OBJECTIVES/GOALS: Contingency management (CM) procedures yield measurable reductions in cocaine use. This poster describes a trial aimed at using CM as a vehicle to show the biopsychosocial health benefits of reduced use, rather than total abstinence, the currently accepted metric for treatment efficacy. METHODS/STUDY POPULATION: In this 12-week, randomized controlled trial, CM was used to reduce cocaine use and evaluate associated improvements in cardiovascular, immune, and psychosocial well-being. Adults aged 18 and older who sought treatment for cocaine use (N=127) were randomized into three groups in a 1:1:1 ratio: High Value ($55) or Low Value ($13) CM incentives for cocaine-negative urine samples or a non-contingent control group. They completed outpatient sessions three days per week across the 12-week intervention period, totaling 36 clinic visits and four post-treatment follow-up visits. During each visit, participants provided observed urine samples and completed several assays of biopsychosocial health. RESULTS/ANTICIPATED RESULTS: Preliminary findings from generalized linear mixed effect modeling demonstrate the feasibility of the CM platform. Abstinence rates from cocaine use were significantly greater in the High Value group (47% negative; OR = 2.80; p = 0.01) relative to the Low Value (23% negative) and Control groups (24% negative;). In the planned primary analysis, the level of cocaine use reduction based on cocaine-negative urine samples will serve as the primary predictor of cardiovascular (e.g., endothelin-1 levels), immune (e.g., IL-10 levels) and psychosocial (e.g., Addiction Severity Index) outcomes using results from the fitted models. DISCUSSION/SIGNIFICANCE: This research will advance the field by prospectively and comprehensively demonstrating the beneficial effects of reduced cocaine use. These outcomes can, in turn, support the adoption of reduced cocaine use as a viable alternative endpoint in cocaine treatment trials.

Background: The Canadian Registry for Amyloidosis Research (CRAR) is a nationwide disease registry of transthyretin (ATTR) and light-chain (AL) amyloidosis. Recent advances in disease-modifying therapy have improved prognosis, however there is a critical need for real-world evidence to address knowledge gaps, particularly longer-term therapeutic outcomes and surveillance strategies. Methods: A multi-stakeholder process was undertaken to develop a consensus dataset for ATTR- and AL-amyloidosis. This process included surveys to rank the importance of potential data items, and a consensus meeting of the CRAR steering committee, (comprised of multidisciplinary clinical experts, and patient organization representatives). Patients and patient organizations supported the development and implementation of a patient-reported dataset. Results: Consensus data items include disease onset, progression, severity, treatments, and outcomes, as well as patient-reported outcomes. Both prospective and retrospective (including deceased) patient cohorts are included. Further baseline data will be presented on an initial cohort of patients. Conclusions: CRAR has been established to collect a longitudinal, multidisciplinary dataset that will evaluate amyloidosis care and outcomes. CRAR has launched at multiple specialty amyloidosis centers nationally and is continually expanding. The growth of this program will promote opportunities to assess real-world safety and efficacy and inform the cost-effectiveness of therapies while supporting patient recruitment for research.

Shallow firn cores, in addition to a near-basal ice core, were recovered in 2018 from the Quelccaya ice cap (5470 m a.s.l) in the Cordillera Vilcanota, Peru, and in 2017 from the Nevado Illimani glacier (6350 m a.s.l) in the Cordillera Real, Bolivia. The two sites are ~450 km apart. Despite meltwater percolation resulting from warming, particle-based trace element records (e.g. Fe, Mg, K) in the Quelccaya and Illimani shallow cores retain well-preserved signals. The firn core chronologies, established independently by annual layer counting, show a convincing overlap indicating the two records contain comparable signals and therefore capture similar regional scale climatology. Trace element records at a ~1–4 cm resolution provide past records of anthropogenic emissions, dust sources, volcanic emissions, evaporite salts and marine-sourced air masses. Using novel ultra-high-resolution (120 μm) laser technology, we identify annual layer thicknesses ranging from 0.3 to 0.8 cm in a section of 2000-year-old radiocarbon-dated near-basal ice which compared to the previous annual layer estimates suggests that Quelccaya ice cores drilled to bedrock may be older than previously suggested by depth-age models. With the information collected from this study in combination with past studies, we emphasize the importance of collecting new surface-to-bedrock ice cores from at least the Quelccaya ice cap, in particular, due to its projected disappearance as soon as the 2050s.

Patient safety is a complex systems issue. In this study, we used a scoping review of peer-reviewed literature and a case study of provincial and territorial legislation in Canada to explore the influence of mandatory reporting legislation on patient safety outcomes in hospital settings. We drew from a conceptual model that examines the components of mandatory reporting legislation that must be in place as a part of a systems governance approach to patient safety and used this model to frame our results. Our results suggest that mandatory reporting legislation across Canada is generally designed to gather information about – rather than respond to and prevent – patient safety incidents. Overall, we found limited evidence of impact of mandatory reporting legislation on patient safety outcomes. Although legislation is one lever among many to improve patient safety outcomes, there are nonetheless several considerations for patient safety legislation to assist in broader system improvement efforts in Canada and elsewhere. Legislative frameworks may be enhanced by strengthening learning systems, accountability mechanisms and patient safety culture.

The medium- to long-term consequences of COVID-19 are not yet known, though an increase in mental health problems are predicted. Multidisciplinary strategies across socio-economic and psychological levels may be needed to mitigate the mental health burden of COVID-19. Preliminary evidence from the rapidly progressing field of psychedelic science shows that psilocybin therapy offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and maladaptive habitual patterns of cognition and behaviour, notably depression, addiction and obsessive compulsive disorder. The COMPASS Pathways (COMPASS) phase 2b double-blind trial of psilocybin therapy in antidepressant-free, treatment-resistant depression (TRD) is underway to determine the safety, efficacy and optimal dose of psilocybin. Results from the Imperial College London Psilodep-RCT comparing the efficacy and mechanisms of action of psilocybin therapy to the selective serotonin reuptake inhibitor (SSRI) escitalopram will soon be published. However, the efficacy and safety of psilocybin therapy in conjunction with SSRIs in TRD is not yet known. An additional COMPASS study, with a centre in Dublin, will begin to address this question, with potential implications for the future delivery of psilocybin therapy. While at a relatively early stage of clinical development, and notwithstanding the immense challenges of COVID-19, psilocybin therapy has the potential to play an important therapeutic role for various psychiatric disorders in post-COVID-19 clinical psychiatry.

The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Conservation resources are limited, yet an increasing number of species are under threat. Assessing species for their conservation needs is, therefore, a vital first step in identifying and prioritizing species for both ex situ and in situ conservation actions. Using a transparent, logical and objective method, the Conservation Needs Assessment process developed by Amphibian Ark uses current knowledge of species in the wild to determine those with the most pressing conservation needs, and provides a foundation for the development of holistic conservation action plans that combine in situ and ex situ actions as appropriate. These assessments allow us to maximize the impact of limited conservation resources by identifying which measures could best serve those species requiring help. The Conservation Needs Assessment complements the IUCN Red List assessment, and together they provide a more holistic guide to conservation priorities and actions. Conservation Needs Assessments generate national prioritized lists of species recommended for conservation action. These can subsequently be used to assist in the development of species recovery plans and national action plans, or to inform national conservation priorities better. Additional tools that will evaluate the recommendations for ex situ rescues, to determine the best candidates for conservation breeding programmes, are currently under development.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.

The physiological basis for tolerance and susceptibility of four lines of cucumber (Cucumis sativus L.) to the methyl ester of 3-amino-2,5-dichlorobenzoic acid (chloramben) was investigated. ‘MSU 3207’ and ‘MSU 0612’ were tolerant (T), whereas ‘MSU 3159’ and ‘MSU 0866’ were susceptible (S). Intraspecific variability was related to higher concentrations of chloramben in the roots of the susceptible lines, resulting from metabolic differences in these lines and rapid absorption of the herbicide by the roots of ‘S-MSU 3159’. Tolerance of ‘T-MSU 3207’ resulted primarily from low uptake and reduced translocation of the herbicide, while tolerance of ‘T-MSU 0612’ was related to, but not necessarily explained by, a peculiar 14C-label distribution pattern in the leaves. Thin-layer chromatographic analysis of methanol-soluble extracts from the lines studied 3 days after 14C-chloramben methyl ester treatment separated six 14C-metabolites in the roots and five in the shoots. After a 4-hr treatment, 14C-chloramben methyl ester was absorbed and translocated more rapidly than 14C-chloramben by all four lines. Tolerance or susceptibility did not always correlate with the total concentration of radioactivity in methanol-soluble shoot and root extracts.

A 136-m-long drill core of sediments was recovered from tropical high-altitude Lake Titicaca, Bolivia-Peru, enabling a reconstruction of past climate that spans four cycles of regional glacial advance and retreat and that is estimated to extend continuously over the last 370,000 yr. Within the errors of the age model, the periods of regional glacial advance and retreat are concordant respectively with global glacial and interglacial stages. Periods of ice advance in the southern tropical Andes generally were periods of positive water balance, as evidenced by deeper and fresher conditions in Lake Titicaca. Conversely, reduced glaciation occurred during periods of negative water balance and shallow closed-basin conditions in the lake. The apparent coincidence of positive water balance of Lake Titicaca and glacial growth in the adjacent Andes with Northern Hemisphere ice sheet expansion implies that regional water balance and glacial mass balance are strongly influenced by global-scale temperature changes, as well as by precessional forcing of the South American summer monsoon.

A 90,000-yr record of environmental change before 18,000 cal yr B.P. has been constructed using pollen analyses from a sediment core obtained from Salar de Uyuni (3653 m above sea level) on the Bolivian Altiplano. The sequence consists of alternating mud and salt, which reflect shifts between wet and dry periods. Low abundances of aquatic species between 108,000 and 50,000 yr ago (such as Myriophyllum and Isoëtes) and marked fluctuations in Pediastrum suggest generally dry conditions dominated by saltpans. Between 50,000 yr ago and 36,000 cal yr B.P., lacustrine sediments become increasingly dominant. The transition to the formation of paleolake “Minchin” begins with marked rises in Isoëtes and Myriophyllum, suggesting a lake of moderate depth. Similarly, between 36,000 and 26,000 cal yr B.P., the transition to paleolake Tauca is also initiated by rises in Isoëtes and Myriophyllum; the sustained presence of Isoëtes indicates the development of flooded littoral communities associated with a lake maintained at a higher water level. Polylepis tarapacana-dominated communities were probably an important component of the Altiplano terrestrial vegetation during much of the Last Glacial Maximum (LGM) and previous wet phases.