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.

Victimhood and Attitudes towards Dealing with the Legacy of the Past: Northern Ireland as a Case Study

Research Highlights and Abstract: Using Northern Ireland as a case study, this article provides the first nationally representative and systematic study of victims' views on how to deal with the past; Focusing specifically on Northern Ireland, it both investigates and provides a comprehensive account of the marked divisions between the various religious groupings-Protestants, Catholics and the non-affiliated-in terms of a range of truth recovery mechanisms to deal with legacy of its violent past; It empirically investigates and validates two key predictors-perceptions of victimhood and general attitudes towards the past-in determining the source of these divisions It outlines the implications of our findings for other societies emerging from conflict. Truth recovery mechanisms have become a cornerstone of peacebuilding efforts in societies emerging from conflict. Yet, to date, the view of victims in post-conflict societies concerning such arrangements remains highly anecdotal and often second-hand in nature. Mindful of this omission and using Northern Ireland as a case study, this article investigates the views of victims towards a range of mechanisms to deal with the legacy of Northern Ireland's violent past. Based on the 2011 Northern Ireland Social and Political Attitudes Survey, the results suggest some marked divisions in relation to this issue, with victims within the Catholic community being significantly more supportive of such initiatives than either Protestants or those with no religion. Moreover, while perceptions of victimhood emerge as the key predictor of attitudes among Protestants and the non-affiliated, general opinions on how to deal with the past are the key determinant of views among members of the Catholic community

Processing of short auditory stimuli:The rapid audio sequential presentation paradigm (RASP)

Human listeners seem to be remarkably able to recognise acoustic sound sources based on timbre cues. Here we describe a psychophysical paradigm to estimate the time it takes to recognise a set of complex sounds differing only in timbre cues: both in terms of the minimum duration of the sounds and the inferred neural processing time. Listeners had to respond to the human voice while ignoring a set of distractors. All sounds were recorded from natural sources over the same pitch range and equalised to the same duration and power. In a first experiment, stimuli were gated in time with a raised-cosine window of variable duration and random onset time. A voice/non-voice (yes/no) task was used. Performance, as measured by d', remained above chance for the shortest sounds tested (2 ms); d's above 1 were observed for durations longer than or equal to 8 ms. Then, we constructed sequences of short sounds presented in rapid succession. Listeners were asked to report the presence of a single voice token that could occur at a random position within the sequence. This method is analogous to the "rapid sequential visual presentation" paradigm (RSVP), which has been used to evaluate neural processing time for images. For 500-ms sequences made of 32-ms and 16-ms sounds, d' remained above chance for presentation rates of up to 30 sounds per second. There was no effect of the pitch relation between successive sounds: identical for all sounds in the sequence or random for each sound. This implies that the task was not determined by streaming or forward masking, as both phenomena would predict better performance for the random pitch condition. Overall, the recognition of familiar sound categories such as the voice seems to be surprisingly fast, both in terms of the acoustic duration required and of the underlying neural time constants.

Rapid climate change did not cause population collapse at the end of the European Bronze Age

The impact of rapid climate change on contemporary human populations is of global concern. To contextualize our understanding of human responses to rapid climate change it is necessary to examine the archeological record during past climate transitions. One episode of abrupt climate change has been correlated with societal collapse at the end of the northwestern European Bronze Age. We apply new methods to interrogate archeological and paleoclimate data for this transition in Ireland at a higher level of precision than has previously been possible. We analyze archeological 14C dates to demonstrate dramatic population collapse and present high-precision proxy climate data, analyzed through Bayesian methods, to provide evidence for a rapid climatic transition at ca. 750 calibrated years B.C. Our results demonstrate that this climatic downturn did not initiate population collapse and highlight the nondeterministic nature of human responses to past climate change.

Type-I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors

The role of proteases in viral infection of the lung is poorly understood. Thus, we examined matrix metalloproteinases (MMPs) and cathepsin proteases in respiratory syncytial virus (RSV)-infected mouse lungs. RSV-induced gene expression for MMPs -2, -3, -7, -8, -9, -10, -12, -13, -14, -16, -17, -19, -20, -25, -27, and -28 and cathepsins B, C, E, G, H, K, L1, S, W, and Z in the airways of Friend leukemia virus B sensitive strain mice. Increased proteases were present in the bronchoalveolar lavage fluid (BALF) and lung tissue during infection. Mitochondrial antiviral-signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-β-deficient mice were exposed to RSV. Mavs-deficient mice had significantly lower expression of airway MMP-2, -3, -7, -8, -9, -10, -12, -13, and -28 and cathepsins C, G, K, S, W, and Z. In lung epithelial cells, retinoic acid-inducible gene-1 (RIG-I) was identified as the major RIG-I-like receptor required for RSV-induced protease expression via MAVS. Overexpression of RIG-I or treatment with interferon-β in these cells induced MMP and cathepsin gene and protein expression. The significance of RIG-1 protease induction was demonstrated by the fact that inhibiting proteases with batimastat, E64 or ribavirin prevented airway hyperresponsiveness and enhanced viral clearance in RSV-infected mice.

A New Analysis of Mars "Special Regions": Findings of the Second MEPAG Special Regions Science Analysis Group (SR-SAG2)

A committee of the Mars Exploration Program Analysis Group (MEPAG) has reviewed and updated the description of Special Regions on Mars as places where terrestrial organisms might replicate (per the COSPAR Planetary Protection Policy). This review and update was conducted by an international team (SR-SAG2) drawn from both the biological science and Mars exploration communities, focused on understanding when and where Special Regions could occur. The study applied recently available data about martian environments and about terrestrial organisms, building on a previous analysis of Mars Special Regions (2006) undertaken by a similar team. Since then, a new body of highly relevant information has been generated from the Mars Reconnaissance Orbiter (launched in 2005) and Phoenix (2007) and data from Mars Express and the twin Mars Exploration Rovers (all 2003). Results have also been gleaned from the Mars Science Laboratory (launched in 2011). In addition to Mars data, there is a considerable body of new data regarding the known environmental limits to life on Earth—including the potential for terrestrial microbial life to survive and replicate under martian environmental conditions. The SR-SAG2 analysis has included an examination of new Mars models relevant to natural environmental variation in water activity and temperature; a review and reconsideration of the current parameters used to define Special Regions; and updated maps and descriptions of the martian environments recommended for treatment as “Uncertain” or “Special” as natural features or those potentially formed by the influence of future landed spacecraft. Significant changes in our knowledge of the capabilities of terrestrial organisms and the existence of possibly habitable martian environments have led to a new appreciation of where Mars Special Regions may be identified and protected. The SR-SAG also considered the impact of Special Regions on potential future human missions to Mars, both as locations of potential resources and as places that should not be inadvertently contaminated by human activity. Key Words: Martian environments—Mars astrobiology—Extreme environment microbiology—Planetary protection—Exploration resources. Astrobiology 14, 887–968.

CCAAT/enhancer binding protein α predicts poorer prognosis and prevents energy starvation-induced cell death in hepatocellular carcinoma

CCAAT enhancer binding protein α (C/EBPα) plays an essential role in cellular differentiation, growth, and energy metabolism. Here, we investigate the correlation between C/EBPα and hepatocellular carcinoma (HCC) patient outcomes and how C/EBPα protects cells against energy starvation. Expression of C/EBPα protein was increased in the majority of HCCs examined (191 pairs) compared with adjacent nontumor liver tissues in HCC tissue microarrays. Its upregulation was correlated significantly with poorer overall patient survival in both Kaplan-Meier survival (P = 0.017) and multivariate Cox regression (P = 0.028) analyses. Stable C/EBPα-silenced cells failed to establish xenograft tumors in nude mice due to extensive necrosis, consistent with increased necrosis in human C/EBPα-deficient HCC nodules. Expression of C/EBPα protected HCC cells in vitro from glucose and glutamine starvation-induced cell death through autophagy-involved lipid catabolism. Firstly, C/EBPα promoted lipid catabolism during starvation, while inhibition of fatty acid beta-oxidation significantly sensitized cell death. Secondly, autophagy was activated in C/EBPα-expressing cells, and the inhibition of autophagy by ATG7 knockdown or chloroquine treatment attenuated lipid catabolism and subsequently sensitized cell death. Finally, we identified TMEM166 as a key player in C/EBPα-mediated autophagy induction and protection against starvation.

CONCLUSION: The C/EBPα gene is important in that it links HCC carcinogenesis to autophagy-mediated lipid metabolism and resistance to energy starvation; its expression in HCC predicts poorer patient prognosis.

DEAD-box helicase DP103 defines metastatic potential of human breast cancers

Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB-mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.

Manganese Superoxide Dismutase Is a Promising Target for Enhancing Chemosensitivity of Basal-Like Breast Carcinoma

AIMS: Although earlier reports highlighted a tumor suppressor role for manganese superoxide dismutase (MnSOD), recent evidence indicates increased expression in a variety of human cancers including aggressive breast carcinoma. In the present article, we hypothesized that MnSOD expression is significantly amplified in the aggressive breast carcinoma basal subtype, and targeting MnSOD could be an attractive strategy for enhancing chemosensitivity of this highly aggressive breast cancer subtype.

RESULTS: Using MDA-MB-231 and BT549 as a model of basal breast cancer cell lines, we show that knockdown of MnSOD decreased the colony-forming ability and sensitized the cells to drug-induced cell death, while drug resistance was associated with increased MnSOD expression. In an attempt to develop a clinically relevant approach to down-regulate MnSOD expression in patients with basal breast carcinoma, we employed activation of the peroxisome proliferator-activated receptor gamma (PPARγ) to repress MnSOD expression; PPARγ activation significantly reduced MnSOD expression, increased chemosensitivity, and inhibited tumor growth. Moreover, as a proof of concept for the clinical use of PPARγ agonists to decrease MnSOD expression, biopsies derived from breast cancer patients who had received synthetic PPARγ ligands as anti-diabetic therapy had significantly reduced MnSOD expression. Finally, we provide evidence to implicate peroxynitrite as the mechanism involved in the increased sensitivity to chemotherapy induced by MnSOD repression.

INNOVATION AND CONCLUSION: These data provide evidence to link increased MnSOD expression with the aggressive basal breast cancer, and underscore the judicious use of PPARγ ligands for specifically down-regulating MnSOD to increase the chemosensitivity of this subtype of breast carcinoma.

Discovery of Main-Belt Comet P/2006 VW139 by Pan-STARRS1

We describe the discovery of comet-like activity in main-belt asteroid (300163) 2006 VW139 (later re-designated as Comet P/2006 VW139) by Pan-STARRS1. We also detail follow-up photometric, spectroscopic, and dynamical analyses of the object.

Cystic Fibrosis Foundation and European Cystic Fibrosis Society Survey of cystic fibrosis mental health care delivery

Background: Psychological morbidity in individuals with cystic fibrosis (CF) and their caregivers is common. The Cystic Fibrosis Foundation (CFF) and European Cystic Fibrosis Society (ECFS) Guidelines Committee on Mental Health sought the views of CF health care professionals concerning mental health care delivery. Methods: An online survey which focused on the current provision and barriers to mental health care was distributed to CF health care professionals. Results: Of the 1454 respondents, many did not have a colleague trained in mental health issues and 20% had no one on their team whose primary role was focused on assessing or treating these issues. Insufficient resources and a lack of competency were reported in relation to mental health referrals. Seventy-three percent of respondents had no experience with mental health screening. Of those who did, they utilized 48 different, validated scales. Conclusions: These data have informed the decision-making, dissemination and implementation strategies of the Mental Health Guidelines Committee sponsored by the CFF and ECFS.

Health professionals' and service users' perspectives of shared care for monitoring wet age-related macular degeneration: a qualitative study alongside the ECHoES trial

Objectives: To explore the views of eye health professionals and service users on shared community and hospital care for wet or neovascular age-related macular degeneration (nAMD).

Method: Using maximum variation sampling, 5 focus groups and 10 interviews were conducted with 23 service users and 24 eye health professionals from across the UK (consisting of 8 optometrists, 6 ophthalmologists, 6 commissioners, 2 public health representatives and 2 clinical eye care advisors to local Clinical Commissioning Groups). Data were transcribed verbatim and analysed thematically using constant comparative techniques derived from grounded theory methodology.

Results: The needs and preferences of those with nAMD appear to be at odds with the current service being provided. There was enthusiasm among health professionals and service users about the possibility of shared care for nAMD as it was felt to have the potential to relieve hospital eye service burden and represent a more patient-centred option, but there were a number of perceived barriers to implementation. Some service users and ophthalmologists voiced concerns about optometrist competency and the potential for delays with referrals to secondary care if stable nAMD became active again. The health professionals were divided as to whether shared care was financially more efficient than the current model of care. Specialist training for optometrists, under the supervision of ophthalmologists, was deemed to be the most effective method of training and was perceived to have the potential to improve the communication and trust that shared care would require.

Conclusions: While shared care is perceived to represent a promising model of nAMD care, voiced concerns suggest that there would need to be greater collaboration between ophthalmology and optometry, in terms of interprofessional trust and communication.

Tumorigenesis and peritoneal colonization from fallopian tube epithelium

Ovarian cancer is the most lethal gynecological malignancy, primarily because its origin and initiation factors are unknown. A secretory murine oviductal epithelial (MOE) model was generated to address the hypothesis that the fallopian tube is an origin for high-grade serous cancer. MOE cells were stably altered to express mutation in p53, silence PTEN, activate AKT, and amplify KRAS alone and in combination, to define if this cell type gives rise to tumors and what genetic alterations are required to drive malignancy. Cell lines were characterized in vitro and allografted into mice. Silencing PTEN formed high-grade carcinoma with wide spread tumor explants including metastasis into the ovary. Addition of p53 mutation to PTEN silencing did not enhance this phenotype, whereas addition of KRAS mutation reduced survival. Interestingly, PTEN silencing and KRAS mutation originating from ovarian surface epithelium generated endometrioid carcinoma, suggesting that different cellular origins with identical genetic manipulations can give rise to distinct cancer histotypes. Defining the roles of specific signaling modifications in tumorigenesis from the fallopian tube/oviduct is essential for early detection and development of targeted therapeutics. Further, syngeneic MOE allografts provide an ideal model for pre-clinical testing in an in vivo environment with an intact immune system.