Objectives/Goals: One in 14 individuals have a substance use disorder (SUD). We suggest that a trait of poor impulse control, or high impulsivity, may predict relapse risk. We explore how changes in brain structure linked to decision-making and reward might drive high impulsivity, helping create a “biosignature” to identify those most at risk and guide treatment choices. Methods/Study Population: Male rats were phenotyped as high impulsive (HI) or low impulsive (LI) based on premature responses on the one-choice serial reaction time (1-CSRT) task. Rats then received an intracranial infusion of a retrograde virus (AAVr2) in the nucleus accumbens (NAc) to trace corticoaccumbens neurons back to the medial prefrontal cortex (mPFC). After impulsivity phenotyping (ITI8), another cohort of animals performed cocaine self-administration followed by 30 days of abstinence. Cue reactivity, a measure of relapse-like behaviors, was performed on abstinence day 30. Analyses of microtubule-associated protein 2 (MAP2), a cytoskeletal marker of dendrites, spines, and somas was performed with western blotting and fluorescent images of brain slices after phenotyping and cocaine abstinence. Results/Anticipated Results: HI rats made greater premature responses, a marker of impulsive action vs. LI rats at baseline (p Discussion/Significance of Impact: Poor inherent impulse control and drug cues heighten relapse risk. We found high impulsivity linked to brain structure differences and lower protein markers of synaptic (units supporting signaling) strengthening. Future investigations into brain-behavior links with impulsivity may further identify a SUD relapse vulnerability biosignature.

There is strong evidence for a general psychopathology dimension which captures covariance among all forms of psychopathology, yet its nature and underlying association with personality remain unclear. This study examined the co-development of general psychopathology and four high-risk personality traits: anxiety sensitivity, negative thinking, sensation seeking, and impulsivity. Data from two large Australian school-based randomised controlled trials of substance use prevention programs were analysed (N = 2,083, mean age at baseline = 13.49 years). Adolescents completed self-report measures of psychopathology symptoms and personality at baseline, one-, two-, and three-years post-baseline. Latent curve models with structured residuals, were used to examine the co-development of general psychopathology (extracted from a higher-order model) and personality traits from 13 to 16 years of age, controlling for age, sex, and cohort. Higher than usual levels of anxiety sensitivity and impulsivity were associated with higher than usual levels of general psychopathology at subsequent time points, and higher than usual levels of general psychopathology were associated with higher than usual levels of negative thinking at later time points. Sensation seeking was unrelated to general psychopathology. These findings enhance our understanding of the meaning and validity of general psychopathology, highlighting potential personality-based prevention and intervention targets.

Background: Despite efforts to advance equity, women face gender-based barriers in research, including fewer senior authorship and grant opportunities. We examined gender disparities in Canadian Institutes of Health Research (CIHR) funding for Canadian neurology divisions and departments. Methods: Data on CIHR grant recipients and metrics (duration, quantity, and contribution) within Canadian neurology divisions and departments (2008-2022) were acquired from the CIHR Funding Decisions Database. Gender-based differences in grant prevalence, duration, and contribution amount within neurology were calculated with subgroup analysis for Canadian neurologists and Project Grant awards. Results: 1604 grants were awarded to Canadian neurology divisions and departments between 2008-2022. Women received fewer grants (41.46%), less funding (p<0.0001), and shorter grant durations (p<0.0001) than men annually. Women comprised the minority of recipients (45.47%) and were less likely to be awarded grants (p<0.001) annually relative to men. Differences were consistent in subgroup analyses, except grant durations were equal across genders in Project Grant awards. Conclusions: Gender disparities persist in CIHR grant funding to Canadian neurology divisions and departments. Women receive fewer grants, lower contribution amounts, and are less likely to be recipients compared to men. Future work includes addressing gender differences and continuing to evaluate CIHR funding to provide equitable opportunities for women.

Background: Intravenous Immunoglobulin (IVIg) use for Central Nervous System (CNS) conditions has increased over the last decade. In many CNS disorders, robust evidence for IVIg efficacy is still lacking. Building on the success of the British Columbia (BC) Neuromuscular IVIg utilization initiative, Guidelines for IVIg use in CNS conditions were developed. A provincial screening program was launched in 2023. Methods: For CNS IVIg, requests, diagnosis, dosing, consultation letters and treatment questionnaires were reviewed. Patient management was compared to provincial guidelines. A letter was sent to the ordering physician with the results of the review and treatment recommendations when management differed significantly from guidelines. Review of the first year’s cases was conducted. Results: Over the first 11 months of the program, 79 IVIg renewal requests were reviewed. The most common diagnoses were antibody mediated autoimmune encephalitis, severe drug resistant non-surgical epilepsy and Susac’s syndrome. Recommendations included dose reduction, discontinuation of IVIg, or initiation of alternative therapies for many of the requests. Conclusions: IVIg may be effective in the management of some CNS inflammatory conditions. A physician-led utilization program in BC with targeted education to ordering physicians promotes best practice. Review of year one data will inform a quality improvement cycle to optimize the guidelines.

The general public and scientific community alike are abuzz over the release of ChatGPT and GPT-4. Among many concerns being raised about the emergence and widespread use of tools based on large language models (LLMs) is the potential for them to propagate biases and inequities. We hope to open a conversation within the environmental data science community to encourage the circumspect and responsible use of LLMs. Here, we pose a series of questions aimed at fostering discussion and initiating a larger dialogue. To improve literacy on these tools, we provide background information on the LLMs that underpin tools like ChatGPT. We identify key areas in research and teaching in environmental data science where these tools may be applied, and discuss limitations to their use and points of concern. We also discuss ethical considerations surrounding the use of LLMs to ensure that as environmental data scientists, researchers, and instructors, we can make well-considered and informed choices about engagement with these tools. Our goal is to spark forward-looking discussion and research on how as a community we can responsibly integrate generative AI technologies into our work.

OBJECTIVES/GOALS: Neuropsychiatric disorders classified as synaptopathies are marked by a glutamate-associated hypofrontality which impacts decision making and impulsivity. We hypothesized that behavioral efficacy of the psychoplastogen ketamine is mediated in part through lasting promotion of markers of synaptic strength in corticoaccumbens circuit. METHODS/STUDY POPULATION: Male, Sprague-Dawley rats received an intraperitoneal (i.p.) injection of saline, single ketamine (10 mg/kg; 1x/day), or repeated ketamine (10 mg/kg; 1x/day for three days). Twenty-four hrs following the dosing regimen, animals were euthanized, and brains dissected to harvest corticoaccumbens structures including the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc). mRNA was extracted and converted to cDNA. Levels of brain derived neurotrophic factor (BDNF) exon II mRNA were quantified using reverse transcriptase polymerase chain reaction (RT-PCR); cyclophilin A (PPIA) was used as a loading control. Gene expression differences in ketamine-treated rats were identified versus saline-treated rats. BDNF protein levels were quantified using capillary-electrophoresis immunoblotting. RESULTS/ANTICIPATED RESULTS: Repeated, but not single, ketamine administration decreased mPFC, but increased NAc, BDNF exon II mRNA levels versus saline (p<0.05). Single and repeated ketamine administration increased NAC BDNF protein (p<0.05), while both dosing paradigms induced a trend towards an increase in mPFC BDNF levels. DISCUSSION/SIGNIFICANCE: We discovered a dosing regimen-dependent and sustained effects of ketamine administration on BDNF levels in the rodent brain. Taken together, ketamine-mediated BDNF levels may sustain synaptic strengthening mechanisms supporting future investigation into the utility of ketamine for diseases characterized by synaptopathies.

Human infection with antimicrobial-resistant Campylobacter species is an important public health concern due to the potentially increased severity of illness and risk of death. Our objective was to synthesise the knowledge of factors associated with human infections with antimicrobial-resistant strains of Campylobacter. This scoping review followed systematic methods, including a protocol developed a priori. Comprehensive literature searches were developed in consultation with a research librarian and performed in five primary and three grey literature databases. Criteria for inclusion were analytical and English-language publications investigating human infections with an antimicrobial-resistant (macrolides, tetracyclines, fluoroquinolones, and/or quinolones) Campylobacter that reported factors potentially linked with the infection. The primary and secondary screening were completed by two independent reviewers using Distiller SR®. The search identified 8,527 unique articles and included 27 articles in the review. Factors were broadly categorised into animal contact, prior antimicrobial use, participant characteristics, food consumption and handling, travel, underlying health conditions, and water consumption/exposure. Important factors linked to an increased risk of infection with a fluoroquinolone-resistant strain included foreign travel and prior antimicrobial use. Identifying consistent risk factors was challenging due to the heterogeneity of results, inconsistent analysis, and the lack of data in low- and middle-income countries, highlighting the need for future research.

Background: Patient-centred care is important in the management of chronic inflammatory neuropathies (CIN) given the heterogeneity in disease course and treatment response. Patient Reported Outcome Measures (PROMs) support value-based healthcare by aligning treatment goals with what matters most to patients. This study evaluated the relevance of PROMs to patients and the feasibility of use in clinical management. Methods: PROMs assessing quality of life, pain, fatigue, and overall disability were collected prospectively from 32 patients with CIN every three months over a 12-month period. Patients provided feedback on relevance of the measures. PROMs were sent electronically prior to the visit. Results: Completion rate was 92%. Home vs. in-clinic completion increased from 56% to 85% over the course of the study. There was an association between completion of the panel and perceived relevance. The PROMs were consistently rated as highly relevant, with disability and fatigue measures rated highest. Conclusions: PROMs are appraised as highly relevant among patients with CIDP and MMN. Patients require support initially but adapt to electronically delivered home completion of questionnaires. We recommend inclusion of PROMs into routine clinical practice as a means of capturing aspects of health that are not easily assessed in a clinic visit.

Background: Our aim was to develop a National Quality Indicators Set for the Care of Adults Hospitalized for Neurological Problems, to serve as a foundation to build regional or national quality initiatives in Canadian neurology centres. Methods: We used a national eDelphi process to develop a suite of quality indicators and a parallel process of surveys and patient focus groups to identify patient priorities. Canadian content and methodology experts were invited to participate. To be included, >70% of participants had to rate items as critical and <15% had to rate it as not important. Two rounds of surveys and consensus meetings were used identify and rank indicators, followed by national consultation with members of the Canadian Neurological Society. Results: 38 neurologists and methodologists and 56 patients/caregivers participated in this project. An initial list of 91 possible quality indicators was narrowed to 40 indicators across multiple categories of neurological conditions. 21 patient priorities were identified. Conclusions: This quality indicators suite can be used regionally or nationally to drive improvement initiatives for inpatient neurology care. In addition, we identified multiple opportunities for further research where evidence was lacking or patient and provider priorities did not align.

Distributed Acoustic Sensing (DAS) is increasingly recognised as a valuable tool for glaciological seismic applications, although analysing the large data volumes generated in acquisitions poses computational challenges. We show the potential of active-source DAS to image and characterise subglacial sediment beneath a fast-flowing Greenlandic outlet glacier, estimating the thickness of sediment layers to be 20–30 m. However, the lack of subglacial velocity constraint limits the accuracy of this estimate. Constraint could be provided by analysing cryoseismic events in a counterpart 3-day record of passive seismicity through, for example, seismic tomography, but locating them within the 9 TB data volume is computationally inefficient. We describe experiments with data compression using the frequency-wavenumber (f-k) transform ahead of training a convolutional neural network, that provides a ~300-fold improvement in efficiency. In combining active and passive-source and our machine learning framework, the potential of large DAS datasets could be unlocked for a range of future applications.

Scholars have expressed concern over waning support for democracy worldwide. But what do ordinary citizens mean by the term “democracy," and how do their definitions of democracy influence their support for it? Using global cross-national survey data, this study demonstrates that individual variation in the understanding of democracy is substantively linked to democratic support across countries and regime contexts. Individuals who define democracy in terms of elections and the protection of civil liberties and those with greater conceptual complexity express higher support for democracy. This relationship between democratic conceptualization and support holds across diverse political contexts and alternative explanations. These results suggest that it is essential to consider divergent conceptualizations of democracy—and how they may vary systematically—when analyzing popular opinions of democracy.

The present study examined high-risk personality traits and associations with psychopathology across multiple levels of a hierarchical-dimensional model of psychopathology in a large adolescent, general population sample. Confirmatory factor analyses were run using data from two randomized controlled trials of Australian adolescents (N = 8,654, mean age = 13.01 years, 52% female). A higher-order model – comprised of general psychopathology, fear, distress, alcohol use/harms, and conduct/inattention dimensions – was selected based on model fit, reliability, and replicability. Indirect-effects models were estimated to examine the unique associations between high-risk personality traits (anxiety sensitivity, negative thinking, impulsivity, and sensation seeking) and general and specific dimensions and symptoms of psychopathology. All personality traits were positively associated with general psychopathology. After accounting for general psychopathology, anxiety sensitivity was positively associated with fear; negative thinking was positively associated with distress; impulsivity was positively associated with conduct/inattention; and sensation seeking was positively associated with alcohol use/harms and conduct/inattention, and negatively associated with fear. Several significant associations between personality traits and individual symptoms remained after accounting for general and specific psychopathology. These findings contribute to our understanding of the underlying structure of psychopathology among adolescents and have implications for the development of personality-based prevention and early intervention programs.

Background: Intravenous immunoglobulin (IVIG) may benefit many inflammatory central nervous system (CNS) disorders based on multiple immunomodulatory effects. IVIg is being used in inflammatory CNS conditions however robust evidence and guidelines are lacking in many disorders. Over the last 5 years, the percentage of IVIg used for CNS indications within neurology almost doubled in British Columbia (BC), Canada. Clear local guidelines may guide rational use. Methods: Consensus guidelines for IVIG use for CNS indications were developed by a panel of subspecialty neurologists and the Provincial Blood Coordinating Office, informed by focused literature review. Guidelines were structured similarly to existing BC peripheral nervous system guidelines and Australian Consensus Guidelines. Utilization and efficacy will be monitored provincewide on an ongoing basis. Results: Categories of conditions for Conditionally Approved (N=11) and Exceptional Circumstance Use (N=5) were created based on level of evidence for efficacy. Dosing and monitoring recommendations were made and outcomes measures defined. Rationale for Not Indicated conditions (N=2) was included. Guidelines were distributed to BC neurologists for feedback. This system will be re-evaluated after 1 year. Conclusions: IVIG use in CNS inflammatory conditions has an emerging role. Guidelines for use and monitoring of outcomes will help improve resource utilization and provide further evidence regarding effectiveness.

Background: Sensory ganglionopathy (SG) is a rare form of neuropathy affecting the dorsal root ganglia and leading to non-length-dependent sensory abnormalities. Although balance problems are frequently reported by patients, a comprehensive balance assessment in SG has not been conducted. This study quantifies balance deficits in SG and examines their relation to patient-reported outcome measures (PROMs). Methods: Prospective data was collected from five participants with SG. Balance assessments included Fullerton Advanced Balance scale, Berg Balance scale, and 360 degree turn. Participants completed PROMs assessing balance confidence (ABC scale), pain, fatigue, quality of life (QoL), and daily activity and participation. Assessment also included neurological exam, nerve conduction studies (NCS) and posturography. Results: All participants had severe SG on NCS with normal strength and significant sensory abnormalities. Balance scores indicated severe balance deficits in all participants and aligned with posturography and truncal sway measures. PROMs revealed low confidence in balance, high levels of pain and fatigue, difficulties with daily activities, and reduced QoL. Conclusions: Although balance testing is not part of routine clinical practice, PROMs and targeted assessment may help monitor patients with SG and their response to treatment. Larger sample sizes are needed to understand the impact of balance on PROMs and optimize bedside balance testing.

Background: Recent advances in management of peripheral nerve injuries is leading to a paradigm shift in the treatment of Canadian patients. Multi-disciplinary care models provide diagnostic, surgical and rehabilitative consultations within a single clinical encounter. Involvement of allied health care professionals has been shown to improve outcome. The purpose of this study was to ascertain the distribution and composition of multidisciplinary teams, and identify regional disparities. Methods: Representatives from clinics across Canada were invited to participate in a survey at the Annual Canadian Peripheral Nerve Symposium in London, Ontario in November 2019, with telephone follow up. Results: Delegates from 17 programs responded to the survey (12 academic centre and 5 community setting). Program provides electrodiagnostic testing, neuromuscular, rehabilitation and surgical assessment. Access to the following services was reported: occupational therapy=53% (9/17), physiotherapy 29% (5/17), research assistant=17% (3/17), social work=12% (2/17), mental health=6% (1/17). Conclusions: Complex nerve injury clinics are being established throughout Canada. Allied health care and research support are limited in many multi-disciplinary complex nerve injury programs. There is variable access, likely resulting in disparities in patient care across Canada. This data will be valuable for lobbying for resources for resources to improve the care of these complex patients.