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The ability to assess oneself is important in higher education, on the job, and throughout all aspects of life. Knowledge surveys (KS) are a self-assessment tool where students rate their ability to answer a knowledge question or perform a skills task. Previous research has shown that students are accurate self-assessors compared to instructor assessments when KS questions are specific and well-aligned with learning objectives and course content. Although it has been suggested as a use of KS in the literature, there are few data on the specific use of KS as a part of a continuous improvement process for program assessment. In this case study, KS were implemented in a Fundamentals of Engineering (FE) exam review course at an undergraduate-only civil engineering program in the western U.S. The paper will outline several components of our continuous improvement process, then compare KS with FE exam results from a cohort of students. The comparison demonstrates the utility of student self-assessment data as one artifact that helps to paint a more complete picture for program assessment. In addition, we will present several assessment benefits to implementing KS in courses and throughout an undergraduate program.

Abstract Mount Rainier has had at least 11 large lahars over the last 6,000 years, including one occurring without evidence of eruptive activity. This prompted the creation of a lahar detection system that uses a combination of seismic, infrasound, and tripwires. We test a laser rangefinder placed on a river channel bank for detecting and confirming mass movements flowing past a station as an alternative to the physical tripwires. After testing the device at an experimental debris-flow flume, the laser rangefinder successfully captured a small debris flow on Mount Rainier in 2023, confirming its effectiveness as a lahar detection and monitoring tool. Over the 2-month deployment at Mount Rainier, we find that spurious recordings in the laser rangefinder data (noise) tend to correlate with high humidity, and that periods of noise do not correlate with increased co-located seismic amplitude. Therefore, the impact of the noise on future alarms can be mitigated by coupling a laser rangefinder alarm with that of independent datasets.

Abstract Background Implementation science scholars have made significant progress identifying factors that enable or obstruct the implementation of evidence-based interventions, and testing strategies that may modify those factors. However, little research sheds light on how or why strategies work, in what contexts, and for whom. Studying implementation mechanisms—the processes responsible for change—is crucial for advancing the field of implementation science and enhancing its value in facilitating equitable policy and practice change. The Agency for Healthcare Research and Quality funded a conference series to achieve two aims: (1) develop a research agenda on implementation mechanisms, and (2) actively disseminate the research agenda to research, policy, and practice audiences. This article presents the resulting research agenda, including priorities and actions to encourage its execution. Method Building on prior concept mapping work, in a semi-structured, 3-day, in-person working meeting, 23 US-based researchers used a modified nominal group process to generate priorities and actions for addressing challenges to studying implementation mechanisms. During each of the three 120-min sessions, small groups responded to the prompt: “What actions need to be taken to move this research forward?” The groups brainstormed actions, which were then shared with the full group and discussed with the support of facilitators trained in structured group processes. Facilitators grouped critical and novel ideas into themes. Attendees voted on six themes they prioritized to discuss in a fourth, 120-min session, during which small groups operationalized prioritized actions. Subsequently, all ideas were collated, combined, and revised for clarity by a subset of the authorship team. Results From this multistep process, 150 actions emerged across 10 priority areas, which together constitute the research agenda. Actions included discrete activities, projects, or products, and ways to shift how research is conducted to strengthen the study of implementation mechanisms. Conclusions This research agenda elevates actions to guide the selection, design, and evaluation of implementation mechanisms. By delineating recommended actions to address the challenges of studying implementation mechanisms, this research agenda facilitates expanding the field of implementation science, beyond studying what works to how and why strategies work, in what contexts, for whom, and with which interventions.

For patients with recurrent brain metastases, there is an urgent need for a more effective and less toxic treatment approach. Accumulating evidence has shown that spatially fractionated radiation therapy (SFRT) is able to provide a significantly higher therapeutic ratio with lower toxicity compared to conventional radiation using a uniform dose. The purpose of this study was to explore the potential low toxicity benefit of mini-beam radiotherapy (MBRT), a form of SFRT, for whole-brain re-irradiation in a healthy mouse model. Animals first received an initial 25 Gy of uniform whole-brain irradiation. Five weeks later, they were randomized into three groups to receive three different re-irradiation treatments as follows: (1) uniform irradiation at 25 Gy; (2) MBRT at a 25 Gy volume-averaged dose (106.1/8.8 Gy for peak/valley dose, 25 Gy-MBRT); and (3) MBRT at a 43 Gy volume-averaged dose (182.5/15.1 Gy for peak/valley dose, 43 Gy-MBRT). Animal survival and changes in body weight were monitored for signs of toxicity. Brains were harvested at 5 weeks after re-irradiation for histologic evaluation and immunostaining. The study showed that 25 Gy-MBRT resulted in significantly less body weight loss than 25 Gy uniform irradiation in whole-brain re-irradiation. Mice in the 25 Gy-MBRT group had a higher level of CD11b-stained microglia but also maintained more Ki67-stained proliferative progenitor cells in the brain compared to mice in the uniform irradiation group. However, the high-dose 43 Gy-MBRT group showed severe radiation toxicity compared to the low-dose 25 Gy-MBRT and uniform irradiation groups, indicating dose-dependent toxicity. Our study demonstrates that MBRT at an appropriate dose level has the potential to provide less toxic whole-brain re-irradiation. Future studies investigating the use of MBRT for brain metastases are warranted.

Abstract Charge, spin and Cooper-pair density waves have now been widely detected in exotic superconductors. Understanding how these density waves emerge — and become suppressed by external parameters — is a key research direction in condensed matter physics. Here we study the temperature and magnetic-field evolution of charge density waves in the rare spin-triplet superconductor candidate UTe2 using scanning tunneling microscopy/spectroscopy. We reveal that charge modulations composed of three different wave vectors gradually weaken in a spatially inhomogeneous manner, while persisting to surprisingly high temperatures of 10–12 K. We also reveal an unexpected decoupling of the three-component charge density wave state. Our observations match closely to the temperature scale potentially related to short-range magnetic correlations, providing a possible connection between density waves observed by surface probes and intrinsic bulk features. Importantly, charge density wave modulations become suppressed with magnetic field both below and above superconducting T c in a comparable manner. Our work points towards an intimate connection between hidden magnetic correlations and the origin of the unusual charge density waves in UTe2.

Abstract Reentrant superconductivity is an uncommon phenomenon in which the destructive effects of magnetic field on superconductivity are mitigated, allowing a zero-resistance state to survive under conditions that would otherwise destroy it. Typically, the reentrant superconducting region derives from a zero-field parent superconducting phase. Here, we show that in UTe2 crystals extreme applied magnetic fields give rise to an unprecedented high-field superconductor that lacks a zero-field antecedent. This high-field orphan superconductivity exists at angles offset between 29o and 42o from the crystallographic b to c axes with applied fields between 37 T and 52 T. The stability of field-induced orphan superconductivity presented in this work defies both empirical precedent and theoretical explanation and demonstrates that high-field superconductivity can exist in an otherwise non-superconducting material.

Abstract Background While the broader medical community grapples with the widely accepted notion that it takes an average of 17 years for research evidence to be incorporated into clinical practice, the implementation of evidence-based interventions in carceral settings (i.e., jails and prisons) faces longer delays, exacerbating health disparities. Main body The “prison implementation penalty” describes the significant delay in and limited adoption of evidence-based healthcare practices in carceral settings. We explore the complex challenges of implementing evidence-based interventions in jails and prisons, environments where healthcare often plays a secondary role under security and discipline. We use specific frameworks to highlight the unique barriers within these settings and propose potential implementation strategies. These challenges have broad implications for health equity due to the disproportionate impact on the marginalized groups affected by mass incarceration. Implementation science has potential to mitigate these disparities. Conclusion Bridging the gap between healthcare evidence and practice in carceral settings offers a public health opportunity. Implementation science offers a unique role in improving healthcare standards and reducing health inequities in this environment.

Abstract Background Food insecurity is common in the United States, especially in Rhode Island, where it affects up to 33% of residents. Food insecurity is associated with adverse health outcomes and disproportionally affects people from minoritized backgrounds. Produce prescription programs, in which healthcare providers write “prescriptions” for free or reduced cost vegetables, have been used to address food insecurity and diet-related chronic disease. Although there is growing evidence for the effectiveness of produce prescription programs in improving food security and diet quality, there have been few efforts to use implementation science methods to improve the adoption of these programs. Methods This two-phase pilot study will examine determinants and preliminary implementation and effectiveness outcomes for an existing produce prescription program. The existing program is funded by an Accountable Care Organization in Rhode Island and delivered in primary care practices. For the first phase, we conducted a formative evaluation, guided by the Consolidated Framework for Implementation Research 2.0, to assess barriers, facilitators, and existing implementation strategies for the produce prescription program. Responses from the formative evaluation were analyzed using a rapid qualitative analytic approach to yield a summary of existing barriers and facilitators. In the second phase, we presented our formative evaluation findings to a community advisory board consisting of primary care staff, Accountable Care Organization staff, and staff who source and deliver the vegetables. The community advisory board used this information to identify and refine a set of implementation strategies to support the adoption of the program via an implementation blueprint. Guided by the implementation blueprint, we will conduct a single-arm pilot study to assess implementation antecedents (i.e., feasibility, acceptability, appropriateness, implementation climate, implementation readiness), implementation outcomes (i.e., adoption), and preliminary program effectiveness (i.e., food and nutrition security). The first phase is complete, and the second phase is ongoing. Discussion This study will advance the existing literature on produce prescription programs by formally assessing implementation determinants and developing a tailored set of implementation strategies to address identified barriers. Results from this study will inform a future fully powered hybrid type 3 study that will use the tailored implementation strategies and assess implementation and effectiveness outcomes for a produce prescription program. Trial registration Clinical trials: NCT05941403 , Registered June 9, 2023.

The rapid growth of special needs vouchers has been accompanied by the loss of historic civil rights and protections under the Individuals with Disabilities in Education Act (IDEA) and the Americans with Disabilities Act (ADA). We examine three of the largest special needs voucher programs in the United States: those in Florida, Georgia and Ohio. We find that these programs and the largest private special education schools within these states are silent on the right to education in the LRE. This study focuses on how silencing the right to be educated in the least restrictive environment (LRE), thus inclusive education, is taking place. Using Huckin's framework of textual silence and critical discourse analysis, we identify this silence as manipulative, drawing connections between historical segregation, neoliberal ideology and the rhetoric of market choice in the United States. We discuss implications regarding segregation, equity, and education policy.

Dispersal by grazing and browsing animals has the potential to structure plant-associated microbes in plant communities. Bison are one of the largest grazing animals in North America and charismatic symbols of the Great Plains. They have an important role in maintaining plant communities in tallgrass prairie and may have played a significant role in microbial dispersal across the Great Plains, along with other grazers and herbivores in general. To determine whether bison saliva could maintain viable fungal propagules, we sampled saliva from bison at Konza Prairie Biological Station. Fifty-nine internal transcribed spacer sequences were recovered from distinct fungal colonies on media selective for Fusarium species and Macrophomina phaseolina, representing at least 26 fungal species. Most sequences were identified as originating from potential plant pathogens, indicating that bison may play a role in spreading plant pathogens throughout the prairie. Given their historic numbers and extensive migration across North America, bison may have had a role in establishing the current structure of the prairie microbiome. [Figure: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background Sepsis is the leading cause of intensive care unit (ICU) admission and ICU death. In recognition of the burden of sepsis, the Surviving Sepsis Campaign (SSC) and the Institute for Healthcare Improvement developed sepsis “bundles” (goals to accomplish over a specific time period) to facilitate SSC guideline implementation in clinical practice. Using the SSC 3-h bundle as a base, the Centers for Medicare and Medicaid Services developed a 3-h sepsis bundle that has become the national standard for early management of sepsis. Emerging observational data, from an analysis conducted for the AIMS grant application, suggest there may be additional mortality benefit from even earlier implementation of the 3-h bundle, i.e., the 1-h bundle. Method The primary aims of this randomized controlled trial are to: (1) examine the effect on clinical outcomes of Emergency Department initiation of the elements of the 3-h bundle within the traditional 3 h versus initiating within 1 h of sepsis recognition and (2) examine the extent to which a rigorous implementation strategy will improve implementation and compliance with both the 1-h bundle and the 3-h bundle. This study will be entirely conducted in the Emergency Department at 18 sites. A secondary aim is to identify clinical sepsis phenotypes and their impact on treatment outcomes. Discussion This cluster-randomized trial, employing implementation science methodology, is timely and important to the field. The hybrid effectiveness-implementation design is likely to have an impact on clinical practice in sepsis management by providing a rigorous evaluation of the 1- and 3-h bundles. Funding NHLBI R01HL162954. Trial registration ClinicalTrials.gov NCT05491941. Registered on August 8, 2022.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson’s disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Abstract Background Juvenile legal involved youth (JLIY) experience disproportionately high rates of suicidal and self-injurious thoughts and behaviors (SSITB). Many JLIY lack access to evidence-based treatment specifically designed to treat SSITB, thereby increasing the overall risk of suicide. The overwhelming majority of JLIY are not placed in secure facilities and almost all incarcerated youth are eventually released to the community. Consequently, SSITB are a major concern of JLIY residing in the community and it is critical that this population has access to evidence-based treatment for SSITB. Unfortunately, most community mental health providers who treat JLIY have not been trained in evidence-based interventions that are specifically designed to SSITB, which often leads to youth experiencing prolonged periods of SSITB. Training community mental health providers who serve JLIY in the detection and treatment of SSITB shows promise for decreasing the overall suicide risk for JLIY. Methods The current proposal aims to reduce SSITB among JLIY, and thus reduce mental health disparities in this vulnerable and underserved youth population, by increasing access to evidence-based treatment strategies specifically designed to treat SSITB behaviors. We will implement an agency-wide training among at least 9 distinct community mental health agencies that serve JLIY referred to treatment by a statewide court system in the Northeast. Agencies will be trained in an adapted version of the COping, Problem Solving, Enhancing life, Safety, and Parenting (COPES+) intervention. Training will be implemented via a cluster-randomized stepped wedge trial that proceeds through multiple phases. Discussion This research engages multiple systems (i.e., juvenile legal and mental health systems) serving JLIY and has the potential to directly inform treatment practices in juvenile legal and mental health systems. The current protocol has significant public health implications as the primary goals are to reduce SSITB among adolescents involved in the juvenile legal system. By implementing a training protocol with community-based providers to help them learn an evidence-based intervention, this proposal aims to reduce mental health disparities in a marginalized and underserved population. Trial registration osf.io/sq9zt

Objective: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2high ESCC. Design: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays. Results: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as potential NRF2 inhibitors with minimal cytotoxicity at specified concentrations. We then validated two of these compounds, pyrimethamine and mitoxantrone, by demonstrating their dose- and time-dependent inhibitory effects on the expression of NRF2 and its target genes in two NRF2Mut human ESCC cells (KYSE70 and KYSE180). RNAseq and qPCR confirmed the suppression of global NRF2 signaling by these two compounds. Mechanistically, pyrimethamine reduced NRF2 half-life by promoting NRF2 ubiquitination and degradation in KYSE70 and KYSE180 cells. Expression of an Nrf2E79Q allele in mouse esophageal epithelium (Sox2CreER;LSL-Nrf2E79Q/+) resulted in an NRF2high phenotype, which included squamous hyperplasia, hyperkeratinization, and hyperactive glycolysis. Treatment with pyrimethamine (30 mg/kg/day, p.o.) suppressed the NRF2high esophageal phenotype with no observed toxicity. Conclusion: We have identified and validated pyrimethamine as an NRF2 inhibitor that may be rapidly tested in the clinic for NRF2high ESCC.

Abstract Brown adipose tissue (BAT) is a fat tissue specialized in heat production (non-shivering thermogenesis) and used by mammals to defend core body temperature when exposed to cold. Several studies have shown that during non-shivering thermogenesis the increase in BAT oxygen demand is met by a local and specific increase in tissue’s blood flow. While the vasculature of BAT has been extensively studied postmortem in rodents using histology, optical and CT imaging techniques, vasculature changes during stimulation of non-shivering thermogenesis have never been directly detected in vivo. Here, by using computed tomography (CT) angiography with gold nanoparticles we investigate, non-invasively, changes in BAT vasculature during adrenergic stimulation of non-shivering thermogenesis by norepinephrine, a vasoconstrictor known to mediate brown fat heat production, and by CL 316,243, a specific β3-adrenergic agonist also known to elicit BAT thermogenesis in rodents. We found that while CL 316,243 causes local vasodilation in BAT, with little impact on the rest of the vasculature throughout the body, norepinephrine leads to local vasodilation in addition to peripheral vasoconstriction. As a result, a significantly greater relative increase in BAT perfusion is observed following the injection of NE compared to CL. This study demonstrates the use of in vivo CT angiography as an effective tool in assessing vascular reactivity in BAT both qualitatively and quantitatively in preclinical studies.

Abstract Machine learning can be used to explore the complex multifactorial patterns underlying postsurgical graft detachment after endothelial corneal transplantation surgery and to evaluate the marginal effect of various practice pattern modulations. We included all posterior lamellar keratoplasty procedures recorded in the Dutch Cornea Transplant Registry from 2015 through 2018 and collected the center-specific practice patterns using a questionnaire. All available data regarding the donor, recipient, surgery, and practice pattern, were coded into 91 factors that might be associated with the occurrence of a graft detachment. In this research, we used three machine learning methods; a regularized logistic regression (lasso), classification tree analysis (CTA), and random forest classification (RFC), to select the most predictive subset of variables for graft detachment. A total of 3647 transplants were included in our analysis and the overall prevalence of graft detachment was 9.9%. In an independent test set the area under the curve for the lasso, CTA, and RFC was 0.70, 0.65, and 0.72, respectively. Identified risk factors included: a Descemet membrane endothelial keratoplasty procedure, prior graft failure, and the use of sulfur hexafluoride gas. Factors with a reduced risk included: performing combined procedures, using pre-cut donor tissue, and a pre-operative laser iridotomy. These results can help surgeons to review their practice patterns and generate hypotheses for empirical research regarding the origins of graft detachments.

Abstract Introduction Resting‐state functional magnetic resonance imaging (fMRI) is widely used for measuring functional interactions between brain regions, significantly contributing to our understanding of large‐scale brain networks and brain–behavior relationships. Furthermore, idiosyncratic patterns of resting‐state connections can be leveraged to identify individuals and predict individual differences in clinical symptoms, cognitive abilities, and other individual factors. Idiosyncratic connectivity patterns are thought to persist across task states, suggesting task‐based fMRI can be similarly leveraged for individual differences analyses. Method Here, we tested the degree to which functional interactions occurring in the background of a task during slow event‐related fMRI parallel or differ from those captured during resting‐state fMRI. We compared two approaches for removing task‐evoked activity from task‐based fMRI: (1) applying a low‐pass filter to remove task‐related frequencies in the signal, or (2) extracting residuals from a general linear model (GLM) that accounts for task‐evoked responses. Result We found that the organization of large‐scale cortical networks and individual's idiosyncratic connectivity patterns are preserved during task‐based fMRI. In contrast, individual differences in connection strength can vary more substantially between rest and task. Compared to low‐pass filtering, background connectivity obtained from GLM residuals produced idiosyncratic connectivity patterns and individual differences in connection strength that more resembled rest. However, all background connectivity measures were highly similar when derived from the low‐pass‐filtered signal or GLM residuals, indicating that both methods are suitable for measuring background connectivity. Conclusion Together, our results highlight new avenues for the analysis of task‐based fMRI datasets and the utility of each background connectivity method.

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BackgroundYouth with anxiety and obsessive–compulsive disorder (OCD) rarely access exposure therapy, an evidence-based treatment. Known barriers include transportation, waitlists, and provider availability. Efforts to improve access to exposure require an understanding of the process that families take to find therapists, yet no prior studies have examined parents’ perspectives of the steps involved.MethodsParents of children who have received exposure therapy for anxiety and/or OCD (N = 23) were recruited from a hospital-based specialty anxiety clinic where the majority of their children previously received exposure. Recruitment was ongoing until thematic saturation was reached. Parents completed questionnaires and attended an online focus group during which they were asked to describe each step they took—from recognizing their child needed treatment to beginning exposure. A process map was created and shown in real-time, edited for clarity, and emailed to parents for member checking. Authors analyzed process maps to identify common themes.ResultsSeveral themes emerged, as visually represented in a final process map. Participants identified a “search-outreach” loop, in which they repeated the cycle of looking for therapists, contacting them, and being unable to schedule an appointment due to factors such as cost, waitlists, and travel time. Parents often did not know about exposure and reported feeling guilty about their lack of knowledge and inability to find a suitable provider. Parents reported frustration that medical providers did not often know about exposure and sometimes dismissed parents’ concerns. Participants emphasized the difficulty of navigating the mental health system; many reported that it took years to find an exposure therapist, and that the search was sometimes stalled due to fluctuating symptoms.ConclusionA common thread among identified barriers was the amount of burden placed on parents to find treatment with limited support, and the resultant feelings of isolation and guilt. Findings point to several directions for future research, such as the development of parent support groups for navigating the mental health system; enhancing coordination of care between medical and mental health providers; and streamlining referral processes.

Trauma sensitive approaches are being adopted in schools across the U.S. While responding to children's trauma is imperative, this analysis points to significant limitations posed by individual pathology-focused science and neoliberal influences, including an outline of fundamental contradictions. This is followed by a conceptualization of trauma which illustrates alignment with and the necessity of critical pedagogy as a means for developing critical knowledge and world views that are resistant to domination and may counter the effects of trauma.

BackgroundExposure therapy is a highly effective but underutilized treatment for anxiety disorders. A primary contributor to its underutilization is therapist-level negative beliefs about its safety and tolerability for patients. Given functional similarities between anxious beliefs among patients and negative beliefs among therapists, the present protocol describes how exposure principles can be leveraged during training to target and reduce therapist negative beliefs.MethodsThe study will take place in two phases. First, is a case-series analysis to fine-tune training procedures that is already complete, and the second is an ongoing randomized trial that tests the novel exposure to exposure (E2E) training condition against a passive didactic approach. A precision implementation framework will be applied to evaluate the mechanism(s) by which training influences aspects of therapist delivery following training.Anticipated resultsIt is hypothesized that the E2E training condition will produce greater reductions in therapists’ negative beliefs about exposure during training relative to the didactic condition, and that greater reduction in negative beliefs will be associated with higher quality exposure delivery as measured by coding of videotaped delivery with actual patients.ConclusionImplementation challenges encountered to date are discussed along with recommendations for future training interventions. Considerations for expansion of the E2E training approach are also discussed within the context of parallel treatment and training processes that may be tested in future training trials.

Abstract Background Trauma narratives are a critical, exposure-based component of trauma-focused cognitive-behavioral therapy, yet community therapists rarely use them. Given evidence that intentions to deliver elements of cognitive behavioral therapy vary by component, and that intentions to deliver exposure are the weakest, this study focused specifically on trauma narratives. We drew on a social psychology causal theory (Theory of Planned Behavior (TPB)) and an implementation science framework (the Consolidated Framework for Implementation Research (CFIR)) to glean insight into multilevel influences on trauma narrative use. While the CFIR offers a broad list of factors potentially affecting implementation, the TPB offers causal pathways between individual-level constructs that predict behavior, including the uptake of an evidence-based intervention. The integration of these approaches may provide a more complete understanding of factors affecting therapists’ use of TNs. Methods Therapists (n=65) trained in trauma-focused cognitive behavioral therapy completed a survey about their use of and beliefs about trauma narratives. Content analysis was used to identify common beliefs about trauma narratives. A subset of participants (n=17) completed follow-up qualitative interviews, which were analyzed using an integrated approach informed by the CFIR. Results While most participants reported high intentions to use TNs, nearly half reported that they did not use TNs in the last 6 months. Survey data indicate a number of TPB-related determinants related to using trauma narratives. Qualitative interviews identified CFIR-relevant contextual factors that may influence constructs central to TPB. Conclusions These results highlight the importance of integrating approaches that address multiple theoretical determinants of therapist behavior, including therapist, organizational, and client factors with causal explanations to explain implementation behavior.

Leishmaniasis encompasses a group of vector-borne parasitic diseases, characterized by their diversity and complexity, that affect both humans and other vertebrates. They are caused by different species of parasites of the Leishmania genus, which are transmitted by bites from hematophagous female sandflies. This work proposed to model the occurrence probability of five sandflies species of sanitary interest for South America, from a bibliographic compilation of records of the last 10 years. To develop the model, the free software MaxEnt was used. This exploratory analysis made it possible to visualize the areas where the species are distributed. In addition, we analyzed land changes in vegetation around a town in Jujuy province, Argentina, where a leishmaniasis outbreak occurred during the years 2017 and 2018. For this, Sentinel-2 images were used, and a change vector was calculated for the difference between two dates of the Normalized Difference Vegetation Index (NDVI). This part of the work was made using SNAP software for images pre-procesing, Python for the change vector obtention and QGIS for the result post-procesing. From the exploration of MaxEnt software we were able to know the most suitable places for the distribution of the most important five species in the study region, and therefore, to project future decision-making to prevent and control leishmaniasis transmission. And in turn, obtain an approximation of how anthropogenic activities, as deforestation, can have an influence on leishmaniasis specific outbreaks transmitted by these species. Finally, from the exploration of the different tools used in this work, the importance of validation with field data for the generation of accurate analyses and predictions is highlighted. It implies that more data collection is necessary to validate the models and analyzes generated, to guarantee the contribution of the tools in macro-ecological studies of species linked to disease transmission.

The current movement toward increasing privatization in general and market education in particular has been extensively examined in terms of its neoliberal roots and incompatibility with the aims of public, democratic education. This analysis presents a different critique, one that draws upon current economic theory and research to challenge the most fundamental assumptions and claims of market education. Contrary to presumed virtues of profit, competition and choice, we argue that the forces of rent seeking in the market model of education do not operate according to these principles and are exacerbating structures of inequality and segregation. We outline an alternative conceptual framework for understanding this model.

Abstract Background Trauma-focused cognitive behavioral therapy (TF-CBT) is an evidence-based intervention for youth with posttraumatic stress disorder. An important component of TF-CBT is the trauma narrative (TN), a phase in the intervention in which youth are guided to process the memories, thoughts, and feelings associated with their traumatic experience(s). Previous work has shown that TF-CBT clinicians complete TNs with only half of their clients, yet little is known about what determines TF-CBT clinicians’ use of TNs. The behavioral insights literature—an interdisciplinary field studying judgment and decision-making—offers theoretical and empirical tools to conceptualize what drives complex human behaviors and decisions. Drawing from the behavioral insights literature, the present study seeks to understand what determines clinician use of TNs and to generate strategies that target these determinants. Methods Through semi-structured qualitative interviews, we sought the perspectives of trained TF-CBT clinicians working in public mental health settings across the city of Philadelphia (N = 17) to understand their decisions to use TNs with clients. We analyzed the qualitative data using a coding approach informed by the behavioral insights literature. We used an iterative process of structured hypothesis generation, aided by a behavioral insights guide, and rapid validation informed by behavioral insights to uncover the determinants of TN use. We then generated implementation strategies that targeted these determinants using the “Easy Attractive Social Timely” framework, a behavioral insights design approach. Results We generated and validated three broad themes about what determines clinician implementation of TNs: decision complexity, clinician affective experience, and agency norms. We hypothesized behavioral insights that underlie these implementation determinants and designed a list of nine corresponding behavioral insights strategies that may facilitate TN implementation. Conclusions Our study investigated why an effective component of an evidence-based intervention is difficult to implement. We leveraged robust scientific theories and empirical regularities from the behavioral insights literature to understand clinician perspectives on TN implementation. These factors were theoretically linked to implementation strategies. Our work revealed the potential for using behavioral insights in the diagnosis of evidence-based intervention determinants and the design of implementation strategies.

In human cells homologous recombination (HR) is critical for repair of DNA double strand breaks (DSBs) and rescue of stalled or collapsed replication forks. HR is facilitated by RAD51 which is loaded onto DNA by either BRCA2-BRCA1-PALB2 or RAD52. In human culture cells, double-knockdowns of RAD52 and genes in the BRCA1-BRCA2-PALB2 axis are lethal. Mutations in BRCA2, BRCA1 or PALB2 significantly impairs error free HR as RAD51 loading relies on RAD52 which is not as proficient as BRCA2-BRCA1-PALB2. RAD52 also facilitates Single Strand Annealing (SSA) that produces intra-chromosomal deletions. Some RAD52 mutations that affect the SSA function or decrease RAD52 association with DNA can suppress certain BRCA2 associated phenotypes in breast cancers. In this report we did a pan-cancer analysis using data reported on the Catalogue of Somatic Mutations in Cancers (COSMIC) to identify double mutants between RAD52 and BRCA1, BRCA2 or PALB2 that occur in cancer cells. We find that co-occurring mutations are likely in certain cancer tissues but not others. However, all mutations occur in a heterozygous state. Further, using computational and machine learning tools we identified only a handful of pathogenic or driver mutations predicted to significantly affect the function of the proteins. This supports previous findings that co-inactivation of RAD52 with any members of the BRCA2-BRCA1-PALB2 axis is lethal. Molecular modeling also revealed that pathogenic RAD52 mutations co-occurring with mutations in BRCA2-BRCA1-PALB2 axis are either expected to attenuate its SSA function or its interaction with DNA. This study extends previous breast cancer findings to other cancer types and shows that co-occurring mutations likely destabilize HR by similar mechanisms as in breast cancers.

Background Most evidence-based treatments (EBTs) for posttraumatic stress disorder (PTSD) and anxiety disorders include exposure; however, in community settings, the implementation of exposure lags behind other EBT components. Clinician-level determinants have been consistently implicated as barriers to exposure implementation, but few organizational determinants have been studied. The current study examines an organization-level determinant, implementation climate, and clinician-level determinants, clinician demographic and background factors, as predictors of attitudes toward exposure and changes in attitudes following training. Method Clinicians ( n = 197) completed a 3-day training with 6 months of twice-monthly consultation. Clinicians were trained in cognitive behavioral therapy (CBT) for anxiety, depression, behavior problems, and trauma-focused CBT (TF-CBT). Demographic and background information, implementation climate, and attitudes toward exposure were assessed in a pre-training survey; attitudes were reassessed at post-consultation. Implementation climate was measured at the aggregated/group-level and clinician-level. Results Attitudes toward exposure significantly improved from pre-training to post-consultation ( t (193) = 9.9, p .05) but did predict more positive attitudes at post-consultation (ß = −2.46; p .05). Higher frequency of self-reported CBT use was associated with more positive attitudes at pre-training (ß = −0.81; p .05) or with changes in attitudes (all p > .05). Conclusions Clinician perceptions of implementation climate predicted greater improvement of attitudes toward exposure following EBT training and consultation. Findings suggest that organizational determinants outside of training impact changes in clinicians’ attitudes. Training in four EBTs, only two of which include exposure as a component, resulted in positive changes in clinicians’ attitudes toward exposure, which suggests non-specialty trainings can be effective at changing attitudes, which may enable scale-up.

Disability and dependence are integral to the human experience and yet have been largely marginalized or denigrated within Western philosophy. Joining a growing counter narrative from the disability studies movement, several mainstream moral philosophers are helping to redress this error. In this essay, the author discusses ideas from four such writers; Eva Kittay, Leslie Pickering Francis, Anita Silvers, and Alasdair MacIntyre, that he believes help foreground and elevate the moral centrality of disability and dependence. The author argues that this work helps rearticulate an understanding of human dignity and virtue in a way that illuminates the ethical imperative of inclusive education. (Contains 38 notes.)

Background: This study examined the transition to telehealth services during the COVID-19 pandemic in terms of attendance rates, the provision of evidence-based interventions, and clinical outcomes. Methods: The feasibility of in-person versus telehealth visits for integrated primary care sessions was compared using chart review data. Data on patient characteristics, attendance, symptom severity and improvement, and evidence-based intervention use were collected for patients (N = 173) from an integrated primary clinic that primarily serves a low-income, diverse sample of adults and children whose primary presenting problems are depression and anxiety. Results: Attendance significantly improved after the transition to telehealth, as indicated by fewer cancellations and more appointments attended. Patients showed significant improvement and decreases in symptoms. The quality of care was maintained, as indicated by consistent evidence-based intervention use over time. Limitations: This study was limited by the fact that it took place in an academically-affiliated primary care clinic, which may not be representative of all community settings. In addition, analyses related to clinical symptoms were only conducted with a small subset of participants and there was no comparison group. Conclusions: Telehealth through integrated primary care might be a viable option to improve accessibility of mental health services for low-income, racial/ethnic minority adults and children.

Solar radiation management (SRM) has been proposed as a means to reduce global warming in spite of high greenhouse-gas concentrations and to lower the chance of warming-induced tipping points. However, SRM may cause economic damages and its feasibility is still uncertain. To investigate the trade-off between these (economic) gains and damages, we incorporate SRM into a stochastic dynamic integrated assessment model and perform the first rigorous cost–benefit analysis of sulfate-based SRM under uncertainty, treating warming-induced climate tipping and SRM failure as stochastic elements. We find that within our model, SRM has the potential to greatly enhance future welfare and merits being taken seriously as a policy option. However, if only SRM and no CO2 abatement is used, global warming is not stabilised and will exceed 2 K. Therefore, even if successful, SRM can not replace but only complement CO2 abatement. The optimal policy combines CO2 abatement and modest SRM and succeeds in keeping global warming below 2 K.

Abstract Background 13‐Deoxy, 5‐iminodoxorubicin (GPX‐150) is a doxorubicin (DOX) analog synthesized to reduce the formation of reactive oxygen species and the cardiotoxic metabolite, doxorubiciniol, the two pathways that are linked to the irreversible, cumulative dose‐dependent cardiotoxicity of DOX. In a preclinical chronic models and a phase I clinical study of GPX‐150, no irreversible, cumulative dose‐dependent cardiotoxicity was demonstrated. Recent studies suggest that DOX cardiotoxicity may be mediated, at least in part, by the poisoning of topoisomerase IIβ. Patients and Methods An open‐label, single‐arm phase II clinical study in metastatic and unresectable soft tissue sarcoma (STS) patients was initiated to further evaluate the efficacy and safety of GPX‐150, including cardiac function, specifically left ventricular ejection fraction (LVEF). Results GPX‐150 was administered at 265 mg/m2 every 3 weeks for up to 16 doses with prophylactic G‐CSF until progression, death, or patient withdrawal from the study. GPX‐150 exhibited efficacy assessed as progression‐free survival (PFS) rates of 38% and 12% at 6 and 12 months and an overall survival rate of 74% and 45% at 6 and 12 months. GPX‐150–treated patients did not develop any evidence of irreversible, cumulative dose‐dependent chronic cardiotoxicity. Toxicities included grade 3 anemia, neutropenia, and one grade 4 leukopenia. Correlative analysis demonstrated that GPX‐150 was more selective than DOX for the inhibition of topoisomerase IIα over IIβ in vitro. Conclusion These results suggest future studies are warranted to further evaluate the clinical efficacy of GPX‐150 in STS, perhaps at doses higher than 265 mg/m2.

Abstract Background Implementation researchers have typically studied organizational culture and climate by testing whether individual dimensions are linked to the implementation of evidence-based practices (EBPs) rather than examining how the overarching social context influences implementation. This approach may limit implementation theory and strategy development to the extent that individual dimensions of culture and climate interact, mutually reinforce or counteract one another, or exhibit non-linear relationships. This study tests whether empirically identifiable culture and climate profiles emerge in a sample of organizations and examines how these profiles relate to EBP fidelity and work attitudes that support EBP sustainment, focusing on three EBPs for youth with autism delivered in schools as an example. Methods The study included 65 elementary schools in the U.S. that implemented three EBPs—discrete trial training, pivotal response training, and visual schedules—for youth with autism. Organizational culture and climate and work attitudes were assessed using the Organizational Social Context measure at the beginning of the school year. Observations of EBP fidelity occurred mid school-year. We used bias-adjusted stepwise latent profile modeling to (1) identify subpopulations of schools that share similar culture and climate profiles, and (2) test for mean differences across profiles in observed EBP fidelity and teacher and staff work attitudes. Results Controlling for region, four profiles best characterized the organizational cultures and climates of schools. Teachers and staff in schools with a comprehensive profile (high proficiency culture, positive climate) exhibited higher fidelity to two of three EBPs (d’s = .95 to 1.64) and reported superior work attitudes (d’s = .71 to 1.93) than teachers and staff in all other schools. Teachers and staff in supportive schools (low rigidity culture, positive climate) had better work attitudes, but not better fidelity, than those in schools with indifferent (low culture/climate, elevated stress) and constrained (high rigidity and resistance, high stress) profiles. Conclusions Organizational culture and climate profiles are a strong predictor of EBP fidelity and work attitudes that support EBP sustainment, highlighting the importance of an organization’s overarching social context when developing implementation theory and strategies. Strategies that foster a comprehensive profile may improve EBP implementation.