This paper describes the collaborative development of an inclusive maker program called Inventing, Designing, and Engineering for All Students (IDEAS) and the results of a study on the impact of that program on autistic students and their neurotypical peers. The IDEAS project brought together experts in maker education, autism inclusion, engineering, co-design, and research. Over 2 years, this group adapted and pilot tested a museum-based maker program so that it could be run as an informal club in autism-inclusion middle schools (students ages 10–14) in New York City. in the United States. In the third year, teachers in each school implemented the redesigned program on their own. Researchers conducted a mixed-methods study of the impact of the program on participants. The study used observations and interviews; social interaction analysis, a pre/post survey of science, technology, and engineering self-efficacy and career interest; and a pre/post assessment of understanding of the engineering design process (EDP). Autistic and neurotypical students were in either the treatment condition (if they joined the maker program) or a business-as-usual comparison condition (if they did not join the club). Our analyses of the survey and EDP assessment compared the maker group with the comparison group and showed that participating in the maker program led to improved outcomes in the following constructs: technology and engineering self-efficacy (effect size = 0.80), technology and engineering interest (effect size = 1.73), vicarious experience (effect size = 0.57), science appreciation (effect size = 0.21), and understanding of the engineering design process (effect size = 0.44). The maker program benefited neurotypical students more than autistic students on technology and engineering interest and science appreciation, possibly because autistic students started with a high level of STEM interest. Qualitative analysis demonstrated that all students engaged in the EDP and pursued a wide range of interests, that autistic students who struggled in normal school settings were successful in creating their projects and communicating with peers about those projects, and that teachers reported being better able to see what their autistic students were capable of accomplishing when they were freed from the constraints of typical classroom instruction.
The use of immersive virtual reality and slow breathing to enhance relaxation and sleep in adolescents
Introduction: Sleep disturbances frequently emerge during adolescence amongst profound, normative, sleep maturation and biopsychosocial changes. Factors like stress, worry or rumination may make falling asleep and maintaining sleep more difficult. Here, we evaluate the efficacy of a novel intervention based on virtual reality (VR) and slow breathing to promote bedtime relaxation and facilitate sleep in high-school adolescents.
Methods: Twenty-nine 16-18 year-old adolescents with (N=9, 6 girls) and without (N=20, 11 girls) sleep difficulties underwent two counterbalanced in-lab relaxation and baseline polysomnography (PSG) nights. For the relaxation condition, immediately preceding bedtime, participants were engaged in slow diaphragmatic breathing (to promote physiological downregulation) whilst passively experiencing a relaxation immersive VR environment, designed to promote cognitive relaxation/distraction (20min). On the baseline night, participants engaged in quiet activities (e.g., reading a book) before bedtime (20min).
Results: The VR intervention resulted in a significant immediate increase in perceived relaxation and reduced worry (p<0.05). Also, heart rate dropped (~5bpm) in the pre-to-post intervention (p<0.05), while no significant change in heart rate was evident before and after the time spent in quiet activities on the baseline night. PSG-defined sleep onset latency was shorter (~6min reduction) and sleep efficiency was greater (~3% increase) on the VR relaxation night compared to the baseline night (p<0.05). In addition, baseline sleep onset latency was related to the magnitude of the baseline-to-relaxation reduction in sleep onset latency in participants (R2=0.70; p<0.01). There was no apparent difference in responses to the VR intervention between adolescents with or without insomnia. Conclusion: Our data highlight the potential for combining cognitive relaxation/distraction strategies, using immersive VR technology and physiological downregulation, to promote bedtime relaxation and improve overall sleep quality in adolescents. Further research is needed to evaluate the feasibility and effectiveness of such interventions over time. Support: National Heart, Lung and Blood Institute (NHLBI) R01HL139652 (to MdZ)
Synthetic torpor is an induced state of deep metabolic depression (MD) in an organism that does not naturally employ regulated and reversible MD. If applied to spaceflight crewmembers, this metabolic state may theoretically mitigate numerous biological and logistical challenges of human spaceflight. These benefits have been the focus of numerous recent articles where, invariably, they are discussed in the context of hypothetical deep MD states in which the metabolism of crewmembers is profoundly depressed relative to basal rates. However, inducing these deep MD states in humans, particularly humans aboard spacecraft, is currently impossible. Here, we discuss shallow MD as a feasible first step toward synthetic torpor during spaceflight and summarize perspectives following a recent NASA-hosted workshop. We discuss methods to safely induce shallow MD (e.g., sleep and slow wave enhancement via acoustic and photoperiod stimulation; moderate sedation via dexmedetomidine), which we define as an ~20% depression of metabolic rate relative to basal levels. We also discuss different modes of shallow MD application (e.g., habitual versus targeted, whereby shallow MD is induced routinely throughout a mission or only under certain circumstances, respectively) and different spaceflight scenarios that would benefit from its use. Finally, we propose a multistep development plan toward the application of synthetic torpor to human spaceflight, highlighting shallow MD’s role. As space agencies develop missions to send humans further into space than ever before, shallow MD has the potential to confer health benefits for crewmembers, reduce demands on spacecraft capacities, and serve as a testbed for deeper MD technologies.
A set of genetically engineered isogenic cell lines is developed to express either folate receptor alpha or mesothelin, and a control cell line negative for both antigens. These cell lines also express fluorescent and bioluminescent reporter transgenes. The cell lines are used to authenticate specificity and function of a T‐cell biofactory, a living vector that is developed to express proportionate amounts of engineered proteins upon engaging with disease cells through their specific antigenic biomarkers. The engineered cell lines are also used to assess the cytolytic function and specificity of primary T cells engineered with chimeric antigen receptors; and the specificity of monoclonal antibodies. The strategy described can be used to generate other cell lines to present different disease‐specific biomarkers for use as quality control tools.
Elementary English learner classroom composition and academic achievement: The role of classroom-level segregation, number of english proficiency levels, and opportunity to learn
Using mixed methods, we investigated (a) the association of the extent of English learner (EL) classroom-level segregation (proportion EL) and number of EL English proficiency levels with elementary EL academic achievement, using 2 years of administrative data, and (b) school staff–reported opportunity to learn–related advantages and disadvantages in segregated versus integrated compositions, using 3 years of interviews. Findings were corroborative across methods. After accounting for student-, classroom-, and school-level covariates, we found that ELs in more segregated classrooms exhibited lower performance, on average, on state tests of English language arts, mathematics, and English proficiency, and little evidence that classroom number of EL English proficiency levels was related to achievement. School staff consistently detailed the instructional, academic, and socio-emotional opportunities to learn afforded by the diversity/heterogeneity of integrated classrooms.
Viral proteins evade host immune function by molecular mimicry, often achieved by short linear motifs (SLiMs) of three to ten consecutive amino acids (AAs). Motif mimicry tolerates mutations, evolves quickly to modify interactions with the host, and enables modular interactions with protein complexes. Host cells cannot easily coordinate changes to conserved motif recognition and binding interfaces under selective pressure to maintain critical signaling pathways. SLiMs offer potential for use in synthetic biology, such as better immunogens and therapies, but may also present biosecurity challenges. We survey viral uses of SLiMs to mimic host proteins, and information resources available for motif discovery. As the number of examples continues to grow, knowledge management tools are essential to help organize and compare new findings.
Advice is a powerful tool for learning. But advice also presents the challenge of bridging the gap between the high-level representations that easily capture human advice and the low-level representations that systems must operate with using that advice. Drawing inspiration from studies on human motor skills and memory systems, we present an approach that converts human advice into synthetic or imagined training experiences, serving to scaffold the low-level representations of simple, reactive learning systems such as reinforcement learners. Research on using mental imagery and directed attention in motor and perceptual skills motivates our approach. We introduce the concept of a cognitive advice template for generating scripted, synthetic experiences and use saliency masking to further conceal irrelevant portions of training observations. We present experimental results for a deep reinforcement learning agent in a Minecraft-based game environment that show how such synthetic experiences improve performance, enabling the agent to achieve faster learning and higher rates of success.
Background: Microbiomes are complex aggregates of organisms, each of which has its own extensive metabolic network. A variety of metabolites are exchanged between the microbes. The challenge we address is understanding the overall metabolic capabilities of a microbiome: through what series of metabolic transformations can a microbiome convert a starting compound to an ending compound?
Results: We developed an efficient software tool to search for metabolic routes that include metabolic reactions from multiple organisms. The metabolic network for each organism is obtained from BioCyc, where the network was inferred from the annotated genome. The tool searches for optimal metabolic routes that minimize the number of reactions in each route, maximize the number of atoms conserved between the starting and ending compounds, and minimize the number of organism switches. The tool pre-computes the reaction sets found in each organism from BioCyc to facilitate fast computation of the reactions defined in a researcher-specified organism set. The generated routes are depicted graphically, and for each reaction in a route, the tool lists the organisms that can catalyze that reaction. We present solutions for three route-finding problems in the human gut microbiome: (1) production of indoxyl sulfate, (2) production of trimethylamine N-oxide (TMAO), and (3) synthesis and degradation of autoinducers. The optimal routes computed by our multi-organism route-search (MORS) tool for indoxyl sulfate and TMAO were the same as routes reported in the literature.
Conclusions: Our tool quickly found plausible routes for the discussed multi-organism route-finding problems. The routes shed light on how diverse organisms cooperate to perform multi-step metabolic transformations. Our tool enables scientists to consider multiple alternative routes and identifies the organisms responsible for each reaction.
Who gets what? Describing the non‐supervisory training and supports received by home visiting staff members and its relationship with turnover
The early childhood home visiting field lacks a basic understanding of home visiting program staff members’ receipt of on‐the‐job training from experts outside of their programs who are not their immediate colleagues or supervisors. To address this gap, we created a unique dataset by asking program leaders to log the external technical assistance (TA) that staff members received, and we collected a survey from 288 of the same staff members. We performed descriptive analyses to learn how many hours of TA staff members were receiving, what topics the TA most commonly addressed, and what formats (e.g., in‐person or virtual/remote, individual, or group) the TA was most commonly provided in. We then associated characteristics of the TA received with staff and program characteristics, as well as with staff members’ turnover. Multilevel analyses showed the TA supports that home visiting staff members received differed by role (home visitor or supervisor) and program characteristics, including home visiting model—Nurse Family Partnership (NFP) or Parents as Teachers (PAT)—program size, and maturity. About 23% of the home visiting staff members left their programs over the course of 18 months. PAT staff members were more likely to leave their programs than NFP staff members. We did not find that characteristics of TA received were predictive of staff members’ turnover. Implications and the need for further research are discussed.
To examine the Research + Practice Collaboratory’s strategy, SRI interviewed project leadership and professional association contacts, conducted observations at events, and reviewed documents to develop descriptions of strategies, activities, and routines. We later refined these descriptions by checking them against findings from other analysis tasks. To examine the Collaboratory’s outcomes, we used digital metrics (e.g., Google Analytics) to gauge the project’s reach and the uptake of its products, and then benchmarked the results of this analysis against the same metrics from several other similar entities. We also used interviews and surveys to gather the perspectives of people who partnered with the Collaboratory, participated in its events, and used its tools and resources, including professional association leaders, workshop participants, and website users. We also sought to place the Collaboratory in the broader education research-and-practice landscape by investigating the views, priorities, and needs of people involved in research-practice partnerships who had not participated in Collaboratory activities (including people who had not heard of it), as well of people who fund research-practice partnerships in education. In this way, the evaluation draws on findings regarding views and experience both within and beyond the Collaboratory’s sphere of influence.
This article provides candid advice for evaluators seeking to transition from K-12 to afterschool research. This advice may also help program directors and other stakeholders who want to make the research process work more effectively for them. We aim to help evaluators understand what is and is not possible (or advisable) in afterschool evaluations and to help practitioners serve as more effective partners by anticipating evaluator assumptions and other challenges that can derail a study. This article addresses a broad spectrum of research designs, from formative assessments to confirmatory analyses, in varied OST settings. In the authors experience, regardless of the intended audience for the report or the level of rigor in the study design, evaluators transitioning to afterschool are challenged by a common set of issues related to data collection and communication. This article addresses those challenges.
Excessive daytime sleepiness (EDS) and cataplexy are common symptoms of narcolepsy, a sleep disorder associated with the loss of hypocretin/orexin (Hcrt) neurons. Although only a few drugs have received regulatory approval for narcolepsy to date, treatment involves diverse medications that affect multiple biochemical targets and neural circuits. Clinical trials have demonstrated efficacy for the following classes of drugs as narcolepsy treatments: alerting medications (amphetamine, methylphenidate, modafinil/armodafinil, solriamfetol [JZP-110]), antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors), sodium oxybate, and the H 3 -receptor inverse agonist/antagonist pitolisant. Enhanced catecholamine availability and regulation of locus coeruleus (LC) norepinephrine (NE) neuron activity is likely central to the therapeutic activity of most of these compounds. LC NE neurons are integral to sleep/wake regulation and muscle tone; reduced excitatory input to the LC due to compromise of Hcrt/orexin neurons (likely due to autoimmune factors) results in LC NE dysregulation and contributes to narcolepsy/cataplexy symptoms. Agents that increase catecholamines and/or LC activity may mitigate EDS and cataplexy by elevating NE regulation of GABAergic inputs from the amygdala. Consequently, novel medications and treatment strategies aimed at preserving and/or modulating Hcrt/orexin-LC circuit integrity are warranted in narcolepsy/cataplexy.
Reducing bedtime physiological arousal levels using immersive audio-visual respiratory bio-feedback: a pilot study in women with insomnia symptoms
Hyperarousal is a critical component of insomnia, particularly at bedtime when individuals are trying to fall asleep. The current study evaluated the effect of a novel, acute behavioral experimental manipulation (combined immersive audio-visual relaxation and biofeedback) in reducing bedtime physiological hyperarousal in women with insomnia symptoms. After a clinical/adaptation polysomnographic (PSG) night, sixteen women with insomnia symptoms had two random-order PSG nights: immersive audio-visual respiratory bio-feedback across the falling asleep period (manipulation night), and no pre-sleep arousal manipulation (control night). While using immersive audio-visual respiratory bio-feedback, overall heart rate variability was increased and heart rate (HR) was reduced (by ~ 5 bpm; p < 0.01), reflecting downregulation of autonomic pre-sleep arousal, relative to no-manipulation. HR continued to be lower during sleep, and participants had fewer awakenings and sleep stage transitions on the manipulation night relative to the control night (p < 0.05). The manipulation did not affect sleep onset latency or other PSG parameters. Overall, this novel behavioral approach targeting the falling asleep process emphasizes the importance of pre-sleep hyperarousal as a potential target for improving sleep and nocturnal autonomic function during sleep in insomnia.
Modular Antigen-Specific T-cell Biofactories for Calibrated In Vivo Synthesis of Engineered Proteins
An artificial cell-signaling pathway is developed that capitalizes on the T-cell’s innate extravasation ability and transforms it into a vector (T-cell Biofactory) for synthesizing calibrated amounts of engineered proteins in vivo. The modularity of this pathway enables reprogramming of the T-cell Biofactory to target biomarkers on different disease cells, e.g. cancer, viral infections, autoimmune disorders. It can be expected that the T-cell Biofactory leads to a “living drug” that extravasates to the disease sites, assesses the disease burden, synthesizes the calibrated amount of engineered therapeutic proteins upon stimulation by the diseased cells, and reduces targeting of normal cells.
To increase participation in science, technology, engineering, and mathematics (STEM) studies and careers, some states have promoted inclusive STEM high schools. This study addressed the question of whether these high schools improve the odds that their graduates will pursue a STEM major in college. State higher education records were obtained for students surveyed as seniors in 23 inclusive STEM high schools and 19 comparison schools without a STEM focus. Propensity score weighting was used to ensure that students in the comparison school sample were very similar to those in the inclusive STEM school sample in terms of demographic characteristics and Grade 8 achievement. Students overall and from under-represented groups who had attended inclusive STEM high schools were significantly more likely to be in a STEM bachelor’s degree program two years after high school graduation. For students who entered two-year colleges, on the other hand, attending an inclusive STEM high school was not associated with entry into STEM majors.