The Environmental Context and Function of Burnt-Mounds : New Studies of Irish Fulachtaí Fiadh

The authors acknowledge funding from The Leverhulme Trust (F/00144/AI) and assistance from a large number of individuals including; Margaret Gowen (access to sites and assistance throughout),A. Ames, H, Essex (pollen processing), S. Rouillard & R. Smith (illustrations), C. McDermott, S. Bergerbrandt, all the staff of Margaret Gowen & Co. Ltd, TVAS Ireland and CRDS. Excavation works and some post-excavation analysis was paid for my Bord Gáis and the National Roads Authority (now Transport Infrastructure Ireland). Thanks also to David Smith for access to the Maureen Girling collection and assistance with identifications.Peer reviewedPostprintPostprin

Functional characterization of T2D-associated SNP effects on baseline and ER stress-responsive β cell transcriptional activation.

Genome-wide association studies (GWAS) have linked single nucleotide polymorphisms (SNPs) at \u3e250 loci in the human genome to type 2 diabetes (T2D) risk. For each locus, identifying the functional variant(s) among multiple SNPs in high linkage disequilibrium is critical to understand molecular mechanisms underlying T2D genetic risk. Using massively parallel reporter assays (MPRA), we test the cis-regulatory effects of SNPs associated with T2D and altered in vivo islet chromatin accessibility in MIN6 β cells under steady state and pathophysiologic endoplasmic reticulum (ER) stress conditions. We identify 1,982/6,621 (29.9%) SNP-containing elements that activate transcription in MIN6 and 879 SNP alleles that modulate MPRA activity. Multiple T2D-associated SNPs alter the activity of short interspersed nuclear element (SINE)-containing elements that are strongly induced by ER stress. We identify 220 functional variants at 104 T2D association signals, narrowing 54 signals to a single candidate SNP. Together, this study identifies elements driving β cell steady state and ER stress-responsive transcriptional activation, nominates causal T2D SNPs, and uncovers potential roles for repetitive elements in β cell transcriptional stress response and T2D genetics

Direct Identification of Hundreds of Expression-Modulating Variants using a Multiplexed Reporter Assay

Although studies have identified hundreds of loci associated with human traits and diseases, pinpointing causal alleles remains difficult, particularly for non-coding variants. To address this challenge, we adapted the massively parallel reporter assay (MPRA) to identify variants that directly modulate gene expression. We applied it to 32,373 variants from 3,642 cis-expression quantitative trait loci and control regions. Detection by MPRA was strongly correlated with measures of regulatory function. We demonstrate MPRA’s capabilities for pinpointing causal alleles, using it to identify 842 variants showing differential expression between alleles, including 53 well-annotated variants associated with diseases and traits. We investigated one in detail, a risk allele for ankylosing spondylitis, and provide direct evidence of a non-coding variant that alters expression of the prostaglandin EP4 receptor. These results create a resource of concrete leads and illustrate the promise of this approach for comprehensively interrogating how non-coding polymorphism shapes human biology.National Institutes of Health (U.S.) (grant DP2OD006514)National Institutes of Health (U.S.) (grant K99HG0081)National Institutes of Health (U.S.) (grant R01HG006785

The environmental context and function of Burnt-Mounds: new studies of Irish Fulachtaí Fiadh

Burnt mounds, or fulachtaí fiadh as they are known in Ireland, are probably the most common prehistoric site type in Ireland and Britain. Typically Middle–Late Bronze Age in age (although both earlier and later examples are known), they are artefact-poor and rarely associated with settlements. The function of these sites has been much debated with the most commonly cited uses being for cooking, as steam baths or saunas, for brewing, tanning, or textile processing. A number of major infrastructural development schemes in Ireland in the years 2002–2007 revealed remarkable numbers of these mounds often associated with wood-lined troughs, many of which were extremely well-preserved. This afforded an opportunity to investigate them as landscape features using environmental techniques – specifically plant macrofossils and charcoal, pollen, beetles, and multi-element analyses. This paper summarises the results from eight sites from Ireland and compares them with burnt mound sites in Great Britain. The fulachtaí fiadh which are generally in clusters, are all groundwater-fed by springs, along floodplains and at the bases of slopes. The sites are associated with the clearance of wet woodland for fuel; most had evidence of nearby agriculture and all revealed low levels of grazing. Multi-element analysis at two sites revealed elevated heavy metal concentrations suggesting that off-site soil, ash or urine had been used in the trough. Overall the evidence suggests that the most likely function for these sites is textile production involving both cleaning and/or dyeing of wool and/or natural plant fibres and as a functionally related activity to hide cleaning and tanning. Whilst further research is clearly needed to confirm if fulachtaí fiadh are part of the ‘textile revolution’ we should also recognise their important role in the rapid deforestation of the wetter parts of primary woodland and the expansion of agriculture into marginal areas during the Irish and British Bronze Ages

Longitudinal change in the BODE index predicts mortality in severe emphysema

Rationale: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients. Objectives: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival. Methods: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components. Measurements and Main Results: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91943/1/2008 AJRCCM Longitudinal change in the BODE index predicts mortality in severe emphysema.pd

Report on the Workshop on Transversal Variables. (Linking economic and biological effort data (call) design). 19th -23rd January 2015

The Workshop on the Transversal Variables took place in Zagreb from the 19th to 23rd of January, 2015 mainly to tackle the issues related to the increasing need of having fisheries fleet economic data and fisheries biologic data on a level of disaggregation that would allow a proper interoperability between datasets to underpin bioeconomic modelling. For that, several analyses were carried out and conclusions taken. These analyses were : 1. comparison of economic and biological effort data calls both with respect to their level of resolution and the landings and effort values obtained from equivalent aggregations was performed. This was compared to what would be needed in order to undertake bioeconomic modelling for a chosen management plan. 2. The description of how MS are calculating effort variables and a proposal on the way forward to harmonize approaches, 3. Conclusions on how to harmonize levels of resolution, the variable definitions and the codification in use amongst data calls, in order to make them comparable and based on coherent standard codifications.JRC.G.3-Maritime affair

HERALD (Health Economics using Routine Anonymised Linked Data)

<b>Background</b> Health economic analysis traditionally relies on patient derived questionnaire data, routine datasets, and outcomes data from experimental randomised control trials and other clinical studies, which are generally used as stand-alone datasets. Herein, we outline the potential implications of linking these datasets to give one single joined up data-resource for health economic analysis.<p></p> <b>Method</b> The linkage of individual level data from questionnaires with routinely-captured health care data allows the entire patient journey to be mapped both retrospectively and prospectively. We illustrate this with examples from an Ankylosing Spondylitis (AS) cohort by linking patient reported study dataset with the routinely collected general practitioner (GP) data, inpatient (IP) and outpatient (OP) datasets, and Accident and Emergency department data in Wales. The linked data system allows: (1) retrospective and prospective tracking of patient pathways through multiple healthcare facilities; (2) validation and clarification of patient-reported recall data, complementing the questionnaire/routine data information; (3) obtaining objective measure of the costs of chronic conditions for a longer time horizon, and during the pre-diagnosis period; (4) assessment of health service usage, referral histories, prescribed drugs and co-morbidities; and (5) profiling and stratification of patients relating to disease manifestation, lifestyles, co-morbidities, and associated costs.<p></p> <b>Results</b> Using the GP data system we tracked about 183 AS patients retrospectively and prospectively from the date of questionnaire completion to gather the following information: (a) number of GP events; (b) presence of a GP 'drug' read codes; and (c) the presence of a GP 'diagnostic' read codes. We tracked 236 and 296 AS patients through the OP and IP data systems respectively to count the number of OP visits; and IP admissions and duration. The results are presented under several patient stratification schemes based on disease severity, functions, age, sex, and the onset of disease symptoms.<p></p> <b>Conclusion</b> The linked data system offers unique opportunities for enhanced longitudinal health economic analysis not possible through the use of traditional isolated datasets. Additionally, this data linkage provides important information to improve diagnostic and referral pathways, and thus helps maximise clinical efficiency and efficiency in the use of resources

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200