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"Opportunity to learn" has evolved into an umbrella phrase for describing a large range of settings, resources, structures, and processes. The aim of this study is to develop a conceptual framework that can accommodate a wide range of opportunities to learn, not just those provided by teachers in classrooms. An inclusive framework can bring together diverse studies about opportunity to learn, increasing synergies and uncovering interconnections, and making more visible marginalized forms of learning. It can also be used as a framework for holding governments, education authorities, and policy makers accountable for providing equitable opportunities and conditions to learn. This article presents a three-dimensional conceptual framework of opportunities and conditions to learn (OCL) that captures (a) notions of what opportunities exist and where those opportunities exist and opportunities offered by whom, as well as (b) a spate of conditions that can shape those opportunities.

Abstract Background Research dissemination is essential to accelerate the translating of evidence into practice. Little is known about dissemination among Chinese public health researchers. This study aimed to explore the understanding and practices of disseminating research findings and to identify barriers and facilitators that influence dissemination activities to non-research audiences. Methods This study deployed an exploratory qualitative design with purposive and snowball sampling. One focus group with 5 participants and 12 in-depth interviews were conducted with participants working in diverse fields from universities (n = 10), the National Chinese Center for Disease Control and Prevention (n = 4), the Chinese National Cancer Center (n = 1), the Chinese National Center for Cardiovascular Disease (n = 1), and China office of a global research institute (n = 1) from May to December 2021 to reach saturation. Data were initially analyzed using inductive thematic analysis. The designing for dissemination (D4D) logic model was then used to organize themes and subthemes. Two coders independently coded all transcripts and discussed disparities to reach a consensus. Results Out of 17 participants, 12 misunderstood the concept of dissemination; 14 had disseminated to non-research audiences: 10 to the public, 10 to practitioners, and 9 to policymakers. We identified multiple barriers to dissemination to non-research audiences across four phases of the D4D logic model, including low priority of dissemination, limited application of D4D strategies, insufficient support from the research organizations, practice settings, and health systems, and overemphasis on academic publications. Conclusions There was a lack of understanding and experience of dissemination, indicating a lack of emphasis on active dissemination in China. We provide implications for raising awareness, building capacity, facilitating multidisciplinary collaboration, providing incentives and infrastructure, changing climate and culture, establishing communication and executive networks, and accelerating systematic shifts in impact focus.

Abstract Background and objectives Tolebrutinib is a covalent BTK inhibitor designed and selected for potency and CNS exposure to optimize impact on BTK-dependent signaling in CNS-resident cells. We applied a translational approach to evaluate three BTK inhibitors in Phase 3 clinical development in MS with respect to their relative potency to block BTK-dependent signaling and exposure in the CNS Methods We used in vitro kinase and cellular activation assays, alongside pharmacokinetic sampling of cerebrospinal fluid (CSF) in the non-human primate cynomolgus to estimate the ability of these candidates (evobrutinib, fenebrutinib, and tolebrutinib) to block BTK-dependent signaling inside the CNS. Results In vitro kinase assays demonstrated that tolebrutinib reacted with BTK 65-times faster than evobrutinib, while fenebrutinib, a classical reversible antagonist with a K i value of 4.7 nM and slow off-rate (1.54 x 10-5 s-1), also had an association rate 1760-fold slower (0.00245 μM-1 * s-1). Estimates of cellular potency were largely consistent with the in vitro kinase assays, with an estimated IC50 of 0.7 nM for tolebrutinib against 33.5 nM for evobrutinib and 2.9 nM for fenebrutinib. We then observed that evobrutinib, fenebrutinib, and tolebrutinib achieved similar levels of exposure in non-human primate CSF after oral doses of 10 mg/kg. However, tolebrutinib CSF exposure (4.8 ng/mL) (k p,uu CSF=0.40) exceeded the IC90 (the estimated concentration inhibiting 90% of kinase activity) value, while evobrutinib (3.2 ng/mL) (k p,uu CSF=0.13) and fenebrutinib (12.9 ng/mL) (kp,uu CSF=0.15) failed to reach the estimated IC90 values. Conclusions Tolebrutinib was the only candidate of the three that attained relevant CSF exposure in non-human primates. Graphical Abstract

Abstract In their article on “Navigating the Field of Implementation Science Towards Maturity: Challenges and Opportunities,” Chambers and Emmons describe the rapid growth of implementation science along with remaining challenges. A significant gap remains in training and capacity building. Formats for capacity building include university degree programs, summer training institutes, workshops, and conferences. In this letter, we describe and amplify on five key areas, including the need to (1) identify advanced competencies, (2) increase the volume and reach of trainings, (3) sustain trainings, (4) build equity focused trainings, and (5) develop global capacity. We hope that the areas we highlight will aid in addressing several key challenges to prioritize in future efforts to build greater capacity in implementation science.

The purpose of this article is to introduce an action-oriented framework aimed at clarifying and promoting a principled approach to creativity in education. A principled approach to creativity refers to the design and implementation of positive creative educational endeavors, which are guided by a set of agreed-upon commitments aimed at making a positive contribution to the learning and lives of others. We open by discussing how our conception of a principled approach to creativity connects to positive creativity and how this approach can guide creative educational endeavors. More specifically, we discuss the opportunities and responsibilities associated with a principled approach to creativity, including how educators, students, and researchers can re-conceptualize creative opportunities, creative risk-taking, creative action, and the intended and unintended outcomes that result from promoting creative thought and action in and beyond the walls of schools and classrooms.

CRISPR-mediated genome editing of primary human lymphocytes is typically carried out via electroporation, which can be cytotoxic, cumbersome and costly. Here we show that the yields of edited primary human lymphocytes can be increased substantially by delivering a CRISPR ribonucleoprotein mixed with an amphiphilic peptide identified through screening. We evaluated the performance of this simple delivery method by knocking out genes in T cells, B cells and natural killer cells via the delivery of Cas9 or Cas12a ribonucleoproteins or an adenine base editor. We also show that peptide-mediated ribonucleoprotein delivery paired with an adeno-associated-virus-mediated homology-directed repair template can introduce a chimaeric antigen receptor gene at the T-cell receptor α constant locus, and that the engineered cells display antitumour potency in mice. The method is minimally perturbative, does not require dedicated hardware, and is compatible with multiplexed editing via sequential delivery, which minimizes the risk of genotoxicity. The peptide-mediated intracellular delivery of ribonucleoproteins may facilitate the manufacturing of engineered T cells.

Abstract Spins of electrons in silicon MOS quantum dots combine exquisite quantum properties and scalable fabrication. In the age of quantum technology, however, the metrics that crowned Si/SiO2 as the microelectronics standard need to be reassessed with respect to their impact upon qubit performance. We chart spin qubit variability due to the unavoidable atomic-scale roughness of the Si/SiO2 interface, compiling experiments across 12 devices, and develop theoretical tools to analyse these results. Atomistic tight binding and path integral Monte Carlo methods are adapted to describe fluctuations in devices with millions of atoms by directly analysing their wavefunctions and electron paths instead of their energy spectra. We correlate the effect of roughness with the variability in qubit position, deformation, valley splitting, valley phase, spin-orbit coupling and exchange coupling. These variabilities are found to be bounded, and they lie within the tolerances for scalable architectures for quantum computing as long as robust control methods are incorporated.

Abstract Background The characteristics of the implementation process of interventions are essential for bridging the gap between research and practice. This scoping review aims to identify the implementation process of social network interventions (SNI) to address physical activity and sedentary behaviors in children and adolescents. Methods The scoping review was conducted adhering to the established guidelines. The search was carried out in the ERIC, EBSCO, EMBASE, SCOPUS, and Lilacs databases in April 2023. Social network intervention studies in children and adolescents were included, addressing physical activity or sedentary behaviors. Replicability (TIDieR), applicability (PRECIS-2), and generalizability (RE-AIM) were the explored components of the implementation process. Each component was quantitatively and separately analyzed. Then, a qualitative integration was carried out using a narrative method. Results Most SNI were theoretically framed on the self-determination theory, used social influence as a social mechanism, and used the individual typology of network intervention. Overall, SNI had strong replicability, tended to be pragmatic, and three RE-AIM domains (reach, adoption (staff), and implementation) showed an acceptable level of the generalizability of findings. Conclusions The analyzed SNI for physical activity and sedentary behaviors in adolescents tended to be reported with high replicability and were conducted pragmatically, i.e., with very similar conditions to real settings. The RE-AIM domains of reach, adoption (staff), and implementation support the generalizability of SNI. Some domains of the principles of implementation strategies of SNI had acceptable external validity (actor, action targets, temporality, dose, and theoretical justification).

PurposeIn the U.S., the percentage of youth in need of evidence-based mental health practices (EBPs) who receive them (i.e., coverage rate) is low. We know little about what influences coverage rates. In 2010, the Los Angeles County Department of Mental Health (LACDMH) launched a reimbursement-driven implementation of multiple EBPs in youth mental health care. This study examines two questions: (1) What was the coverage rate of EBPs delivered three years following initial implementation? (2) What factors are associated with the coverage rates?MethodsTo assess coverage rates of publicly insured youth, we used LACDMH administrative claims data from July 1, 2013 to June 30, 2014 and estimates of the size of the targeted eligible youth population from the 2014 American Community Survey (ACS). The unit of analysis was clinic service areas (n = 254). We used Geographic Information Systems and an OLS regression to assess community and clinic characteristics related to coverage.ResultsThe county coverage rate was estimated at 17%, much higher than national estimates. The proportion of ethnic minorities, individuals who are foreign-born, adults with a college degree within a geographic area were negatively associated with clinic service area coverage rates. Having more therapists who speak a language other than English, providing care outside of clinics, and higher proportion of households without a car were associated with higher coverage rates.ConclusionHeterogeneity in municipal mental health record type and availability makes it difficult to compare the LACDMH coverage rate with other efforts. However, the LACDMH initiative has higher coverage than published national rates. Having bilingual therapists and providing services outside the clinic was associated with higher coverage. Even with higher coverage, inequities persisted.

Older adults have the highest incidence of traumatic brain injury globally. Accurate blood-based biomarkers are needed to assist with diagnosis of patients across the spectrum of age and time post-injury. Several reports have suggested lower accuracy for blood-based biomarkers in older adults, and there is a paucity of data beyond day-1 post-injury. Our aims were to investigate age-related differences in diagnostic accuracy and 2-week evolution of four leading candidate blood-based traumatic brain injury biomarkers-plasma glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, S100 calcium binding protein B and neuron-specific enolase-among participants in the 18-site prospective cohort study Transforming Research And Clinical Knowledge in Traumatic Brain Injury. Day-1 biomarker data were available for 2602 participants including 2151 patients with traumatic brain injury, 242 orthopedic trauma controls and 209 healthy controls. Participants were stratified into 3 age categories (young: 17-39 years, middle-aged: 40-64 years, older: 65-90 years). We investigated age-stratified biomarker levels and biomarker discriminative abilities across three diagnostic groups: head CT-positive/negative; traumatic brain injury/orthopedic controls; and traumatic brain injury/healthy controls. The difference in day-1 glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1 and neuron-specific enolase levels across most diagnostic groups was significantly smaller for older versus younger adults, resulting in a narrower range within which a traumatic brain injury diagnosis may be discriminated in older adults. Despite this, day-1 glial fibrillary acidic protein had good to excellent performance across all age-categories for discriminating all three diagnostic groups (area under the curve 0.84-0.96; lower limit of 95% confidence intervals all >0.78). Day-1 S100 calcium-binding protein B and ubiquitin carboxy-terminal hydrolase L1 showed good discrimination of CT-positive versus negative only among adults under age 40 years within 6 hours of injury. Longitudinal blood-based biomarker data were available for 522 hospitalized patients with traumatic brain injury and 24 hospitalized orthopaedic controls. Glial fibrillary acidic protein levels maintained good to excellent discrimination across diagnostic groups until day 3 post-injury irrespective of age, until day 5 post-injury among middle-aged or younger patients and until week 2 post-injury among young patients only. In conclusion, the blood-based glial fibrillary acidic protein assay tested here has good to excellent performance across all age-categories for discriminating key traumatic brain injury diagnostic groups to at least 3 days post-injury in this trauma centre cohort. The addition of a blood-based diagnostic to the evaluation of traumatic brain injury, including geriatric traumatic brain injury, has potential to streamline diagnosis.

Background There is limited data on the incidence of gastrointestinal-specific pathology in gender non-conforming (GNC) populations.Methods Retrospective analysis of pancreatitis incidence rates in transgender and GNC persons exposed and not exposed to gender-affirming hormone therapy (GAHT).Results 7 of the 1333 patients on hormone therapy had an incidence of pancreatitis. 0 of the 615 patients with no history of GAHT use developed pancreatitis. Representing a 6.96 (95% CI 2.76 to 848.78) for the development of pancreatitis in patients with exposure to GAHT therapy.Conclusion Clinicians working with GNC individuals should be aware of this possible association

This study examines the experiences of 15 Latinx sixth-grade students in Los Angeles who participated in a yearlong journalism-based media literacy program embedded in their social studies classes. Students researched, interviewed, wrote, and published articles on the Internet about social justice themes, like immigration, racism, and LGBTQ rights. The intervention uses critical pedagogy and social justice pedagogy. This study seeks to understand how key aspects of these philosophies emerge in students' reflections of their journalistic learning experiences. Deductive qualitative analysis of focus group data indicates that students experienced transformational, agentic experiential learning that allowed them to explore and question the world. The limited comments about funds of knowledge, local communities, and critical co-investigation suggest that these areas need additional attention during intervention implementation. The journalistic approach illustrates new ways educators can engage in critical and social justice pedagogy in middle school media education.