Search

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5 splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.

Abundant research has covered the benefits of and barriers to partnerships between schools and community-based organizations (CBOs; Sanders, 2001; Valli et al., 2016). The aim is for schools and CBOs to come together to foster student growth, particularly during out-of-school time. If two independent organizations, such as a school and a nonprofit CBO, are to work together to provide out-of-school time (OST) programming, then they must have common goals and set clear expectations. This study conceptualizes school-CBO collaboration as coordination of services and resources for children and their families through transparent and open dialogue about children's specific needs. Although literature detailing the characteristics of healthy school-CBO partnerships is abundant, few studies focus specifically on school staff members' perceptions of these partnerships. The authors' study aims to fill this gap. It suggests that schools take an active role in determining what their student body needs regarding OST programming and continually evaluate the fit between the needs and the programming. The aim of this study is to understand how school staff perceived OST programming provided by a CBO in their schools. The authors focused on four public schools in a single district in the southern U.S. where a single nonprofit CBO offered three empowerment-focused OST programs.

Training the next generation of public health practitioners to promote health equity requires public health graduate programs to cultivate students' skills in community partnership. The Council on Education for Public Health (CEPH) requires Master of Public Health (MPH) students to produce a high-quality written product as part of their culminating Integrative Learning Experience (ILE). Because CEPH recommends that ILE written products be useful to community partners, ILEs can draw lessons from the field of experiential education, especially the social justice aligned principles of critical service-learning (CSL). However, the current literature lacks descriptions of how to operationalize CSL's principles within graduate-level culminating experiences. To help fill this gap, we discuss a CSL ILE for MPH students, called Capstone. We describe CSL's key components and explain and assess how each is operationalized. We hope Capstone's model will help educators engage more deeply with CSL practices to advance health equity.

For too many community college students, transferring to a four-year institution for a bachelor's degree (i.e., vertical transfer) remains an unrealized aspiration. Prior research suggests that forms of capital can assist students in realizing their goals. Therefore, we sought to explore how relationships both within and outside of their institutions serve as sources of capital to support students' vertical transfer journeys. Utilizing a qualitative research design, we applied Putnam's (2000) two forms of social capital (bridging and bonding) and eight social support-related constructs from Moser's (2013) expanded transfer student capital framework to data from focus groups and interviews with 33 pre- and post-transfer students. We found that participants actively constructed a patchwork of supportive relationships with both institutional agents and individuals external to the institution, which they utilized to search for, gather, and employ transfer capital. Our findings highlight that relationships outside of institutions are as crucial as relationships within the institution as sources of capital for vertical transfer students, suggesting a need to incorporate extra-institutional relationships into transfer capital frameworks and institutional initiatives to support transfer students. We also recommend institutions invest in programs designed to build students' social and transfer capital.

The personnel preparation of early intervention/early childhood special educator (EI/ECSE) candidates is a pivotal stage in supporting the development of professionals who can effectively work with young children with and at-risk of developmental disabilities, their families, and other service providers. This process encompasses a multifaceted approach to equip candidates with knowledge, skills, and attitudes/dispositions to successfully work within the field. This compilation article includes multiple authors of each section who share strategies, assignments, tools, and experiences to center the Initial Practice-Based Standards for Early Interventionists/Early Childhood Special Educators (Division for Early Childhood [DEC] of the Council for Exceptional Children [CEC], 2020; hereafter referred to as the EI/ECSE Standards) and DEC's Recommended Practices (RPs). These strategies are shared through a "spiraling curriculum" framework, and progress from an awareness level to reflection of candidates' own practice. In addition, this article shares related resources to consider in planning for innovative coursework and practicum/student teaching opportunities. Specific examples of spiraling experiences to deepen learning through opportunities to introduce content aligned to RPs and EI/ECSE Standards are included.

This study aimed to validate a modified Statistics Anxiety Scale for students in the United States taking university courses. Modifications were made by changing the wording of several items to be consistent with American English, and to accommodate students taking statistics courses in various formats. Items were added to investigate anxiety toward the use of statistical packages, and peer mentoring. Data from 352 participants and exploratory factor analyses were used to analyze the original 24-item SAS (SAS-O) and a version of the SAS with six additional items (SAS-M). The three-factor structure for SAS-O was consistent with the original validation study, explaining about 64% of the items' variance. The factor structure for SAS-M contained an additional two factors, that explained a total of 68 % of the items' variance. The factors were internally consistent, correlated with one another, and negatively correlated with Wise's Attitude Toward Statistics scale. Male students generally had lower application anxiety and examination anxiety than female students, and lower asking for help anxiety than non-traditional students.

In the context of an established research-practice partnership with the Hope Resource Center, we piloted The Stories Project, a narrative inquiry study alongside refugee-background youth workers and U.S.-born community members. Our inquiry explored the process by which storytelling could be used to humanize and advocate for refugee-background youth in the United States. Data sources included interviews, dialogue session recordings, participant artifacts, and researcher memos. Findings centered the voices of refugee-background youth workers as they honored each other's unique perspectives and life experiences as well as recognized each other's shared humanity. Collectively, the youth workers identified the importance of being vulnerable, humanizing the refugee experience, and building advocacy as ways to promote social change.

During the COVID-19 pandemic, two higher education teachers, located respectively in the United States and Aotearoa New Zealand, collaborated in the design of curricula on the relationship between identity and food for their students. Intended to help their students develop cross-cultural knowledge and relationships, they hoped that their collaboration would also benefit their professional relationship and learning at a time when these aspects of their teaching lives were negatively impacted by COVID-19. As a contribution to the scholarship of teaching and learning (SoTL), they undertook, with the help of a researcher colleague, an investigation of (a) factors that influenced their ability to start and sustain a successful international collaboration, and (b) its subsequent impact on their on-going relationship and learning. In this article, the rationale, purpose, and design of the study are outlined, and findings and associated theory presented and discussed. A key conclusion reflects the relationship between the hospitality 'mindset' of the teachers and their ability to conceptualize, enact and benefit from their collaboration in meaningful ways. Insights into the way SoTL can enhance teachers' ability to navigate such periods of deep uncertainty are also presented and discussed.

Learning Assistants (LAs) are undergraduates who work in active-learning classrooms with students facilitating discussions and encouraging deeper thinking, while also receiving pedagogical training. We describe how we built an LA program at a regional comprehensive university starting as a grassroots STEM initiative to recruit teachers, and expanding into a campus-wide multi-disciplinary program focusing on student success in a variety of general education courses. Additionally, in the 2020-2021 academic year, we conducted a formative assessment to further understand the program's impact. Our findings revealed strong alignment among students, faculty, and LAs regarding the LA's role in student learning. Qualitative themes from student surveys and faculty expectations resonated with LAs' weekly field note reflections. One surprising discovery was the consensus that LAs provided substantial support beyond the classroom. This suggests that LAs play a multifaceted role in enhancing student success, extending their influence beyond facilitating in-class discussions.

Meeting the needs of students in schools has been challenging for many years. Consequently, some schools have responded with comprehensive, multi-tiered intervention systems (e.g., MTSS) aimed at addressing students' academic, behavioral, and social-emotional needs. However, most educators have a rudimentary understanding of these systems and the impact of trauma and traumatic experiences on students' response to interventions. Currently, there is limited research on how building level-administrators integrate trauma-informedness into these tiered systems. This conceptual article outlines the importance of administrators' perception, understanding, and implementation of using a trauma-informed lens in educational decision making, specifically regarding MTSS implementation. This article presents an overview of the literature and an approach to trauma-informed approach that administrators can utilize when making educational decisions, specifically within multi-tiered systems of intervention and student supports.

Preliminary evidence from the Childhood Joint Attention Rating Scale (C-JARS; Mundy et al., 2017) suggests symptoms related to diminished joint attention and the spontaneous sharing of experience with others can be assessed with a parent-report measure in children and adolescents with autism. This study was designed to expand on the previous study by examining the validity of both a Social Symptom (SS) and a Prosocial (PS) scale of the C-JARS in a study of school-aged autistic children (n = 89) with and without co-occurring intellectual disability (ID), as well as an age matched neurotypical sample (n = 62). Results indicated that both C-JARS scales were sensitive and specific with respect to identifying the diagnostic status of the children. In addition, the PS scale was sensitive to differences in cognitive abilities (IQ) and sex differences in the autism group. These results are consistent with the hypothesis that joint attention and spontaneous sharing of experience symptoms are not only characteristic of preschool children with autism but may also constitute a developmentally continuous dimension of the social phenotype of autism that can be measured in school-aged children.

Recent research on curricular analytics suggests that the structure of a college major may impact major persistence and degree completion. Contributing to this line of research, we propose and test a new measure of the "lived curriculum" that captures the extent to which cohorts within a major take the same exact course-taking path as they advance from matriculation to graduation (or institutional exit). First, we describe variation in path homogeneity across both STEM and non-STEM majors at one public research-intensive institution. Second, we show that a major's level of path homogeneity is correlated with the percentage of "locked" requirements in its stated curriculum, but that the stated curriculum cannot account for all observed differences in path homogeneity. Third, we conduct a correlational analysis of early exposure to path homogeneity and graduation likelihood. Findings show that students with average levels of academic preparation are less likely to graduate if enrolled in path-homogeneous majors compared to more path-heterogeneous (i.e., flexible) majors, and that negative outcomes associated with a path-homogeneous major are exacerbated for students with below-average preparation. Supplemental analyses show that this relationship holds for STEM and non-STEM majors, cannot be explained away by the competitiveness of a major, and that students generally switched from more to less path-homogeneous majors over the course of their college careers. Taken together, these findings urge re-examination of the ways college majors can promote retention.

Infants are immersed in a world of sounds from the moment their auditory system becomes functional, and experience with the auditory world shapes how their brain processes sounds in their environment. Across cultures, speech and music are two dominant auditory signals in infants' daily lives. Decades of research have repeatedly shown that both quantity and quality of speech input play critical roles in infant language development. Less is known about the music input infants receive in their environment. This study is the first to compare music input to speech input across infancy by analyzing a longitudinal dataset of daylong audio recordings collected in English-learning infants' home environments, at 6, 10, 14, 18, and 24 months of age. Using a crowdsourcing approach, 643 naïve listeners annotated 12,000 short snippets (10 s) randomly sampled from the recordings using Zooniverse, an online citizen-science platform. Results show that infants overall receive significantly more speech input than music input and the gap widens as the infants get older. At every age point, infants were exposed to more music from an electronic device than an in-person source; this pattern was reversed for speech. The percentage of input intended for infants remained the same over time for music while that percentage significantly increased for speech. We propose possible explanations for the limited music input compared to speech input observed in the present (North American) dataset and discuss future directions. We also discuss the opportunities and caveats in using a crowdsourcing approach to analyze large audio datasets. A video abstract of this article can be viewed at https://youtu.be/lFj_sEaBMN4

This brief analyzes 4-year graduation rates among students ever classified as English learners (ever-ELs) and those never classified as English learners (never-ELs) at the intersections of gender, race/ethnicity, and neighborhood income. We follow two cohorts of New York City students who entered ninth grade in 2013-2014 and 2014-2015 (N = 127,931). We find substantial variations in 4-year graduation among these subgroups, with differential predicted probabilities depending on the student's ever-EL status, race/ethnicity, and neighborhood income. These findings reveal important intersectional disparities in this diverse group of ELs--nuances that are lost when analyzing across a single social dimension and that push us to adopt an intersectional lens in quantitative research on ELs.

This systematic review explores the emerging themes in the design and implementation of student-facing learning analytics dashboards in higher education. Learning Analytics has long been criticised for focusing too much on the analytics, and not enough on the learning. The review is then guided by an interest in whether these dashboards are still primarily analytics-driven or if they have become pedagogically informed over time. By mapping the identified themes of technological maturity, informing frameworks, affordances, data sources, and analytical levels over publications per year, the review identifies an emerging trajectory towards student-focused dashboards. These dashboards are informed by theory-oriented frameworks, designed to incorporate affordances that supporting student learning, and realised through integration of more than just activity data from learning management systems -- allowing the dashboards to better support students' learnings processes. Based on this emerging trajectory, the review provides a series of design recommendations for student-focused dashboards that are connected to learning sciences as well as analytics.

Self-regulation is an essential component of school readiness. Although in educational contexts self-regulation is typically defined in terms of volitional processes, it also encompasses the activity of neurophysiological systems, including the parasympathetic nervous system (PNS). In a prospective longitudinal study, 102 preschoolers (M[subscript age] = 4.82 years; 52% female) completed two measures of volitional self-regulation (the gift-wrap task and a battery of EF tasks) at the beginning of their final preschool year, and then completed the Bracken School Readiness Assessment (BSRA) at year's end. Larger increases in parasympathetic function (indexed by respiratory sinus arrythmia, or RSA) during both the gift-wrap and EF tasks were correlated with better performance on the BSRA at levels approaching significance, and subsequent regression models that controlled for relevant covariates revealed robust associations between increases in RSA and improved BSRA performance (gift wrap: B = 5.49, p = 0.012; EF: B = 7.77, p = 0.001). We interpret these results in light of polyvagal theory and discuss their implications for incorporating measures of parasympathetic activity into future educational neuroscience research.

Metaphor generation is both a creative act and a means of learning. When learning a new concept, people often create a metaphor to connect the new concept to existing knowledge. Does the manner in which people generate a metaphor, via sudden insight (Aha! moment) or deliberate analysis, influence the quality of generation and subsequent learning outcomes? According to some research, deliberate processing enhances knowledge retention; hence, generation via analysis likely leads to better concept learning. However, other research has shown that solutions generated via insight are better remembered. In the current study, participants were presented with science concepts and descriptions, then generated metaphors for the concepts. They also indicated how they generated each metaphor and rated their metaphor for novelty and aptness. We assessed participants' learning outcomes with a memory test and evaluated the creative quality of the metaphors based on self- and crowd-sourced ratings. Consistent with the deliberate processing benefit, participants became more familiar with the target science concept if they previously generated a metaphor for the concept via analysis compared to via insight. We also found that metaphors generated via analysis did not differ from metaphors generated via insight in quality (aptness or novelty) nor in how well they were remembered. However, participants' self-evaluations of metaphors generated via insight showed more agreement with independent raters, suggesting the role of insight in modulating the creative ideation process. These preliminary findings have implications for understanding the nature of insight during idea generation and its impact on learning.

Purpose: Print knowledge is a powerful predictor of later reading abilities, which are crucial to children's academic success. Children with speech sound disorders (SSDs) are at risk for literacy difficulties. Speech sound therapy is an opportune time to address not only speech sound production but also the connections between speech sounds and their associated letters and letter patterns. This tutorial aims to provide a rich source of evidence to support the use of print and print-referencing in speech sound therapy sessions. We include feasible suggestions for speech-language pathologists (SLPs) to facilitate print-rich experiences for children with SSDs. Incorporating orthography into therapy sessions, through activities such as shared book reading, allows SLPs to address speech sound errors while supporting children's literacy development. Conclusions: This tutorial provides an overview of the risk of literacy deficits in children with SSDs and describes the theoretical underpinnings of why incorporating print is a powerful learning tool. We expand on the research behind print referencing in preschool classrooms. Finally, we provide detailed examples, including book lists and therapy ideas for a variety of ages, to help SLPs add print referencing to their therapy toolkit.

Through a lens for engaged scholarship (Boyer in "Journal of Public Service and Outreach," 1(1), 11-20, 1996) this multiple case study (Merriam, 1996) explores the potential of scholarly podcasts for public knowledge dissemination, highlighting the misalignment of university impact metrics with this medium. Our team collected qualitative and numerical data from six podcasters across our university system. We identify metrics for assessing scholarly podcast value, offer recommendations for institutional communication, and share our insights and challenges. Data analysis suggests that a Listen Score (Listen Notes, ND) and an increasing Podcast Success Index (Singh et al. "JMIR Medical Education," 2(2), 1-10, 2016) may be consistent with a wider reach. Consistent production and promotion are key and infrastructure support for scholarly podcasters is necessary.

Coaching is an essential component of supporting teachers to implement evidence-based practices (EBPs) in classrooms. The Self-Determined Learning Model of Instruction (SDLMI), an EBP designed to promote student self-determination, uses a research-based coaching model with six guiding principles. This qualitative study analyzed the content of coaching conversations between coaches and general and special education high school teachers implementing the SDLMI with autistic students to explore alignment with the guiding principles of the SDLMI coaching model. Findings highlighted the usefulness of the coaching principles in building trust between coaches and teachers, supporting teachers to set meaningful goals and build skills and competencies related to SDLMI implementation, promoting innovation and fidelity, and facilitating reflective dialogue. Implications for research and practice are discussed.

Although visual arts pedagogies are considered central within early childhood education programs, teacher self-efficacy has a direct impact on the quality and delivery of visual arts curricula. Until recently, the visual arts self-efficacy, pedagogical knowledge, and practice of in-service early childhood teachers have remained largely unexplored. The authors of this paper present a qualitative, iterative re-analysis of their three PhD studies which broadly focussed on early childhood visual arts praxis and specifically examined the visual arts beliefs and pedagogy of early childhood teachers in Australia and New Zealand. A thematic analysis of the intersecting self-efficacy findings raised in the three studies identifies the powerful influence of self-efficacy on teaching practice in the visual arts domain and offers new understandings about visual arts self-efficacy amongst early childhood teachers. The combined findings reveal several factors that restrain or enhance teachers' visual arts self-efficacy across time, including the impact of childhood experiences, pre-service training and epistemological beliefs. The paper also identifies several enabling conditions that appear to support teachers to develop and maintain positive visual arts self-efficacy beliefs, including practical engagement with materials, sustained professional learning, relational trust and intentional leadership. These enabling conditions offer practical strategies and research recommendations in service of positive visual arts self-efficacy to enhance quality visual arts teaching in early childhood contexts.

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

Preliminary evidence from the Childhood Joint Attention Rating Scale (C-JARS; Mundy et al., 2017) suggests symptoms related to diminished joint attention and the spontaneous sharing of experience with others can be assessed with a parent-report measure in children and adolescents with autism. This study was designed to expand on the previous study by examining the validity of both a Social Symptom (SS) and a Prosocial (PS) scale of the C-JARS in a study of school-aged autistic children (n  = 89) with and without co-occurring intellectual disability (ID), as well as an age matched neurotypical sample (n  = 62). Results indicated that both C-JARS scales were sensitive and specific with respect to identifying the diagnostic status of the children. In addition, the PS scale was sensitive to differences in cognitive abilities (IQ) and sex differences in the autism group. These results are consistent with the hypothesis that joint attention and spontaneous sharing of experience symptoms are not only characteristic of preschool children with autism but may also constitute a developmentally continuous dimension of the social phenotype of autism that can be measured in school-aged children.

Adequate concentrations of human milk (HM) nutrients, including macro- and trace-elements, are essential for healthy growth and development of exclusively breastfed (EBF) infants. To monitor potential risk of deficiencies, and evaluate the effects of interventions like supplementation, accurate analysis is crucial. Even recent methods reporting on HM macro- and/or trace-elements describe multiple methodological approaches and the need for several milliliters. We optimized and validated a comprehensive method for simultaneous analysis of 13 macro- and trace-elements for simultaneous analysis by inductively-coupled plasma-mass spectrometry. 100-600 μL HM were microwave digested with ≤1.5 mL HNO3 (70 %). The digest was diluted to 5 % final acid concentration. He-Kinetic Energy Discrimination (KED; Na, K, P, Ca, Mg, Fe, Cu, Zn, Cr, Mo) and O2-Dynamic Reaction Cell (DRC; As, Mn, Se) modes minimized remaining interferences. Accuracy (NIST SRM 1869 infant formula; n = 15, 4 weeks) varied from 93.2 to 103 % (CV: 2.8-8.5 %) with trueness ranging from 93.9 to 104 %. Inter-day variation of a HM-pool (n = 20, 3 weeks) varied between 4.1 and 8.5 % for most elements; Cr, Mo, Mn (all80 %) with concentrations below the Adequate Intake. Our method allows for simultaneous and reproducible analysis of macro- and trace-elements with concentrations ranging over 6 orders of magnitude, without the need for separate analytics and sample preparations, and requiring only sub-milliliter amounts of HM. Additional elements may be included after optimization and validation. The results from Bangladeshi HM samples indicate selective supplementation effects and concerningly low concentrations for some elements, which could adversely affect the EBF infant.

Maleimide and amidine functionalities often appear in medicinal and natural product targets. We describe a catalyst-free, three-component coupling reaction for the synthesis of amidinomaleimides. This one-pot reaction fuses a broad range of secondary amines and aldehydes with azidomaleimides. The conditions are mild, simple, modular, high yielding, and amenable to aqueous solvents. Most reaction products can be sufficiently purified without column chromatography. The synthesis creates complex, multifunctional molecules with four different molecules, including a tripeptide, arrayed around an amidinomaleimide core.

AbstractCompared with the general population, hematopoietic cell transplantation (HCT) survivors are at elevated risk for developing solid subsequent neoplasms (SNs). The Center for International Blood and Marrow Transplant Research (CIBMTR) is a key resource for quantifying solid SN incidence following HCT, but the completeness of SN ascertainment is uncertain. Within a cohort of 18 450 CIBMTR patients linked to the California Cancer Registry (CCR), we evaluated the completeness of solid SN data reported to the CIBMTR from 1991 to 2018 to understand the implications of using CIBMTR data alone or combined with CCR data to quantify the burden of solid SNs after HCT. We estimated the cumulative incidence of developing a solid SN, accounting for the competing risk of death. Within the cohort, solid SNs were reported among 724 patients; 15.6% of these patients had an SN reported by CIBMTR only, 36.9% by CCR only, and 47.5% by both. The corresponding cumulative incidence of developing a solid SN at 10 years following a first HCT was 4.0% (95% confidence interval [CI], 3.5-4.4) according to CIBMTR data only, 5.3% (95% CI, 4.9-5.9) according to CCR data only, and 6.3% (95% CI, 5.7-6.8) according to both sources combined. The patterns were similar for allogeneic and autologous HCT recipients. Linking detailed HCT information from CIBMTR with comprehensive SN data from cancer registries provides an opportunity to optimize SN ascertainment for informing follow-up care practices and evaluating risk factors in the growing population of HCT survivors.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further how these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research. METHODS AND FINDINGS: A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery. CONCLUSIONS: The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.

RATIONALE: The alcohol cue exposure paradigm is a common method for evaluating new treatments for alcohol use disorder (AUD); however, it is unclear if medication-related reductions in cue-induced craving in the human laboratory can predict the clinical success of those medications in reducing alcohol consumption during clinical trials. OBJECTIVES: To use a novel meta-analytic approach to test whether medication effect sizes on cue-induced alcohol craving are associated with clinical efficacy in clinical trials. METHOD: We searched the literature for medications tested for AUD treatment using both the alcohol cue-reactivity paradigm and randomized clinical trials (RCTs). For alcohol cue-reactivity studies, we computed medication effect sizes for cue-induced alcohol craving (k = 36 studies, 15 medications). For RCTs, we calculated medication effect sizes for heavy drinking and abstinence (k = 139 studies, 19 medications). Using medication as the unit of analysis, we applied the Williamson-York bivariate weighted least squares estimation to account for errors in both independent and dependent variables. We also conducted leave-one-out cross validation simulations to examine the predictive utility of cue-craving medication effect sizes on RCT heavy drinking and abstinence endpoints. RESULTS: There was no significant relationship between medication effects on cue-induced alcohol craving in the human laboratory and medication effects on heavy drinking ( β ^ = 0.253, SE = 0.189, p = 0.090) and abstinence ( β ^ = 0.829, SE = 0.747, p = 0.133) in RCTs. CONCLUSIONS: The preliminary results of the current study challenge the assumption that alcohol cue-reactivity alone can be used as an early efficacy indicator for AUD pharmacotherapy development. These findings suggest that a wider range of early efficacy indicators and experimental paradigms be considered for Phase II testing of novel compounds.