A study to evaluate the introduction of simulation as a teaching strategy for the mental health and learning disability fields of nursing, in an undergraduate nursing curriculum within one higher education institution

High Fidelity Simulation or Human Patient Simulation is an educational strategy embedded within nursing curricula throughout many healthcare educational institutions. This paper reports on an evaluative study that investigated the views of a group of Year 2 undergraduate nursing students from the mental health and the learning disability fields of nursing (n = 75) in relation to simulation as a teaching pedagogy. The study took place in the simulation suite within a School of Nursing and Midwifery in the UK. Two patient scenarios were used for the session and participants completed a 22-item questionnaire consisting of three biographical information questions and a 19-item Likert scale. Descriptive statistics were employed to illustrate the data and non-parametric testing (Mann-Whitney U test) was employed to test a number of hypotheses. Overall students were positive about the introduction of patient scenarios using the human patient simulator into the undergraduate nursing curriculum. This study used a small, convenience sample in one institution and therefore the results obtained cannot be generalised to nursing education before further research can be conducted with larger samples and a mixed-method research approach. However these results provide encouraging evidence to support the use of simulation within the mental health and the learning disability fields of nursing, and the development and implementation of further simulations to complement the students’ practicum.

Models of Mortality - Analysing the Residuals

The area of mortality modelling has received significant attention over the last 20 years owing to the need to quantify and forecast improving mortality rates. This need is driven primarily by the concern of governments, professionals, insurance and actuarial professionals and individuals to be able to fund their old age. In particular, to quantify the costs of increasing longevity we need suitable model of mortality rates that capture the dynamics of the data and forecast them with sufficient accuracy to make them useful. In this paper we test several of those models by considering the fitting quality and in particular, testing the residuals of those models for normality properties. In a wide ranging study considering 30 countries we find that almost exclusively the residuals do not demonstrate normality. Further, in Hurst tests of the residuals we find evidence that structure remains that is not captured by the models.

A Lagrangian approach for modeling road collisions using second-order models of traffic flow

In [M. Herty, A. Klein, S. Moutari, V. Schleper, and G. Steinaur, IMA J. Appl. Math., 78(5), 1087–1108, 2013] and [M. Herty and V. Schleper, ZAMM J. Appl. Math. Mech., 91, 763–776, 2011], a macroscopic approach, derived from fluid-dynamics models, has been introduced to infer traffic conditions prone to road traffic collisions along highways’ sections. In these studies, the governing equations are coupled within an Eulerian framework, which assumes fixed interfaces between the models. A coupling in Lagrangian coordinates would enable us to get rid of this (not very realistic) assumption. In this paper, we investigate the well-posedness and the suitability of the coupling of the governing equations within the Lagrangian framework. Further, we illustrate some features of the proposed approach through some numerical simulations.

Animal models of diabetic retinopathy

Diabetic retinopathy (DR) is a major cause of visual impairment worldwide. The precise pathogenesis of this diabetic complication remains ill-defined and this is reflected in the limited options for preventing development and progression of this disease. The value of animal models to understand and treat human disease is well recognised and this chapter focuses on the range of in vivo model systems that are available for studying DR. These models have been developed over many decades and utilised to aid our understanding of what causes DR, about how microvascular and neural lesions develop and to provide evidence for key cellular and molecular mechanisms that drive this pathology. A wide range of animal models of DR are currently available, each with advantages and disadvantages that need to be understood and evaluated for their scientific and clinical value. As transgenic and imaging technology improves, more models will be developed and they will continue to play a critical role in the development of new therapeutic approaches to DR by providing robust, preclinical evidence prior to clinical trial.

Sustained inhibition of deacetylases is required for the antitumor activity of the histone deactylase inhibitors panobinostat and vorinostat in models of colorectal cancer

Despite compelling preclinical data in colorectal cancer (CRC), the efficacy of HDACIs has been disappointing in the clinic. The goal of this study was to evaluate the effectiveness of vorinostat and panobinostat in a dose- and exposure-dependent manner in order to better understand the dynamics of drug action and antitumor efficacy. In a standard 72 h drug exposure MTS assay, notable concentration-dependent antiproliferative effects were observed in the IC50 range of 1.2-2.8 μmol/L for vorinostat and 5.1-17.5 nmol/L for panobinostat. However, shorter clinically relevant exposures of 3 or 6 h failed to elicit any significant growth inhibition and in most cases a >24 h exposure to vorinostat or panobinostat was required to induce a sigmoidal dose-response. Similar results were observed in colony formation assays where ≥ 24 h of exposure was required to effectively reduce colony formation. Induction of acetyl-H3, acetyl-H4 and p21 by vorinostat were transient and rapidly reversed within 12 h of drug removal. In contrast, panobinostat-induced acetyl-H3, acetyl-H4, and p21 persisted for 48 h after an initial 3 h exposure. Treatment of HCT116 xenografts with panobinostat induced significant increases in acetyl-H3 and downregulation of thymidylate synthase after treatment. Although HDACIs exert both potent growth inhibition and cytotoxic effects when CRC cells were exposed to drug for ≥ 24 h, these cells demonstrate an inherent ability to survive HDACI concentrations and exposure times that exceed those clinically achievable. Continued efforts to develop novel HDACIs with improved pharmacokinetics/phamacodynamics, enhanced intratumoral delivery and class/isoform-specificity are needed to improve the therapeutic potential of HDACIs and HDACI-based combination regimens in solid tumors.

Mitochondrial Transfer via Tunneling Nanotubes (TNT) is an Important Mechanism by which Mesenchymal Stem Cells Enhance Macrophage Phagocytosis in the in vitro and in vivo Models of ARDS

Mesenchymal stromal cells (MSC) have been reported to improve bacterial clearance in pre-clinical models of Acute Respiratory Distress Syndrome (ARDS) and sepsis. The mechanism of this effect is not fully elucidated yet. The primary objective of this study was to investigate the hypothesis that the anti-microbial effect of MSC in vivo depends on their modulation of macrophage phagocytic activity which occurs through mitochondrial transfer. We established that selective depletion of alveolar macrophages (AM) with intranasal (IN) administration of liposomal clodronate resulted in complete abrogation of MSC anti-microbial effect in the in vivo model of E.coli pneumonia. Furthermore, we showed that MSC administration was associated with enhanced AM phagocytosis in vivo. We showed that direct co-culture of MSC with monocyte-derived macrophages (MDMs) enhanced their phagocytic capacity. By fluorescent imaging and flow cytometry we demonstrated extensive mitochondrial transfer from MSC to macrophages which occurred at least partially through TNT-like structures. We also detected that lung macrophages readily acquire MSC mitochondria in vivo, and macrophages which are positive for MSC mitochondria display more pronounced phagocytic activity. Finally, partial inhibition of mitochondrial transfer through blockage of TNT formation by MSC resulted in failure to improve macrophage bioenergetics and complete abrogation of the MSC effect on macrophage phagocytosis in vitro and the anti-microbial effect of MSC in vivo.

Collectively, this work for the first time demonstrates that mitochondrial transfer from MSC to innate immune cells leads to enhancement in phagocytic activity and reveals an important novel mechanism for the anti-microbial effect of MSC in ARDS.

Murine Models of Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction

Left ventricular diastolic dysfunction leads to heart failure with preserved ejection fraction, an increasingly prevalent condition largely driven by modern day lifestyle risk factors. As heart failure with preserved ejection fraction accounts for almost one-half of all patients with heart failure, appropriate nonhuman animal models are required to improve our understanding of the pathophysiology of this syndrome and to provide a platform for preclinical investigation of potential therapies. Hypertension, obesity, and diabetes are major risk factors for diastolic dysfunction and heart failure with preserved ejection fraction. This review focuses on murine models reflecting this disease continuum driven by the aforementioned common risk factors. We describe various models of diastolic dysfunction and highlight models of heart failure with preserved ejection fraction reported in the literature. Strengths and weaknesses of the different models are discussed to provide an aid to translational scientists when selecting an appropriate model. We also bring attention to the fact that heart failure with preserved ejection fraction is difficult to diagnose in animal models and that, therefore, there is a paucity of well described animal models of this increasingly important condition.

Predicting polarization signatures for double-detonation and delayed-detonation models of Type Ia supernovae

Calculations of synthetic spectropolarimetry are one means to test multidimensional explosion models for Type Ia supernovae. In a recent paper, we demonstrated that the violent merger of a 1.1 and 0.9 M⊙ white dwarf binary system is too asymmetric to explain the low polarization levels commonly observed in normal Type Ia supernovae. Here, we present polarization simulations for two alternative scenarios: the sub-Chandrasekhar mass double-detonation and the Chandrasekhar mass delayed-detonation model. Specifically, we study a 2D double-detonation model and a 3D delayed-detonation model, and calculate polarization spectra for multiple observer orientations in both cases. We find modest polarization levels (<1 per cent) for both explosion models. Polarization in the continuum peaks at ∼0.1–0.3 per cent and decreases after maximum light, in excellent agreement with spectropolarimetric data of normal Type Ia supernovae. Higher degrees of polarization are found across individual spectral lines. In particular, the synthetic Si II λ6355 profiles are polarized at levels that match remarkably well the values observed in normal Type Ia supernovae, while the low degrees of polarization predicted across the O I λ7774 region are consistent with the non-detection of this feature in current data. We conclude that our models can reproduce many of the characteristics of both flux and polarization spectra for well-studied Type Ia supernovae, such as SN 2001el and SN 2012fr. However, the two models considered here cannot account for the unusually high level of polarization observed in extreme cases such as SN 2004dt.