Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells.

Patients with estrogen receptor-positive breast cancer receive adjuvant endocrine therapies (ET) that delay relapse by targeting clinically undetectable micrometastatic deposits. Yet, up to 50% of patients relapse even decades after surgery through unknown mechanisms likely involving dormancy. To investigate genetic and transcriptional changes underlying tumor awakening, we analyzed late relapse patients and longitudinally profiled a rare cohort treated with long-term neoadjuvant ETs until progression. Next, we developed an in vitro evolutionary study to record the adaptive strategies of individual lineages in unperturbed parallel experiments. Our data demonstrate that ETs induce nongenetic cell state transitions into dormancy in a stochastic subset of cells via epigenetic reprogramming. Single lineages with divergent phenotypes awaken unpredictably in the absence of recurrent genetic alterations. Targeting the dormant epigenome shows promising activity against adapting cancer cells. Overall, this study uncovers the contribution of epigenetic adaptation to the evolution of resistance to ETs. SIGNIFICANCE: This study advances the understanding of therapy-induced dormancy with potential clinical implications for breast cancer. Estrogen receptor-positive breast cancer cells adapt to endocrine treatment by entering a dormant state characterized by strong heterochromatinization with no recurrent genetic changes. Targeting the epigenetic rewiring impairs the adaptation of cancer cells to ETs. See related commentary by Llinas-Bertran et al., p. 704. This article is featured in Selected Articles from This Issue, p. 695.

Natural ballistic gelatine ultrasound phantoms are suitable to be used for student education and can be produced cheaply and effectively.

Practical experience in ultrasonography at medical and veterinary schools is difficult to achieve using live models due to ethical considerations. A solution to this problem has been the creation of synthetic ultrasound phantoms that allow simulation of both ultrasound scans and ultrasound-guided procedures. Whilst commercially available phantoms are expensive in a resource-limited environment, it would be desirable to create affordable, reusable, homemade phantoms which could be used to aid student learning. Recent studies have indicated that ballistic gelatine is an excellent material for this. A prospective, experimental study was performed with three ultrasound phantoms for student use. Vascular, bladder, and liver parenchymal models were produced with a natural ballistic gel, along with instructions for their construction and maintenance. Model efficacy was evaluated by assessing students' performance in completing a set of tasks when performing ultrasound on a dog. Group one received training with the models, group two received prior training without the models and the group three received no training. Entry and exit questionnaires assessed students' confidence in ultrasound scanning having used the models. Student questionnaires showed that students enjoyed using the models and found them more useful than existing teaching aids. It was also found that the models produced better practical skills in students that trained with them, in comparison to existing teaching. The models were easy to make, produced good images, and are reusable.

Limitations of current spatial ability testing for military aviators.

Spatial ability has long been considered an important attribute when identifying military aviators. This paper examines the Direction Orientation Task (DOT), which is currently used by the US military to assess spatial ability in aviation applicants. Several limitations of the test, such as a limited number of trials and the availability of practice trials online, make it subject to potential ceiling effects. The paper presents historical data of all Naval Aviator applicants over a six-year time period and revealed that 22% of applicants answered 90% or more of the questions correctly. Furthermore, test performance has significantly increased in the years since the test was first administered and there is evidence that DOT is no longer contributing incremental validity. A follow-up empirical study looked at DOT performance and strategy in a group of military student aviators and student air traffic controllers. The results of the empirical investigation reveal that the use of an analytic strategy was associated with higher performance on the DOT, whereas the use of a spatial strategy was not associated with performance. Taken together, the improved performance data over time and the data on strategy use suggest the test's ability to measure spatial ability may be diminishing, ultimately reducing its construct and incremental validity. This is problematic and should be addressed, since the DOT is the only measure of spatial ability used by the Navy to assess aviation applicants.

A Team Training Field Research Study: Extending a Theory of Team Development.

Recent advances in the science of teams have provided much insight into the important attitudes (e.g., team cohesion and efficacy), cognitions (e.g., shared team cognition), and behaviors (e.g., teamwork communications) of high performing teams and how these competencies emerge as team members interact, and appropriate measurement methods for tracking development. Numerous training interventions have been found to effectively improve these competencies, and more recently have begun addressing the problem of team dynamics. Team science researchers have increasingly called for more field studies to better understand training and team development processes in the wild and to advance the theory of team development. In addition to the difficulty of gaining access to teams that operate in isolated, confined, and extreme environments (ICE), a major practical challenge for trainers of ICE teams whose schedules are already strained is the need to prioritize the most effective strategies to optimize the time available for implementation. To address these challenges, we describe an applied research experiment that developed and evaluated an integrated team training approach to improve Tactical Combat Casualty (TC3) skills in U.S. Army squads. Findings showed that employing effective team training best practices improved learning, team cognition, emergent team processes, and performance. We recommend future research should focus on understanding the types of training strategies needed to enable teams and team leaders to develop from novices to experts. Effectively modifying training to scale it to team expertise requires more research. More laboratory and field research is needed to further develop measures of team knowledge emergence for complex task domains, and include other potential emergent factors such as team leadership and resilience. Practical implications for research include developing automated tools and technologies needed to implement training and collect team data, and employ more sensitive indicators (e.g., behavioral markers) of team attitudes, cognitions and behaviors to model the dynamics of how they naturally change over time. These tools are critical to understanding the dynamics of team development and to implement interventions that more effectively support teams as they develop over time.

Assessing task importance and anxiety in medical school: an instrument development and initial validation study.

Recent research in medical education suggests that students' motivational beliefs, such as their beliefs about the importance of a task, and their emotions are meaningful predictors of learning and performance. The primary purpose of this study was to develop a self-report measure of "task importance" and "anxiety" in relation to several medical education competencies and to collect validity evidence for the new measures. The secondary purpose was to evaluate differences in these measures by year of medical school. Exploratory factor analysis of scores from 368 medical school students suggested two task importance factors and three anxiety factors. The task importance and anxiety subscales were weakly related to each other and exhibited consistently negative and positive correlations, respectively, with three self-efficacy subscales. The task importance subscales were positively related to "metacognition," whereas "interpersonal skills anxiety" and "health knowledge anxiety" were positively related to "procrastination." All three anxiety factors were positively related to "avoidance of help seeking," whereas "interpersonal skills and professionalism importance" was negatively related to help avoidance behaviors. Finally, comparisons across the 4 years of medical school indicated that some aspects of task importance and anxiety varied significantly. Overall, findings from this study provide validity evidence for the psychometric quality of these scales, which capture task importance and anxiety in medical students. Limitations and implications for medical education research are discussed.