Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside re- verse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities consid- ered sufficient to maintain vaginal fluid concentrations at levels 82–860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal trans- mission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median con- centrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo–in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mecha- nism rather than the expected diffusion-controlled mechanism.

Levoglucosan formation mechanisms during cellulose pyrolysis

Levoglucosan is one important primary product during cellulose pyrolysis either as an intermediate or as a product. Three available mechanisms for levoglucosan formation have been studied theoretically in this paper, which are free-radical mechanism; glucose intermediate mechanism; and levoglucosan chain-end mechanism. All the elementary reactions included in the pathway of every mechanism were investigated; thermal properties including activation energy, Gibbs free energy, and enthalpy for every pathway were also calculated. It was concluded that free-radical mechanism has the highest energy barrier during the three levoglucosan formation mechanisms, glucose intermediate mechanism has lower energy barrier than free-radical mechanism, and levoglucosan chain-end mechanism is the most reasonable pathway because of the lowest energy barrier. By comparing with the activation energy obtained from the experimental results, it was also concluded that levoglucosan chain-end mechanism fits better with the experimental data for the formation of levoglucosan. © 2013 Elsevier B.V. All rights reserved.

Performing Struggle: Parrhesia in Ferguson

‘The enigma of revolts.’ You can almost hear the sigh at the end of this sentence. Foucault is making a statement here, published under the title ‘Useless to Revolt’, on that ‘impulse by which a single individual, a group, a minority, or an entire people says, “I will no longer obey”’. In this short piece, I question the two sides of the enigma – how to label the revolt – is the act of rioting, such as what we witnessed in Ferguson, Missouri in August 2014 ‘proper resistance’ – and, how to understand the ēthos of the rioter. The label of counter-conduct, I argue clarifies the enigma as it allows us, challenges us even, to see the event as political. Counter-conduct provides a new framework for reading spontaneous and improvised forms of political expression. The rioter can then be seen as political and rational, as demonstrating ethical behavior. The ēthos of this behavior is represented as an ethics of the self, a form of parrhēsia where the rioter risks herself and shows courage to tell the truth, the story of her community.

(Dis‑)Harmony in movement: effects of musical dissonance on movement timing and form

While the origins of consonance and dissonance in terms of acoustics, psychoacoustics and physiology have been debated for centuries, their plausible effects on movement synchronization have largely been ignored. The present study aims to address this by investigating whether, and if so how, consonant/dissonant pitch intervals affect the spatiotemporal properties of regular reciprocal aiming movements. We compared movements synchronized either to consonant or to dissonant sounds, and showed that they were differently influenced by the degree of consonance of the sound presented. Interestingly, the difference was present after the sound stimulus was removed. In this case, the performance measured after consonant sound exposure was found to be more stable and accurate, with a higher percentage of information/movement coupling (tau-coupling) and a higher degree of movement circularity when compared to performance measured after the exposure to dissonant sounds. We infer that the neural resonance representing consonant tones leads to finer perception/action coupling which in turn may help explain the prevailing preference for these types of tones.

Economic Stress and the Great Recession in Ireland: Polarization, Individualization or ‘Middle Class Squeeze’?

Following an unprecedented boom, since 2008 Ireland has experienced a severe economic crisis. Considerable debate persists as to where the heaviest burden of the recession has fallen. Conventional measures of income poverty and inequality have a limited capacity to answer this question. Our analysis, which focuses on economic stress and the mediating role of material deprivation, provides no evidence for individualization or class polarization. Instead we find that while economic stress level are highly stratified in income class and social class terms in both boom and bust periods, the changing impact of class is contingent on life course stage. The affluent income class remained largely insulated from the experience of economic stress. However, it saw its relative advantage overthe income poor class decline at the earlier stage of the life-course. At the other end of the hierarchy, the income poor experienced a relative improvement in their situation in the early life course phases. The precarious income class experienced some improvement in its situation at the earlier life course stages while the outcomes for the middle classes remain unchanged. In the mid-life course stages the precarious and lower middle classes experienced disproportionate increase in their stress levels while at the later life-cycle stage it is the combined middle classes that lost out. Additional effects over time relating to social class are restricted to the deteriorating situation of the petit bourgeoisie at the middle stage of the life-course. The pattern is clearly a good deal more complex that suggested by conventional notions of ‘middle class squeeze’ and points to the distinctive challenges relating to welfare and taxation policy faced by governments in the Great Recession.

Impact of tooth replacement on the nutritional status of partially dentate elders

OBJECTIVES: The aim of this study was to compare the impact of two different tooth replacement strategies on the nutritional status of partially dentate older patients. Nutritional status was measured using the full version of the Mini Nutritional Assessment (MNA) and the short form of the Mini Nutritional Assessment (MNA-SF).

MATERIALS AND METHODS: A randomised controlled clinical trial was conducted (Trial Registration no. ISRCTN26302774). Partially dentate patients aged 65 years and older were recruited and randomly allocated to the two different treatment groups: the removable partial dentures (RPD) group and the shortened dental arch (SDA) group. Nutritional status was measured using the MNA and MNA-SF administered at baseline and 1, 6 and 12 months after treatment intervention by a research nurse blinded to the treatment group allocation of all participants.

RESULTS: Data collected using the full version of the MNA showed significant improvements in mean MNA scores over the length of the study (p < 0.05). For the entire patient group, there was a mean increase of 0.15 points at 6 months and a further increase of 0.19 points at 12 months. These increases were similar within the treatment groups (p > 0.05). For MNA-SF, the analysis showed that there were no significant differences recorded over the data collection points after treatment intervention (p < 0.05).

CONCLUSION: Tooth replacement using conventional and functionally orientated treatment for the partially dentate elderly showed significant improvements in MNA score 12 months after intervention.

CLINICAL RELEVANCE: Prosthodontic rehabilitation may play an important role in the nutritional status of partially dentate elders.