A Simulation-Based Teaching Strategy to Achieve Competence in Learners

Background: Simulation-based education has become the mainstay of clinical education in health sciences and medical education. A simulation-based education is a result of work hour restriction placed on graduate learners, increased number of students requiring clinical experience, decreased number of clinical sites and lack of the availability to perform certain procedures by learners. Research has demonstrated that integration of a simulation-based educational teaching strategy in a curriculum and throughout continued learning achieves competence in learners. Methods: The review of the literature highlighted the following topics: (a) history of medical simulation, (b) fidelity used in simulation training, devices and equipment, (c) learning theories associated with simulation-based education, (d) role of simulation training in medical and health sciences education, e) advantages and disadvantages of simulation training, f) competence in simulation-based education, g) debriefing/reflection in simulation. Results: An extensive review of the literature supports the use of a simulation-based teaching strategy in health sciences and medical education. Learning theories associated with simulation-based education allow educators to provide teaching strategies that align with learner’s ability to achieve competence in learning clinical and procedural skills required for their profession. Conclusion: A simulation-based education integrated in all stages of learner education that provides deliberate/repetitive practice and feedback achieves competence in learners throughout a life-time of learning

Signatures of the super fluid-insulator phase transition in laser driven dissipative nonlinear cavity arrays

We analyze the non-equilibrium dynamics of a gas of interacting photons in an array of coupled dissipative nonlinear cavities driven by a pulsed external coherent field. Using a mean-field approach, we show that the system exhibits a phase transition from a Mott-insulator-like to a superfluid regime. For a given single-photon nonlinearity, the critical value of the photon tunneling rate at which the phase transition occurs increases with the increasing photon loss rate. We checked the robustness of the transition by showing its insensitivity to the initial state prepared by the the pulsed excitation. We find that the second-order coherence of cavity emission can be used to determine the phase diagram of an optical many-body system without the need for thermalization.Comment: 4 pages, 4 figure

Diabetes reversal via gene transfer: building on successes in animal models

Type 1 diabetes (T1D) is caused by the autoimmune destruction of the insulin-producing pancreatic β-cells. People with T1D manage their hyperglycemia using daily insulin injections; however, this does not prevent the development of long-term diabetic complications such as retinopathy, nephropathy, neuropathy, and various macrovascular disorders. Currently, the only "cure" for T1D is pancreas transplantation or islet-cell transplantation; however, this is hampered by the limited number of donors and the requirement for life-long immunosuppression. As a result, the need for alternative therapies is vital. One of the strategies employed to correct T1D is the use of gene transfer to generate the production of an “artificial” β-cell that is capable of secreting insulin in response to fluctuating glucose concentrations that normally occurs in people without T1D. The treatment of many diseases using cell and gene therapy is generating significant attention in the T1D research community; however, for a cell therapy to enter clinical trials, success and safety must first be shown in an appropriate animal model. Animal models have been used in diabetes research for over a century, have improved our understanding of the pathophysiology of diabetes, and have led to the discovery of useful drugs for the treatment of the disease. Currently, the nonobese diabetic mouse is the animal model of choice for the study of T1D as it most closely reflects disease development in humans. The aim of this review is to evaluate the success of cell and gene therapy to reverse T1D in animal models for future clinical application

Photon correlations in a two-site non-linear cavity system under coherent drive and dissipation

We calculate the normalized second-order correlation function for a system of two tunnel-coupled photonic resonators, each one exhibiting a single-photon nonlinearity of the Kerr type. We employ a full quantum formulation: the master equation for the model, which takes into account both a coherent continuous drive and radiative as well as non-radiative dissipation channels, is solved analytically in steady state through a perturbative approach, and the results are compared to exact numerical simulations. The degree of second-order coherence displays values between 0 and 1, and divides the diagram identified by the two energy scales of the system - the tunneling and the nonlinear Kerr interaction - into two distinct regions separated by a crossover. When the tunneling term dominates over the nonlinear one, the system state is delocalized over both cavities and the emitted light is coherent. In the opposite limit, photon blockade sets in and the system shows an insulator-like state with photons locked on each cavity, identified by antibunching of emitted light.Comment: 9 pages, 4 figures, to appear in Phys. Rev.

Luciferase-based reporting of suicide gene activity in murine mesenchymal stem cells

© 2019 Gerace et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Due to their ease of isolation, gene modification and tumor-homing properties, mesenchymal stem cells (MSCs) are an attractive cellular vehicle for the delivery of toxic suicide genes to a variety of cancers in pre-clinical models. In addition, the incorporation of suicide genes in stem cell-derived cell replacement therapies improves their safety profile by permitting graft destruction in the event of unexpected tumorigeneses or unwanted differentiation. Due to the functional requirement of ATP for the Firefly luciferase gene Luc2 to produce light, luciferase-based reporting of cytotoxicity can be engineered into potential cell therapies. Consequently, we nucleofected mammalian expression plasmids containing both the Luc2 and the yeast fusion cytosine deaminase uracil phosphoribosyltransferase (CDUPRT) genes for expression in murine MSCs to assess luciferase as a reporter of suicide gene cytotoxicity, and MSC as vehicles of suicide gene therapy. In vitro bioluminescence imaging (BLI) showed that following the addition of the non-toxic prodrug fluorocytosine (5-FC), CDUPRT-expressing MSCs displayed enhanced cytotoxicity in comparison to Luc2 reporter MSC controls. This study demonstrates the utility of luciferase as a reporter of CDUPRT-mediated cytotoxicity in murine MSC using BLI

The use of β-cell transcription factors in engineering artificial β cells from non-pancreatic tissue

Type 1 diabetes results from the autoimmune destruction of the insulin-producing pancreatic beta (β) cells. Patients with type 1 diabetes control their blood glucose levels using several daily injections of exogenous insulin; however, this does not eliminate the long-term complications of hyperglycaemia. Currently, the only clinically viable treatments for type 1 diabetes are whole pancreas and islet transplantation. As a result, there is an urgent need to develop alternative therapies. Recently, cell and gene therapy have shown promise as a potential cure for type 1 diabetes through the genetic engineering of 'artificial' β cells to regulate blood glucose levels without adverse side effects and the need for immunosuppression. This review compares putative target cells and the use of pancreatic transcription factors for gene modification, with the ultimate goal of engineering a glucose-responsive 'artificial' β cell that mimics the function of pancreatic β cells, while avoiding autoimmune destruction

CRISPR-targeted genome editing of mesenchymal stem cell-derived therapies for type 1 diabetes: A path to clinical success?

© 2017 The Author(s). Due to their ease of isolation, differentiation capabilities, and immunomodulatory properties, the therapeutic potential of mesenchymal stem cells (MSCs) has been assessed in numerous pre-clinical and clinical settings. Currently, whole pancreas or islet transplantation is the only cure for people with type 1 diabetes (T1D) and, due to the autoimmune nature of the disease, MSCs have been utilised either natively or transdifferentiated into insulin-producing cells (IPCs) as an alternative treatment. However, the initial success in pre-clinical animal models has not translated into successful clinical outcomes. Thus, this review will summarise the current state of MSC-derived therapies for the treatment of T1D in both the pre-clinical and clinical setting, in particular their use as an immunomodulatory therapy and targets for the generation of IPCs via gene modification. In this review, we highlight the limitations of current clinical trials of MSCs for the treatment of T1D, and suggest the novel clustered regularly interspaced short palindromic repeat (CRISPR) gene-editing technology and improved clinical trial design as strategies to translate pre-clinical success to the clinical setting

Ex vivo expansion of murine MSC impairs transcription factor-induced differentiation into pancreatic β-cells

© 2019 Dario Gerace et al. Combinatorial gene and cell therapy as a means of generating surrogate β-cells has been investigated for the treatment of type 1 diabetes (T1D) for a number of years with varying success. One of the limitations of current cell therapies for T1D is the inability to generate sufficient quantities of functional transplantable insulin-producing cells. Due to their impressive immunomodulatory properties, in addition to their ease of expansion and genetic modification ex vivo, mesenchymal stem cells (MSCs) are an attractive alternative source of adult stem cells for regenerative medicine. To overcome the aforementioned limitation of current therapies, we assessed the utility of ex vivo expanded bone marrow-derived murine MSCs for their persistence in immune-competent and immune-deficient animal models and their ability to differentiate into surrogate β-cells. CD45-/Ly6+ murine MSCs were isolated from the bone marrow of nonobese diabetic (NOD) mice and nucleofected to express the bioluminescent protein, Firefly luciferase (Luc2). The persistence of a subcutaneous (s.c.) transplant of Luc2-expressing MSCs was assessed in immune-competent (NOD) (n=4) and immune-deficient (NOD/Scid) (n=4) animal models of diabetes. Luc2-expressing MSCs persisted for 2 and 12 weeks, respectively, in NOD and NOD/Scid mice. Ex vivo expanded MSCs were transduced with the HMD lentiviral vector (MOI = 10) to express furin-cleavable human insulin (INS-FUR) and murine NeuroD1 and Pdx1. This was followed by the characterization of pancreatic transdifferentiation via reverse transcriptase polymerase chain reaction (RT-PCR) and static and glucose-stimulated insulin secretion (GSIS). INS-FUR-expressing MSCs were assessed for their ability to reverse diabetes after transplantation into streptozotocin- (STZ-) diabetic NOD/Scid mice (n=5). Transduced MSCs did not undergo pancreatic transdifferentiation, as determined by RT-PCR analyses, lacked glucose responsiveness, and upon transplantation did not reverse diabetes. The data suggest that ex vivo expanded MSCs lose their multipotent differentiation potential and may be more useful as gene therapy targets prior to expansion

Exciton polaritons in two-dimensional photonic crystals

Experimental evidence of strong coupling between excitons confined in a quantum well and the photonic modes of a two-dimensional dielectric lattice is reported. Both resonant scattering and photoluminescence spectra at low temperature show the anticrossing of the polariton branches, fingerprint of strong coupling regime. The experiments are successfully interpreted in terms of a quantum theory of exciton-photon coupling in the investigated structure. These results show that the polariton dispersion can be tailored by properly varying the photonic crystal lattice parameter, which opens the possibility to obtain the generation of entangled photon pairs through polariton stimulated scattering.Comment: 5 pages, 4 figure

The use of restraint in four general hospital emergency departments in Australia

Author version made available in accordance with publisher copyright policy.Objective: The purpose of this study was to investigate restraint use in Australian emergency departments (EDs). Method: A retrospective audit of restraint incidents in four EDs (from 1 January 2010 to 31 December 2011). Results: The restraint rate was 0.04% of total ED presentations. Males and females were involved in similar numbers of incidents. Over 90% of restrained patients had a mental illness diagnosis and were compulsorily hospitalised. Mechanical restraint with the use of soft shackles was the main method used. Restraint was enacted to prevent harm to self and/or others. Median incident duration was 2 hours 5 minutes. Conclusions: In order to better integrate the needs of mental health clients, consideration is needed as to what improvements to procedures and the ED environment can be made. EDs should particularly focus on reducing restraint duration and the use of hard shackles