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Background: Implementing ecological momentary assessment (EMA) methodology to evaluate the substance use disorder (SUD) treatment pipeline has clear advantages, including learning about participants’ day-to-day experiences to aid in the improvement of services and accessibility for those seeking treatment. Given that the SUD treatment pipeline spans long periods of time, EMA burst designs (deployment of multiple short EMA periods spread over time) can be advantageous for evaluating the treatment pipeline over time while keeping participant burden low. Objectives: This feasibility study describes (1) the process and study design of implementing EMA burst methodology to evaluate the SUD treatment pipeline experience; (2) study implementation from the perspective of researchers, including discussion of collaboration with community partners; and (3) participant feedback on the experience of engaging with this type of research. Method: EMA metrics, feasibility ratings, and general experience ratings in the study are presented from 22 participants (64% women) who participated in a parent EMA study evaluating the SUD treatment pipeline and 8 who provided feedback in a follow-up survey. Results: Participants found the EMA burst design to be acceptable and not burdensome, although technology issues were present for some participants. Steps to partnering with community treatment programs and implementation of a burst design are outlined. Conclusions: Strategies and recommendations for implementation of an EMA burst study with community partners are provided, including aspects of study design, technology issues, retention, and funding.

Alcohol-induced blackouts have been associated concurrently and prospectively with alcohol-related harm. Although rates of heavy drinking among military samples tend to be comparable or higher than rates among civilian samples, the prevalence and correlates of blackout in the military population are understudied.Veterans (N = 241, 29% female, 39% Black) reported on their alcohol consumption and mental health as part of a larger health-related study among veterans. In this secondary analysis, we tested theoretically and empirically informed predictors (gender, drinking quantity, and other drug use) and consequences [depression, posttraumatic stress disorder (PTSD)] of alcohol-induced blackout. Given the diversity of the sample, potential roles of racial/ethnic discrimination and drinking to cope in alcohol-induced blackout were also tested.Past-year prevalence of alcohol-induced blackout was 53% among veterans who drank alcohol and 68% among those who screened positive for hazardous drinking. Everyday experience of racial discrimination was the strongest concurrent predictor of alcohol-induced blackout. Drinking quantity and use of other drugs were significant correlates only in bivariate models. Controlling for gender, race, drinking quantity, other drug use, and discrimination, blackout frequency was significantly associated with symptoms of depression, but not symptoms of PTSD. Both blackout and racial discrimination were associated with drinking to cope.The prevalence and correlates of alcohol-induced blackout among veterans are largely consistent with those documented in civilian and young adult populations. Among racially diverse groups, racial discrimination may be more strongly associated with mental health symptoms than alcohol consumption or acute alcohol consequences such as blackout.

To examine associations between alcohol use and sleep in middled-aged/older adults and to test sex as a moderator of this relationship.Participants were 183 adults (46% female) ages 50 and above who consumed alcohol in the past year. Linear regressions tested sex as a moderator of associations between alcohol use and sleep parameters. Alcohol use was measured using the Alcohol Use Disorders Identification Test (AUDIT). Overall sleep health and sleep quality were assessed using the Pittsburgh Sleep Quality Index (PSQI), and pre-sleep arousal was assessed using the Pre-Sleep Arousal Scale.Overall, 11% of participants screened positive for hazardous drinking (AUDIT scores of 7+/8+ for women/men), and 59% reported poor overall sleep health (scores5 on the PSQI). Alcohol use was not associated with overall sleep health (B = -0.25, p = .08) or pre-sleep arousal (B = 0.15, p = .64). However, contrary to hypotheses, more hazardous drinking was associated with better subjective sleep quality, only among women (B = -0.08, p = .009). Alcohol use was not associated with sleep quality among men (B = 0.01, p = .58). Associations remained significant when controlling for age, symptoms of anxiety and depression, body mass index, use of sleep medication, number of medical conditions, and chronic pain.Among middle-aged and older adults, alcohol use is more strongly associated with sleep patterns among women than men, when assessed concurrently (i.e., at the same time point). Findings support the need for further consideration of sex differences in associations between alcohol use and sleep.

Quantum sensors offer unparalleled precision, accuracy, and sensitivity for a variety of measurement applications. We report a compact magnetometer based on a ferrimagnetic sensing element in an oscillator architecture that circumvents challenges common to other quantum sensing approaches such as limited dynamic range, limited bandwidth, and dependence on vacuum, cryogenic, or laser components. The device exhibits a fixed, calibration-free response governed by the electron gyromagnetic ratio. Exchange narrowing in the ferrimagnetic material produces sub-MHz transition linewidths despite the high unpaired spin density ($\sim 10^{22}$ cm$^{-3}$). The magnetometer achieves a minimum sensitivity of 100 fT/$\sqrt{\text{Hz}}$ to AC magnetic fields of unknown phase and a sensitivity below 200 fT/$\sqrt{\text{Hz}}$ over a bandwidth $\gtrsim \! 1$ MHz. By encoding magnetic field in frequency rather than amplitude, the device provides a dynamic range in excess of 1 mT. The passive, thermal initialization of the sensor's quantum state requires only a magnetic bias field, greatly reducing power requirements compared to laser-initialized quantum sensors. With additional development, this device promises to be a leading candidate for high-performance magnetometry outside the laboratory, and the oscillator architecture is expected to provide advantages across a wide range of sensing platforms., 18 pages, 4 figures

The most frequent genetic alterations in melanoma are gain-of-function (GOF) mutations in BRAF, which result in RAF–MEK–ERK signaling pathway addiction. Despite therapeutic success of RAF and MEK inhibitors in treating BRAFV600-mutant tumors, a major challenge is the inevitable emergence of drug resistance, which often involves reactivation of the MAPK pathway. Interestingly, resistant tumors are often sensitive to drug withdrawal, suggesting that hyperactivation of the MAPK pathway is not tolerated. To further characterize this phenomenon, isogenic models of inducible MAPK hyperactivation in BRAFV600E melanoma cells were generated by overexpression of ERK2. Using this model system, supraphysiologic levels of MAPK signaling led to cell death, which was reversed by MAPK inhibition. Furthermore, complete tumor regression was observed in an ERK2-overexpressing xenograft model. To identify mediators of MAPK hyperactivation–induced cell death, a large-scale pooled shRNA screen was conducted, which revealed that only shRNAs against BRAF and MAP2K1 rescued loss of cell viability. This suggested that no single downstream ERK2 effector was required, consistent with pleiotropic effects on multiple cellular stress pathways. Intriguingly, the detrimental effect of MAPK hyperactivation could be partially attributed to secreted factors, and more than 100 differentially secreted proteins were identified. The effect of ERK2 overexpression was highly context dependent, as RAS/RAF mutant but not RAS/RAF wild-type melanoma were sensitive to this perturbation.Implications:This vulnerability to MAPK hyperactivation raises the possibility of novel therapeutic approaches for RAS/RAF-mutant cancers.

Supplementary Figure S6 shows loading controls for all Western blot analyses from Figure 5.

All supplementary figure and table titles and legends.

Figure S1. Cellular phenotypes observed in response to ERK2 overexpression in A-375 cells. Figure S2. No paracrine effect was produced by cells dying due to knockdown of the essential gene PSMA3. Figure S3. A-375 xenograft tumors with ERK2 overexpression displayed necrosis and/or fibrosis. Figure S4. Paradoxical activation triggered by low doses of BRAFi in GR-M augmented the growth suppression caused by ERK2 overexpression. Figure S5. Graphical representations of vector constructs used in this study. Table S1. MSigDB Hallmark pathways that were significantly enriched in genes upregulated after 20 h treatment with doxycycline in A-375 ERK2 cells. Table S2. Transcription factor targets (from MSigDB C3 TFT) for known ERK targets were significantly enriched in genes upregulated after 20 h treatment with doxycycline in A-375 ERK2 cells.

Half of advanced human melanomas are driven by mutant BRAF and dependent on MAPK signaling. Interestingly, the results of three independent genetic screens highlight a dependency of BRAF-mutant melanoma cell lines on BRAF and ERK2, but not ERK1. ERK2 is expressed higher in melanoma compared with other cancer types and higher than ERK1 within melanoma. However, ERK1 and ERK2 are similarly required in primary human melanocytes transformed with mutant BRAF and are expressed at a similar, lower amount compared with established cancer cell lines. ERK1 can compensate for ERK2 loss as seen by expression of ERK1 rescuing the proliferation arrest mediated by ERK2 loss (both by shRNA or inhibition by an ERK inhibitor). ERK2 knockdown, as opposed to ERK1 knockdown, led to more robust suppression of MAPK signaling as seen by RNA-sequencing, qRT-PCR, and Western blot analysis. In addition, treatment with MAPK pathway inhibitors led to gene expression changes that closely resembled those seen upon knockdown of ERK2 but not ERK1. Together, these data demonstrate that ERK2 drives BRAF-mutant melanoma gene expression and proliferation as a function of its higher expression compared with ERK1. Selective inhibition of ERK2 for the treatment of melanomas may spare the toxicity associated with pan-ERK inhibition in normal tissues.Implications:BRAF-mutant melanomas overexpress and depend on ERK2 but not ERK1, suggesting that ERK2-selective inhibition may be toxicity sparing.

STUDY OBJECTIVES: Cannabis use is common among young adults and has been proposed as a potential treatment for insomnia. However, controlled studies examining the impact of cannabis use on insomnia symptoms are rare. This secondary analysis of published trial data tested cannabis use during cognitive behavioral treatment for insomnia (CBT-I) as a moderator of treatment efficacy. METHODS: Young adults (ages 18–30 years) who reported past-month binge drinking (4/5+ drinks for women/men) and met diagnostic criteria for insomnia disorder were randomized to CBT-I (n = 28) or sleep hygiene (n = 28) groups. Interaction effects were tested using multilevel models. Outcomes included insomnia severity, actigraphy-assessed sleep efficiency, diary-assessed sleep quality, drinking quantity, and alcohol-related consequences. RESULTS: Twenty-six participants (46%; 12 in the sleep hygiene group and 14 in the CBT-I group) reported using cannabis during the treatment phase of the study, on an average of 23% of treatment days (range, 3%–100%). Relative to those who did not use cannabis, participants who used cannabis during treatment reported heavier drinking and more frequent cigarette use. Approximately 1 in 4 cannabis users (27%) reported using cannabis to help with sleep; however, cannabis users and nonusers did not differ in the use of alcohol as a sleep aid. Controlling for sex, race, drinking quantity, cigarette use, symptoms of depression, and symptoms of anxiety, use of cannabis during treatment did not moderate CBT-I effects on insomnia severity (b, –.002; p = .99) or other outcomes (all p > .20). CONCLUSIONS: CBT-I is effective in reducing insomnia symptoms among young adult drinkers with insomnia, regardless of cannabis use. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: The Insomnia Treatment and Problems (iTAP) Study; URL: https://clinicaltrials.gov/ct2/show/NCT03627832; Identifier: NCT03627832. CITATION: Miller MB, Carpenter RW, Freeman LK, Curtis AF, Yurasek AM, McCrae CS. Cannabis use as a moderator of cognitive behavioral therapy for insomnia. J Clin Sleep Med. 2022;18(4):1047–1054.

STUDY OBJECTIVES: Empirical evidence linking individual sleep hygiene practices to subsequent sleep parameters is limited, particularly at the daily level. This study compared the strength of daily, within-person associations between these modifiable sleep behaviors and nighttime sleep in young adult drinkers with insomnia. METHODS: Young adults (ages 18–30 years; n = 56) who met diagnostic criteria for insomnia and reported past-month binge drinking wore wrist actigraphy and completed online sleep diaries for 8.5 days (standard deviation = 2.3; 477 reports). Diaries assessed engagement in 11 sleep hygiene recommendations. Multilevel models tested daily associations between sleep behaviors and 3 outcomes: sleep quality, self-reported sleep efficiency, and actigraphy-measured sleep efficiency. RESULTS: Participants self-reported better sleep quality/efficiency on days that they slept in a comfortable environment, limited naps to 30 minutes, and maintained a consistent wake time. They self-reported worse sleep quality and efficiency on nights that they avoided alcohol use before bedtime. No sleep behaviors were significantly associated with actigraphy-measured sleep efficiency after correcting for inflation in type I error. CONCLUSIONS: The sleep hygiene recommendations most strongly associated with sleep at the daily level were consistent with stimulus control. Creating a comfortable sleep environment also emerged as an important correlate of daily sleep. Heavy drinkers with insomnia may perceive better sleep if they drink before bedtime; however, this finding may be unique to this population. CITATION: Miller MB, Curtis AF, Hall NA, et al. Daily associations between modifiable sleep behaviors and nighttime sleep among young adult drinkers with insomnia. J Clin Sleep Med. 2022;18(3):703–712.

To evaluate the feasibility and validity of a new method of quantifying cannabis flower use, integrating the amount of cannabis flower smoked, and the potency of the cannabis flower.Ecological momentary assessment (EMA) for 14 days.Participants' daily lives in Columbia, Missouri, USA.A total of 50 community participants, who were regular cannabis flower smokers (48% female).Momentary subjective intoxication ratings following cannabis flower smoking; momentary quantity of cannabis flower smoked; potency of cannabis flower smoked in terms of percentage of tetrahydrocannabinol (THC) concentration assessed with a portable device, the Purpl Pro; and time since finished smoking.Participants completed our field testing of their cannabis flower (96.2%) and were compliant with our 2-week EMA protocol (73% for random prompts and 91% for morning reports). Momentary subjective intoxication ratings trended down as a function of time since smoking (r = -0.10, P = 0.004, 95% CI, [-0.17, -0.03]). Multi-level model (MLM) results indicated the momentary standard THC units (mg THC) were positively associated with momentary subjective intoxication ratings (b = 0.01, P = 0.03, 95% CI, [0.01, 0.012]).There is evidence to support the feasibility and initial validity of a new method of quantifying cannabis flower use into standard tetrahydrocannabinol units. Researchers investigating the effects of cannabis flower use on a range of outcomes (e.g. neurobehavioral effects, emotional sequelae, and driving impairment) as well as in clinical treatment trials might adopt this method to provide estimates of cannabis flower use.

Background Bacteremia is a life-threatening illness. Delayed treatment increases patient morbidity and healthcare costs. Accelerate Pheno™ Blood Culture Detection System (AXDX) is a novel diagnostic technology for rapid detection of gram-negative bacteremia. Studies have shown accurate and faster time to speciation and sensitivity (TTSS) by AXDX compared to conventional modality. Our unique study examined the direct impact of AXDX on clinical outcomes and cost. Methods This retrospective study consisted of 213 patients aged 18 years and older admitted to our academic institution with gram-negative bacteremia. The pre-AXDX group had 109 patients admitted in 2019 and the post-AXDX group had 104 patients admitted in 2021. Demographics, microbes, TTSS, time to de-escalation of therapy (TTDeT), length of stay (LOS), readmissions, mortality rates, and Clostridioides difficile infection (CDI) rates were recorded. Results The pre-AXDX group had 51.4% females, mean age of 60.3 years, mean Charlson Comorbidity Index (CCMI) of 2.2, mean LOS of 21.2 days, and mean Pitt Bacteremia Score (PBS) of 2.4. The post-AXDX group had 52.0% females, mean age of 63.7 years, mean CCMI of 3.0, mean LOS of 15.0 days, and mean PBS of 2.7. Both groups’ top 2 sources of bacteremia were urinary and gastrointestinal and top 2 microbes were Escherichia coli and Klebsiella pneumoniae. Pre-AXDX's mean TTSS was 71.9 hours and 23.6 hours for post-AXDX. Pre-AXDX's mean TTDeT was 74.0 hours and 43.9 hours for post-AXDX. The pre-AXDX cohort had 7.4% more related readmissions, 5.5% more CDI, and 0.3% more inpatient mortality than post-AXDX group. Conclusion In addition to faster TTSS with AXDX as seen with previous studies, our study shows clinical advantages with AXDX use. Both groups were comparable in bacteremia sources and microbes. The post-AXDX group had higher CCMI and PBS scores, indicating they were more ill. Despite this, the pre-AXDX group had 30.05 hours longer TTDeT, 6.17 days longer mean LOS, 5.45% more CDI, 7.12% more readmissions, and 0.26% higher mortality. The pre-AXDX group also reported adverse reactions to antibiotics, while post-AXDX did not. Our data shows AXDX use improves clinical outcomes with reduced adverse effects, mortality and CDI rate and lower costs with less LOS and readmission rates. Disclosures All Authors: No reported disclosures.

Background Current treatment guidelines for invasive candidiasis (IC) largely recommend an echinocandin as initial therapy. Echinocandins have demonstrated non-inferiority to previously utilized agents for the treatment of IC with low toxicity, few drug-drug interactions, and activity against azole-resistant Candida species. Although echinocandins are suggested empirically when IC is suspected, recommendations for empiric therapy based upon IC risk factors do not exist. The primary objective is to develop a risk score to predict probability of IC to help triage when empiric therapy with an echinocandin is likely warranted. Methods This evaluation is a retrospective, case-control design of hospitalized adults that received at least one dose of micafungin between July 1, 2020 and June 30, 2021 for proven or suspected IC at a large academic medical center. Descriptive statistics were used to describe all variables collected. A multivariable logistic regression analysis was used to determine the predictability of identified risk factors on IC. The predictability of the model was quantified using a nomogram which sums the odds of experiencing IC based on the presence of selected predictors. The sum is correlated to a linear predictor which corresponds to the log odds of experiencing IC. The exponential on the log odds gives the predicted probability of IC. Results Three hundred eighteen patients that received at least one dose of micafungin during the time frame for proven or suspected IC were included. IC was confirmed in 105 patients (33%) with endovascular source being the most common (56.2%). The most common Candida species isolated was C. albicans (47.6%). Independent risk factors for development of IC included anti-anaerobic antimicrobial therapy (adjusted odds ratio [aOR], 0.4611; 95% confidence interval [CI], 0.232, 0.914), parenteral nutrition (aOR, 2.115; 95% CI, 1.019, 4.388), and critical illness (aOR, 0.511; 95% CI, 0.315, 0.829). Patients with prediction scores of greater than 50 had an estimated probability of IC greater than 20%. Conclusion A prediction score can be a useful tool to estimate the patient-specific risk of IC development. Integration of a risk score for IC into clinical workflow may improve empiric antifungal prescribing and reduce echinocandin utilization. Disclosures All Authors: No reported disclosures.

This study compares three methods of cannabis and of alcohol use assessment in a sample of regular cannabis users: (a) ecological momentary assessment (EMA) repeated momentary surveys aggregated to the daily level, (b) EMA morning reports (MR) where participants reported on their total use from the previous day, and (c) retrospective timeline followback (TLFB) interviews covering the same period of time as the EMA portion of the study. We assessed the overall correspondence between these methods in terms of cannabis and alcohol use occasions and also investigated predictors of agreement between methods.Forty-nine individuals aged 18-50 (Daily aggregated EMA and TLFB reports showed a low to modest agreement for both alcohol and cannabis use. Overall, agreement between EMA and MR was better than agreement between EMA and TLFB, likely because less retrospection is required when only reporting on behavior from the previous day. Quantity and frequency of use differentially predicted agreement across reporting methods when assessing alcohol compared to cannabis. When reporting cannabis use, but not alcohol use, individuals who used more demonstrated higher agreement between EMA and TLFB.Results suggest that retrospective reporting methods assessing alcohol and cannabis should not be considered a direct "substitute" for momentary or daily assessments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).