OBJECTIVES/GOALS: Reveal common immune mechanisms in dysregulated age-related lobular involution (ARLI) and post-partum lobular involution (PPLI) to understand their link to increased breast cancer risk, challenging the traditional view of their distinctiveness. Ultimately, to improve breast cancer risk assessment and personalized prevention METHODS/STUDY POPULATION: The Mayo Clinic Benign Breast Disease (BBD) cohort comprises of ~20,000 women with benign biopsies, including ~1000 women with sequential benign biopsies. Lobular involution (LI) status was assessed by selecting perimenopausal women, ages 45-55, with sequential biopsies, comparing acini number and lobule size between initial and subsequent biopsies. NanoString IO360/ BC360 RNA profiling identified differentially expressed genes associated with dysregulated LI. Using multiplex immunofluorescence (mIF), I'll analyze and spatially map immune biomarkers related to dysregulated ARLI and PPLI in BBD tissue from perimenopausal women who did or did not go on to develop breast cancer, assessing the commonality of ARLI and PPLI markers and exploring their potential as risk biomarkers for breast cancer. RESULTS/ANTICIPATED RESULTS: Preliminary findings link patients who display dysregulated ARLI with an increased breast cancer risk and identify vital PPLI biomarkers in perimenopausal women. I expect the biopsies of women who developed post-menopausal breast cancer (PMBC) and post-partum breast cancer (PPBC) to exhibit elevated levels of dysregulated ARLI immune biomarkers and PPLI biomarkers. Spatially mapping these markers promises to provide a more comprehensive understanding of their interactions, potentially revealing common immunological pathways. These findings could transform our current paradigm of ARLI and PPLI as distinct processes and demonstrate their interconnection in shaping breast cancer risk. DISCUSSION/SIGNIFICANCE: PMBC and PPBC dominate majority of breast cancer cases. Both involve activation of the understudied process of lobular involution, which has been shown to have pro-tumorigenic traits. Elucidating these mechanisms will aid more efficient risk stratification and personalized prevention to reduce incidence and mortality of breast cancer.

Community research advisory councils (C-RAC) bring together community members with interest in research to support design, evaluation, and dissemination of research in the communities they represent. There are few ways for early career researchers, such as TL1 trainees, to develop skills in community-engaged research, and there are limited opportunities for C-RAC members to influence early career researchers. In our novel training collaboration, TL1 trainees presented their research projects to C-RAC members who provided feedback. We present on initial evidence of student learning and summarize lessons learned that TL1 programs and C-RACs can incorporate into future collaborations.

Mobile devices with health apps, direct-to-consumer genetic testing, crowd-sourced information, and other data sources have enabled research by new classes of researchers. Independent researchers, citizen scientists, patient-directed researchers, self-experimenters, and others are not covered by federal research regulations because they are not recipients of federal financial assistance or conducting research in anticipation of a submission to the FDA for approval of a new drug or medical device. This article addresses the difficult policy challenge of promoting the welfare and interests of research participants, as well as the public, in the absence of regulatory requirements and without discouraging independent, innovative scientific inquiry. The article recommends a series of measures, including education, consultation, transparency, self-governance, and regulation to strike the appropriate balance.

Australian mosquito species significantly impact human health through nuisance biting and the transmission of endemic and exotic pathogens. Surveillance programmes designed to provide an early warning of mosquito-borne disease risk require reliable identification of mosquitoes. This study aimed to investigate the viability of Matrix-Assisted Laser Desorption/Ionization–Time-of-Flight Mass Spectrometry (MALDI-TOF MS) as a rapid and inexpensive approach to the identification of Australian mosquitoes and was validated using a three-step taxonomic approach. A total of 300 mosquitoes representing 21 species were collected from south-eastern New South Wales and morphologically identified. The legs from the mosquitoes were removed and subjected to MALDI-TOF MS analysis. Fifty-eight mosquitoes were sequenced at the cytochrome c oxidase subunit I (cox1) gene region and genetic relationships were analysed. We create the first MALDI-TOF MS spectra database of Australian mosquito species including 19 species. We clearly demonstrate the accuracy of MALDI-TOF MS for identification of Australian mosquitoes. It is especially useful for assessing gaps in the effectiveness of DNA barcoding by differentiating closely related taxa. Indeed, cox1 DNA barcoding was not able to differentiate members of the Culex pipiens group, Cx. quinquefasciatus and Cx. pipiens molestus, but these specimens were correctly identified using MALDI-TOF MS.

Evidence on the intergenerational continuity of intimate partner violence (IPV) suggests small to moderate associations between childhood exposure and young adult IPV involvement, suggesting an indirect effects model. Yet, few prospective studies have formally tested meditational mechanisms. The current study tested a prospective (over 9 years) moderated-mediational model in which adolescent psychopathology symptoms (i.e., internalizing, externalizing, and combined) mediated the association between exposure to IPV in middle childhood and young adult IPV perpetration. In a more novel contribution, we controlled for proximal young adult partner and relationship characteristics. The sample consisted of n = 205 participants, who were, on average, assessed for exposure to parent IPV at age 12.30 years, adolescent psychopathology symptoms at age 15.77 years, and young adult IPV at 21.30 years of age. Data suggest a small, significant direct path from IPV exposure to young adult perpetration, mediated only through adolescent externalizing. Gender moderation analyses reveal differences in sensitivity to exposure across developmental periods; for males, effects of exposure were intensified during the transition to adolescence, whereas for females, effects were amplified during the transition to adulthood. In both cases, the mediational role of psychopathology symptoms was no longer significant once partner antisocial behavior was modeled. Findings have important implications for both theory and timing of risk conveyance.

Characterizing scalar dispersion is a key concern in a wide variety of applications, including both steady-state and time-dependent studies of wastewater outfalls, salinity distribution in estuaries, and the spreading of pollutants from industrial spills. As the size of a scalar plume grows with respect to the size of the containing water body, the effective dispersion varies, from the well-known ${ \sigma }_{x}^{2} \sim {t}^{3} $ behaviour for a plume enveloped in a region of linear shear, to the ${ \sigma }_{x}^{2} \sim t$ behaviour at the limit of a laterally well-mixed plume. We introduce an additional regime in which the plume extends across the full range of the available shear, but is not significantly affected by the lateral bounds of the water body. Through an analytic treatment we show that this regime exhibits a ${ \sigma }_{x}^{2} \sim {t}^{2} $ behaviour, independent of lateral mixing coefficient. Particle tracking results in an idealized, tidal channel–shoal basin demonstrate this regime as particle clouds straddle the channel–shoal interface. Quantitative analysis of spatial moments as plumes transition between regimes show good correlation between the observed parameters and parameters predicted by the analytic framework.