Vascular rings represent a heterogeneous set of aberrant great vessel anatomic configurations which can cause respiratory symptoms or dysphagia due to tracheal or oesophageal compression. These symptoms can be subtle and may present at varied ages. More recently, many have been identified in patients without symptoms, including fetal echocardiogram, resulting in a conundrum for practitioners when attempting to determine who will benefit from surgical correction. Here, we provide a review of vascular rings and a guide to the practitioner on when to consider additional imaging or referral. Additionally, we discuss the changing landscape regarding asymptomatic patients and fetal echocardiogram.

Background: Climate change, and fossil fuel combustion threaten the health of children globally through direct and indirect mechanisms,1 such as the exacerbation of ambient air pollution.1,2 Increased ambient air pollutant concentrations are associated with emergency department (ED) visits for episodic and paroxysmal neurologic conditions in adults in the Toronto region of Canada.4,5 We hypothesize that, in Calgary, Alberta, increased ambient air pollutants will be positively associated with the daily burden of pediatric ED presentations for migraine and seizures, and that a greater effect size may be present due to increased regional variability in ambient PM2.5 concentrations.3,4 Methods: Emergency records from the National Ambulatory Care Reporting System, comprising 17552 primary seizure and headache cases between 0-18 years of age and presenting to Calgary-region emergency departments between January 2012-December 2021, will be included. Quasi-Poisson regression modeling incorporating ambient air pollutants, seasonality and meteorological covariates will estimate relative risk and 95% confidence intervals of ED visit counts relative to increases in air pollutants. Results: Results currently pending and will be available for presentation. Conclusions: Significant results may inform further inquiry into the impact of air pollutants on children with neurological conditions and identify potential contributions of air quality to healthcare service demand in the Calgary region.

OBJECTIVES/GOALS: Determine if the Conserved Transcriptional Response to Adversity transcriptomic profile established in primary blood mononuclear cells (PBMC) of chronically stress caregivers, is present in individuals with early Alzheimer’s disease. Chronic stress is a risk factor for Alzheimer’s, and may be an untapped biomarker for disease risk and pathology. METHODS/STUDY POPULATION: To collect preliminary data on the Conserved Transcriptional Response to Adversity profile in individuals with Alzheimer’s disease, we were able to utilize primary blood mononuclear cell samples from a small open label pilot study called Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease, designed to clear stressed senescent cells. We hypothesized senolytics may beneficially reverse this stress profile. We developed a NanoString assay (measuring 19 inflammatory, 31 type-1 interferon, and 3 antibody synthesis genes) to compare these transcriptomic changes within 4 individuals measured at baseline, post-treatment with an intermittent 12-week senolytic therapy, and at an optional extended post-treatment follow-up time point > 3 months after their post treatment visit. RESULTS/ANTICIPATED RESULTS: There was relative downregulation of expression in transcription in 7 of 19 measured inflammatory genes (FOS, PTGS2, IL8, FOS, Il1b, JUNB, and JUN) in Alzheimer’s disease participants after receiving senolytic treatment (baseline vs. post-treatment). This is consistent with a decrease in the inflammatory arm of the Conserved Transcriptional Response to Adversity profile. These differences were not significant between baseline and the extended follow-up, indicative of a transient effect of senolytic. There were no changes in type 1 interferon or antibody synthesis genes. This data provides preliminary evidence for larger controlled studies to further establish this profile in Alzheimer’s disease, providing exciting evidence for transcript changes that may be reproducible with senolytic therapy. DISCUSSION/SIGNIFICANCE: Literature relevant to Alzheimer’s disease indicates global increases in inflammation paired with deficits in immune response, capturing some genes associated with the Conserved Transcriptional Response to Adversity. This profile may be a useful biomarker for prediction of disease severity or risk of dementia due to chronic stress.

A reproductive population of the Asian longhorned beetle, Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae), an adventive insect from Asia, was discovered in 2003 in an urban landscape in Ontario, Canada. This polyphagous beetle, which attacks maples, Acer spp. (Sapindaceae), had the potential to seriously and permanently alter the composition and structure of forests in eastern North America. The Canadian Food Inspection Agency (CFIA) developed and implemented an eradication programme, with partners from various agencies in both Canada and the United States of America. Surveys were used to delineate the infestation and establish a regulated area around it. Treatment consisted of removing and destroying both trees with signs of A. glabripennis injury and trees assumed at high risk of being injured within the regulated area. After nine years of monitoring the regulated area, the CFIA declared A. glabripennis eradicated on 5 April 2013. Herein, we detail the response undertaken, summarise lessons learned, and provide preliminary observations and results pertaining to the arrival, establishment, and spread of A. glabripennis in Ontario.

ABSTRACT IMPACT: We hope to provide a more nuanced understanding of the type-III IFN system, thereby exploring its therapeutic potential in the realm of infectious diseases. OBJECTIVES/GOALS: The role of IFNLR1 receptor dynamics and plasticity in regulating the type-III IFN response is largely unknown. As a specific, powerful component of innate immunity, understanding how the type-III IFN system is regulated could lead to the development of novel therapeutic targets and strategies to face a multitude of viral illnesses. METHODS/STUDY POPULATION: To facilitate our investigation, we will generate doxycycline-inducible FLAG-tagged IFNLR1-expression plasmids representing all known transcriptional variants. These plasmids will allow us to: 1) Evaluate the effect of IFNLR1 surface abundance on the type-III IFN transcriptional profile and 2) Assess the extent of IFNLR1-FLAG co-localization with several notable intracellular structures using immunofluorescence, before and after stimulation with IFNL3. RESULTS/ANTICIPATED RESULTS: We have successfully generated three IFNLR1-FLAG transcriptional variants and confirmed inducible-expression and function in vitro. We are currently assessing the role of surface abundance, internalization, differential isoform expression, and trafficking. DISCUSSION/SIGNIFICANCE OF FINDINGS: By completing this study, we hope to provide a more nuanced understanding of the type-III IFN system, thereby exploring its therapeutic potential in the realm of infectious diseases.

Since opening in 1863 Broadmoor Hospital, in Crowthorne, Berkshire, 30 miles west of London, has admitted or readmitted over 2000 women. This is a tiny proportion of the women who have been incarcerated in prison over this time, but the level of public interest and ethical issues involved in their care, far outweighs the number of cases. Their stories and reasons for admission are of great interest and complexity.

At first infanticide was the usual offence resulting in admission, but with increasing knowledge of the causes and consequences of mental illness, and new legislation to deal with it, reasons for admission became much more varied. Arson became the commonest reason for admission in recent years. Also, over the last 40 years, those admitted are younger and stay for a shorter time.

The treatment of the disturbed and often tragic women patients in Broadmoor has also changed. Primitive surgery and blunderbuss drug regimes have evolved into multidisciplinary practices and widely varied therapies.

Political pressure groups campaigning against the admission of mentally ill women to high security hospitals have succeeded in changing government policy. Three high security units in England will be reduced to one, accommodating only the most dangerous women. The rapidly growing range of public and private medium security units will treat all other women detained under the Mental Health Act.

This is a time of change in the treatment of mentally abnormal women offenders in England. It presents an opportunity for those of us who care about these women to share knowledge and experience with professionals from other countries.

Climate change is one of the biggest challenges facing the world. Scientific research points out that it is predominately driven by human activity. There are three different types of risks that arise from this change. These have been broadly grouped into physical, transition and liability risks. These risks can impact general insurers to different degrees, depending on their business areas and investment strategies. These may pose different strategic, investment, market, operational and reputational risks. This paper provides General Insurance Practitioners with an overview of different aspects of insurance operations that may be affected by climate change. It highlights the impact of these risks on pricing and underwriting, reserving, reinsurance, catastrophe modelling, investment, risk management and capital management processes.

Frozen raw breaded chicken products (FRBCP) have been identified as a risk factor for Salmonella infection in Canada. In 2017, Canada implemented whole genome sequencing (WGS) for clinical and non-clinical Salmonella isolates, which increased understanding of the relatedness of Salmonella isolates, resulting in an increased number of Salmonella outbreak investigations. A total of 18 outbreaks and 584 laboratory-confirmed cases have been associated with FRBCP or chicken since 2017. The introduction of WGS provided the evidence needed to support a new requirement to control the risk of Salmonella in FRBCP produced for retail sale.

For livestock production systems to play a positive role in global food security, the balance between their benefits and disbenefits to society must be appropriately managed. Based on the evidence provided by field-scale randomised controlled trials around the world, this debate has traditionally centred on the concept of economic-environmental trade-offs, of which existence is theoretically assured when resource allocation is perfect on the farm. Recent research conducted on commercial farms indicates, however, that the economic-environmental nexus is not nearly as straightforward in the real world, with environmental performances of enterprises often positively correlated with their economic profitability. Using high-resolution primary data from the North Wyke Farm Platform, an intensively instrumented farm-scale ruminant research facility located in southwest United Kingdom, this paper proposes a novel, information-driven approach to carry out comprehensive assessments of economic-environmental trade-offs inherent within pasture-based cattle and sheep production systems. The results of a data-mining exercise suggest that a potentially systematic interaction exists between ‘soil health’, ecological surroundings and livestock grazing, whereby a higher level of soil organic carbon (SOC) stock is associated with a better animal performance and less nutrient losses into watercourses, and a higher stocking density with greater botanical diversity and elevated SOC. We contend that a combination of farming system-wide trials and environmental instrumentation provides an ideal setting for enrolling scientifically sound and biologically informative metrics for agricultural sustainability, through which agricultural producers could obtain guidance to manage soils, water, pasture and livestock in an economically and environmentally acceptable manner. Priority areas for future farm-scale research to ensure long-term sustainability are also discussed.

Head lice (Pediculus humanus capitis) infestations are a public health concern. The insecticidal properties of the Australian native plant Kunzea ambigua (commonly known as tick bush) have been documented. In this study, we tested activity of kunzea oil (KO) against head lice through in vitro bioassays. Head lice were exposed to filter paper treated with either KO, as either a 5 or 100% oil, or commercial formulations containing either permethrin or tea tree oil (TTO) for 120 min. Head lice exposure to KO, both as a 5 and 100% solution oil, resulted in 100% mortality within 120 min with a mean survival times of 17·1 and 34·8 min, respectively. There was no significant difference between the mean mortality of head lice exposed to 5% KO (17·1 ± 1·0; 95% CI: 115·2–19·0) and 5% TTO (21·2 ± 1·9; 95% CI: 17·4–25·1). This study revealed, for the first time, that KO holds great potential as an effective alternative to current active ingredients contained within commercial pediculicide formulations.

The relationships between total and free serum valproate (VPA) concentrations and seizure control, serum liver enzyme activity and plasma ammonia concentration were studied in 61 epileptic children. Enzymeimmunoassay (EMIT)R methods gave higher values of total VPA concentration than gas-liquid chromatography (GLC) methods. In over 80% of children with complete seizure control the ranges of total VPA concentration were 140-420 umol/L with GLC methods and 210-560 umol/L with EMIT methods. The range of free VPA concentrations in 78% of children with complete seizure control was 8.8-26.4 umol/L. Increased liver enzyme activity was observed in 6 of the 61 children and raised plasma ammonia concentration in 11 of 50 children. Plasma ammonia concentration was related to total serum VPA but was not related to free serum VPA. Increased serum liver enzyme activity was related to VPA dose per kg but not to free or total serum VPA concentration. Thus free VPA concentrations do not appear to be more useful than total VPA concentrations in predicting seizure control and do not correlate with liver enzyme activity or plasma ammonia concentration.

Background: Video feedback (VF) interventions effectively reduce social anxiety symptoms and negative self-perception, particularly when they are preceded by cognitive preparation (CP) and followed by cognitive review. Aims: In the current study, we re-examined data from a study on the efficacy of a novel VF intervention for individuals high in social anxiety to test the hypothesis that physical appearance anxiety would moderate the effects of VF. Method: Data were analyzed from 68 socially anxious participants who performed an initial public speech, and were randomly assigned to an Elaborated VF condition (VF plus cognitive preparation and cognitive review), a Standard VF condition (VF plus cognitive preparation) or a No VF condition (exposure alone), and then performed a second speech. Results: As hypothesized, when appearance concerns were low, both participants who received Elaborated and Standard VF were significantly less anxious during speech 2 than those in the No VF condition. However, when levels of appearance concern were high, neither Elaborated nor Standard VF reduced anxiety levels during speech 2 beyond the No VF condition. Conclusions: Results from our analog sample suggest the importance of tailoring treatment protocols to accommodate the idiosyncratic concerns of socially anxious patients.