Release:A Theatre of Witness Documentary

‘RELEASE’ a documentary by Declan Keeney

Everyone has a past; but should they be defined by it? The legacy of the conflict in Northern Ireland weighs heavily on many of those who experienced it. The pain and loss is as relevant today as it was 30 years ago. The act of remembering itself can be a difficult and dangerous journey. The documentary film 'Release' shot and directed by Declan Keeney explores the life stories of six remarkable men, told in their own words and in their own way through an original Theatre of Witness production of the same name that toured Northern Ireland and the Border Counties in 2012. The film explores themes of forgiveness, remembering and the pain of living with our ever-present past.
With great courage and conviction, a former RUC detective, a former Prison Governor, a former British soldier, two ex-prisoners and a community activist who survived a car bomb as a child come together across the sectarian divide to create a group of men working for peace. Their journey is at times heart breaking, extraordinary, breathtakingly brave but ultimately transformational. It is a story of survival, but most importantly it is their story and in their own words.

Pre-clinical development of a combination microbicide vaginal ring containing dapivirine and darunavir

Objectives: Combination microbicide vaginal rings may be more effective than single microbicide rings at reducing/preventing sexual transmission of HIV. Here, we report the preclinical development and macaque pharmacokinetics of matrix-type silicone elastomer vaginal rings containing dapivirine and darunavir.

Methods: Macaque rings containing 25 mg dapivirine, 300 mg darunavir and 100 mg dapivirine, and 300 mg darunavir were manufactured and characterised by differential scanning calorimetry. In vitro release was assessed into isopropanol/water and simulated vaginal fluid. Macaque vaginal fluid and blood serum concentrations for both antiretrovirals were measured during 28-day ring use. Tissue levels were measured on day 28. Ex vivo challenge studies were performed on vaginal fluid samples and IC50 values calculated.

Results: Darunavir caused a concentration-dependent reduction in the dapivirine melting temperature in both solid drug mixes and in the combination ring. In vitro release from rings was dependent on drug loading, the number of drugs present, and the release medium. In macaques, serum concentrations of both microbicides were maintained between 101–102 pg/mL. Vaginal fluid levels ranged between 103–104 ng/g and 104–105 ng/g for dapivirine and darunavir, respectively. Tissue concentrations ranges for each drug were: vagina (1.8×103–3.8×103 ng/g) > cervix (9.4×101–3.9×102 ng/g) > uterus (0–108 ng/g) > rectum (0–40 ng/g). Measured IC50 values were > 2 ng/mL for both compounds.

Conclusions: Based on these results, and in light of recent clinical progress of the 25mg dapivirine ring, a combination vaginal ring containing dapivirine and darunavir is a viable second-generation HIV microbicide candidate.

Victimisation and Attitudes Towards Former Political Prisoners in Northern Ireland

The release of ex-combatants and the mechanisms for their re-integration within society has become an increasingly controversial issue in peace settlements. Yet to date, the view of victims concerning such arrangements in post-conflict societies remains unexplored. Mindful of this omission and using Northern Ireland as a case study, this article investigates the relationship between victimisation and attitudes towards the treatment of former political prisoners. Based on the 2011 Northern Ireland Social and Political Attitudes Survey, the results suggest that individual victims—those who directly and/or indirectly experienced violent incidents—are notably less supportive of a punitive approach towards the treatment of former political prisoners than non-victims. Moreover, this is particularly the case when victims from within the Catholic community are considered. The Northern Ireland evidence suggests that victims can act as a positive and inclusive force in terms of the rehabilitation and re-integration of former combatants in societies emerging from conflict.

Respiratory Infections Cause the Release of Extracellular Vesicles: Implications in Exacerbation of Asthma/COPD

Background: Infection-related exacerbations of respiratory diseases are a major health concern; thus understanding the mechanisms driving them is of paramount importance. Despite distinct inflammatory profiles and pathological differences, asthma and COPD share a common clinical facet: raised airway ATP levels. Furthermore, evidence is growing to suggest that infective agents can cause the release of extracellular vesicle (EVs) in vitro and in bodily fluids. ATP can evoke the P2X7/caspase 1 dependent release of IL-1β/IL-18 from EVs; these cytokines are associated with neutrophilia and are increased during exacerbations. Thus we hypothesized that respiratory infections causes the release of EVs in the airway and that the raised ATP levels, present in respiratory disease, triggers the release of IL-1β/IL-18, neutrophilia and subsequent disease exacerbations.

Methods: To begin to test this hypothesis we utilised human cell-based assays, ex vivo murine BALF, in vivo pre-clinical models and human samples to test this hypothesis.

Results: Data showed that in a murine model of COPD, known to have increased airway ATP levels, infective challenge causes exacerbated inflammation. Using cell-based systems, murine models and samples collected from challenged healthy subjects, we showed that infection can trigger the release of EVs. When exposed to ATP the EVs release IL-1b/IL-18 via a P2X₇/caspase-dependent mechanism. Furthermore ATP challenge can cause a P2X₇ dependent increase in LPS-driven neutrophilia.

Conclusions: This preliminary data suggests a possible mechanism for how infections could exacerbate respiratory diseases and may highlight a possible signalling pathway for drug discovery efforts in this area.

When opportunity matters: Comparing the risk taking attitudes of prisoners and recently released ex-prisoners

Risk-taking tendencies and environmental opportunities to commit crime are two key features in understanding criminal behavior. Upon release from prison, ex-prisoners have a much greater opportunity to engage in risky activity and to commit criminal acts. We hypothesized that ex-prisoners would exhibit greater risk-taking tendencies compared to prisoners who have fewer opportunities to engage in risky activity and who are monitored constantly by prison authorities. Using cumulative prospect theory to compare the risky choices of prisoners and ex-prisoners our study revealed that ex-prisoners who were within 16 weeks of their prison release made riskier choices than prisoners. Our data indicate that previous studies comparing prisoners behind bars with nonoffenders may have underestimated the risk-taking tendencies of offenders. The present findings emphasize the central role played by risk-taking attitudes in criminal offending and highlight a need to examine offenders after release from prison.

Transiting Exoplanet Studies and Community Targets for JWST's Early Release Science Program

The James Webb Space Telescope (JWST) will likely revolutionize transiting exoplanet atmospheric science, due to a combination of its capability for continuous, long duration observations and its larger collecting area, spectral coverage, and spectral resolution compared to existing space-based facilities. However, it is unclear precisely how well JWST will perform and which of its myriad instruments and observing modes will be best suited for transiting exoplanet studies. In this article, we describe a prefatory JWST Early Release Science (ERS) Cycle 1 program that focuses on testing specific observing modes to quickly give the community the data and experience it needs to plan more efficient and successful transiting exoplanet characterization programs in later cycles. We propose a multi-pronged approach wherein one aspect of the program focuses on observing transits of a single target with all of the recommended observing modes to identify and understand potential systematics, compare transmission spectra at overlapping and neighboring wavelength regions, confirm throughputs, and determine overall performances. In our search for transiting exoplanets that are well suited to achieving these goals, we identify 12 objects (dubbed “community targets”) that meet our defined criteria. Currently, the most favorable target is WASP-62b because of its large predicted signal size, relatively bright host star, and location in JWST's continuous viewing zone. Since most of the community targets do not have well-characterized atmospheres, we recommend initiating preparatory observing programs to determine the presence of obscuring clouds/hazes within their atmospheres. Measurable spectroscopic features are needed to establish the optimal resolution and wavelength regions for exoplanet characterization. Other initiatives from our proposed ERS program include testing the instrument brightness limits and performing phase-curve observations. The latter are a unique challenge compared to transit observations because of their significantly longer durations. Using only a single mode, we propose to observe a full-orbit phase curve of one of the previously characterized, short-orbital-period planets to evaluate the facility-level aspects of long, uninterrupted time-series observations.