Quality assurance in CT: implementation of the updated national diagnostic reference levels using an automated CT dose monitoring system.

AIM: To evaluate the implementation of the updated computed tomography (CT) diagnostic reference levels (DRLs) from the German Federal Office for Radiation Protection into clinical routine using an automatic CT dose monitoring system. METHODS AND MATERIALS: CT radiation exposure was analysed before and after implementing the updated national DRLs into routine clinical work in 2016. After the implementation process, institutional CT protocols were mapped to the anatomical regions for which DRLs were provided. Systematically, protocols that exceeded the thresholds were optimised and analysed in detail. The CT radiation output parameters analysed were volumetric CT dose index (CTDIvol) and dose-length product (DLP). Three radiologists evaluated subjective image quality using a three-point Likert scale. RESULTS: The study included 94,258 CT series (from 27,103 CT examinations) in adult patients performed in 2016. When averaged over all body regions with available DRL, institutional CTDIvol/DLP values were always below the DRLs (65.2±32.9%/67.3±41.5% initially; 59.4±32%/60.5±39.9% after optimisation). Values exceeding the national DRLs were found for pelvis (n=268; CTDIvol 107.7±65.7%/DLP 106.3±79.3%), lumbar spine (n=91; 160.8±74.7%/175.2±104.1%), and facial bones (n=527; 108±39%/152.7±75.7%). After optimisation, CTDIvol and DLP were 87.9±73%/87.8±80.8% for the pelvis, 67.8±33.2%/74.5±50.6% for the lumbar spine and 95.1±45.8%/133.3±74.6% for the viscerocranium. CONCLUSION: An automatic CT dose monitoring system enabled not only comprehensive monitoring of a DRL implementation process but can also help to optimise radiation exposure.

Micro-morphological adaptations of the wing nodus to flight behaviour in four dragonfly species from the family Libellulidae (Odonata: Anisoptera).

Adult dragonflies can be divided into two major groups, perchers and fliers, exhibiting notably different flight behaviour. Previous studies have yielded conflicting results regarding the link between the wing macro-morphology and flight style in these two groups. In this study, we present the first systematic investigation of the micro-morphological differences of wings of percher and flier dragonflies in four closely related species from the family Libellulidae. Our results suggest that the shape and material composition of wing microstructural components and, in particular, the nodus are adapted to facilitate the specific wing functioning in fliers and perchers. The findings further indicate a decreasing trend in the area proportion of the soft resilin-dominated cuticle in the nodus in the series of species from typical perchers to typical fliers. Such a reduction in the resilin proportion in the nodus of fliers is associated with an increase in the wing aspect ratio. The knot-shaped protrusion at the nodus of perchers, which becomes notably smaller in that of strong fliers, is likely to act as a mechanical stopper, avoiding large wing displacements. This study aims to develop a novel framework for future research on the relationship between wing morphology and flight behaviour in dragonflies.

Dragonfly wing nodus: A one-way hinge contributing to the asymmetric wing deformation.

Dragonfly wings are highly specialized locomotor systems, which are formed by a combination of several structural components. The wing components, also known as structural elements, are responsible for the various aspects of the wing functionality. Considering the complex interactions between the wing components, modelling of the wings as a whole is only possible with inevitable huge oversimplifications. In order to overcome this difficulty, we have recently proposed a new approach to model individual components of complex wings comparatively. Here, we use this approach to study nodus, a structural element of dragonfly wings which has been less studied to date. Using a combination of several imaging techniques including scanning electron microscopy (SEM), wide-field fluorescence microscopy (WFM), confocal laser scanning microscopy (CLSM) and micro-computed tomography (micro-CT) scanning, we aim to characterize the spatial morphology and material composition of fore- and hindwing nodi of the dragonfly Brachythemis contaminata. The microscopy results show the presence of resilin in the nodi, which is expected to help the deformability of the wings. The computational results based on three-dimensional (3D) structural data suggest that the specific geometry of the nodus restrains its displacements when subjected to pressure on the ventral side. This effect, resulting from an interlocking mechanism, is expected to contribute to the dorso-ventral asymmetry of wing deformation and to provide a higher resistance to aerodynamic forces during the downstroke. Our results provide an important step towards better understanding of the structure-property-function relationship in dragonfly wings. STATEMENT OF SIGNIFICANCE: In this study, we investigate the wing nodus, a specialized wing component in dragonflies. Using a combination of modern imaging techniques, we demonstrate the presence of resilin in the nodus, which is expected to facilitate the wing deformability in flight. The specific geometry of the nodus, however, seems to restrain its displacements when subjected to pressure on the ventral side. This effect, resulting from an interlocking mechanism, is suggested to contribute to dorso-ventral asymmetry of wing deformations and to provide a higher resistance to aerodynamic forces during the downstroke. Our results provide an important step towards better understanding of the structure-property-function relationship in dragonfly wings and might help to design more efficient wings for biomimetic micro-air vehicles.

Effects of multiple vein microjoints on the mechanical behaviour of dragonfly wings: numerical modelling.

Dragonfly wings are known as biological composites with high morphological complexity. They mainly consist of a network of rigid veins and flexible membranes, and enable insects to perform various flight manoeuvres. Although several studies have been done on the aerodynamic performance of Odonata wings and the mechanisms involved in their deformations, little is known about the influence of vein joints on the passive deformability of the wings in flight. In this article, we present the first three-dimensional finite-element models of five different vein joint combinations observed in Odonata wings. The results from the analysis of the models subjected to uniform pressures on their dorsal and ventral surfaces indicate the influence of spike-associated vein joints on the dorsoventral asymmetry of wing deformation. Our study also supports the idea that a single vein joint may result in different angular deformations when it is surrounded by different joint types. The developed numerical models also enabled us to simulate the camber formation and stress distribution in the models. The computational data further provide deeper insights into the functional role of resilin patches and spikes in vein joint structures. This study might help to more realistically model the complex structure of insect wings in order to design more efficient bioinspired micro-air vehicles in future.

Effect of microstructure on the mechanical and damping behaviour of dragonfly wing veins.

Insect wing veins are biological composites of chitin and protein arranged in a complex lamellar configuration. Although these hierarchical structures are found in many 'venous wings' of insects, very little is known about their physical and mechanical characteristics. For the first time, we carried out a systematic comparative study to gain a better understanding of the influence of microstructure on the mechanical characteristics and damping behaviour of the veins. Morphological data have been used to develop a series of three-dimensional numerical models with different material properties and geometries. Finite-element analysis has been employed to simulate the mechanical response of the models under different loading conditions. The modelling strategy used in this study enabled us to determine the effects selectively induced by resilin, friction between layers, shape of the cross section, material composition and layered structure on the stiffness and damping characteristics of wing veins. Numerical simulations suggest that although the presence of the resilin-dominated endocuticle layer results in a much higher flexibility of wing veins, the dumbbell-shaped cross section increases their bending rigidity. Our study further shows that the rubber-like cuticle, friction between layers and material gradient-based design contribute to the higher damping capacity of veins. The results of this study can serve as a reference for the design of novel bioinspired composite structures.

A comparative study of the effects of vein-joints on the mechanical behaviour of insect wings: I. Single joints.

The flight performance of insects is strongly affected by the deformation of the wing during a stroke cycle. Many insects therefore use both active and passive mechanisms to control the deformation of their wings in flight. Several studies have focused on the wing kinematics, and plenty is known about the mechanism of their passive deformability. However, given the small size of the vein-joints, accurate direct mechanical experiments are almost impossible to perform. We therefore developed numerical models to perform a comparative and comprehensive investigation of the mechanical behaviour of the vein-joints under external loading conditions. The results illustrate the effect of the geometry and the presence of the rubberlike protein resilin on the flexibility of the joints. Our simulations further show the contribution of the spikes to the anisotropic flexural stiffness in the dorsal and ventral directions. In addition, our results show that the cross veins, only in one joint type, help to transfer the stress to the thicker longitudinal veins. The deformation pattern and the stress distribution in each vein-joint are discussed in detail. This study provides a strong background for further realistic modelling of the dragonfly wing deformation.

Discrete event simulation of patient admissions to a neurovascular unit.

Evidence exists that clinical outcomes improve for stroke patients admitted to specialized Stroke Units. The Toronto Western Hospital created a Neurovascular Unit (NVU) using beds from general internal medicine, Neurology and Neurosurgery to care for patients with stroke and acute neurovascular conditions. Using patient-level data for NVU-eligible patients, a discrete event simulation was created to study changes in patient flow and length of stay pre- and post-NVU implementation. Varying patient volumes and resources were tested to determine the ideal number of beds under various conditions. In the first year of operation, the NVU admitted 507 patients, over 66% of NVU-eligible patient volumes. With the introduction of the NVU, length of stay decreased by around 8%. Scenario testing showed that the current level of 20 beds is sufficient for accommodating the current demand and would continue to be sufficient with an increase in demand of up to 20%.

Determination of anthropogenic boundary depth in industrially polluted soil and semi-quantification of heavy metal loads using magnetic susceptibility.

This study focuses on magnetic susceptibility processing and analysis towards fast and cost-efficient discrimination and semi-quantification of anthropogenic heavy metal loads in soil. Spatial variability of magnetic susceptibility was investigated on sets of soil cores from both "polluted" and "less polluted" forest soil close to a steel mill near Leoben, Austria. Test sites of approximately 10 m(2) represent "site scale" dimensions. Statistical analysis of magnetic data provides a boundary depth indicating the transition from the "polluted" to the deeper, "unpolluted" zone in contaminated natural soil. Introduction of a block master curve simplifies the complex variations of individual curves, and represents magnetic susceptibility at "site scale". For linking the block master curve to heavy metals we only require magnetic susceptibility data from one soil core and heavy metal data from two sub-samples from the same core. Our optimized magnetic susceptibility data processing scheme provides an applicable tool to semi-quantify anthropogenic heavy metal loads in soil.

Caspase-8 deficiency facilitates cellular transformation in vitro.

Caspase-8 is frequently deficient in several kinds of human tumors, suggesting that certain effects of this enzyme restrict tumor development. To examine the nature of the cellular function whose regulation by caspase-8 contributes to its antitumor effect, we assessed the impact of caspase-8 deficiency on cell transformation in vitro. Caspase-8-deficient mouse embryonic fibroblasts immortalized with the SV40 T antigen did not survive when cultured in soft agar, and were nontumorogenic in nude mice. However, the rate of transformation of these cells during their continuous growth in culture, as reflected in the observed emergence of cells that do grow in soft agar and are able to form tumors in nude mice, was far higher than that of cells expressing caspase-8. These findings indicate that caspase-8 deficiency can contribute to cancer development in a way that does not depend on the enzyme's participation in killing of the tumor cells by host immune cytotoxic mechanisms, or on its involvement in the cell-death process triggered upon detachment of the cells from their substrate, but rather concerns cell-autonomous mechanisms that affect the rate of cell transformation.

vFLIP protects PC-12 cells from apoptosis induced by Sindbis virus: implications for the role of TNF-alpha.

Sindbis virus (SV) is an alphavirus used as a model for studying the pathogenesis of viral encephalitis. In this study we examined the effects and the mechanisms involved in the apoptosis induced by SV in PC-12 cells, and the role of a vFLIP in this process. Infection of PC-12 cells with a neurovirulent strain of SV, SVNI, induced cell apoptosis. Overexpression of vFLIP encoded by the HHV-8 or treatment with a caspase-8 inhibitor inhibited cell apoptosis. SVNI induced an increase in the expression of tumor necrosis factor alpha (TNF-alpha), and pre-treatment of the cells with an anti-TNF-alpha blocking antibody or with soluble TNF-alpha receptor abrogated the apoptotic effect of SVNI. Moreover, TNF-alpha R1 knockout mice were more resistant to the cytopathic effects of the virus as compared to control animals. Our results indicate that the apoptosis induced by SVNI is mediated by activation of caspase-8, and that TNF-alpha plays an important role in the apoptotic response.

Nerve growth factor regulates TNF-alpha production in mouse macrophages via MAP kinase activation.

In this study, we examined the expression of nerve growth factor (NGF) and its receptors in mouse macrophages and the mechanisms involved in the effect of NGF on tumor necrosis factor (TNF)-alpha production. Macrophages expressed NGF and the NGF receptors TrkA and p75. Treatment of J744 cells or peritoneal macrophages with NGF induced a large increase in the production of TNF-alpha. In addition, NGF induced the secretion of nitric oxide in interferon-gamma-treated J774 cells or lipopolysaccharide-treated peritoneal macrophages. The induction of TNF-alpha production by NGF was blocked by K252a, an inhibitor of the TrkA receptor. NGF induced phosphorylation and activation of extracellular signal-regulated kinase, Erk1/Erk2 and c-Jun amino-terminal kinase, whereas it did not induce phosphorylation of p38 mitogen-activated protein kinase. Inhibition of the MAP kinase-Erk kinase pathway with PD 098059 decreased the secretion of TNF-alpha by NGF. Our results suggest that NGF has an important role in the activation of macrophages during inflammatory responses via activation of mitogen-activated protein kinases.

Macrophages express neurotrophins and neurotrophin receptors. Regulation of nitric oxide production by NT-3.

In this study we examined the expression of neurotrophins and their receptors in mouse macrophages and the effects of the neurotrophins on nitric oxide secretion. Macrophages expressed TrkB and TrkC but not BDNF, NT-3 or NT-4. LPS induced up-regulation of TrkB and TrkC and of BDNF and NT-3 expression. Treatment of macrophages with NT-3 increased the secretion of nitric oxide in LPS-treated macrophages and this increase was blocked by K252a, a Trk kinase inhibitor. In contrast, BDNF and NT-4 had no significant effects on the induction of nitric oxide. Our results suggest that NT-3 play important roles in the function of macrophages during inflammatory responses and in tissue repair.

Roles of BCL-2 and caspase 3 in the adenosine A3 receptor-induced apoptosis.

Selective A3 adenosine receptor agonists have been shown to induce apoptosis in a variety of cell types. In this study we examined the effects of adenosine receptor agonists selective for A1, A2A, or A3 receptors on the induction of apoptosis in primary cultures of rat astrocytes and in C6 glial cells. Treatment of the cells with the A3 receptor agonist Cl-IB-MECA (10 microM) induced apoptosis in both cell types. The effects of Cl-IB-MECA were partially antagonized by the A3 receptor-selective antagonist MRS 1191. In contrast, the A1 and A2A receptor agonists, CPA and CGS 21680, respectively, did not have significant effects on apoptosis in these cells. Cl-IB-MECA reduced the expression of endogenous Bcl-2, whereas it did not affect the expression of Bax. Overexpression of Bcl-2 in C6 cells abrogated the induction of apoptosis induced by the A3 agonist. Cl-IB-MECA also induced an increase in caspase 3 activity and caspase inhibitors decreased the apoptosis induced by the A3 agonist. These findings suggest that intense activation of the A3 receptor is pro-apoptotic in glial cells via bcl2 and caspase-3 dependent pathways.

Differential regulation of Bcl-2 and Bax expression in cells infected with virulent and nonvirulent strains of sindbis virus.

Sindbis virus is an alphavirus that infects cells in either lytic or persistent infection. In this study we examined the effects of Sindbis virus on cell apoptosis and on the expression of Bcl-2 and Bax. Of the two strains studied, SVA and SVNI, only the neurovirulent strain, SVNI, induced apoptosis of astrocytes and PC-12 cells. SVA, which infects cells in a persistent manner, induced up-regulation of bcl-2 mRNA and Bcl-2 protein, whereas SVNI induced an increase in Bax levels. Our results indicate a differential regulation of Bcl2 and Bax expression by SVA and SVNI, which may be associated with the apoptotic potential of the viruses.

Differential regulation of neurotrophin expression by mitogens and neurotransmitters in mouse lymphocytes.

In this study, we examined the expression of neurotrophins in mouse lymphocytes and the regulation of their expression by mitogens and neurotransmitters. We found that mixed splenocytes as well as T and B lymphocytes expressed mRNA for all the neurotrophins examined. Differential regulation of the neurotrophins was obtained upon stimulation of the cells. Thus, LPS increased the expression of NGF, BDNF and NT-3 in splenocytes and B cells, whereas Con-A increased the mRNA of NT-3 and NT-4 in T cells and NGF expression in splenocytes. The neurotransmitter substance P and the beta-adrenergic agonist, isoproterenol induced an increase in the expression of NGF. Our results suggest an important role for the different neurotrophins in the function of the immune system and point to a bi-directional interaction between neurotrophins and neurotransmitters in this system.

Role of nerve growth factor in a mouse model of allergic airway inflammation and asthma.

The role of nerve growth factor (NGF), a potent mediator acting in the development and differentiation of both neuronal and immune cells, was examined in a mouse model of allergic asthma. NGF-positive cells were detected in the inflammatory infiltrate of the lung and enhanced levels of NGF were detected in serum and broncho-alveolar lavage fluids. Mononuclear cells in inflamed airway mucosa as well as broncho-alveolar macrophages were identified as one source of NGF production. Splenic mononuclear cells from allergen-sensitized mice produced NGF in response to allergen. They responded to exogenously added NGF with a dose-dependent increase in IL-4 and IL-5 production and augmented IgE and IgG1 synthesis. In contrast, IFN-gamma and IgG2alpha levels remained unaffected. The effects were NGF specific, since they could be blocked by an anti-NGF-antibody. Nasal application of anti-NGF to allergen-sensitized mice significantly reduced IL-4 and prevented development of airway hyperreactivity. These results show that allergic airway inflammation is accompanied by enhanced local NGF production that acts as an amplifier for Th2 effector functions and plays an important role in the development of airway hyperreactivity. Therefore it is suggested that NGF may serve as a link between the immune and nerve system.

Regulation of GDNF expression in cultured astrocytes by inflammatory stimuli.

Astrocytes express increased levels of neurotrophic factors in response to pathological conditions in the CNS such as injury and inflammation. We have examined the effects of lipopolysaccharide (LPS) and inflammatory cytokines on the expression of GDNF by mouse astrocytes and by C6 glial cells. LPS and tumor necrosis factor-alpha (TNF-alpha) induced an increase in level of glial-derived neurotrophic factor (GDNF) mRNA in both cell types. Similarly, the synthesis of GDNF protein was increased by both treatments. Interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) induced similar effects on GDNF production, whereas IL-2 and IL-6 had no significant effects. These results indicate that the expression of GDNF in astrocytes is regulated by inflammatory stimuli and therefore may provide neurotrophic support to injured neurons in inflammatory conditions in the CNS.

Improved PCR amplification/Hhal restriction for unambiguous determination of apolipoprotein E alleles.

We present a modification to the polymerase chain reaction amplification/Hhal restriction isotyping method for human apolipoprotein (apo) E. This method includes a mutagenic forward primer and 5'-end labeling of both primers. These modifications of the original method described by Hixon and Vernier (J Lipid Res 1990;31:545-8) allow sensitive and unambiguous determination of apoE genotypes.