Defining next-generation additive manufacturing applications for the Ministry of Defence (MoD)

“Additive Manufacturing” (AM) is an emerging, highly promising and disruptive technology which is catching the attention of the Defence sector due to the versatility it is offering. Through the combination of design freedom, technology compactness and high deposition rates, technology stakeholders can potentially exploit rapid, delocalized and flexible production. Having the capability to produce highly tailored, fully dense, potentially optimized products, on demand and next to the point of use makes this emerging and immature technology a game changer in the “Defence Support Service” (DS2) sector. Furthermore, if the technology is exploited for the Royal Navy, featured with extended and disrupted supply chains, the benefits are very promising. While most of the AM research and efforts are focusing on the manufacturing/process and design opportunities/topology optimization, this paper aims to provide a creative but educated and validated forecast on what AM can do for the Royal Navy in the future. This paper aims to define the most promising next generation Additive Manufacturing applications for the Royal Navy in the 2025 – 2035 decade. A multidisciplinary methodology has been developed to structure this exploratory applied research study. Moreover, different experts of the UK Defence Value Chain have been involved for primary research and for verification/validation purposes. While major concerns have been raised on process/product qualification and current AM capabilities, the results show that there is a strong confidence on the disruptive potential of AM to be applied in front-end of DS2 systems to support “Complex Engineering Systems” in the future. While this paper provides only next-generation AM applications for RN, substantial conceptual development work has to be carried out to define an AM based system which is able to, firstly satisfy the “spares demands” of a platform and secondly is able to perform in critical environments such as at sea

Impact of caring for someone with a rare rheumatic condition, views from patients and informal carers – the need for cat-like vigilance

Objective ANCA-associated vasculitis (AAV) is a rare multisystem disease. Modern therapeutic protocols have turned AAV from an acute frequently fatal disease into a chronic disease requiring long-term immunosuppression. Patients must often manage substantial burdens related to chronic illness and treatment-related side effects, requiring help from informal carers. This study aimed to explore the experience of patients and of informal carers of patients with AAV about the impact of managing a rare rheumatic condition. Methods A qualitative approach using semi-structured interviews was used. Interviews were conducted with a purposeful sample of 18 pairs of patients with AAV and their informal carers. The interviews were used to explore the participants’ experience and effects of caring. The interviews were recorded and transcribed as verbatim text and analysed using the framework technique. Results 18 patients (seven female) [disease: ten granulomatosis with polyangiitis (GPA); four microscopic polyangiitis (MPA); four eosinophilic granulomatosis with polyangiitis (EGPA), age range 34-78, disease duration 1- 20 years. Caregiver and patient perspectives were shared. The emerging themes were the physical and psychological impact of the disease, the need for constant vigilance and fear of the future. Conclusion Both patients and carers faced a range of challenges in managing a rare condition, from the seriousness of the illness, dealing with the emotional toll and knowing what to expect. This study offers insight into the experiences of patients and informal carers, and health care professionals should address individuals’ fears and expectations for recovery

275 Impact of caring for someone with a rare rheumatic condition: views from patients and informal carers

Background: ANCA-associated vasculitis is a rare multisystem disease. Modern therapeutic protocols have turned ANCA-associated vasculitis from an acute frequently fatal disease into a chronic disease requiring long-term immunosuppression. Patients must often manage substantial burdens related to chronic illness and treatment-related side effects. Patients often need help and support to manage their disease. The aim of this study was to explore the experience of patients and of informal carers of patients about the impact of managing a rare rheumatic condition. Methods: A qualitative approach using semi-structured interviews was used. Interviews were conducted with a purposeful sample of 18 pairs of patients with ANCA-associated vasculitis and their informal carers. The interviews were used to explore the participants experience and affects of caring. The interviews were recorded and transcribed as verbatim text and analysed using the framework technique. Results: 18 patients (seven female) [disease: ten granulomatosis with polyangiitis (GPA); four microscopic polyangiitis (MPA); four eosinophilic granulomatosis with polyangiitis (EGPA), age range 34-78, disease duration 1- 20 years. Caregiver and patient perspectives were shared. The emerging themes were the physical and psychological impact of the disease, the need for constant vigilance and fear of the future. Conclusion: Both patients and carers faced a range of challenges in managing a rare condition. From the seriousness of the illness, dealing with the emotional toll and knowing what to expect. This study offers insight into the experiences of patients and informal carers and health care professionals should address individuals’ fears and expectations for recovery. Disclosures: J.M. honoraria; Abbvie, Bristol Myres Squibb. K.G. and R.A.W. have declared no conflicts of interest

Incidence of ANCA-associated vasculitis in a UK mixed ethnicity population

Objectives: We aimed to estimate the incidence of ANCA-associated vasculitis in the UK and how this varied by ethnic group. Methods: We identified incident cases of ANCA-associated vasculitis between March 2007 and June 2013 in the Nottingham–Derby urban area from medical records using multiple sources. We derived the denominator population from the 2011 census, and we calculated incidence rate ratios using Poisson regression. Results: Overall, we identified 107 cases of ANCA-associated vasculitis, giving an incidence of 23.1 per million person-years (95% CI: 18.9, 27.9). The incidence among the white population was 25.8 per million person-years (95% CI: 21.0, 31.3) and among the black and minority ethnic (BME) population 8.4 per million person-years (95% CI: 3.1, 18.3). After adjustment for age and sex, the difference between ethnic groups was not statistically significant (incidence rate ratio 0.7, 95% CI: 0.3, 1.5, P = 0.3). Conclusion: Overall, the incidence of ANCA-associated vasculitis was similar to other epidemiological studies. Crude incidence rates were lower in the BME than in the white population, but this was partly explained by the older age profile among the white compared with BME population

Improved implementation of the silicon cochlea

The original “analog electronic cochlea” of Lyon and Mead (1988) used a cascade of second-order filter sections in subthreshold analog VLSI to implement a low-power, real-time model of early auditory processing. Experience with many silicon-cochlea chips has allowed the identification of a number of important design issues, namely dynamic range, stability, device mismatch, and compactness. In this paper, the original design is discussed in light of these issues, and circuit and layout techniques are described which significantly improve its performance, robustness, and efficiency. Measurements from test chips verify the improved performance

Structural Classification of Metal Complexes with Three-Coordinate Centres

Attempts to describe the geometry about three-coordinate silver(I) complexes have proven difficult because interatomic angles generally vary wildly and there is no adequate or readily available classification system found in the literature. A search of the Cambridge Structural Database shows that complexes formed between any metal centre and three non-metal donors (18001 examples) usually adopt geometries that are quite different than ideal ‘textbook’ extremes of either trigonal planar (∼4% with α = β = γ = 120 ± 2°), T-shaped (∼0.05% with α = 180 ± 2°, β = γ = 90 ± 2°), or trigonal pyramidal (∼0.3% with α = β = γ = 110 ± 2°). Moreover, there are multiple variations of “Y-type” and “other” shapes that require elaboration. Thus, to assist in future structural descriptions, we developed a classification system that spans all known and yet-to-be-discovered three-coordinate geometries. A spreadsheet has also been constructed that utilizes the “shape-space” approach to extract the structural description from a user input of three angles about a tri-coordinate centre and the number of atoms in a plane. The structures of two silver(I) complexes of new N-donor ligands p-NH2C6H4C6H4CH(pz = pyrazol-1-yl)2, L1, and 2-ferrocenyl-4,5-di(2-pyridyl)imidazole, L2, illustrate the utility of this classification system

Dissecting gene expression at the blood-brain barrier

The availability of genome-wide expression data for the blood-brain barrier is an invaluable resource that has recently enabled the discovery of several genes and pathways involved in the development and maintenance of the blood-brain barrier, particularly in rodent models. The broad distribution of published datasets represents a viable starting point for the molecular dissection of the blood-brain barrier and will further direct the discovery of novel mechanisms of blood-brain barrier formation and function. Technical advances in purifying brain endothelial cells, the key cell that forms the critical barrier, have allowed for greater specificity in gene expression comparisons with other central nervous system cell types, and more systematic characterizations of the molecular composition of the blood-brain barrier. Nevertheless, our understanding of how the blood-brain barrier changes during aging and disease is underrepresented. Blood-brain barrier datasets from a wider range of experimental paradigms and species, including invertebrates and primates, would be invaluable for investigating the function and evolution of the blood-brain barrier. Newer technologies in gene expression profiling, such as RNA-sequencing, now allow for finer resolution of transcriptomic changes, including isoform specificity and RNA-editing. As our field continues to utilize more advanced expression profiling in its ongoing efforts to elucidate the blood-brain barrier, including in disease and drug delivery, we will continue to see rapid advances in our understanding of the molecular mediators of barrier biology. We predict that the recently published datasets, combined with forthcoming genomic and proteomic blood-brain barrier datasets, will continue to fuel the molecular genetic revolution of blood-brain barrier biology

Twitchy, the Drosophila orthologue of the ciliary gating protein FBF1/dyf-19, is required for coordinated locomotion and male fertility

Primary cilia are compartmentalised from the rest of the cell by a ciliary gate comprising transition fibres and a transition zone. The ciliary gate allows the selective import and export of molecules such as transmembrane receptors and transport proteins. These are required for the assembly of the cilium, its function as a sensory and signalling centre and to maintain its distinctive composition. Certain motile cilia can also form within the cytosol as exemplified by human and Drosophila sperm. The role of transition fibre proteins has not been well described in the cytoplasmic cilia. Drosophila have both compartmentalised primary cilia, in sensory neurons, and sperm flagella that form within the cytosol. Here, we describe phenotypes for twitchy the Drosophila orthologue of a transition fibre protein, mammalian FBF1/C. elegans dyf-19. Loss-of-function mutants in twitchy are adult lethal and display a severely uncoordinated phenotype. Twitchy flies are too uncoordinated to mate but RNAi-mediated loss of twitchy specifically within the male germline results in coordinated but infertile adults. Examination of sperm from twitchy RNAi-knockdown flies shows that the flagellar axoneme forms, elongates and is post-translationally modified by polyglycylation but the production of motile sperm is impaired. These results indicate that twitchy is required for the function of both sensory cilia that are compartmentalised from the rest of the cell and sperm flagella that are formed within the cytosol of the cell. Twitchy is therefore likely to function as part of a molecular gate in sensory neurons but may have a distinct function in sperm cells.ISSN:2046-639