"...and they won land among the Picts by friendly treaty or the sword": How a re-examination of early historical sources and an analysis of early medieval settlement in north Co. Antrim confirms the validity of traditional accounts of Dál Riatic migration to Scotland from Ulster

Much recent scholarship has been critical of the concept of a Dál Riatic migration to, or colonisation of, Argyll. Scepticism of the accuracy of the early medieval accounts of this population movement, arguing that these are late amendments to early sources, coupled with an apparent lack of archaeological evidence for such a migration have led to its rejection. It is argued here, however, that this rejection has been based on too narrow a reading of historical sources and that there are several early accounts which, while differing in detail, agree on one point of substance, that the origin of Scottish Dál Riata lies in Ireland. Also, the use of archaeological evidence to suggest no migration to Argyll by the Dál Riata is flawed, misunderstanding the nature of early migrations and how they might be archaeologically identified, and it's proposed that there is actually quite a lot of evidence for migration to Argyll by the Dál Riata, in the form of settlement and artefactural evidence, but that it is to be found in Ireland through the mechanism of counterstream migration, rather than in Scotland./>

Intermarriage in a Divided Society: Ireland a Century Ago

This paper explores the characteristics associated with marriages between Roman Catholics and members of other religious denominations in Ireland before the Great War. Using the entire digitized returns of the 1911 population census, we find that such marriages were relatively rare, occurring in less than one percent of total marriages. Some of this infrequency can be attributed to ethno-religious hostility-especially in the north of the country. However, we also show that the rarity of intermarriage reflects local marriage markets, as non-Roman Catholics living in communities with fewer coreligionists were more likely to intermarry. We examine the individual characteristics of partners in these marriages, looking at the religious denomination of their children, their decision to marry out, and their fertility behavior. Our findings illustrate how the frequency of intermarriage reflects historical levels of intolerance, but only after local marriage market conditions have been accounted for.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.>

Hirschsprung's disease prevalence in Europe: A register based study

Background: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence, trends, and association with maternal age. <b style="margin: 0px; padding: 0px; border: 0px; outline: 0px; vertical-align: baseline; font-family: Arial, 'Lucida Grande', Geneva, Verdana, Helvetica, 'Lucida Sans Unicode', sans-serif; line-height: 18px; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">Methods:> Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population-based case-series. Prevalence rates and 95% confidence intervals were calculated as the number of cases per 10,000 births. Multilevel Poisson regression was performed to investigate trends in prevalence, geographical variation and the association with maternal age. <b style="margin: 0px; padding: 0px; border: 0px; outline: 0px; vertical-align: baseline; font-family: Arial, 'Lucida Grande', Geneva, Verdana, Helvetica, 'Lucida Sans Unicode', sans-serif; line-height: 18px; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">Results:> There were 1,322 cases of Hirschsprung's disease among 12,146,210 births. The total prevalence was 1.09 (95% confidence interval, 1.03–1.15) per 10,000 births and there was a small but significant increase in prevalence over time (relative risk = 1.01; 95% credible interval, 1.00–1.02; m style="margin: 0px; padding: 0px; border: 0px; outline: 0px; vertical-align: baseline; font-family: Arial, 'Lucida Grande', Geneva, Verdana, Helvetica, 'Lucida Sans Unicode', sans-serif; line-height: 18px; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">p</em> = 0.004). There was evidence of geographical heterogeneity in prevalence (<em style="margin: 0px; padding: 0px; border: 0px; outline: 0px; vertical-align: baseline; font-family: Arial, 'Lucida Grande', Geneva, Verdana, Helvetica, 'Lucida Sans Unicode', sans-serif; line-height: 18px; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">p</em> &lt; 0.001). Excluding 146 (11.0%) cases with chromosomal anomalies or genetic syndromes, there were 1,176 cases (prevalence = 0.97; 95% confidence interval, 0.91–1.03 per 10,000 births), of which 137 (11.6%) had major structural anomalies. There was no evidence of a significant increased risk of Hirschsprung's disease in cases born to women aged ≥35 years compared with those aged 25 to 29 (relative risk = 1.09; 95% credible interval, 0.91–1.31; m style="margin: 0px; padding: 0px; border: 0px; outline: 0px; vertical-align: baseline; font-family: Arial, 'Lucida Grande', Geneva, Verdana, Helvetica, 'Lucida Sans Unicode', sans-serif; line-height: 18px; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">p</em> = 0.355). <b style="margin: 0px; padding: 0px; border: 0px; outline: 0px; vertical-align: baseline; font-family: Arial, 'Lucida Grande', Geneva, Verdana, Helvetica, 'Lucida Sans Unicode', sans-serif; line-height: 18px; background-image: initial; background-attachment: initial; background-size: initial; background-origin: initial; background-clip: initial; background-position: initial; background-repeat: initial;">Conclusion:> This large population-based study found evidence of a small increasing trend in Hirschsprung's disease and differences in prevalence by geographic location. There was also no evidence of an association with maternal age.p>

Geographical differences in first acquisition of Pseudomonas aeruginosa in cystic fibrosis

RATIONALE: Risk of infection with Pseudomonas aeruginosa in cystic fibrosis (CF) may be associated with environmental factors.</p>

OBJECTIVES: To determine whether residential location is associated with risk of first acquisition of P. aeruginosa.</p>

METHODS: We performed bronchoalveolar lavage and upper airway cultures in children newly diagnosed with CF to identify infection with P. aeruginosa during infancy and early childhood. Children were assessed according to their residence in a regional or metropolitan area. Multilocus sequence typing was used to determine P. aeruginosa genotype. An environmental questionnaire was also administered.>>MEASUREMENTS AND MAIN RESULTS: A total of 105 of 120 (87.5%) infants diagnosed with CF were included in this study. Diagnosis in 65 infants (61.9%) followed newborn screening at mean age of 4.6 weeks. Sixty subjects (57.1%) were homozygous ΔF508, and 47 (44.8%) were female. Fifty-five (52.3%) infants were regional, of whom 26 (47.3%), compared with 9 of 50 (18.0%) metropolitan children, acquired infection with P. aeruginosa (odds ratio, 4.084; 95% confidence interval, 1.55-11.30). Age at acquisition was similar (regional: median, 2.31 yr; range, 0.27-5.96 yr; metropolitan: median, 3.10 yr, range, 0.89-3.70 yr). Strain typing identified P. aeruginosa genotypes often encountered in different ecological settings and little evidence of cross-infection. Ninety questionnaires (85.7%) were completed. Those who acquired P. aeruginosa were more likely to be living in a household that used water sprinkler systems (P = 0.032), but no differences were identified to explain increased risk of acquisition of P. aeruginosa in regional children.</p>

CONCLUSIONS: Geographical difference in residence of children with CF was associated with increased risk of first acquisition of P. aeruginosa, usually with strains associated with the environment rather than with cross-infection.</p>

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P &lt; 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.</p>

Impact of geometric variations on delivered dose in highly focused single vocal cord IMRT

Purpose. To investigate the robustness of single vocal cord intensity modulated radiation therapy (IMRT) treatment plans for set-up errors, respiration, and deformation. Material and methods. Four-dimensional computed tomography (4D-CT) scans of 10 early glottic carcinoma patients, previously treated with conventional techniques, were used in this simulation study. For each patient a pre-treatment 4D-CT was used for IMRT planning, generating a reference dose distribution. Prescribed PTV dose was 66 Gy. The impact of systematic set-up errors was simulated by applying shifts of ± 2 mm to the planning CT scans, followed by dose re-calculation with original beam segments, MUs, etc. Effects of respiration and deformation were determined utilizing extreme inhale and exhale CT scans, and repeat scans acquired after 22 Gy, 44 Gy, and 66 Gy, respectively. All doses were calculated using Monte Carlo dose simulations. Results. Considering all investigated geometrical perturbations, reductions in the clinical target volume (CTV) V95%, D98%, D2%, and generalized equivalent uniform dose (gEUD) were limited to 1.2 ± 2.2%, 2.4 ± 2.9%, 0.2 ± 1.8%, and 0.6 ± 1.1 Gy, respectively. The near minimum dose, D98%, was always higher than 89%, and gEUD always remained higher than 66 Gy. Planned contra-lateral (CL) vocal cord DMean, gEUD, and V40 Gy were 38.2 ± 6.0 Gy, 43.4 ± 5.6 Gy, and 42.7 ± 14.9%. With perturbations these values changed by -0.1 ± 4.3 Gy, 0.1 ± 4.0 Gy, and -1.0 ± 9.6%, respectively. Conclusions. On average, CTV dose reductions due to geometrical perturbations were very low, and sparing of the CL vocal cord was maintained. In a few observations (6 of 103 simulated situations), the near-minimum CTV-dose was around 90%, requiring attention in deciding on a future clinical protocol. p>

Novel Hypoxia-Associated Markers of Chemoresistance in Ovarian Cancer

Background:<br/>Ovarian cancer is the fifth leading cause of cancer in women and has poor/>long-term survival, in part, due to chemoresistance. Tumour hypoxia is associated with/>chemoresistance in ovarian cancer. However, relatively little is known about the genes/>activated in ovarian cancer which cause chemoresistance due to hypoxia. This studyr/>aimed to firstly identify genes whose expression is associated with hypoxia-induced<br/>chemoresistance, and secondly select hypoxia-associated biomarkers and evaluate theirr/>expression in ovarian tumours./>Design:/>Cisplatin-sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer<br/>cell lines were exposed to combinations of hypoxia and/or cisplatin as part of a matrixr/>designed to reflect clinically relevant scenarios. RNA was extracted and interrogatedr/>on Affymetrix Human Gene arrays. Differential gene expression was analysed for cells/>exposed to hypoxia and/or treated with cisplatin. Potential markers of chemoresistancer/>were selected for evaluation in a cohort of ovarian tumour samples by R/>T-PCR.<br/>Results:/>A wide range of genes associated with chemoresistance were differentially/>expressed in cells exposed to hypoxia and/or cisplatin. Selected genes [ANGPTL4,/>HER3 and HIF-1r/>α<br/>] were chosen for further validation in a cohort of ovarian tumourr/>samples. High expression of ANGPTL4 trended towards reduced progression-free and<br/>overall survival. High expression of HER3 trended to increased progression-free but/>reduced overall survival, while high expression of HIF-1/>αr/>trended towards reduced<br/>progression-free and increased overall survival./>Conclusions:<br/>In conclusion, this study has further characterized the relationship betweenr/>hypoxia and chemoresistance in an ovarian cancer model. We have also identified manyr/>potential biomarkers of hypoxia and platinum resistance and provided initial validation/>of a subset of these markers in ovarian cancer tissues.

Using Brain Data for Sentiment Analysis

We present the results of exploratory experiments using lexical valence extracted from brain using electroencephalography (EEG) for sentiment analysis. We selected 78 English words (36 for training and 42 for testing), presented as stimuli to 3 English native speakers. EEG signals were recorded from the subjects while they performed a mental imaging task for each word stimulus. Wavelet decomposition was employed to extract EEG features from the time-frequency domain. The extracted features were used as inputs to a sparse multinomial logistic regression (SMLR) classifier for valence classification, after univariate ANOVA feature selection. After mapping EEG signals to sentiment valences, we exploited the lexical polarity extracted from brain data for the prediction of the valence of 12 sentences taken from the SemEval-2007 shared task, and compared it against existing lexical resources.

New design of a multi-jet target for quasi phase matching

An improved dual-gas quasi-phase matching (QPM) foil target for high harmonic generation (HHG) is presented. The target can be setup with 12 individual gas inlets each feeding multiple nozzles separated by a minimum distance of 10 μm. Three-dimensional gas density profiles of these jets were measured using a Mach-Zehnder Interferometer. These measurements reveal how the jets influence the density of gas in adjacent jets and how this leads to increased local gas densities. The analysis shows that the gas profiles of the jets are well defined up to a distance of about 300 μm from the orifice. This target design offers experimental flexibility, not only for HHG/QPM investigations, but also for a wide range of experiments due to the large number of possible jet configurations. We demonstrate the application to controlled phase tuning in the extreme ultraviolet using a 1 kHz-10 mJ-30 fs-laser system where interference between two jets in the spectral range from 17 to 30 nm was observed.</p>

Metabolic signatures of human Alzheimer's disease (AD): H-1 NMR analysis of the polar metabolome of post-mortem brain tissue

Brain tissue from so-called Alzheimer's disease (AD) mouse models has previously been examined using H-1 NMR-metabolomics, but comparable information concerning human AD is negligible. Since no animal model recapitulates all the features of human AD we undertook the first H-1 NMR-metabolomics investigation of human AD brain tissue. Human post-mortem tissue from 15 AD subjects and 15 age-matched controls was prepared for analysis through a series of lyophilised, milling, extraction and randomisation steps and samples were analysed using H-1 NMR. Using partial least squares discriminant analysis, a model was built using data obtained from brain extracts. Analysis of brain extracts led to the elucidation of 24 metabolites. Significant elevations in brain alanine (15.4 %) and taurine (18.9 %) were observed in AD patients (p ≤ 0.05). Pathway topology analysis implicated either dysregulation of taurine and hypotaurine metabolism or alanine, aspartate and glutamate metabolism. Furthermore, screening of metabolites for AD biomarkers demonstrated that individual metabolites weakly discriminated cases of AD [receiver operating characteristic (ROC) AUC &lt;0.67; p &lt; 0.05]. However, paired metabolites ratios (e.g. alanine/carnitine) were more powerful discriminating tools (ROC AUC = 0.76; p &lt; 0.01). This study further demonstrates the potential of metabolomics for elucidating the underlying biochemistry and to help identify AD in patients attending the memory clinic