompt additional research to ensure replicability. The present study demonstrates the utility of the MNLFA technique for examining comprehensive measurement invariance, particularly for applied researchers who seek to examine substantive research questions while accounting for any DIF present in the scales used.

Understanding the motives, contexts, and consequences of unplanned versus planned drinking in daily life.

OBJECTIVE: Problematic alcohol use among college students remains a public health concern; thus, there is a need to understand distinct drinking events, such as unplanned and planned drinking. The present study examined motives and social and physical contexts as correlates of unplanned and planned drinking to help inform prevention and intervention. METHOD: College student alcohol and cannabis users (N = 341; 53% women) completed 56 days of data collection (two 28-day bursts) with five repeated daily surveys. Three-level generalized linear mixed-effects models were used to examine associations among motives, physical and social contexts, and unplanned versus planned drinking. We also examined whether unplanned or planned drinking resulted in greater consumption and negative consequences. RESULTS: Social and enhancement motives were related to planned drinking, whereas offered motives (i.e., offers of alcohol) and coping motives were linked to unplanned drinking. Drinking at home, with roommates, or alone was associated with unplanned drinking. Drinking at a bar/restaurant, a party, at a friend's place, with friends, with strangers/acquaintances, with a significant other, or with intoxicated people was linked to planned drinking. Unplanned drinking was related to fewer drinks consumed and fewer negative consequences endorsed. CONCLUSIONS: Findings showed that planned drinking-irrespective of consumption-was related to more negative consequences than unplanned drinking. In addition to targeting intentions to drink, the present study provided specific motives and social and physical contexts that are associated with planned drinking that could be incorporated into ecological momentary interventions focused on harm reduction. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Examining the heterogeneity of polysubstance use patterns in young adulthood by age and college attendance.

Substance use in young adulthood and polysubstance users (PSU), in particular, pose unique risks for adverse consequences. Prior research on young adult PSU has identified multiple classes of users, but most work has focused on college students. We examined PSU patterns by age and college attendance during young adulthood in two nationally representative samples. Using National Epidemiological Survey on Alcohol and Related Conditions (NESARC) Wave 1 and NESARC-III data sets, multigroup latent class analysis (MG-LCA) was employed to examine PSU patterns based on age (18-24 vs. 25-34) and determine whether solutions were similar (i.e., statistically invariant) by college attendance/graduation. Classes were estimated by binary past-year use of sedatives, tranquilizers, opioids/painkillers, heroin, amphetamines/stimulants, cocaine, hallucinogens, club drugs, and inhalants, and past-year frequency of alcohol, cigarette, and cannabis use. PSU patterns are largely replicated across waves. Model fit supported 3-class solutions in each MG-LCA: Low frequency-limited-range PSU (alcohol, cigarettes, and cannabis only), medium-to-high frequency limited-range PSU (alcohol, cigarettes, and cannabis only), and extended-range PSU (ER PSU; all substances). Apart from one model, MG-LCA solutions were not invariant by college attendance/graduation, suggesting important differences between these groups. Except for alcohol, cannabis, and cigarette use frequency, results showed that probabilities of illicit and prescription drug use declined in the older age group. Findings also supported examining college and noncollege youth separately when studying PSU. ER PSU may be uniquely vulnerable to coingesting substances, particularly for nongraduates, warranting future research to classify patterns of simultaneous PSU and identify predictors and consequences of high-risk combinations (e.g., alcohol and opioids). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Discussion of alcohol consequences during a brief motivational intervention session: Comparing those who do and do not increase readiness to change.

The present study was designed to take an inductive, qualitative approach to understanding how discussion of alcohol-related consequences during brief motivational interventions (BMI) relate to readiness to change (RTC) prior to versus at the end of a session. Participants were thirty-four adults (35% female) recruited from the emergency room and enrolled in a randomized clinical trial of a BMI for risky alcohol use and risky sex. Seventeen participants both began and remained low on RTC over the course of the session. We selected 17 additional participants, matched on demographics, but who increased RTC over the session. Transcripts were qualitatively coded and analyzed separately within groups. Among participants who increased their RTC relative to participants who remained low on RTC by BMI end, evaluation of alcohol consequences as negative was more typical. In both groups, several consequences were neutrally evaluated. Many who remained low on RTC attributed consequences to something other than alcohol and/or minimized consequence severity. Study findings highlight the value for clinicians in eliciting and maximizing the importance of subjectively negative recent consequences to perhaps increase heavy drinkers' readiness to decrease heavy alcohol use.