A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action

Vaginal rings are currently being developed for the long-term (at least 30 days) continuous delivery of microbicides against human immunodeficiency virus (HIV). Research to date has mostly focused on devices containing a single antiretroviral compound, exemplified by the 25 mg dapivirine ring currently being evaluated in a Phase III clinical study. However, there is a strong clinical rationale for combining antiretrovirals with different mechanisms of action in a bid to increase breadth of protection and limit the emergence of resistant strains. Here we report the development of a combination antiretroviral silicone elastomer matrix-type vaginal ring for simultaneous controlled release of dapivirine, a non-nucleoside reverse transcriptase inhibitor, and maraviroc, a CCR5-targeted HIV-1 entry inhibitor. Vaginal rings loaded with 25 mg dapivirine and various quantities of maraviroc (50– 400 mg) were manufactured and in vitro release assessed. The 25 mg dapivirine and 100 mg maraviroc formulation was selected for further study. A 24-month pharmaceutical stability evaluation was conducted, indicating good product stability in terms of in vitro release, content assay, mechanical properties and related substances. This combination ring product has now progressed to Phase I clinical testing.

Successful colonoscopy; completion rates and reasons for incompletion

Factors such as poor bowel preparation or obstructing colonic disease may confound the reporting of colonoscopy completion rates, as these factors are outside of the control of the endoscopist performing the procedure. By adjusting for these factors when calculating a colonoscopy completion rate, it may be possible to make a more accurate assessment of a unit's or individuals' competence. Details of two thousand two hundred and sixteen colonoscopies performed by four consultants and their trainees between 1993-2000 were analysed retrospectively from a prospective endoscopy database. Crude (all cases) and adjusted (excluding poor bowel preparation and disease as causes of incompletion) rates were recorded for each sex, and by age according to cause. Overall crude and adjusted completion rates were 77.9% and 85.0% respectively. There was a significant difference between male and female completion rates due to a difference in the incidence of excess looping and intolerance of the procedure (adjusted rate 88.9% in males vs. 81.6% in females, p

Monochloroacetic acid and 60% salicylic acid as a treatment for simple plantar warts:effectiveness and mode of action

Monochloroacetic acid crystals and 60% salicylic acid ointment was found to be more effective than placebo as a treatment for simple plantar warts in a double blind study on 57 patients. Nineteen (66%) patients in the active treatment group compared with five (18%) patients in the placebo group were cured after 6 weeks (P = 0.002). The active treatment was associated with a significantly higher cure rate 6 months after entry (P = 0.04). Treatments were well tolerated. IgG or IgM antibodies or both to human papilloma virus (HPV) types 1 or 2 or both were detected significantly more frequently in the actively treated group 6 weeks after entry (P = 0.0005). Twelve (50%) patients considered to be cured had no detectable secondary immune response. Our results suggest that cure does not depend primarily on the humoral system but rather on mechanical destruction of wart tissue, or occurs as a result of cell mediated immunity.

Assessing the sensitivity and specificity of fish community indicators to management action

We assessed ten trophodynamic indicators of ecosystem status for their sensitivity and specificity to fishing management using a size-resolved multispecies fish community model. The responses of indicators to fishing depended on effort and the size selectivity (sigmoid or Gaussian) of fishing mortality. The highest specificity against sigmoid (trawl-like) size selection was seen from inverse fishing pressure and the large fish indicator, but for Gaussian size selection, the large species indicator was most specific. Biomass, mean trophic level of the community and of the catch, and fishing in balance had the lowest specificity against both size selectivities. Length-based indicators weighted by biomass, rather than abundance, were more sensitive and specific to fishing pressure. Most indicators showed a greater response to sigmoid than Gaussian size selection. Indicators were generally more sensitive at low levels of effort because of nonlinear sensitivity in trophic cascades to fishing mortality. No single indicator emerged as superior in all respects, so given available data, multiple complementary indicators are recommended for community monitoring in the ecosystem approach to fisheries management.

'Sometimes I wish I was an "ex" ex-prisoner': identity processes in the collective action participation of former prisoners in Northern Ireland

Since the signing of the Northern Ireland peace agreement a plethora of community based prisoner self-help organisations have been established wherein former prisoners staff, manage and deliver services to colleagues. By forging and maintaining their collective identities through community based mutual aid, members of these self-help organisations have progressed to create not only individual change/assistance but have also developed and evolved to tackle serious wider social issues which impact on the members of their organisations. This article critically analyses how the conditions of a post conflict society can influence both the development and evolution of these organisations and also how members situate their claims about the self in the organisation and beyond. Using the social movement framework it is argued that the work of these self-help organisations have given rise to a new politics of identity … that is the ‘politically motivated’ ex-prisoner. ©2013 Taylor & Francis

Does Affirmative Action Work? Evidence from the Operation of Fair Employment Legislation in Northern Ireland

An affirmative action programme, established by the Fair Employment (Northern Ireland) Act 1989, has been an important attempt to ensure ‘fair participation’ in employment for both Catholics and Protestants in Northern Ireland since 1990. The programme includes detailed monitoring of the community background of employees and requires employers to undertake remedial action where fair participation is not evident. Agreements were concluded between the regulatory agency and many employers specifying what affirmative action measures were required. Based on the annual monitoring returns submitted between 1990 and 2005, this article evaluates the effectiveness of the affirmative action programme in promoting fair employment participation using fixed effects models. The analysis shows that there has been a general shift towards workforce integration in Northern Ireland but the increase of under-represented groups in agreement concerns is greater than in concerns with no agreement. The success of agreements, however, is limited to certain industrial sectors and medium-sized enterprises.

Pain expression in neonates:facial action and cry

Pain expression in neonates instigated by heel-lance for blood sampling purposes was systematically described using measures of facial expression and cry and compared across sleep/waking states and sex. From gate-control theory it was hypothesized that pain behavior would vary with the ongoing functional state of the infant, rather than solely reflecting tissue insult. Awake-alert but inactive infants responded with the most facial activity, consistent with current views that infants in this state are most receptive to environmental stimulation. Infants in quiet sleep showed the least facial reaction and the longest latency to cry. Fundamental frequency of cry was not related to sleep/waking state. This suggested that findings from the cry literature on qualities of pain cry as a reflection of nervous system 'stress', in unwell newborns, do not generalize directly to healthy infants as a function of state. Sex differences were apparent in speed of response, with boys showing shorter time to cry and to display facial action following heel-lance. The findings of facial action variation across sleep/waking state were interpreted as indicating that the biological and behavioral context of pain events affects behavioral expression, even at the earliest time developmentally, before the opportunity for learned response patterns occurs. Issues raised by the study include the importance of using measurement techniques which are independent of preconceived categories of affective response.

Arching or Compressive Membrane Action in Reinforced Concrete Slabs

Arching or compressive membrane action (CMA) in reinforced concrete slabs occurs as a result of the great difference between the tensile and compressive strength of concrete. Cracking of the concrete causes a migration of the neutral axis which is accompanied by in-plane expansion of the slab at its boundaries. If this natural tendency to expand is restrained, the development of arching action enhances the strength of the slab. The term arching action is normally used to describe the arching phenomenon in one-way spanning slabs and compressive membrane action is normally used to describe the arching phenomenon in two-
way spanning slabs. This encyclopedic article presents the background to the discovery of the phenomenon of arching action and presents a factual history of the approaches to the treatment of arching action in the United Kingdom and North American bridge deck design codes. The article summarises the theoretical methodology used in the United Kingdom Design Manual for Roads and Bridges, BD81/02, which was based on the work by Kirkpatrick, Rankin & Long at Queen's University Belfast.

Community identity as resource and context: A mixed method investigation of coping and collective action in a disadvantaged community

Community identities enhance well-being through the provision of social support and feelings of collective efficacy as well as by acting as a basis for collective action and social change. However, the precise mechanisms through which community identity acts to enhance well-being are complicated by stigmatisation which potentially undermines solidarity and collective action. The present research examines a real-world stigmatised community group in order to investigate: (1) the community identity factors that act to enhance well-being, and (2) the consequences of community identity for community action. Study 1 consisted of a household survey conducted in disadvantaged areas of Limerick city in Ireland. Participants (n=322) completed measures of community identification, social support, collective efficacy, community action, and psychological well-being. Mediation analysis indicated that perceptions of collective efficacy mediated the relationship between identification and well-being. However, levels of self-reported community action were low and unrelated to community identification. In Study 2, twelve follow–up multiple-participant interviews with residents and community group workers were thematically analysed, revealing high levels of stigmatisation and opposition to identity-related collective action. These findings suggest the potential for stigma to reduce collective action through undermining solidarity and social support.