Biomolecular Modeling and Simulation: A Prospering Multidisciplinary Field.

We reassess progress in the field of biomolecular modeling and simulation, following up on our perspective published in 2011. By reviewing metrics for the field's productivity and providing examples of success, we underscore the productive phase of the field, whose short-term expectations were overestimated and long-term effects underestimated. Such successes include prediction of structures and mechanisms; generation of new insights into biomolecular activity; and thriving collaborations between modeling and experimentation, including experiments driven by modeling. We also discuss the impact of field exercises and web games on the field's progress. Overall, we note tremendous success by the biomolecular modeling community in utilization of computer power; improvement in force fields; and development and application of new algorithms, notably machine learning and artificial intelligence. The combined advances are enhancing the accuracy andscope of modeling and simulation, establishing an exemplary discipline where experiment and theory or simulations are full partners.

Gender Bias in Collaborative Medical Decision Making: Emergent Evidence.

This initial, exploratory study on gender bias in collaborative medical decision making examined the degree to which physicians' reliance on a team member's patient care advice differs as a function of the gender of the advice giver. In 2018, 283 anesthesiologists read a brief, online clinical vignette and were randomly assigned to receive treatment advice from 1 of 8 possible sources (physician or nurse, man or woman, experienced or inexperienced). They then indicated their treatment decision, as well as the degree to which they relied upon the advice given.The results revealed 2 patterns consistent with gender bias in participants' advice taking. First, when treatment advice was delivered by an inexperienced physician, participants reported replying significantly more on the advice of a man versus a woman, F(1,61) = 4.24, P = .04. Second, participants' reliance on the advice of the woman physician was a function of her experience, F(1,62) = 6.96, P = .01, whereas reliance on the advice of the man physician was not, F(1,60) = 0.21, P = .65.These findings suggest women physicians, relative to men, may encounter additional hurdles to performing their jobs, especially at early stages in their careers. These hurdles are rooted in psychological biases of others, rather than objective features of cases or treatment settings. Cultural stereotypes may shape physicians' information use and decision-making processes (and hinder collaboration), even in contexts that appear to have little to do with social category membership. The authors recommend institutions adopt policies and practices encouraging equal attention to advice, regardless of the source, to help ensure advice taking is a function of information quality rather than the attributes of the advice giver. Such policies and practices may help surface and implement diverse expert perspectives in collaborative medical decision making, promoting better and more effective patient care.

The genealogy of teaching clinical reasoning and diagnostic skill: the GEL Study.

The genealogy of graduate medical education in America begins at the bedside. However, today's graduate medical trainees work in a training environment that is vastly different from medical training a century ago. The goal of the Graduate Medical Education Laboratory (GEL) Study, supported by the American Medical Association's (AMA) "Reimagining Residency" initiative, is to determine the factors in the training environment that most contribute to resident well-being and developing diagnostic skills. We believe that increasing time at the bedside will improve clinical skill, increase professional fulfillment, and reduce workplace burnout. Our graduate medical education laboratory will test these ideas to understand which interventions can be shared among all training programs. Through the GEL Study, we aim to ensure resident readiness for practice as we understand, then optimize, the learning environment for trainees and staff.

Mesoscale Modeling of Nucleosome-Binding Antibody PL2-6: Mono- versus Bivalent Chromatin Complexes.

Interactions of chromatin with bivalent immunoglobin nucleosome-binding antibodies and their monovalent (papain-derived) antigen-binding fragment analogs are useful probes for examining chromatin conformational states. To help interpret antibody-chromatin interactions and explore how antibodies might compete for interactions with chromatin components, we incorporate coarse-grained PL2-6 antibody modeling into our mesoscale chromatin model. We analyze interactions and fiber structures for the antibody-chromatin complexes in open and condensed chromatin, with and without H1 linker histone (LH). Despite minimal and transient interactions at physiological salt, we capture significant differences in antibody-chromatin complex configurations in open fibers, with more intense interactions between the bivalent antibody and chromatin compared to monovalent antigen-binding fragments. For these open chromatin fiber morphologies, antibody binding to histone tails is increased and compaction is greater for bivalent compared to monovalent and antibody-free systems. Differences between monovalent and bivalent binding result from antibody competition with internal chromatin fiber components (nucleosome core and linker DNA) for histone tail (H3, H4, H2A, H2B) interactions. This antibody competition for tail contacts reduces tail-core and tail-linker interactions and increases tail-antibody interactions. Such internal structural changes in open fibers resemble mechanisms of LH condensation, driven by charge screening and entropy changes. For condensed fibers at physiological salt, the three systems are much more similar overall, but some subtle tail interaction differences can be noted. Adding LH results in less-dramatic changes for all systems, except that the bivalent complex at physiological salt shows cooperative effects between LH and the antibodies in condensing chromatin fibers. Such dynamic interactions that depend on the internal structure and complex-stabilizing interactions within the chromatin fiber have implications for gene regulation and other chromatin complexes such as with LH, remodeling proteins, and small molecular chaperones that bind and modulate chromatin structure.

Treating the "Not-Invented-Here Syndrome" in Medical Leadership: Learning From the Insights of Outside Disciplines.

Physicians are being increasingly called upon to engage in leadership at all levels of modern health organizations, leading many to call for greater research and training interventions regarding physician leadership development. Yet, within these calls to action, the authors note a troubling trend toward siloed, medicine-specific approaches to leadership development and a broad failure to learn from the evidence and insight of other relevant disciplines, such as the organizational sciences. The authors describe how this trend reflects what has been called the "not-invented-here syndrome" (NIHS)-a commonly observed reluctance to adopt and integrate insights from outside disciplines-and highlight the pitfalls of NIHS for effective physician leadership development. Failing to learn from research and interventions in the organizational sciences inhibits physician leadership development efforts, leading to redundant rediscoveries of known insights and reinventions of existing best practices. The authors call for physician leaders to embrace ideas that are "proudly developed elsewhere" and work with colleagues in outside disciplines to conduct collaborative research and develop integrated training interventions to best develop physician leaders who are prepared for the complex, dynamic challenges of modern health care.

Mesoscale modeling reveals formation of an epigenetically driven HOXC gene hub.

Gene expression is orchestrated at the structural level by nucleosome positioning, histone tail acetylation, and linker histone (LH) binding. Here, we integrate available data on nucleosome positioning, nucleosome-free regions (NFRs), acetylation islands, and LH binding sites to "fold" in silico the 55-kb HOXC gene cluster and investigate the role of each feature on the gene's folding. The gene cluster spontaneously forms a dynamic connection hub, characterized by hierarchical loops which accommodate multiple contacts simultaneously and decrease the average distance between promoters by ∼100 nm. Contact probability matrices exhibit "stripes" near promoter regions, a feature associated with transcriptional regulation. Interestingly, while LH proteins alone decrease long-range contacts and acetylation alone increases transient contacts, combined LH and acetylation produce long-range contacts. Thus, our work emphasizes how chromatin architecture is coordinated strongly by epigenetic factors and opens the way for nucleosome resolution models incorporating epigenetic modifications to understand and predict gene activity.

Social Media as a Platform for Surgical Learning: Use and Engagement Patterns Among Robotic Surgeons.

: In response to technological advances and growing dispersion of surgical practice around the globe, social media platforms have emerged in recent years as channels for surgeons to share experiences, ask questions, and learn from one another. To better understand surgeons' engagement with these platforms, we analyzed data from a closed-membership Facebook group for robotic surgeons. Our analysis revealed that surgeons posted more frequently on midweek days, and further that text posts received significantly more comments, and significantly fewer "likes," than posts containing links, photos, or videos. We discuss the implications of these use and engagement patterns for the viability of social media platforms as tools for surgeons to learn vicariously from their peers' experiences and expertise.

Incorporating Interpersonal Skills into Otolaryngology Resident Selection and Training.

Increasing attention has been paid to the selection of otolaryngology residents, a highly competitive process but one with room for improvement. A recent commentary in this journal recommended that residency programs more thoroughly incorporate theory and evidence from personnel psychology (part of the broader field of organizational science) in the resident selection process. However, the focus of this recommendation was limited to applicants' cognitive abilities and independent work-oriented traits (eg, conscientiousness). We broaden this perspective to consider critical interpersonal skills and traits that enhance resident effectiveness in interdependent health care organizations and we expand beyond the emphasis on selection to consider how these skills can be honed during residency. We advocate for greater use of standardized team-based care simulations, which can aid in assessing and developing the key interpersonal leadership skills necessary for success as an otolaryngology resident.

Making Management Skills a Core Component of Medical Education.

Physicians are being called upon to engage in greater leadership and management in increasingly complex and dynamic health care organizations. Yet, management skills are largely undeveloped in medical education. Without formal management training in the medical curriculum, physicians are left to cultivate their leadership and management abilities through a haphazard array of training programs or simply through trial and error, with consequences that may range from frustration among staff to reduced quality of care and increased risk of patient harm. To address this issue, the authors posit that medical education needs a more systematic focus on topics related to management and organization, such as individual decision making, interpersonal communication, team knowledge sharing, and organizational culture. They encourage medical schools to partner with business school faculty or other organizational scholars to offer a "Management 101" course in the medical curriculum to provide physicians-in-training with an understanding of these topics and raise the quality of physician leadership and management in modern health care organizations.

Phage-like packing structures with mean field sequence dependence.

Packing of double-stranded DNA in phages must overcome both electrostatic repulsions and the problem of persistence length. We consider coarse-grained models with the ability to kink and with randomly generated disorder. We show that the introduction of kinking into configurations of the DNA polymer packaged within spherical confinement results in significant reductions of the overall energies and pressures. We use a kink model which has the ability to deform every 24 bp, close to the average length predicted from phage sequence. The introduction of such persistence length defects even with highly random packing models increases the local nematic ordering of the packed DNA polymer segments. Such local ordering allowed by kinking not only reduces the total bending energy of confined DNA due to nonlinear elasticity but also reduces the electrostatic component of the energy and pressure. We show that a broad ensemble of polymer configurations is consistent with the structural data. © 2016 Wiley Periodicals, Inc.

Cooperation in multicultural negotiations: How the cultures of people with low and high power interact.

This study examined whether the cultures of low- and high-power negotiators interact to influence cooperative behavior of low-power negotiators. Managers from 4 different cultural groups (Germany, Hong Kong, Israel, and the United States) negotiated face-to-face in a simulated power-asymmetric commons dilemma. Results supported an interaction effect in which cooperation of people with lower power was influenced by both their culture and the culture of the person with higher power. In particular, in a multicultural setting, low-power managers from Hong Kong, a vertical-collectivist culture emphasizing power differences and group alignment, adjusted their cooperation depending on the culture of the high-power manager with whom they interacted. This study contributes to understanding how culture shapes behavior of people with relatively low power, illustrates how a logic of appropriateness informs cooperation, and highlights the importance of studying multicultural social interactions in the context of negotiations, work teams, and global leadership. (PsycINFO Database Record

Twist-induced defects of the P-SSP7 genome revealed by modeling the cryo-EM density.

We consider the consequences of assuming that DNA inside of phages can be approximated as a strongly nonlinear persistence length polymer. Recent cryo-EM experiments find a hole in the density map of P-SSP7 phage, located in the DNA segment filling the portal channel of the phage. We use experimentally derived structural constraints with coarse-grained simulation techniques to consider contrasting model interpretations of reconstructed density in the portal channel. The coarse-grained DNA models used are designed to capture the effects of torsional strain and electrostatic environment. Our simulation results are consistent with the interpretation that the vacancy or hole in the experimental density map is due to DNA strain leading to strand separation. We further demonstrate that a moderate negative twisting strain is able to account for the strand separation. This effect of nonlinear persistence length may be important in other aspects of phage DNA packing.