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MotivationWhile evolutionary approaches to medicine show promise, measuring evolution itself is difficult due to experimental constraints and the dynamic nature of body systems. In cancer evolution, continuous observation of clonal architecture is impossible, and longitudinal samples from multiple timepoints are rare. Increasingly available DNA sequencing datasets at single-cell resolution enable the reconstruction of past evolution using mutational history, allowing for a better understanding of dynamics prior to detectable disease. There is an unmet need for an accurate, fast, and easy-to-use method to quantify clone growth dynamics from these datasets.ResultsWe derived methods based on coalescent theory for estimating the net growth rate of clones using either reconstructed phylogenies or the number of shared mutations. We applied and validated our analytical methods for estimating the net growth rate of clones, eliminating the need for complex simulations used in previous methods. When applied to hematopoietic data, we show that our estimates may have broad applications to improve mechanistic understanding and prognostic ability. Compared to clones with a single or unknown driver mutation, clones with multiple drivers have significantly increased growth rates (median 0.94 versus 0.25 per year; P = 1.6×10-6). Further, stratifying patients with a myeloproliferative neoplasm (MPN) by the growth rate of their fittest clone shows that higher growth rates are associated with shorter time to MPN diagnosis (median 13.9 versus 26.4 months; P = 0.0026).Availability and implementationWe developed a publicly available R package, cloneRate, to implement our methods (Package website: https://bdj34.github.io/cloneRate/). Source code: https://github.com/bdj34/cloneRate/.

Introduction: Applicants to residency face a number of difficult questions during the interview process, one of which is when a program asks for a commitment to rank the program highly. The regulations governing the National Resident Matching Program (NRMP) match explicitly forbid any residency programs asking for a commitment. Methods: We conducted a cross-sectional survey of applicants from U.S. medical schools to five specialties during the 2006-2007 interview season using the Electronic Residency Application Service of the Association of American Medical Colleges. Applicants were asked to recall being asked to provide any sort of commitment (verbal or otherwise) to rank a program highly. Surveys were sent after rank lists were submitted, but before match day. We analyzed data using descriptive statistics and logistic regression. Results: There were 7,028 unique responses out of 11,983 surveys sent for a response rate of 58.6%. Of those who identified their specialty (emergency medicine, internal medicine, obstetrics and gynecology [OBGYN], general surgery and orthopedics), there were 6,303 unique responders. Overall 19.6% (1380/7028) of all respondents were asked to commit to a program. Orthopedics had the highest overall prevalence at 28.9% (372/474), followed by OBGYN (23.7%; 180/759), general surgery (21.7%; 190/876), internal medicine (18.3%; 601/3278), and finally, emergency medicine (15.4%; 141/916). Of those responding, 38.4% stated such questions made them less likely to rank the program. Conclusion: Applicants to residencies are being asked questions expressly forbidden by the NRMP. Among the five specialties surveyed, orthopedics and OBGYN had the highest incidence of this violation. Asking for a commitment makes applicants less likely to rank a program highly. [West J Emerg Med. 2015;16(2):331-335.]

Introduction: Residency interview apparel has traditionally been the dark business suit. We changed the interview dress code from a traditionally established unwritten ‘formal’ attire to an explicitly described ‘informal’ attire. We sought to assess if the change in dress code attire changed applicants’ perceptions of the residency program or decreased costs. Methods: The authors conducted an anonymous survey of applicants applying to one emergency medicine residency program during two application cycles ending in 2012 and 2013. Applicants were asked if the change in dress code affected their perception of the program, comfort level, overall costs and how it affected their rank lists. Results: We sent the survey to 308 interviewed applicants over two years. Of those, 236 applicants completed the survey for a combined response rate of 76.6% (236/308). Among respondents, 85.1% (200 of 235) stated they appreciated the change; 66.7% (154 of 231) stated the change caused them to worry more about what to wear. Males were more uncomfortable than females due to the lack of uniformity on the interview day (18.5% of males [25/135] vs. 7.4% of females [7/95], collapsed results p-value 0.008). A total of 27.7% (64/231) agreed that the costs were less overall. The change caused 50 of 230 (21.7%) applicants to rank the program higher on their rank list and only one applicant to rank the program lower. Conclusion: A change to a more informal dress code resulted in more comfort and fewer costs for applicants to a single residency program. The change also resulted in some applicants placing the program higher on their rank order list. [West J Emerg Med. 2015;16(1):127-132.]

Infectious flexor tenosynovitis (FTS) is a serious infection of the hand and wrist that can lead to necrosis and amputation without prompt diagnosis and surgical debridement. Despite the growing use of point-of-care ultrasound (POCUS) by emergency physicians there is only one reported case of the use of POCUS for the diagnosis of infectious FTS in the emergency department setting. We present a case of a 58 year-old man where POCUS identified tissue necrosis and fluid along the flexor tendon sheath of the hand. Subsequent surgical pathology confirmed the diagnosis of infectious FTS. [West J Emerg Med. 2015;16(2):260–262.]

We describe two established STEM camps that went virtual following the outbreak of COVID-19 during the summer of 2020. Our Summer Research Opportunity (SRO) camp engages middle school science fair winners in a forensic research opportunity, while The Immokalee Foundation (TIF) camp introduces middle school students from historically underrepresented groups to STEM topics. Home kits were carefully prepared and delivered to all participants to enhance their engagement with our faculty facilitators. Modifications to accommodate the virtual experience are discussed. Our program assessment used a retrospective pretest-posttest design delivering a modified STEM Semantics survey to measure interest in STEM topics and STEM careers. While the programming and the population was different for each camp, both programs achieved positive outcomes in the virtual environment enhancing participant interest in, excitement for, and importance of STEM topics and STEM careers. The local TV news even broadcasted a short video of one of the camps.

We describe a long-standing weeklong K-12 STEM teacher workshop that shifted to a virtual platform in 2020. We re-engaged former participants during this STEM Institute with goals of (1) modeling ways to connect best practices for STEM education gained in previous workshops to a virtual environment, (2) providing space for teacher reflection on their virtual learning implementation during Spring 2020 without sufficient planning time, (3) offering collaborative planning time as they prepared for the Fall 2020 semester, and (4) supporting Southwest Florida STEM teachers through community building during the institute. We continued to focus our delivery (previously in person now virtually) on the 5E model (BSCS, 1987). Drawing upon past participant surveys and anecdotal data from previous years, facilitators addressed teachers' need for tools and lessons they could implement in their own virtual classes in the fall with plenty of time to listen and learn from each other. Here we discuss our virtual STEM Institute structure in contrast to previous years, virtual tools demonstrated by facilitators and teacher participants, and facilitator experiences and outcomes during the virtual workshop. We provide both qualitative and quantitative summary data from participant surveys on satisfaction with STEM Institute components related to the goals described.

Myeloblast expansion is a hallmark of disease progression and comprises CD34+ hematopoietic stem and progenitor cells (HSPC). How this compartment evolves during disease progression in chronic myeloid neoplasms is unknown. Using single-cell RNA sequencing and high-parameter flow cytometry, we show that chronic myelomonocytic leukemia (CMML) CD34+ HSPC can be classified into three differentiation trajectories: monocytic, megakaryocyte-erythroid progenitor (MEP), and normal-like. Hallmarks of monocytic-biased trajectory were enrichment of CD120b+ inflammatory granulocyte-macrophage progenitor (GMP)-like cells, activated cytokine receptor signaling, phenotypic hematopoietic stem cell (HSC) depletion, and adverse outcomes. Cytokine receptor diversity was generally an adverse feature and elevated in CD120b+ GMPs. Hypomethylating agents decreased monocytic-biased cells in CMML patients. Given the enrichment of RAS pathway mutations in monocytic-biased cells, NRAS-competitive transplants and LPS-treated xenograft models recapitulated monocytic-biased CMML, suggesting that hematopoietic stress precipitates the monocytic-biased state. Deconvolution of HSPC compartments in other myeloid neoplasms and identifying therapeutic strategies to mitigate the monocytic-biased differentiation trajectory should be explored.SignificanceOur findings establish that multiple differentiation states underlie CMML disease progression. These states are negatively augmented by inflammation and positively affected by hypomethylating agents. Furthermore, we identify HSC depletion and expansion of GMP-like cells with increased cytokine receptor diversity as a feature of myeloblast expansion in inflammatory chronic myeloid neoplasms. This article is highlighted in the In This Issue feature, p. 476.

Managing the stability of today's electric power systems is based on decades of experience with the physical properties and control responses of large synchronous generators. Today's electric power systems are rapidly transitioning toward having an increasing proportion of generation from nontraditional sources, such as wind and solar (among others), as well as energy storage devices, such as batteries. In addition to the variable nature of many renewable generation sources (because of the weather-driven nature of their fuel supply), these newer sources vary in size - from residential-scale rooftop systems to utility-scale power plants - and they are interconnected throughout the electric grid, both from within the distribution system and directly to the high-voltage transmission system. Most important for our purposes, many of these new resources are connected to the power system through power electronic inverters. Collectively, we refer to these sources as inverter-based resources.

It is a critical time to reflect on the National Ecological Observatory Network (NEON) science to date as well as envision what research can be done right now with NEON (and other) data and what training is needed to enable a diverse user community. NEON became fully operational in May 2019 and has pivoted from planning and construction to operation and maintenance. In this overview, the history of and foundational thinking around NEON are discussed. A framework of open science is described with a discussion of how NEON can be situated as part of a larger data constellation—across existing networks and different suites of ecological measurements and sensors. Next, a synthesis of early NEON science, based on >100 existing publications, funded proposal efforts, and emergent science at the very first NEON Science Summit (hosted by Earth Lab at the University of Colorado Boulder in October 2019) is provided. Key questions that the ecology community will address with NEON data in the next 10 yr are outlined, from understanding drivers of biodiversity across spatial and temporal scales to defining complex feedback mechanisms in human–environmental systems. Last, the essential elements needed to engage and support a diverse and inclusive NEON user community are highlighted: training resources and tools that are openly available, funding for broad community engagement initiatives, and a mechanism to share and advertise those opportunities. NEON users require both the skills to work with NEON data and the ecological or environmental science domain knowledge to understand and interpret them. This paper synthesizes early directions in the community’s use of NEON data, and opportunities for the next 10 yr of NEON operations in emergent science themes, open science best practices, education and training, and community building.

This study sought to understand challenges that teachers (N = 15) in poverty settings encountered during information literacy instruction (ILI) and inquiry-based learning. First order barriers focused on insufficient support for instruction (training to align ILI in poverty settings; integrate diverse information resources/technology tools), administrative support (differing administrative priorities toward ILI); and access to technology (lack of broadband internet; paywalled information/learning resources). Second-order barriers consisted of the following: teachers' pedagogical beliefs (empowering student IL through question-generation); teachers' beliefs about computers/technology (challenge of misinformation and knowledge gaps); and teachers' beliefs about students' roles (strategies for structuring and limiting resources; addressing affective deficits due to poverty through ILI). Lastly, third-order barriers explored teachers' design-thinking in ways that employed multiple visualizations. Implications for theory and practice are discussed.

STEM students often struggle in their first-year fundamental courses. Negative psychological states after the first exam in those courses can serve as either a source of demotivation or motivation throughout the semester. We examined how self-efficacy altered the effect of regret about their first exam on course performance. Using a longitudinal study of students enrolled in early courses that engineering majors take in their first semester, we measured cognitive and affective regret about their first exam, both right after that first exam and a month later, and self-efficacy before the first exam. We found that regret right after the exam did not predict course grade. However, affective regret a month later reduced course grade, controlling for first exam grade. In addition, self-efficacy buffered that effect; students with high self-efficacy did not have their course grade affected by regret whereas those with low self-efficacy showed declines in their course grade due to regret.

Background: Concussion underreporting is endemic, and social norms are an established predictor of concussion reporting behavior. However, pluralistic ignorance--a situation in which most individuals in a group hold the belief that their peers' views differ from their own, despite views actually being similar--has not been studied in this context. Aim: To assess whether pluralistic ignorance contributes to concussion underreporting. Method: We surveyed 2,504 military service academy cadets. Each cadet was presented with a survey asking about their willingness to self-report a concussion, their perception of other cadets' willingness to report a concussion, and personal and demographic factors. Results. Most cadets viewed themselves as more willing to report a concussion than others (mean difference = 1.12, 95% CI [1.02, 1.21]), a belief consistent with pluralistic ignorance. Demographic characteristics were associated with holding this belief. For example, female cadets and upper-class cadets were more likely to show this disparity than male or under-class cadets, respectively. Collegiate athletes not only showed similar willingness to report concussion as nonathletes but also perceived other cadets as less likely to report concussions. Meanwhile, future pilots showed less self-report willingness and perceived that others were similarly unwilling to report concussions. Discussion: A majority of this economically and geographically diverse population displays characteristics of pluralistic ignorance: They largely share proconcussion reporting sentiments but incorrectly perceive that others do not. This belief is not held uniformly in all subpopulations, which may inform how these beliefs are developed and maintained. Conclusions: Pluralistic ignorance is an important consideration in concussion education efforts.

Two free fully online courses were offered by Peoples-uni on its Open Online Courses site, both as self-paced courses available any time and as courses run over four weeks with tutor-led discussions. We tested the hypothesis that there are no measurable differences in outcomes between the two delivery methods. Similar numbers attended both versions of each course; students came from multiple countries and backgrounds. Numbers of discussion forum posts were greater in tutor-led than self-paced courses. Measured outcomes of certificates of completion, quiz completion and marks gained were very similar and not statistically significantly different between the tutor-led and the self-paced versions of either course. In light of little discernible difference in outcome between self-paced learning compared with courses including tutor-led discussions, the utility of the time cost to tutors is in question. The findings may be relevant to others designing online courses, including MOOCs.