Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body’s natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.

The quenching of cluster satellite galaxies is inextricably linked to the suppression of their cold interstellar medium (ISM) by environmental mechanisms. While the removal of neutral atomic hydrogen (H i) at large radii is well studied, how the environment impacts the remaining gas in the centres of galaxies, which are dominated by molecular gas, is less clear. Using new observations from the Virgo Environment traced in CO survey (VERTICO) and archival H i data, we study the H i and molecular gas within the optical discs of Virgo cluster galaxies on 1.2-kpc scales with spatially resolved scaling relations between stellar ( $\Sigma_{\star}$ ), H i ( $\Sigma_{\text{H}\,{\small\text{I}}}$ ), and molecular gas ( $\Sigma_{\text{mol}}$ ) surface densities. Adopting H i deficiency as a measure of environmental impact, we find evidence that, in addition to removing the H i at large radii, the cluster processes also lower the average $\Sigma_{\text{H}\,{\small\text{I}}}$ of the remaining gas even in the central $1.2\,$ kpc. The impact on molecular gas is comparatively weaker than on the H i, and we show that the lower $\Sigma_{\text{mol}}$ gas is removed first. In the most H i-deficient galaxies, however, we find evidence that environmental processes reduce the typical $\Sigma_{\text{mol}}$ of the remaining gas by nearly a factor of 3. We find no evidence for environment-driven elevation of $\Sigma_{\text{H}\,{\small\text{I}}}$ or $\Sigma_{\text{mol}}$ in H i-deficient galaxies. Using the ratio of $\Sigma_{\text{mol}}$ -to- $\Sigma_{\text{H}\,{\small\text{I}}}$ in individual regions, we show that changes in the ISM physical conditions, estimated using the total gas surface density and midplane hydrostatic pressure, cannot explain the observed reduction in molecular gas content. Instead, we suggest that direct stripping of the molecular gas is required to explain our results.

OBJECTIVES/GOALS: To assess barriers and recommendations for improving delivery of care for chronic obstructive pulmonary disease (COPD) in rural clinics, we assessed COPD care metrics and obtained perspectives of primary care providers (PCPs) who practice in rural clinics. METHODS/STUDY POPULATION: Quantitative retrospective analysis of patients with COPD using VA data. We included patients whose primary care clinic is located in a rural VA Midwest Health Care Network (HCN) facility and quantified binary measures for receipt of: spirometry, pulmonary specialty care, and optimal inhaler therapy (regimen with LAMA or LABA monotherapy) Qualitative semi-structured individual interviews of PCPs (physicians, nurse practitioners, and physician assistants) whose clinics are located in a rural VA Midwest HCN facility. We elicited perceived barriers to and recommendations for receiving spirometry, pulmonary specialty care, and optimal inhaler therapy from PCPs. RESULTS/ANTICIPATED RESULTS: 6,350 rural patients had a new diagnosis of COPD in 2016-2019. 48.4% had spirometry, 14.4% had pulmonary encounters, and among patients who were prescribed long-acting inhaler therapy, 48.8% received optimal inhaler regimens. Rural PCPs (n=14) highlighted lack of access to spirometry, pulmonary specialty care, and clinic staff support in local clinics and suggested: 1) leveraging the expertise of pharmacists in COPD management and 2) improving access to resources, including use of telehealth technologies. DISCUSSION/SIGNIFICANCE: Less than 50% of rural COPD patients received recommended diagnostic testing and therapy. Resource limitations in rural clinics were the main barrier. The main recommendation was to leverage pharmacists’ expertise in COPD care. These findings provide a pathway forward to improving rural COPD care.

A disproportionate share of the health impacts of COVID-19 has been borne by older adults, particularly those in long-term care facilities (LTCs). Vaccination has been critical to efforts to combat this issue, but as we begin to emerge from this pandemic, questions remain about how to protect the health of residents of LTC and assisted living facilities proactively in order to prevent such a disaster from occurring again. Vaccination, not just against COVID-19, but also against other vaccine-preventable illness, will be a key component of this effort. However, there are currently substantial gaps in the uptake of vaccines recommended for older adults. Technology offers an opportunity to assist in filling these vaccination gaps. Our experiences in Fredericton, New Brunswick suggest that a digital immunization solution would facilitate better uptake of adult vaccines for older adults in assisted and independent living facilities and would help policy and decision makers to identify coverage gaps and develop interventions to protect these individuals.

The optimum parameters for the generation of synchrotron radiation in ultraintense laser pulse interactions with planar foils are investigated with the application of Bayesian optimization, via Gaussian process regression, to 2D particle-in-cell simulations. Individual properties of the synchrotron emission, such as the yield, are maximized, and simultaneous mitigation of bremsstrahlung emission is achieved with multi-variate objective functions. The angle-of-incidence of the laser pulse onto the target is shown to strongly influence the synchrotron yield and angular profile, with oblique incidence producing the optimal results. This is further explored in 3D simulations, in which additional control of the spatial profile of synchrotron emission is demonstrated by varying the polarization of the laser light. The results demonstrate the utility of applying a machine learning-based optimization approach and provide new insights into the physics of radiation generation in laser–foil interactions, which will inform the design of experiments in the quantum electrodynamics (QED)-plasma regime.

For primary care clinics at a Veterans’ Affairs (VA) medical center, the shift from in-person to telehealth visits during the coronavirus disease 2019 (COVID-19) pandemic was associated with low rates of antibiotic prescription. Understanding contextual factors associated with antibiotic prescription practices during telehealth visits may help promote antibiotic stewardship in primary care settings.

Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.

Many decisions in everyday life involve a choice between exploring options that are currently unknown and exploiting options that are already known to be rewarding. Previous work has suggested that humans solve such “explore-exploit” dilemmas using a mixture of two strategies: directed exploration, in which information seeking drives exploration by choice, and random exploration, in which behavioral variability drives exploration by chance. One limitation of this previous work was that, like most studies on explore-exploit decision making, it focused exclusively on the domain of gains, where the goal was to maximize reward. In many real-world decisions, however, the goal is to minimize losses and it is well known from Prospect Theory that behavior can be quite different in this domain. In this study, we compared explore-exploit behavior of human subjects under conditions of gain and loss. We found that people use both directed and random exploration regardless of whether they are exploring to maximize gains or minimize losses and that there is quantitative agreement between the exploration parameters across domains. Our results also revealed an overall bias towards the more uncertain option in the domain of losses. While this bias towards uncertainty was qualitatively consistent with the predictions of Prospect Theory, quantitatively we found that the bias was better described by a Bayesian account, in which subjects had a prior that was optimistic for losses and pessimistic for gains. Taken together, our results suggest that explore-exploit decisions are driven by three independent processes: directed and random exploration, and a baseline uncertainty seeking that is driven by a prior.

Helminth species of Neotropical bats are poorly known. In Mexico, few studies have been conducted on helminths of bats, especially in regions such as the Yucatan Peninsula where Chiroptera is the mammalian order with the greatest number of species. In this study, we characterized morphologically and molecularly the helminth species of bats and explored their infection levels and parasite–host interactions in the Yucatan Peninsula, Mexico. One hundred and sixty-three bats (representing 21 species) were captured between 2017 and 2022 in 15 sites throughout the Yucatan Peninsula. Conventional morphological techniques and molecular tools were used with the 28S gene to identify the collected helminths. Host–parasite network analyses were carried out to explore interactions by focusing on the level of host species. Helminths were found in 44 (26.9%) bats of 12 species. Twenty helminth taxa were recorded (7 trematodes, 3 cestodes and 10 nematodes), including 4 new host records for the Americas. Prevalence and mean intensity of infection values ranged from 7.1 to 100% and from 1 to 56, respectively. Molecular analyses confirmed the identity of some helminths at species and genus levels; however, some sequences did not correspond to any of the species available on GenBank. The parasite–host network suggests that most of the helminths recorded in bats were host-specific. The highest helminth richness was found in insectivorous bats. This study increases our knowledge of helminths parasitizing Neotropical bats, adding new records and nucleotide sequences.

We describe the investigations and management of a Cryptosporidium parvum outbreak of linked to consumption of pasteurised milk from a vending machine. Multiple locus variable number of tandem repeats analysis was newly used, confirming that C. parvum detected in human cases was indistinguishable from that in a calf on the farm. This strengthened the evidence for milk from an on-farm vending machine as the source of the outbreak because of post-pasteurisation contamination. Bacteriological indicators of post-pasteurisation contamination persisted after the initial hygiene improvement notice. We propose that on-farm milk vending machines may represent an emerging public health risk.

Contaminated shoes are a potential vector for dissemination of healthcare-associated pathogens. We demonstrated that healthcare personnel walking into patient rooms frequently transferred pathogens from their shoes to the floor. An 8-second treatment of shoes with a UV-C decontamination device significantly reduced the frequency of transfer of vegetative bacterial pathogens.

The updated vancomycin guideline for treatment of serious methicillin-resistant Staphylococcus aureus infections prompted institutions to convert from trough to area-under-the-curve monitoring. The physician perception of the transition, coupled with that of pharmacists, was measured by pre- and postimplementation surveys. Both groups believed safety would be increased without efficacy changes.