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Objectives/Goals: This study tests how fiber microstructural integrity and myelination levels within the cingulum connectome are associated with information processing speed (IPS) in relapsing-remitting multiple sclerosis (RRMS). We investigate the functional impact of structural coherence, myelin content, and white matter hyperintensities (WMH) load on IPS. Methods/Study Population: Data from 63 RRMS and 25 healthy controls (HC) were used. We hypothesize that the structural integrity of the cingulum bundle and its structural network – or connectome – is distinctly associated with IPS function in people with RRMS (vs. HC) due to myelin-related plasticity across the wiring. Using diffusion spectrum imaging and high-resolution tract segmentation, we constructed individualized white matter connectomes. Diffusion quantitative anisotropy (QA) and myelin fractions (MWF) were used to quantify structural coherence and myelination. WMH load was measured with T2-FLAIR imaging. Bayesian–Pearson correlations, mixed-linear, and moderation models explored how fiber-specific QA, MWF, and WMH load relate to IPS function in RRMS, as measured by Symbol Digit Modalities Test (SDMT). Results/Anticipated Results: We theorize that (1) QA in the cingulum connectome correlates with SDMT performance dimensionally, indicating that structural coherence in the white matter supports IPS function among both groups; (2) increased myelination will strengthen the positive association between QA and SDMT scores, suggesting that connectome-specific myelin content facilitates IPS; (3) conversely, WMH load within the cingulum connectome is expected to inversely correlate with SDMT scores, reflecting the detrimental impact of lesion burden on IPS function; (4) myelination in specialized tracts within the cingulum connectome play a compensatory role to support IPS function in the RRMS group. These investigations can offer a mechanistic clue to potential neuroplastic targets for cognitive interventions in MS. Discussion/Significance of Impact: By linking white matter integrity to cognitive function at the connectome level, this study can support neuroregenerative strategies to mitigate cognitive burden in RRMS. Our findings may advance understanding of how structural coherence, tract myelination, and WMH affect IPS, shaping personalized prognostic and therapeutic interventions.
Objectives/Goals: Radiation nephropathy results in morbidity and mortality in patients receiving cancer treatment. In addition, low birth weight and low nephron number are associated with increased risk for chronic kidney disease. This study examined the development and severity of radiation-induced renal hemodynamic dysfunction in a low renal mass mouse model. Methods/Study Population: Male mice (C57Bl/6, 8–12-weeks) were used to determine a suitable radiation dose regimen. Mice were subjected to fractionated bilateral kidney irradiation with 5–6 fractions of an X-ray dose of 0, 6, 8, and 10 Gy at 24-hr intervals using a CT-image-guided irradiator. Body weight and mortality were monitored for 5 weeks in mice. In a separate set of experiments, the low renal mouse model, ROP Os/+, and their normal counterpart, ROP +/+ mice were subjected to 5 fractionated bilateral kidney irradiations at 24-hr intervals with an X-ray dose of 6 Gy. Renal blood flow was assessed from renal artery resistive index (RRI) over 5 weeks post-irradiation using an ultrasound system. Transcutaneous measurement of FITC-sinistrin clearance was used to determine glomerular filtration rate (GFR). Results/Anticipated Results: The C57Bl/6 mice that received 5–6 fractions of 8 and 10 Gy had more than 50% mortality, while 100% of the mice exposed to 5 fractions of 6 Gy survived for 5 weeks. Body weight was also significantly decreased in mice exposed to 5 or 6 fractions of 8 or 10 but not 6 Gy radiation. Nonirradiated C57Bl/6, ROP +/+, and ROP Os/+ mice had similar baseline GFR and RRI. Irradiation of 5 fractions at 6 Gy decreased GFR and increased RRI in C57Bl/6 and ROP +/+ mice. Interestingly, following 5 fractions at 6 Gy irradiation ROP Os/+ mice had 25% lower GFR than wild-type ROP +/+ mice (946.3 ± 50.3 vs. 1232.9 ± 69.3 µL/min/100g BW, p Discussion/Significance of Impact: Our study determined a suitable fractionated bilateral kidney irradiation dose regimen to evaluate radiation nephropathy. Data demonstrated that fractionated bilateral kidney irradiation leads to decreased renal hemodynamics in mice. We also demonstrated that irradiation caused greater renal hemodynamic dysfunction in low renal mass mice.
Objectives/Goals: Youth with IBD have preventive, psychosocial, and acute care needs beyond those of peers, yet receipt of services does not match those needs. Our objectives are to assess the feasibility of (1) an individualized care plan intervention to improve perceived and measured care quality and (2) a pragmatic trial design embedded in pediatric IBD practice. Methods/Study Population: This is a pilot rollout-design randomized trial (n = 60) at a regional academic medical center. Eligible patients are 13–19 years old with IBD for at least 3 months and scheduled for a follow-up visit during the trial. Research staff recruits from one cluster at a time until goal enrollment (14–16). Enrollees are randomized 1:1 to intervention (MyIBD now) or control (MyIBD after the trial). MyIBD combines a tabular summary of individualized acute, chronic, and preventive care needs with nurse facilitator support for patients to use the information. Surveys at baseline, 6 and 12 months measure care quality (Patient Assessment of Chronic Illness Care scale, vaccines, health services) and patient self-management skills (Partners in Health scale). Implementation outcomes are collected via chart review. Results/Anticipated Results: To date, 44 subjects have been randomized. Among subjects, the mean age is 16 years; 73% have Crohn’s disease, 77% have commercial insurance, 75% receive anti-TNF therapy, and 14% live in a rural area. Mean baseline perceived care quality (PACIC scale) is 76.9 (sd 16.3; out of 100); mean baseline perceived self-management skill (PIH scale) is 78.1 (sd 13.4; out of 96). On objective care quality measures, 59% have completed the HPV vaccine series, 32% have received an additional pneumonia vaccine; in the past year 68% have had a screening for mood disorders, 20% an emergency department visit for IBD, and 18% an IBD hospitalization. To date, the IBD clinical team has achieved 100% completion (intervention subjects receive MyIBD plus nurse facilitation) and 0% contamination (control subjects inappropriately receive MyIBD). Discussion/Significance of Impact: Study results to date support the feasibility of the pragmatic, embedded trial design and indicate opportunities for improvement in care quality as perceived by patients and as measured by common preventive and acute care quality indicators. An individualized care plan supported with nurse facilitation may improve pediatric IBD care quality.
Objectives/Goals: Clinical relevance of preclinical animal models is commonly in question. Herein, we investigated locoregional tumor immune microenvironment (TIME) differences in tumor-bearing murine oral cancer models, unresponsive to traditional immunotherapy, and also developed an oral tumor resection model to ultimately enhance translational relevance. Methods/Study Population: Here, we utilized carcinogen-induced, HPV-negative preclinical oral cancer models. For TIME studies, ROC1 cells were maintained as published. ROC1 tumors were established in the murine flank and oral cavity of wildtype C57Bl/6 mice, and tumor growth kinetics were assessed at each site. At distinct stages of tumor growth, tumors were harvested, as well as their respective corresponding inguinal and cervical tumor-draining lymph nodes (tdLNs). Multiparameter 28-marker spectral flow cytometry was performed to analyze immune cell populations at each site. For tumor resection studies, MOC2 tumors were similarly maintained and established in the oral cavity. MOC2 tumors were accessed via midline transcervical incisions. Upon tumor excision, wounds were closed with multiple interrupted Vicryl sutures. Results/Anticipated Results: We anticipated no differences between heterotopic and orthotopic tumor sites. Both sites displayed an initial period of delayed ROC1 tumor growth followed by rapid progression. Comprehensive analyses revealed low T cell infiltration overall and increases in select myeloid cells (i.e., macrophages and dendritic cells) over time in both models. Other immune cell types, however, generally increased over time in the flank. Differences between corresponding tdLNs further indicate deviating changes in immunosuppressive phenotypes (i.e., regulatory T cells and macrophages) and immune checkpoint marker expression. Additionally, MOC2 oral tumors were successfully resected with no visible remaining tumor. No subsequent healing complications were observed, and tumor recurrence occurred within 1 week post-surgery. Discussion/Significance of Impact: Tissue-specific TIME and tdLN differences may impact antitumor treatment and response. Ability to resect orthotopic tumors allows for modeling of standard-of-care treatment for oral cancer. These studies can enable tailoring of therapeutic strategies and provide insight into model selection and data interpretation from translational studies.
Objectives/Goals: The creatine (Cr) system is impaired in Alzheimer’s disease (AD). Data show that creatine monohydrate (CrM) supplementation may improve AD symptoms in AD mouse models, but no human studies have been reported. Thus, we investigated whether an eight-week CrM supplementation was feasible and associated with increased brain creatine in patients with AD. Methods/Study Population: Twenty participants with probable AD were allocated to an open-label, eight-week intervention of 20 g/day CrM. Fasting blood draws were taken at baseline, 4-, and 8-week visits to measure serum creatine (Quest Diagnostics). 1H magnetic resonance spectroscopy was performed at baseline and 8-week visits to measure brain Cr as a ratio to unsuppressed water. Self-reported compliance (with assistance from study partners) was assessed with daily CrM trackers. The mean compliance percentage across all participants was used to describe overall compliance with the intervention. We used paired t-tests to analyze the mean changes in serum Cr levels from baseline to 4- and 8-week visits and the mean change in brain Cr from baseline to 8-week visits. Statistical significance was set at p<0.05. Results/Anticipated Results: Participants were 65% male with a mean age of 73.1±6.3 years. All participants completed the study, with 19 out of 20 achieving the dose compliance target of ≥80%. The mean self-reported dose intake was 90%. Serum Cr levels were significantly increased at 4- and 8-week visits compared to baseline (0.6±0.4 mg/dL vs. 14.0±9.9 mg/dL and 15.0±13.6 mg/dL, respectively; p<0.001). Brain Cr levels also significantly increased (330.5±36.80 i.u. vs. 366.9±57.52 i.u., p<0.001). Discussion/Significance of Impact: We are the first to demonstrate that 20 g/day of CrM for eight weeks is feasible and associated with increased brain Cr in patients with AD. Our findings support further investigation of brain target engagement of CrM and its efficacy in AD. With AD cases expected to rise, CrM could serve as an effective, affordable therapeutic to slow AD progression.
Objectives/Goals: Communication between clinicians and parents of seriously ill infants is understudied. This study aims to 1) define high-quality communication with parents of critically ill infants and 2) evaluate the psychometric properties and validity of a measure of high-quality communication in parents of critically ill infants. Methods/Study Population: 1) Using participant observation and semi-structured interviews of 35 parents of hospitalized infants, I will conduct content analysis to describe high-quality prognostic communication with parents of infants in the pediatric intensive care unit. Using descriptions captured during participant observation and in semi-structured interviews, I will produce a novel definition of high-quality communication with parents of seriously ill infants. I will also explore parent experiences of communication by race. 2) I will validate a measure of communication quality in parents of 200 neonatal and pediatric intensive care unit patients. I will use factor analysis to evaluate the extent to which responses map onto an established construct and assess dimensionality and reliability. Results/Anticipated Results: 1) I anticipate finding that identification of high-quality communication will be consistent between participant observation and interviews and will track with Wreesmann’s framework. I hypothesize that minoritized parents are more likely to receive low-quality communication. 2) I hypothesize that the measure of communication quality will be valid and reliable in the neonatal and pediatric intensive care units. Discussion/Significance of Impact: I will explore communication quality in a novel setting for which limited data are currently available, establishing a measure for future pediatric communication research and identifying targets for interventions to improve communication quality. Better understanding of communication with parents of sick infants will lead to improved outcomes.
Unhealthy lifestyle behaviors are prevalent among people with mental illness (MI), affecting their physical and mental health. Most research has focused on the isolated effects of lifestyle behaviors, leaving the interconnectedness between these behaviors and health outcomes unexplored. This study aimed to examine these relationships and identify the most strongly connected lifestyle behavior or health outcome within a network.
Methods
We conducted a cross-sectional study with 423 inpatients with MI, receiving care as usual. Lifestyle behaviors, physical and mental health outcomes were assessed through questionnaires and routine data. A Gaussian Graphical Model was estimated, and strength centrality was calculated to identify the most influential nodes.
Results
Mean age was 55.5 years, 42% were female, and 41% were diagnosed with schizophrenia. Psychological and physical quality of life (QoL), nighttime sleep problems, and overall sleep quality were the most strongly connected nodes. Sleep was strongly associated with physical QoL. Furthermore, there were negative associations between healthy food intake and cholesterol ratio, and positive associations between daily doses of antipsychotics and length of hospital stay. Node strength was stable (CS(cor = 0.7) = 0.75). No clear pattern emerged among other lifestyle behaviors and health outcomes.
Conclusions
This study offers insights into the interrelatedness of lifestyle behaviors and health outcomes. Addressing sleep problems could enhance QoL and potentially influence other health outcomes. Psychological and physical QoL were also strongly associated, emphasizing the importance of perceived well-being in health outcomes. Future research could explore causal pathways to identify treatment targets to improve care.
Objectives/Goals: Investigating the B-cell acute lymphoblastic leukemia (B-ALL)-associated germline SNP rs7090445, located in intron 3 of ARID5B, which is more frequently observed in individuals of Hispanic/Latino descent. Investigating the mechanisms behind this inherited single nucleotide polymorphisms (SNP) that may contribute to the higher incidence of B-ALL in this population. Methods/Study Population: Specific Aim 1: We hypothesize ARID5B SNP rs7090445 disrupts intrinsic enhancer function. Identification of critical DNA looping events impacted by ARID5B variants using Capture C. Affinity purification-mass spectrometry to identify potential ARID5B transcription mediators. Specific Aim 2: We hypothesize the B-ALL-associated SNP leads to a partial human B-cell differentiation block. Utilize Cas9-mediated homology-directed repair to create ARID5B SNP in primary human hematopoietic stem cells. Gene-edited HSCs will be differentiated into B cells using an ex vivo system. Fluorescence-activated cell sorting to sort our pool of cells into stages of B-cell development spectrum. Amplicon sequencing and variant allele frequency of rs7090445 SNP to evaluate its impact on B-cell development. Results/Anticipated Results: This proposal is conceptually innovative as it seeks to understand the mechanism by which the B-ALL-associated SNP rs7090445 in intron 3 of ARID5B disrupts enhancer function and investigates its impact on human B-cell development. Future research will investigate a tumor-suppressive role of ARID5B and whether it constitutes a “first-hit” of leukemogenesis. Discussion/Significance of Impact: Successful completion of this research will elucidate the critical role of the B-ALL-associated ARID5B SNP rs7090445 in human B-cell development and leukemogenesis. As this SNP is more prevalent in Hispanic/Latino populations, it will also provide crucial insights into the genetic factors behind the elevated incidence of B-ALL.
Objectives/Goals: Youth-onset diabetes and its risk factors are increasing in ethnic and racial minority communities. Our mixed-methods study aimed to explore the associations between participation in a community youth sports program and key diabetes risk factors in youth, including mental health, physical activity, nutrition, and weight status. Methods/Study Population: We used a single cohort, mixed-methods design focused on the Community Leadership Revolution (CLR) Academy, a local youth sports program. Participants, ethnic and racial minority youth ages 5–14, were recruited to assess their mental health, physical activity, and nutrition using validated and reliable questionnaires. Weight status was measured via bioelectrical impedance. Group interviews with youth and individual interviews with staff provided context for the quantitative results. A thematic analysis of the qualitative data will further explore how CLR Academy may impact diabetes risk factors. Results/Anticipated Results: We recruited 24 CLR participants (16 boys/8 girls) and 4 CLR staff (3 males/1 female). Sixteen youth identified as African-American, while the rest identified as multiracial. Correlations revealed that higher attendance at CLR Academy was negatively associated with mental health scores, specifically total, externalizing, and hyperactive scores (all p < 0.01). Higher CLR attendance was negatively associated with physical activity during spare time (p < 0.05), waist circumference (p< 0.05), and waist-to-height ratio (p < 0.01). Being a girl was associated with lower diet quality and physical activity (both p < 0.05). Qualitative data highlighted life skills and supportive relationships in CLR as key factors in improving health outcomes. Thematic analysis is ongoing to clarify these relationships. Discussion/Significance of Impact: This study highlights how participation in programs like CLR Academy may improve ethnic and racial minority youth diabetes risk factors. Staff and participant insights on mechanisms driving these health improvements may offer strategies that can be applied to similar programs focused on reducing marginalized youth’s diabetes risk.
Objectives/Goals: This study aims to gather user feedback from clinical research professionals on the usefulness and relevance of regulatory resources found on a new regulatory web portal, OpenRegSource, to enhance its usability, thereby advancing this project from the initial to the full implementation phase of the implementation science framework. Methods/Study Population: The Regulatory Knowledge and Support core of the Southern California Clinical and Translational Science Institute developed a regulatory web portal called OpenRegSource to help researchers gain basic regulatory information prior to professional and/or paid consultation. Before publicly launching, a virtual focus group (FG) composed of 21 members of the local clinical research workforce was given two weeks to explore the web portal and answer three surveys. Two other research professionals also gave feedback outside of the focus group. The user feedback data was analyzed and discussed by the web portal project team. Updates were then made accordingly. Once the portal was launched, a plan was implemented to collect usage metrics and additional feedback for continuous improvement. Results/Anticipated Results: Of the 21 FG participants, 20 completed the feedback survey specifically for their experience with the web portal. 65% (13/20) said the number of resources was just right. 90% (18/20) found the resources to be very relevant to their respective topics. 85% (17/20) found the resources very useful and somewhat useful to their daily work activities. 75% (15/20) found the organization of the portal to be good or very good. 85% (17/20) found it very easy and somewhat easy to navigate the web portal. 90% (18/20) found the portal to be effective in providing its audience with a basic understanding of regulatory requirements. 95% (19/20) found the portal useful for novice research professionals. 85% (17/20) found the web portal useful overall. Participants were also able to provide commentary feedback for specific pages. Discussion/Significance of Impact: Obtaining stakeholder input during the development of a resource or tool is essential to ensure the final product meets user needs and is effectively utilized. In this case, involving the feedback of clinical researchers will help improve OpenRegSource to better facilitate the advancement of their work.
Objectives/Goals: By synergizing our efforts, we believe this to be a fruitful collaboration for UCLA Clinical and Translational Science Institute (CTSI) and California Institute for Regenerative Medicine (CIRM). With multiple levels to stem cell training, focusing on specific educational goals is integral to our pilot event. This was held on July 26th and offered an exciting and valuable day for trainees. Methods/Study Population: Leadership was comprised of leaders at the UCLA Health Alpha Clinic, Broad Stem Cell Research Center (BSCRC), Human Gene and Cell Therapy Facility (HGCTF), UCLA Campus, Clinical and Translational Research Center (CTRC), and the Santa Barbara COMPASS program. Trainees from UCLA, CSUN, and UCSB were represented. The agenda included a didactic overview of the entire translational and clinical research process from discovery in the laboratory to bedside nursing in the patient care areas. Onsite tours were conducted at the HGCTF and the CTRC with a meet and greet with the nurses. The curriculum covered the clinical research process, regulatory requirements, ethics, current clinical trials, manufacturing, quality control, and compliance. A career opportunities discussion and network sessions closed out the day. Results/Anticipated Results: Of the 13 trainees who attended the session, 10 replied to the evaluation survey. All the responding students (100%) rated the event as “excellent” and found it to be “highly valuable” to their current training program. The trainees indicated that they were “very likely” (100%) to recommend a friend to attend this type of event. When asked what they liked most about the event, they indicated that the programming was “insightful, and “inspiring” for seeing beyond their current trainee responsibilities. They valued the responsiveness to questions, sharing experiences, and mentoring for career advancement. They especially liked the tours at the HGCTF and the session with the front-line nurses. Changes for the future will include timing and length, information on graduate programs and more student interactions. Discussion/Significance of Impact: Overall, our first educational session was very well-received by both trainees and staff involved as stakeholders. Due to the success of this inaugural event, we intend to continue to draw on the expertise of this collaboration and use a similar blueprint for future events and scientific sessions.
Objectives/Goals: This Weill Cornell Clinical and Translational Science Collaborative (CTSC) project evaluates whether large language models (LLMs) can generate accurate summaries of translational science benefits using the Translational Science Benefits Model (TSBM) framework, aiming to identify optimal LLMs and prompting strategies via expert review. Methods/Study Population: We are using prompt engineering to train multiple LLMs to generate one-page impact profiles based on the TSBM framework. LLMs will be selected via benchmarks, focusing on models excelling in information extraction. Leading LLMs (e.g., Llama 3.2, ChatGPT 4.0, Gemini 1.5 Pro, and Claude) and other high-performing models will be considered. Initial work has utilized Gemini 1.5 Pro. Models use data from CTSC-supported projects in WebCAMP, our local instantiation of a translational research activity tracking system used by >20 CTSA hubs, and manuscripts from the Overton database cited in policy documents. Human experts will evaluate the quality and accuracy of LLM-generated profiles. Results/Anticipated Results: Preliminary results using Gemini 1.5 Pro indicate that LLMs can generate coherent and informative impact profiles encompassing diverse areas within the TSBM. Face validity appears satisfactory, suggesting the outputs align with expectations. We anticipate that further exploration with other LLMs and expert validation will reveal strengths and weaknesses of the LLM approach, including the potential for naccuracies (“hallucinations”), informing further refinement of models and prompting strategies. Analysis of manuscripts cited in policy will provide valuable insights into communicating policy-relevant benefits effectively, and benchmark comparisons will identify optimal LLMs for this use case. Discussion/Significance of Impact: This project demonstrates LLMs’ potential for streamlining and enhancing impact reporting in translational science, enabling broader dissemination of research outcomes and promoting better understanding among stakeholders. Future work will integrate LLM-based reporting into research infrastructure.
Objectives/Goals: Ventilator-associated pneumonia (VAP) is an infection caused by bacteria, viruses, or fungi during mechanical ventilation. We analyzed a cohort of COVID-19 patients admitted to the intensive care unit with respiratory failure with different VAP outcomes. We hypothesize that the multiomics data can help predict VAP development within this cohort. Methods/Study Population: We recruited participants from a cohort on a NYU IRB protocol (i22–00616), who had COVID19 respiratory failure, admitted to ICU, and required invasive mechanical ventilation (n = 245). We collected and analyzed research specimens (bronchoalveolar lavage [BAL, n = 213], tracheal aspirates [n = 246], background [n = 18]) and clinical cultures (sputum and BAL) for 245 participants. A panel of experts adjudicated VAP within the cohort, resulting in 92 VAP diagnoses. We annotated metatranscriptome (Illumina NovaSeq) using a Kraken/Bracken database, and KEGG for functional annotation of transcriptome data (Illumina HiSeq). We used edgeR (v.4.0.16) to analyze differential expression of metatranscriptome and transcriptome data. Results/Anticipated Results: We diagnosed VAP in n = 92 (38%) participants. We found significant differences in days of overall hospital stay (p Discussion/Significance of Impact: VAP is a serious complication of mechanical ventilation, and oral commensals alter the lung microbiome and host immunity. We identified a transcriptome-metatranscriptome signature that identifies those at VAP risk. VAP was associate with both pro- and anti-inflammatory gene expression resulting in increased risk for lower airway infection.
Objectives/Goals: The prevalence of type 2 diabetes (T2D) in adolescents is rising, presenting unique challenges for recruitment in clinical research – particularly among adolescents who belong to minoritized race/ethnic backgrounds. The primary aims of our study are to identify and address barriers to recruiting adolescents, particularly around community trust. Methods/Study Population: This study employed a two-phase approach to evaluate recruitment strategies for underrepresented adolescent populations in genomics studies of T2D. After IRB approval, in Phase 1, we utilized the electronic medical record (EMR) system at Children’s of Alabama to prescreen based on inclusion criteria (adolescents aged 12–18 years with T2D). Recruitment efforts were tailored to address barriers unique to underrepresented populations, such as flexibility in scheduling contact times to accommodate family availability. In Phase 2, we are implementing and assessing the effectiveness of a peer recruitment model, wherein adolescents from underrepresented groups are trained to engage peers within their community. Focus groups (6–8 participants per group) will explore facilitators and barriers to recruitment. Results/Anticipated Results: Phase 1 revealed that EMR prescreening effectively identified eligible participants, and direct outreach (phone calls, face-to-face contact during clinical visits) significantly improved recruitment success, especially among underrepresented adolescents. Flexible scheduling and consolidating study appointments enhanced participation, addressing logistical challenges like geographic distance. However, frequent changes in contact information (phone and email information) created barriers. In Phase 2, early focus group results suggest that peer recruitment is promising, with trust and community engagement being key factors. Adolescents recruited by peers were more likely to participate, though logistical hurdles such as transportation and family concerns remain. Discussion/Significance of Impact: Our study demonstrates the value of personalized outreach and prescreening in improving recruitment among adolescents. These strategies can engage communities that include Black, Indigenous, and People of Colored. These findings underscore the need for flexible recruitment strategies to ensure their participation in T2D adolescent research.
Objectives/Goals: Returning genetic research results to participants can improve community engagement and enhance health equity. Providing research investigators with a convenient and cost-effective pathway for returning genetic findings, along with ensuring the necessary criteria for validity and utility, may reduce the barriers to returning results. Methods/Study Population: The ICTS Precision Health Genomic Return of Research Service Core (ICTS PH gROR) developed a process of returning genetic findings to participants who have indicated their preference to be notified of any findings that may impact their health. The service includes returning primary findings (actionable results discovered as part of the Investigator’s approved IRB study) and/or secondary findings [clinically actionable genes by the American College of Medical Genetic and Genomics (ACMG)]. Participants with positive findings will receive a written report, generated by a board-certified clinician specializing in genetics or molecular genetic pathology. A visit with a genetic counselor provides additional resources and guidance on the identified health risks. Results/Anticipated Results: Centralizing a service for the return of genetic results will ensure best-practices and minimize the burden. By offering results at no cost to the participant or their family, the service promotes accessibility and removes financial barriers that could otherwise prevent individuals from benefiting from genetic insights. Furthermore, by involving expert oversight committees and genetic counselors in the process, participants will receive accurate information and appropriate guidance, enhancing their understanding of the results and empowering them to address any potential health risks. Subsidizing the service with the CTSA grant keeps the costs predictable and manageable for investigators. Discussion/Significance of Impact: This approach recognizes the importance of informed consent, ethical considerations, and the potential social implications associated with genetic findings. Through open communication, participants are actively involved in the decision-making process and have the opportunity to seek further resources and support.
Objectives/Goals: Syncope is a common diagnosis in observation medicine, and characterization of observation patients is often limited to single unit, single center, or single payer systems. TriNetX, a federated deidentified multicenter national public database, provides an opportunity to study these patients from across the USA. Methods/Study Population: This retrospective cohort study queried data from 56 health care organizations (HCO) in TriNetX to examine differences between observation patients with syncope who required admission vs. those who were discharged. All observation stays with a diagnosis of syncope, defined by ICD-10, CPD, and SNOWMED codes, were queried. A total of 281,162 observation encounters were included in analysis, of which 46.4% (n = 130,357) were admitted and 53.6% (n = 150,805) were discharged. Data on age, gender, race, ethnicity, presence of congestive heart failure, EKG, and serum labs were collected for comparative analysis. T-test and Chi-square analyses were deployed with significance = p Results/Anticipated Results: The cohorts demonstrated statistically significant differences across all demographic factors, however, they were not clinically meaningful. Clinically significant differences include that only 72.8% of admitted patients and 68.3% of discharged patients had an EKG recorded in TriNetX during the period of observation (p Discussion/Significance of Impact: Patients admitted from observation status were more likely to have CHF, higher BNP, and pro-BNP values. TriNetX is a powerful tool to study patients across multiple hospital systems and payer types. Limitations, however, include incomplete data and inaccuracies among claims records.
Objectives/Goals: The goal of this proposal is to better understand how informing African Americans of their genetic risk affects their behavior as part of a cardiovascular disease (CVD) risk reduction intervention. Aim 1: To determine the effect of genetic risk knowledge on CVD health behavior. Aim 2: To determine the effect of genetic risk knowledge on secondary variables. Methods/Study Population: Method: Fifty participants from the Baton Rouge metropolitan area will be recruited. Participants must be African American adults over the age of 18. Potential participants will be recruited using community-based efforts that have been successful in recruiting this population specifically. Participants will be randomized into one of two groups. Genetically Unblinded Group (GU) will be “genetically unblinded” after baseline orientation. Genetically Blinded Group (GB) will be “genetically blinded” until the end of the study. This study design ensures that we can measure the impact of knowledge of genetic risk on participant behavior. Results/Anticipated Results: Baseline participants’ characteristics (body mass index, blood glucose, and cholesterol) will be summarized by intervention group, with counts and percentages for categorical variables and means and 95% confidence intervals for continuous variables. Primary Outcomes: Attendance in intervention sessions will be counted across groups. Effect on genetic risk knowledge will be determined via comparing the difference between the increased healthy lifestyle behaviors at endpoint between Genetically Unblinded (Cases) and Genetically Blinded Groups (Control). Secondary and Tertiary Outcomes: Mean change in secondary outcomes in the GU group will be compared against the mean change in the GB group. Participant’s survey responses and changes in physical measurement from baseline to endpoint will be observed. Discussion/Significance of Impact: This study empowers African Americans in Baton Rouge by providing genetic risk knowledge for cardiovascular disease. By addressing social determinants of health, it promotes behavior change, improves health outcomes, and fosters trust, potentially reducing health disparities and advancing health equity.
This paper considers how education can address two persistent problems concerning directors of smaller companies. Virtually anyone can be a company director, even though this is a complex role with significant impacts. Director disqualification is the main filter, to instil market morality and improve standards among directors. Yet disqualification lacks any rehabilitative element, and it is doubtful whether it is effective in raising standards, given persistent problems, including phoenix companies and rogue traders. We consider whether education might usefully improve the effectiveness of disqualification through a rehabilitative element. Rehabilitative approaches can also potentially help other directors, who have failed, to try again. We also consider the potential of an optional education programme for directors who have experienced company failures and have not been disqualified.
Drawing upon examples of education being used to raise standards in other contexts, as well as educational theories in relation to adult learners, the paper shows how education might: (1) strengthen the disqualification system; and (2) support directors who are outside the disqualification system to start again after a failure. Both aspects are important to market integrity as well as economic opportunity.
Objectives/Goals: Research supports the use of music to improve the care and well-being of adults living with dementia; however, the practice and implementation of music in elder care communities is not regulated. The goal of this qualitative study was to survey elder care communities in Northeast Kansas to determine the use of music with people living with dementia. Methods/Study Population: We interviewed staff (n = 10) at five elder care communities in the Kansas City Metro area and observed musical activities and artifacts in shared living spaces within each community. Interview questions included details of the frequency and purpose of using music, who determined which music to use, and any effects, positive or negative, the interviewee believed to be associated with the use of music. Musical events, visiting musicians or music therapists leading group sing-alongs were observed at two communities, and music-related activities led by staff were observed at two others. Results/Anticipated Results: Music was used in some way at each of the five communities. Each location had recorded music available to residents in the shared living spaces, and most had a piano in the main lounge area. During the sing-along and music-related activities, residents were observed singing along to songs from memory, engaging with one another and the group leader and smiling. Staff employed by each community varied in their level of musical training and experience, from none to a full-time music therapist in residence. Staff interviewed said they believed music was helpful to aid memory recall, reduce anxiety, and to engage interest. Interestingly, a music therapist at one site also described how music during mealtimes created too much of a distraction for residents and interfered with dietary care. Discussion/Significance of Impact: It is clear from both the staff interviews and direct observations of musical activities that music is important to consider for people living with dementia in care communities. Guidelines for implementation and minimum standards would be helpful to ensure all care community residents can experience benefits highlighted by staff in this study.
One of the tendencies among scribes who transmitted the corpus Philonicum was to divide treatises into smaller units. This article argues that Philo’s De gigantibus and Quod Deus sit immutabilis were originally a single treatise that scribes split in an effort to create thematic unities for each half. Two lines of evidence support this conclusion. There is significant evidence that the two treatises circulated as a single work in antiquity. The most important evidence lies in the titles. Eusebius knew a compound title for a single work and the eighth-century compilers of the Sacra parallela attributed fragments from Quod Deus sit immutabilis to De gigantibus. The second line of evidence is internal. De gigantibus is noticeably shorter than any other treatise in the Allegorical Commentary with the exception of De sobrietate that may be incomplete. More importantly, the work concludes with an internal transitional phrase that introduces the citation that opens Quod Deus sit immutabilis. While Philo creates a bridge between treatises, this is an internal transition marker. For these reasons, we should discontinue following the scribal tradition and reunite the two halves of Philo’s treatise.