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Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
Over recent decades, biomass gains in remaining old-growth Amazonia forests have declined due to environmental change. Amazonia’s huge size and complexity makes understanding these changes, drivers, and consequences very challenging. Here, using a network of permanent monitoring plots at the Amazon–Cerrado transition, we quantify recent biomass carbon changes and explore their environmental drivers. Our study area covers 30 plots of upland and riparian forests sampled at least twice between 1996 and 2016 and subject to various levels of fire and drought. Using these plots, we aimed to: (1) estimate the long-term biomass change rate; (2) determine the extent to which forest changes are influenced by forest type; and (3) assess the threat to forests from ongoing environmental change. Overall, there was no net change in biomass, but there was clear variation among different forest types. Burning occurred at least once in 8 of the 12 riparian forests, while only 1 of the 18 upland forests burned, resulting in losses of carbon in burned riparian forests. Net biomass gains prevailed among other riparian and upland forests throughout Amazonia. Our results reveal an unanticipated vulnerability of riparian forests to fire, likely aggravated by drought, and threatening ecosystem conservation at the Amazon southern margins.
There is a clear need to educate and train the clinical research workforce to conduct scientifically sound clinical research. Meeting this need requires the creation of tools to assess both an individual’s preparedness to function efficiently in the clinical research enterprise and tools to evaluate the quality and effectiveness of programs that are designed to educate and train clinical research professionals. Here we report the development and validation of a competency self-assessment entitled the Competency Index for Clinical Research Professionals, version II (CICRP-II).
CICRP-II was developed using data collected from clinical research coordinators (CRCs) participating in the “Development, Implementation and Assessment of Novel Training In Domain-Based Competencies” (DIAMOND) project at four clinical and translational science award (CTSA) hubs and partnering institutions.
An exploratory factor analysis (EFA) identified a two-factor structure: the first factor measures self-reported competence to perform Routine clinical research functions (e.g., good clinical practice regulations (GCPs)), while the second factor measures competence to perform Advanced clinical functions (e.g., global regulatory affairs). We demonstrate the between groups validity by comparing CRCs working in different research settings.
The excellent psychometric properties of CICRP-II and its ability to distinguish between experienced CRCs at research-intensive CTSA hubs and CRCs working in less-intensive community-based sites coupled with the simplicity of alternative methods for scoring respondents make it a valuable tool for gauging an individual’s perceived preparedness to function in the role of CRC as well as an equally valuable tool to evaluate the value and effectiveness of clinical research education and training programs.
OBJECTIVES/SPECIFIC AIMS: The purpose of this study was to summarize the existing literature on clinical research competencies and determine what competency assessments currently exist. We also wished to assess which competencies should be included in a research competency assessment tool and to evaluate the validity of current competency assessments. We also examined whether these competency assessments can be used for the purposes of formative and summative evaluation. METHODS/STUDY POPULATION: Prior to conducting our search of the literature, we first compiled a list of search terms (e.g., clinical, research, training, competencies) that could be used to locate articles. We then entered these search terms, in various combinations, on several relevant databases. We evaluated abstracts of the articles revealed by this search to determine whether they met three criteria. The first criterion was that the subjects of the article must be clinical investigators or clinical investigators in training. Relevant disciplines included medicine, public health, nursing, pharmacy, dentistry, and other related fields. The second criterion was that articles should focus on research-based (as opposed to clinical) skills. The last criterion was that research-based competencies (or related terms like skills, abilities, mastery, knowledge) must be assessed in some way. If the abstract suggested that the article met all three criteria, the full article was retrieved and analyzed in-depth. To identify articles that eluded literature search, we then examined the reference section of these articles and examined articles that cited these articles. When no additional articles could be located, the search for articles stopped. Once a pool of potentially eligible articles was identified, the articles underwent peer review by several researchers experienced with clinical research and competency-based education and assessment. Articles that were unanimously judged to meet the criteria were included in the systematic review. RESULTS/ANTICIPATED RESULTS: Approximately 75 articles were selected and reviewed for eligibility. After peer review, we found that only a small fraction of these articles met our criteria for inclusion in the systematic literature review. Our preliminary findings suggest that there are few assessments of clinical research competency and that many of these assessments are poorly validated. DISCUSSION/SIGNIFICANCE OF IMPACT: The findings of the present study suggest that the validation methods used thus far are limited and so the validity of many of these assessments is effectively unproven. Future research on assessments of clinical research competency ought to address these limitations by sampling clinical researchers, using more rigorous validation methods, and by confirming hypothesized factor structures in new samples. The use of better-validated instruments may enhance measurement of trainees’ knowledge and skill levels for the purposes of formative and summative assessment.
OBJECTIVES/SPECIFIC AIMS: The DIAMOND project encourages study team workforce development through the creation of a digital learning space that brings together resources from across the CTSA consortium. This allows for widespread access to and dissemination of training and assessment materials. DIAMOND also includes access to an ePortfolio that encourages CRPs to define career goals and document professional skills and training. METHODS/STUDY POPULATION: Four CTSA institutions (the University of Michigan, the Ohio State University, University of Rochester, and Tufts CTSI) collaborated to develop and implement the DIAMOND portal. The platform is structured around eight competency domains, making it easy for users to search for research training and assessment materials. Contributors can upload links to (and meta-data about) training and assessment materials from their institutions, allowing resources to be widely disseminated through the DIAMOND platform. Detailed information about materials included in DIAMOND is collected through an easy to use submission form. DIAMOND also includes an ePortfolio designed for CRPs. This encourages workforce development by providing a tool for self-assessment of clinical research skills, allowing users to showcase evidence of experience, training and education, and fosters professional connections. RESULTS/ANTICIPATED RESULTS: To date, more than 100 items have been posted to DIAMOND from nine contributors. In the first 30 days there were 229 active users with more than 500 page views from across the U.S. as well as China and India. Training materials were viewed most often from four competency domains: 1) Scientific Concepts & Research Design, 2) Clinical Study Operations, 3) Ethical & Participant Safety, and 4) Leadership & Professionalism. Additionally, over 100 CRPs have created a DIAMOND ePortfolio account, using the platform to document skills, connect with each other, and search for internships and job opportunities. DISCUSSION/SIGNIFICANCE OF IMPACT: Lessons learned during development of the DIAMOND digital platform include defining relevant information to collect for the best user experience; selection of a standardized, user-friendly digital platform; and integration of the digital network and ePortfolio. Combined, the DIAMOND portal and ePortfolio provide a professional development platform for clinical research professionals to contribute, access, and benefit from training and assessment opportunities relevant to workforce development and their individual career development needs.
It goes without saying that feminist International Political Economy (IPE) is concerned in one way or another with the everyday – conceptualised as both a site of political struggle and a site within which social relations are (re)produced and governed. Given the longstanding grounding of feminist research in everyday gendered experiences, many would ask: Why do we need an explicit feminist theorisation of the everyday? After all, notions of everyday life and everyday political struggle infuse feminist analysis. This article seeks to interrogate the concept of the everyday – questioning prevalent understandings of the everyday and asking whether there is analytical and conceptual utility to be gained in articulating a specifically feminist understanding of it. We argue that a feminist political economy of the everyday can be developed in ways that push theorisations of social reproduction in new directions. We suggest that one way to do this is through the recognition that social reproduction is the everyday alongside a three-part theorisation of space, time, and violence (STV). It is an approach that we feel can play an important role in keeping IPE honest – that is, one that recognises how important gendered structures of everyday power and agency are to the conduct of everyday life within global capitalism.
Childhood obesity is a common concern across global cities and threatens sustainable urban development. Initiatives to improve nutrition and encourage physical exercise are promising but are yet to exert significant influence on prevention. Childhood obesity in London is associated with distinct ethnic and socio-economic patterns. Ethnic inequalities in health-related behaviour endure, underpinned by inequalities in employment, housing, access to welfare services, and discrimination. Addressing these growing concerns requires a clearer understanding of the socio-cultural, environmental and economic contexts of urban living that promote obesity. We explore opportunities for prevention using asset based-approaches to nutritional health and well-being, with a particular focus on adolescents from diverse ethnic backgrounds living in London. We focus on the important role that community engagement and multi-sectoral partnership play in improving the nutritional outcomes of London's children. London's children and adolescents grow up in the rich cultural mix of a global city where local streets are characterised by diversity in ethnicities, languages, religions, foods, and customs, creating complex and fluid identities. Growing up with such everyday diversity we argue can enhance the quality of life for London's children and strengthen their social capital. The Determinants of young Adult Social well-being and Health longitudinal study of about 6500 of London's young people demonstrated the positive impact of cultural diversity. Born to parents from over a hundred countries and exposed to multi-lingual households and religious practices, they demonstrated strong psychological resilience and sense of pride from cultural straddling, despite material disadvantage and discrimination. Supporting the potential contribution of such socio-cultural assets is in keeping with the values of social justice and equitable and sustainable development. Our work signals the importance of community engagement and multisectoral partnerships, involving, for example, schools and faith-based organisations, to improve the nutrition of London's children.
Three-dimensional (3D) printing technology is a promising method for bone tissue engineering applications. For enhanced bone regeneration, it is important to have printable ink materials with appealing properties such as construct interconnectivity, mechanical strength, controlled degradation rates, and the presence of bioactive materials. In this respect, we develop a composite ink composed of polycaprolactone (PCL), poly(D,L-lactide-co-glycolide) (PLGA), and hydroxyapatite particles (HAps) and 3D print it into porous constructs. In vitro study revealed that composite constructs had higher mechanical properties, surface roughness, quicker degradation profile, and cellular behaviors compared to PCL counterparts. Furthermore, in vivo results showed that 3D-printed composite constructs had a positive influence on bone regeneration due to the presence of newly formed mineralized bone tissue and blood vessel formation. Therefore, 3D printable ink made of PCL/PLGA/HAp can be a highly useful material for 3D printing of bone tissue constructs.
OBJECTIVES/SPECIFIC AIMS: As the sole Clinical and Translational Science Award (CTSA) site in Michigan, the Michigan Institute for Clinical & Health Research (MICHR) at the University of Michigan (UM) is working to develop community networks that drive clinical and translational research on community-identified health priorities. METHODS/STUDY POPULATION: These CBRNs will be modeled from successful work that has been accomplished in Jackson, MI where stakeholders from the local healthcare community, County Health Department, Health Improvement Organization, and grassroots community members created a Community of Solution to address the unmet behavioral health and social needs of community members. The CBRN’s will focus on identifying community health priorities by receiving input from community members in underserved communities using deliberative software called Choosing All Together (CHAT). RESULTS/ANTICIPATED RESULTS: In the fall of 2017, 3 focus groups were held in Northern Michigan to identify community health priorities. The top 5 community health priorities include; (1) mental wellness, (2) long-term illness, (3) alcohol and drugs, (4) air, water, and land, and (5) affording care. Additional focus groups are scheduled for the winter in 2 additional geographic areas. DISCUSSION/SIGNIFICANCE OF IMPACT: Future work for the creation of CBRNs includes building leadership groups comprised of clinicians, community leaders, public health leaders, health system leaders and researchers to inform the leadership groups of community-identified health priorities. In addition, the team is working to identify a platform to connect academic investigators across UM and community partners on shared research priorities in real time. In order to measure and map relationships within the networks, we are planning to utilize Social Network Analysis as an evaluation tool.
OBJECTIVES/SPECIFIC AIMS: Identify the impact of the provision of clinical and translational research training awards on investigators’ pursuit of clinical and translational research careers. METHODS/STUDY POPULATION: Propensity score matching and qualitative analysis/investigators receiving MICHR’s KL2 research training awards. RESULTS/ANTICIPATED RESULTS: While the evaluations of the impact of this service have shown participants find them to be valuable it is expected that participation in the workshop may be more beneficial to investigators with certain types of prior research experiences and who utilize more CTSA research support. DISCUSSION/SIGNIFICANCE OF IMPACT: Because this evaluation of a research service incorporate data representing investigator’s receipt of different CTSA resources, the findings can be used to inform the ongoing coordination of these services in ways that optimize their impact on the production of clinical and translational research. There is an enduring need for evaluations of CTSA programs to account for investigators’ use of different constellations of research services in order to identify what combinations of services over time are most effective at fostering successful clinical and translational research careers.
OBJECTIVES/SPECIFIC AIMS: To evaluate the NIH-sponsored Best Practices for Social and Behavioral Research e-learning course. METHODS/STUDY POPULATION: Four universities partnered in a pilot study to evaluate this new course. Outcomes from 294 participants completing the course included efficient progress through the training, perceived relevance of the course to current work, level of engagement with the course material, intent to work differently as a result of the course, and downloading digital resources. RESULTS/ANTICIPATED RESULTS: Participants rated the course as relevant and engaging (6.4 and 5.8 on a 7-point Likert scale) and 96% of respondents said they would recommend the course to colleagues. Qualitative analysis of participant testimonials suggested that most respondents had a readiness to change in the way they worked as a result of the course. Overall, results suggest participants completed the course efficiently, perceived outcomes positively and worked differently after the training. DISCUSSION/SIGNIFICANCE OF IMPACT: These results will inform new guidelines for future participants (e.g., average time to complete, expectations for knowledge checks in the training). Future studies should include larger samples and closer coordination and communication between study sites.
The Best Practices in Social and Behavioral Research Course was developed to provide instruction on good clinical practice for social and behavioral trials. This study evaluated the new course.
Participants across 4 universities took the course (n=294) and were sent surveys following course completion and 2 months later. Outcomes included relevance, how engaging the course was, and working differently because of the course. Open-ended questions were posed to understand how work was impacted.
Participants rated the course as relevant and engaging (6.4 and 5.8/7 points) and reported working differently (4.7/7 points). Participants with less experience in social and behavioral trials were most likely to report working differently 2 months later.
The course was perceived as relevant and engaging. Participants described actions taken to improve rigor in implementing trials. Future studies with a larger sample and additional participating sites are recommended.
OBJECTIVES/SPECIFIC AIMS: The first goal of this project is to test the reliability and validity of an objective structured clinical exam (OSCE) that was designed to assess competency in clinical and translational research. The second goal is to evaluate the impact of MICHR’s Summer Research Program on the participating trainee’s competency development. METHODS/STUDY POPULATION: The methodology used for this study was reviewed and exempted from oversight by the U-M Institutional Review Board (HUM00113293). The participants in the study include 17 pre-doctoral students in health professions programs at U-M who participated MICHR’s Summer Research Program. The Research OSCE was administered using a pretest, post-test design. The pretest was administered once during the 1st week of program in the Summer of 2016 and the post-test during the 10th week of the program. The Research OSCE was proctored and rated by trained staff members. We will assess the reliability of the Research OSCE using Generalizability Theory (Webb et al., 2006). And the construct validity of the Research OSCE will be tested using factor analysis and other statistical analyses. Growth in the competence of the trainees participating in the Summer Research program will be evaluated by testing for significant differences between their pretest and post-test scores. RESULTS/ANTICIPATED RESULTS: We anticipate that this study will show that the Research OSCE is a reliable competency assessment with proven construct validity. We also anticipate that the use of the Research OSCE will show the trainees participating in the Summer Research program experienced a gain in competence during the course of the 10-week program. DISCUSSION/SIGNIFICANCE OF IMPACT: This project uses a common and standardized testing approach. The primary goal of this project is to evaluate the reliability and validity of an OSCE to assess competency in clinical and translational research. It represents a new application for a well-studied testing method used extensively in the health professions to assess the clinical competency of health practitioners. This project will lead to a better understanding of (a) the reliability and validity of the Research OSCE designed to test research competency and (b) the effectiveness of the Summer Research Program curriculum in better preparing participants to conduct clinical and translational research. Showing how a specific competency assessment can be used for this purpose will provide the administrators, evaluators, and other stakeholders of clinical and translational research training programs with information that can be used to design more rigorous and relevant evaluations of their research training programs.
OBJECTIVES/SPECIFIC AIMS: To conduct a preliminary evaluation of the Social and Behavioral Research Best Practices Course. METHODS/STUDY POPULATION: Learners are sampled from 5 institutions: University of Michigan, University of Rochester, University of Florida, Boston University, and University of Buffalo. Learners who take the course and consent to be in the study receive a web link to a survey immediately after course completion and at 2–3 months follow up. In addition to demographic information, learners will report their perceptions of usefulness and relevance of the course to their job, their satisfaction with the course and associated job aids, and at follow-up, if and how the course impacted their work. Additional information will be collected from the learning management systems which host the course at each institution. The data collected will include the number of participants who take the course, the number who complete, how many times the course was attempted, and pass rates. RESULTS/ANTICIPATED RESULTS: We anticipate that several hundred learners will take the course by the end of our project. Of learners who agree to participate in the survey, we anticipate that they will find the course useful and relevant to social and behavioral clinical trials and will be satisfied with the course. Information including suggestions about missing content, items or content that were not extremely clear, or any other comments will be collected to iterate and expand the course. DISCUSSION/SIGNIFICANCE OF IMPACT: This course was developed to fill a gap in training in good clinical practice for social and behavioral research. An evaluation of how the training provided in the course impacts the jobs of learners is needed both to ensure that the most relevant information is included in the course as well as to identify ways that the training may contribute to the quality and safety of social and behavioral clinical trials.
Among the polychaetes, the family Cirratulidae is one of the most challenging taxonomically because most of the currently used diagnostic characters change during ontogeny. It is therefore necessary to use a combination of characters to make an accurate identification. The present work is the first of a planned revision of the genus Cirratulus from coastal zones of Argentina. The examined material came from the two largest natural history museums of the country, and showed several morphotypes. Some specimens corresponded to described species, but others were undoubtedly undescribed. Among the previously known Cirratulidae, Cirratulus jucundus (Kinberg, 1866) and Cirratulus patagonicus (Kinberg, 1866), formerly distributed for Antarctica are now also present in coastal continental areas of Argentina. The new species Cirratulus mianzanii sp. nov. is described from subtidal areas off Peninsula Valdés, Patagonia. This species is distinguished from its congeners by the segmental origin of both tentacular filaments and first pair of branchiae in the junction between the peristomium and first chaetiger. Branchiae arise some distance from the notopodium but not at the dorsal midline of the body. Ventral groove present along the body, with a fine dark midline. Capillary chaetae are serrate seen under an optical microscope, and the segmental origin of neuro- and notopodial spines is different from other species of the genus.
The complexity of helminth macroparasites is reflected in the intricate network of host cell types that participate in the Type 2 immune response needed to battle these organisms. In this context, adaptive T helper 2 cells and the Type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have been the focus of research for years, but recent work has demonstrated that the innate immune system plays an essential role. Some innate immune cells that promote Type 2 immunity are relatively abundant, such as macrophages and eosinophils. However, we now appreciate that more rare cell types including group 2 innate lymphoid cells, basophils, mast cells and dendritic cells make significant contributions to these responses. These cells are found at low frequency but they are specialized to their roles – located at sites such as the skin, lung and gut, where the host combats helminth parasites. These cells respond rapidly and robustly to worm antigens and worm-induced damage to produce essential cytokines, chemokines, eicosanoids and histamine to activate damaged epithelium and to recruit other effectors. Thus, a greater understanding of how these cells operate is essential to understand how the host protects itself during helminth infection.
Anomalous aortic origin of the coronary arteries is associated with exercise-induced ischaemia, leading some physicians to restrict exercise in patients with this condition. We sought to determine whether exercise restriction was associated with increasing body mass index over time. From 1998 to 2015, 440 patients ⩽30 years old were enrolled into an inception cohort. Exercise-restriction status was documented in 143 patients. Using linear mixed model repeated-measures regression, factors associated with increasing body mass index z-score over time, including exercise restriction and surgical intervention as time-varying covariates, were investigated. The 143 patients attended 558 clinic visits for which exercise-restriction status was recorded. The mean number of clinic visits per patient was 4, and the median duration of follow-up was 1.7 years (interquartile range (IQR) 0.5–4.4). The median age at first clinic visit was 10.3 years (IQR 7.1–13.9), and 71% (101/143) were males. All patients were alive at their most recent follow-up. At the first clinic visit, 54% (78/143) were exercise restricted, and restriction status changed in 34% (48/143) during follow-up. The median baseline body mass index z-score was 0.2 (IQR 0.3–0.9). In repeated-measures analysis, neither time-related exercise restriction nor its interaction with time was associated with increasing body mass index z-score. Surgical intervention and its interaction with time were associated with decreasing body mass index z-score. Although exercise restriction was not associated with increasing body mass index over time, surgical intervention was associated with decreasing body mass index z-score over time in patients with anomalous aortic origin of the coronary arteries.
Recent studies regarding non-suicidal self-injury (NSSI) among adolescents have focused primarily on individual characteristics (e.g., depressive symptoms) and background factors (e.g., parental relationship), whereas less emphasis has been given to the role of school-related factors in NSSI. Therefore, the purpose of the current study was to explore the relationships between teachers’ support, peer climate, and NSSI within the school context.
The sample consisted of 594 high school students nested within 27 regular classes (54.4% boys; mean age 14.96, SD = 1.33 years). The students were evaluated for NSSI behaviors, perception of teacher support, peer climate, relationships with mothers, and depressive symptoms using validated scales.
The primary analysis used hierarchical linear modeling (HLM), controlling for gender and age. The main findings indicated that teacher support was positively associated with NSSI at the classroom-level (OR = 6.15, 95% CI = 2.05–18.5) but negatively associated at the student-level (OR = 0.66, 95% CI = 0.49–0.89). There was a trend toward an association between positive peer climate and NSSI at the classroom-level (OR = 0.43, 95% CI = 0.18–1.05), while negative peer climate was associated with NSSI at the student-level (OR = 1.37, 95% CI = 1.00–1.87).
School-related factors are associated with NSSI behaviors among students. Teachers and educators should focus on both individual-level and classroom-level perceptions of school context. Students who feel supported by their teachers and who are exposed to a positive peer climate are less likely to engage in NSSI.