Study protocol for a cluster-randomized trial of a bundle of implementation support strategies to improve the fidelity of implementation of schoolwide Positive Behavioral Interventions and Supports in rural schools.

Background: Improving the implementation of evidence-based interventions is important for population-level impacts. Positive Behavioral Interventions and Supports (PBIS) is effective for improving school climate and students' behavioral outcomes, but rural schools often lag behind urban and suburban schools in implementing such initiatives. Methods/Design: This paper describes a Type 3 hybrid implementation-effectiveness trial of Rural School Support Strategies (RS3), a bundle of implementation support strategies selected to improve implementation outcomes in rural schools. In this two-arm parallel group trial, 40 rural public schools are randomized to receive: 1) a series of trainings about PBIS; or 2) an enhanced condition with training plus RS3. The trial was planned for two years, but due to the pandemic has been extended another year. RS3 draws from the Interactive Systems Framework, with a university-based team (support system) that works with a team at each school (school-based delivery system), increasing engagement through strategies such as: providing technical assistance, facilitating school team functioning, and educating implementers. The primary organizational-level outcome is fidelity of implementation, with additional implementation outcomes of feasibility, acceptability, appropriateness, and cost. Staff-level outcomes include perceived climate and self-reported adoption of PBIS core components. Student-level outcomes include disciplinary referrals, academic achievement, and perceived climate. Mediators being evaluated include organizational readiness, school team functioning, and psychological safety. Discussion: The study tests implementation strategies, with strengths including a theory-based design, mixed methods data collection, and consideration of mediational mechanisms. Results will yield knowledge about how to improve implementation of universal prevention initiatives in rural schools.

Initial Evaluation of a Novel Cone-Beam CT-Based Semi-Automated Online Adaptive Radiotherapy System for Head and Neck Cancer Treatment - A Timing and Automation Quality Study.

Introduction A novel on-line adaptive radiotherapy (ART) system based on O-ring linear accelerator (LINAC) and cone-beam CT (CBCT) was evaluated for treatment and management of head & neck (H&N) cancer in an emulated environment accessed via remote desktop connection. In this on-line ART system, organs-at-risk (OARs) and target contours and radiotherapy (RT) plans are semi-automatically generated based on the patient CBCT, expediting a typically hours-long RT planning session to under half an hour. In this paper, we describe our initial experiences with the system and explore optimization strategies to expedite the process further. Methods We retroactively studied five patients with head and neck cancers, treated 16-35 fractions to 50-70 Gys. For each patient, on-line ART was simulated with one planning CT and three daily CBCT images taken beginning, middle, and end of treatment (tx). Key OAR (mandible, parotids, and spinal cord) and target (planning target volume (PTV) = clinical target volume (CTV) + 3 mm margin) contours were auto-generated and adjusted as needed by therapist/dosimetrist and attending physician, respectively. Duration of OAR contouring, target contouring, and plan review was recorded. Key OAR auto-contours were qualitatively rated from 1 (unacceptable) - 5 (perfect OAR delineation), and then quantitatively compared to human-adjusted "ground truth" contours via dice similarity coefficient (DSC) and 95-percentile Hausdorff distance (HD95%). Once contours were approved, adapted RT plans were auto-generated for physician review. Simulated doses to OARs and targets from the adapted plan were compared to that from the original (un-adapted) plan. Results Median on-line ART planning duration in the remote emulated environment was 19 min 34 sec (range: 13 min 10 sec - 31 min 20 sec). Automated key OAR quality was satisfactory overall (98% scored ≥3; 82% ≥4), though mandible was rated lower than others (p < 0.05). Most key OARs and all targets were within 2 mm margin of human-adjusted contours, but a few parotid and spinal cord contours deviated up to 5 mm. Anatomical changes over tx course further increased auto-contour error (p < 0.05, ΔHD95% = 0.77 mm comparing start and end of tx). Further optimizing auto-contoured OAR and target quality could reduce the on-line treatment planning duration by ~5 min and ~4.5 min, respectively. Dosimetrically, adapted plan spared OARs at a rate much greater than random chance compared to the original plan (χ2 = 22.3, p << 0.001), while maintaining similar therapeutic dose to treatment target CTV (χ2 = 1.14, p > 0.05). In addition, a general decrease in accumulated OAR dose was observed with adaptation. Unsupervised adapted plans where contours were auto-generated without human review still spared OAR at a greater rate than the original plans, suggesting benefits of adaptation can be maintained even with some leniency in contour accuracy. Conclusion Feasibility of a novel, semi-automated on-line ART system for various head and neck (H&N) cancer sites was demonstrated in terms of treatment duration, dosimetric benefits, and automated contour accuracy in a remote emulator environment. Adaptive planning duration was clinically viable at 19 min and 34 sec, but further improvements in automated contour accuracy and performance improvements of plan auto-generation may reduce adaptive planning duration by up to 10 minutes.

Beyond the Fold: Emerging Biological Applications of DNA Origami.

The use of DNA as a material for nanoscale construction has blossomed in the past decade. This is largely attributable to the DNA origami technique, which has enabled construction of nanostructures ranging from simple two-dimensional sheets to complex three-dimensional objects with defined curves and edges. These structures are amenable to site-specific functionalization with nanometer precision, and have been shown to exhibit cellular biocompatibility and permeability. The DNA origami technique has already found widespread use in a variety of emerging biological applications such as biosensing, enzyme cascades, biomolecular analysis, biomimetics, and drug delivery. We highlight a few of these applications and comments on the prospects for this rapidly expanding field of research.