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Macro X-ray Fluorescence (MA-XRF) scanning is an increasingly widely used technique for analytical imaging of paintings and other artworks. The datasets acquired must be processed to produce maps showing the distribution of the chemical elements that are present in the painting. Existing approaches require varying degrees of expert user intervention, in particular to select a list of target elements against which to fit the data. In this paper, we propose a novel approach that can automatically extract and identify chemical elements and their distributions from MA-XRF datasets. The proposed approach consists of three parts: 1) pre-processing steps, 2) pulse detection and model order selection based on Finite Rate of Innovation theory, and 3) chemical element estimation based on Cramér-Rao bounding techniques. The performance of our approach is assessed using MA-XRF datasets acquired from paintings in the collection of the National Gallery, London. The results presented show the ability of our approach to detect elements with weak X-ray fluorescence intensity and from noisy XRF spectra, to separate overlapping elemental signals and, excitingly, to aid visualisation of hidden underdrawing in a masterpiece by Leonardo da Vinci.

Aims The Irish DNA Atlas is a DNA collection being assembled with the aim of describing the fine-scale population structure in Ireland. Understanding such structure can inform on optimal design of clinical genetic studies as well as the history of the Irish population. We will present an overview of and the preliminary findings from the study. Methods We are recruiting individuals with all eight greatgrandparents born in Ireland, within 30 kilometres of each other. Participants are asked to complete a detailed birth-brief, which records place and date of birth of three generations of ancestors. We also collect some basic health-related details. DNA is extracted from a saliva sample. We have genotyped using an Illumina OmniExpressdense SNP genotyping platform. We present a number of analyses designed to visualise genetic structure, including; Principle Component, ADMIXTURE, and Runs of Homozygosity analysis. Results To date we have recruited 162 participants. The mean great-grandparental area is 32 kilometres, with an average greatgrandparental date of birth of 1850. Therefore the individuals in the Atlas provide insight to the genetic landscape of Ireland before significant movement of people from the 20th century onwards. An analysis of dense genotyping data from 142participants shows that the Atlas participants cluster closely with British individuals in a Europe wide PCA, but present different ancestral population components when compared with British, and other European populations. Irish individuals also present slightly higher levels of homozygosity relative to mainland European levels. PCA targeted at specific areas of interest within Ireland also hint at fine-scale substructure. Conclusion Ireland shows typical features of a homogenous population, well suited to the study of rare variation in disease risk., Background Progress in diagnostic and therapeutic strategies in medicine is dependent upon high-quality biomedical research. Translation of research findings into the clinic relies on patient participation in innovative clinical trials. We investigated attitudes to genetic research in Ireland, in particular with respect to commercial and financial implications. Methods A multi-centre cross-sectional survey study was performed. Consecutive patients attending four out-patient clinics were asked to complete paper-based questionnaires. An electronic version of the same questionnaire was created on Survey Monkey with a link made public on a social media website for a period of 24 hours. Data was analysed using SPSS. Results 351 questionnaires were completed (99 paper, 252 electronic). The majority of respondents were female (n = 288, 82%), and highly educated, with 244 (70%) attending college/university. Most participants supported genetic research (267, 76%), more frequently for common diseases (274, 78%) than rare disorders (204, 58%, p < 0.001, x2). 103 (29%) had participated in scientific research, and 57(16%) had donated material to a bio-bank. The majority (n = 213, 61%) would not support research with potential financial/commercial gain. 106(30%) would decline to participate in research if researchers would benefit financially, compared to 49(14%) if the research was supported by a pharmaceutical company, (p < 0.001, x2). Respondents would provide buccal samples (258, 74%) more readily than tissue (225, 64%) or blood (222, 63%). Conclusion A high level of support for genetic research exists among the Irish population, but active participation is dependent upon a number of factors, notably, type of biological material required, frequency of the disease in question, and commercial interest of the researchers., Introduction Although the etiology of schizophrenia (SZ) is largely unknown, it is increasingly clear that genetic and environmental interactions contribute to cognitive deficits associated with this disorder. Recent Genome wide association studies (GWAS) have indicated a link between SZ and immune dysregulation, especially genetic mutations related to the major histocompatibility complex (MHC). Cognitive deficits are core features of Schizophrenia and related disorders, which relate to genetic risk. This study aims to explore the relationship between MHC risk variants for SZ and cognitive deficits, while also relating findings to brain activity. Methods To test if MHC risk variants impair cognition, ANCOVA analysis is performed on genetics data previously collected in a GWAS. Cognition measures are compared in groups with and without MHC genetic risk, in a population of SZ sufferers and healthy controls. Functional MRI imaging will also be performed to test if genetic risk relates to altered neural activity. Results Preliminary analyses suggest that MHC risk variants contribute to impairments in cognition in domains of social cognition, IQ and attention. Further analysis will be performed to test for environmental mediators of this relationship, looking at cannabis use and urbanicity. BOLD fMRI will also be used to test for a relationship between MHC risk and altered neural activity, using MATLAB SPM. Conclusions The MHC genetic variant may serve as a significant risk marker for schizophrenia, and further elucidate etiology of this neurodevelopmental disorder. Future studies on neurobiology of social cognition, and greater knowledge of genetic risk may establish targets for interventions., Aim To create a bioluminescence mouse model which expresses firefly luciferase in the corneal epithelium to assess gene editing and gene silencing for the cornea. Methods A gene targeting vector was generated where the Krt12 coding sequence in and the splice donor site of exon 1 were replaced with a transgene cassette containing a luc2-Multiple Targeting Cassette (MTC) gene fusion. The vector was transfected by electroporation into the Taconic Artemis C57BL/6N Tac ES cell line. Homologous recombinant clones were isolated and validated, and the mice bred with luc2-positive/ PuroR-negative offspring used for colony establishment. To visualise the expression of luc2 within the corneal epithelium, luciferin substrate diluted in viscotears was applied to the front of the eye and then luciferase expression was imaged and assessed using a Xenogen IVIS Lumina Imager and LivingImage 3.2 software. Intrastromal injection of siGlo siRNA was used to determine the localisation of siRNA within the corneal epithelium and then the established mouse model was treated with either native or Accell “self-delivery” siRNA. Results The Accell “self-delivery” siRNA induced potent sustained allele specific silencing for 7 days, while native versions of siRNA resulted in significant knock-down for 1 day only (p < 0.05). We have created and validated a bioluminescence mouse model and have utilised it to assess siRNA in vivo. This mouse model coupled with the Lumina imager will allow us to assess topical delivery of gene therapies to the ocular surface allowing validation for future translation to clinical use., Background Methylation of DNA sequences at promoters, CpG islands and other elements plays a vital role in regulating gene activity. In human, loss of methylation is known to play a causative role in imprinting disorders and in inappropriate germline gene expression in cancers. While in mouse, loss of function mutants have given great insight into the targets of methylation, functional studies in human have been largely limited to cancer cells and more recently stem cells, not normal adult cells. Methods Stable knockdowns of the maintenance methyltransferase DNMT1 were generated in normosomic hTERT-immortalised adult fibroblasts. Genome-wide methylation levels were assayed using the Illumina 450K bead array. Results were analysed using RnBeads and Galaxy. Locusspecific methylation was verified using pyrosequencing and clonal analysis. Validation was achieved using transient siRNA. Results Loss of function was poorly tolerated and all clonally-expanded cell lines had spontaneously restored DNMT1 levels by silencing of the shRNA. Evidence for a genome-wide methylation erasure event followed by a wave of remethylation could be clearly traced. Gene bodies and the shores of CpG islands showed the clearest loss of methylation overall. While most CpG islands are normally unmethylated and so unaffected, both imprints and germline genes fall into the rarer category of normally methylated islands: of these two, lasting loss of methylation was much more common among imprints than germline genes. Conclusions 1: transient loss of methylation is poorly tolerated; 2: a robust mechanism for remethylation exists even in adult cells; 3: aberrant remethylation is frequent on recovery and 4: Imprints are particularly sensitive., Background Dihydrofolate reductase (DHFR) is essential for the conversion of folic acid to active folate needed for one-carbon metabolism. Common genetic variation within DHFR is restricted to the noncoding regions and previous studies have focused on a 19 bp deletion/insertion polymorphism (rs70991108) within intron 1. Reports of an association between this polymorphism and blood folate biomarker concentrations are conflicting. Objective We aimed to evaluate whether the DHFR 19bp deletion/ insertion polymorphism affects circulating folate biomarkers in the largest cohort to address this question to date. Methods Young healthy Irish individuals (n= 2,507) between 19 to 36 years old were recruited between February 2003 and 2004. Folic acid intake from supplements and fortified foods was assessed using a customized food intake questionnaire. Concentrations of serum folate and vitamin B-12, red blood cell (RBC) folate and plasma total homocysteine (tHcy) concentration were measured. Data were analysed using linear regression models. Results Folic acid intake was positively associated with serum (P 326μg folic acid/day; P = 0.96). A non-significant trend towards lower RBC folate by genotype (P = 0.09) was observed in the lowest folic acid intake quintile (0 – 51 μg/day). Conclusion In this cohort of young healthy individuals the DHFR 19bp deletion allele does not significantly affect circulating folate status, irrespective of folic acid intake. Our data rule out a strong functional effect of this polymorphism on blood folate concentrations.

5th International Jellyfish Bloom Symposium, 30 May to 3 June 2016, Barcelona., Aurelia spp. are cosmopolitan scyphozoan species and probably the most studied jellyfish in the world. They inhabit nearshore waters, especially closed basins, such as coastal embayments, fjords and estuaries, occupying a great variety of habitats worldwide. Recent studies have addressed the biogeography of the genus Aurelia and reported that it constitutes a speciescomplex embracing numerous locally adapted species. The Mediterranean Sea is a hotspot of biodiversity threatened by climate change, which is expected to have a significant influence on the biodiversity and biogeography of marine populations. Here we compiled a comprehensive data set on Aurelia spp. occurrence in the Mediterranean Sea and assessed the thermal niches as well as the phenology of the various populations. Our results indicate that the species biogeography is restricted to temperate areas of the Mediterranean basin, whereas the seasonal pattern generally displayed an unimodal peak that occurs earlier in warmer systems. Our results highlight that the thermal niche of the species, where the bulk of the population (90%) is present, shows a temperature window from 12 to 20°C, although it is further constrained when accounting only for the northern populations of the western and Adriatic basins. Hence, while global warming has been claimed as one of the most important triggers for jellyfish outbreaks, the projected temperature increase of the Mediterranean Sea warns on the shrinking of favorable environmental conditions for the species with the concomitant risk of its potential decline and perhaps extinction in the Mediterranean Sea.

Obese women are more likely to require general anaesthesia for an obstetric intervention than non-obese. Difficult tracheal intubation and oxygen desaturation is more common in pregnancy. Failed tracheal intubation has been associated with an increase in neck circumference (NC). We studied the relationship between maternal obesity and NC as pregnancy advanced in women attending a standard antenatal clinic. Of the 96 women recruited, 13.5% were obese. The mean NC was 36.8cm (SD 1.9) in the obese women compared with 31.5cm (SD 1.6) in women with a normal BMI (pp

Cyclotides are plant peptides comprising a circular backbone and three conserved disulfide bonds that confer them with exceptional stability. They were originally discovered in Oldenlandia affinis based on their use in traditional African medicine to accelerate labor. Recently, cyclotides have been identified in numerous plant species of the coffee, violet, cucurbit, pea, potato, and grass families. Their unique structural topology, high stability, and tolerance to sequence variation make them promising templates for the development of peptide-based pharmaceuticals. However, the mechanisms underlying their biological activities remain largely unknown; specifically, a receptor for a native cyclotide has not been reported hitherto. Using bioactivity-guided fractionation of an herbal peptide extract known to indigenous healers as "kalata-kalata," the cyclotide kalata B7 was found to induce strong contractility on human uterine smooth muscle cells. Radioligand displacement and second messenger-based reporter assays confirmed the oxytocin and vasopressin V-1a receptors, members of the G protein-coupled receptor family, as molecular targets for this cyclotide. Furthermore, we show that cyclotides can serve as templates for the design of selective G protein-coupled receptor ligands by generating an oxytocin-like peptide with nanomolar affinity. This nonapeptide elicited dose-dependent contractions on human myometrium. These observations provide a proof of concept for the development of cyclotide-based peptide ligands.

Congenital convex pes valgus, frequently termed vertical talus in past descriptions, is a malformed foot that requires early diagnosis and treatment. A brief review of clinical features and a case presentation are provided to enhance the understanding of this complex deformity. A successful treatment regimen for infants and children is described, involving manipulation and early surgical correction.

An unusual case of suspected lateral subtalar joint dislocation was reported. A review of the literature found that medial dislocations were reported four times more frequently than lateral dislocations. Half of the cases of subtalar dislocation reviewed here described associated fractures, the incidence of which was higher in lateral dislocations. In both types of dislocations examined, almost half were reduced nonoperatively. In most cases, long-term results of repair of these injuries were considered favorable.

The authors present an in-depth discussion of Lisfranc's fracture-dislocations, including classifications, mechanisms of injury, radiographic evaluation, and a literature review. Four cases are presented for review. Lisfranc's fracture-dislocation is a rare injury that can lead to prolonged disability if undiagnosed or if there is a delay in treatment.