As TeV gamma-ray astronomy progresses into the era of the Cherenkov Telescope Array (CTA), instantaneously following up on gamma-ray transients is becoming more important than ever. To this end, a worldwide network of Imaging Atmospheric Cherenkov Telescopes has been proposed. Australia is ideally suited to provide coverage of part of the Southern Hemisphere sky inaccessible to H.E.S.S. in Namibia and the upcoming CTA-South in Chile. This study assesses the sources detectable by a small, transient-focused array in Australia based on CTA telescope designs. The TeV emission of extragalactic sources (including the majority of gamma-ray transients) can suffer significant absorption by the extragalactic background light. As such, we explored the improvements possible by implementing stereoscopic and topological triggers, as well as lowered image cleaning thresholds, to access lower energies. We modelled flaring gamma-ray sources based on past measurements from the satellite-based gamma-ray telescope Fermi-LAT. We estimate that an array of four Medium-Sized Telescopes (MSTs) would detect $\sim$24 active galactic nucleus flares >5$\sigma$ per year, up to a redshift of $z\approx1.5$. Two MSTs achieved $\sim$80–90% of the detections of four MSTs. The modelled Galactic transients were detectable within the observation time of one night, 11 of the 21 modelled gamma-ray bursts were detectable, as were $\sim$10% of unidentified transients. An array of MST-class telescopes would thus be a valuable complementary telescope array for transient TeV gamma-ray astronomy.

The administration of Pre-Mortem Interventions (PMIs) to preserve the opportunity to donate, to assess the eligibility to donate, or to optimize the outcomes of donation and transplantation are controversial as they offer no direct medical benefit and include at least the possibility of harm to the still-living patient. In this article, we describe the legal analysis surrounding consent to PMIs, drawing on existing legal commentary and identifying key legal problems. We provide an overview of the approaches in several jurisdictions that have chosen to explicitly address PMIs within codified law. We then provide, as an example, a detailed exploration of how PMIs are likely to be addressed in one jurisdiction where general medical consent law applies because there is no specific legislation addressing PMIs — the province of Ontario in Canada.

OBJECTIVES/GOALS: Our overall goal is to identify the processes used by the human visual system to encode visual stimuli into perceptual representations. In this project, our objective is (i) to collect a dataset of human neural activity in response to 1000 naturalistic color images and (ii) to determine how image parameters drive different parts of the human brain. METHODS/STUDY POPULATION: We recorded iEEG data in 4 human subjects who had been implanted for epilepsy monitoring. Each subject was presented 10 sets of 100 naturalistic stimuli, taken from the Natural Scenes Dataset (Allen et al., 2021), on a screen for 1 second each with 1 second rest intervals between stimuli. The subjects were instructed to fixate on a red dot at the center of the screen and were prompted to recall whether they had seen 3 additional test stimuli at the end of each set to encourage attentiveness. We calculated significant neural responses at each electrode by comparing evoked potentials and high frequency power changes during each stimulus vs. rest. Electrodes with significant responses were then mapped to anatomic locations in each subjects brain and then collectively to a standard brain. RESULTS/ANTICIPATED RESULTS: The natural image set elicited significant evoked potentials and high frequency responses at electrodes in each subject. Response latencies, from 80 to 300 ms after stimulus onset, portrayed the evolution of visual processing along the visual pathways, through key sites such as the early visual cortex, ventral temporal cortex, intraparietal sulcus, and frontal eye field. These responses differed significantly from those elicited by simple patterns, which drove early visual cortex but less so in later regions. DISCUSSION/SIGNIFICANCE: These data show that the human brain responds differently to more complex images. Determining the human brains response to naturalistic images is essential for encoding models that describe the processing in the human visual system. These models may further future efforts for electrical neurostimulation therapies such as for restoring vision.

ABSTRACT IMPACT: This study characterizes interactions between human limbic circuitry and ventral temporal cortex using single pulse electrical stimulation, which may inform emerging stimulation therapies for epilepsy. OBJECTIVES/GOALS: The goal of electrical brain stimulation treatment is to modulate brain network function. However, stimulation inputs to different brain sites alter the network in a variety of ways. This study examines that variability by characterizing responses in a target region while stimulating multiple other brain sites. METHODS/STUDY POPULATION: We measured voltages in intracranial EEG in 6 patients who had electrodes implanted for epilepsy monitoring. We stimulated pairs of electrodes at multiple sites in the brain with a single pulse every 5 to 7 s and measured the resulting corticocortical evoked potential (CCEP) responses in the ventral temporal cortex (VTC). Using a novel clustering method, we uncovered sets of distinct canonical response shapes from the 20 to 500 ms post-stimulation period. This allowed us to group stimulation sites that evoked similar responses. We then related each group to high frequency, broadband, changes in spectral power as a reflection of local neuronal activity. RESULTS/ANTICIPATED RESULTS: We found that the VTC receives strong inputs specifically from the amygdala and hippocampus, both in terms of amplitude and broadband spectral power change. However, inputs from the hippocampus produced a different canonical shape than those from the amygdala. We also observed that VTC responses to inputs from the insula clustered in shape with those from the amygdala. These clustering patterns were consistent across subjects, although the actual shapes of the clusters showed variability. We further observed that some shapes were more associated with increases in overall neuronal activity than others, as reflected by broadband spectral power change. DISCUSSION/SIGNIFICANCE OF FINDINGS: Stimulation of connected sites may drive excitability at the target region in ways that are described by sets of full-time-course responses. By capturing their shapes, we can begin to decipher canonical input types at the circuit level. This approach might identify how stimulation inputs can be tailored to therapy while mitigating adverse effects.

The Orion facility at the Atomic Weapons Establishment in the United Kingdom has the capability to operate one of its two 500 J, 500 fs short-pulse petawatt beams at the second harmonic, the principal reason being to increase the temporal contrast of the pulse on target. This is achieved post-compression, using 3 mm thick type-1 potassium dihydrogen phosphate crystals. Since the beam diameter of the compressed pulse is ${\sim}600$ mm, it is impractical to achieve this over the full aperture due to the unavailability of the large aperture crystals. Frequency doubling was originally achieved on Orion using a circular sub-aperture of 300 mm diameter. The reduction in aperture limited the output energy to 100 J. The second-harmonic capability has been upgraded by taking two square 300 mm $\times$ 300 mm sub-apertures from the beam and combining them at focus using a single paraboloidal mirror, thus creating a 200 J, 500 fs, i.e., 400 TW facility at the second harmonic.

Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6–7 years in 724 mother–child pairs from the Southampton Women’s Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (β=0·36, P<0·001). DHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (β=0·46, P<0·001). Children’s cognitive function at the age of 4 years was assessed by the Wechsler Preschool and Primary Scale of Intelligence and at the age of 6–7 years by the Wechsler Abbreviated Scale of Intelligence. Executive function at the age of 6–7 years was assessed using elements of the Cambridge Neuropsychological Test Automated Battery. Neither DHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6–7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.

Salmonella is a leading cause of bacterial foodborne illness. We report the collaborative investigative efforts of US and Canadian public health officials during the 2013–2014 international outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder. The investigation included open-ended interviews of ill persons, traceback, product testing, facility inspections, and trace forward. Ninety-four persons infected with outbreak strains from 16 states and four provinces were identified; 21% were hospitalized and none died. Fifty-four (96%) of 56 persons who consumed chia seed powder, reported 13 different brands that traced back to a single Canadian firm, distributed by four US and eight Canadian companies. Laboratory testing yielded outbreak strains from leftover and intact product. Contaminated product was recalled. Although chia seed powder is a novel outbreak vehicle, sprouted seeds are recognized as an important cause of foodborne illness; firms should follow available guidance to reduce the risk of bacterial contamination during sprouting.

Background: Disgust is thought to play a prominent role in multiple anxiety disorders and fears, including spider phobia, though little attention has been given to specific treatment strategies that may be effective for multiple disgust-based fears. Aims: In the present study, we evaluated contamination-focused exposure as a potential transdiagnostic treatment strategy for disgust-based fears in a spider fearful sample. Method: Women with significant spider fear were randomized to three 30-minute sessions of exposure therapy involving repeated contact with a dirt mixture (n=17) or a waitlist control condition (n=17). Assessments of spider fear and disgust were administered at baseline and at one-week posttreatment. Results: At high (but not low) levels of pretreatment disgust propensity, exposure led to lower in vivo spider fear and perceived danger than waitlist, though exposure had no effects on spider-related disgust. Similar effects of exposure on spider fear were found at high levels of pretreatment spider-related disgust. Exposure also reduced fear and danger perceptions, but not disgust, related to a separate contamination assessment (touching a toilet). No effects of treatment were found on self-report measures of spider fear or disgust propensity. Conclusions: These findings suggest contamination-focused exposure therapy may be an effective transdiagnostic treatment strategy for individuals with elevated disgust propensity. Limitations and directions for future research are discussed.

Osteoporosis-related fractures have a major impact on health at the individual and societal levels, through associated morbidity and increased mortality. Up to 50% of women and 20% of men at age 50 years may have a fragility fracture in their remaining lifetimes. Nutrition is important throughout the life course. Thus, adequate Ca and vitamin D intake has been shown to reduce risk of fracture in old age. Other factors such as protein and vitamin K may also be important, although the evidence here is less strong. In childhood Ca or vitamin D supplementation trials have demonstrated modest short-term increases in bone mass, but the long-term implications have not been established. Over recent years it has become apparent that maternal nutrition may have critical and far-reaching persistent consequences for offspring health. Thus, reduced maternal fat stores and low levels of circulating 25-hydroxyvitamin D in pregnancy are associated with reduced bone mass in the offspring; placental Ca transport may be key to these relationships. Wider maternal dietary patterns have also been shown to predict offspring bone mass. These data suggest that an interventional approach aimed at specific micronutrients, such as vitamin D, should be complemented by general optimisation of the mother's diet and lifestyle in order to maximise intrauterine bone mineral accrual and postnatal skeletal growth and thus reduce the burden of osteoporotic fractures in future generations.

The impact of variations in current infant feeding practice on bone mineral accrual is not known. We examined the associations between duration of breast-feeding and compliance with infant dietary guidelines and later bone size and density at age 4 years. At total of 599 (318 boys) mother–child pairs were recruited from the Southampton Women's Survey. Duration of breast-feeding was recorded and infant diet was assessed at 6 and 12 months using FFQ. At 6 and 12 months the most important dietary pattern, defined by principal component analysis, was characterised by high consumption of vegetables, fruits and home-prepared foods. As this was consistent with infant feeding recommendations, it was denoted the ‘infant guidelines’ pattern. At age 4 years, children underwent assessment of whole-body bone size and density using a Hologic Discovery dual-energy X-ray absorptiometry instrument. Correlation methods were used to explore the relationships between infant dietary variables and bone mineral. There was no association between duration of breast-feeding in the first year of life and 4-year bone size or density. ‘Infant guidelines’ pattern scores at 6 and 12 months were also unrelated to bone mass at age 4 years. We observed wide variations in current infant feeding practice, but these variations were not associated with differences in childhood bone mass at age 4 years.