OBJECTIVES/GOALS: We aimed to conduct an updated genome-wide meta-analysis of keloids in expanded populations, including those most afflicted by keloids. Our overall objective was to improve understanding of keloid development though the identification and further characterization of keloid-associated genes with genetically predicted gene expression (GPGE). METHODS/STUDY POPULATION: We used publicly available summary statistics from several large-scale DNA biobanks, including the UK Biobank, FinnGen, and Biobank Japan. We also leveraged data from the Million Veterans Program and performed genome-wide association studies of keloids in BioVU and eMERGE. For each of these datasets, cases were determined from ICD-9/ICD-10 codes and phecodes. With these data we conducted fixed effects meta-analysis, both across ancestries and stratified by broad ancestry groups. This approach allowed us to consider cumulative evidence for genetic risk factors for keloids and explore potential ancestry-specific components of risk. We used FUMA for functional annotation of results and LDSC to estimate ancestry-specific heritability. We performed GPGE analysis using S-PrediXcan with GTEx v8 tissues. RESULTS/ANTICIPATED RESULTS: We detected 30 (23 novel) genomic risk loci in the cross-ancestry analysis. Major risk loci were broadly consistent between ancestries, with variable effects. Keloid heritability estimates from LDSC were 6%, 21%, and 34% for European, East Asian, and African ancestry, respectively. The top hit (P = 1.7e-77) in the cross-ancestry analysis was at a replicated variant (rs10863683) located downstream of LINC01705. GPGE analysis identified an association between decreased risk of keloids and increased expression of LINC01705 in fibroblasts (P = 3.6e10-20), which are important in wound healing. The top hit in the African-ancestry analysis (P = 5.5e-31) was a novel variant (rs34647667) in a conserved region downstream of ITGA11. ITGA11 encodes a collagen receptor and was previously associated with uterine fibroids. DISCUSSION/SIGNIFICANCE: This work significantly increases the yield of discoveries from keloid genetic association studies, describing both common and ancestry-specific effects. Stark differences in heritability support a potential adaptive origin for keloid disparities. Further work will continue to examine keloids in the broader context of other fibrotic diseases.

OBJECTIVES/GOALS: Empowering the Participant Voice (EPV) is a 6-CTSA Rockefeller-led collaboration to developcustom REDCap infrastructure to collect participant feedback using the validated Research Participant Perception Survey (RPPS), demonstrate its value in use cases, and disseminate it for broad adoption. METHODS/STUDY POPULATION: The EPV team developed data and survey implementation standards, and specifications for the dashboard and multi-lingual RPPS/REDCap project XML file. The VUMC built a custom At-a-Glance Dashboard external module that displays Top Box scores (percent best answer), with conditional formatting to aid analysis, and response/completion rates. Results populate site dashboards, and aggregate to a multi-site dashboard for benchmarking. Results can be filtered by participant/study characteristics. Sites developed individual use cases, leveraging local infrastructure, initiatives and stakeholder input. Infrastructure and guides were designed for dissemination through public websites. RESULTS/ANTICIPATED RESULTS: Five sites sent 23,797surveys via email, patient portal or SMS. 4,133 (19%) participants diverse in age, race, and ethnicity, returned responses. Sites analyzed their data and acted on selected findings, improving recruitment, communication and feeling valued. Aggregate scores for feeling listened to and respected were hight (>90%%); scores for feeling prepared by the consent process were lower (57-77%) and require action. Some groups experiences were better than others. Sites differed significantly in some scores. Dissemination of EPV is underway. Infrastructure and guides are downloadable free of charge, with advice from the EPV team. In 2023, a sixth site began piloting a lower literacy survey version and syncing data to the consortium dashboard. DISCUSSION/SIGNIFICANCE: The EPV RPPS/REDCap infrastructure enabled sites to collect participant feedback, identify actionable findings and benchmark with peers. Stakeholders and collaborators designed and tested local initiatives to increase responses and diversity, address disparities, and discover better practices.

Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother–infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament.

Young people who leave Out-of-Home Care (OoHC) are a significantly vulnerable cohort. No after-care support program to date has been completely informed by young people and their care team. This scoping study explored the perspectives of young people and their wider care team on: (1) challenges surrounding the transition process; and (2) how these challenges can be addressed. Semi-structured interviews and focus group sessions were conducted with 33 stakeholders from OoHC (i.e., young people in care; young people who had transitioned from care; carers; caseworkers and senior OoHC executives). Four themes captured the challenges of transitioning out of care, including: (1) inadequate processes underpinning the transition; (2) instability within the family unit; (3) financial challenges and (4) lack of independence during care. Stakeholders agreed that greater support during the transition process is necessary, including life-skills training while in care and a post-care worker and/or mentor to provide after-care support. These findings provide compelling insights into the challenges that young people transitioning from OoHC experience and possible solutions for how such challenges can be addressed. These findings will inform the development and delivery of a co-designed and specialised after-care support service for this population.

Considering the important role that paid support workers play in care of older people with dementia, it is vital that researchers and relevant organisations understand the factors that lead to them feeling valued for the work that they do, and the consequences of such valuing (or lack thereof). The current study employed semi-structured interviews to understand the individual experiences of 15 support workers based both in residential care homes and private homes. The General Inductive Approach was used to analyse the interview transcriptions and to develop a conceptual model that describes the conditions that lead to support workers feeling valued for the work that they do. This model consists of organisational or individual strategies, the context in which support work takes place, and various interactions, actions and intervening conditions that facilitate or prevent support workers feeling valued. A significant finding in this research was the role of interpersonal relationships and interactions which underlie all other aspects of the conceptual model developed here. By understanding the importance of how employers, families of older adults with dementia and peers interact with support workers, we may promote not only the quality of work that support workers deliver, but also the wellbeing of the support workers themselves.

In an era of free movement UK employers have had ready access to a supply of labour from the European Union to fill low-skilled jobs. This has enabled them to adopt business models, operating within broader supply chains, that take advantage of this source of labour and the flexibility that many migrant workers – especially those who are new arrivals to the UK – are prepared to offer them. Drawing mainly on evidence from employers on the role of migrant workers in selected sectors with a substantial proportion of low-skilled jobs, this article explores the challenges and opportunities they face in transitioning to a new post-Brexit immigration regime.

Active labour market policy (ALMP) is a well-established strategy but one aspect is greatly neglected – employer participation – about which there is a lack of systematic evidence. The question of why and how employers participate in ALMP, and whether there may be some shift from employers solely being passive recipients of job-ready candidates to having a more proactive and strategic role, is addressed by drawing on new research into Talent Match, a contemporary UK employability programme which places particular emphasis on employer involvement. The research findings point to a conceptual distinction between employers’ roles as being reactive gatekeepers to jobs and/or being proactive strategic partners, with both evident. It is argued that the Talent Match programme demonstrates potential to benefit employers, jobseekers and programme providers, with devolution of policy to the local level a possible way forward. The conclusion, however, is that the barrier to wider replication is not necessarily a problem of practice but of centralised control of policy and, in particular, commitment to a supply-side approach. Empirical, conceptual and policy contributions are made to this under-researched topic.

Prenatal maternal depression and a multilocus genetic profile of two susceptibility genes implicated in the stress response were examined in an interaction model predicting negative emotionality in the first 3 years. In 179 mother–infant dyads from the Maternal Adversity, Vulnerability, and Neurodevelopment cohort, prenatal depression (Center for Epidemiologic Studies Depressions Scale) was assessed at 24 to 36 weeks. The multilocus genetic profile score consisted of the number of susceptibility alleles from the serotonin transporter linked polymorphic region gene (5-HTTLPR): no long-rs25531(A) (LA: short/short, short/long-rs25531(G) [LG], or LG/LG] vs. any LA) and the dopamine receptor D4 gene (six to eight repeats vs. two to five repeats). Negative emotionality was extracted from the Infant Behaviour Questionnaire—Revised at 3 and 6 months and the Early Child Behavior Questionnaire at 18 and 36 months. Mixed and confirmatory regression analyses indicated that prenatal depression and the multilocus genetic profile interacted to predict negative emotionality from 3 to 36 months. The results were characterized by a differential susceptibility model at 3 and 6 months and by a diathesis–stress model at 36 months.

Disorganized attachment is an important early risk factor for socioemotional problems throughout childhood and into adulthood. Prevailing models of the etiology of disorganized attachment emphasize the role of highly dysfunctional parenting, to the exclusion of complex models examining the interplay of child and parental factors. Decades of research have established that extreme child birth weight may have long-term effects on developmental processes. These effects are typically negative, but this is not always the case. Recent studies have also identified the dopamine D4 receptor (DRD4) as a moderator of childrearing effects on the development of disorganized attachment. However, there are inconsistent findings concerning which variant of the polymorphism (seven-repeat long-form allele or non–seven-repeat short-form allele) is most likely to interact with caregiving in predicting disorganized versus organized attachment. In this study, we examined possible two- and three-way interactions and child DRD4 polymorphisms and birth weight and maternal caregiving at age 6 months in longitudinally predicting attachment disorganization at 36 months. Our sample is from the Maternal Adversity, Vulnerability and Neurodevelopment project, a sample of 650 mother–child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 was obtained with buccal swabs and categorized according to the presence of the putative allele seven repeat. Macroanalytic and microanalytic measures of maternal behavior were extracted from a videotaped session of 20 min of nonfeeding interaction followed by a 10-min divided attention maternal task at 6 months. Attachment was assessed at 36 months using the Strange Situation procedure, and categorized into disorganized attachment and others. The results indicated that a main effect for DRD4 and a two-way interaction of birth weight and 6-month maternal attention (frequency of maternal looking away behavior) and sensitivity predicted disorganized attachment in robust logistic regression models adjusted for social demographic covariates. Specifically, children in the midrange of birth weight were more likely to develop a disorganized attachment when exposed to less attentive maternal care. However, the association reversed with extreme birth weight (low and high). The DRD4 seven-repeat allele was associated with less disorganized attachment (protective), while non–seven-repeat children were more likely to be classified as disorganized attachment. The implications for understanding inconsistencies in the literature about which DRD4 genotype is the risk direction are also considered. Suggestions for intervention with families with infants at different levels of biological risk and caregiving risk are also discussed.

Introduction: The National Comprehensive Cancer Control Program (NCCCP) and National Tobacco Control Program (NTCP) are both well-positioned to promote the use of population-based tobacco cessation interventions, such as state quitlines and Web-based interventions.

Aims: This paper outlines the methodology used to conduct a comparative effectiveness research (CER) study of traditional and Web-based tobacco cessation and quitline promotion approaches.

Methods: A mixed-methods study with three components was designed to address the effect of promotional activities on service usage and the comparative effectiveness of population-based smoking cessation activities across multiple states.

Results/Findings: The cessation intervention component followed 7,902 smokers (4,307 quitline users and 3,595 Web intervention users) to ascertain prevalence of 30-day abstinence rates seven months after registering for smoking cessation services. User characteristics and quit success was compared across the two modalities. In the promotions component, reach and use of traditional and innovative promotion strategies were assessed for 24 states, including online advertising, state Web sites, social media, mobile applications, and their effects on quitline call volume. The partnership intervention component studied the extent of collaboration among six selected NCCCPs and NTCPs.

Conclusions: This study will guide program staff and clinicians with evidence-based recommendations and best practices for implementation of tobacco cessation within their patient and community populations and establish an evidence base that can be used for decision making.