Antibody responses require the proliferative expansion of B cells controlled by affinity-dependent signals. Yet, proliferative bursts are heterogeneous, varying between 0 and 8 divisions in response to the same stimulus. NFκB cRel is activated in response to immune stimulation in B cells and is genetically required for proliferation. Here, we asked whether proliferative heterogeneity is controlled by natural variations in cRel abundance. We developed a fluorescent reporter mTFP1-cRel for the direct observation of cRel in live proliferating B cells. We found that cRel is heterogeneously distributed among naïve B cells, which are enriched for high expressors in a heavy-tailed distribution. We found that high cRel expressors show faster activation of the proliferative program, but do not sustain it well, with population expansion decaying earlier. With a mathematical model of the molecular network, we showed that cRel heterogeneity arises from balancing positive feedback by autoregulation and negative feedback by its inhibitor IκBε, confirmed by mouse knockouts. Using live-cell fluorescence microscopy, we showed that increased cRel primes B cells for early proliferation via higher basal expression of the cell cycle driver cMyc. However, peak cMyc induction amplitude is constrained by incoherent feedforward regulation, decoding the fold change of cRel activity to terminate the proliferative burst. This results in a complex nonlinear, nonmonotonic relationship between cRel expression and the extent of proliferation. These findings emphasize the importance of direct observational studies to complement gene knockout results and to learn about quantitative relationships between biological processes and their key regulators in the context of natural variations.

Direct observation is a ground-truth measure for physical behavior, but the high cost limits widespread use. The purpose of this study was to develop and test machine learning methods to recognize aspects of physical behavior and location from videos of human movement: Adults (N = 26, aged 18-59 y) were recorded in their natural environment for two, 2- to 3-h sessions. Trained research assistants annotated videos using commercially available software including the following taxonomies: (1) sedentary versus non-sedentary (two classes); (2) activity type (four classes: sedentary, walking, running, and mixed movement); and (3) activity intensity (four classes: sedentary, light, moderate, and vigorous). Four machine learning approaches were trained and evaluated for each taxonomy. Models were trained on 80% of the videos, validated on 10%, and final accuracy is reported on the remaining 10% of the videos not used in training. Overall accuracy was as follows: 87.4% for Taxonomy 1, 63.1% for Taxonomy 2, and 68.6% for Taxonomy 3. This study shows it is possible to use computer vision to annotate aspects of physical behavior, speeding up the time and reducing labor required for direct observation. Future research should test these machine learning models on larger, independent datasets and take advantage of analysis of video fragments, rather than individual still images.

BACKGROUND: Social skills are frequently impaired in neurodevelopmental disorders and genetic conditions, including 22q11.2 deletion syndrome (22q11DS) and autism spectrum disorders (ASD). Although often assessed with questionnaires, direct assessment provides a more valid estimate of the constructs. Role-plays (i.e., simulates situational settings) therefore appear to be an appropriate indicator of social skills in daily life.
METHODS: This co-registered study involved 53 individuals with 22q11DS, 34 individuals with ASD, and 64 typically developing (TD) peers aged 12-30 years. All participants were assessed with role-plays as well as parent-reported questionnaires and clinical interviews focusing on social skills, functioning and anxiety.
RESULTS: Both clinical groups showed impaired social skills compared to TD, but distinct social profiles emerged between the groups. Individuals with 22q11DS displayed higher social appropriateness and clarity of speech but weaker general argumentation and negotiation skills, with the opposite pattern observed in participants with ASD. No association was found between social skills measured by direct observation and caregiver reports. Social anxiety, although higher in clinical groups than in TD, was not associated with role-plays.
CONCLUSIONS: This study highlights the need to train social skills through tailored interventions to target the specific difficulties of each clinical population. It also highlights the importance of combining measures as they do not necessarily provide the same outcome.

This article was migrated. The article was marked as recommended. Background: Canadian family medicine residency programs have the challenge of training in a wide breadth of topics and competencies within a two-year program, including training residents to be effective teachers. There has been a gap in knowledge with regards to the most effective method to train residents to teach. We developed, implemented, and evaluated a novel multi-level resident-as-teacher (RAT) coaching curriculum to provide training and authentic experiences for family medicine residents in teaching medical students. Methods: A curriculum centred around multi-level coaching was designed where family medicine faculty members directly observed and provided feedback to family medicine residents teaching small group clinical skills to first and second year medical students. Family medicine residents received didactic training on how to provide effective feedback to students and manage small group dynamics, after reviewing the learning objectives that students were to achieve. This was followed by the authentic small group teaching experiences. A survey was sent out by email to all residents and faculty members who had participated in the RAT curriculum at the end of the 2013-2014 and 2014-2015 academic years. Quantitative survey data were analyzed using descriptive statistics (frequencies, percentages, correlation coefficients (Spearman\'s rho)). Qualitative analysis was completed through thematic analysis of respondents\' written comments to open-ended survey questions. Results: 80% of 127 residents strongly agreed (26%) or agreed (54%) that the RAT program effectively developed their teaching skills. 57% either strongly agreed (17%) or agreed (40%) that the direct observation and feedback from faculty coaches helped to improve their teaching skills. There was a significant positive correlation between residents\' perceptions of the usefulness of the feedback from faculty coaches and residents\' perceptions of the overall RAT program\'s effectiveness in developing their teaching skills (r=0.42; p=0.001). Qualitative analysis revealed that residents perceived the RAT program to have solidified their own knowledge base for the content covered in the sessions. Residents also perceived a benefit of near-peer teaching for the medical students and an elevated family physicians\' profile as teachers. They found the active learning experience increased their self-awareness of their teaching skills. Time away from clinical rotations and preparation time were derived as a potential drawback of the program. All faculty coaches agreed or strongly agreed that the RAT curriculum improved the teaching skills of family medicine residents. Thematic analysis of the faculty coaches\' comments revealed that participating as coaches allowed for their own professional development in that their feedback and coaching skills improved. Conclusions: Our experiences and program evaluation of a novel multi-level resident-as-teacher coaching curriculum show that direct observation with feedback of authentic teaching activities is highly valued, and appears to be effective in developing resident teaching skills while fostering interest in future teaching.

This article was migrated. The article was marked as recommended. Objectives: To evaluate satisfaction among third year medical students with a bedside teaching exercise comprised of direct observation of student-performed physical examination skills and related feedback. Methods: An observational, cross-sectional study design was employed to study third year medical students undergoing the Neurology clerkship at the Ohio State University College of Medicine between June and October 2015. Immediately following the bedside physical examination teaching exercise, student satisfaction data was obtained in anonymous survey (n=21). In addition, student satisfaction data from the class cohort (n=51), regarding various learning formats in the curriculum, were collected at the end of a 16-week block of rotations including the Neurology clerkship. Data were summarized using descriptive statistics. Results: Most students felt that their level of confidence increased as a result (85.0%, n=17/21), and they felt they would use what they had learned in the future (95%, n=19/21). Only about half of the students felt strongly that reflection on the learning experience was sought (47.6%, n= 10/21). At the end of the 16 weeks block, the Neurology examination exercise was rated among the most highly in student satisfaction (3.35/4, SD=0.89) as compared to procedural workshops (2.76/4, SD= 0.76), other small group topic format (2.78/4, SD= 0.85), and traditional lecture (2.39/ 4, SD= 0.89). Conclusions: The bedside direct observation of physical examination performed by medical students is highly rated in student satisfaction, and students are most satisfied with this format of teaching among all formats studied. Increased opportunity for reflection in this setting represents an area for further development.

In the United States, the number of state policies mandating recess in schools has rapidly increased over the past decade; however, few policies specify recess frequency. Informed by an ecological model of physical activity (PA) policy, this study examined and compared total amounts and intensity of PA expended during recess among children attending schools in compliance with Arizona recess policy ARS§ 15-118 mandating 2 + daily recess periods versus not.
PA during recess was measured among grade three children (ages 8-10) in four randomly selected elementary schools (two complying averaging 30 daily recess minutes; two non-complying averaging 15 daily recess minutes) in Maricopa County, Arizona. Group-level PA was assessed by direct observation using the System for Observing Play and Leisure (137 observations). A subset of students (N = 134) from all schools wore ActiGraph GT3X + devices during recess to measure individual PA. General linear mixed effects models were used to analyze the impact of recess frequency on group and individual PA during recess.
Students attending complying schools spent significantly greater proportions of time in moderate-to-vigorous PA (MVPA) based on direct observation (5%) and accelerometry (15%) and less time being sedentary based on accelerometry (14%) during recess. Across the school day, this would equate to 5.1 more MVPA minutes based on systematic direct observation and 9.5 more MVPA minutes based on accelerometry, and 4.1 less minutes being sedentary based on accelerometry if students received two daily 15-minute recess periods compared to one.
Students attending elementary schools implementing 2 + recesses, in accordance with state policy, demonstrated greater MVPA and less sedentary time, providing preliminary evidence that recess frequency is associated with greater PA intensity among children during recess. Schools that adhere to state-level PA policies may provide a more supportive environment for PA, resulting in increased movement among students. Specifying recess frequency should be considered in statewide recess policy.

Purpose: To identify practice and social contextual factors that associate with physical activity (PA) levels of children during their participation in a youth soccer program. Methods: Twenty-seven youth soccer teams serving children ages 6-11 years participated. Research staff directly observed and recorded PA intensity and practice and social contextual factors using momentary time-sampling procedures. Each team was observed for 1 practice, during which approximately 6 children were each observed for twenty 30-s observation blocks (10-s observation, 20-s recording). In total, children were observed for 3,102 intervals. Multilevel logistic regression analyses were conducted to describe associations between PA intensity and practice and social contexts. Interaction terms were introduced into the models to determine if the associations differed across girls-only, boys-only, and coed teams. Results: A total of 158 children were observed across the 27 teams. Children were more likely to engage in moderate or vigorous PA while performing fitness (Odds Ratio [OR], 9.9, 95% CI = 5.34-18.04), game (OR, 4.0, 95% CI = 2.88-5.66), warm-up (OR, 2.8, 95% CI = 1.85-4.11), and drill (OR, 1.9, 95% CI = 1.41-2.67) activities compared to tactic/instructional activities. The associations between PA intensity levels and practice and social contexts did not differ across girls-only, boys-only, and coed teams. Conclusions: Fitness activities and full-team game play were associated with higher PA intensity levels during children\'s participation in youth soccer practices. Youth sport practice protocols can be modified to increase children\'s physical activity.

Precursor liquid is a nanoscale liquid creeping ahead of the macroscopic edge of spreading liquids, whose behaviors tightly correlate with the three-phase reaction efficiency and patterning accuracy. However, the important spatial-temporal characteristic of the precursor liquid still remains obscure because its real-time spreading process has not been directly observed. Here, we report that the spreading ionic liquid precursors in a silicon corner can be directly captured on video using in situ scanning electron microscopy. In situ spreading videos show that the precursor liquid spreads linearly over time ([Formula: see text]) rather than obeying the classic Lucas-Washburn law ([Formula: see text]) and possesses a characteristic width of ∼250-310 nm. Theoretical analyses and molecular dynamics simulations demonstrate that the unique behaviors of precursor liquids originate from the competing effect of van der Waals force and surface energy. These findings provide avenues for directly observing liquid/solid interfacial phenomena on a microscopic level.

Development of standardized diagnostic instruments has facilitated the systematic characterization of individuals with autism spectrum disorders (ASD) in clinical and research settings. However, overemphasis on scores from specific instruments has significantly detracted from the original purpose of these tools. Rather than provide a definitive \"answer,\" or even a confirmation of diagnosis, standardized diagnostic instruments were designed to aid clinicians in the process of gathering information about social communication, play, and repetitive and sensory behaviors relevant to diagnosis and treatment planning. Importantly, many autism diagnostic instruments are not validated for certain patient populations, including those with severe vision, hearing, motor, and/or cognitive impairments, and they cannot be administered via a translator. In addition, certain circumstances, such as the need to wear personal protective equipment (PPE), or behavioral factors (e.g., selective mutism) may interfere with standardized administration or scoring procedures, rendering scores invalid. Thus, understanding the uses and limitations of specific tools within specific clinical or research populations, as well as similarities or differences between these populations and the instrument validation samples, is paramount. Accordingly, payers and other systems must not mandate the use of specific tools in cases when their use would be inappropriate. To ensure equitable access to appropriate assessment and treatment services, it is imperative that diagnosticians be trained in best practice methods for the assessment of autism, including if, how, and when to appropriately employ standardized diagnostic instruments.

OBJECTIVE: The authors evaluated the validity of a structured direct observation form (DOF) to assess medical student performance on psychiatric interviews for use in the psychiatry clerkship.
METHODS: One hundred and forty-eight third-year medical students were evaluated by two DOFs completed by a supervising resident, fellow, attending, or another team member. One DOF was completed early (time 1) and the other late (time 2) during a 4-week psychiatry clerkship.
RESULTS: The DOF showed good internal consistency (Cronbach\'s alpha = 0.88-0.89). DOFs submitted at time 2 were positively associated with end-of-course clinical grades (p < 0.001); this association remained significant while controlling for time of academic year the course was completed, rater rank, complexity of the case, and difficulty of the interview (time 2 p < 0.001). Mean scores from the DOF were associated with the time of year students took the course with students assessed early in the academic year having lower average scores (p-values = 0.01 at time 1, 0.002 at time 2). Scores on time 1 DOFs were positively associated with rater rank (p = 0.005; residents gave higher scores than faculty). DOFs also correlated with an Entrustable Professional Activity (EPA) assessment of the interview (time 1 r = 0.76, p < 0.001; time 2 r = 0.79, p < 0.001), but not with shelf exam scores (time 1 r = 0.10, p = 0.24; time 2 r = 0.11, p = 0.21).
CONCLUSIONS: A brief structured form evaluating medical student performance on psychiatric interviews provided valid information about performance by third-year medical students during the psychiatry clerkship.