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Enrollment Patterns and Site-Level Predictors of Black Participant Recruitment to a Multisite Randomized Cancer Clinical Trial
Get PDFPURPOSE Lack of race- and age-diversity in clinical trials adversely affects generalizability of trial results and equity of trial access. Research on barriers to representative accrual has focused on patient-level factors. We aimed to define site-level factors affecting the diversity of accrual to a multicenter clinical trial. METHODS Alliance 191901 (GETSET) is a national randomized controlled trial testing interventions to promote breast cancer endocrine therapy adherence, which oversamples Black women and those under age 50 years at 30% thresholds. A secondary study objective is to examine site-level factors associated with accrual of Black and younger participants. At 50% accrual to the parent study, we performed prespecified analyses of association between site characteristics (region, neighborhood racial composition, Alliance membership type, number of recent accruals to cooperative research group trials) and the proportion of Black patients and younger patients accrued. We also examined trajectories of accrual over time for race- and age-specified subgroups. RESULTS The analysis included 124 sites. Among 590 participants, 9.7% were Black, and 22.4% were age <50 years. Neither site type nor historical accrual volume was associated with Black participant recruitment. Southern sites recruited higher proportions of Black participants (19.0% v 7.3% for West, P < .001). Neighborhood racial composition was positively associated with recruitment of Black participants (16.2% at sites from highest Black composition v 1.4% in lowest, P < .01). Recruitment trajectories of Black participants were slower than target rates, whereas those among non-Black participants were faster. CONCLUSION Neighborhood composition and geographic region were predictors of proportions of Black participants accrued to A191901 sites, but site type and historical accrual volume were not. When trials must limit site selection, identifying sites based on neighborhood composition and geography may be an appropriate tool for increasing trial diversity
Functional analysis of TWIST1 domains regulating smooth muscle cell phenotype
Get PDFIntroduction TWIST1, a bHLH transcription factor, regulates mesenchymal specification, differentiation, proliferation and migration during development and in diseases such as cancer. More recently, genome-wide association studies have identified TWIST1 as a causal gene that increases risk for multiple vascular diseases, including atherosclerosis and hypertension. However, its molecular role in the vascular wall remains unclear. Methods In this study, we interrogated how TWIST1 dimer composition and discrete TWIST1 domains affect SMC phenotype by expressing forced TWIST1 dimers or TWIST1 variants lacking specific domains, followed by bulk RNA sequencing and proliferation and migration assays in human coronary artery SMCs (HCASMCs). Results We found that TWIST1 homodimers had only modest transcriptomic effects but strongly promoted migration and proliferation–effects abolished by deletion of the TWIST1 N-terminus. Heterodimerization of TWIST1 with TCF3-encoded E proteins resulted in larger transcriptomic effects, promoting Rho/ROCK signaling and extracellular matrix production/organization, but had only modest effects on proliferation and no effect on migration. Deletion of the TWIST1 C-terminus resulted in a very large transcriptomic shift with predicted downregulation of angiotensin and Rho/ROCK signaling as well as ECM production/organization pathways, in a manner suggesting a dominant negative effect on TWIST1-E12 function. Comparison with single-cell RNA-seq data from human endarterectomy samples placed the function of these TWIST1 variants in a disease context and showed that deletion of the C-terminal domain prevented a modulated SMC phenotype. Discussion These studies demonstrate that TWIST1 influences different aspects of SMC phenotype independently via discrete domains and dimer composition, and link TWIST1 to key signaling pathways that influence SMC phenotype during disease
A Practitioner‐Informed Decision Tree for Selecting Harmful Cyanobacteria Bloom Control and Mitigation Techniques
Get PDFHarmful Cyanobacterial Blooms (HCBs) threaten ecological and human health, and their incidence and magnitude appear to be rising globally. However, a lack of guidance exists on how to choose the best HCB control and mitigation strategy for different types of water bodies. The portfolio of available in situ control techniques is diverse, ranging from experimental to well established, with complicated and poorly‐documented records of effectiveness across different settings and a range of unintended ecological consequences. We introduce a decision tree that synthesizes current science and practitioner experience in a framework that can be used to examine conditions under which HCB control techniques are likely to be appropriate and most effective. The factors that establish branching and the classification of techniques within the decision tree were based on the review of peer‐reviewed and gray literature, and on responses to a national survey. Key factors influencing the feasibility and effectiveness of HCB control include whether nutrient loads are sourced externally or internally, the size of the treatment area, and the vulnerability of and regulations governing the receiving water body. Survey results point to important regional differences in the application of HCB control techniques, whereas demonstration of the decision tree with real‐world case studies highlights some of the practical issues managers face in making decisions about treatment techniques. provides a comprehensive review of current science, appropriate use, and costs for individual techniques
Frequency of left common iliac vein compression in asymptomatic adolescents and young adults.
Get PDFVenous compression at the iliac confluence is a reported risk factor for deep vein thrombosis, with venous stenting as the standard management for relieving this compression. Kibbe et al demonstrated that left common iliac vein (LCIV) compression is present in 35.3% of asymptomatic patients. However, this study included only adults with an average age of 40 years. The iliac vein confluence in patients under 21 years with no symptoms attributable to venous disease was evaluated in this study. The study goal is to determine prevalence of LCIV narrowing in patients under age 21 years, and as such, assist in determining the appropriate treatment for iliac vein compression in this patient population.A retrospective review of patients aged 13-20 undergoing abdominal/pelvic computed tomography (CT) imaging for nonvascular indications was performed. This group was compared with patients aged 35 to 65 years undergoing CT imaging for similar reasons. Axial CT images were reviewed by two independent examiners to identify the diameter of the noncompressed left and right CIVs below the confluence and the diameter of the LCIV at the site of compression between the right common iliac artery and spine.A total of 122 patients aged 13 to 20 years were identified with high-quality CT imaging and no venous symptoms for image review. Mean LCIV diameter was 12.7 ± 2.5 mm, and mean right CIV diameter was 13.1 ± 2.2 mm. The diameter of the LCIV at the confluence was 4.2 ± 1.8 mm, resulting in a mean diameter stenosis of the LCIV of 69.4% ± 12.6%. In this population, 55.7% of patients were found to have ≥70% stenosis of the LCIV on CT imaging compared with 1.7% of patients aged 35 to 65 years (P < .001). There was no statistical difference in the percentage of LCIV stenosis in young patients based on body mass index, gender, race, or ethnicity.Severe compression of the LCIV at the iliac confluence was identified in over 50% of asymptomatic patients aged 13 to 20 years on CT imaging performed for nonvascular reasons. This suggests that narrowing of the LCIV is a normal anatomic finding in this age group. The incidence of severe compression is significantly lower in older asymptomatic persons. In young persons, the high incidence of iliac vein compression on CT imaging suggests that this finding may not be a significant risk factor for deep vein thrombosis or limb symptoms, questioning the need for routine intervention for compression correction in this patient population
Operationalizing Inclusion of Diverse Older Adults in Aging Services Information.
Get PDFAs the United States' population ages, it is also becoming more diverse. The country's Older Americans Act requires county-level offices on aging to be both service and information providers. But it is unclear to what extent offices on aging can identify gaps within the aging services information they provide and improve efforts to meet the information needs of diverse older adults. Utilizing an action research methodology, this study describes a partnership with an office on aging which ultimately resulted in the development and deployment of a diversity audit which is used to increase diverse representation in the aging services information their organization provides. The results reinforce the importance of designing resources with diversity in mind. By implementing the diversity audit and its recommendations, other aging services providers worldwide can ensure they are prepared to serve all older adults who may benefit from the services and information they have to offer
Nucleosome context regulates chromatin reader preference
Get PDFChromatin is more than a simple genome packaging system but rather locally distinguished by histone post-translational modifications (PTMs) that can directly change nucleosome structure and/or be “read” by chromatin-associated proteins to mediate downstream events. An accurate understanding of histone PTM binding preference is vital to explain normal function and pathogenesis and has revealed multiple therapeutic opportunities. Such studies most often use histone peptides, though these cannot represent the full regulatory potential of nucleosome context. Here we apply a range of complementary and easily adoptable biochemical and genomic approaches to interrogate fully defined peptide and nucleosome targets with a diversity of mono- or multivalent chromatin readers. In the resulting data, nucleosome context consistently refined reader binding, and multivalent engagement was more often regulatory than simply additive. This included abrogating binding of the Polycomb group malignant brain tumor (MBT) protein L3MBTL1 to lysine methylated histone tails and confirmation that the CBX7 chromodomain and AT-hook-like motif (CD-ATL) tandem act as a functional unit to confer specificity for H3K27me3. These in vitro nucleosome preferences were confirmed by in vivo reader-CUT&RUN genomic mapping. Such data confirms that more representative chromatin substrates provide greater insight into biological mechanism and human disease
The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment
Get PDFINTRODUCTION The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI.
METHODS We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts.
RESULTS Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site‐level strategies in enrollment into CLARiTI versus other imaging efforts.
DISCUSSION We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network.
Highlights The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi‐etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs)
Evaluation of race, ethnicity, and language mischaracterizations in the electronic medical record for Hispanic/Latinx patients
Get PDFObjective Accurate documentation of interpreter requirements and language preference within the electronic medical record (EMR) is essential for ensuring appropriate care and effective communication with patients who have non-English language preference (NELP). Our objective was to examine the accuracy of EMR documentation related to interpreter needs and language preferences for Hispanic patients at a large academic medical center. Methods This was a cross-sectional study conducted at the University of North Carolina Medical Center from May 2023 to July 2023. A total of 156 Hispanic patients were surveyed based on their clinical records and self-reported language needs. The main measure was the accuracy of EMR documentation compared to patients’ self-reported interpreter needs and preferred language. Results Among 156 Hispanic inpatients, 30.13% had mischaracterized interpreter needs in the EMR, with discrepancies including missing documentation (22%) and direct contradictions (9.92%). Mischaracterizations were significantly associated with male gender (OR = 0.310; 95% CI [0.140, 0.685]; p = 0.0038) and self-reported English proficiency (OR = 0.124; 95% CI [0.041, 0.374]; p < 0.001). Preferred language misclassification occurred in 9.68% of cases, and 7% had incorrect ethnicity documentation. Conclusion Significant inaccuracies in race, ethnicity, and language data documentation hinder equitable care. Addressing these gaps requires standardized documentation protocols, staff training, and objective language assessment tools to improve interpreter utilization and mitigate disparities for NELP patients
Anthropometric Measures
Get PDFThis document summarizes the rationale, equipment, measurement, protocol and data cleaning procedures for each of the anthropometric measures collected at the Wave VI home exam. It also documents how constructed variables were derived from the anthropometric measures collected in the field. Whenever possible, data collection and methods in Wave VI mirrored those of Wave V to ensure comparability of data between waves. This document is one in a set of Wave VI user guides.
Cardiovascular Measures
Get PDFThis document summarizes the rationale, equipment, measurement, protocol and data cleaning procedures for each of the cardiovascular measures collected at the Wave VI home exam. It also documents how constructed variables were derived from the cardiovascular measures collected in the field. Whenever possible, data collection and methods in Wave VI mirrored those of Wave V to ensure comparability of data between waves. This document is one in a set of Wave VI user guides.