OBJECTIVES/GOALS: Determine how a history of unpredictable foot shock in mice affects brain wide patterns of neural activation to future stressors. Additionally, we aimed to characterize how the paraventricular nucleus of the thalamus (PVT) is involved in the fear sensitization process. METHODS/STUDY POPULATION: We used a mouse model of stress enhanced fear learning, where stressed mice are first subjected to a series of unpredictable foot shocks in a novel context while control mice undergo exposure to the novel context without experiencing foot shock. Mice are then left undisturbed for 28 days, following which they are exposed to a single foot shock in a novel context. Mice are tested in the second context 24 hours after single shock, and the amount of time spent frozen in the context provides a measure of fear sensitization. Whole brain patterns of activation during the second context test will be assessed via whole brain optical clearing with antibody staining of immediate early genes. The role of the PVT in fear sensitization will be characterized using chemogenetic approaches. RESULTS/ANTICIPATED RESULTS: Our preliminary results demonstrate that mice display enhanced fear acquisition long after the initial experience of unpredictable shocks. We anticipate to identify regions previously implicated in fear learning and novel regions not previously described through our brain clearing approach. In addition, we anticipate chemogenetic inhibition of the PVT will reduce freezing to an auditory cue associated with the shock in the second context but not to the context itself. DISCUSSION/SIGNIFICANCE: Our findings will provide a comprehensive view of how a history of unpredictable stress affects whole brain processing of subsequent stressful experiences, and describe the role of the PVT in cued fear sensitization.

Extreme precipitation events are occurring more intensely in Canada. This can contaminate water sources with enteric pathogens, potentially increasing the risk of acute gastrointestinal illness. This study aimed to investigate the relationship between extreme precipitation and emergency department (ED) visits for acute gastrointestinal illness in Toronto from 2012 to 2022. Distributed lag non-linear models were constructed on ED visit counts with a Quasi Poisson distribution. Extreme precipitation was modelled as a 21-day lag variable, with a linear relationship assumed at levels ≧95th percentile. Separate models were also conducted on season-specific data sets. Daily precipitation and gastrointestinal illness ED visits ranged between 0 to 126 mm, and 12 to 180 visits respectively. Overall, a 10-mm increase in precipitation >95th percentile had no significant relationship with the risk of ED visits. However, stratification by seasons revealed significant relationships during spring (lags 1–19, peak at lag 14 RR = 1.04; 95% CI: 1.03, 1.06); the overall cumulative effect across the 21-day lag was also significant (RR = 1.94; 95% CI: 1.47, 2.57). Extreme precipitation has a seasonal effect on gastrointestinal health outcomes in Toronto city, suggesting varying levels of enteric pathogen exposures through drinking water or other environmental pathway during different seasons.

Non-communicable diseases (NCD) such as CVD and type 2 diabetes mellitus are major contributors to the burden of disease. NCD are largely driven by modifiable lifestyle factors including poor diet and insufficient physical activity, and consequently, prevention is a public health priority. Although diet and physical activity levels can be improved via lifestyle interventions, long-term adherence to such interventions remains low, which limits their effectiveness. Thus, it is critical to identify the underlying mechanisms that challenge uptake and adherence to such interventions. The current commentary discusses an important, but underexplored, psychological driver of poor adherence to lifestyle interventions, namely, future discounting, which describes the tendency to prefer smaller, short-term rewards over larger, long-term rewards. For example, in the nutrition domain, future discounting refers to valuing the immediate reward of excessive intake of energy-dense, nutrient-poor, discretionary foods high in salt, sugar, and saturated fat, and insufficient intake of low-energy, nutrient-dense, whole foods such as vegetables. Prominent theoretical models propose that excessive future discounting is a major contributor to the development of unhealthy lifestyle behaviours. Furthermore, a vast body of evidence suggests that future discounting plays a key role in risk of NCD. Thus, the evidence to date supports the idea that future discounting is an important multi-behaviour target for supporting lifestyle behaviour change; however, this approach has been largely neglected in preventive health efforts. Furthermore, this commentary discusses promising techniques (e.g. Episodic Future Thinking) for disrupting future discounting to promote improved adherence to lifestyle interventions aimed at reducing NCD risk.

Impulsive and compulsive problem behaviours are associated with a variety of mental disorders. Latent phenotyping indicates the expression of impulsive and compulsive problem behaviours is predominantly governed by a transdiagnostic ‘disinhibition’ phenotype. In a cohort of 117 individuals, recruited as part of the Neuroscience in Psychiatry Network (NSPN), we examined how brain functional connectome and network properties relate to disinhibition. Reduced functional connectivity within a subnetwork of frontal (especially right inferior frontal gyrus), occipital and parietal regions was linked to disinhibition. Findings provide insights into neurobiological pathways underlying the emergence of impulsive and compulsive disorders.

We develop a two-dimensional, plan-view formulation of ice-shelf flow and viscoelastic ice-shelf flexure. This formulation combines, for the first time, the shallow-shelf approximation for horizontal ice-shelf flow (and shallow-stream approximation for flow on lubricated beds such as where ice rises and rumples form), with the treatment of a thin-plate flexure. We demonstrate the treatment by performing two finite-element simulations: one of the relict pedestalled lake features that exist on some debris-covered ice shelves due to strong heterogeneity in surface ablation, and the other of ice rumpling in the grounding zone of an ice rise. The proposed treatment opens new venues to investigate physical processes that require coupling between the longitudinal deformation and vertical flexure, for instance, the effects of surface melting and supraglacial lakes on ice shelves, interactions with the sea swell, and many others.

Diurnal depth cycles of decimeter scale are observed in a supraglacial lake on the McMurdo Ice Shelf, Antarctica. We evaluate two possible causes: (1) tidal tilt of the ice shelf in response to the underlying ocean tide, and (2) meltwater input variation. We find the latter to be the most likely explanation of our observations. However, we do not rule out tidal tilt as a source of centimeter scale variations, and point to the possibility that other, larger supraglacial lake systems, particularly those on ice shelves that experience higher amplitude tidal tilts, such as in the Weddell Sea, may have depth cycles driven by ocean tide. The broader significance of diurnal cycles in meltwater depth is that, under circumstances where the ice shelf is thin, tidal-tilt amplitudes are high, and meltwater runoff rates are large, there may be associated flexure stresses that can contribute to ice-shelf fracture and destabilization. For the McMurdo Ice Shelf (~20–50 m thickness, ~ 1 m tidal amplitude and ~10 cm water-depth variations), these stresses amount to several 10's of kPa.

Surface debris covers much of the western portion of the McMurdo Ice Shelf and has a strong influence on the local surface albedo and energy balance. Differential ablation between debris-covered and debris-free areas creates an unusual heterogeneous surface of topographically low, high-ablation, and topographically raised (‘pedestalled’), low-ablation areas. Analysis of Landsat and MODIS satellite imagery from 1999 to 2018, alongside field observations from the 2016/2017 austral summer, shows that pedestalled relict lakes (‘pedestals’) form when an active surface meltwater lake that develops in the summer, freezes-over in winter, resulting in the lake-bottom debris being masked by a high-albedo, superimposed, ice surface. If this ice surface fails to melt during a subsequent melt season, it experiences reduced surface ablation relative to the surrounding debris-covered areas of the ice shelf. We propose that this differential ablation, and resultant hydrostatic and flexural readjustments of the ice shelf, causes the former supraglacial lake surface to become increasingly pedestalled above the lower topography of the surrounding ice shelf. Consequently, meltwater streams cannot flow onto these pedestalled features, and instead divert around them. We suggest that the development of pedestals has a significant influence on the surface-energy balance, hydrology and flexure of the ice shelf.

Fighting and dying, or what Whitehouse calls “out-group hostility” and “extreme self-sacrifice,” are not conceptually overlapping, but in fact are highly distinguishable, both theoretically and empirically. I present empirical evidence from a reanalysis of Ginges et al. (2009, Study 4), demonstrating the potentially inverse relationship between “parochial hostility” – fighting and “sacrificial altruism” – “and” dying.

Seismograms acquired on the McMurdo Ice Shelf, Antarctica, during an Austral summer melt season (November 2016–January 2017) reveal a diurnal cycle of seismicity, consisting of hundreds of thousands of small ice quakes limited to a 6–12 hour period during the evening, in an area where there is substantial subsurface melting. This cycle is explained by thermally induced bending and fracture of a frozen surface superimposed on a subsurface slush/water layer that is supported by solar radiation penetration and absorption. A simple, one-dimensional model of heat transfer driven by observed surface air temperature and shortwave absorption reproduces the presence and absence (as daily weather dictated) of the observed diurnal seismicity cycle. Seismic event statistics comparing event occurrence with amplitude suggest that the events are generated in a fractured medium featuring relatively low stresses, as is consistent with a frozen surface superimposed on subsurface slush. Waveforms of the icequakes are consistent with hydroacoustic phases at frequency $ {\bf \gt} \bf 75\,{\bf Hz}$ and flexural-gravity waves at frequency $ \bf {\bf \lt}25\,{\bf Hz}$. Our results suggest that seismic observation may prove useful in monitoring subsurface melting in a manner that complements other ground-based methods as well as remote sensing.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease resulting in muscle weakness, dysarthria and dysphagia, and ultimately respiratory failure leading to death. Half of the ALS patients survive less than 3 years, and 80% of the patients survive less than 5 years. Riluzole is the only approved medication in Canada with randomized controlled clinical trial evidence to slow the progression of ALS, albeit only to a modest degree. The Canadian Neuromuscular Disease Registry (CNDR) collects data on over 140 different neuromuscular diseases including ALS across ten academic institutions and 28 clinics including ten multidisciplinary ALS clinics. Methods: In this study, CNDR registry data were analyzed to examine potential differences in ALS care among provinces in time to diagnosis, riluzole and feeding tube use. Results: Significant differences were found among provinces, in time to diagnosis from symptom onset, in the use of riluzole and in feeding tube use. Conclusions: Future investigations should be undertaken to identify factors contributing to such differences, and to propose potential interventions to address the provincial differences reported.