On 19 January 2020, the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was identified in the United States, with the first cases in South Carolina confirmed on 06 March 2020. Due to initial limited testing capabilities and potential for asymptomatic transmission, it is possible that SARS-CoV-2 may have been present earlier than previously thought, while the immune status of at-risk populations was unknown. Saliva from 55 South Carolina emergency healthcare workers (EHCWs) was collected from September 2019 to March 2020, pre- and post-healthcare shifts, and stored frozen. To determine the presence of SARS-CoV-2-reactive antibodies, saliva-acquired post-shift was analysed by enzyme-linked immunosorbent assay (ELISA) with a repeat of positive or inconclusive results and follow-up testing of pre-shift samples. Two participants were positive for SARS-CoV-2 N/S1-reactive IgG, confirmed by follow-up testing, with S1 receptor binding domain (RBD)-specific IgG present in one individual. Positive samples were collected from medical students working in emergency medical services (EMSs) in October or November 2019. The presence of detectable anti-SARS-CoV-2 antibodies in 2019 suggests that immune responses to the virus existed in South Carolina, and the United States, in a small percentage of EHCWs prior to the earliest documented coronavirus disease 2019 (COVID-19) cases. These findings suggest the feasibility of saliva as a noninvasive tool for surveillance of emerging outbreaks, and EHCWs represent a high-risk population that should be the focus of infectious disease surveillance.

OBJECTIVES/GOALS: 48,000,000 people in the U.S. have hearing loss, negatively impacting quality of life and work. Unveiling axon guidance for auditory type II spiral ganglia neurons (SGNs) will aid development of new therapies. I study the role of Eph/Ephrin and planar cell polarity (PCP) signaling during type II SGN turning and outer hair cell (OHC) innervation. METHODS/STUDY POPULATION: This quantitative study was conducted on Efna3 and Vangl2 null mice possessing Neurog1CreERT2 and R26RtdTomato mutations. Spontaneous Cre activity within the Neurogenin1CreERT2 line causes recombination and expression of fluorescent Rosa26 Reporter (R26R)tdTomatoin a restricted number of SGNs, including type IIs. Together, these lines permit SGN sparse labeling. Immunostaining and confocal imaging were used to analyze dsRed in Efna3 and Vangl2 mice and quantify type II SGN turning. In combination, Imaris 3D renderings were used to quantify type II SGN turning, branching, navigation features and temporal effects of EPHRIN-A3-Fc on type IIs via cochlear cultures (a gain-of-function manipulation). For both sexes, 5-6 cochleae per genotype were analyzed and compared by t-test to wildtype (WT) controls. RESULTS/ANTICIPATED RESULTS: Efna3 nulls showed a small rise in type II SGNs incorrectly turning toward the apex at an error rate of 16.0% compared to WTs (n=6; p=0.05). P0 Efna3 nulls had reduced branch number compared to WTs, 4.1 and 7.2, respectively (n=129; p=<0.0001), suggesting EPHRIN-A3 acts as a positive growth cue. In cochlear cultures, EPHRIN-A3-Fc led to type II SGN collapse at E15.5, indicating a repulsive function. However, at P0, EPHRIN-A3-Fc treatment led to type II SGNs with elevated branch numbers compared to Control-Fc treatment: 18.1 and 11.4, respectively (n=116; p=<0.0001). This indicates a positive growth function. At E16.5, EPHRIN-A3 protein immunoreactivity on Deiters’ and pillar cells appears reduced in Vangl2 nulls compared to WT cochleae, suggesting that EPHRIN-A3 acts downstream of PCP signaling. DISCUSSION/SIGNIFICANCE: Results suggest that Eph/Ephrin signaling acts downstream of PCP signaling to mediate type II SGN guidance and EPHRIN-A3 switches its mode of activation. The clinical implications of these findings are that therapeutics targeting EPHRIN-A3 and/or VANGL2 in their given pathways could stimulate new OHC innervation following auditory damage.

OBJECTIVES/GOALS: We adapted the Serious Illness Care Program (SICP), an evidence-based intervention designed to promote early serious illness conversation, to be delivered via telehealth for older patients with acute myeloid leukemia and myelodysplastic syndromes. The purpose of this study is to assess the feasibility and usability of the adapted intervention. METHODS/STUDY POPULATION: We are conducting a single-arm pilot study of an adapted SICP that is delivered via telehealth for older patients with AML or MDS (>=60 years) and their caregivers (if available). The adapted SICP includes: 1) Patient preparation pamphlet: sent to patient prior the visit with their clinician, 2) Geriatric assessment: completed by study team and provided to clinician prior to their visit with the patient, 3) A 30-60 minute telehealth visit with their primary oncologist or oncology advance practitioner, 4) Serious Illness Conversation Guide (SICG): used by the clinician during the visit to elicit patient values, 5) Family guide: provided to patient following their visit to help patient’s share their values with their family, 6) Electronic medical record note template for clinicians to document their visit the patient. RESULTS/ANTICIPATED RESULTS: We hypothesize that the adapted SICP intervention will be feasible and usable. We will assess feasibility based on retention rate (percent of patients who consent and complete the visit); >80% is considered feasible. Usability will be assessed using the telehealth usability questionnaire; an average score of >5 is considered usable. Other measures include psychological health, advance care planning engagement, quality of life, and disease understanding. We plan to enroll 20 patients in this study. To date, 11 patients have consented to participate, 10 patients have scheduled SICP visits, 9 patients have completed their visits, 7 patients have completed post-intervention qualitative interviews, and 4 patients have completed post-intervention surveys. DISCUSSION/SIGNIFICANCE: The adapted telehealth-based SICP may promote early serious illness conversation, patient-reported outcomes, and end-of-life experience for older patients with AML and MDS. Results from this study will be used to inform development of clinical trials testing the impact of the adapted SICP on patient- and caregiver-reported outcomes.

OBJECTIVES/GOALS: 30,000,000 people in the U.S. have hearing loss, negatively impacting quality of life and work. Understanding auditory axon guidance for spiral ganglia neurons (SGNs) will aid development of new therapies. I study role of Eph/Ephrin signaling in mediating type II SGN turning events, and how planar cell polarity (PCP) signaling modulates this process. METHODS/STUDY POPULATION: This quantitative study was conducted on Efna3 and Vangl2 null mice possessing Neurog1CreERT2 and R26RtdTomato mutations. Spontaneous Cre activity within the Neurogenin 1 CreERT2 line causes recombination and expression of fluorescent Rosa26 Reporter (R26R)tdTomato in a restricted number of SGNs, including type IIs. Together these lines permit SGN sparse labeling. Bulk-labeling was used for Efna3;Vangl2 double knockout (DKO) mutants. Immunostaining and confocal imaging was used to analyze dsRed in Efna3; Vangl2 and NF-200 in DKOs to quantify type II SGN turning. In combination, 3D rendering in Imaris software was used to quantify type II SGN turning, branching and other growth and navigation characteristics. 5-6 cochleae per genotype were analyzed and compared by t-test to wildtype controls. RESULTS/ANTICIPATED RESULTS: EPHRIN-A3 is expressed on the membranes of outer pillar and Deiters’cells of the cochlear epithelium. Efna3 nulls showed a small rise in type II SGNs incorrectly turning toward the apex at an error frequency of 16.9% compared to controls (n=6; p=0.05). Efna3 nulls had reduced branch number/fiber compared to controls, 4.14 and 7.22, respectively (n=129; p DISCUSSION/SIGNIFICANCE: Our results suggest that Eph/Ephrin signaling acts parallel of PCP signaling to mediate type II SGN guidance during development. The clinical implications of these findings are that therapeutics targeting EPHRIN-A3 and/or VANGL2 in this pathway could stimulate new outer hair cell innervation by type II SGNs following auditory damage.

Olive oil (OO) polyphenols have been shown to improve HDL anti-atherogenic function, thus demonstrating beneficial effects against cardiovascular risk factors. The aim of the present study was to investigate the effect of extra virgin high polyphenol olive oil (HPOO) v. low polyphenol olive oil (LPOO) on the capacity of HDL to promote cholesterol efflux in healthy adults. In a double-blind, randomised cross-over trial, fifty participants (aged 38·5 (sd 13·9) years, 66 % females) were supplemented with a daily dose (60 ml) of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for 3 weeks. Following a 2-week washout period, participants crossed over to the alternate treatment. Serum HDL-cholesterol efflux capacity, circulating lipids (i.e. total cholesterol, TAG, HDL, LDL) and anthropometrics were measured at baseline and follow-up. No significant between-group differences were observed. Furthermore, no significant changes in HDL-cholesterol efflux were found within either the LPOO and HPOO treatment arms; mean changes were 0·54 % (95 % CI (0·29, 1·37)) and 0·10 % (95 % CI (0·74, 0·94)), respectively. Serum HDL increased significantly after LPOO and HPOO intake by 0·13 mmol/l (95 % CI (0·04, 0·22)) and 0·10 mmol/l (95 % CI (0·02, 0·19)), respectively. A small but significant increase in LDL of 0·14 mmol/l (95 % CI (0·001, 0·28)) was observed following the HPOO intervention. Our results suggest that additional research is warranted to further understand the effect of OO with different phenolic content on mechanisms of cholesterol efflux via different pathways in multi-ethnic populations with diverse diets.

The importance of patient and public involvement (PPI) is recognized by agencies involved in health technology assessment (HTA) and guideline development. However, a comprehensive overview of the underlying PPI principles, values, strategies, and frameworks is lacking. This scoping review aimed to summarize the available evidence on principles, values, frameworks, and strategies underpinning PPI carried out by agencies involved in HTA and guideline development. A total of twelve records were included, of which four referred to guidelines and eight to HTA. Overall, this review demonstrated a lack of consistency in the definition and application of the concepts of values and principles to PPI in the context of guideline development and HTA. There was significant overlap between values and principles, with some broad themes emerging, such as representation, transparency, relevance, equity, fairness, and reconciling different types of knowledge. Frameworks were typically based on the stages of guideline development or HTA, despite heterogeneity in how stages were labeled and described. Strategies were also mapped to the stages of guideline development and HTA and varied substantially depending on the context and setting. Both strategies and frameworks demonstrated patients and the public can be involved, albeit to a variable extent, throughout the stages of guideline development and HTA. However, frameworks often failed to explicitly link the values and principles with the HTA and guideline development stages through actionable PPI strategies. Further research is warranted to better understand the values, principles, and frameworks underpinning PPI in guideline development and HTA.

Background: Prostate cancer is the leading cancer diagnosis and the second leading cause of cancer deaths in men. Definitive diagnosis is made by prostate biopsy. This procedure poses a risk of infection and, rarely, sepsis. Studies have found the incidence of symptomatic urinary tract infection (UTI) after biopsy to be 2%–3%, and the rate of infection-related hospitalization (IRH) to be 0.6%–4.1%. An initial review at our facility found the IRH rate to be 3.7%. The primary purpose of this study was to determine the incidence of IRH following prostate biopsy in patients at the Memphis VA Medical Center (VAMC) after initial review and education. Methods: All transrectal prostate biopsies performed at the Memphis VAMC from October 2017 through May 2021 were analyzed. Patients were excluded if they had a spinal cord injury or concomitant procedure. The primary outcome was IRH occurring within 30 days of the procedure. Variables collected included risk factors, antibiotic choice and duration, and details of postprocedural infections. Analyses were performed on a per-procedure basis. Results: Overall, 601 procedures were identified; 13 were excluded, for a total of 588 transrectal prostate biopsies on 533 patients. All patients were given antibiotics. Oral antibiotics alone were provided for 306 procedures (52%) for an average duration of 3 days. A combination of both oral and intramuscular antibiotics were provided for 282 (48%) procedures. The most common oral antibiotics used were cefuroxime (538, 91.4%), ciprofloxacin (17, 2.9%), amoxicillin–clavulanate (16, 2.7%), and sulfamethoxazole–trimethoprim (12, 2%). Intramuscular antibiotics included ceftriaxone (263, 93.3%) and gentamicin (19, 6.7%). An infectious complication occurred in 29 patients (4.9%): 26 (3.4%) were urogenital and 5 (0.8%) required hospitalization. Of the procedures complicated by a postprocedure infection, 22 (75.9%) received an oral antibiotic alone, 21 (95.4%) of which were cefuroxime, and 7 (24.1%) received both an intramuscular and an oral agent. Conclusions: In our initial review, the most common antibiotics used were fluroquinolones, with an average duration of 3 days periprocedure and an IRH rate of 3.7%. These findings were used to reinforce practices compliant with American Urological Association (AUA) guidelines. This follow-up review reveals that the first-line choice changed from fluroquinolones to cephalosporins, with average duration remaining at 3 days. Although the overall infection rate was 4.9%, the IRH rate decreased from 3.7% to 0.8%.

Funding: None

Disclosures: None

Invasion and spread of alien species can drive ecosystem changes, such as, the dynamics of infectious diseases. The non-native, marine gastropod Crepidula fornicata has become established across European coastlines over the last century, but there remains little insight into its disease carrying capacity and potential role as a source/sink of parasites. To address this knowledge gap, we surveyed limpets from two sites in South Wales, UK for signatures of disease/pathology using polymerase chain reaction-based methods (haemolymph) and histology (solid tissue). We encountered trematode-like parasites in ~1% individuals (5 out of 462). Three limpets displayed gross damage in the gonad, i.e. castration, and encysted metacercariae were found in the muscle of two other individuals. On the basis of 28S rDNA and internal transcribed spacer 2 genomic targets, we identified the gonad-infecting trematodes as members of the family Microphallidae – putative novel species related to the genus Longiductotrema. Earlier reports suggest that C. fornicata is not a host for trematode parasites in either its native or alien range but may act as a sink due to its filter feeding lifestyle. We provide clear evidence that C. fornicata is parasitized by at least one trematode species at two sites in Wales, UK, and likely act as a spillback or accidental host among native littorinids.

UK universities re-opened in September 2020, amidst the coronavirus epidemic. During the first term, various national social distancing measures were introduced, including banning groups of >6 people and the second lockdown in November; however, outbreaks among university students occurred. We aimed to measure the University of Bristol staff and student contact patterns via an online, longitudinal survey capturing self-reported contacts on the previous day. We investigated the change in contacts associated with COVID-19 guidance periods: post-first lockdown (23/06/2020–03/07/2020), relaxed guidance period (04/07/2020–13/09/2020), ‘rule-of-six’ period (14/09/2020–04/11/2020) and the second lockdown (05/11/2020–25/11/2020). In total, 722 staff (4199 responses) and 738 students (1906 responses) were included in the study. For staff, daily contacts were higher in the relaxed guidance and ‘rule-of-six’ periods than the post-first lockdown and second lockdown. Mean student contacts dropped between the ‘rule-of-six’ and second lockdown periods. For both staff and students, the proportion meeting with groups larger than six dropped between the ‘rule-of-six’ period and the second lockdown period, although was higher for students than for staff. Our results suggest university staff and students responded to national guidance by altering their social contacts. Most contacts during the second lockdown were household contacts. The response in staff and students was similar, suggesting that students can adhere to social distancing guidance while at university. The number of contacts recorded for both staff and students were much lower than those recorded by previous surveys in the UK conducted before the COVID-19 pandemic.

North-western Arabia is marked by thousands of prehistoric stone structures. Of these, the monumental, rectilinear type known as mustatils has received only limited attention. Recent fieldwork in AlUla and Khaybar Counties, Saudi Arabia, demonstrates that these monuments are architecturally more complex than previously supposed, featuring chambers, entranceways and orthostats. These structures can now be interpreted as ritual installations dating back to the late sixth millennium BC, with recent excavations revealing the earliest evidence for a cattle cult in the Arabian Peninsula. As such, mustatils are amongst the earliest stone monuments in Arabia and globally one of the oldest monumental building traditions yet identified.

Since its release in October 2018, Red Dead Redemption 2 has generated considerable controversy. Redemption 2, Rockstar Games’ highly popular video game set in a sprawling open world that resembles America’s southern and western states at the turn of the twentieth century, has attracted criticism from players who have disliked the perceived political messages the game presents. With numerous interactions with people of color, Native Americans, and feminist (suffragette) characters, the game prompts players to engage with the ongoing effects of colonialism, sexism, and racism, as well as the rising problems of an industrial and financial capitalist society. As such, the game’s depiction of Gilded Age and Progressive Era politics has resulted in a large amount of online criticism from a group of traditionally white, male, right-wing players. This article argues that Redemption 2 utilizes the Progressive Era as a vehicle to capture and speak to the current political climate, and that it is the game’s dual relationship with the past and the present that has aroused animosity from part of the game’s audience. Ultimately, it demonstrates how contemporary mainstream progressive politics can be interpreted within and projected upon the politics of the Progressive Era.

Compared to the general population, individuals with complex congenital heart disease are at increased risk for deficits in cognitive, neurodevelopmental, psychosocial, and physical functioning, resulting in a diminished health-related quality of life. These deficits have been well described over the past 25 years, but significant gaps remain in our understanding of the best practices to improve neurodevelopmental and psychosocial outcomes and health-related quality of life for individuals with paediatric and congenital heart disease. Innovative clinical, quality improvement, and research opportunities with collaboration across multiple disciplines and institutions were needed to address these gaps. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with a described mission to determine and implement best practices of neurodevelopmental and psychosocial services for individuals and their families with paediatric and congenital heart disease through clinical, quality improvement, and research initiatives. The vision is to be a multi-centre, multi-national, multi-disciplinary group of healthcare professionals committed to working together and partnering with families to optimise neurodevelopmental outcomes for individuals with paediatric and congenital heart disease through clinical, quality, and research initiatives, intending to maximise quality of life for every individual across the lifespan. This manuscript describes the development and organisation of the Cardiac Neurodevelopmental Outcome Collaborative.

Over the last two decades, heart centres have developed strategies to meet the neurodevelopmental needs of children with congenital heart disease. Since the publication of guidelines in 2012, cardiac neurodevelopmental follow-up programmes have become more widespread. Local neurodevelopmental programmes, however, have been developed independently in widely varying environments. We sought to characterise variation in structure and personnel in cardiac neurodevelopmental programmes. A 31-item survey was sent to all member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. Multidisciplinary teams at each centre completed the survey. Responses were compiled in a descriptive fashion. Of the 29 invited centres, 23 responded to the survey (79%). Centres reported more anticipated neurodevelopment visits between birth and 5 years of age (median 5, range 2–8) than 5–18 years (median 2, range 0–10) with 53% of centres lacking any standard for routine neurodevelopment evaluations after 5 years of age. Estimated annual neurodevelopment clinic volume ranged from 85 to 428 visits with a median of 16% of visits involving children >5 years of age. Among responding centres, the Bayley Scales of Infant and Toddler Development and Wechsler Preschool and Primary Scale of Intelligence were the most routinely used tests. Neonatal clinical assessment was more common (64%) than routine neonatal brain imaging (23%) during hospitalisation. In response to clinical need and published guidelines, centres have established formal cardiac neurodevelopment follow-up programmes. Centres vary considerably in their approaches to routine screening and objective testing, with many centres currently focussing their resources on evaluating younger patients.