'Just be Brave' - The Experiences of Young Witnesses in Criminal Proceedings in Northern Ireland

The last three decades have witnessed considerable interest in the position of children and young people acting as witnesses in criminal cases and on how best to facilitate them to give their best evidence and minimise the trauma involved. This paper presents the findings of a small-scale study in Northern Ireland examining the experiences of young witnesses pre-trial, during the trial and post-trial. Interviews were carried out with 37 young witnesses and 33 parents, and a questionnaire was completed by 16 volunteers and practitioners working in a local young witness support scheme. The findings indicate that the prospect and actuality of giving evidence in a criminal trial are anxiety-provoking and stressful for the majority of young witnesses. Particular issues identified are delay, both in terms of cases coming to court and in waiting times at court, the availability of pre-trial preparation and support, facilities at court buildings and the treatment of young people during cross-examination by defence lawyers. The paper concludes that there is a continuing need to strive for improvement, and that this necessarily involves reviewing the experiences of young witnesses and seeking their views on measures designed to enable them to give their best evidence. Copyright © 2013 John Wiley & Sons, Ltd.

Fasciola hepatica:The therapeutic potential of a worm secretome

The success of helminth parasites is partly related to their ability to modulate host immune responses towards an anti-inflammatory/regulatory phenotype. This ability resides with the molecules contained in the secretome of various helminths that have been shown to interact with host immune cells and influence their function. Consequently, there exists a unique opportunity to exploit these molecules for the prophylactic and therapeutic treatment of human pro- and auto-inflammatory disorders (for example septic shock, transplant rejection and autoimmune disease). In this review, we describe the mechanisms used by the trematode parasite, Fasciola hepatica, to modulate the immune responses of its host and discuss the potent immune-modulatory effects of three individual molecules within the secretome; namely cathepsin L1, peroxiredoxin and helminth defence molecule. With a focus on the requirements from industry, we discuss the strategies by which these molecules may be clinically developed to control human immune responses in a way that is conducive to the prevention of immune-mediated diseases.

Age-related changes in non-receptor dependent generation of reactive oxygen species from phagocytes of healthy adults

Several authors have shown that neutrophil generation of reactive oxygen species (ROS) declines with advancing age. Similar changes have also been suggested in monocytes. In both cases alterations in second messenger activity have been implicated as the most likely explanation for these observations. The aim of this study was to investigate the effect of age on phagocyte ROS generation, stimulated by the direct activation of protein kinase C (PKC). Venous blood was drawn from normal healthy subjects, cells were separated on a double density gradient into mononuclear and polymorphonuclear (pmn) cells. Phorbol myristate acetate (PMA) was employed as a cell stimulus. Superoxide generation was measured by cytochrome c reduction and myeloperoxidase (MPO) products by measurement of peak luminol chemiluminescence (CL). Fifty-eight subjects, 25 males and 33 females, were studied, median age 49 years (range 26-88 years). Polymorphonuclear cell superoxide generation was significantly higher in males and there was a trend towards higher pmn MPO product generation in males. Using Spearman's ranked correlation coefficient, monocyte superoxide generation was negatively correlated with age (r = -0.473, P <0.001). No changes in the generation of MPO products was found. There were also trends towards a negative correlation of pmn cytochrome c reduction and peak luminol CL with age in males but not females. Since PMA directly activates protein kinase C, reduced monocyte superoxide generation with increasing age appears to be related to alterations in the ROS generating system downstream of the cell receptor. Impaired monocyte superoxide generation may have implications for non-specific defence against certain infections and early tumour growth in the elderly. Factors underlying these changes in monocyte function therefore require further study.

Molecular cloning of the trypsin inhibitor from the skin secretion of the Madagascan Tomato Frog, Dyscophus guineti (Microhylidae), and insights into its potential defensive role

In this study, we investigate the skin secretion of the Madagascan Tomato Frog, Dyscophus guineti, which is characterized by its peculiarly adhesive and viscous nature, with a view toward the function of the member of the Kunitz/bovine pancreatic trypsin inhibitor family (BPTI) it is known to contain. Using “shotgun” cloning of a skin secretion-derived cDNA library, we obtained the full-length sequence of the respective precursor that encodes this trypsin inhibitor. Furthermore, we demonstrated that this enzyme has inhibitory activity against trypsin, but not against thrombin, and also has no antimicrobial activity. Moreover, we confirm that it appears to be the only bioactive peptide in the skin secretion of this species. Using these observations, we attempt to posit a role for this inhibitor. In particular, we hypothesize that the trypsin inhibitor in D. guineti (and possibly other microhylid frogs) maintains the soluble state of the skin secretion during storage in the glands. Upon discharge of the secretion, the trypsin inhibitor, which occurs in low concentrations, can no longer prevent the polymerisation process of other yet unidentified skin proteins, thereby resulting in the conversion of the secretion to its final glue-like state. Thus, the major defensive value of the skin secretion appears to be mechanical, impeding ingestion through a combination of adhesion and the body inflation typical for some microhylid frogs rather than chemical through antimicrobial activity or toxicity.

Defending the Irish Border: The Map of Watchful Architecture

This chapter offers an analysis of a map of the Irish border. The Map of Watchful Architecture charts the history of defensive structures in the border region.

Lipopolysaccharide-binding protein and CD14 are increased in the bronchoalveolar lavage fluid of smokers

Lipopolysaccharide-binding protein (LBP) and CD14 contribute to the recognition of pathogens by cells, which triggers the activation of defence responses. Smoking is a risk factor for the development of chronic obstructive pulmonary disease (COPD) and respiratory infections. The current authors theorised that levels of LBP and CD14 in the lungs of smokers would be higher than those in the lungs of never-smokers. These elevated levels could affect host responses upon infection. LBP, soluble CD14 (sCD14) and interleukin (IL)-8 were detected by ELISA. Nuclear factor (NF)- ?B, p38 and the inhibitor I?Ba were studied by immunoassays. Gene expression was assessed by RT-PCR. Bronchoalveolar lavage levels of LBP and CD14 were significantly higher in smokers and COPD patients than in never-smokers, whereas levels of both proteins were not significantly different between smokers and COPD patients. IL-6, IL-1ß5 and cigarette smoke condensate induced the expression of LBP and CD14 by airway epithelial cells. LBP and sCD14 inhibited the nontypeable Haemophilus influenzae (NTHi)-dependent secretion of IL-8 and the activation of NF-?B and p38 mitogen-activated protein kinase signalling pathways but they increased the internalisation of NTHi by airway epithelial cells. Thus, in the inflamed airways of smokers both proteins could contribute to inhibit bacteria-dependent cellular activation without compromising the internalisation of pathogens by airway cells. Copyright©ERS Journals Ltd 2009.

The lipopolysaccharide outer core of Yersinia enterocolitica serotype O:3 is required for virulence and plays a role in outer membrane integrity

Lipopolysaccharide (LPS) of Yersinia enterocolitica O:3 has an inner core linked to both the O-antigen and to an outer core hexasaccharide that forms a branch. The biological role of the outer core was studied using polar and non-polar mutants of the outer core biosynthetic operon. Analysis of O-antigen- and outer core-deficient strains suggested a critical role for the outer core in outer membrane properties relevant in resistance to antimicrobial peptides and permeability to hydrophobic agents, and indirectly relevant in resistance to killing by normal serum. Wild-type bacteria but not outer core mutants killed intragastrically infected mice, and the intravenous lethal dose was approximately 10(4)-fold higher for outer core mutants. After intragastric infection, outer core mutants colonized Peyer's patches and invaded mesenteric lymph nodes, spleen and liver, and induced protective immunity against wild-type bacteria. In mice co-infected intragastrically with an outer core mutant-wild type mixture, both strains colonized Peyer's patches similarly during the first 2 days, but the mutant was much less efficient in colonizing deeper organs and was cleared faster from Peyer's patches. The results demonstrate that outer core is required for Y. enterocolitica O:3 full virulence, and strongly suggest that it provides resistance against defence mechanisms (most probably those involving bactericidal peptides).

Integrating nutrition and immunology: A new frontier

Nutrition is critical to immune defence and parasite resistance, which not only affects individual organisms, but also has profound ecological and evolutionary consequences. Nutrition and immunity are complex traits that interact via multiple direct and indirect pathways, including the direct effects of nutrition on host immunity but also indirect effects mediated by the host's microbiota and pathogen populations. The challenge remains, however, to capture the complexity of the network of interactions that defines nutritional immunology. The aim of this paper is to discuss the recent findings in nutritional research in the context of immunological studies. By taking examples from the entomological literature, we argue that insects provide a powerful tool for examining the network of interactions between nutrition and immunity due to their tractability, short lifespan and ethical considerations. We describe the relationships between dietary composition, immunity, disease and microbiota in insects, and highlight the importance of adopting an integrative and multi-dimensional approach to nutritional immunology. 

NO-loaded Zn2+-exchanged zeolite materials: A potential bifunctional anti-bacterial strategy

Nitric oxide (NO) is important for the regulation of a number of diverse biological processes, including vascular tone, neurotransmission, inflammatory cell responsiveness, defence against invading pathogens and wound healing. Transition metal exchanged zeolites are nanoporous materials with high-capacity storage properties for gases such as NO. The NO stores are liberated upon contact with aqueous environments, thereby making them ideal candidates for use in biological and clinical settings. Here, we demonstrate the NO release capacity and powerful bactericidal properties of a novel NO-storing Zn2+-exchanged zeolite material at a 50 wt.% composition in a polytetrafluoroethylene polymer. Further to our published data showing the anti-thrombotic effects of a similar NO-loaded zeolite, this study demonstrates the antibacterial properties of NO-releasing zeolites against clinically relevant strains of bacteria, namely Gram-negative Pseudomonas aeruginosa and Gram-positive methicillin-sensitive and methicillin-resistant Staphylococcus aureus and Clostridium difficile. Thus our study highlights the potential of NO-loaded zeolites as biocompatible medical device coatings with anti-infective properties. (C) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Equal Security: Europe and the Strategic Arms Limitation Talks, 1968-1976

SALT threatened to institutionalize a bipolar world order. NWS and NNWS alike feared that the US and SU will prioritize global security principles such as systemic stability and conflict stability to Atlantic and European security. Endangered was Europe’s security and position in the future world order. Parity in strategic weapons invalidated the US nuclear umbrella. An ABM deployment and a non-transfer regime threatened Europe’s nuclear defence options. The danger of a Limited War or a denuclearization of Central Europe led to a European co-ordination on nuclear arms control to assure the preservation of the West and the future of Europe.

Immunomodulatory molecules of Fasciola hepatica:Candidates for both vaccine and immunotherapeutic development

The liver fluke, Fasciola hepatica, causes fascioliasis in domestic animals (sheep, cattle), a global disease that is also an important infection of humans. As soon as the parasite invades the gut wall its interaction with various host immune cells (e.g. dendritic cells, macrophages and mast cells) is complex. The parasite secretes a myriad of molecules that direct the immune response towards a favourable non-protective Th2-mediate/regulatory environment. These immunomodulatory molecules, such as cathepsin L peptidase (FhCL1), are under development as the first generation of fluke vaccines. However, this peptidase and other molecules, such as peroxiredoxin (FhPrx) and helminth defence molecule (FhHDM-1), exhibit various immunomodulatory properties that could be harnessed to help treat immune-related conditions in humans and animals.

Hylaranins: prototypes of a new class of amphibian antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii

Amphibian skin secretions contain a broad spectrum of biologically active compounds, particularly antimicrobial peptides, which are considered to constitute a first line of defence against bacterial infection. Here we describe the identification of two prototype peptides representing a novel structural class of antimicrobial peptide from the skin secretion of the oriental broad-folded frog, Hylarana latouchii. Named hylaranin-L1 (GVLSAFKNALPGIMKIIVamide) and hylaranin-L2 (GVLSVIKNALPGIMRFIAamide), both peptides consist of 18 amino acid residues, are C-terminally amidated and are of unique primary structures. Their primary structures were initially deduced by MS/MS fragmentation sequencing from reverse-phase HPLC fractions of skin secretion that demonstrated antimicrobial activity. Subsequently, their precursor-encoding cDNAs were cloned from a skin secretion-derived cDNA library and their primary structures were confirmed unequivocally. Synthetic replicates of both peptides exhibited broad-spectrum antimicrobial activity with mean inhibitory concentrations (MICs) of 34 µM against Gram-negative Escherichia coli, 4.3 µM against Gram-positive Staphylococcus aureus and 4–9 µM against the yeast, Candida albicans. Both peptides exhibited little haemolytic activity (<6 %) at the MICs for S. aureus and C. albicans. Amphibian skin secretions thus continue to provide novel antimicrobial peptide structures that may prove to be lead compounds in the design of new classes of anti-infection therapeutics.

Non-apologies and prolonged silences in post-conflict settings: The case of post-colonial Cyprus

Despite the growing use of apologies in post-conflict settings, cases of non-apology remain unaddressed and continue to puzzle scholars. This article focuses on the absence of apology by non-state and anti-state actors by examining the case of the Cypriot armed group EOKA, which has refused to offer an apology to the civilian victims of its ‘anti-colonial’ struggle (1955–1959). Using field data and parliamentary debates, and drawing on comparisons, this article analyses the factors that contributed to a lack of apology. It is argued that the inherited timelessness of Greek nationalism, and the impression of a perpetual need for defence, set up textbook conditions for the development of a hegemonic discourse and prevented an apology for human rights violations.