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Colleges and universities have implemented a broad range of initiatives to support student success. Problem solving courses and course supplements are one approach. Evaluation of these courses has shown positive outcomes in terms of improved academic performance and other benefits. A number of these studies have also reported the largest positive effects with underperforming student groups. To further explore this approach a novel general education academic success course was developed. The course integrated a comprehensive problem-solving model into lectures and assignments as the basis of an active learning instructional strategy. Students were taught the model along with relevant academic skills content. They then applied the model to a personal challenge affecting their success in school and life. Using a matched cohort design, 826 course participants were compared with a campus-wide sample matched on key variables. Generalized linear models were used to estimate between group mean differences, and a Cox proportional hazards model was used to compare time to graduation. Results showed that students who successfully completed the course achieved higher cumulative GPAs overall compared with matched peers. Highest GPAs for students who took the course as freshmen suggested a transfer of knowledge over time. Results also showed that the course significantly benefited students from historically at-risk populations in terms of higher GPAs, units earned, retention, and graduation rates. This study shows that a well designed problem solving course can help students, especially those who struggle academically, to more effectively meet the challenges of college and daily life.

Background: The National Federation of State High School Associations provides recommendations regarding health and safety policies; however, policy development is governed at the state level. Given interstate differences in governance, the primary purpose was to describe processes that State High School Athletic Associations (SHSAAs) utilize to develop a new policy. The secondary objective was to determine what methods associations use to implement new policies. Methods: A cross-sectional survey requested SHSAA (n = 51) representatives to report how athlete health and safety policies are introduced, revised, approved, and implemented within their state. The 22-question survey was developed to gather variables for the aims of the study. Descriptive statistics were calculated for each survey item. Results: Of states who responded (n = 33), most reported a 2-committee (n = 24, 72.7%) process for developing and vetting policies, with initiation from the Sports Medicine Advisory Committee (n = 27, 81.8%), followed by an executive-level committee (n = 18, 66.7%). States reported total time from policy initiation to final approval ranged from 2 weeks to over 12 months. When a new policy was approved, most states indicated implementation began with an e-mail (n = 24, 72.7%) sent to Athletic Directors (n = 26, 78.8%). School principal or district superintendent were reported as the position in charge of compliance (36.4%, n = 12). Conclusions: Most SHSAAs use a 2-step process to write and review an athlete health and safety policy before approval. SHSAAs that require a longer policy development time could delay the implementation of important health measures. SHSAAs could consider additional communication methods to ensure information reaches all stakeholders.

Background: Nutrition plays a vital role in children's physical and emotional health. More than half of school age children's calories are provided in the school food environment, making school interventions an opportunity to address child nutrition. Methods: The Creating Health Environments for Schools (CHEFS) program is designed to leverage local resources to create customized solutions that improve the nutritional content of school food and encourage children to choose healthier food. There are 8 components: (1) customizing nutrition plans, (2) modifying/replacing menu items, (3) helping procure healthier food, (4) providing equipment grants, (5) training cafeteria staff, (6) implementing environmental changes and nudges, (7) engaging students and parents, and (8) supporting sustainability. Supporting child nutrition directors is key to facilitating cooperation with schools. Implications for School Health Policy, Practice, and Equity: Menu modifications and procurement are interrelated and depend on successfully collaborating with corporate, independent, and local food services organizations. Limited school budgets require low or no-cost solutions and staff training. Student and parent engagement are critical to facilitate culturally-appropriate solutions that increase awareness of healthy food. Conclusions: Every school district has particular resources and constraints. CHEFs engaged stakeholders to design customized solutions and encourage healthier nutrition for school children.

Black women remain severely underrepresented in computing despite ongoing efforts to diversify the field. Given that Black women exist at the intersection of both racial and gendered identities, tailored approaches are necessary to address the unique barriers Black women face in computing. However, it is difficult to quantitatively evaluate the efficacy of interventions designed to retain Black women in computing, since samples of computing students typically contain too few Black women for robust statistical analysis. Using about a decade of student survey responses from an National Science Foundation--funded Broadening Participation in Computing alliance, we use regression analyses to quantitatively examine the connection between different types of interventions and Black women's intentions to persist in computing and how this compares to other students (specifically, Black men, white women, and white men). This comparison allows us to quantitatively explore how Black women's needs are both distinct from--and similar to--other students. We find that career awareness and faculty mentorship are the two interventions that have a statistically significant, positive correlation with Black women's computing persistence intentions. No evidence was found that increasing confidence or developing skills/knowledge was correlated with Black women's computing persistence intentions, which we posit is because Black women must be highly committed and confident to pursue computing in college. Last, our results suggest that many efforts to increase the number of women in computing are focused on meeting the needs of white women. While further analyses are needed to fully understand the impact of complex intersectional identities in computing, this large-scale quantitative analysis contributes to our understanding of the nuances of Black women's needs in computing.

Contribution: This article focuses on the study of Native Hawaiian student experiences in engineering education. Telling these stories illustrates the importance of legitimizing and appreciating different knowledge types in engineering as we move toward a more inclusive and sustainable field. Background: Native Hawaiian engineering students live oppressive realities due to the history of settler colonialism and occupation that attempted to erase their culture and ways of knowing, including in engineering education. This study shows how students overcome these realities to enact their ways of knowing in a field where it is not always respected. Informing the field of ways to promote and respect the different knowledge types of marginalized groups can help to create a more inclusive and sustainable engineering field. Research Question: In what ways do Native Hawaiian students bring their cultural ways of knowing into engineering education? Methodology: We conducted semi-structured interviews with three undergraduate Native Hawaiian students using Manulani Aluli Meyer's Holographic Epistemology as a theoretical lens to inform the questions and qualitative analysis. The analysis uses a combination of inductive and deductive analyses to create the hologram that Meyer outlines in her work. Findings: The participants found different ways to enact their cultural ways of knowing. We interpret them through the Native Hawaiian values of pono, kuleana, and ho'ihi. This illustrates how engineering educators, researchers, and programs can legitimize the knowledges of the students by promoting authenticity and reciprocity toward marginalized students and their ways of knowing.

Purpose: The aim of the present study was to compare scale and conditional reliability derived from item response theory analyses among the most commonly used, as well as several newly developed, observation, interview, and parent-report autism instruments. Methods: When available, data sets were combined to facilitate large sample evaluation. Scale reliability (internal consistency, average corrected item-total correlations, and model reliability) and conditional reliability estimates were computed for total scores and for measure subscales. Results: Generally good to excellent scale reliability was observed for total scores for all measures, scale reliability was weaker for RRB subscales of the ADOS and ADI-R, reflecting the relatively small number of items for these measures. For diagnostic measures, conditional reliability tended to be very good (> 0.80) in the regions of the latent trait where ASD and non-ASD developmental disability cases would be differentiated. For parent-report scales, conditional reliability of total scores tended to be excellent (> 0.90) across very wide ranges of autism symptom levels, with a few notable exceptions. Conclusions: These findings support the use of all of the clinical observation, interview, and parent-report autism symptom measures examined, but also suggest specific limitations that warrant consideration when choosing measures for specific clinical or research applications.

Massive Open Online Courses (MOOCs) can be considered an important tool for professionals to reskill and upskill as well as a cost-efficient way to stay relevant. However, evidence-based research is still needed to identify why specific categories of people, especially professionals, take paid MOOCs. The paper aims to analyze the factors that influence IT working Professionals to adopt paid MOOCs using the UTAUT 2 model. Based on a survey conducted on 250 respondents, the study uses multiple regression to understand the significance of factors affecting the intention to adopt paid MOOCs. A multigroup analysis was also done to understand the differences among different age groups and genders. The results establish that social influence, facilitating conditions, brand credibility and price value are significant in the adoption of MOOCs. Performance expectancy, effort expectancy, and curiosity were found to be insignificant. Based on the research findings, the implication of the study and future scope for research have been suggested.

Numerous studies show that children and young people in out-of-home care (OOHC) face significant disadvantage in completing high school and accessing post-secondary education. The current research involved a two-round Delphi survey which aimed to identify educational challenges and school reforms to improve the educational experiences of children and young people in OOHC. A total of 45 participants from three OOHC stakeholder groups (carers of children in OOHC, professionals/educators, and young people with lived experience of OOHC) completed the round one survey which consisted of open-ended questions analysed using thematic analysis. In the second survey round, 19 participants completed a Likert scale questionnaire which drew on themes from the round one thematic analysis. Using a consensus threshold of 70% for the round two survey, participants agreed that students in OOHC face a myriad of educational challenges, such as dealing with a history of trauma, frequent home and school transitions, mental health issues and stigma as a result of being in OOHC. It was agreed that teachers lack knowledge and experience, and schools lack support for students in OOHC. Stakeholders recommended provision of greater mental health support, coordination of services and more autonomy for OOHC students regarding their education.

The remarkable strides in artificial intelligence (AI), exemplified by ChatGPT, have unveiled a wealth of opportunities and challenges in assessment. Applying cutting-edge large language models (LLMs) and generative AI to assessment holds great promise in boosting efficiency, mitigating bias, and facilitating customized evaluations. Conversely, these innovations raise significant concerns regarding validity, reliability, transparency, fairness, equity, and test security, necessitating careful thinking when applying them in assessments. In this article, we discuss the impacts and implications of LLMs and generative AI on critical dimensions of assessment with example use cases and call for a community effort to equip assessment professionals with the needed AI literacy to harness the potential effectively.

Playgroups are a unique form of early childhood provision involving parents and their children attending together. Parents' attendance at playgroups provides opportunities for involvement in play. However, little is known about parents' practices of co-play in playgroups and the potential for these practices to enhance children's play experiences in early childhood. Drawing on practice architectures theory, this paper identifies parents' practices of co-play in a community playgroup, and the enablers and constraints on those practices. Data were collected through ethnographic methods, which included participant observation and informal individual interviews. The findings show that parents' practices of co-play consider the child's needs and interests in ways that support development and enhance children's play in the community playgroup. This research contributes new knowledge about the range of co-play practices engaged in by parents with children in community playgroups.

This study contributes to the growing body of research that highlights the usefulness of professional noticing of children's mathematical thinking for understanding the complexity and variability in teaching expertise. We explored the noticing expertise of 72 upper elementary school teachers engaged in multi-year professional development focused on children's fraction thinking. Our assessment addressed the three component skills of professional noticing of children's mathematical thinking: (a) attending to children's strategy details, (b) interpreting children's understandings, and (c) deciding how to respond on the basis of children's understandings. We used a latent class analysis to empirically identify three distinct "profiles" of noticing expertise--subgroups of teachers who responded similarly to each other and differently from teachers in other profiles. The profiles differed in their overall noticing expertise as well as their patterns of strengths and areas for growth across the component skills. Thus, the profiles provide a concise, multi-dimensional characterization of noticing expertise that integrates expertise in each of the component skills. The profiles also provide tools for differentiating learning opportunities for teachers in professional development. In addition, our design allowed us to compare teachers' expertise in two common forms of deciding how to respond: deciding on follow-up questions and deciding on next problems. In all three profiles, teachers demonstrated more expertise when deciding on follow-up questions than when deciding on next problems, suggesting not only a starting point for teacher learning but also the need for a line of research focused on different forms of this component skill.

Mortality disparities among persons with intellectual disability are important to guide health-care practices. The objective was to evaluate mortality patterns of persons with intellectual disability in a nationwide study from 1976 to 2020. This study establishes a Danish nationwide cohort of persons with intellectual disability and age- and sex-matched reference cohort through linkage between several registers. We established a cohort of 79,114 persons with intellectual disability. Standardized mortality ratios were increased for persons with intellectual disability, most pronounced among younger persons and among females. Life expectancies were markedly lower; among persons with intellectual disability 63.6 years among females and 59.8 years among males in 2016-2020 compared to 82.4 and 78.7 years among females and males in the reference cohort. Life expectancies decreased with severity of intellectual disability. This study reports the establishment of a nationwide Danish cohort of persons with intellectual disability.

The prevalence and pervasive nature of emerging chemicals of concern have created widespread environmental injustice apprehensions in vulnerable communities. To alleviate and address these concerns, identifying, engaging, and training a diverse environmental health research workforce will be critical and necessary steps to combat and prevent the consequences of environmental injustice. While there is an obvious need to enhance diversity in environmental health research, this process is hampered by facets of systemic racism that reduce access to educational resources needed to build interest and knowledge in students and teachers. We present here a historical perspective to offer a guide for building programs and relationships with underserved schools to help overcome limiting factors that have plagued certain public school systems. With the proper training and mentorship, the untapped workforce present within these schools will be empowered to understand and address current and emerging environmental health and safety threats. Through this transformative 8-week high school research program, we will develop well-prepared, ethical researchers committed to scientific inquiry, intensive fieldwork, and collaborative problem solving to address environmental health challenges. Following the four-step risk assessment process, students, teachers, and faculty mentors will work collaboratively to identify toxicants, potential hazards and risks, and environmental disparities in urban neighborhoods, which provides the necessary training to formulate critical thinking skills for use in academic or nonacademic careers.

Pharmacists are increasingly becoming the healthcare professional who interacts most regularly with patients who have diseases or disorders for which exercise is an effective and recommended treatment. With the relative scarcity of clinical exercise physiologists in the United States, pharmacists are expected to provide lifestyle advice to their patients, especially in community (i.e. retail) pharmacy settings, but student pharmacists typically receive no formal or informal training in exercise physiology and prescription. To address this deficit, an elective course was developed to provide student pharmacists with the knowledge and skill set that will enable them to apply evidence-based physical activity guidelines in the pharmacy. The course utilized the Exercise is Medicine resources for chronic diseases and disorders that are routinely encountered in community pharmacies, in addition to analysis of interactions between exercise and medications commonly prescribed for these conditions. After completion of the course, students reported being significantly more comfortable discussing physical activity with their patients compared to the start of the course (P < 0.001). Similarly, at the end of the course, 99% of students reported that they felt confident in their ability to apply evidence-based recommendations of common diseases and disorders to their patients. Postcourse student evaluations clearly demonstrated that student pharmacists viewed the course positively and as essential in their professional training. These data highlight the feasibility and efficacy of improving self-perceptions for the provision of physical activity recommendations via an elective course in physical activity prescription in a Doctor of Pharmacy program.

Professionals and communication partners report experiencing challenges with regard to developing the knowledge and skills needed to support individuals with complex communication needs who use augmentative and alternative communication (AAC). These challenges can be exacerbated in rural and remote areas where access to resources and training may be limited. This practitioner-focused article provides evidence-based strategies for addressing the knowledge and skill needs experienced by professionals and communication partners in rural communities, including strategies for (a) identifying AAC knowledge and skill needs, (b) accessing AAC resources, (c) using principles of instructional design and instructional coaching to address identified areas of need, (d) considering contexts for instruction, and (e) examining contextual fit.

The Institute of Teacher Education and Development (INTED) was founded in Accra, Ghana, in 2011, thanks to a fellowship from Stanford University. The institute is a nongovernmental organization whose objective is to improve learner outcomes by supporting the professional growth of educators. At the center of INTED's model is a professional learning initiative for teacher leaders called the Master Fellows Program. The Masters Fellow Program builds the capacity of teachers to become instructional leaders who support professional learning communities, engage other educators in the institute's professional learning activities, share their experiences at conferences and community events, and act as mentors and champions of teachers. Looking into the future, INTED is seeking to expand offerings to include online learning opportunities to ensure that greater numbers of teachers and schools can access its programs at lower costs and improved convenience.

Purpose: Verbal working memory is poorer for children with hearing loss than for peers with normal hearing (NH), even with cochlear implantation and early intervention. Poor verbal working memory can affect academic performance, especially in higher grades, making this deficit a significant problem. This study examined the stability of verbal working memory across middle childhood, tested working memory in adolescents with NH or cochlear implants (CIs), explored whether signal enhancement can improve verbal working memory, and tested two hypotheses proposed to explain the poor verbal working memory of children with hearing loss: (a) Diminished auditory experience directly affects executive functions, including working memory; (b) degraded auditory inputs inhibit children's abilities to recover the phonological structure needed for encoding verbal material into storage. Design: Fourteen-year-olds served as subjects: 55 with NH; 52 with CIs. Immediate serial recall tasks were used to assess working memory. Stimuli consisted of nonverbal, spatial stimuli and four kinds of verbal, acoustic stimuli: nonrhyming and rhyming words, and nonrhyming words with two kinds of signal enhancement: audiovisual and indexical. Analyses examined (a) stability of verbal working memory across middle childhood, (b) differences in verbal and nonverbal working memory, (c) effects of signal enhancement on recall, (d) phonological processing abilities, and (e) source of the diminished verbal working memory in adolescents with cochlear implants. Results: Verbal working memory remained stable across middle childhood. Adolescents across groups performed similarly for nonverbal stimuli, but those with CIs displayed poorer recall accuracy for verbal stimuli; signal enhancement did not improve recall. Poor phonological sensitivity largely accounted for the group effect. Conclusions: The central executive for working memory is not affected by hearing loss or cochlear implantation. Instead, the phonological deficit faced by adolescents with CIs denigrates the representation in storage and augmenting the signal does not help.

Population aging presents opportunities and challenges for higher education. Increasingly, age-diverse student populations are entering into or returning to postsecondary education; meanwhile, campuses are workplaces where faculty and staff are aging-in-place. Yet, age bias and discrimination continue to exist in institutions of higher education. As encouraged by the Age-Friendly University (AFU) initiative, higher education should foster age-inclusive environments. However, empirical measures are needed to document what it means to be age inclusive. To this end, the present study used the Inventory and Campus Climate Survey (ICCS; Silverstein et al., Silverstein et al., The Gerontologist 62:e48-e61, 2022), based on social-ecological theory, to assess age-inclusive practices and awareness of these practices across seven campus domains, along with personal beliefs regarding age inclusivity, as predictors of perceived age-friendliness. AFU network institutions in the U.S. (23 campuses) provided data from a total sample of 1549 faculty, 2582 staff, and 2700 students. Confirmatory Factor Analysis established the proposed structure of the Age-Friendliness and Personal Beliefs scales of the Campus Climate Survey. Model testing revealed that campus constituents, regardless of role, were largely unaware of age-friendly practices reported by campus administrators, and that the degree of fit between actual practices and constituents' awareness of them predicted perceptions of age inclusivity. Constituents differed in their assessment of which age-friendly practices most contributed to their own sense of age inclusivity, with physical environment playing an important predictive role across all groups. The findings indicated that, even among institutions that endorse AFU principles, there is an overall disconnect between practices and perceptions that can impede the impact of age-inclusive efforts for age-diverse individuals who might benefit from them.

Intended for researchers and clinical leaders, this article suggests that embedded program evaluation is a good fit with the desired features of practice-oriented research. The systematic nature of evaluation that is built into the operational workflow of a practice setting may increase the diversity of methods available to explore processes and outcomes of interest. We propose a novel conceptual framework that uses a human-centered systems lens to foster such embedded evaluation in clinical routine. This approach emphasizes the evaluator-practitioner partnership to build confidence in the bi-directional learning of practice-based evidence with evidence-based practice. The iterative cycles inherent to design thinking are aimed at developing better evaluation questions. The attention to structure and context inherent to systems thinking is intended to support meaningful perspectives in the naturally complex world of health care. Importantly, the combined human-centered systems lens can create greater awareness of the influence of individual and systemic biases that exist in any endeavor or institution that involves people. Recommended tools and strategies include systems mapping, program theory development, and visual facilitation using a logic model to represent the complexity of mental health treatment for communication, shared understanding, and connection to the broader evidence base. To illustrate elements of the proposed conceptual framework, two case examples are drawn from routine outcome monitoring (ROM) and progress feedback. We conclude with questions for future collaboration and research that may strengthen the partnership of evaluators and practitioners as a community of learners in service of local and system-level improvement.

Faculty mentorship is associated with improved career outcomes, yet only a third of faculty report receiving formal mentoring. A first step in formal mentoring is acknowledging the mentoring relationship; acknowledgment can then lead to delineation of roles and responsibilities. We analyzed the mentoring relationships reported by our faculty in the 2020 Annual Faculty Review (AFR) and found only 24% of relationships were reciprocally reported, i.e., a relationship reported by both mentor and mentee, raising questions about the nature of these relationships. Institutional efforts to improve upon faculty mentoring can focus on relationship acknowledgment as a first critical step.

Young people struggle to seek help for their mental health, despite having different resources available. As the coping process is very complex, and elements such as trust and availability of resources have been said to influence it, this study aimed to understand how young people cope with their own or a friend's symptoms of poor mental health. Eleven young people (13-15 years old) were interviewed. Thematic Analysis of the interviews showed that participants reported different coping strategies for dealing with their own hypothetical symptoms and those of a friend. Participants identified the social impact of experiencing symptoms of poor mental health and choice of resources as the main factors influencing their coping strategies. For their own symptoms, young people expressed concern about being judged and that they would only disclose to someone they trust. Participants would not disclose a friend's symptoms because they did not want to break their trust. Finally, choice of resources was mainly influenced by the severity of symptoms being experienced, especially when it comes to asking for professional help. This study contributes to a better understanding of the different ways in which young people cope with their own symptoms and symptoms experienced by a friend.

We examined relationships between measures of adaptive behavior, cognitive ability, and autism symptom severity in 1458 preschool-aged children with autism from the Study to Explore Early Development. While publications commonly describe autistic children as "low-" or "high-functioning" based on cognitive ability, relying solely on cognitive scores may obscure meaningful variation in functioning. We found significant heterogeneity in adaptive behavior scores of children with cognitive scores both above and below the threshold of two or more standard deviations below the population mean specified in the diagnostic criteria for intellectual disability (ID). Although cognitive and adaptive behavior scores were strongly associated in our sample, considerable variation in overall adaptive behavior and more than half in socialization and motor skills was unaccounted for by cognitive ability, autism symptom severity, and other covariates. Among children who could be designated "low-functioning" based on cognitive scores, 39.7% had composite adaptive behavior scores indicating no significant delays, while among those who might be designated "high-functioning," 9.0% had significant delays in overall adaptive behavior and 22.2% in socialization. These results suggest adaptive behavior scores capture variations in the autism phenotype not accounted for by other measures we considered.

Healthcare in Aotearoa New Zealand is changing with the aim of becoming truly universal. Development of a new curriculum model in the education of health professionals can aid this goal through increased focus on community needs and flexibility for multiple health professional registrations. Universal healthcare and disability support are promoted as a defining feature of Aotearoa New Zealand, yet inequities are blatantly evident, with increasing calls for equity. Complexity of the issue and the multitude of stakeholders favour action research founded on Vision Matauranga, a problem-solving philosophy which embraces the potential for innovation of Maori -- people, knowledge and resources. Action research embraces collaboration with stakeholders to identify and implement solutions. Government ministries determine policy, with Responsible Authorities accrediting educational institutions, which in turn provide educational programs. Changing what and how students learn can increase their understanding of equity and community needs when they become practitioners, with the voice of service users being paramount.

Background: The Reducing Disability in Alzheimer's Disease in Kansas City (RDAD-KC) intervention has been shown to improve the health of individuals with dementia and caregiver dyads. This manuscript reports the results of implementing the RDAD among individuals with intellectual disabilities and caregiver dyads. Methods: Nine community agencies deployed the 12-week intervention. We assessed changes in individuals with intellectual disabilities' behavioural symptom related severity and physical activity, and caregivers' behavioural symptom-related distress, unmet needs, and caregiver strain. Results: Forty-four dyads enrolled, and 23 (~60 years, 48% female) completed [greater than or equal to] 75% of the intervention. We observed decreases in behavioural symptom related severity (p = 0.07) and increases in physical activity (p = 0.20) among individuals with intellectual disabilities. We also observed decreases in behavioural symptom related distress (p = 0.14), unmet needs (p = 0.50), and caregiver strain (p = 0.50) among caregivers. Conclusions: The RDAD-KC intervention showed promising, although statistically non-significant, benefits among individuals with intellectual disabilities and their caregivers.

This research investigates how children located in separate homes use the psychological function of imagination to engage in sociodramatic play using networked digital technologies. Specifically, it examines how 7- to 8-year-old children create imaginary play situations in the same "Minecraft: Education Edition" digitally-mediated environment whilst synchronously using the "FaceTime" video-communication tool to discuss their play. Drawing on cultural-historical conceptualizations of play, findings identified in this study describe how children reworked and combined elements of reality via imagination to enable online sociodramatic play. This study provides theoretical insight into how adults may best foster children's imagination in digitally-mediated environments to support online sociodramatic play, of especial benefit to children during periods of lockdown associated with the global pandemic.

The present study employed a quasi-experimental design to evaluate the effectiveness and acceptability of a 6-hr mandatory stress management and well-being program for preservice teachers. A program group of 157 preservice teachers (M[subscript age]= 22.46 years; 88% women) completed the program as well as baseline, post program, and follow-up measures. A comparison group of 63 preservice teachers (M[subscript age] = 23.50 years; 85% women) completed measures at similar time points but did not receive the program. All participants completed measures of stress, coping self-efficacy, anxiety, mindfulness, and well-being. The program group completed additional measures of well-being, affect, and program satisfaction. Findings revealed significant improvements in key indices of mental health and well-being for those in the program group relative to the comparison group and high ratings of program satisfaction. Discussion focuses on implications of present findings for mandatory inclusion of wellness curriculum in teacher preparation programs with instruction on enhancing their own "and "their students' well-being.

This paper summarizes the results of a qualitative study focused on the career shifts of professionals who previously worked in non-academic organizations and transitioned into academic careers. It explores the factors that influence the decision of professionals to reinvent themselves as career academics as well as their level of satisfaction with their career shifts. The paper provides the results of a survey that was conducted with 336 survey respondents coming from an online university, an on-ground state university, a community college and a LinkedIn group focused on education. The results of the survey indicate that 90% of the respondents were satisfied or very satisfied with their new academic career and the reasons for their career changes are detailed. Gaining an understanding of why professionals decide to transition to academia and their satisfaction with their transition will be useful for talent acquisition and retention in higher education organizations as well as being helpful for those professionals who are considering making the transition to academia.

The human brain undergoes rapid development during the first years of life. Beginning in utero, a wide array of biological, social, and environmental factors can have lasting impacts on brain structure and function. To understand how prenatal and early life experiences alter neurodevelopmental trajectories and shape health outcomes, several NIH Institutes, Centers, and Offices collaborated to support and launch the HEALthy Brain and Child Development (HBCD) Study. The HBCD Study is a multi-site prospective longitudinal cohort study, that will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Influenced by the success of the ongoing Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) and in partnership with the NIH Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, the HBCD Study aims to establish a diverse cohort of over 7000 pregnant participants to understand how early life experiences, including prenatal exposure to addictive substances and adverse social environments as well as their interactions with an individuals genes, can affect neurodevelopmental trajectories and outcomes. Knowledge gained from the HBCD Study will help identify targets for early interventions and inform policies that promote resilience and mitigate the neurodevelopmental effects of adverse childhood experiences and environments.

Covid-19 led to a dramatic change in the academic library work environment, with many workers shifting to a hybrid work schedule once they returned to in person work. The authors describe the impact of this schedule shift through the novel use of the socio-ecological model. The socio-ecological model looks at the impact of choices through varying circles or levels. The authors discuss the individual, interpersonal, community, and societal levels of impact that the switch to hybrid work had within their context and discuss their role as unit leaders and the decisions made to address these varying impacts.

AimThe current study investigated the prospective relationships between parental monitoring, family conflict, and screen time across six screen time modalities in early adolescents in the USA.MethodsWe utilised prospective cohort data of children (ages 10-14 years) from the Adolescent Brain Cognitive Development (ABCD) Study (years baseline to Year 2 of follow-up; 2016-2020; N = 10 757). Adjusted coefficients (B) and 95% confidence intervals (CIs) were estimated using mixed-effect models with robust standard errors.ResultsA higher parental monitoring score was associated with less total screen time (B = -0.37, 95% CI -0.58, -0.16), with the strongest associations being with video games and YouTube videos. Conversely, a higher family conflict score was associated with more total screen time (B = 0.08, 95% CI 0.03, 0.12), with the strongest associations being with YouTube videos, video games, and watching television shows/movies in Years 1 and 2.ConclusionThe current study found that greater parental monitoring was associated with less screen time, while greater family conflict was linked to more screen time. These results may inform strategies to reduce screen time in adolescence, such as improving communication between parents and their children to strengthen family relationships.

BACKGROUND: Assessment of eating disorders (ED) in youth relies heavily on self-report, yet persistent lack of recognition of the presence and/or seriousness of symptoms can be intrinsic to ED. This study examines the psychometric properties of a semi-structured interview, the parent version of the Eating Disorder Examination (PEDE), developed to systematically assess caregiver report of symptoms. METHODS: A multi-site, clinical sample of youth (N = 522; age range: 12 to 18 years) seeking treatment for anorexia nervosa (AN) and subsyndromal AN were assessed using the Eating Disorder Examination (EDE) for youth and the PEDE for collateral caregiver report. RESULTS: Internal consistencies of the four PEDE subscales were on par with established ranges for the EDE. Significant medium-sized correlations and poor to moderate levels of agreement were found between the corresponding subscales on each measure. For the PEDE, confirmatory factor analysis of the EDE four-factor model provided a poor fit; an exploratory factor analysis indicated that a 3-factor model better fits the PEDE. CONCLUSIONS: Findings suggest that the PEDE has psychometric properties on par with the original EDE. The addition of the caregiver perspective may provide incremental information that can aid in the assessment of AN in youth. Future research is warranted to establish psychometric properties of the PEDE in broader transdiagnostic ED samples.

Nineteen genetic therapies have been approved by the U.S. Food and Drug Administration (FDA) to date, a number that now includes the first CRISPR genome editing therapy for sickle cell disease, CASGEVY (exagamglogene autotemcel). This extraordinary milestone is widely celebrated because of the promise for future genome editing treatments of previously intractable genetic disorders and cancers. At the same time, such genetic therapies are the most expensive drugs on the market, with list prices exceeding $4 million per patient. Although all approved cell and gene therapies trace their origins to academic or government research institutions, reliance on for-profit pharmaceutical companies for subsequent development and commercialization results in prices that prioritize recouping investments, paying for candidate product failures, and meeting investor and shareholder expectations. To increase affordability and access, sustainable discovery-to-market alternatives are needed that address system-wide deficiencies. Here, we present recommendations of a multi-disciplinary task force assembled to chart such a path. We describe a pricing structure that, once implemented, could reduce per-patient cost tenfold and propose a business model that distributes responsibilities while leveraging diverse funding sources. We also outline how academic licensing provisions, manufacturing innovation and supportive regulations can reduce cost and enable broader patient treatment.

Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal trajectory of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

(1) Background: A significant proportion of cancer survivors report experiencing a cognitive fog that affects their ability to think coherently and quickly, and reason with clarity. This has been referred to as cancer-related cognitive impairment (CRCI). CRCI has extensive impacts on the daily lives of people living with or beyond cancer, including occupational, social, and psychological functioning. Oncology health professionals report feeling under-resourced to effectively assess the needs of an individual with CRCI and then provide optimal care and referral. (2) Methods: The objective of this project is to develop and provide an initial validation of the first purpose-built unmet needs assessment for CRCI: the Unmet Needs Assessment of Cancer-Related Cognitive Impairment Impact (COG-IMPACT). We will use a multiple-stage, co-design, mixed-methods approach to develop and provide an initial validation of the COG-IMPACT. (3) Results: The primary anticipated result of this research is the production of the COG-IMPACT, the first purpose-built unmet needs assessment for CRCI. The assessment could be used by health professionals to understand the unmet needs and facilitate optimal care and referral for cancer survivors, by survivors to elucidate their supportive needs and advocate for their care, and by researchers to examine the correlates of unmet needs relating to CRCI, as well as how best to support people with CRCI.

Gregor Mendel developed the principles of segregation and independent assortment in the mid-1800s based on his detailed analysis of several traits in pea plants. Those principles, now called Mendels laws, in fact, explain the behavior of genes and alleles during meiosis and are now understood to underlie Mendelian inheritance of a wide range of traits and diseases across organisms. When asked to give examples of inheritance that do NOT follow Mendels laws, in other words, examples of non-Mendelian inheritance, students sometimes list incomplete dominance, codominance, multiple alleles, sex-linked traits, and multigene traits and cite as their sources the Khan Academy, Wikipedia, and other online sites. Against this background, the goals of this Perspective are to (1) explain to students, healthcare workers, and other stakeholders why the examples above, in fact, display Mendelian inheritance, as they obey Mendels laws of segregation and independent assortment, even though they do not produce classic Mendelian phenotypic ratios and (2) urge individuals with an intimate knowledge of genetic principles to monitor the accuracy of learning resources and work with us and those resources to correct information that is misleading.

Up to 80% of Parkinson's disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson's disease dementia, but cognitive impairment precedes or coincides with motor onset. It remains controversial whether dementia with Lewy bodies and Parkinson's disease dementia are distinct conditions or represent part of a disease spectrum. The biological mechanisms underlying disease heterogeneity, in particular the development of dementia, remain poorly understood, but will likely be the key to understanding disease pathways and, ultimately, therapy development. Previous genome-wide association studies in Parkinson's disease and dementia with Lewy bodies/Parkinson's disease dementia have identified risk loci differentiating patients from controls. We collated data for 7804 patients of European ancestry from Tracking Parkinson's, The Oxford Discovery Cohort, and Accelerating Medicine Partnership-Parkinson's Disease Initiative. We conducted a discrete phenotype genome-wide association study comparing Lewy body diseases with and without dementia to decode disease heterogeneity by investigating the genetic drivers of dementia in Lewy body diseases. We found that risk allele rs429358 tagging APOEe4 increases the odds of developing dementia, and that rs7668531 near the MMRN1 and SNCA-AS1 genes and an intronic variant rs17442721 tagging LRRK2 G2019S on chromosome 12 are protective against dementia. These results should be validated in autopsy-confirmed cases in future studies.

The phytocannabinoid cannabinol (CBN) has a potential mechanism of action as an alternative sleep aid but there is minimal evidence to support its effectiveness. The aim of this randomized, double-blind, placebo-controlled study was to assess the safety and effects of three formulations of a hemp-derived CBN sleep aid, TruCBN™ [25 mg (n = 206), 50 mg (n = 205), 100 mg (n = 203)], on sleep quality (PROMIS Sleep Disturbance 8A), relative to placebo (n = 204). The effectiveness and safety of these formulations relative to 4 mg of melatonin (n = 202) was assessed. Exploratory measures were stress (PROMIS Stress 4A), anxiety (Anxiety 4A), pain (PROMIS™ PEG), and well-being (WHO 5). All groups and the 4 mg melatonin group experienced significant improvement in sleep quality relative to the placebo group with no significant differences between any group and the melatonin group. Participants taking 100 mg showed a larger decrease in stress compared to the placebo group. There were no significant differences in anxiety, pain, well-being, or the frequency of side effects between any group and the placebo group. There was no significant difference in improvements in sleep quality between any of the treatment groups and the 4 mg melatonin group. Orally ingested CBN, at 25 mg, 50 mg, and 100 mg, is a safe and effective alternative for the improvement of sleep.

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.

Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 CCUS patients investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count

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BACKGROUND: Monitoring genotypes of HIV infections in blood donors may provide insights into infection trends in the general population. METHODS: HIV RNA was extracted from plasma samples of blood donors confirmed as HIV positive by blood screening nucleic acid and antibody tests. HIV genome target regions were amplified using nested real time-polymerase chain reaction followed by next-generation sequencing. Sequences were compared to those in the Los Alamos National Laboratory (LANL) database. Sequences were also assessed for drug resistance mutations (DRM) using the Stanford HIV DRM Database. RESULTS: From available HIV-positive donations collected between 1 September 2015 and 31 December 2020, 563 of 743 (75.8%) were successfully sequenced; 4 were subtype A, 543 subtype B, 5 subtype C, 1 subtype G, 5 circulating recombinant forms (CRF), and 2 were subtype B and D recombinants. Overall, no significant differences between blood donor and available LANL genotypes were found, and the genotypes of newly acquired versus prevalent HIV infections in donors were similar. The proportion of non-B subtypes and CRF remained a small fraction, with no other subtype or CRF representing more than 1% of the total. DRM were identified in 122 (21.6%) samples with protease inhibitor, nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor DRMs identified in 4.9%, 4.6% and 14.0% of samples, respectively. CONCLUSIONS: HIV genetic diversity and DRM in blood donors appear representative of circulating HIV infections in the US general population and may provide more information on infection diversity than sequences reported to LANL, particularly for recently transmitted infections.

Background and aimsThe precise roles of screen media activity (SMA) and sleep problems in relation to child/adolescent psychopathology remain ambiguous. We investigated temporal relationships among sleep problems, SMA, and psychopathology and potential involvement of thalamus-prefrontal-cortex (PFC)-brainstem structural covariation.MethodsThis study utilized data from the Adolescent Brain Cognitive Development study (n = 4,641 ages 9-12) at baseline, Year1, and Year2 follow-up. Cross-Lagged Panel Models (CLPMs) investigated reciprocal predictive relationships between sleep duration/problems, SMA, and psychopathology symptoms. A potential mediating role of baseline Thalamus-PFC-brainstem covariation on SMA-externalizing relationships was examined.ResultsParticipants were divided into discovery (n = 2,359, 1,054 girls) and replication (n = 2,282, 997 girls) sets. CLPMs showed 1) bidirectional associations between sleep duration and SMA in late childhood, with higher frequency SMA predicting shorter sleep duration (β = -0.10 [95%CI: -0.16, -0.03], p = 0.004) and vice versa (β = -0.11 [95%CI: -0.18, -0.05], p < 0.001); 2) externalizing symptoms at age 10-11 predicting sleep problems (β = 0.11 [95%CI: 0.04, 0.19], p = 0.002), SMA (β = 0.07 [95%CI: 0.01, 0.13], p = 0.014), and internalizing symptoms (β = 0.09 [95%CI: 0.05, 0.13], p < 0.001) at age 11-12; and 3) externalizing behavior at age 10-11 partially mediating the relationship between baseline thalamus-PFC-brainstem covariation and SMA at age 11-12 (indirect effect = 0.032 [95%CI: 0.003, 0.067], p-value = 0.030). Findings were replicable.ConclusionWe found bi-directional SMA-sleep-duration associations in late childhood. Externalizing symptoms preceded future SMA and sleep disturbances and partially mediated relationships between structural brain covariation and SMA. The findings emphasize the need for understanding individual differences and developing and implementing integrated strategies addressing both sleep concerns and screen time to mitigate potential impacts on psychopathology.

The phase 3 INO-VATE trial demonstrated higher rates of remission, measurable residual disease negativity, and improved overall survival for patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) who received inotuzumab ozogamicin (InO) vs standard-of-care chemotherapy (SC). Here, we examined associations between genomic alterations and the efficacy of InO. Of 326 randomized patients, 91 (InO, n = 43; SC, n = 48) had samples evaluable for genomic analysis. The spectrum of gene fusions and other genomic alterations observed was comparable with prior studies of adult ALL. Responses to InO were observed in all leukemic subtypes, genomic alterations, and risk groups. Significantly higher rates of complete remission (CR)/CR with incomplete count recovery were observed with InO vs SC in patients with BCR::ABL1-like ALL (85.7% [6/7] vs 0% [0/5]; P = .0076), with TP53 alterations (100% [5/5] vs 12.5% [1/8]; P = .0047), and in the high-risk BCR::ABL1- (BCR::ABL1-like, low-hypodiploid, KMT2A-rearranged) group (83.3% [10/12] vs 10.5% [2/19]; P < .0001). This retrospective, exploratory analysis of the INO-VATE trial demonstrated potential for benefit with InO for patients with R/R ALL across leukemic subtypes, including BCR::ABL1-like ALL, and for those bearing diverse genomic alterations. Further confirmation of the efficacy of InO in patients with R/R ALL exhibiting the BCR::ABL1-like subtype or harboring TP53 alterations is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT01564784.

ImportanceUrinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed.ObjectiveTo evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI.Design, setting, and participantsCluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020).InterventionsCPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (

ImportancePneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed.ObjectiveTo evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia.Design, setting, and participantsCluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020.InterventionCPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (

Growing poverty in America’s suburbs challenges their image as single-family residential communities for middle class, predominantly white families. Research shows that suburban areas now have the largest share of households under the poverty line. Since these areas have lower density development and lower levels of public transit service compared to urban areas, living in the suburbs may pose accessibility challenges for low-income households, particularly those without a personal vehicle. To explore housing and transportation issues associated with the suburbanization of poverty, we combined U.S. Census data from Contra Costa County, which has the highest rates of suburban poverty in the San Francisco Bay Area, and online and in-person surveys with individuals who earn less than 80% of the Area Median Income (AMI), around $75,000. This research identifies demographic and external factors that lead low- and moderate-income households to move to suburban areas, accessibility barriers faced by low- and moderate-income suburban households, and how transportation use and transportation and housing costs differ between urban and suburban low-income residents in the Bay Area.

7009 Background: The phase 2 CAPTIVATE study evaluated first-line ibrutinib (Ibr) + venetoclax (Ven) for CLL/SLL in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). Ibr±Ven retreatment was allowed in patients (pts) who had progressive disease (PD). Here, we report outcomes for pts with high-risk genomic features from the FD cohort and retreatment outcomes in pts from the FD cohort and MRD cohort placebo arm. Methods: Pts aged ≤70 y with previously untreated CLL/SLL without restriction on genomic risk factors received 3 cycles of Ibr, then 12 cycles of Ibr+Ven (Ibr, 420 mg/d orally; Ven, 5-wk ramp up to 400 mg/d orally). On-study retreatment included single-agent Ibr (FD cohort or MRD cohort placebo arm); pts with PD >2 y after end of treatment (EOT) could be retreated with FD Ibr+Ven (FD cohort). Results: In the FD cohort (n=159) with a median follow-up of 61.2 mo (range, 0.8–66.3), 5-y PFS and OS rates (95% CI) were 67% (59–74) and 96% (91–98), respectively. 5-y PFS rates were higher in pts with undetectable MRD at 3 mo after EOT in peripheral blood (83%) or bone marrow (84%) vs those without (48% and 50%, respectively). 5-y PFS rates (95% CI) in pts with genomic risk factors were: del(17p)/mutated TP53 41% (21–59), complex karyotype 57% (37–72), del(11q) 64% (30–85), and unmutated IGHV 68% (50–80) (Table). In total, 18 second malignancies occurred in 13 pts (10 events in 8 pts during FD Ibr+Ven, 6 events in 4 pts after EOT and before retreatment, and 2 events in 2 pts during retreatment). Of 202 pts who completed Ibr+Ven (FD cohort, n=159; MRD cohort placebo arm, n=43), 63 have had PD to date; PD occurred >2 y after EOT in 43/63 pts (68%). 32/63 (51%) pts initiated retreatment with Ibr (n=25) or Ibr+Ven (n=7). With a median time on Ibr retreatment of 21.9 mo (range, 0.03–50.4), ORR was 86% in 22 evaluable pts (best response: 1 CR; 1 nodular PR; 17 PR; 2 SD; 1 PD [Richter transformation]). With a median time on Ibr+Ven retreatment of 13.8 mo (range, 3.7–15.1), ORR was 71% in 7 evaluable pts (best response: 1 CR; 4 PR; 1 PR with lymphocytosis; 1 SD). Conclusions: With up to 5.5 y of follow-up, FD Ibr+Ven continues to provide clinically meaningful PFS in pts with high-risk genomic features, as well as in the overall population. Ibr-based retreatment provides promising responses in pts needing subsequent therapy after the all-oral FD regimen of Ibr+Ven. Clinical trial information: NCT02910583 . [Table: see text]

OBJECTIVE: Mitochondrial impairments have been implicated in the pathogenesis of Fragile X-associated tremor/ataxia syndrome (FXTAS) based on analysis of mitochondria in peripheral tissues and cultured cells. We sought to assess whether mitochondrial abnormalities present in postmortem brain tissues of patients with FXTAS are also present in plasma neuron-derived extracellular vesicles (NDEVs) from living carriers of fragile X messenger ribonucleoprotein1 (FMR1) gene premutations at an early asymptomatic stage of the disease continuum. METHODS: We utilized postmortem frozen cerebellar and frontal cortex samples from a cohort of eight patients with FXTAS and nine controls and measured the quantity and activity of the mitochondrial proteins complex IV and complex V. In addition, we evaluated the same measures in isolated plasma NDEVs by selective immunoaffinity capture targeting L1CAM from a separate cohort of eight FMR1 premutation carriers and four age-matched controls. RESULTS: Lower complex IV and V quantity and activity were observed in the cerebellum of FXTAS patients compared to controls, without any differences in total mitochondrial content. No patient-control differences were observed in the frontal cortex. In NDEVs, FMR1 premutation carriers compared to controls had lower activity of Complex IV and Complex V, but higher Complex V quantity. INTERPRETATION: Quantitative and functional abnormalities in mitochondrial electron transport chain complexes IV and V seen in the cerebellum of patients with FXTAS are also manifest in plasma NDEVs of FMR1 premutation carriers. Plasma NDEVs may provide further insights into mitochondrial pathologies in this syndrome and could potentially lead to the development of biomarkers for predicting symptomatic FXTAS among premutation carriers and disease monitoring.

Suburban areas have lower density development than urban areas, which may make them less accessible for the growingpopulation of low- and moderate-income suburban residents, particularly those without a personal vehicle. This research examines factors that lead these households to move to suburban areas and identifies accessibility barriers they face. We use a mixed-methods approach with Public Use Microdata Sample (PUMS) data from the U.S. Census, online/in-person surveys (n=208), and interviews conducted in English and Spanish (n=25) with households in Contra Costa County with an income of less than $75,000. To understand key differences in housing and transportation choices between urban and suburban residents, these data were compared to survey and interview data from low-income Oakland residents from 2020-2021. We found that low- and moderate-income households choose to live in suburbs due to rising rents and otherrequirements (e.g., credit score, rental history) in urban areas, and a desire for home ownership and safer environment for children. Yet lack of tenant protections is leaving them vulnerable to rising rents in suburban areas. Transportation costs are higher in suburbs due to longer commutes and higher reliance on personal vehicles. Despite higher levels of carownership in the suburbs, households often go without a car due to maintenance issues or inability to make car payments. When faced with the lack of an automobile, suburban households have few quality transportation alternatives.

Oculomotor deficits are common in hereditary ataxia, but disproportionally neglected in clinical ataxia scales and as outcome measures for interventional trials. Quantitative assessment of oculomotor function has become increasingly available and thus applicable in multicenter trials and offers the opportunity to capture severity and progression of oculomotor impairment in a sensitive and reliable manner. In this consensus paper of the Ataxia Global Initiative Working Group On Digital Oculomotor Biomarkers, based on a systematic literature review, we propose harmonized methodology and measurement parameters for the quantitative assessment of oculomotor function in natural-history studies and clinical trials in hereditary ataxia. MEDLINE was searched for articles reporting on oculomotor/vestibular properties in ataxia patients and a study-tailored quality-assessment was performed. One-hundred-and-seventeen articles reporting on subjects with genetically confirmed (n=1134) or suspected hereditary ataxia (n=198), and degenerative ataxias with sporadic presentation (n=480) were included and subject to data extraction. Based on robust discrimination from controls, correlation with disease-severity, sensitivity to change, and feasibility in international multicenter settings as prerequisite for clinical trials, we prioritize a core-set of five eye-movement types: (i) pursuit eye movements, (ii) saccadic eye movements, (iii) fixation, (iv) eccentric gaze holding, and (v) rotational vestibulo-ocular reflex. We provide detailed guidelines for their acquisition, and recommendations on the quantitative parameters to extract. Limitations include low study quality, heterogeneity in patient populations, and lack of longitudinal studies. Standardization of quantitative oculomotor assessments will facilitate their implementation, interpretation, and validation in clinical trials, and ultimately advance our understanding of the evolution of oculomotor network dysfunction in hereditary ataxias.