An interpenetrating-network theory of cytoplasm.

Under many physiological and pathological conditions such as division and migration, cells undergo dramatic deformations, under which their mechanical integrity is supported by cytoskeletal networks (i.e. intermediate filaments, F-actin, and microtubules). Recent observations of cytoplasmic microstructure indicate interpenetration among different cytoskeletal networks, and micromechanical experiments have shown evidence of complex characteristics in the mechanical response of the interpenetrating cytoplasmic networks of living cells, including viscoelastic, nonlinear stiffening, microdamage, and healing characteristics. However, a theoretical framework describing such a response is missing, and thus it is not clear how different cytoskeletal networks with distinct mechanical properties come together to build the overall complex mechanical features of cytoplasm. In this work, we address this gap by developing a finite-deformation continuum-mechanical theory with a multi-branch visco-hyperelastic constitutive relation coupled with phase-field damage and healing. The proposed interpenetrating-network model elucidates the coupling among interpenetrating cytoskeletal components, and the roles of finite elasticity, viscoelastic relaxation, damage, and healing in the experimentally-observed mechanical response of interpenetrating-network eukaryotic cytoplasm.

Torsion-induced stick-slip phenomena in the delamination of soft adhesives.

Soft adhesive contacts are ubiquitous in nature and are increasingly used in synthetic systems, such as flexible electronics and soft robots, due to their advantages over traditional joining techniques. While methods to study the failure of adhesives typically apply tensile loads to the adhesive joint, less is known about the performance of soft adhesives under shear and torsion, which may become important in engineering applications. A major challenge that has hindered the characterization of shear/torsion-induced delamination is imposed by the fact that, even after delamination, contact with the substrate is maintained, thus allowing for frictional sliding and re-adhesion. In this work, we address this gap by studying the controlled delamination of soft cylinders under combined compression and torsion. Our experimental observations expose the nucleation of delamination at an imperfection and its propagation along the circumference of the cylinder. The observed sequence of 'stick-slip' events and the sensitivity of the delamination process to material parameters are explained by a theoretical model that captures axisymmetric delamination patterns, along with the subsequent frictional sliding and re-adhesion. By opening up an avenue for improved characterization of adhesive failure, our experimental approach and theoretical framework can guide the design of adhesives in future applications.

Biofilms as self-shaping growing nematics.

Active nematics are the nonequilibrium analogue of passive liquid crystals. They consist of anisotropic units that consume free energy to drive emergent behaviour. Like liquid crystal molecules in displays, ordering and dynamics in active nematics are sensitive to boundary conditions. However, unlike passive liquid crystals, active nematics have the potential to regulate their boundaries through self-generated stresses. Here, we show how a three-dimensional, living nematic can actively shape itself and its boundary to regulate its internal architecture through growth-induced stresses, using bacterial biofilms confined by a hydrogel as a model system. We show that biofilms exhibit a sharp transition in shape from domes to lenses upon changing environmental stiffness or cell-substrate friction, which is explained by a theoretical model that considers the competition between confinement and interfacial forces. The growth mode defines the progression of the boundary, which in turn determines the trajectories and spatial distribution of cell lineages. We further demonstrate that the evolving boundary and corresponding stress anisotropy define the orientational ordering of cells and the emergence of topological defects in the biofilm interior. Our findings may provide strategies for the development of programmed microbial consortia with emergent material properties.

Interfacial cavitation.

Cavitation has long been recognized as a crucial predictor, or precursor, to the ultimate failure of various materials, ranging from ductile metals to soft and biological materials. Traditionally, cavitation in solids is defined as an unstable expansion of a void or a defect within a material. The critical applied load needed to trigger this instability -- the critical pressure -- is a lengthscale independent material property and has been predicted by numerous theoretical studies for a breadth of constitutive models. While these studies usually assume that cavitation initiates from defects in the bulk of an otherwise homogeneous medium, an alternative and potentially more ubiquitous scenario can occur if the defects are found at interfaces between two distinct media within the body. Such interfaces are becoming increasingly common in modern materials with the use of multimaterial composites and layer-by-layer additive manufacturing methods. However, a criterion to determine the threshold for interfacial failure, in analogy to the bulk cavitation limit, has yet to be reported. In this work, we fill this gap. Our theoretical model captures a lengthscale independent limit for interfacial cavitation, and is shown to agree with our observations at two distinct lengthscales, via two different experimental systems. To further understand the competition between the two cavitation modes (bulk versus interface), we expand our investigation beyond the elastic response to understand the ensuing unstable propagation of delamination at the interface. A phase diagram summarizes these results, showing regimes in which interfacial failure becomes the dominant mechanism.

Value of General Medical Knowledge Examinations in Performance Assessment of Practicing Physicians With Potential Competence and Performance Deficiencies.

INTRODUCTION: Problems with a physician's performance may arise at any point during their career. As such, there is a need for effective, valid tools and processes to accurately assess and identify deficiencies in competence or performance. Although scores on multiple-choice questions have been shown to be predictive of some aspects of physician performance in practicing physicians, their relationship to overall clinical competence is somewhat uncertain particularly after the first 10 years of practice. As such, the purpose of this study was to examine how a general medical knowledge multiple-choice question examination is associated with a comprehensive assessment of competence and performance in experienced practicing physicians with potential competence and performance deficiencies. METHODS: The study included 233 physicians, of varying specialties, assessed by the University of California, San Diego Physician Assessment and Clinical Education Program (PACE), between 2008 and 2012, who completed the Post-Licensure Assessment System Mechanisms of Disease (MoD) examination. Logistic regression determined if the examination score significantly predicted passing assessment outcome after correcting for gender, international medical graduate status, certification status, and age. RESULTS: Most physicians (89.7%) received an overall passing assessment outcome on the PACE assessment. The mean MoD score was 66.9% correct, with a median of 68.0%. Logistic regression (P = .038) was significant in indicating that physicians with higher MoD examination scores had an increased likelihood of achieving a passing assessment outcome (odds ratio = 1.057). DISCUSSION: Physician MoD scores are significant predictors of overall physician competence and performance as evaluated by PACE assessment.

Remediation of the deficiencies of physicians across the continuum from medical school to practice: a thematic review of the literature.

Despite widespread endorsement of competency-based assessment of medical trainees and practicing physicians, methods for identifying those who are not competent and strategies for remediation of their deficits are not standardized. This literature review describes the published studies of deficit remediation at the undergraduate, graduate, and continuing medical education levels. Thirteen studies primarily describe small, single-institution efforts to remediate deficient knowledge or clinical skills of trainees or below-standard-practice performance of practicing physicians. Working from these studies and research from the learning sciences, the authors propose a model that includes multiple assessment tools for identifying deficiencies, individualized instruction, deliberate practice followed by feedback and reflection, and reassessment. The findings of the study reveal a paucity of evidence to guide best practices of remediation in medical education at all levels. There is an urgent need for multiinstitutional, outcomes-based research on strategies for remediation of less than fully competent trainees and physicians with the use of long-term follow-up to determine the impact on future performance.

Toward meeting the challenge of physician competence assessment: the University of California, San Diego Physician Assessment and Clinical Education (PACE) Program.

Physician competence and performance problems contribute to medical errors and substandard health care quality. Assessment of the clinical competence of practicing physicians, however, is challenging. Although physician competence assessment undoubtedly does take place at the local level (e.g., hospital, medical group), it is difficult to objectively assess a partner, colleague, or friend. Moreover, the methodologies used and the outcomes are necessarily veiled by peer review statutes. Consequently, there is a need for regional or national assessment centers with the knowledge, skill, and experience to perform clinical competence assessments on individual physicians and provide or direct remediation, when appropriate. The University of California, San Diego (UCSD) Physician Assessment and Clinical Education (PACE) Program was founded at the UCSD School of Medicine in 1996 for this purpose. From inception in 1996 through the first quarter of 2009, 867 physicians have participated in the UCSD PACE Program. The PACE Program is divided into two components. Phase I includes two days of multilevel, multimodal testing, and Phase II is a five-day, preceptor-based formative assessment program taking place in the residency program of the physician's specialty. From July 2002 through December 2005, a study of 298 physician participants of the UCSD PACE Program was conducted.The future of the comprehensive assessment of practicing physicians depends on (1) development and standardization of instruments, techniques, and procedures for measuring competence and performance, including in-practice measures, (2) collaborative networking of assessment programs, (3) cost control, and (4) continued development of remedial measures that correspond to assessment findings.