Crystallographic polarity measurements in two-terminal GaN nanowire devices by lateral piezoresponse force microscopy.

Lateral piezoresponse force microscopy (L-PFM) is demonstrated as a reliable method for determining the crystallographic polarity of individual, dispersed GaN nanowires that were functional components in electrical test structures. In contrast to PFM measurements of vertically oriented (as-grown) nanowires, where a biased probe tip couples to out-of-plane deformations through the d33 piezoelectic coefficient, the L-PFM measurements in this study were implemented on horizontally oriented nanowires that coupled to shear deformations through the d15 coefficient. L-PFM phase-polarity relationships were determined experimentally using a bulk m-plane GaN sample with a known [0001] direction and further indicated that the sign of the d15 piezoelectric coefficient was negative. L-PFM phase images successfully revealed the in-plane [0001] orientation of self-assembed GaN nanowires as part of a growth polarity study and results were validated against scanning transmission electron microscopy lattice images. Combined characterization of electrical properties and crystallographic polarity was also implemented for two-terminal GaN/Al0.1Ga0.9N/GaN nanowires devices, demonstrating L-PFM measurements as a viable tool for assessing correlations between device rectification and polarization-induced band bending.

Extracellular matrix dynamics in tubulogenesis.

Biological tubes form in a variety of shapes and sizes. Tubular topology of cells and tissues is a widely recognizable histological feature of multicellular life. Fluid secretion, storage, transport, absorption, exchange, and elimination-processes central to metazoans-hinge on the exquisite tubular architectures of cells, tissues, and organs. In general, the apparent structural and functional complexity of tubular tissues and organs parallels the architectural and biophysical properties of their constitution, i.e., cells and the extracellular matrix (ECM). Together, cellular and ECM dynamics determine the developmental trajectory, topological characteristics, and functional efficacy of biological tubes. In this review of tubulogenesis, we highlight the multifarious roles of ECM dynamics-the less recognized and poorly understood morphogenetic counterpart of cellular dynamics. The ECM is a dynamic, tripartite composite spanning the luminal, abluminal, and interstitial space within the tubulogenic realm. The critical role of ECM dynamics in the determination of shape, size, and function of tubes is evinced by developmental studies across multiple levels-from morphological through molecular-in model tubular organs.

Core Disaster Medicine Education (CDME) for Emergency Medicine Residents in the United States.

OBJECTIVES: Disaster Medicine (DM) education for Emergency Medicine (EM) residents is highly variable due to time constraints, competing priorities, and program expertise. The investigators' aim was to define and prioritize DM core competencies for EM residency programs through consensus opinion of experts and EM professional organization representatives. METHODS: Investigators utilized a modified Delphi methodology to generate a recommended, prioritized core curriculum of 40 DM educational topics for EM residencies. RESULTS: The DM topics recommended and outlined for inclusion in EM residency training included: patient triage in disasters, surge capacity, introduction to disaster nomenclature, blast injuries, hospital disaster mitigation, preparedness, planning and response, hospital response to chemical mass-casualty incident (MCI), decontamination indications and issues, trauma MCI, disaster exercises and training, biological agents, personal protective equipment, and hospital response to radiation MCI. CONCLUSIONS: This expert-consensus-driven, prioritized ranking of DM topics may serve as the core curriculum for US EM residency programs.

Label-free detection of conformational changes in switchable DNA nanostructures with microwave microfluidics.

Detection of conformational changes in biomolecular assemblies provides critical information into biological and self-assembly processes. State-of-the-art in situ biomolecular conformation detection techniques rely on fluorescent labels or protein-specific binding agents to signal conformational changes. Here, we present an on-chip, label-free technique to detect conformational changes in a DNA nanomechanical tweezer structure with microwave microfluidics. We measure the electromagnetic properties of suspended DNA tweezer solutions from 50 kHz to 110 GHz and directly detect two distinct conformations of the structures. We develop a physical model to describe the electrical properties of the tweezers, and correlate model parameters to conformational changes. The strongest indicator for conformational changes in DNA tweezers are the ionic conductivity, while shifts in the magnitude of the cooperative water relaxation indicate the addition of fuel strands used to open the tweezer. Microwave microfluidic detection of conformational changes is a generalizable, non-destructive technique, making it attractive for high-throughput measurements.

Integrating Simulation-Based Exercises into Public Health Emergency Management Curricula.

The aim of this study is to enrich public health emergency management (PHEM) curricula and increase the workforce readiness of graduates through the implementation of an innovative curriculum structure centered around simulation and the creation of authentic learning experiences into a mastery-based Disaster Preparedness graduate certificate program launched in 2016 at the Colorado School of Public Health. Learners progress through a sequence of increasingly complex discussion and operations-based exercises designed to align with training methodologies used by future employers in the disaster response field, covering PHEM fundamentals and domestic and international disaster preparedness and response. Preliminary feedback is overwhelmingly positive, equating the experience to securing an internship. Embedding simulation-based exercises and authentic learning environments into graduate curricula exposes learners to diverse disaster scenarios, provides occasion for practicing critical thinking and dynamic problem solving, increases familiarity with anticipated emergency situations, and builds the confidence necessary for exercising judgment in a real-world situation. This novel curriculum should serve as a model for graduate programs wishing to enrich traditional training tactics using a typical school of public health support and alignment with community resources. (Disaster Med Public Health Preparedness. 2019;13:777-781).

Altered VEGF Signaling Leads to Defects in Heart Tube Elongation and Omphalomesenteric Vein Fusion in Quail Embryos.

Formation of the endocardial and myocardial heart tubes involves precise cardiac progenitor sorting and tissue displacements from the primary heart field to the embryonic midline-a process that is dependent on proper formation of conjoining great vessels, including the omphalomesenteric veins (OVs) and dorsal aortae. Using a combination of vascular endothelial growth factor (VEGF) over- and under-activation, fluorescence labeling of cardiac progenitors (endocardial and myocardial), and time-lapse imaging, we show that altering VEGF signaling results in previously unreported myocardial, in addition to vascular and endocardial phenotypes. Resultant data show: (1) exogenous VEGF leads to truncated endocardial and myocardial heart tubes and grossly dilated OVs; (2) decreased levels of VEGF receptor 2 tyrosine kinase signaling result in a severe abrogation of the endocardial tube, dorsal aortae, and OVs. Surprisingly, only slightly altered myocardial tube fusion and morphogenesis is observed. We conclude that VEGF has direct effects on the VEGF receptor 2-bearing endocardial and endothelial precursors, and that altered vascular morphology of the OVs also indirectly results in altered myocardial tube formation. Anat Rec, 302:175-185, 2019. © 2018 Wiley Periodicals, Inc.

The Role of Hospital Medicine in Emergency Preparedness: A Framework for Hospitalist Leadership in Disaster Preparedness, Response, and Recovery.

Recent high-profile mass casualty events illustrate the unique challenges that such occurrences pose to normal hospital operations. These events create patient surges that overwhelm hospital resources, space, and staff. However, in most healthcare systems, hospitalists currently show no integration within emergency planning or incident response. This review aims to provide hospitalists with an overview of disaster management principles so that they can engage their hospitals' disaster management system with a working fluency in emergency management and the incident command system. This review also proposes a framework for hospitalist involvement in preparation, response, and coordination during periods of crisis.

Using Rapid Improvement Events for Disaster After-Action Reviews: Experience in a Hospital Information Technology Outage and Response.

The use of after-action reviews (AARs) following major emergency events, such as a disaster, is common and mandated for hospitals and similar organizations. There is a recurrent challenge of identified problems not being resolved and repeated in subsequent events. A process improvement technique called a rapid improvement event (RIE) was used to conduct an AAR following a complete information technology (IT) outage at a large urban hospital. Using RIE methodology to conduct the AAR allowed for the rapid development and implementation of major process improvements to prepare for future IT downtime events. Thus, process improvement methodology, particularly the RIE, is suited for conducting AARs following disasters and holds promise for improving outcomes in emergency management. Little CM , McStay C , Oeth J , Koehler A , Bookman K . Using rapid improvement events for disaster after-action reviews: experience in a hospital information technology outage and response. Prehosp Disaster Med. 2018;33(1):98-100.

Live tissue antibody injection: A novel method for imaging ECM in limb buds and other tissues.

Understanding the morphogenesis and differentiation of tissues and organs from progenitor fields requires methods to visualize this process. Despite an ever-growing recognition that ECM plays an important role in tissue development, studies of ECM movement, and patterns in live tissue are scarce. Here, we describe a method in which a living limb bud is immunolabeled prior to fixation using fluorescent antibodies that recognize two ECM constituents, fibronectin and fibrillin 2. The results show that undifferentiated mesenchyme in quail embryos can be distinguished from prechondrogenic cellular condensations, in situ, via ECM antibodies-indicating the developmental transition from naïve mesenchyme to committed skeletal tissue. We conclude that our live tissue injection method is a general approach that allows visualization of the structural characteristics and the distribution pattern of ECM scaffolds, in situ. With slight modifications, the method will produce robust fluorescence images of ECM scaffolds in any suitable tissue mass and allow multiple kinds of optical analyses including virtual 3D reconstructions.

Jetting of a shear banding fluid in rectangular ducts.

Non-Newtonian fluids are susceptible to flow instabilities such as shear banding, in which the fluid may exhibit a markedly discontinuous viscosity at a critical stress. Here we report the characteristics and causes of a jetting flow instability of shear banding wormlike micelle solutions in microfluidic channels with rectangular cross sections over an intermediate volumetric flow regime. Particle-tracking methods are used to measure the three-dimensional flow field in channels of differing aspect ratios, sizes, and wall materials. When jetting occurs, it is self-contained within a portion of the channel where the flow velocity is greater than the surroundings. We observe that the instability forms in channels with aspect ratio greater than 5, and that the location of the high-velocity jet appears to be sensitive to stress localizations. Jetting is not observed in a lower concentration solution without shear banding. Simulations using the Johnson-Segalman viscoelastic model show a qualitatively similar behavior to the experimental observations and indicate that compressive normal stresses in the cross-stream directions support the development of the jetting flow. Our results show that nonuniform flow of shear thinning fluids can develop across the wide dimension in rectangular microfluidic channels, with implications for microfluidic rheometry.

Modeling electrical double-layer effects for microfluidic impedance spectroscopy from 100 kHz to 110 GHz.

Broadband microfluidic-based impedance spectroscopy can be used to characterize complex fluids, with applications in medical diagnostics and in chemical and pharmacological manufacturing. Many relevant fluids are ionic; during impedance measurements ions migrate to the electrodes, forming an electrical double-layer. Effects from the electrical double-layer dominate over, and reduce sensitivity to, the intrinsic impedance of the fluid below a characteristic frequency. Here we use calibrated measurements of saline solution in microfluidic coplanar waveguide devices at frequencies between 100 kHz and 110 GHz to directly measure the double-layer admittance for solutions of varying ionic conductivity. We successfully model the double-layer admittance using a combination of a Cole-Cole response with a constant phase element contribution. Our analysis yields a double-layer relaxation time that decreases linearly with solution conductivity, and allows for double-layer effects to be separated from the intrinsic fluid response and quantified for a wide range of conducting fluids.

Preparing Emergency Physicians for Acute Disaster Response: A Review of Current Training Opportunities in the US.

Study Objective This study aimed to review available disaster training options for health care providers, and to provide specific recommendations for developing and delivering a disaster-response-training program for non-disaster-trained emergency physicians, residents, and trainees prior to acute deployment. METHODS: A comprehensive review of the peer-reviewed and grey literature of the existing training options for health care providers was conducted to provide specific recommendations. RESULTS: A comprehensive search of the Pubmed, Embase, Web of Science, Scopus, and Cochrane databases was performed to identify publications related to courses for disaster preparedness and response training for health care professionals. This search revealed 7,681 unique titles, of which 53 articles were included in the full review. A total of 384 courses were found through the grey literature search, and many of these were available online for no charge and could be completed in less than six hours. The majority of courses focused on management and disaster planning; few focused on clinical care and acute response. CONCLUSION: There is need for a course that is targeted toward emergency physicians and trainees without formal disaster training. This course should be available online and should utilize a mix of educational modalities, including lectures, scenarios, and virtual simulations. An ideal course should focus on disaster preparedness, and the clinical and non-clinical aspects of response, with a focus on an all-hazards approach, including both terrorism-related and environmental disasters. Hansoti B , Kellogg DS , Aberle SJ , Broccoli MC , Feden J , French A , Little CM , Moore B , Sabato J Jr. , Sheets T , Weinberg R , Elmes P , Kang C . Preparing emergency physicians for acute disaster response: a review of current training opportunities in the US. Prehosp Disaster Med. 2016;31(6):643-647.

Extracellular matrix motion and early morphogenesis.

For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale 'total' cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis.

In vivo time-lapse imaging reveals extensive neural crest and endothelial cell interactions during neural crest migration and formation of the dorsal root and sympathetic ganglia.

During amniote embryogenesis the nervous and vascular systems interact in a process that significantly affects the respective morphogenesis of each network by forming a "neurovascular" link. The importance of neurovascular cross-talk in the central nervous system has recently come into focus with the growing awareness that these two systems interact extensively both during development, in the stem-cell niche, and in neurodegenerative conditions such as Alzheimer's Disease and Amyotrophic Lateral Sclerosis. With respect to the peripheral nervous system, however, there have been no live, real-time investigations of the potential relationship between these two developing systems. To address this deficit, we used multispectral 4D time-lapse imaging in a transgenic quail model in which endothelial cells (ECs) express a yellow fluorescent marker, while neural crest cells (NCCs) express an electroporated red fluorescent marker. We monitored EC and NCC migration in real-time during formation of the peripheral nervous system. Our time-lapse recordings indicate that NCCs and ECs are physically juxtaposed and dynamically interact at multiple locations along their trajectories. These interactions are stereotypical and occur at precise anatomical locations along the NCC migratory pathway. NCCs migrate alongside the posterior surface of developing intersomitic vessels, but fail to cross these continuous streams of motile ECs. NCCs change their morphology and migration trajectory when they encounter gaps in the developing vasculature. Within the nascent dorsal root ganglion, proximity to ECs causes filopodial retraction which curtails forward persistence of NCC motility. Overall, our time-lapse recordings support the conclusion that primary vascular networks substantially influence the distribution and migratory behavior of NCCs and the patterned formation of dorsal root and sympathetic ganglia.

Vulnerable Populations in Hospital and Health Care Emergency Preparedness Planning: A Comprehensive Framework for Inclusion.

INTRODUCTION: As attention to emergency preparedness becomes a critical element of health care facility operations planning, efforts to recognize and integrate the needs of vulnerable populations in a comprehensive manner have lagged. This not only results in decreased levels of equitable service, but also affects the functioning of the health care system in disasters. While this report emphasizes the United States context, the concepts and approaches apply beyond this setting. OBJECTIVE: This report: (1) describes a conceptual framework that provides a model for the inclusion of vulnerable populations into integrated health care and public health preparedness; and (2) applies this model to a pilot study. METHODS: The framework is derived from literature, hospital regulatory policy, and health care standards, laying out the communication and relational interfaces that must occur at the systems, organizational, and community levels for a successful multi-level health care systems response that is inclusive of diverse populations explicitly. The pilot study illustrates the application of key elements of the framework, using a four-pronged approach that incorporates both quantitative and qualitative methods for deriving information that can inform hospital and health facility preparedness planning. CONCLUSIONS: The conceptual framework and model, applied to a pilot project, guide expanded work that ultimately can result in methodologically robust approaches to comprehensively incorporating vulnerable populations into the fabric of hospital disaster preparedness at levels from local to national, thus supporting best practices for a community resilience approach to disaster preparedness.

Active cell and ECM movements during development.

Dynamic imaging of the extracellular matrix (ECM) and cells can reveal how tissues are formed. Displacement differences between cells and the adjacent ECM scaffold can be used to establish active movements of mesenchymal cells. Cells can also generate large-scale tissue movements in which cell and ECM displacements are shared. We describe computational methods for analyzing multi-spectral time-lapse image sequences. The resulting data can distinguish between local "active" cellular motion versus large-scale, tissue movements, both of which occur during organogenesis. The movement data also provide the basis for construction of realistic biomechanical models and computer simulations of in vivo tissue formation.

Identification of emergent motion compartments in the amniote embryo.

The tissue scale deformations (≥ 1 mm) required to form an amniote embryo are poorly understood. Here, we studied ∼400 µm-sized explant units from gastrulating quail embryos. The explants deformed in a reproducible manner when grown using a novel vitelline membrane-based culture method. Time-lapse recordings of latent embryonic motion patterns were analyzed after disk-shaped tissue explants were excised from three specific regions near the primitive streak: 1) anterolateral epiblast, 2) posterolateral epiblast, and 3) the avian organizer (Hensen's node). The explants were cultured for 8 hours-an interval equivalent to gastrulation. Both the anterolateral and the posterolateral epiblastic explants engaged in concentric radial/centrifugal tissue expansion. In sharp contrast, Hensen's node explants displayed Cartesian-like, elongated, bipolar deformations-a pattern reminiscent of axis elongation. Time-lapse analysis of explant tissue motion patterns indicated that both cellular motility and extracellular matrix fiber (tissue) remodeling take place during the observed morphogenetic deformations. As expected, treatment of tissue explants with a selective Rho-Kinase (p160ROCK) signaling inhibitor, Y27632, completely arrested all morphogenetic movements. Microsurgical experiments revealed that lateral epiblastic tissue was dispensable for the generation of an elongated midline axis- provided that an intact organizer (node) is present. Our computational analyses suggest the possibility of delineating tissue-scale morphogenetic movements at anatomically discrete locations in the embryo. Further, tissue deformation patterns, as well as the mechanical state of the tissue, require normal actomyosin function. We conclude that amniote embryos contain tissue-scale, regionalized morphogenetic motion generators, which can be assessed using our novel computational time-lapse imaging approach. These data and future studies-using explants excised from overlapping anatomical positions-will contribute to understanding the emergent tissue flow that shapes the amniote embryo.

Embryogenesis of the first circulating endothelial cells.

Prior to this study, the earliest appearance of circulating endothelial cells in warm-blooded animals was unknown. Time-lapse imaging of germ-line transformed Tie1-YFP reporter quail embryos combined with the endothelial marker antibody QH1 provides definitive evidence for the existence of circulating endothelial cells - from the very beginning of blood flow. Blood-smear counts of circulating cells from Tie1-YFP embryos showed that up to 30% of blood-borne cells are Tie1 positive; though cells expressing low levels of YFP were also positive for benzidine, a hemoglobin stain, suggesting that these cells were differentiating into erythroblasts. Electroporation-based time-lapse experiments, exclusively targeting the intra-embryonic mesoderm were combined with QH1 immunostaining. The latter antibody marks quail endothelial cells. Together the optical data provide conclusive evidence that endothelial cells can enter blood flow from vessels of the embryo proper, as well as from extra-embryonic areas. When Tie1-YFP positive cells and tissues are transplanted to wild type host embryos, fluorescent cells emigrate from such transplants and join host vessels; subsequently a few YFP cells are shed into circulation. These data establish that entering circulation is a commonplace activity of embryonic vascular endothelial cells. We conclude that in the class of vertebrates most closely related to mammals a normal component of primary vasculogenesis is production of endothelial cells that enter circulation from all vessels, both intra- and extra-embryonic.