A forced titration study of the antioxidant and immunomodulatory effects of Ambrotose AO supplement

Background Oxidative stress plays a role in acute and chronic inflammatory disease and antioxidant supplementation has demonstrated beneficial effects in the treatment of these conditions. This study was designed to determine the optimal dose of an antioxidant supplement in healthy volunteers to inform a Phase 3 clinical trial. Methods The study was designed as a combined Phase 1 and 2 open label, forced titration dose response study in healthy volunteers (n = 21) to determine both acute safety and efficacy. Participants received a dietary supplement in a forced titration over five weeks commencing with a no treatment baseline through 1, 2, 4 and 8 capsules. The primary outcome measurement was ex vivo changes in serum oxygen radical absorbance capacity (ORAC). The secondary outcome measures were undertaken as an exploratory investigation of immune function. Results A significant increase in antioxidant activity (serum ORAC) was observed between baseline (no capsules) and the highest dose of 8 capsules per day (p = 0.040) representing a change of 36.6%. A quadratic function for dose levels was fitted in order to estimate a dose response curve for estimating the optimal dose. The quadratic component of the curve was significant (p = 0.047), with predicted serum ORAC scores increasing from the zero dose to a maximum at a predicted dose of 4.7 capsules per day and decreasing for higher doses. Among the secondary outcome measures, a significant dose effect was observed on phagocytosis of granulocytes, and a significant increase was also observed on Cox 2 expression. Conclusion This study suggests that Ambrotose AO® capsules appear to be safe and most effective at a dosage of 4 capsules/day. It is important that this study is not over interpreted; it aimed to find an optimal dose to assess the dietary supplement using a more rigorous clinical trial design. The study achieved this aim and demonstrated that the dietary supplement has the potential to increase antioxidant activity. The most significant limitation of this study was that it was open label Phase 1/Phase 2 trial and is subject to potential bias that is reduced with the use of randomization and blinding. To confirm the benefits of this dietary supplement these effects now need to be demonstrated in a Phase 3 randomised controlled trial (RCT).

Machine recognition of hand-drawn circuit diagrams

An application of image processing techniques to recognition of hand-drawn circuit diagrams is presented. The scanned image of a diagram is pre-processed to remove noise and converted to bilevel. Morphological operations are applied to obtain a clean, connected representation using thinned lines. The diagram comprises of nodes, connections and components. Nodes and components are segmented using appropriate thresholds on a spatially varying object pixel density. Connection paths are traced using a pixel-stack. Nodes are classified using syntactic analysis. Components are classified using a combination of invariant moments, scalar pixel-distribution features, and vector relationships between straight lines in polygonal representations. A node recognition accuracy of 82% and a component recognition accuracy of 86% was achieved on a database comprising 107 nodes and 449 components. This recogniser can be used for layout “beautification” or to generate input code for circuit analysis and simulation packages

Sensitivity of building zones to potential global warming

As global warming entails new conditions for the built environment, the thermal and energy performance of existing buildings, which are designed based on current weather data, may become unclear and remain a great concern. Through building computer simulation and qualitative analysis of the weighted factor for the outdoor temperature impact on building energy and thermal performance, this paper investigates the sensitivity of different office building zoning to the potential global warming. A standard office building type is examined for all eight capital cities in Australia. Results show that comparing the middle and top floors, except for cool climate (i.e. Hobart), the ground floor appears to be the most sensitive to the effect of global warming and has the highest tendency for a overheating problem. From the analysis of the responses of different zone orientations to the outdoor air temperature increase, it is also found that there are widely varied responses between zone orientations, with South zone (in the southern hemisphere) being the most sensitive. With an increased external air temperature, the variation between different floors or zone orientations will become more significant, up to 53 percent increase of overheating hours in Darwin and 47 percent increase of cooling load in Hobart.

Exploring the parameter space of a rabbit ventricular action potential model to investigate the effect of variation on action potential and calcium transients

Computational models for cardiomyocyte action potentials (AP) often make use of a large parameter set. This parameter set can contain some elements that are fitted to experimental data independently of any other element, some elements that are derived concurrently with other elements to match experimental data, and some elements that are derived purely from phenomenological fitting to produce the desired AP output. Furthermore, models can make use of several different data sets, not always derived for the same conditions or even the same species. It is consequently uncertain whether the parameter set for a given model is physiologically accurate. Furthermore, it is only recently that the possibility of degeneracy in parameter values in producing a given simulation output has started to be addressed. In this study, we examine the effects of varying two parameters (the L-type calcium current (I(CaL)) and the delayed rectifier potassium current (I(Ks))) in a computational model of a rabbit ventricular cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+)) transient. It will subsequently be determined if there is degeneracy in this model to these parameter values, which will have important implications on the stability of these models to cell-to-cell parameter variation, and also whether the current methodology for generating parameter values is flawed. The accuracy of AP duration (APD) as an indicator of AP shape will also be assessed.