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Increasing and diversifying STEM college graduates, and consequently the STEM workforce, remains a pressing national priority. As such, the purpose of this quantitative study was to evaluate the Educate to Innovate campaign within higher education. Using preexisting public survey data together with interrupted and comparative interrupted time series techniques, this inquiry aimed to determine whether STEM education has been rejuvenated and broadened or if there remains work to be done. Results ultimately showed that the campaign exerted a statistically significant positive effect on the trend of STEM college graduates. However, no significant difference in the trend between STEM college graduates who are women and STEM college graduates who are men or between minority and nonminority STEM college graduates was observed. Such comprehension is both timely and useful as individuals and organizations along with federal, state, and local policymakers continue to refine and tailor the development of future STEM education interventions.

Prosody is an important indicator of reading development, but many teachers are unclear about how it can help students improve their reading fluency. Beyond demonstrating expressive or flowing reading, specific components of "reading prosody" can distinctly reveal how well word recognition and comprehension processes coalesce, providing teachers with useful information for their instruction. In this article, we review the research on reading prosody to clarify how differences in "intonation," "amplitude," and "timing" components distinguish struggling and strong readers. In addition, we discuss reading prosody considerations for classroom assessment and intervention by sharing insights drawn from educators trained to evaluate it systematically. We aim to clarify how teachers can use these reading prosody components to enhance classroom reading fluency practices.

Objective: Very few studies have investigated intervention approaches that may be efficacious for youth with ADHD and co-occurring cognitive disengagement syndrome (CDS) symptoms. This study examined the feasibility, acceptability, and preliminary efficacy of a mindfulness-based intervention for adolescents with ADHD and co-occurring CDS symptoms. Methods: Fourteen adolescents ages 13 to 17 years (35.71% female; 64.29% White, 7.14% Black, 28.57% Multiracial) with ADHD and elevated CDS symptoms completed the 8-week group-based Mindful Awareness Practices (MAPs) program developed for individuals with ADHD. We collected measures of CDS, ADHD, mind-wandering, mindfulness, and other difficulties and functioning at baseline, 1-month post-intervention, and 3-month post-intervention to examine preliminary efficacy. We measured participant session attendance, session engagement, at-home practice adherence, and satisfaction of adolescents and caregivers at 1-month post-intervention to examine feasibility and acceptability. We also collected qualitative feedback from adolescents and caregivers at 1-month post-intervention. Results: The intervention was overall feasible to administer, and caregivers and adolescents reported satisfaction with the intervention despite some difficulties with attendance and engagement. We observed improvements to both caregiver- and adolescent-reported CDS symptoms and ADHD-inattentive symptoms from pre-intervention to post-intervention time points, though findings across 1- and 3-month follow-up differed based on informant. We also observed improvements to some indices of adolescent-reported mind-wandering, mindfulness, brooding rumination, and academic functioning. For caregiver report, the only other noted improvement was for executive functioning. No improvements were reported by teachers. Conclusions: Findings support the initial feasibility, acceptability, and preliminary efficacy of MAPs for adolescents with ADHD and co-occurring CDS symptoms on a range of outcomes. Larger trials with a randomized design are warranted to further examine mindfulness-based interventions for adolescents with ADHD and co-occurring CDS symptoms.

Objective: To test whether pediatrician training leads to provider utilization of stimulant diversion prevention strategies as reported by adolescent patients with ADHD. Methods: Pediatric practices received a stimulant diversion prevention workshop (SDP) or continued treatment-as-usual (TAU) in a cluster-randomized controlled trial. Surveys were completed by 341 stimulant-treated patients at baseline and three follow-up assessments. Results: In intent-to-treat analyses of patient reports, SDP adolescents reported more provider use of diversion prevention strategies compared to TAU. They also reported more parent-patient communication about diversion. Provider satisfaction with the training was strong. Conclusions: Pediatricians can make use of clinical practice strategies for the prevention of stimulant diversion following a 1-hr training; findings are novel given their reliance on confidential patient report of provider behavior and increase confidence in the results. Coupled with the positive provider satisfaction ratings, results suggest that this brief workshop may be an option for concerned providers that also has the effect of increasing discussion at home about safe use of stimulants.

Prospective graduate students' noncognitive attributes are commonly evaluated as a part of a holistic review of their admission applications. Yet it is difficult to determine which noncognitive attributes are considered by those who evaluate graduate admissions applications and what approaches they take to measure applicants' noncognitive attributes. It is even less clear to what degree prospective graduate students understand how they are evaluated for graduate admissions and how the evaluation of their noncognitive attributes factor into admissions decisions. Drawing on surveys of graduate enrollment management (GEM) professionals and prospective graduate students in the United States, our study investigated the noncognitive attributes prospective graduate students and GEM professionals deem important to success in graduate school and the application components each group believes demonstrate those attributes. Results suggest that some alignment exists between the perspectives of prospective graduate students and GEM professionals on the noncognitive attributes most important for completing a graduate program of study. We share recommendations for improving the agreement between prospective graduate students and GEM professionals including the need for more explicit and transparent communication about how graduate admissions applications are evaluated, which is of particular importance as admissions processes forgo the consideration of applicants' race.

This article discusses multimodal practices in the context of teaching and learning and how this idea might inform and facilitate mathematical learning, especially for Latinx students. We discuss qualitative data drawn from a study of an elementary bilingual classroom (age 10 and age 11) in a Midwestern city (USA) that is exceptional because the students successfully do high-level mathematics. We describe one class episode and one student's use of multiple resources to create meaning. Through this we highlight the nature and relevance of multimodal practices for learning mathematics. This case highlights the necessity of creating environments, where students, especially those who have been historically excluded, use resources to make meaning and gain greater access to mathematics.

Today math teachers can best reach their students and show them how math surrounds us by using manipulatives, children's literature, and GeoGebra while teaching mathematics. These are some of the best pedagogical practices for teaching mathematics today. In our high-tech world, students need to be proficient in science, technology, engineering, and mathematics (STEM) fields. As endorsed by National Council of Teachers of Mathematics (2000) and stressed in common core state standards in mathematics, it is important that we teach with technology, address dispositions and math anxiety, and make the math that young people are learning pertinent and meaningful. Frequently, it may be best to start teaching young people geometry first as opposed to numbers, which are considered more abstract and difficult to learn. Geometry is one of the most tangible divisions of math and concentrating on this first can help students' whole view of mathematics and their insolences towards learning the subject. Nowadays teachers also need to be cognizant and checking for attitudes and dispositions toward learning mathematics, as math anxiety is an issue in today's classrooms. This paper will revisit the best pedagogical practices for teaching math, the review of the use of math manipulatives, children's books, and GeoGebra to help teachers create mathematically confident young people.

The purpose of this synthesis study was to assess the reliability and validity of the Draw-A-Scientist Test (DAST) and its variations across multiple studies, aiming to understand limitations and propose modifications for future application within and beyond the science domain. Given the existence of multiple DAST versions, this study quantified the frequency of validity threats across various DAST variations. Literature review results indicated that despite its widespread use, the DAST and its variations consistently encounter challenges related to construct validity and external validity. Additionally, this synthesis identified literature limitations in testing concurrent validity, predictive validity, and inter-rater reliability when applicable.

A pervasive issue in the school choice literature is whether schools of choice cream skim students by enrolling high-achieving, less-challenging, or less-costly students. Similarly, schools of choice may "push out" low-achieving, more-challenging, or more-costly students. Using longitudinal student-level data from Indiana, we created multiple measures to examine whether there is evidence consistent with the claims of voucher-participating private schools cream skimming the best students from public schools or pushing out voucher-receiving students. We do not find evidence consistent with the claim of cream skimming. However, we find evidence consistent with the claim of private schools pushing out the lowest-achieving voucher students. This is the first study to examine these two issues within a statewide private school voucher program.

Objectives: This review examines the sexual development of young men through a precarious manhood framework. The teenage and emerging adulthood years are a time of change and uncertainty for many boys and young men, heightening concerns about manhood. They are also a time when boys and young men are learning about and experimenting with sex. Sex and (hetero)sexuality are means for establishing and proving manhood, especially during a developmental period when other avenues (e.g. financial success) may be less available. Methods and Results: This paper reviews research connecting precarious notions of manhood to sexual development across three areas. First, we examine how precarious manhood encourages sexual risk-taking and objectification of sexual partners. Second, we review research connecting precarious manhood to men's sexual violence. Third, we link precarious manhood to men's derogation of gender and sexuality minority (LGBTQ+) individuals and groups. Conclusion: We end the paper by suggesting how sexual education programmes may consider a precarious manhood framework to foster healthier sexual development.

This chapter critiques and builds upon critical digital literacy studies by synthesizing queer theory to inspire more inclusive approaches to understandings of digital literacy.

Self-efficacy has emerged as a popular construct in second language research, especially in the frontline and practitioner-researcher spaces. A troubling trend in the relevant literature is that self-efficacy is often measured in a general or global manner. Such research ignores the fact that self-efficacy is a smaller context-driven construct that should be measured within a specific task or activity where time, place, and purpose domains are considered in the creation of the measurement. Task-based language teaching researchers have also largely neglected the affective factors that may influence task participation, including self-efficacy, despite its potential application to understanding task performance. In this report, we present an instrument specifically developed to measure English as a foreign language students' self-efficacy beliefs when performing a dialogic, synchronous, quasi-formal group discussion task. The instrument's underlying psychometric properties were assessed (N = 130; multisite sample from Japanese universities) and evidence suggested that it could measure a unidimensional construct with high reliability. The aggregate scale constructed from the instrument's items also displayed a central tendency and normal unimodal distribution. This was a positive finding and suggested that the instrument could be useful in producing a self-efficacy measurement for use in the testing designs preferred by second language researchers. The potential applications of this instrument are discussed while highlighting how this report acts as an illustration for investigators to use when researching self-efficacy.

The use of natural and non-natural play materials in early childhood education is a critical facilitator to children's learning and development. Different materials vary in their affordances for sophisticated play, imagination, and creativity, which contribute to children's complex thinking; with the current focus on technology, it has been suggested to balance its use with other materials. While childhood experiences with nature carry numerous benefits for development and complex thinking, most of the natural affordances have been documented in outdoor settings or with nature-based pedagogical approaches. The purpose, here, is to gain a better understanding of natural and non-natural material use across matched activities and approaches, in their affordances for preschool children's complex thinking during quality play. Using a cultural-historical interpretivist analysis of children's playful work and comments, findings indicated that both material types contributed to complex thinking, imagination, and creativity, but deeper connections and wider variety arose with natural materials. Findings suggest that teachers increase their use of natural materials in teaching, to help children develop deeper conceptual understandings and representations of their world.

The purpose of this article is to share the examination of inclusivity as a paradigm for fostering authenticity and agency (Moore, 2017) among teacher candidates. This framing challenges the notion of inclusion as a tool of meritocracy used to manage learners through expectations that uphold monolingualism, decenter racial histories, and rely on rigid behavior plans. In this work, the authors interrogate the impact inclusion as assimilation has on English learners' authentic ways of knowing and being. Thus, they present a conceptualization of spaces of difference (Agbenyaga & Klibthong, 2012) within the context of an Inclusive Early Childhood Teacher Education (IECTE) program and the objectives of the Preparing Inclusive Early Childhood Educators (PIECE) project. With its rigorous coursework, clinical experiences, multi-tiered mentorship, and practice-based professional development, the PIECE project aims to develop inclusive early childhood educators at the preservice and in-service levels. Infused throughout the PIECE project is an emphasis on cultivating the knowledge and skills needed to provide high-quality instruction that improves educational outcomes for English learners (ELs). Frameworks of transformative theory and intersectionality perspectives provided the authors with a grounding for the work within the PIECE project community of learners (i.e., teacher candidates, teacher educators, and school district partners). This article summarizes critical concepts of inclusivity centered in the PIECE project work. These concepts include (1) understanding oneself to look beyond; (2) disrupting notions of normalcy and naturalized language; and (3) reconceptualizing inclusivity as a social justice act.

School psychology professionals rely on professional literature to access information on scientifically supported practices. Counseling is certainly one of those practices. The purpose of this review was to determine how many articles published in prominent peer-reviewed school psychology journals have addressed providing effective counseling services to children and youth. We wanted to determine the types of counseling approaches that were described in those articles and which approaches garnered the most attention. Findings revealed that there were relatively few articles about counseling in prominent school psychology journals. Interestingly, most studies employed quantitative rather than qualitative designs and analyses. Cognitive behavior therapy (CBT) was the approach that was implemented the most in empirical studies across the school psychology journals. Empirical studies mainly included elementary and middle school students from diverse racial and ethnic groups who were receiving counseling services in a small group (tier 2) format. Implications for the profession of school psychology are provided.

This study investigated how students' self-reported individual differences predicted second language (L2) spoken discussion task output, an objective behavioral outcome, in the Japanese university English as a Foreign Language (EFL) context. Although numerous psychological theories are used as a rationale for task-based language teaching (TBLT), few studies have investigated the impact of individual differences variables on task performance. To address this gap, a cross-validation procedure was used with students (N = 439) from two different universities. They completed questionnaires to measure willingness to communicate (WTC), speaking self-efficacy (SSE), and perceived communicative competence (PCC). They also engaged in a quasiacademic eight-minute group discussion task (TBLT design). This discussion was recorded and transcribed, with the number of words produced used as an objective measure of L2 task production. In the better fitting mediation structural equation model, the influences of SSE and PCC on spoken L2 task production were fully mediated by WTC (R[superscript 2] = 0.21).

Universities are generally understood as organizations that extend knowledge based on codified bodies of work developed from systematic research and scholarship. This article examines the emergence of an organizational form that increasingly competes in contemporary higher education: the therapeutic university. A recent phenomenon, the therapeutic university is predicated on emotion in which the goal is to make the experience as a student as comfortable as possible. The article discusses organizational morphology of the therapeutic university by identifying practices within it. The practices establish a contest between a rational-universalistic orientation of the university on the one hand and an emotion-particularistic orientation on the other. The article provides an explanation for why this organizational form arose and what it purports to accomplish. Its operations are ensnared by major paradox: as its identity implies, the therapeutic university postures to do good, but its practices, it is argued, debilitate students and higher learning. The mandate that the broader society gives to higher education is thereby susceptible to lost confidence. The article concludes by discussing a way in which universities may be inoculated from the conditions that support their present-day therapeutic proclivities.

This article describes the Boston Teacher Leadership Certificate program created to expand teachers' capacity for teacher leadership roles. The professional learning was designed to strengthen teachers' leadership skills while also paying attention to whether and under what conditions they were more successful in their roles. To monitor the program's impact, the Boston Teacher Leadership Certificate program used four data routines: comparing pre-and post-course surveys, analyzing exit slips, reviewing online discussions, and looking together at student work. These routines supported collaborative inquiry, shared ownership for the quality of the work, and learning at all levels. At the end of the professional learning, 95% of course participants indicated that the course would improve their ability to have a positive impact on others' teaching practice, and 91% felt that the course would have a positive impact on their own teaching practice.

"Quality" refers nominatively to a standard of performance. Quality is the central idea that differentiates speech protected by academic freedom (the right to worthwhile utterances) from constitutionally protected speech (the right to say anything at all). Extant documents and discussions state that professional peers determine quality based on norms of a field. But professional peers deem utterances and activities as consonant with quality only in reference to criteria that establish meaning of the term. In the absence of articulation, these criteria are ambiguous. Consequently, there exists recurrent confusion about what faculty members have a defensible right to say and do. This article develops an ontology of quality in reference to higher education teaching, a component of academic careers generally not subject to extensive peer review and where instructors thereby exercise considerable autonomy. The ontology identifies three criteria that bound quality: "constraint, context," and "amplitude." Boundedness exists only insofar as boundaries are controlled. The article examines two types of problems in professional control that affect quality: "slippage" and "overreach." Both are instances of organizational deviance and abrogation of professional ethics. It is argued that the patterns threaten the structural integrity and public confidence of faculty, fields, and higher education institutions.

Recent reports show that low-income students make up a significant share of those participating in higher education, and their well-being constitutes a key factor that influences their college success. This mixed-methods study examined first-year, low-income students' time use and its relationship to well-being framed by an equity-oriented lens that recognizes the time constraints low-income students navigate. Our mixed methods findings identified the link between time use and well-being and--critically--empirical explanations for these links. First, leveraging a unique experience sampling survey design and multilevel analyses, we found that attending class, studying or doing homework, and working for pay were consistently and adversely related to low-income students' well-being. Low-income students who were also first-generation in college fared worse than continuing-generation students when engaging in these experiences. On the other hand, socializing was positively related to low-income students' well-being. Second, an exploration of longitudinal data from hundreds of student interviews illuminated two primary factors that shaped the relationship between low-income students' time use and well-being: (a) structuring time and developing a routine, and (b) the power of reflection and meaning-making. These findings provide important novel insights about low-income students' college experiences and the relationship between their time use and well-being, and offer crucial guidance for educators on how to support low-income students' well-being as they navigate college.

Background: Gestures are an integral component in human-to-human communication when the speaker is visually present to the listener. In the past several years, research has examined how computer-generated pedagogical agents can be designed to perform the four main gesture types and what this means for agent persona and learning outcomes. The research into agent gesturing has only explored gestures without other presentation strategies such as visual aids or verbal redundancy to properly explore the impact of gestures, and to avoid overly "rich" displays of information. Objective: The objective of this study is to explore the use of static images and varying frequencies of gestures to assess whether two visual inputs increases the risk of the split-attention effect, and to investigate the potential for visual redundancy when two visual inputs coincide with narration. Data on cognitive load, agent persona, and learning outcomes (recall and transfer) will be collected to measure participants' learning experience while acquiring procedural knowledge, specifically regarding the principles of lightning, in comparison to previous research. Method: A mixed methods approach consisted of three gesture frequency conditions (enhanced, average, no) with 118 participants. Quantitative data were analysed using a random-effect linear regression model; whereas qualitative data was collected through individual interviews that lasted 15-20 min. Results and Conclusions: The use of enhanced gesture frequency and images may significantly increase intrinsic cognitive load, but gestures and images do not cause extraneous cognitive load. The enhanced gesture condition significantly outperformed the no-gesture condition. Interviews indicated that depending upon the gesture condition, students selectively attended to information that they perceived as offering them the greatest learning opportunity. Using two visual inputs does not cause split-attention, nor does it provide evidence of a visual redundancy effect.

Skeletal muscle has a classic structure function relationship; both skeletal muscle microstructure and architecture are directly related to force generating capacity. Biopsy, the gold standard for evaluating muscle microstructure, is highly invasive, destructive to muscle, and provides only a small amount of information about the entire volume of a muscle. Similarly, muscle fiber lengths and pennation angles, key features of muscle architecture predictive of muscle function, are traditionally studied via cadaveric dissection. Noninvasive techniques such as diffusion magnetic resonance imaging (dMRI) offer quantitative approaches to study skeletal muscle microstructure and architecture. Despite its prevalence in applications for musculoskeletal research, clinical adoption is hindered by a lack of understanding regarding its sensitivity to clinically important biomarkers such as muscle fiber cross-sectional area. This review aims to elucidate how dMRI has been utilized to study skeletal muscle, covering fundamentals of muscle physiology, dMRI acquisition techniques, dMRI modeling, and applications where dMRI has been leveraged to noninvasively study skeletal muscle changes in response to disease, aging, injury, and human performance. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Community engagement in the planning process to build large-scale solar (LSS) projects can win local support and advance procedural justice. However, an understanding of community engagement in current LSS development is lacking. Using responses from a U.S. nationwide survey (n = 979) of residential neighbors living within 3 miles (4.8 km) of completed LSS projects (i.e. “solar neighbors”) and project details from the U.S. Large-Scale Solar Photovoltaic Database (USPVDB), this study seeks to answer the following questions: How are solar neighbors' perceptions of community engagement associated with their attitudes toward their LSS projects? How do solar neighbors' perceptions of community engagement compare to their expectations? And, how do neighbors explain what they perceived about the planning process? We answer these questions using mixed methods, including regression modeling, a new gap analysis technique, and qualitative coding. We find that higher perceived engagement is associated with more positive attitudes toward the project, even when controlling for respondents who acted in opposition. Supporters and opponents alike expect more engagement than they perceived and information about projects both before construction and after operation is lacking. Awareness and engagement expectations increase at certain project size and proximity thresholds. However, most neighbors expect the public to offer input during engagement, but not make decisions. We contextualize these findings with explanatory comments from respondents.

With the goal of better understanding stimulation in crystalline rock for improving enhanced geothermal systems (EGS), the EGS Collab Project performed a series of stimulations and flow tests at 1.25 and 1.5 km depths. The tests were performed in two well-instrumented testbeds in the Sanford Underground Research Facility in Lead, South Dakota, United States. The testbed for Experiment 1 at 1.5 km depth contained two open wells for injection and production and six instrumented monitoring wells surrounding the targeted stimulation zone. Four multi-step stimulation tests targeting hydraulic fracturing and nearly year-long ambient temperature and chilled water flow tests were performed in Experiment 1. The testbed for Experiments 2 and 3 was at 1.25 km depth and contained five open wells in an outwardly fanning five-spot pattern and two fans of well-instrumented monitoring wells surrounding the targeted stimulation zone. Experiment 2 targeted shear stimulation, and Experiment 3 targeted low-flow, high-flow, and oscillating pressure stimulation strategies. Hydraulic fracturing was successful in Experiments 1 and 3 in generating a connected system wherein injected water could be collected. However, the resulting flow was distributed dynamically, and not entirely collected at the anticipated production well. Thermal breakthrough was not observed in the production well, but that could have been masked by the Joule-Thomson effect. Shear stimulation in Experiment 2 did not occur – despite attempting to pressurize the fractures most likely to shear – because of the inability to inject water into a mostly-healed fracture, and the low shear-to-normal stress ratio. The EGS Collab experiments are described to provide a background for lessons learned on topics including induced seismicity, the correlation between seismicity and permeability, distributed and dynamic flow systems, thermoelastic and pressure effects, shear stimulation, local geology, thermal breakthrough, monitoring stimulation, grouting boreholes, modeling, and system management.

Introduction: Advance practice clinicians (APC) play significant roles in academic and community emergency departments (ED). In attendings and residents, prior research demonstrated that productivity is dynamic and changes throughout a shift in a predictable way. However, this has not been studied in APCs. The primary outcome of this study was to model productivity for APCs in community EDs to determine whether it changes during a shift similar to the way it does for attendings and residents.Methods: This was a retrospective, observational analysis of 10-hour APC shifts at two suburban hospitals, worked by 14 total individuals. We examined the number of patients seen per hour of the shift by experienced APCs who see all acuity and staff all patients with an attending. We used a generalized estimating equation to construct the model of hour-by-hour productivity change.Results: We analyzed 862 shifts over one year across two sites, with three shift start times. Site 1 10 AM–8 PM saw an average of 13.31 (95% confidence interval [CI] 13.02–13.63) patients per shift; Site 2 8 AM–6 PM saw an average of 12.64 (95% CI 12.32–13.06) patients per shift; Site 2 4 PM–2 AM saw an average of 12.53 (95% CI 12.04–12.82) patients per shift. Across all sites and shifts, hour 1 saw the highest number of patients. Each subsequent hour was associated with a small, statistically significant decrease over the previous hours. This was most pronounced in the shift’s last two hours.Conclusion: The productivity of APCs demonstrates a similar pattern of hourly declines observed in both resident and attending physicians. This corroborates prior findings that patients per hour is a dynamic variable, decreasing throughout a shift. This provides further external validity to prior research to include both APCs and community EDs. These departments must take this phenomenon into account, as it has scheduling and operational consequences.

PURPOSE OF REVIEW: Chronic pain is highly prevalent and involves a complex interaction of sensory, emotional, and cognitive processes, significantly influenced by ambient temperature. Despite advances in pain management, many patients continue to experience inadequate pain relief. This review aims to consolidate and critically evaluate the current evidence on the impact of ambient temperature on chronic pain conditions such as fibromyalgia (FM), multiple sclerosis (MS), complex regional pain syndrome (CRPS), and osteoarthritis (OA). RECENT FINDINGS: Patients with FM often report pain exacerbations due to temperature changes, with studies showing lower thresholds for heat and cold-induced pain compared to healthy controls. In MS, the Uhthoff phenomenon, characterized by temperature-induced neurological deterioration, underscores the significance of ambient temperature in pain management. CRPS patients exhibit heightened pain sensitivity to temperature changes, with both warm and cold stimuli potentially aggravating symptoms. OA patients frequently report increased pain and rigidity associated with lower temperatures and higher humidity. Understanding the mechanisms through which temperature influences pain can enhance pain management strategies. This review highlights the need for further research to elucidate these mechanisms and develop targeted interventions, ultimately improving the quality of life for individuals with chronic pain conditions.

The field of bioelectronic medicine has advanced rapidly from rudimentary electrical therapies to cutting-edge closed-loop systems that integrate real-time physiological monitoring with adaptive neuromodulation. Early innovations, such as cardiac pacemakers and deep brain stimulation, paved the way for these sophisticated technologies. This review traces the historical and technological progression of bioelectronic medicine, culminating in the emerging potential of closed-loop devices for multiple disorders of the brain and body. We emphasize both invasive techniques, such as implantable devices for brain, spinal cord and autonomic regulation, while we introduce new prospects for non-invasive neuromodulation, including focused ultrasound and newly developed autonomic neurography enabling precise detection and titration of inflammatory immune responses. The case for closed-loop non-invasive autonomic neuromodulation (incorporating autonomic neurography and splenic focused ultrasound stimulation) is presented through its applications in conditions such as sepsis and chronic inflammation, illustrating its capacity to revolutionize personalized healthcare. Today, invasive or non-invasive closed-loop systems have yet to be developed that dynamically modulate autonomic nervous system function by responding to real-time physiological and molecular signals; it represents a transformative approach to therapeutic interventions and major opportunity by which the bioelectronic field may advance. Knowledge gaps remain and likely contribute to the lack of available closed loop autonomic neuromodulation systems, namely, (1) significant exogenous and endogenous noise that must be filtered out, (2) potential drift in the signal due to temporal change in disease severity and/or therapy induced neuroplasticity, and (3) confounding effects of exogenous therapies (e.g., concurrent medications that dysregulate autonomic nervous system functions). Leveraging continuous feedback and real-time adjustments may overcome many of these barriers, and these next generation systems have the potential to stand at the forefront of precision medicine, offering new avenues for individualized and adaptive treatment.

Disulfide bonds are ubiquitous molecular motifs that influence the tertiary structure and biological functions of many proteins. Yet, it is well known that the disulfide bond is photolabile when exposed to ultraviolet C (UVC) radiation. The deep-UV-induced S─S bond fragmentation kinetics on very fast timescales are especially pivotal to fully understand the photostability and photodamage repair mechanisms in proteins. In 1,2-dithiane, the smallest saturated cyclic molecule that mimics biologically active species with S─S bonds, we investigate the photochemistry upon 200-nm excitation by femtosecond time-resolved x-ray scattering in the gas phase using an x-ray free electron laser. In the femtosecond time domain, we find a very fast reaction that generates molecular fragments with one and two sulfur atoms. On picosecond and nanosecond timescales, a complex network of reactions unfolds that, ultimately, completes the sulfur dissociation from the parent molecule.

Introduction: Lower extremity injuries are commonly evaluated and treated in the emergency department (ED). Pain management for these injuries often consists of acetaminophen, non-steroidal anti-inflammatories, and opioids. Despite this treatment regimen, adequate analgesia is not always achieved.Case Report: A 38-year-old man presented to the ED with a non-displaced tibia-fibula fracture. The patient did not attain analgesia with intravenous medications but did get complete anesthesia of his lower leg with a combination saphenous and popliteal sciatic nerve block.Conclusion: Emergency physicians possess the skill set required to effectively perform a saphenous and popliteal sciatic nerve block and should consider adding this procedure to their armamentarium of pain management techniques in treating injuries distal to the knee.

Amidst the rising prevalence of respiratory diseases, the importance of effective lung treatment modalities is more critical than ever. However, current drug delivery systems face significant limitations that impede their efficacy and therapeutic outcome. Biohybrid microrobots have shown considerable promise for active in vivo drug delivery, especially for pulmonary applications via intratracheal routes. However, the invasive nature of intratracheal administration poses barriers to its clinical translation. Herein, we report on an efficient non-invasive inhalation-based method of delivering microrobots to the lungs. A nebulizer is employed to encapsulate picoeukaryote algae microrobots within small aerosol particles, enabling them to reach the lower respiratory tract. Post nebulization, the microrobots retain their motility (~55 μm s-1) to help achieve a homogeneous lung distribution and long-term retention exceeding five days in the lungs. Therapeutic efficacy is demonstrated in a mouse model of acute methicillin-resistant Staphylococcus aureus pneumonia using this pulmonary inhalation approach to deliver microrobots functionalized with platelet membrane-coated polymeric nanoparticles loaded with vancomycin. These promising findings underscore the benefits of inhalable biohybrid microrobots in a setting that does not require anesthesia, highlighting the substantial translational potential of this delivery system for routine clinical applications.

BackgroundDespite recent advances in the biology of IDH-wildtype glioblastoma, it remains a devastating disease with median survival of less than 2 years. However, the molecular underpinnings of the heterogeneous response to the current standard-of-care treatment regimen consisting of maximal safe resection, adjuvant radiation, and chemotherapy with temozolomide remain unknown.MethodsComprehensive histopathologic, genomic, and epigenomic evaluation of paired initial and recurrent glioblastoma specimens from 106 patients was performed to investigate the molecular evolution and cellular phenotypes underlying differential treatment responses.ResultsWhile TERT promoter mutation and CDKN2A homozygous deletion were early events during gliomagenesis shared by initial and recurrent tumors, most other recurrent genetic alterations (eg, EGFR, PTEN, and NF1) were commonly private to initial or recurrent tumors indicating acquisition later during clonal evolution. Furthermore, glioblastomas exhibited heterogeneous epigenomic evolution with subsets becoming more globally hypermethylated, hypomethylated, or remaining stable. Glioblastoma that underwent sarcomatous transformation had shorter interval to recurrence and were significantly enriched in NF1, TP53, and RB1 alterations and the mesenchymal epigenetic class. Patients who developed somatic hypermutation following temozolomide treatment had significantly longer interval to disease recurrence and prolonged overall survival, and increased methylation at 4 specific CpG sites in the promoter region of MGMT was significantly associated with this development of hypermutation. Finally, an epigenomic evolution signature incorporating change in DNA methylation levels across 347 critical CpG sites was developed that significantly correlated with clinical outcomes.ConclusionsGlioblastoma undergoes heterogeneous genetic, epigenetic, and cellular evolution that underlies prognostically different treatment responses.

ObjectivesOpioid use disorder (OUD) remains a common cause of overdose and mortality in the United States. Emergency medical services (EMS) clinicians often interact with patients with OUD, including during or shortly after an overdose. The aim of this study was to describe the characteristics and outcomes of patients receiving prehospital buprenorphine for the treatment of opioid withdrawal in an urban EMS system.MethodsWe performed a retrospective chart review of all initial cases of administration of buprenorphine-naloxone from April 2023 - July 2024 during the first 16 months of a program involving prehospital EMS administration of buprenorphine-naloxone by EMS clinicians to patients with OUD experiencing acute opioid withdrawal in San Francisco. The primary outcome involved reduction in Clinical Opioid Withdrawal Score (COWS) and other adverse events including worsened withdrawal (or increased COWS), nausea, patient destination, and loss to follow up were also assessed.ResultsBuprenorphine was administered to 131 patients. In 82 (62.6%) cases, patients presented in withdrawal after receiving naloxone from bystanders or EMS as a treatment for overdose. The average COWS prior to administration was 16.1 ± 6.5 and the median COWS prior to administration was 15 (IQR: 11-19). Of the 78 cases where a COWS was available, 74 (94.9%) experienced symptom improvement, with the median COWS dropping from 15 (IQR: 11-19) to 7 (IQR: 4-13) between first and last recorded values. No adverse effects were reported in prehospital records. There was one reported in-hospital incident of withdrawal in the Emergency Department presumably precipitated by buprenorphine. Data on outcomes after EMS transport were limited. Only six patients were successfully contacted at 30 day follow up, but five of these patients were in long-term OUD treatment programs, and three reported sustained abstinence from opioid use. During case review, we found two cases where physicians assisted EMS personnel in recognizing recent methadone use, but no other missed exclusion criteria requiring physician input.ConclusionsIn San Francisco, prehospital administration of buprenorphine for acute opioid withdrawal by EMS clinicians resulted in symptomatic improvement, and case review suggests administration can be safe without direct EMS physician oversight.

BACKGROUNDS: Digital, online assessments are efficient means to detect early cognitive decline, but few studies have investigated the relationship between remotely collected subjective cognitive change and cognitive decline. We hypothesized that the Everyday Cognition Scale (ECog), a subjective change measure, predicts longitudinal change in cognition in the Brain Health Registry (BHR), an online registry for neuroscience research. METHODS: This study included BHR participants aged 55 + who completed both the baseline ECog and repeated administrations of the CANTAB® Paired Associates Learning (PAL) visual learning and memory test. Both self-reported ECog (Self-ECog) and study partner-reported ECog (SP-ECog), and two PAL scores (first attempt memory score [FAMS] and total errors adjusted [TEA]) were assessed. We estimated associations between multiple ECog scoring outputs (ECog positive [same or above cut-off score], ECog consistent [report of consistent decline in any item], and total score) and longitudinal change in PAL. Additionally we assessed the ability of ECog to identify decliners, who exhibited the worst PAL progression slopes corresponding to the fifth percentile and below. RESULTS: Participants (n = 16,683) had an average age of 69.07 ± 7.34, 72.04% were female, and had an average of 16.66 ± 2.26 years of education. They were followed for an average of 2.52 ± 1.63 visits over a period of 11.49 ± 11.53 months. Both Self-ECog positive (estimate = -0.01, p

Brain inflammation, with an increased density of microglia and macrophages, is an important component of Alzheimer's disease and a potential therapeutic target. However, it is incompletely characterized, particularly in patients whose disease begins before the age of 65 years and, thus, have few co-pathologies. Inflammation has been usefully imaged with translocator protein (TSPO) PET, but most inflammation PET tracers cannot image subjects with a low-binder TSPO rs6971 genotype. In an important development, participants with any TSPO genotype can be imaged with a novel tracer, 11C-ER176, that has a high binding potential and a more favourable metabolite profile than other TSPO tracers currently available. We applied 11C-ER176 to detect brain inflammation in mild cognitive impairment (MCI) caused by early-onset Alzheimer's disease. Furthermore, we sought to correlate the brain localization of inflammation, volume loss, elevated amyloid-β (Aβ)and tau. We studied brain inflammation in 25 patients with early-onset amnestic MCI (average age 59 ± 4.5 years, 10 female) and 23 healthy controls (average age 65 ± 6.0 years, 12 female), both groups with a similar proportion of all three TSPO-binding affinities. 11C-ER176 total distribution volume (VT), obtained with an arterial input function, was compared across patients and controls using voxel-wise and region-wise analyses. In addition to inflammation PET, most MCI patients had Aβ (n = 23) and tau PET (n = 21). For Aβ and tau tracers, standard uptake value ratios were calculated using cerebellar grey matter as region of reference. Regional correlations among the three tracers were determined. Data were corrected for partial volume effect. Cognitive performance was studied with standard neuropsychological tools. In MCI caused by early-onset Alzheimer's disease, there was inflammation in the default network, reaching statistical significance in precuneus and lateral temporal and parietal association cortex bilaterally, and in the right amygdala. Topographically, inflammation co-localized most strongly with tau (r = 0.63 ± 0.24). This correlation was higher than the co-localization of Aβ with tau (r = 0.55 ± 0.25) and of inflammation with Aβ (0.43 ± 0.22). Inflammation co-localized least with atrophy (-0.29 ± 0.26). These regional correlations could be detected in participants with any of the three rs6971 TSPO polymorphisms. Inflammation in Alzheimer's disease-related regions correlated with impaired cognitive scores. Our data highlight the importance of inflammation, a potential therapeutic target, in the Alzheimer's disease process. Furthermore, they support the notion that, as shown in experimental tissue and animal models, the propagation of tau in humans is associated with brain inflammation.

Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimers disease, Parkinsons disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of AREG+ dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases.

PurposeTo validate automated counts of presumed anterior chamber (AC) cells in eyes with histories of uveitis involving the anterior segment using swept-source (SS) anterior segment optical coherence tomography (AS-OCT) against manual counts and compare automated counts against Standardized Uveitis Nomenclature (SUN) criteria.MethodsEyes were imaged with the ANTERION SS AS-OCT device (Heidelberg Engineering). A fully automated custom algorithm quantified the number of hyper-reflective foci (HRF) in line-scan images. Automated and manual counts were compared using interclass correlation (ICC) and Pearson correlation coefficient. Automated counts were compared to SUN grades using a mixed-effects linear regression model.Results90 eyes (54 participants) were included; 67 eyes (41 participants) had histories of uveitis, while 23 eyes (13 healthy participants) served as controls. ICC comparing automated to manual counts was 0.99 and the Pearson correlation coefficient was 0.98. Eyes at each SUN grade with corresponding median HRF (interquartile range [IQR]) were: Grade 0, 42 eyes, 2 HRF (0,4); 0.5+, 10 eyes, 10 HRF (8,15); 1+, 9 eyes, 22 HRF (15,33); 2+, 3 eyes, 27 HRF; 3+, 2 eyes, 128 HRF; 4+, 1 eye, 474 HRF. For every 1-step increase in grade, automated count increased by 38 (p

Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution. Tumor initiating cells displayed a distinct stem-like state, defined by aberrant proliferative, hypoxic, squamous differentiation, and partial epithelial to mesenchymal invasive gene programs. YAP-mediated tumor initiating cell programs included activation of oncogenic transcriptional networks and mTOR signaling, and recruitment of myeloid cells to the invasive front contributing to tumor infiltration. Tumor initiating cell transcriptional programs are conserved in human head and neck cancer and associated with poor patient survival. These findings illuminate processes underlying cancer initiation at single cell resolution, and identify candidate targets for early cancer detection and prevention.

People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure. We discover a plasma proteomic signature that may in part reflect or contribute to HIV-associated atrial remodeling, many features of which are associated with older age and time to incident heart failure among an independent community-based cohort without HIV. This proteomic profile was statistically enriched for immune checkpoint proteins, tumor necrosis factor signaling, ephrin signaling, and extracellular matrix organization, identifying possible shared pathways in HIV and aging that may contribute to risk of heart failure.

PurposeCorneal dysmorphologies (CDs) are typically classified as either regressive degenerative corneal dystrophies (CDtrs) or defective growth and differentiation-driven corneal dysplasias (CDyps). Both eye disorders have multifactorial etiologies. While previous work has elucidated many aspects of CDs, such as presenting symptoms, epidemiology, and pathophysiology, the genetic mechanisms remain incompletely understood. The purpose of this study was to analyze phenotype data from 8,707 knockout mouse lines to identify new genes associated with the development of CDs in humans.Methods8,707 knockout mouse lines phenotyped by the International Mouse Phenotyping Consortium were queried for genes associated with statistically significant (P

BackgroundPerivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility.MethodsWe developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer's Disease Neuroimaging Initiative, the National Alzheimer's Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models.FindingsOur fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer's disease biomarkers.InterpretationThese robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia.FundingUS National Institutes of Health.

BackgroundFew studies have investigated associations between per- and polyfluoroalkyl substances (PFAS) and childhood cancers. Detectable levels of PFAS in California water districts were reported in the Third Unregulated Contaminant Monitoring Rule for 2013-2015.MethodsGeocoded residences at birth were linked to corresponding water district boundaries for 10,220 California-born children (aged 0-15 years) diagnosed with cancers (2000-2015) and 29,974 healthy controls. A pharmacokinetic model was used to predict average steady-state maternal serum concentrations of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) from contaminated drinking water. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) per doubling of background exposure were calculated for cancers with at least 90 cases.ResultsPredicted PFOS and PFOA maternal serum concentrations ranged from background (5 ng/ml PFOS and 2 ng/ml PFOA) to 22.89 ng/ml and 6.66 ng/ml, respectively. There were suggestive associations between PFOS and nonastrocytoma gliomas (n = 268; AOR = 1.26; 95% CI: 0.99, 1.60), acute myeloid leukemia (n = 500; AOR = 1.14; 95% CI: 0.94, 1.39), Wilms tumors (n = 556, AOR = 1.15; 95% CI: 0.96, 1.38), and noncentral system embryonal tumors (n = 2,880; AOR = 1.07; 95% CI: 0.98, 1.17), and between PFOA and non-Hodgkin lymphoma (n = 384; AOR = 1.19; 95% CI: 0.95, 1.49). Among children of Mexico-born mothers, there was increased risk of Wilms tumor (n = 101; AORPFOS = 1.52; 95% CI: 1.06, 2.18; AORPFOA = 1.59, 95% CI: 1.12, 2.24) and noncentral system embryonal tumors (n = 557; AORPFOS = 1.24, 95% CI: 1.03, 1.50; AORPFOA = 1.19, 95% CI: 0.98, 1.45).ConclusionResults suggest associations between predicted prenatal maternal PFAS serum concentrations and some childhood cancers. Future analyses are warranted.

RATIONALE & OBJECTIVE: Dialysis patient care technicians (PCTs) provide essential, frontline care for patients receiving in-center hemodialysis. We qualitatively explored perceptions of the PCT job role, responsibilities, and training among current PCTs, non-PCT dialysis staff, and patients receiving hemodialysis. STUDY DESIGN: Focus group study. SETTING & PARTICIPANTS: Discussions were conducted in March-May 2023 among US PCTs, non-PCT staff, and patients. ANALYTICAL APPROACH: Thematic analysis was conducted using inductive and deductive strategies. RESULTS: Seven focus groups (N = 36 participants) were conducted (3 with PCTs [n = 19], 2 with non-PCT staff [n = 6], and 2 with patients [n = 11]). Eight themes emerged: (1) value of PCT role is not reflected in job or organizational policies and structures; (2) PCTs play a flexible and often ill-defined role in dialysis clinics; (3) despite being in a position with high risk of burnout, PCTs find ways to persevere and provide high-quality care; (4) PCTs are often perceived as helpers or ancillary rather than an integral part of the dialysis care team; (5) PCT job training and qualifications are not standardized and often not commensurate with job expectations and responsibilities; (6) PCT-patient relationships are deeply valued, but boundaries can be fluid and become blurred because of the frequency and nature of dialysis care; (7) dialysis patients and staff are vulnerable to multilevel workplace safety issues; and (8) PCT-staff dynamics have a strong impact on employee morale, clinic efficiency, and patient satisfaction. LIMITATIONS: Non-English-speaking participants and physicians were excluded, limiting diversity in perspectives. CONCLUSIONS: PCTs play a multifaceted role in dialysis care that is highly valued among patients and staff but not always reflected in actual tasks performed by PCTs, training received by PCTs, or the respect afforded to PCTs. Our findings are actionable and can inform future intervention-based work aimed at improving the PCT role in US hemodialysis care.

A significant challenge on an exascale computer is the speed at which we compute results exceeds by many orders of magnitude the speed at which we save these results. Therefore the Exascale Computing Project (ECP) ALPINE project focuses on providing exascale-ready visualization solutions including in situ processing. In situ visualization and analysis runs as the simulation is run, on simulations results are they are generated avoiding the need to save entire simulations to storage for later analysis. The ALPINE project made post hoc visualization tools, ParaView and VisIt, exascale ready and developed in situ algorithms and infrastructures. The suite of ALPINE algorithms developed under ECP includes novel approaches to enable automated data analysis and visualization to focus on the most important aspects of the simulation. Many of the algorithms also provide data reduction benefits to meet the I/O challenges at exascale. ALPINE developed a new lightweight in situ infrastructure, Ascent.