Experimental and computer simulation validation of ultrasound phase interference created by lateral inhomogeneity of transit time in replica bone marrow composite models

Purpose: The measurement of broadband ultrasonic attenuation (BUA) in cancellous bone for the assessment of osteoporosis follows a parabolic-type dependence with bone volume fraction; having minima values corresponding to both entire bone and entire marrow. Langton has recently proposed that the primary BUA mechanism may be significant phase interference due to variations in propagation transit time through the test sample as detected over the phase-sensitive surface of the receive ultrasound transducer. This fundamentally simple concept assumes that the propagation of ultrasound through a complex solid : liquid composite sample such as cancellous bone may be considered by an array of parallel ‘sonic rays’. The transit time of each ray is defined by the proportion of bone and marrow propagated, being a minimum (tmin) solely through bone and a maximum (tmax) solely through marrow. A Transit Time Spectrum (TTS), ranging from tmin to tmax, may be defined describing the proportion of sonic rays having a particular transit time, effectively describing lateral inhomogeneity of transit time over the surface of the receive ultrasound transducer. Phase interference may result from interaction of ‘sonic rays’ of differing transit times. The aim of this study was to test the hypothesis that there is a dependence of phase interference upon the lateral inhomogenity of transit time by comparing experimental measurements and computer simulation predictions of ultrasound propagation through a range of relatively simplistic solid:liquid models exhibiting a range of lateral inhomogeneities. Methods: A range of test models was manufactured using acrylic and water as surrogates for bone and marrow respectively. The models varied in thickness in one dimension normal to the direction of propagation, hence exhibiting a range of transit time lateral inhomogeneities, ranging from minimal (single transit time) to maximal (wedge; ultimately the limiting case where each sonic ray has a unique transit time). For the experimental component of the study, two unfocused 1 MHz ¾” broadband diameter transducers were utilized in transmission mode; ultrasound signals were recorded for each of the models. The computer simulation was performed with Matlab, where the transit time and relative amplitude of each sonic ray was calculated. The transit time for each sonic ray was defined as the sum of transit times through acrylic and water components. The relative amplitude considered the reception area for each sonic ray along with absorption in the acrylic. To replicate phase-sensitive detection, all sonic rays were summed and the output signal plotted in comparison with the experimentally derived output signal. Results: From qualtitative and quantitative comparison of the experimental and computer simulation results, there is an extremely high degree of agreement of 94.2% to 99.0% between the two approaches, supporting the concept that propagation of an ultrasound wave, for the models considered, may be approximated by a parallel sonic ray model where the transit time of each ray is defined by the proportion of ‘bone’ and ‘marrow’. Conclusions: This combined experimental and computer simulation study has successfully demonstrated that lateral inhomogeneity of transit time has significant potential for phase interference to occur if a phase-sensitive ultrasound receive transducer is implemented as in most commercial ultrasound bone analysis devices.

A case for optimising fracture healing through inverse dynamization

The mechanical conditions in the repair tissues are known to influence the outcome of fracture healing. These mechanical conditions are determined by the stiffness of fixation and limb loading. Experimental studies have shown that there is a range of beneficial fixation stiffness for timely healing and that fixation stiffness that is either too flexible or too stiff impairs callus healing. However, much less is known about how mechanical conditions influence the biological processes that make up the sequence of bone repair and if indeed mechanical stimulation is required at all stages of repair. Secondary bone healing occurs through a sequence of events broadly characterised by inflammation, proliferation, consolidation and remodelling. It is our hypothesis that a change in fixation stiffness from very flexible to stiff can shorten the time to healing relative to constant fixation stiffness. Flexible fixation has the benefit of promoting greater callus formation and needs to be applied during the proliferative stage of repair. The greater callus size helps to stabilize the fragments earlier allowing mineralization to occur faster. Together with stable/rigid fixation applied during the latter stage of repair to ensure mineralization of the callus. The predicted benefits of inverse dynamization are shortened healing in comparison to very flexible fixation and healing time comparable or faster than stable fixation with greater callus stiffness.

Intracellular trafficking and secretion of inflammatory cytokines

The secretion of cytokines by immune cells plays a significant role in determining the course of an inflammatory response. The levels and timing of each cytokine released are critical for mounting an effective but confined response, whereas excessive or dysregulated inflammation contributes to many diseases. Cytokines are both culprits and targets for effective treatments in some diseases. The multiple points and mechanisms that have evolved for cellular control of cytokine secretion highlight the potency of these mediators and the fine tuning required to manage inflammation. Cytokine production in cells is regulated by cell signaling, and at mRNA and protein synthesis levels. Thereafter, the intracellular transport pathways and molecular trafficking machinery have intricate and essential roles in dictating the release and activity of cytokines. The trafficking machinery and secretory (exocytic) pathways are complex and highly regulated in many cells, involving specialized membranes, molecules and organelles that enable these cells to deliver cytokines to often-distinct areas of the cell surface, in a timely manner. This review provides an overview of secretory pathways - both conventional and unconventional - and key families of trafficking machinery. The prevailing knowledge about the trafficking and secretion of a number of individual cytokines is also summarized. In conclusion, we present emerging concepts about the functional plasticity of secretory pathways and their modulation for controlling cytokines and inflammation.

Learning in host selection in Helicoverpa armigera (Hubner) (Lepidoptera : Noctuidae)

The effect of experience on pre- and post-alighting host selection in adult female Helicoverpa armigera was tested in an indoor flight cage, and in a large greenhouse. The moths had experienced either tobacco or tomato plants (both are hosts of H. armigera) for 3 days, or were given no experience. Individuals were then released and their host selection assessed. All individuals caught in the greenhouse were identified and tested for post-alighting acceptance on each host. Experience significantly influenced both pre- and post-alighting host selection in ovipositing moths. This modification in behaviour is attributed to 'learning', and presents the first detailed evidence for learning in moths. Possible behavioural mechanisms involved are discussed, and a hypothesis is presented regarding learning in post-alighting host acceptance. The existence of learning in H. armigera, a highly polyphagous agricultural pest, is discussed in the light of current theories on environmental predictability and the advantages of learning. Copyright 1998 The Association for the Study of Animal Behaviour.

Australasian Torrens automation, its integrity, and the three proof requirements

New Zealand and Australia are leading the world in terms of automated land registry systems. Landonline was introduced some ten years ago for New Zealand, and the Electronic Conveyancing National Law (ECNL) is to be released over the next few years in support of a national electronic conveyancing system to be used throughout Australia. With the assistance of three proof requirements, developed for this purpose, this article measures the integrity of both systems as against the old, manual Torrens system. The authors take the position that any introduced system should at least have the same level of integrity and safety as the originally conceived manual system. The authors argue both Landonline and ECNL, as presently set up, have less credibility than the manual system as it was designed to operate, leading to the possibility of increased fraud or misuse.

Modelling risk at low exposure railway level crossings : supporting an argument for low-cost level crossing warning devices with lower levels of safety integrity

This paper describes a risk model for estimating the likelihood of collisions at low-exposure railway level crossings, demonstrating the effect that differences in safety integrity can have on the likelihood of a collision. The model facilitates the comparison of safety benefits between level crossings with passive controls (stop or give-way signs) and level crossings that have been hypothetically upgraded with conventional or low-cost warning devices. The scenario presented illustrates how treatment of a cross-section of level crossings with low cost devices can provide a greater safety benefit compared to treatment with conventional warning devices for the same budget.

Improving level crossing safety through enhanced data recording and reporting : The CRC for Rail Innovation’s Baseline Rail Level Crossing Video project

This paper describes the work being conducted in the baseline rail level crossing project, supported by the Australian rail industry and the Cooperative Research Centre for Rail Innovation. The paper discusses the limitations of near-miss data for analysis obtained using current level crossing occurrence reporting practices. The project is addressing these limitations through the development of a data collection and analysis system with an underlying level crossing accident causation model. An overview of the methodology and improved data recording process are described. The paper concludes with a brief discussion of benefits this project is expected to provide the Australian rail industry.

Estimating the robustness of long-haul train plans

In Australia, and elsewhere, the movement of trains on long-haul rail networks is usually planned in advance. Typically, a train plan is developed to confirm that the required train movements and track maintenance activities can occur. The plan specifies when track segments will be occupied by particular trains and maintenance activities. On the day of operation, a train controller monitors and controls the movement of trains and maintenance crews, and updates the train plan in response to unplanned disruptions. It can be difficult to predict how good a plan will be in practice. The main performance indicator for a train service should be reliability - the proportion of trains running the service that complete at or before the scheduled time. We define the robustness of a planned train service to be the expected reliability. The robustness of individual train services and for a train plan as a whole can be estimated by simulating the train plan many times with random, but realistic, perturbations to train departure times and segment durations, and then analysing the distributions of arrival times. This process can also be used to set arrival times that will achieve a desired level of robustness for each train service.

Cytogenetics of melanoma and nonmelanoma skin cancer

Cytogenetic analysis of melanoma and nonmelanoma skin cancers has revealed recurrent aberrations, the frequency of which is reflective of malignant potential. Highly aberrant karyotypes are seen in melanoma, squamous cell carcinoma, solar keratosis and Merkel cell carcinoma with more stable karyotypes seen in basal cell carcinoma, keratoacanthoma, Bowen’s disease, dermatofibrosarcomarotuberans and cutaneous lymphomas. Some aberrations were common amongst a number of skin cancer types including rearrangements and numerical abnormalities of chromosome 1, −3p, +3q, partial or entire trisomy 6, trisomy 7, +8q, −9p, +9q, partial or entire loss of chromosome 10, −17p, + 17q and partial or entire gain of chromosome 20. Combination of cytogenetic analysis with other molecular genetic techniques has enabled the identification of not only aberrant chromosomal regions, but also the genes that contribute to a malignant phenotype. This review provides a comprehensive summary of the pertinent cytogenetic aberrations associated with a variety of melanoma and nonmelanoma skin cancers.

Detecting anomalous events at railway level crossings

Collisions between pedestrians and vehicles continue to be a major problem throughout the world. Pedestrians trying to cross roads and railway tracks without any caution are often highly susceptible to collisions with vehicles and trains. Continuous financial, human and other losses have prompted transport related organizations to come up with various solutions addressing this issue. However, the quest for new and significant improvements in this area is still ongoing. This work addresses this issue by building a general framework using computer vision techniques to automatically monitor pedestrian movements in such high-risk areas to enable better analysis of activity, and the creation of future alerting strategies. As a result of rapid development in the electronics and semi-conductor industry there is extensive deployment of CCTV cameras in public places to capture video footage. This footage can then be used to analyse crowd activities in those particular places. This work seeks to identify the abnormal behaviour of individuals in video footage. In this work we propose using a Semi-2D Hidden Markov Model (HMM), Full-2D HMM and Spatial HMM to model the normal activities of people. The outliers of the model (i.e. those observations with insufficient likelihood) are identified as abnormal activities. Location features, flow features and optical flow textures are used as the features for the model. The proposed approaches are evaluated using the publicly available UCSD datasets, and we demonstrate improved performance using a Semi-2D Hidden Markov Model compared to other state of the art methods. Further we illustrate how our proposed methods can be applied to detect anomalous events at rail level crossings.

Investigation of the low-density lipoprotein receptor gene and cholesterol as a risk factor for migraine

The Low-Density Lipoprotein Receptor (LDLR) gene is a cell surface receptor that plays an important role in cholesterol homeostasis. We investigated the (TA)n polymorphism in exon 18 of the LDLR gene on chromosome 19p13.2 performing an association analysis in 244 typical migraine-affected patients, 151 suffering from migraine with aura (MA), 96 with migraine without aura (MO) and 244 unaffected controls. The populations consisted of Caucasians only, and controls were age- and sex-matched. The results showed no significant difference between groups for allele frequency distributions of the (TA)n polymorphism even after separation of the migraine-affected individuals into subgroups of MA and MO affected patients. This is in contradiction to Mochi et al. who found a positive association of this variant with MO. Our study discusses possible differences between the two studies and extends this research by investigating circulating cholesterol levels in a migraine-affected population.

An improved method for the assay of platelet pyruvate dehydrogenase

An improved method for the assay of human platelet pyruvate dehydrogenase is described. By generating the substrate [1-14C]pyruvate in situ from [1-14C]lactate plus l-lactate dehydrogenase, the rate of spontaneous decarboxylation is dramatically reduced, allowing far greater sensitivity in the assay of low activities of pyruvate dehydrogenase. In addition, no special precautions are required for the storage and use of [1-14C]lactate, in contrast to those for [1-14C] pyruvate. These factors allow a 5–10-fold increase in sensitivity compared with current methods. The pyruvate dehydrogenase activity of normal subjects as determined by the [1-14C]lactate system was 215 ± 55 pmol · min−1 · mg−1 protein (n = 18). The advantages of this assay system are discussed.

Destination marketing organizations and destination marketing : a narrative analysis of the literature

This article presents the first narrative analysis of the areas of research that have developed within the destination marketing field since its commencement in 1973. Given the broad extent of the field, and the absence of any previous reviews in four decades, a key challenge is in providing a focus for such a disparate body of knowledge. The review is structured around one principal question: ‘To what extent is the Destination Marketing Organisation (DMO) responsible for the competitiveness of the destination’? In pursuit of this underlying question, we address a number of themes including nomenclature and the DMO, the evolution of the destination marketing literature, competitiveness as the DMO reason d’être, and DMO effectiveness including issues of branding and positioning, and future research themes in the field.

Non-covalent surface modification of boron nitride nanotubes for enhanced catalysis

Boron nitride nanotubes were functionalized by microperoxidase-11 in aqueous media, showing improved catalytic performance due to a strong electron coupling 10 between the active centre of microperoxidase-11 and boron nitride nanotubes. One main application challenge of enzymes as biocatalysts is molecular aggregation in the aqueous solution. This issue is addressed by immobilization of enzymes on solid supports which 15 can enhance enzyme stability and facilitate separation, and recovery for reuse while maintaining catalytic activity and selectivity. The protein-nanoparticle interactions play a key role in bio-nanotechnology and emerge with the development of nanoparticle-protein “corona”. Bio-molecular coronas provide a 20 unique biological identity of nanosized materials.1, 2 As a structural analogue to carbon nanotubes (CNTs), Boron nitride nanotubes have boron and nitrogen atoms distributed equally in hexagonal rings and exhibit excellent mechanical strength, unique physical properties, and chemical stability at high-temperatures. 25 The chemical inertness of BN materials suits to work in hazardous environments, making them an optimal candidate in practical applications in biological and medical field.3, 4