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  • 1
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    Online Resource
    Barriers to Providing Prehospital Care to Ischemic Stroke Patients: Predictors and Impact on Care
    Cambridge University Press (CUP) ; 2018
    In:  Prehospital and Disaster Medicine Vol. 33, No. 5 ( 2018-10), p. 501-507
    Details
    In: Prehospital and Disaster Medicine, Cambridge University Press (CUP), Vol. 33, No. 5 ( 2018-10), p. 501-507
    Abstract: Ischemic stroke treatment is time-sensitive, and barriers to providing prehospital care encountered by Emergency Medical Services (EMS) providers have been under-studied. Hypothesis/Problem This study described barriers to providing prehospital care, identified predictors of these barriers, and assessed the impact of these barriers on EMS on-scene time and administration of tissue plasminogen activator (tPA) in the emergency department (ED). Methods A retrospective cohort study was performed using the Get With The Guidelines-Stroke (GWTG-S; American Heart Association [AHA]; Dallas, Texas USA) registry at two hospitals to identify ischemic stroke patients arriving by EMS. Variables were abstracted from prehospital and hospital medical records and merged with registry data. Barriers to care were grouped into themes. Logistic regression was used to identify predictors of barriers to care, and bi-variate tests were used to assess differences in EMS on-scene time and the proportion of patients receiving tPA between patients with and without barriers. Results Barriers to providing prehospital care were documented for 15.5% of patients: 29.6% related to access, 26.7% communication, 23.0% extrication and transportation, 20.0% refusal, and 14.1% assessment/management. Non-white and non-black race (OR: 3.69; 95% CI, 1.63-8.36) and living alone (OR: 1.53; 95% CI, 1.05-2.23) were associated with greater odds of barriers to providing care. The EMS on-scene time was ≥15 minutes for 70.4% of patients who had a barrier to care, compared with 49.0% of patients who did not (P 〈 .001). There was no significant difference in the proportion of patients who were administered tPA between those with and without barriers to care (14.1% vs 19.2%; P=.159). Conclusions Barriers to providing prehospital care were documented for a sizable proportion of ischemic stroke patients, with the majority related to patient access and communication, and occurred more frequently among non-white and non-black patients and those living alone. Although EMS on-scene time was longer for patients with barriers to care, the proportion of patients receiving tPA in the ED did not differ. Li T , Cushman JT , Shah MN , Kelly AG , Rich DQ , Jones CMC . Barriers to providing prehospital care to ischemic stroke patients: predictors and impact on care . Prehosp Disaster Med. 2018 ; 33 ( 5 ): 501 – 507 .
    Type of Medium: Online Resource
    ISSN: 1049-023X , 1945-1938
    URL: Article
    DOI: 10.1017/S1049023X18000766
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2162069-6
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  • 2
    Online Resource
    Online Resource
    Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age: A Study of the CODATwins Project
    Cambridge University Press (CUP) ; 2015
    In:  Twin Research and Human Genetics Vol. 18, No. 5 ( 2015-10), p. 557-570
    Details
    In: Twin Research and Human Genetics, Cambridge University Press (CUP), Vol. 18, No. 5 ( 2015-10), p. 557-570
    Abstract: A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m 2 in childhood and adolescence and up to 0.2 kg/m 2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
    Type of Medium: Online Resource
    ISSN: 1832-4274 , 1839-2628
    URL: Article
    DOI: 10.1017/thg.2015.57
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2184274-7
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  • 3
    Online Resource
    Online Resource
    The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
    Cambridge University Press (CUP) ; 2015
    In:  Twin Research and Human Genetics Vol. 18, No. 4 ( 2015-08), p. 348-360
    Details
    In: Twin Research and Human Genetics, Cambridge University Press (CUP), Vol. 18, No. 4 ( 2015-08), p. 348-360
    Abstract: For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m 2 ) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
    Type of Medium: Online Resource
    ISSN: 1832-4274 , 1839-2628
    URL: Article
    DOI: 10.1017/thg.2015.29
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2184274-7
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  • 4
    Online Resource
    Online Resource
    Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts
    Cambridge University Press (CUP) ; 2017
    In:  Twin Research and Human Genetics Vol. 20, No. 5 ( 2017-10), p. 395-405
    Details
    In: Twin Research and Human Genetics, Cambridge University Press (CUP), Vol. 20, No. 5 ( 2017-10), p. 395-405
    Abstract: Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21] ) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22] ), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
    Type of Medium: Online Resource
    ISSN: 1832-4274 , 1839-2628
    URL: Article
    DOI: 10.1017/thg.2017.49
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2017
    detail.hit.zdb_id: 2184274-7
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  • 5
    Online Resource
    Online Resource
    361 WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma
    Cambridge University Press (CUP) ; 2023
    In:  Journal of Clinical and Translational Science Vol. 7, No. s1 ( 2023-04), p. 107-107
    Details
    In: Journal of Clinical and Translational Science, Cambridge University Press (CUP), Vol. 7, No. s1 ( 2023-04), p. 107-107
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2059-8661
    URL: Article
    DOI: 10.1017/cts.2023.401
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2898186-8
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  • 6
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    Empowering the Participant Voice (EPV): Design and implementation of collaborative infrastructure to collect research participant experience feedback at scale
    Cambridge University Press (CUP) ; 2024
    In:  Journal of Clinical and Translational Science Vol. 8, No. 1 ( 2024)
    Details
    In: Journal of Clinical and Translational Science, Cambridge University Press (CUP), Vol. 8, No. 1 ( 2024)
    Abstract: Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.
    Type of Medium: Online Resource
    ISSN: 2059-8661
    URL: Article
    DOI: 10.1017/cts.2024.19
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2898186-8
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  • 7
    Online Resource
    Online Resource
    Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project
    Cambridge University Press (CUP) ; 2016
    In:  Twin Research and Human Genetics Vol. 19, No. 2 ( 2016-04), p. 112-124
    Details
    In: Twin Research and Human Genetics, Cambridge University Press (CUP), Vol. 19, No. 2 ( 2016-04), p. 112-124
    Abstract: We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
    Type of Medium: Online Resource
    ISSN: 1832-4274 , 1839-2628
    URL: Article
    DOI: 10.1017/thg.2016.11
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2184274-7
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  • 8
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    Online Resource
    Developing an adolescent and adult Fontan Management Programme
    Cambridge University Press (CUP) ; 2022
    In:  Cardiology in the Young Vol. 32, No. 2 ( 2022-02), p. 230-235
    Details
    In: Cardiology in the Young, Cambridge University Press (CUP), Vol. 32, No. 2 ( 2022-02), p. 230-235
    Abstract: Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.
    Type of Medium: Online Resource
    ISSN: 1047-9511 , 1467-1107
    URL: Article
    DOI: 10.1017/S104795112100175X
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2060876-7
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