Surveillance by clinical epidemiology teams for invasive fungal infections (IFIs) in healthcare settings can be challenging due to several factors including low sensitivity of noninvasive conventional microbiologic diagnostics, nonspecific clinical presentation, and complex patient populations. Recently, availability of microbial cell-free DNA testing (cfDNA) via the Karius Test has shown promise for increased diagnostic sensitivity of IFIs. However, how to best incorporate cfDNA results into IFI surveillance remains a vexing challenge. Herein, we provide perspectives on the benefits and challenges of use of cfDNA for IFI surveillance.

In the United States, New Delhi metallo-beta-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) are frequently associated with healthcare encounters. From September 2021 to September 2022, 21 patients with NDM-CRE identified from urine and without healthcare exposure were reported to the Centers for Disease Control and Prevention. Isolates were genetically similar to healthcare-associated strains.

Analysis of variance and uncertainty analysis are analogous techniques for partitioning variability. In both analyses negative interaction terms due to negative covariance terms that appear when non-orthogonal predictor variables are allowed may occur. Uncertainties can be estimated directly from variances if the form of distribution is assumed. The decision as to which of the techniques to use depends partly on the properties of the criterion variable. Only uncertainty analysis may be used with a non-metric criterion. Since uncertainties are dimensionless (using no metric), however, uncertainty analysis has a generality which may make it useful even when variances can be computed.

Background: Since 2009, the CDC has invested in nationwide outbreak response capacity through Healthcare-associated Infections and Antimicrobial Resistance (HAI/AR) Programs in public health departments. The unpredictable nature of outbreaks requires public health programs to be able to scale operations and adapt strategies to effectively respond to emerging challenges, as demonstrated by the COVID-19 pandemic. This analysis characterizes HAI/AR Programs response capacity in scalability, adaptability, and technical expertise. Method: We reviewed data from HAI/AR Programs in 50 state, 6 local, and 2 territorial health departments (August 2019–December 2022). HAI/AR responses were defined as specific public health actions to assess an acute risk and prevent further harm in the context of a confirmed or possible healthcare outbreak; responses were categorized as involving novel or targeted multi-drug resistant organisms (nMDROs), COVID-19, and HAIs or infection control breaches. Descriptive statistics were used to analyze reported responses in three domains: scalability (number of responses per year), adaptability (number of pathogens and healthcare facility types involved in responses), and technical expertise (number of responses involving onsite or remote infection control assessments). The annual number of responses conducted in 2019 was estimated based on five months of data (Aug–Dec); all other results were calculated directly. Results: From August 2019 to December 2022, 58 HAI/AR Programs reported 141,445 responses (87% COVID-19, 11% nMDROs, 2% other HAIs or infection control breaches). Annually, programs conducted an estimated 5,546 responses in 2019, and this figure rose to 42,359 in 2020, 49,124 in 2021, and 47,651 in 2022. Outbreak responses involved 110 different pathogens, including emerging infectious diseases (e.g., SARS-CoV-2, mpox), nMDRO (e.g., carbapenemase-producing organisms, Candida auris), and other pathogens (e.g., hepatitis viruses, Mycobacterium abscessus) across >20 setting types (e.g., acute care hospitals, skilled nursing facilities, ambulatory surgery centers, assisted living facilities). Additionally, programs responded to infection control breaches in the absence of identified patient infections, including drug diversion, medical device reprocessing, and injection safety breaches. Programs conducted 50,245 infection control assessments during reported responses. Conclusion: From 2019–2022, as the COVID-19 pandemic took hold, HAI/AR Programs effectively utilized CDC funding to scale their response operations with an 8-fold increase in annual response activity, including a 24% increase for non-COVID-19 responses. Programs adapted responses to various pathogens, including emerging infectious diseases, across various setting types. Health department staff utilized technical expertise to conduct infection control assessments. This analysis provides valuable insights into the resilience and impact of HAI/AR Programs nationwide.

Major advancements in ecology and biodiversity conservation have been made thanks to methods for marking and individually tracking animals. Marking animals is both widely used and controversial due to the potential consequences for animal welfare, which are often incompletely evaluated prior to implementation. Two outstanding knowledge gaps concerning the welfare consequences of individual marking are their short-term behavioural impacts and the relative impacts from marking versus the handling of animals while carrying out procedures. We addressed these knowledge gaps through an experimental study of alpine newts (Ichthyosaura alpestris) in which we varied handling and marking procedures. Examining individual responses to handling, toe clipping and visible implant elastomer (VIE) injection over 21 days showed that handling and marking elicited increased newt activity and hesitancy to feed compared to animals that did not get handled or marked. These effects were apparent even when animals were handled only (not marked), and marking did not further increase the magnitude of responses. Increases in newt activity and feeding hesitancy were transient; they were not observed in the weeks following handling and marking. While previous studies emphasise the welfare impacts of marking procedures themselves, these findings highlight that handling alone can elicit behavioural changes with possible costs to welfare. Yet, the transient nature of behavioural responses suggests that immediate costs of handling may be subsequently compensated for in the short term.

OBJECTIVES/GOALS: The goal of this project is to characterize the efficacy of FOXA2 as a potential biomarker for patients with metastatic castrate-resistant prostate adenocarcinoma (CRPC) before transitioning to neuroendocrine prostate cancer (NEPC). NEPC currently has no therapeutic options and poor mechanistic understand of its origins. METHODS/STUDY POPULATION: In our study, we have utilized a multi-omics approach to characterize the potential efficacy of FOXA2 as a prognostic biomarker in numerous patient-derived castrate-resistant prostate cancer (CRPC) models. We have performed ATAC-, ChIP-, RNA-seq and proteomics to fully characterize where FOXA2 is binding genome-wide, how FOXA2 alters chromatin accessibility dynamics, identify regulatory gene targets of FOXA2, and identify FOXA2 protein-protein interactors. We have supported these findings using publicly available data from independent CRPC and NEPC patient cohorts and prostate cancer cell models. RESULTS/ANTICIPATED RESULTS: Our findings show that FOXA2 overexpression suppressed androgen signaling and promoted progression to a NEPC phenotype under short- and long-term androgen deprivation conditions, respectively. Further, FOXA2 redirected the chromatin accessibility landscape to be consistent with an NEPC gene expression program, including increased chromatin accessibility for key NEPC transcription factors. FOXA2 ChIP-seq showed FOXA2 to be bound at known NEPC driver genes and epigenetic modifiers across multiple stages of prostate cancer progression. Lastly, we discovered that FOXA2 physically interacts with key NEPC TFs and epigenetic regulators, suggesting that these FOXA2 physical interactions are required for NEPC progression. DISCUSSION/SIGNIFICANCE: This project will determine the efficacy of FOXA2 as a biomarker in advanced prostatecancer samples, which will translate as a potentially useful tool for clinicians to use for treatment of advanced prostate cancer patients.

Rhodiola rosea (RR) is a plant whose bioactive components may function as adaptogens, thereby increasing resistance to stress and improving overall resilience. Some of these effects may influence exercise performance and adaptations. Based on studies of rodents, potential mechanisms for the ergogenic effects of RR include modulation of energy substrate stores and use, reductions in fatigue and muscle damage and altered antioxidant activity. At least sixteen investigations in humans have explored the potential ergogenicity of RR. These studies indicate acute RR supplementation (∼200 mg RR containing ∼1 % salidroside and ∼3 % rosavin, provided 60 min before exercise) may prolong time-to-exhaustion and improve time trial performance in recreationally active males and females, with limited documented benefits of chronic supplementation. Recent trials providing higher doses (∼1500 to 2400 mg RR/d for 4–30 d) have demonstrated ergogenic effects during sprints on bicycle ergometers and resistance training in trained and untrained adults. The effects of RR on muscle damage, inflammation, energy system modulation, antioxidant activity and perceived exertion are presently equivocal. Collectively, it appears that adequately dosed RR enhances dimensions of exercise performance and related outcomes for select tasks. However, the current literature does not unanimously show that RR is ergogenic. Variability in supplementation dose and duration, concentration of bioactive compounds, participant characteristics, exercise tests and statistical considerations may help explain these disparate findings. Future research should build on the longstanding use of RR and contemporary clinical trials to establish the conditions in which supplementation facilitates exercise performance and adaptations.

This article is based on a course on how to use Moys classification scheme,1 delivered by Helen Garner and Felicity Staveley-Taylor on behalf of the British and Irish Association of Law Librarians (BIALL) in November 2022. The article, which is also written by Helen and Felicity, provides guidance on how to use Moys classification, explaining the features that enable the scheme to be expanded to accommodate new subject areas. The article also explains some of the features which ensure the scheme remains relevant to legal libraries today. Sections from the classification scheme, as published in the fifth edition, appear in the article text. In addition, any references to page numbers are to the fifth edition.

Although the awareness of the environmental damage caused by plastic pollution has recently increased, few steps have been taken to confront its consequences. These consequences are often most severe in the Global South where countries often lack proper waste management infrastructure. Unless the market value of plastic waste increases, it will simply be discarded, eventually making its way to the environment. It has been established that polyolefin plastic can be converted to a sulfur-free fuel oil by pyrolysis, suitable for use in diesel engines or as a clean cooking fuel. However, carrying out this chemistry in the Global South is challenging. Any process intended for use in the Global South must be safe, robust, efficient, simple to operate, low cost, and most importantly profitable for the operator. When the average daily wage in sub-Saharan Africa is less than 3 USD, an income provided from plastic waste fuel can be significant. The research presented herein focuses on the optimization of a plastic-to-fuel processor that can be built using the principles of appropriate technology. The results of this optimization and profitability assessment will be described. This research has been conducted in collaboration with the NGOs Empowered Solutions for Environmental Sustainability and UpCycle Africa.