The overuse and inappropriate use of antimicrobials have led to environmental waste and drug shortages. This challenges the ecological and economical sustainability of our healthcare system and worsens antimicrobial resistance.

Antimicrobial stewardship programs (ASP) commonly consider the cost of drug acquisition but may be failing to recognize the hidden costs of multi-dose intravenous regimens including additional nursing administration time, tubing and fluids, and potentially increased hospital length of stay. They also rarely consider the environmental impact of medical waste creation and disposal, which contributes to the global antimicrobial resistance crisis. These costs are harder to calculate but crucial to a comprehensive assessment of a medication’s total impact. In this invited commentary, we provide an example of a stewardship evaluation at our institution focused on changing from meropenem (MER) to ertapenem (ETP) for infections caused by extended-spectrum beta-lactamase producing organisms. We found that despite an increase in acquisition costs, changing from MER to ETP is associated with overall savings and decreased waste production. A secondary analysis suggests that stay length may also be improved with this substitution.

We present a holistic approach to antimicrobial stewardship that considers the total cost of an antimicrobial. By broadening their view to include hidden costs and secondary effects, ASPs can further demonstrate their value to the healthcare system, reduce resistance, and improve their environmental impact.

The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration and dose needed to elicit gut microbial changes and whether these changes also influence microbial metabolites remain unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)) on the stool microbiota and microbial metabolite concentrations in plasma, stool and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study. The DISC study was a double-blind, randomised controlled trial that supplemented healthy participants with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design. DNA was extracted from stool samples collected pre- and post-intervention, and V4 16S rRNA gene sequencing was used to profile the gut microbiota. Metabolite concentrations were measured in stool, plasma and urine by high-performance liquid chromatography. A total of fifty-eight participants with paired samples available were included. After 50 d, no effects of RS or PD were detected on composition of the gut microbiota diversity (alpha- and beta-diversity), on genus relative abundance or on metabolite concentrations. However, Drichlet’s multinomial mixture clustering-based approach suggests that some participants changed microbial enterotype post-intervention. The gut microbiota and fecal, plasma and urinary microbial metabolites were stable in response to a 50-d fibre intervention in middle-aged adults. Larger and longer studies, including those which explore the effects of specific fibre sub-types, may be required to determine the relationships between fibre intake, the gut microbiome and host health.

The terminal Ediacaran Period is signaled worldwide by the first appearance of skeletonizing tubular metazoan fossils, e.g., Cloudina Germs, 1972 and Sinotubulites Chen, Chen, and Qian, 1981. Although recent efforts have focused on evaluating the taxic composition and preservation of such assemblages from the southwestern United States, comparable forms reported in the 1980s from Mexico remain to be re-examined. Here, we reassess the latest Ediacaran skeletal materials from the La Ciénega Formation of the Caborca region in Sonora, Mexico, using a combination of analytical methods: optical microscopy of extracted fossils, thin-section petrography, scanning electron microscopy and energy dispersive X-ray spectroscopy, and X-ray tomographic microscopy. From our examination, we conclude that the La Ciénega hosts a polytaxic assemblage of latest Ediacaran tubular organisms that have been preserved through two taphonomic pathways: coarse silicification and calcareous recrystallization preserving finer details. Further, these fossils show signs that their shells might not have been inflexible or completely mineralized in vivo, and that they might also record tentatively interpreted predation traces in the form of drill holes or puncture marks. This work, along with ongoing efforts around the world, helps to provide a framework for biostratigraphic correlation and possible subdivision of the Ediacaran Period, and further shapes our view of metazoan evolution and ecology in the interval directly preceding the Cambrian explosion.

OBJECTIVES/GOALS: Fluid boluses are administered to hypotensive, critically ill children but may not reverse hypotension, leading to delay of vasoactive infusion, end-organ damage, and mortality. We hypothesize that a machine learning-based model will predict which children will have sustained response to fluid bolus. METHODS/STUDY POPULATION: We will conduct a single-center retrospective observational cohort study of hypotensive critically ill children who received intravenous isotonic fluid of at least 10 ml/kg within 72 hours of pediatric intensive care unit admission between 2013 and 2023. We will extract physiologic variables from stored bedside monitors data and clinical variables from the EHR. Fluid responsive (FR) will be defined as a MAP increase by 310%. We will construct elastic net, random forest, and a long short-term memory models to predict FR. We will compare complicated course (multiple organ dysfunction on day 7 or death by day 28) between: 1) FRs and non-FRs, 2) predicted FRs and non-FRs, 3), FRs and non-FRs stratified by race/ethnicity, and 4) FRs and non-FRs stratified by sex as a biologic variable. RESULTS/ANTICIPATED RESULTS: We anticipate approximately 800 critically ill children will receive 2,000 intravenous isotonic fluid boluses, with a 60% rate of FR. We anticipate being able to complete all three models. We hypothesize that the model with the best performance will be the long short-term memory model and the easiest to interpret will be the tree-based random forest model. We hypothesize non-FRs will have a higher complicated course than FRs and that predicted non-FRs will have a higher rate of complicated course than FRs. Based on previous adult studies, we hypothesize that there will be a higher rate of complicated course in patients of black race and/or Hispanic ethnicity when compared to non-Hispanic white patients. We also hypothesize that there will be no difference in complicated course when comparing sex as a biologic variable. DISCUSSION/SIGNIFICANCE: We have a critical need for easily-deployed, real-time prediction of fluid response to personalize and improve resuscitation for children in shock. We anticipate the clinical application of such a model will decrease time with hypotension for critically ill children, leading to decreased morbidity and mortality.

Defence Science and Technology Group (DSTG) is currently preparing for the launch of the Buccaneer Main Mission (BMM) satellite, the successor to the Buccaneer Risk Mitigation Mission (BRMM). BMM hosts a high-frequency (HF) antenna and receiver to contribute to the calibration of the Jindalee Operational Radar Network (JORN). Verification of the successful deployment and stability of the large HF antenna is critical to the success of the mission. A bespoke deployable optics payload has been developed by DSTG to fulfil the dual purpose of direct verification of the deployed state of the HF antenna and capturing images of the Earth through a rotatable, dual-surfaced mirror and a variable-focus liquid lens. The payload advances research at DSTG in several fields of space engineering, including deployable mechanisms, precision actuation devices, radiation-tolerant electronics, advanced metal polishing and optical metrology. This paper discusses the payload design, material selection, trade-offs considered for the deployable optics payload and preliminary test results.

Infection preventionist (IP) positions are difficult to fill, and future workforce shortages are anticipated. The IP field has less racial and ethnic diversity than the general nursing workforce or patient population. A targeted fellowship program for underrepresented groups allowed the recruitment and training of IPs while avoiding staffing shortages.

Although being an old concern, phosphate analysis is still a tremendous challenge. While many different experimental techniques are found in the literature, very few use powder X-ray diffraction (PXRD) patterns for quantitative phase analysis of different phosphate types. Our measurements performed in four commercial samples of diammonium hydrogen phosphate ((NH4)2HPO4) (DAP) show the existence of phosphate contamination mixtures, such as ammonium dihydrogen phosphate (NH4H2PO4) (ADP). The larger the amount of ADP, the larger the microstrain induced in the DAP phase, which impacts both the aggregation of the nanoparticles in solution and the final anticancer activity of the nanostructure. This study shows that PXRD is an excellent technique for quantitative phase analysis to determine the presence and amount of phosphate contamination in diammonium hydrogen phosphate samples.

Rabies virus (RABV) is a deadly zoonosis that circulates in wild carnivore populations in North America. Intensive management within the USA and Canada has been conducted to control the spread of the raccoon (Procyon lotor) variant of RABV and work towards elimination. We examined RABV occurrence across the northeastern USA and southeastern Québec, Canada during 2008–2018 using a multi-method, dynamic occupancy model. Using a 10 km × 10 km grid overlaid on the landscape, we examined the probability that a grid cell was occupied with RABV and relationships with management activities (oral rabies vaccination (ORV) and trap-vaccinate-release efforts), habitat, neighbour effects and temporal trends. We compared raccoon RABV detection probabilities between different surveillance samples (e.g. animals that are strange acting, road-kill, public health samples). The management of RABV through ORV was found to be the greatest driver in reducing the occurrence of rabies on the landscape. Additionally, RABV occupancy declined further with increasing duration of ORV baiting programmes. Grid cells north of ORV management were at or near elimination ($\hat{\psi }_{{\rm north}}$ = 0.00, s.e. = 0.15), managed areas had low RABV occupancy ($\hat{\psi }_{{\rm managed}}$ = 0.20, s.e. = 0.29) and enzootic areas had the highest level of RABV occupancy ($\hat{\psi }_{{\rm south}}$ = 0.83, s.e. = 0.06). These results provide evidence that past management actions have been being successful at the goals of reducing and controlling the raccoon variant of RABV. At a finer scale we also found that vaccine bait type and bait density impacted RABV occupancy. Detection probabilities varied; samples from strange acting animals and public health had the highest detection rates. Our results support the movement of the ORV zone south within the USA due to high elimination probabilities along the US border with Québec. Additional enhanced rabies surveillance is still needed to ensure elimination is maintained.

This editorial reflects on current methodological trends in translational research in mental health. It aims to build a bridge between two fields that are frequently siloed off from each other: interventional research and phenomenologically informed research. Recent years have witnessed a revival of phenomenological approaches in mental health, often – but not only – as a means of connecting the subjective character of experience with neurobiological explanatory accounts of illness. Rich phenomenological knowledge accrued in schizophrenia, and wider psychosis research, has opened up new opportunities for improving prediction, early detection, diagnosis, prognostic stratification, treatment and ethics of care. Novel qualitative studies of delusions and hallucinations have challenged longstanding assumptions about their nature and meaning, uncovering highly complex subjective dimensions that are not adequately captured by quantitative methodologies. Interdisciplinary and participatory research efforts, informed by phenomenological insights, have prompted revisions of pre-established narratives of mental disorder dominated by a dysfunction framework and by researcher-centric outcome measures. Despite these recent advances, there has been relatively little effort to integrate and translate phenomenological insights across applied clinical research, with the goal of producing more meaningful, patient-valued results. It is our contention that phenomenological psychopathology – as the basic science of psychiatry – represents an important methodology for advancing evidence-based practices in mental health, and ultimately improving real-world outcomes. Setting this project into motion requires a greater emphasis on subjectivity and the structures of experience, more attention to the quality and patient-centredness of outcome measures, and the identification of treatment targets that matter most to patients.

Housing conditions can alter both the physiology and behaviour of laboratory animals. Forced-air-ventilated micro-isolation systems increase the efficient use of space, decrease the incidence of disease among laboratory rodents, and provide better working conditions for animal care staff; however, such systems can increase breeding variability and mortality. We examined the possibility that stressors associated with automated housing conditions evoke subtle changes among immune, endocrine, and behavioural parameters in mice housed in a static versus a forced-air-ventilated micro-isolation system. In addition, we assessed the effects of housing in the forced-air-ventilated micro-isolation system both with and without the use of an automatic watering system. Housing in the forced-air-ventilated micro-isolation system, using the automatic watering system, suppressed delayed-type hypersensitivity (DTH) responses, a measure of cell mediated immune function, compared with the responses of mice housed in static cages. Hypothalamic–pituitary–adrenal axis function was also altered by housing in the forced-air-ventilated micro-isolation system with the use of the automatic watering system, such that mice in this housing system had lower resting corticosterone concentrations and increased reactivity to restraint. Despite these changes in corticosterone, housing condition did not alter activity level or exploratory, anxiety-like, or depressive-like behaviours. These results suggest that investigators should carefully consider housing conditions in studies of immune and endocrine function.