OBJECTIVES/GOALS: Mechanisms underlying racial and ethnic disparities in rectal cancer care remain poorly understood. We aimed to identify barriers and facilitators to care among rectal cancer patients who identify as Hispanic/Latino (H/L) and to understand how these factors may differ based on rurality, social/physical context, and community support. METHODS/STUDY POPULATION: We utilized qualitative methods and a community-based participatory research framework, including partnership with a community-based organization and oversight from a community advisory board. We developed an initial semi-structured interview guide based on an ecological model of health behavior and then iteratively refined it with the assistance of our partners to incorporate unique aspects of the H/L community in a culturally appropriate manner. Eligible patients and their caregivers are invited to participate in hour-long interviews in both English and Spanish, depending on participants’ preferences. All interviews are recorded, translated, transcribed, and coded. Findings will be compiled and fed back to participantsand community stakeholders as a part of a community forum. RESULTS/ANTICIPATED RESULTS: We identified 6 areas for discussion based on our model: health beliefs (perceived severity, benefit, and barriers; self-efficacy), health literacy, others’ experiences with cancer, patient-provider relationship (patient-provider communication; provider-provider communication; language; cultural competency; discrimination), sources of support, and access to care. Participants are currently being recruited by clinical providers, through flyers in the cancer center, or via outreach from our community partner. We have interviewed 8 participants to date, with discussions ranging from the shock of the initial diagnosis, difficulties with navigating specialty care, and the complexities of shared decision making. We are expecting a total of 30-40 interviews to reach thematic saturation. DISCUSSION/SIGNIFICANCE: We hope to improve our understanding of mechanisms underlying racial and ethnic disparities in rectal cancer care and to identify potential targets for improvement. We plan to use our results to develop community-based policy interventions to improve care delivery, patient experience, and health equity.

Background: Healthcare facilities have experienced many challenges during the COVID-19 pandemic, including limited personal protective equipment (PPE) supplies. Healthcare personnel (HCP) rely on PPE, vaccines, and other infection control measures to prevent SARS-CoV-2 infections. We describe PPE concerns reported by HCP who had close contact with COVID-19 patients in the workplace and tested positive for SARS-CoV-2. Method: The CDC collaborated with Emerging Infections Program (EIP) sites in 10 states to conduct surveillance for SARS-CoV-2 infections in HCP. EIP staff interviewed HCP with positive SARS-CoV-2 viral tests (ie, cases) to collect data on demographics, healthcare roles, exposures, PPE use, and concerns about their PPE use during COVID-19 patient care in the 14 days before the HCP’s SARS-CoV-2 positive test. PPE concerns were qualitatively coded as being related to supply (eg, low quality, shortages); use (eg, extended use, reuse, lack of fit test); or facility policy (eg, lack of guidance). We calculated and compared the percentages of cases reporting each concern type during the initial phase of the pandemic (April–May 2020), during the first US peak of daily COVID-19 cases (June–August 2020), and during the second US peak (September 2020–January 2021). We compared percentages using mid-P or Fisher exact tests (α = 0.05). Results: Among 1,998 HCP cases occurring during April 2020–January 2021 who had close contact with COVID-19 patients, 613 (30.7%) reported ≥1 PPE concern (Table 1). The percentage of cases reporting supply or use concerns was higher during the first peak period than the second peak period (supply concerns: 12.5% vs 7.5%; use concerns: 25.5% vs 18.2%; p Conclusions: Although lower percentages of HCP cases overall reported PPE concerns after the first US peak, our results highlight the importance of developing capacity to produce and distribute PPE during times of increased demand. The difference we observed among selected groups of cases may indicate that PPE access and use were more challenging for some, such as nonphysicians and nursing home HCP. These findings underscore the need to ensure that PPE is accessible and used correctly by HCP for whom use is recommended.

Funding: None

Disclosures: None

Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.

OBJECTIVES/SPECIFIC AIMS: Women with pulmonary arterial hypertension (PAH) exhibit superior right ventricular (RV) function and survival compared with men, a phenomenon attributed to poorly understood cardioprotective effects of 17β-estradiol (E2). We hypothesize that E2, through ERα, attenuates PH-induced RV dysfunction by upregulating the pro-contractile and pro-angiogenic peptide apelin. This ERα-mediated increase in apelin is mediated by the myocardial remodeling effector bone morphogenetic protein receptor 2 (BMPR2). METHODS/STUDY POPULATION: ERα, BMPR2, and apelin were measured (western blot) in RVs from patients with PAH-induced RV failure and in RV homogenates from male or female Sprague-Dawley rats with sugen/hypoxia (SuHx) or monocrotaline (MCT)-induced PH. H9c2 rat cardiomyoblasts and cardiac endothelial cells were stressed with TNF-α (10 ng/mL) or staurosporine (50 nM)±E2 (100 nM; 24 h). ERα-, BMPR2-, and apelin-dependence were evaluated by siRNA (5 pM). Downstream apelin target and pro-survival factor ERK1/2 expression was measured (western blot). p<0.05 by ANOVA was considered significant. RESULTS/ANTICIPATED RESULTS: ERα correlated positively with BMPR2 and apelin expression in SuHx-RVs and human RVs. Treatment of SuHx-PH rats with E2 or ERα agonist increased RV BMPR2 and apelin, whereas RV apelin was decreased in E2-treated hypoxic ERα knockout mice (p<0.05), but not in ERβ knockout mice. In H9c2 cells, E2 or ERα agonist attenuated TNF-α- or staurosporine-induced decreases in BMPR2, apelin, and phospho-ERK1/2 (p<0.05 for all endpoints). E2 protection was lost in presence of siRNA directed against ERα, BMPR2, or apelin (p<0.05). ERα was necessary for E2-mediated increases in BMPR2, apelin, and ERK1/2, and BMPR2 was required for the E2-mediated increase in apelin (p<0.05 for siRNA vs. scramble). ERα, BMPR2, and apelin protein was increased in decompensated human RVs but downstream phospho-ERK signaling was disrupted. DISCUSSION/SIGNIFICANCE OF IMPACT: E2, via ERα, increases BMPR2 and apelin in the failing RV and in stressed rat cardiomyoblasts. The E2-mediated increase in apelin is BMPR2-dependent and likely occurs through direct binding of ERα to the BMPR2 promoter. Harnessing this E2-ERα-BMPR2-apelin axis during RV compensation may lead to novel, RV-targeted therapies for PAH patients of either sex.

We have discovered a well-defined extended conformation of double-stranded DNA, which we call Σ-DNA, using laser-tweezers force-spectroscopy experiments. At a transition force corresponding to free energy change ΔG = 1·57 ± 0·12 kcal (mol base pair)−1 60 or 122 base-pair long synthetic GC-rich sequences, when pulled by the 3′−3′ strands, undergo a sharp transition to the 1·52 ± 0·04 times longer Σ-DNA. Intriguingly, the same degree of extension is also found in DNA complexes with recombinase proteins, such as bacterial RecA and eukaryotic Rad51. Despite vital importance to all biological organisms for survival, genome maintenance and evolution, the recombination reaction is not yet understood at atomic level. We here propose that the structural distortion represented by Σ-DNA, which is thus physically inherent to the nucleic acid, is related to how recombination proteins mediate recognition of sequence homology and execute strand exchange. Our hypothesis is that a homogeneously stretched DNA undergoes a ‘disproportionation’ into an inhomogeneous Σ-form consisting of triplets of locally B-like perpendicularly stacked bases. This structure may ensure improved fidelity of base-pair recognition and promote rejection in case of mismatch during homologous recombination reaction. Because a triplet is the length of a gene codon, we speculate that the structural physics of nucleic acids may have biased the evolution of recombinase proteins to exploit triplet base stacks and also the genetic code.

This paper presents the impact of three undergraduate research projects focusing on constructability assessment of adhesive-based wood-concrete composite structural members, on a solar heating technology that can be utilized in conjunction with this system and how these projects relate to engineering education and program development at Metropolitan State University of Denver (MSU Denver). The sustainable structures topic was pursued within senior project classes offered in summer 2013 and 2014 at MSU Denver. The first project addressed new members, while the second dealt with retrofits. These projects were motivated by faculty research in developing new sustainable construction systems using composites. Since underlining faculty research is on an international scale, students had direct access to researchers world-wide. Such research was used as an instrument in the “Experimental Methods in Structural Engineering” course. The students were also exposed to a broader-range of diverse ideas within the field of research by attending an international conference on timber bridges. The solar furnace project was run in parallel, providing students an opportunity to conduct research targeted at design and performance optimization of the heating units with the intention to assess the benefits of incorporating these devices into future buildings using the sustainable structural system technology. Experiences gained through the undergraduate research activities were applied in the design of a proposed Sustainable Systems Engineering degree program.

To assess recovery of cognitive effects, we investigated neuropsychological performance after 1 month of monitored abstinence in teens with histories of heavy episodic drinking, protracted marijuana use, or concomitant use of alcohol and marijuana. Adolescents (ages 16–18 years) with histories of heavy episodic drinking (HED; n=24), marijuana use (MJ; n=20), both heavy alcohol and marijuana use (HED+MJ; n=29), and socio-demographically similar control teens (CON; n=55) completed a neuropsychological battery following 4 weeks of monitored abstinence. Groups were similar on 5th grade standardized test scores, suggesting comparable academic functioning before onset of substance use. Relative to CON, HED showed poorer cognitive flexibility (p=.006), verbal recall (p=.024), semantic clustering (p=.011), and reading skills (p=.018). MJ performed worse than CON on inhibition task accuracy (p=.015), cued verbal memory (p=.031), and psychomotor speed (p=.027). Similar to HED youth, HED+MJ showed differences relative to CON on cognitive flexibility (p=.024) and verbal recall (p=.049). As with MJ teens, HED+MJ showed poorer task accuracy (p=.020). Unique to the HED+MJ group was poorer working memory (p=.012) relative to CON. For all substance using participants, worse performance across domains correlated with more lifetime use of alcohol and of marijuana, more withdrawal symptoms from alcohol, and earlier age of onset of marijuana use (ps<.05). Heavy alcohol use, marijuana use, and concomitant use of both substances during adolescence appear to be associated with decrements in cognitive functioning, and each substance (or combination of substances) may be linked to poorer performance in specific cognitive domains (JINS, 2014, 20, 784–795).

The present study investigated the rate and pattern of neuropsychological recovery in heavy episodic drinking teens during the initial days to weeks of abstinence from alcohol. Adolescents (ages, 16–18 years) with histories of heavy episodic drinking (HED; N = 39) and socio-demographically similar control teens (CON; N = 26) were recruited from San Diego area schools. HED and CON were comparable on 5th grade standardized math and language arts test performance to ensure similar functioning before onset of substance use. Participants were administered three neuropsychological test batteries with 2-week intervals during a 4-week monitored abstinence period. HED teens performed worse overall than CON on tests of prospective memory (p = .005), cognitive switching (p = .039), inhibition task accuracy (p = .001), verbal memory (p's < .045), visuospatial construction (p's < .043), and language and achievement (p's < .008). The statistically significant group × time interaction for block design demonstrated normalization within the 4 weeks of abstinence for the HED (p = .009). This study identified cognitive performance deficits associated with heavy episodic drinking in adolescence during early abstinence and with sustained 4-week abstention. These findings suggest alcohol-related influences on several underlying brain systems that may predate the onset of alcohol abuse or dependence or take longer than 4 weeks to recover. (JINS, 2014, 20, 218–229)

As part of the Bcool project, over 150 solar-type stars chosen mainly from planet search databases have been observed between 2006 and 2013 using the NARVAL and ESPaDOnS spectropolarimeters on the Telescope Bernard Lyot (Pic du Midi, France) and the Canada France Hawaii Telescope (Mauna Kea, USA), respectively. These single “snapshot” observations have been used to detect the presence of magnetic fields on 40% of our sample, with the highest detection rates occurring for the youngest stars. From our observations we have determined the mean surface longitudinal field (or an upper limit for stars without detections) and the chromospheric surface fluxes, and find that the upper envelope of the absolute value of the mean surface longitudinal field is directly correlated to the chromospheric emission from the star and increases with rotation rate and decreases with age.

Strabismus represents a complex oculomotor disorder characterized by the deviation of one or both eyes and poor vision. A more sophisticated understanding of the genetic liability of strabismus is required to guide searches for associated molecular variants. In this classical twin study of 1,462 twin pairs, we examined the relative influence of genes and environment in comitant strabismus, and the degree to which these influences can be explained by factors in common with refractive error. Participants were examined for the presence of latent (‘phoria’) and manifest (‘tropia’) strabismus using cover–uncover and alternate cover tests. Two phenotypes were distinguished: eso-deviation (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural equation modeling was subsequently employed to partition the observed phenotypic variation in the twin data into specific variance components. The prevalence of eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso-deviation, the polychoric correlation was significantly greater in monozygotic (MZ) (r = 0.65) compared to dizygotic (DZ) twin pairs (r = 0.33), suggesting a genetic role (p = .003). There was no significant difference in polychoric correlation between MZ (r = 0.55) and DZ twin pairs (r = 0.53) for exo-deviation (p = .86), implying that genetic factors do not play a significant role in the etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI 0.50–0.75). The additive genetic correlation for eso-deviation and refractive error was 0.13 and the bivariate heritability (i.e., shared variance) was less than 1%, suggesting negligible shared genetic effect. This study documents a substantial heritability of 64% for eso-deviation, yet no corresponding heritability for exo-deviation, suggesting that the genetic contribution to strabismus may be specific to eso-deviation. Future studies are now needed to identify the genes associated with eso-deviation and unravel their mechanisms of action.