Comprehensive Genome-wide Perturbations via CRISPR Adaptation Reveal Complex Genetics of Antibiotic Sensitivity.

Genome-wide CRISPR screens enable systematic interrogation of gene function. However, guide RNA libraries are costly to synthesize, and their limited diversity compromises the sensitivity of CRISPR screens. Using the Streptococcus pyogenes CRISPR-Cas adaptation machinery, we developed CRISPR adaptation-mediated library manufacturing (CALM), which turns bacterial cells into "factories" for generating hundreds of thousands of crRNAs covering 95% of all targetable genomic sites. With an average gene targeted by more than 100 distinct crRNAs, these highly comprehensive CRISPRi libraries produced varying degrees of transcriptional repression critical for uncovering novel antibiotic resistance determinants. Furthermore, by iterating CRISPR adaptation, we rapidly generated dual-crRNA libraries representing more than 100,000 dual-gene perturbations. The polarized nature of spacer adaptation revealed the historical contingency in the stepwise acquisition of genetic perturbations leading to increasing antibiotic resistance. CALM circumvents the expense, labor, and time required for synthesis and cloning of gRNAs, allowing generation of CRISPRi libraries in wild-type bacteria refractory to routine genetic manipulation.

OASIS: An interpretable, finite-sample valid alternative to Pearson's X2 for scientific discovery.

Contingency tables, data represented as counts matrices, are ubiquitous across quantitative research and data-science applications. Existing statistical tests are insufficient however, as none are simultaneously computationally efficient and statistically valid for a finite number of observations. In this work, motivated by a recent application in reference-free genomic inference [K. Chaung et al., Cell 186, 5440-5456 (2023)], we develop Optimized Adaptive Statistic for Inferring Structure (OASIS), a family of statistical tests for contingency tables. OASIS constructs a test statistic which is linear in the normalized data matrix, providing closed-form P-value bounds through classical concentration inequalities. In the process, OASIS provides a decomposition of the table, lending interpretability to its rejection of the null. We derive the asymptotic distribution of the OASIS test statistic, showing that these finite-sample bounds correctly characterize the test statistic's P-value up to a variance term. Experiments on genomic sequencing data highlight the power and interpretability of OASIS. Using OASIS, we develop a method that can detect SARS-CoV-2 and Mycobacterium tuberculosis strains de novo, which existing approaches cannot achieve. We demonstrate in simulations that OASIS is robust to overdispersion, a common feature in genomic data like single-cell RNA sequencing, where under accepted noise models OASIS provides good control of the false discovery rate, while Pearson's [Formula: see text] consistently rejects the null. Additionally, we show in simulations that OASIS is more powerful than Pearson's [Formula: see text] in certain regimes, including for some important two group alternatives, which we corroborate with approximate power calculations.

Modulation of Motor Vigor by Expectation of Reward Probability Trial-by-Trial Is Preserved in Healthy Ageing and Parkinson's Disease Patients.

Motor improvements, such as faster movement times or increased velocity, have been associated with reward magnitude in deterministic contexts. Yet whether individual inferences on reward probability influence motor vigor dynamically remains undetermined. We investigated how dynamically inferring volatile action-reward contingencies modulated motor performance trial-by-trial. We conducted three studies that coupled a reversal learning paradigm with a motor sequence task and used a validated hierarchical Bayesian model to fit trial-by-trial data. In Study 1, we tested healthy younger [HYA; 37 (24 females)] and older adults [HOA; 37 (17 females)], and medicated Parkinson's disease (PD) patients [20 (7 females)]. We showed that stronger predictions about the tendency of the action-reward contingency led to faster performance tempo, commensurate with movement time, on a trial-by-trial basis without robustly modulating reaction time (RT). Using Bayesian linear mixed models, we demonstrated a similar invigoration effect on performance tempo in HYA, HOA, and PD, despite HOA and PD being slower than HYA. In Study 2 [HYA, 39 (29 females)], we additionally showed that retrospective subjective inference about credit assignment did not contribute to differences in motor vigor effects. Last, Study 3 [HYA, 33 (27 females)] revealed that explicit beliefs about the reward tendency (confidence ratings) modulated performance tempo trial-by-trial. Our study is the first to reveal that the dynamic updating of beliefs about volatile action-reward contingencies positively biases motor performance through faster tempo. We also provide robust evidence for a preserved sensitivity of motor vigor to inferences about the action-reward mapping in aging and medicated PD.SIGNIFICANCE STATEMENT Navigating a world rich in uncertainty relies on updating beliefs about the probability that our actions lead to reward. Here, we investigated how inferring the action-reward contingencies in a volatile environment modulated motor vigor trial-by-trial in healthy younger and older adults, and in Parkinson's disease (PD) patients on medication. We found an association between trial-by-trial predictions about the tendency of the action-reward contingency and performance tempo, with stronger expectations speeding the movement. We additionally provided evidence for a similar sensitivity of performance tempo to the strength of these predictions in all groups. Thus, dynamic beliefs about the changing relationship between actions and their outcome enhanced motor vigor. This positive bias was not compromised by age or Parkinson's disease.

Phenotypic and Genotypic Adaptation of Escherichia coli to Thermal Stress is Contingent on Genetic Background.

Evolution can be contingent on history, but we do not yet have a clear understanding of the processes and dynamics that govern contingency. Here, we performed the second phase of a two-phase evolution experiment to investigate features of contingency. The first phase of the experiment was based on Escherichia coli clones that had evolved at the stressful temperature of 42.2 °C. The Phase 1 lines generally evolved through two adaptive pathways: mutations of rpoB, which encodes the beta subunit of RNA polymerase, or through rho, a transcriptional terminator. We hypothesized that epistatic interactions within the two pathways constrained their future adaptative potential, thus affecting patterns of historical contingency. Using ten different E. coli Founders representing both adaptive pathways, we performed a second phase of evolution at 19.0 °C to investigate how prior genetic divergence or adaptive pathway (rpoB vs. rho) affects evolutionary outcomes. We found that phenotype, as measured by relative fitness, was contingent on founder genotypes and pathways. This finding extended to genotypes, because E. coli from different Phase 1 histories evolved by adaptive mutations in distinct sets of genes. Our results suggest that evolution depends critically on genetic history, likely due to idiosyncratic epistatic interactions within and between evolutionary modules.

Microbial Primer: Phase variation - survival and adaptability by generation of a diverse population.

Phase variation is defined as the rapid and reversible switching of gene expression, and typically occurs in genes encoding surface features in small genome bacterial pathogens. Phase variation has evolved to provide an extra survival mechanism in bacteria that lack multiple 'sense-and-respond' gene regulation systems. Many bacterial pathogens also encode DNA methyltransferases that are phase-variable, controlling systems called 'phasevarions' (phase-variable regulons). This primer will summarize the current understanding of phase variation, describing the role of major phase-variable factors, and phasevarions, in bacterial pathobiology.

A positive affect intervention alters leukocyte DNA methylation in sexual minority men with HIV who use methamphetamine.

OBJECTIVE: This epigenomics sub-study embedded within a randomized controlled trial examined whether an evidenced-based behavioral intervention model that decreased stimulant use altered leukocyte DNA methylation (DNAm). METHODS: Sexual minority men with HIV who use methamphetamine were randomized to a five-session positive affect intervention (n = 32) or an attention-control condition (n = 21), both delivered during three months of contingency management for stimulant abstinence. All participants exhibited sustained HIV virologic control - an HIV viral load less than 40 copies/mL at baseline and six months post-randomization. The Illumina EPIC BeadChip measured leukocyte methylation of cytosine-phosphate-guanosine (CpG) sites mapping onto five a priori candidate genes of interest (i.e., ADRB2, BDNF, FKBP5, NR3C1, OXTR). Functional DNAm pathways and soluble markers of immune dysfunction were secondary outcomes. RESULTS: Compared to the attention-control condition, the positive affect intervention significantly decreased methylation of CpG sites on genes that regulate ß2 adrenergic and oxytocin receptors. There was an inconsistent pattern for the direction of the intervention effects on methylation of CpG sites on genes for glucocorticoid receptors and brain-derived neurotrophic factor. Pathway analyses adjusting for the false discovery rate (padj < 0.05) revealed significant intervention-related alterations in DNAm of Reactome pathways corresponding to neural function as well as dopamine, glutamate, and serotonin release. Positive affect intervention effects on DNAm were accompanied by significant reductions in the self-reported frequency of stimulant use. CONCLUSIONS: There is an epigenetic signature of an evidence-based behavioral intervention model that reduced stimulant use, which will guide the identification of biomarkers for treatment responses.

Categorical linkage-data analysis.

Analysis of integrated data often requires record linkage in order to join together the data residing in separate sources. In case linkage errors cannot be avoided, due to the lack a unique identity key that can be used to link the records unequivocally, standard statistical techniques may produce misleading inference if the linked data are treated as if they were true observations. In this paper, we propose methods for categorical data analysis based on linked data that are not prepared by the analyst, such that neither the match-key variables nor the unlinked records are available. The adjustment is based on the proportion of false links in the linked file and our approach allows the probabilities of correct linkage to vary across the records without requiring that one is able to estimate this probability for each individual record. It accommodates also the general situation where unmatched records that cannot possibly be correctly linked exist in all the sources. The proposed methods are studied by simulation and applied to real data.

The Impact of Monetary Incentives on Delay Discounting Within a Year-Long Physical Activity Intervention.

BACKGROUND: Delay discounting is the depreciation in a reward's perceived value as a function of the time until receipt. Monetary incentive programs that provide rewards contingent on meeting daily physical activity (PA) goals may change participants' delay discounting preferences. PURPOSE: Determine if monetary incentives provided in close temporal proximity to meeting PA goals changed delay discounting, and if such changes mediated intervention effects. METHODS: Inactive adults (n = 512) wore accelerometers during a 12-month intervention where they received proximal monetary incentives for meeting daily moderate-to-vigorous PA (MVPA) goals or delayed incentives for study participation. Delay discount rate and average MVPA were assessed at baseline, end of intervention, and a 24-month follow-up. Using structural equation modeling, we tested effects of proximal versus delayed rewards on delay discounting and whether any changes mediated intervention effects on MVPA. PA self-efficacy was also evaluated as a potential mediator, and both self-efficacy and delay discounting were assessed as potential moderators of intervention effects. RESULTS: Proximal rewards significantly increased participants' delay discounting (ß = 0.238, confidence interval [CI]: -0.078, 0.380), indicating greater sensitivity to reinforcement timing. This change did not mediate incentive-associated increases in MVPA at the end of the 12-month intervention (ß = -0.016, CI: -0.053, 0.019) or at a 24-month follow-up (ß = -0.020, CI: -0.059, 0.018). Moderation effects were not found. CONCLUSIONS: Incentive-induced increases in delay discounting did not deleteriously impact MVPA. This finding may help assuage concerns about using monetary incentives for PA promotion, but further research regarding the consequences of changes in delay discounting is warranted.

This study examined the effects of providing proximal monetary incentives for meeting daily exercise goals on people's tendency to value immediate versus delayed rewards. Inactive adults (n = 512) participated in a year-long program where they wore an accelerometer each day and received either (i) small monetary rewards in close temporal proximity to instances of meeting daily exercise goals or (ii) larger rewards at 2-month intervals for ongoing participation. Those receiving proximal incentives showed an increased preference for immediate rewards, yet this reported change did not compromise long-term physical activity gains. In a comparison analysis, we found that proximal monetary incentives were not associated with changes in exercise self-efficacy. Overall, the findings suggest that monetary incentives for exercise do not negatively impact people's activity levels, though more research is needed to fully understand the implications of changes in reward timing preferences.

Flower position within plants influences reproductive success both directly and via phenology.

PREMISE: In plants, within-individual trait variation might result from mechanisms related to ontogenetic contingency, i.e., to the position of a particular structure within the plant, previous developmental events, and/or the developmental environment. Flower position within inflorescences as well as inflorescence position within plants can influence resource provisioning, phenology, biotic interactions, and reproductive success. Despite the potential implications of within-individual variation in plant reproductive phenotypes, its causes and effects on reproductive success are still little explored. METHODS: We assessed how reproductive success, in terms of fruit and seed set, and seed predation of 5883 flowers in Lathyrus vernus were influenced by their position within and among racemes, to what extent relationships between flower position and reproductive success and seed predation were mediated by phenology, and if positional effects on reproductive success depended on the external environment. RESULTS: In three years, basal flowers and racemes opened earlier and had higher fruit set than distal. Basal flowers also experienced higher seed predation. Differences among racemes in fruit and seed set were largely related to phenology, while differences in fruit set, seed set, and seed predation within racemes were not. In one year, differences in fruit set among flowers at different positions depended on flowering duration. CONCLUSIONS: Our results highlight the important role of ontogenetic contingency for within-individual variation in phenology and reproductive success. As the spatial distribution of reproductive structures affects both within-plant trait distributions and fitness, it is a likely target for natural selection.

Long-Term Effects of Incentives for HIV Viral Suppression: A Randomized Clinical Trial.

Achieving viral suppression in people living with HIV improves their quality of life and can help end the HIV/AIDS epidemic. However, few interventions have successfully promoted HIV viral suppression. The purpose of this study was to evaluate the long-term effectiveness of financial incentives for viral suppression in people living with HIV. People living with a detectable HIV viral load (≥ 200 copies/mL) were randomly assigned to Usual Care (n = 50) or Incentive (n = 52) groups. Incentive participants earned up to $10 per day for providing blood samples with an undetectable or reduced viral load. During the 2-year intervention period, the percentage of blood samples with a suppressed viral load was significantly higher among Incentive participants (70%) than Usual Care participants (43%) (OR = 7.1, 95% CI 2.7 to 18.8, p < .001). This effect did not maintain after incentives were discontinued. These findings suggest that frequent delivery of large-magnitude financial incentives for viral suppression can produce large and long-lasting improvements in viral load in people living with HIV. ClinicalTrials.gov Identifier: NCT02363387.

How does social contingency facilitate vocabulary development?

Previous research shows that infants of parents who are more likely to engage in socially contingent interactions with them tend to have larger vocabularies. An open question is how social contingency facilitates vocabulary growth. One possibility is that parents who speak in response to their infants more often produce larger amount of language input, which accelerates vocabulary growth. Another possibility is that the simplicity of contingent language input is especially suitable to support early word learning. A third possibility is that more evidence of the communicative nature of language, achieved through frequent contingent responses, helps infants build a link between their own words or vocalizations and others' behaviors. This link may lead to a better understanding of the communicative nature of language and further language advances, including vocabulary growth. To distinguish between these hypotheses, we analyzed the relations between parent-infant interactions when infants were 9 months and their vocabulary size at 12 months, using a naturalistic corpus. Our findings show that the frequency of parents' verbal contingent responses predicts receptive vocabulary size at 12 months and this predictive relation is unlikely to be due to the amount of language input or the simplicity of language within socially contingent interactions. RESEARCH HIGHLIGHTS: Infants of parents who respond to their vocalizations more often during the first year of life tend to have larger vocabularies in the second year. It is an open question what drives the predictive relation between parents' responsiveness and infants' vocabulary; we tested three hypotheses that offer competing explanations. More responsive parents might provide (1) more language input, (2) simpler language input, (3) more evidence of the communicative nature of language (via frequent responses). We find support for the third hypothesis; the frequency of parents' responses predicts infants' vocabularies above and beyond the amount and simplicity of language input.

Infant sensitivity to social contingency moderates the predictive link between early maternal reciprocity and infants' emerging social behavior.

The scientific study of love underscores the importance of dyadic reciprocity in laying the foundation for infants' social development. While research establishes links between early reciprocity and children's social capacities, some infants appear to benefit from reciprocity more than others. A central feature of reciprocity is its contingent structure, that is, the extent to which maternal behaviors are temporally associated with and contingent upon infants' dynamically changing cues. As such, infants' sensitivity to social contingencies may define the extent to which an infant benefits from maternal reciprocity. The current study examined the role of infants' sensitivity to social contingency (SC) in moderating associations between early maternal reciprocity and subsequent infants' social behavior. The study followed 157 children (47% females), across the first year of life (4, 10, and 12 months) and at preschool age (48 months). Infants' SC at 4 and 10 months moderated the link between early maternal reciprocity and infants' prosocial behavior observed at 12 months. SC at 10 months moderated the link between early reciprocity and reported peer problems at 48 months. Maternal reciprocity predicted more helping behavior in infancy and fewer peer problems at preschool, but only for infants who displayed high SC. Findings highlight the contingent nature of reciprocal mother-infant interactions revealing that an infant's sensitivity to breaks in social-contingency moderates the developmental benefit of reciprocity. Future research is necessary to directly test the underlying mechanisms of these processes and better understand the individual characteristics of infants' sensitivity to social contingency and its' role in typical and atypical development. RESEARCH HIGHLIGHTS: Individual differences in infants' sensitivity to breaks in social contingencies may moderate the extent to which infants benefit from contingent reciprocal maternal behavior (i.e., maternal reciprocity). Maternal reciprocity predicted more helping behavior in infancy and fewer peer problems at preschool, but only for infants who displayed high sensitivity to breaks in social contingency. Findings highlight the contingent nature of reciprocal mother-infant interactions revealing that infants' sensitivity to breaks in social-contingency moderates the developmental benefit of reciprocity. Findings emphasize the need to develop measurement methods and direct empirical attention to the important yet understudied individual characteristic of infants' sensitivity to social contingency and its role in shaping social development.

Exploring the internal forward model: action-effect prediction and attention in sensorimotor processing.

Action-effect predictions are believed to facilitate movement based on its association with sensory objectives and suppress the neurophysiological response to self- versus externally generated stimuli (i.e. sensory attenuation). However, research is needed to explore theorized differences in the use of action-effect prediction based on whether movement is uncued (i.e. volitional) or in response to external cues (i.e. stimulus-driven). While much of the sensory attenuation literature has examined effects involving the auditory N1, evidence is also conflicted regarding this component's sensitivity to action-effect prediction. In this study (n = 64), we explored the influence of action-effect contingency on event-related potentials associated with visually cued and uncued movement, as well as resultant stimuli. Our findings replicate recent evidence demonstrating reduced N1 amplitude for tones produced by stimulus-driven movement. Despite influencing motor preparation, action-effect contingency was not found to affect N1 amplitudes. Instead, we explore electrophysiological markers suggesting that attentional mechanisms may suppress the neurophysiological response to sound produced by stimulus-driven movement. Our findings demonstrate lateralized parieto-occipital activity that coincides with the auditory N1, corresponds to a reduction in its amplitude, and is topographically consistent with documented effects of attentional suppression. These results provide new insights into sensorimotor coordination and potential mechanisms underlying sensory attenuation.

Contingency Management for Cannabis Use Disorder Treatment.

INTRODUCTION: Although recreational cannabis use and abuse are expressive worldwide, the comparison of worldwide used psychotherapies, such as cognitive behavior therapy, with contingency management in the treatment of cannabis use disorder remains inconclusive. METHODS: We screened all articles published on MEDLINE (via PubMed) published until October 2023 and conducted a systematic review with meta-analysis. RESULTS: Sixteen studies were included, and contingency management intervention likely promotes abstinence outcomes and more negative urinalyses for adults or adolescents with cannabis use disorder. DISCUSSION: This review provides moderate- to high-quality evidence that contingency management can be used to treat cannabis use disorder. However, further trials need to be developed to analyze the quantity of substance use, personal achievements, and operational improvements after treatment.

Contingency inferences from base rates: A parsimonious strategy?

The pseudocontingency framework provides a parsimonious strategy for inferring the contingency between two variables by assessing the base rates. Frequently occurring levels are associated, as are rarely occurring levels. However, this strategy can lead to different contingency inferences in different contexts, depending on how the base rates vary across contexts. Here, we examine how base-rate consistency influences base-rate learning and reliance by contrasting consistent with inconsistent base rates. We hypothesized that base-rate learning is facilitated, and that people rely more on base rates if base rates are consistent. In Experiment 1, the base rates across four contexts implied the same (consistent) or different (inconsistent) contingencies. Base rates were learned equally accurately, and participants inferred contingencies that followed the base rates but deviated from the genuine contingencies within contexts, regardless of consistency. In Experiment 2, we additionally manipulated whether the context was a plausible moderator of the contingency. While we replicated the first experiment's results when the context was a plausible moderator, base-rate inferences were stronger for consistent base rates when the context was an implausible moderator. Possibly, when a moderation-by-context was implausible, participants also relied on the base-rate correlation across contexts, which implied the same contingency when base rates were consistent but was zero when the base rates were inconsistent. Thus, our findings suggest that contingency inferences from base rates involve top-down processes in which people decide how to use base-rate information.

Genomic evolution of antibiotic resistance is contingent on genetic background following a long-term experiment with Escherichia coli.

Antibiotic resistance is a growing health concern. Efforts to control resistance would benefit from an improved ability to forecast when and how it will evolve. Epistatic interactions between mutations can promote divergent evolutionary trajectories, which complicates our ability to predict evolution. We recently showed that differences between genetic backgrounds can lead to idiosyncratic responses in the evolvability of phenotypic resistance, even among closely related Escherichia coli strains. In this study, we examined whether a strain's genetic background also influences the genotypic evolution of resistance. Do lineages founded by different genotypes take parallel or divergent mutational paths to achieve their evolved resistance states? We addressed this question by sequencing the complete genomes of antibiotic-resistant clones that evolved from several different genetic starting points during our earlier experiments. We first validated our statistical approach by quantifying the specificity of genomic evolution with respect to antibiotic treatment. As expected, mutations in particular genes were strongly associated with each drug. Then, we determined that replicate lines evolved from the same founding genotypes had more parallel mutations at the gene level than lines evolved from different founding genotypes, although these effects were more subtle than those showing antibiotic specificity. Taken together with our previous work, we conclude that historical contingency can alter both genotypic and phenotypic pathways to antibiotic resistance.

Implementing contingency management into rural recovery housing: recommendations of a professional advisory expert panel.

Background: Rural areas in the United States have been severely impacted by recent rises in substance use related mortality and psychosocial consequences. There is a dearth of treatment resources to address substance use disorder (SUD). Rural recovery houses (RRH) are important services that provide individuals with SUD with an environment where they can engage in recovery-oriented activities, but dropout rates are unacceptably high, and evidence-based interventions such as contingency management (CM) may reduce dropout and improve outcomes for RRH residents. In this paper, we describe the results of a national convening of experts that addressed important issues concerning the implementation of CM within the context of RRHs.Methods: Twelve experts (five female) in the areas of CM, RRH and rural health participated in a one-day facilitated meeting that used nominal group technique to identify expert consensus in three areas as they pertain to RRH: (a) facilitators and barriers to CM implementation, (b) elements necessary for successful program building based on group feedback, and (c) recommendations for future implementation of CM.Results: Several RRH- and system-level barriers and facilitators to implementing CM were identified by the panel, and these were categorized based on the level of importance for and ease of implementation. CM funding, staff and resident buy-in, set policies, education on CM, and consistent fidelity to CM procedures and tracking were identified as important requirements for implementing CM in RRH.Conclusions: We provide recommendations for the implementation of CM in RRH that may be useful in this context, as well as more broadly.

Feasibility of a telehealth-based contingency management intervention for alcohol use disorders using the phosphatidylethanol (PEth) 16:0/18:1 alcohol biomarker: a pilot randomized trial.

Background: Phosphatidylethanol (PEth) is a blood-based biomarker for alcohol consumption that can be self-collected and has high sensitivity, specificity, and a longer detection window compared to other alcohol biomarkers.Objectives: We evaluated the feasibility and acceptability of a telehealth-based contingency management (CM) intervention for alcohol use disorder (AUD) using the blood-based biomarker PEth to assess alcohol consumption.Methods: Sixteen adults (7 female, 9 male) with AUD were randomized to Control or CM conditions. Control participants received reinforcers regardless of their PEth levels. CM participants received reinforcers for week-to-week decreases in PEth (Phase 1) or maintenance of PEth consistent with abstinence (<20 ng/mL, Phase 2). Blood samples were self-collected using the TASSO-M20 device. Acceptability was assessed by retention in weeks. Satisfaction was assessed with the Client Satisfaction Questionnaire (CSQ-8) and qualitative interviews. The primary efficacy outcome was PEth-defined abstinence. Secondary outcomes included the proportion of visits with PEth-defined heavy alcohol consumption, negative urine ethyl glucuronide results, and self-reported alcohol use.Results: Retention averaged 18.6 ± 8.8 weeks for CM participants. CM participants reported high levels of satisfaction (CSQ-8, Mean = 30.3 ± 1.5). Interview themes included intervention positives, such as staff support, quality of life improvement, and accountability. 72% of PEth samples from CM participants were consistent with abstinence versus 34% for Control participants (OR = 5.0, p = 0.007). PEth-defined heavy alcohol consumption was detected in 28% of CM samples and 52% of Control samples (OR = 0.36, p = 0.159). CM participants averaged 1.9 ± 1.7 drinks/day versus 4.2 ± 6.3 for Control participants (p = 0.304).Conclusion: Results support the acceptability and satisfaction of a telehealth PEth-based CM intervention, though a larger study is needed to assess its efficacy [NCT04038021].

Effectiveness of Contingency Management in Tobacco Smokers with Depressive Symptoms: A Systematic Review.

Background: Effective interventions are required to address tobacco smoking in people with depressive symptomatology. In this context, contingency management could be one useful therapeutic strategy. Objectives: This study is a systematic review of tobacco cessation interventions for smokers with depressive symptomatology including a contingency management component, evaluating their efficacy with regards to tobacco abstinence, depressive symptomatology, adherence to treatment and other variables related to tobacco use. For this purpose, a search was carried out in Pubmed, PsycINFO, Cochrane, Web of Science and ClinicalTrials.gov in September 2022. The quality of the studies was assessed using the Cochrane Risk of Bias tool. Results: Of the 208 articles identified, six were included in this review. Results: For the most part, the research included suggests that contingency management is an effective strategy for improving abstinence outcomes, adherence, and other smoking-related variables such as delay discounting and intensity of cigarette demand in smokers with depressive symptomatology. Conclusions: Although contingency management could be a promising intervention in tobacco smokers with depressive symptomatology, further research in this area is still required.

The Whys and Wherefores of Reducing Cannabis Use in Early Psychosis: A Qualitative Study of Service Users' Experiences of Quitting and the Support.

Objectives: Cannabis is the most widely used substance among people with recent onset psychosis, but it can have significant negative consequences for long term wellbeing in this cohort. We explored the perspectives of people with recent onset psychosis who used cannabis on their motivations for quitting, their experiences of trying to do so, and their views of the support they had received and the strategies that they had tried. Methods: Twenty one-to-one qualitative interviews were conducted with Early Intervention in Psychosis service users in England who had participated in the CIRCLE trial. Purposive sampling was used to recruit a mix of demographic, cannabis use status, and other characteristics. Results: Quitting cannabis is often very challenging for people and can require making substantial changes in their lives, including to their social relationships, living arrangements, or pathways through work or education. Participants reported wanting help, but often experienced support from mental health services as insubstantial and poorly tailored. Support from peers with relevant lived-experience, where available, was highly valued. Common reasons for quitting included its impact on key life goals or engaging with hobbies, finances, mental health, incompatibility with self-image, and negative use expectancies of intoxication. Concerns regarding mental health were primarily related to psychotic illness, including fear of exacerbating symptoms or experiencing future hospital admissions. Discussion: It is currently unclear how best to support people in this cohort. Interventions that provide support from people with relevant lived experience may be more valued and more clinically effective than current offerings.