OBJECTIVES/GOALS: The goal of theIntegrating Special Populations (ISP) Studiosis tointegrate communityvoice into research design and en hance diversity, equity, and inclusion in research, and disseminate findings in ways that improve health literacy and equity. METHODS/STUDY POPULATION: Based on the Vanderbilt Community Engagement Studio model, the ISP Studiowas designed through multiple phases, including Designand PilotStudioSessions. Stakeholders were diverse representatives of community and academic organizations serving special populations, as well asself-identified persons within special populations as defined by the NIH.Each phase of development and implementation of the Studio included an evaluation consisting of Likert scale and open-ended survey questions for process improvement and to integrate voices of the ISP community continuously. Demographic information and program outcomes were also collected via the evaluation survey. RESULTS/ANTICIPATED RESULTS: All Design Session (N=9) and Pilot Studio (N=10) participants indicated that the Design and Pilot were positive, relevant, bidirectionally useful, and fostered respect, trust, and inclusion. 100% of the panel strongly agreed the Studio met its goals and that the ISP Studios have potentialtobenefitspecial and under represented populations. Qualitative data and discussion on design will also be shared. Additi onaland relevant pointsincludepanelisttraining,compensation for community panelists, and ensuring accessibility. Evaluation outcomes from initial implementation of the ISP Studio will be discussed. DISCUSSION/SIGNIFICANCE: The ISP Studio is an innovative model that may increase engagement of special populations in the research process through co-creation and integration of lived experiences.It has the potential to improve research design, implementation, and impact.

There is currently considerable interest in the guided-jet mode, as a result of recent works demonstrating it being the upstream component of various resonant systems in high-speed flows. For given jet operating conditions, the mode is known to exist over only a finite-frequency range that, for a twin-jet system, has been observed to vary with both jet separation and solution symmetry. Vortex-sheet and finite-thickness linear stability models are here employed to consider the behaviour of the guided-jet mode as the two jets are brought together, for both a planar and round twin-jet system. It is demonstrated that in both cases as the twin-jet system merges it forms a higher-order mode of an equivalent single-jet geometry. This then imposes a constraint on the guided-jet mode as the finite-frequency range must change to meet that of the equivalent geometry the system merges to, explaining the previously observed dependence on jet separation.

Bentonites are readily available clays used in the livestock industry as feed additives to reduce aflatoxin (AF) exposure; their potential interaction with nutrients is the main concern limiting their use, however. The objective of the present study was to determine the safety of a dietary sodium-bentonite (Na-bentonite) supplement as a potential AF adsorbent, using juvenile Sprague Dawley (SD) rats as a research model. Animals were fed either a control diet or a diet containing Na-bentonite at 0.25% and 2% (w/w) inclusion rate. Growth, serum, and blood biochemical parameters, including selected serum vitamins (A and E) and elements such as calcium (Ca), potassium (K), iron (Fe), and zinc (Zn) were measured. The mineral characteristics and the aflatoxin B1 sorption capacity of Na-bentonite were also determined. By the end of the study, males gained more weight than females in control and Na-bentonite groups (p ≤ 0.0001); the interaction between treatment and sex was not significant (p = 0.6780), however. Some significant differences between the control group and bentonite treatments were observed in serum biochemistry and vitamin and minerals measurements; however, parameters fell within reference clinical values reported for SD rats and no evidence of dose-dependency was found. Serum Na and Na/K ratios were increased, while K levels were decreased in males and females from Na-bentonite groups. Serum Zn levels were decreased only in males from Na-bentonite treatments. Overall, results showed that inclusion of Na-bentonite at 0.25% and 2% did not cause any observable toxicity in a 3-month rodent study.

Linear stability theory (LST) is often used to model the large-scale flow structures in the turbulent mixing region and near pressure field of high-speed jets. For perfectly expanded single round jets, these models predict the dominance of azimuthal wavenumbers $m=0$ and $m = 1$ helical modes for the lower frequency range, in agreement with empirical data. When LST is applied to twin-jet systems, four solution families appear following the odd/even behaviour of the pressure field about the symmetry planes. The interaction between the unsteady pressure fields of the two jets also results in their coupling. The individual modes of the different solution families no longer correspond to helical motions, but to flapping oscillations of the jet plumes. In the limit of large jet separations, when the jet coupling vanishes, the eigenvalues corresponding to the $m=1$ mode in each family are identical, and a linear combination of them recovers the helical motion. Conversely, as the jet separation decreases, the eigenvalues for the $m=1$ modes of each family diverge, thus favouring a particular flapping oscillation over the others and preventing the appearance of helical motions. The dominant mode of oscillation for a given jet Mach number $M_j$ and temperature ratio $T_R$ depends on the Strouhal number $St$ and jet separation $s$. Increasing both $M_j$ and $T_R$ independently is found to augment the jet coupling and modify the $(St,s)$ map of the preferred oscillation mode. Present results predict the preference of two modes when the jet interaction is relevant, namely varicose and especially sinuous flapping oscillations on the nozzles’ plane.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

At the onset of the Covid-19 crisis, and with one of the largest and best-funded defined contribution programs in Latin America, Chile held over USD $200 bn in assets (or more than 80% of GDP). Reacting to populist pressures during the pandemic, however, the Congress gave non-retired participants three separate opportunities to tap into their retirement accounts, leaving some 4.2 million participants with zero retirement savings and draining around $50 bn from the system. This paper explores several hypotheses regarding why people withdrew their pension money early, and it also presents evidence regarding the likely impact of this short-term policy on long-term retirement wellbeing. We conclude with lessons for global policymakers seeking to protect pension assets critical for retirement security.

The recruitment of participants for research studies may be subject to bias. The Prospective Imaging Study of Ageing (PISA) aims to characterize the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer’s disease (AD). Participants approached to take part in PISA were selected from existing cohort studies with available genomewide genetic data for both successfully and unsuccessfully recruited participants, allowing us to investigate the genetic contribution to voluntary recruitment, including the genetic predisposition to AD. We use a polygenic risk score (PRS) approach to test to what extent the genetic risk for AD, and related risk factors predict participation in PISA. We did not identify a significant association of genetic risk for AD with study participation, but we did identify significant associations with PRS for key causal risk factors for AD, IQ, household income and years of education. We also found that older and female participants were more likely to take part in the study. Our findings highlight the importance of considering bias in key risk factors for AD in the recruitment of individuals for cohort studies.

Spatial linear stability analysis is used to study the axisymmetric screech tones generated by twin converging round nozzles at low supersonic Mach numbers. Vortex-sheet and finite-thickness models allow for identification of the different waves supported by the flow at different conditions. Regions of the frequency–wavenumber domain for which the upstream-propagating guided jet modes are observed to be neutrally stable are observed to vary as a function of solution symmetry, jet separation, $S$, and the velocity profile used. Screech-frequency predictions performed using wavenumbers obtained from both models agree well with experimental data. Predictions obtained from the finite-thickness model better align with the screech tones measured experimentally and so are seen to be an improvement on predictions made with the vortex sheet. Additionally, results from the finite-thickness model predict both symmetric and antisymmetric screech tones for low $S$ that are found in the vortex-sheet model only at greater $S$. The present results indicate that the feedback loop generating these screech tones is similar to that observed for single-jet resonance, with equivalent upstream and downstream modes.

Background: Colony stimulating factor 1 receptor (CSF1R) mutations have various clinical, often overlapping, phenotypes. Methods: Case report and literature review. Results: We present a case of a previously independent 49-year-old woman with a 3-year history of early- and insidious-onset, rapidly progressive symptoms resembling CBS (parkinsonism, severe apraxia, global cognitive impairments, personality changes, depression, and functional decline). Brain MRI showed severe atrophy with frontoparietal predilection, asymmetric ex vacuo dilatation, atrophic corpus callosum, and patchy, asymmetric T2/FLAIR hyperintensities in the subcortical white matter. Spine MRI showed no cord signals. Brain MR spectroscopy revealed elevated choline with reduced N-acetyl-aspartate levels. The vasculitis screening, and leukodystrophy and CADASIL workups were all unremarkable. Finally, whole exome sequencing was done and a heterozygous variant of CSF1R (c.1735C>T, p.Arg579Trp) was found. Conclusions: Our patient’s novel CSF1R variant was found to be associated with ALSP. This report supports the utility of a comprehensive genetic testing in adult patients clinically presenting as CBS but with white matter abnormalities on T2-weighted MRI. Given that ALSP has several other clinical and radiologic mimickers, whole exome sequencing proves fundamental and can improve the diagnostic rates and understanding of ALSP. A well-informed diagnosis can lead to appropriate preventive genetic counseling to affected families.

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.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.