Interaction of combined chloride and sulfate ingression in concrete

Chloride is the most severe form of deterioration experienced by concrete and one of the principal sources of chlorides is sea water. However, the presence of sulfates in seawater will influence the movement of chloride ions and vice versa. This interaction is not well understood and current codes of practice provide no guidelines for such dual exposure.
An investigation to monitor combined effect of the ingress of chlorides and sulfates during a realistic 12 month wetting and drying exposure regime to simulate conditions in which multiple mode transport mechanisms are active was conducted on a variety of binders (PC, PFA and GGBS). Penetration was evaluated using water and acid soluble chloride profiles and sulfate profiles.
It was found that the nature of the exposure provided multiple modes of transport within the concrete, thus creating a complex pattern of distribution of ions. The presence of sulfates decreased the penetration of chlorides in the PC system at all ages relative to a chloride only control. The matrices containing PFA and GGBS also showed an initial decrease in chloride penetration. However, after six months the presence of sulfates then increased chloride penetration.

Public Service Broadcasting, Creative Industries and Innovation Infrastructure: The Case of ABC's Pool

The proliferation of media services enabled by digital technologies poses a serious challenge to public service broadcasting rationales based on media scarcity. Looking to the past and future, we articulate an important role that the Australian Broadcasting Corporation (ABC) might play in the digital age. We argue that historically the ABC has acted beyond its institutional broadcasting remit to facilitate cultural development and, drawing on the example of Pool (an online community of creative practitioners established and maintained by the ABC), point to a key role it might play in fostering network innovation in what are now conceptualised as the creative industries.

Discursive Control, Non-Domination and Hegelian Recognition Theory: Marrying Pettit’s Account(s) of Freedom with a Pippinian/Brandomian Reading of Hegelian Agency

The aim of this article is to combine Pettit’s account(s) of freedom, both his work on discursive control and on non-domination, with Pippin’s and Brandom’s reinterpretation of Hegelian rational agency and the role of recognition theory within it. The benefits of combining these two theories lie, as the article hopes to show, in three findings: first, re-examining Hegelian agency in the spirit of Brandom and Pippin in combination with Pettit’s views on freedom shows clearly why and in which way a Hegelian account of rational agency can ground an attractive socio-political account of freedom; second, the reconciling of discursive control and non-domination with Hegelian agency shows how the force and scope of recognition become finally tangible, without either falling into the trap of overburdening the concept, or merely reducing it to the idea of simple respect; third, the arguments from this article also highlight the importance of freedom as non-domination and how this notion is, indeed, as Pettit himself claims, an agency-freedom which aims at successfully securing the social, political, economic and even (some) psychological conditions for free and autonomous agency.

Evaluation of the Factors Contributing to Levonorgestrel Binding in Addition Cure Silicone Elastomer Vaginal Rings

Background: Following progress of the dapivirine (DPV)-releasing silicone elastomer (SE) vaginal ring (VR) into Phase III clinical studies, there is now interest in developing next-generation rings that additionally provide contraception. Levonorgestrel (LNG) is a safe and effective progestin that is being widely considered for use as a hormonal contraceptive agent in future multipurpose prevention technology (MPT) products. Although LNG has previously been incorporated into various controlled release SE devices, minimal attention has focused on its propensity to irreversibly react with addition cure SE systems. Here, for the first time, we investigate this LNG binding phenomenon and outline strategies for overcoming it.
Methods: VRs containing various loadings of DPV and LNG were manufactured and in vitro release assessed. Different LNG-only SE samples were also prepared to assess the following parameters: (i) addition cure vs. condensation cure SEs; (ii) different types of addition cure SEs; (iii) mixing time, (iv) cure temperature, (v) cure time; and (vi) LNG particle size. After manufacture, the LNG-only samples were assayed for total drug content using a solvent extraction method. The SE curing reaction and the LNG binding reaction was probed using nuclear magnetic resonance (NMR) spectroscopy. Results:
Under certain drug/formulation/processing conditions, LNG was not recoverable from VRs. Further studies using non-ring samples showed that: (a) the phenomenon was only observed with addition cure SEs (and not condensation cure SEs); (b) the extent of binding was dependent upon the type of addition cure SE; (c) micronised LNG showed significantly greater binding than non-micronised LNG; (d) the extent of binding correlated with increased mixing time, cure time and cure temperature.
Conclusions: Careful control of the API characteristics, the SE composition, and the manufacturing conditions will be necessary to establish a practical VR formulation for controlled release of LNG.

Thermal properties and eutectic behaviour of dapivirine in combination with steroid hormones and other antiretrovirals

Background: Combination drug products can display thermal behaviour that is more complex than for the corresponding single drug products. For example, the contraceptive vaginal ring (VR) Nuvaring contains a eutectic (lowest melting) composition of etonogestrel (ETN) and ethinyl estradiol. Here we report the predisposition of dapivirine (DPV) to form reduced melting/eutectic mixtures when combined with other contraceptive hormones and antiretrovirals, and discuss the implications for development of combination microbicide and multipurpose prevention technology (MPT) products.
Methods: Binary mixtures of DPV with darunavir (DRV), levonorgestrel (LNG), ETN or maraviroc (MVC) were prepared either by physical mixing or by solvent evaporation. Selected binary mixtures were also incorporated into silicone elastomer (SE) VR devices. Thermal behavior of the mixtures was analyzed using differential scanning calorimetry (DSC) operating in standard heating ramp mode (10 °C/min). DSC data were used to construct two component phase diagrams for each binary system.
Results: Drug mixtures typically showed reduced melting transitions for both drug components, with clear evidence for a eutectic mixture at a well-defined intermediate composition. Eutectic temperatures and compositions for the various mixtures were: 40% DPV / 60% ETN - 170°C; 25% DPV / 75% MVC - 172°C; 65% DPV / 35% LNG - 192°C. In each case, the eutectic composition was also detected when the drug mixtures were incorporated into SE VRs. For the DPV/DRV system, the thermal behaviour is complicated by desolvation from the darunavir ethanolate polymorph.
Conclusions: When DPV is combined with small molecular weight hydrophobic drugs, the melting temperature for both drugs is typically reduced to a degree dependent on the composition of the mixture. At specified compositions, a low melting eutectic system results. The formation of eutectic behavior in binary drug systems needs to be carefully characterised in order to define product performance and drug release.

Non-domination, non-alienation and social equality: towards a republican understanding of equality

The republican idea of non-domination stresses the importance of certain social relationships for a person’s freedom, showing that freedom is a social-relational state. While the idea of freedom as non-domination receives a lot of attention in the literature, republican theorists say surprisingly little about equality. Therefore, the aim of this paper is to carve out the contours of a republican conception of equality.. In so doing, I will argue that republican accounts of equality share a significant normative overlap with the idea of social equality. However, closer analysis of Philip Pettit’s account of ‘expressive egalitarianism’ (which Pettit sees as inherently connected to non-domination) and recent theories of social equality shows that republican non-domination – in contrast to what Pettit seems to claim – is not sufficient for securing (republican) social equality. In order to secure social equality for all, republicans would have to go beyond non-domination.

Automated tumor analysis for molecular profiling in lung cancer

The discovery and clinical application of molecular biomarkers in solid tumors, increasingly relies on nucleic acid extraction from FFPE tissue sections and subsequent molecular profiling. This in turn requires the pathological review of haematoxylin & eosin (H&E) stained slides, to ensure sample quality, tumor DNA sufficiency by visually estimating the percentage tumor nuclei and tumor annotation for manual macrodissection. In this study on NSCLC, we demonstrate considerable variation in tumor nuclei percentage between pathologists, potentially undermining the precision of NSCLC molecular evaluation and emphasising the need for quantitative tumor evaluation. We subsequently describe the development and validation of a system called TissueMark for automated tumor annotation and percentage tumor nuclei measurement in NSCLC using computerized image analysis. Evaluation of 245 NSCLC slides showed precise automated tumor annotation of cases using Tissuemark, strong concordance with manually drawn boundaries and identical EGFR mutational status, following manual macrodissection from the image analysis generated tumor boundaries. Automated analysis of cell counts for % tumor measurements by Tissuemark showed reduced variability and significant correlation (p < 0.001) with benchmark tumor cell counts. This study demonstrates a robust image analysis technology that can facilitate the automated quantitative analysis of tissue samples for molecular profiling in discovery and diagnostics.