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

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

Effect of abrupt mitral regurgitation after balloon valvuloplasty on myocardial load and performance

AbstractThe concept that mitral regurgitation masks myocardial dysfunction by reducing afterload and augmenting ejection performance has not been well established in humans. The effect of abruptly produced mitral regurgitation on left ventricular loading and performance was therefore evaluated in five patients who developed this complication after an otherwise successful percutaneous balloon mitral valvuloplasty. Mitral valve area by Gorlin formula calculated with forward flow increased from 0.92 ± 0.14 to 2.75 ± 0.82 cm2. Mean left atrial pressure did not decrease (19 ± 4 to 19 ± 6 mm Hg). The size of the left atrial Vwave relative to mean left atrial pressure (peak V— mean left atrial pressure) increased from 7 ± 4 to 19 ± 6 mm Hg. Angiographic mitral regurgitation increased from 0+ or 1 + to >3+ in each patient and regurgitant fraction increased from 0.23 ± 0.11 to 0.55 ± 0.99 (p < 0.01).End-diastolic volume increased modestly from 148 ± 15 to 159 ± 15 ml (p = NS). Heart rate increased from 54 ± 5 to 71 ± 8 heats/min (p < 0.05), which may have prevented further increases in preload by shortening the filling period. End-systolic stress decreased by 32% from 277 ± 34 to 188 ± 52 kdyn/cm2(p < 0.01) as a result of a 25% decrease in end-systolic pressure from 121 ± 8 to 91 ± 7 mm Hg and a 16% decrease in end-systolic volume from 67 ± 13 to 56 ± 8 ml (p = NS). Contractility estimated from the preload-corrected ejection fraction-afterload relation decreased in one of the five patients and did not increase in the others despite an increase in heart rate, possibly as a result of myocardial depression from the balloon procedure itself. Nevertheless, the decrease in end-systolic volume could not be attributed to a net increase in contractility. The result of the changes in loading was an increase in ejection fraction from 0.55 ± 0.05 to 0.65 ± 0.04 (p < 0.05).Thus, abruptly produced mitral regurgitation increases ejection performance by reducing afterload without increasing contractility. This should be taken into consideration when anticipating the results of valve replacement for acute or subacute mitral regurgitation

An Empirical Comparison of Consumer Innovation Adoption Models: Implications for Subsistence Marketplaces

So called “pro-poor” innovations may improve consumer wellbeing in subsistence marketplaces. However, there is little research that integrates the area with the vast literature on innovation adoption. Using a questionnaire where respondents were asked to provide their evaluations about a mobile banking innovation, this research fills this gap by providing empirical evidence of the applicability of existing innovation adoption models in subsistence marketplaces. The study was conducted in Bangladesh among a geographically dispersed sample. The data collected allowed an empirical comparison of models in a subsistence context. The research reveals the most useful models in this context to be the Value Based Adoption Model and the Consumer Acceptance of Technology model. In light of these findings and further examination of the model comparison results the research also shows that consumers in subsistence marketplaces are not just motivated by functionality and economic needs. If organizations cannot enhance the hedonic attributes of a pro-poor innovation, and reduce the internal/external constraints related to adoption of that pro-poor innovation, then adoption intention by consumers will be lower

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Bog surface wetness records covering the mid-late Holocene at Assynt, Northwest Scotland

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