For over 120 years, the shell middens of western Scotland and the series of open-air sites on Oronsay have been the focus of debate in European Mesolithic studies. This paper challenges the significance of Oronsay in light of results from the geophysical survey and test-excavation of a new limpet and periwinkle shell midden dated to the late 5th or start of the 4th millennium cal bc at Port Lobh, Colonsay that offers fresh evidence to re-evaluate critically the role of Oronsay and coastal resources in island settlement models ahead of the Mesolithic–Neolithic transition. Test excavations recovered a marine molluscan assemblage dominated by limpet and periwinkle shells together with crab, sea urchin, a fishbone assemblage composed mainly of Gadidae, some identifiable bird and mammal bone, carbonised macroplant remains, and pumice as well as a bipolar lithic assemblage and coarse stone implements. Novel seasonality studies of saithe otolith thin-sections suggest wintertime tidal fishing practices. At least two activity events may be discerned, dating from the late 5th millennium cal bc. The midden could represent a small number of rapidly deposited assemblages or maybe the result of stocastic events within a more extended timeframe. We argue that alternative research questions are needed to advance long-standing debates about seasonal inter-island mobility versus island sedentism that look beyond Oronsay to better understand later Mesolithic occupation patterns and the formation and date of Oronsay middens. We propose alternative methodological strategies to aid identification of contemporaneous sites using geophysical techniques and lithic technological signatures.

Incidence of human yersiniosis in New Zealand has increased between 2013 and 2017. For surveillance and outbreak investigations it is essential that an appropriate level of discrimination between pathogenic Yersinia enterocolitica isolates is provided, in order to support epidemiological linking of connected cases. Subtyping of 227 Y. enterocolitica isolates was performed using a range of different typing methods, including biotyping, serotyping and seven loci multiple-locus variable-number tandem-repeat analysis (MLVA). In addition, core genome single-nucleotide polymorphism (core SNP) analysis and multi-locus sequence typing were performed on a subset of 69 isolates. Sixty-seven different MLVA types were identified. One MLVA profile was associated with an outbreak in the Bay of Plenty region, supported by epidemiological data. Core SNP analysis showed that all the outbreak-related isolates clustered together. The subtyping and epidemiological evidence suggests that the outbreak of yersiniosis in the Bay of Plenty region between October and December 2016 could be attributed to a point source. However, subtyping results further suggest that the same clone was isolated from several regions between August 2016 and March 2017. Core SNP analysis and MLVA typing failed to differentiate between Y. enterocolitica biotype 2 and biotype 3. For this reason, we propose that these biotypes should be reported as a single type namely: Y. enterocolitica biotype 2/3 and that the serotype should be prioritised as an indicator of prevalence.

This paper presents a review of the current status of photodiode array systems adapted for Energy Dispersive EXAFS (EDE) using a synchrotron radiation source. The performance of a conventional Reticon PDA is compared with that of a hybrid CCD. The specification of a new detector system for EDE is discussed in the light of experience gained with current linear detectors.

The last 12 years have seen the evolution of a new funding regime under the supervision of the Pensions Regulator. Over this period, there has been significant turbulence in financial markets, including record low interest rates. This paper takes a critical look at the development of funding approaches and methodologies over this period. It analyses the Pensions Regulator guidance and how scheme specific actuarial methods have emerged since the move away from the Minimum Funding Requirement in 2001 and the introduction of the Scheme Specific Funding Requirements in 2005. It asks whether these new methodologies have been successful from the perspective of members, trustees, employers and shareholders. At a time when actuarial valuation methodologies have faced considerable criticism, this paper aims to propose a pension funding methodology which is fit for purpose and also reflects the latest guidance from the Pensions Regulator on integrated risk management.

We recently reported an association of offspring educational attainment with polygenic risk scores (PRS) computed on parent’s non-transmitted alleles for educational attainment using the second GWAS meta-analysis article on educational attainment published by the Social Science Genetic Association Consortium. Here we test the replication of these findings using a more powerful PRS from the third GWAS meta-analysis article by the Consortium. Each of the key findings of our previous paper is replicated using this improved PRS (N = 2335 adolescent twins and their genotyped parents). The association of children’s attainment with their own PRS increased substantially with the standardized effect size, moving from β = 0.134, 95% CI = 0.079, 0.188 for EA2, to β = 0.223, 95% CI = 0.169, 0.278, p < .001, for EA3. Parent’s PRS again predicted the socioeconomic status (SES) they provided to their offspring and increased from β = 0.201, 95% CI = 0.147, 0.256 to β = 0.286, 95% CI = 0.239, 0.333. Importantly, the PRS for alleles not transmitted to their offspring — therefore acting via the parenting environment — was increased in effect size from β = 0.058, 95% CI = 0.003, 0.114 to β = 0.067, 95% CI = 0.012, 0.122, p = .016. As previously found, this non-transmitted genetic effect was fully accounted for by parental SES. The findings reinforce the conclusion that genetic effects of parenting are substantial, explain approximately one-third the magnitude of an individual’s own genetic inheritance and are mediated by parental socioeconomic competence.

Birth weight and early growth have been associated with later blood pressure. However, not all studies consistently find a significant reduction in blood pressure with an increase in birth weight. In addition, the relative importance of birth weight and of other lifestyle and environmental factors is often overlooked and the association is rarely studied in adolescents. We investigated early life predictors, including birth weight, of adolescent blood pressure in the Gateshead Millennium Study (GMS). The GMS is a cohort of 1029 individuals born in 1999–2000 in Gateshead in Northern England. Throughout infancy and early childhood, detailed information were collected, including birth weight and measures of height and weight. Assessments of 491 returning participants at age 12 years included measures of body mass and blood pressure. Linear regression and path analysis were used to determine predictors and their relative importance on blood pressure. Birth weight was not directly associated with blood pressure at the age of 12. However, after adjustment for contemporaneous body mass index (BMI), an inverse association of standardized birth weight on systolic blood pressure was significant. The relative importance of birth weight on later systolic blood pressure was smaller than other contemporaneous body measures (height and BMI). There was no independent association of birth weight on blood pressure seen in this adolescent population. Contemporaneous body measures have an important role to play. Lifestyle factors that influence body mass or size, such as diet and physical activity, where interventions are directed at early prevention of hypertension should be targeted.

Cancer-related fatigue (CRF) is one of the most commonly reported disease- and treatment-related side effects that impede quality of life. This systematic review and meta-analysis describes the effects of nutrition therapy on CRF and quality of life in people with cancer and cancer survivors. Studies were identified from four electronic databases until September 2017. Eligibility criteria included randomised trials in cancer patients and survivors; any structured dietary intervention describing quantities, proportions, varieties and frequencies of food groups or energy and macronutrient consumption targets; and measures of CRF and quality of life. Standardised mean differences (SMD) were pooled using random-effects models. The American Dietetic Association’s Evidence Analysis Library Quality Checklist for Primary Research was used to evaluate the methodological quality and risk of bias. A total of sixteen papers, of fifteen interventions, were included, comprising 1290 participants. Nutrition therapy offered no definitive effect on CRF (SMD 0·18 (95 % CI –0·02, 0·39)) or quality of life (SMD 0·07 (95 % CI –0·10, 0·24)). Preliminary evidence indicates plant-based dietary pattern nutrition therapy may benefit CRF (SMD 0·62 (95 % CI 0·10, 1·15)). Interventions using the patient-generated subjective global assessment tool and prescribing hypermetabolic energy and protein requirements may improve quality of life. However, the heterogeneity seen in study design, nutrition therapies, quality-of-life measures and cancer types impede definitive dietary recommendations to improve quality of life for cancer patients. There is insufficient evidence to determine the optimal nutrition care plan to improve CRF and/or quality of life in cancer patients and survivors.

We implemented a cross-sectional study in Tana River County, Kenya, a Rift Valley fever (RVF)-endemic area, to quantify the strength of association between RVF virus (RVFv) seroprevalences in livestock and humans, and their respective intra-cluster correlation coefficients (ICCs). The study involved 1932 livestock from 152 households and 552 humans from 170 households. Serum samples were collected and screened for anti-RVFv immunoglobulin G (IgG) antibodies using inhibition IgG enzyme-linked immunosorbent assay (ELISA). Data collected were analysed using generalised linear mixed effects models, with herd/household and village being fitted as random variables. The overall RVFv seroprevalences in livestock and humans were 25.41% (95% confidence interval (CI) 23.49–27.42%) and 21.20% (17.86–24.85%), respectively. The presence of at least one seropositive animal in a household was associated with an increased odds of exposure in people of 2.23 (95% CI 1.03–4.84). The ICCs associated with RVF virus seroprevalence in livestock were 0.30 (95% CI 0.19–0.44) and 0.22 (95% CI 0.12–0.38) within and between herds, respectively. These findings suggest that there is a greater variability of RVF virus exposure between than within herds. We discuss ways of using these ICC estimates in observational surveys for RVF in endemic areas and postulate that the design of the sentinel herd surveillance should consider patterns of RVF clustering to enhance its effectiveness as an early warning system for RVF epidemics.

OBJECTIVES/SPECIFIC AIMS: The purpose of this study was to characterize the pharmacokinetics of phosphatidylethanol (PEth) 16:0/20:4 homolog in uncoagulated, human blood samples taken from 18 participants in a clinical laboratory setting after consumption of 2 doses of ethanol. METHODS/STUDY POPULATION: Male and female participants received either 0.4 or 0.8 g/kg oral doses of ethanol during a 15-minute period. Blood samples were collected before and throughout 6 hours immediately after alcohol administration, then after 2, 4, 7, 11, and 14 days of administration day. PEth 16:0/20:4 levels were quantified by liquid mass spectrometry. Breath ethanol concentrations were measure concurrently with each blood collection during the administration day, as well as transdermal ethanol concentrations monitored constantly before, during and after ethanol administration day. RESULTS/ANTICIPATED RESULTS: (1) Single doses of 0.4 and 0.8 g ethanol/kg produced proportional increases in BrAC and PEth 16:0/20:4 levels; (2) the increase of Peth 16:0/20:4 from base line to Cmax was less than either PEth 16:0/18:1 or PEth 16:0/18:2 during the 6-hour period after ethanol administration; (3) the mean rate of formation of PEth 16:0/20:4 was lower than those of the other 2 homologs; (4) the mean half-life of PEth 16:0/20:4 was 2.18 days, which was shorter than that of either PEth 16:0/18:1 and PEth 16:0/18:2, which were 6.80 and 6.62, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study further confirm that PEth homologs are a sensitive biomarker for ethanol consumption. The measurement of three PEth homologs appears to provide additional information about the level and time frame of drinking.

Introduction: For patients with chest pain, the target time from first medical contact to obtaining an electrocardiogram (ECG) is 10 minutes, as reperfusion within 120 minutes can reduce the risk of death and adverse outcomes in patients with ST elevation myocardial infarction (STEMI). In 2007, Vancouver Coastal Health (VCH) began tracking key indicators including time to first ECG. The Vancouver General Hospital (VGH) Emergency Department (ED) has been troubled with the longest door to ECG times in the region since 2014. In 2016, the VGH ED Quality Council developed a strategy to address this issue, with an aim of obtaining ECGs on 95% of patients presenting to the VGH ED with active chest pain within 10 minutes of presentation within a 6 month period. Methods: The VGH ED Quality Council brought together frontline clinicians, ECG technicians, and other stakeholders and completed a process map. We obtained baseline data regarding the median time to ECG in both patients with STEMI and all patients presenting with chest pain. Root cause analysis determined two main barriers: access to designated space to obtain ECGs, and the need for patients to be registered in the computer system before an ECG could be ordered. The team identified strategies to eliminate these barriers, identifying a dedicated space and undergoing multiple PDSA cycles to change the workflow to stream patients to this space before registration. Results: Our median times in patients with STEMI have gone from 33 minutes to 8 minutes as of June 2017. In all patients presenting with chest pain, we improved from a median of 36 to 17 minutes. As of April 2017 we are obtaining an ECG within 10 minutes in 27% of our patients, compared to 3% in 2016. Given the limitations in our data extraction process, we were not able to differentiate between patients with active chest pain versus those whose chest pain had resolved. Conclusion: By involving frontline staff, and having frontline champions providing real time support, we were able to make significant changes to the culture at triage. We cultivated sustainability by changing the workflow and physical space, and not relying on education only. While we have improved the times for our walk-in patients, we have not perfected the process when a patient moves immediately to a bed or presents via ambulance. Implementing small changes and incorporating feedback has allowed us to identify these new challenges early.

Research on environmental and genetic pathways to complex traits such as educational attainment (EA) is confounded by uncertainty over whether correlations reflect effects of transmitted parental genes, causal family environments, or some, possibly interactive, mixture of both. Thus, an aggregate of thousands of alleles associated with EA (a polygenic risk score; PRS) may tap parental behaviors and home environments promoting EA in the offspring. New methods for unpicking and determining these causal pathways are required. Here, we utilize the fact that parents pass, at random, 50% of their genome to a given offspring to create independent scores for the transmitted alleles (conventional EA PRS) and a parental score based on alleles not transmitted to the offspring (EA VP_PRS). The formal effect of non-transmitted alleles on offspring attainment was tested in 2,333 genotyped twins for whom high-quality measures of EA, assessed at age 17 years, were available, and whose parents were also genotyped. Four key findings were observed. First, the EA PRS and EA VP_PRS were empirically independent, validating the virtual-parent design. Second, in this family-based design, children's own EA PRS significantly predicted their EA (β = 0.15), ruling out stratification confounds as a cause of the association of attainment with the EA PRS. Third, parental EA PRS predicted the SES environment parents provided to offspring (β = 0.20), and parental SES and offspring EA were significantly associated (β = 0.33). This would suggest that the EA PRS is at least as strongly linked to social competence as it is to EA, leading to higher attained SES in parents and, therefore, a higher experienced SES for children. In a full structural equation model taking account of family genetic relatedness across multiple siblings the non-transmitted allele effects were estimated at similar values; but, in this more complex model, confidence intervals included zero. A test using the forthcoming EA3 PRS may clarify this outcome. The virtual-parent method may be applied to clarify causality in other phenotypes where observational evidence suggests parenting may moderate expression of other outcomes, for instance in psychiatry.

Water wave overwash of a step by small steepness, regular incident waves is analysed using a computational fluid dynamics (CFD) model and a mathematical model, in two spatial dimensions. The CFD model is based on the two-phase, incompressible Navier–Stokes equations, and the mathematical model is based on the coupled potential-flow and nonlinear shallow-water theories. The CFD model is shown to predict vortices, breaking and overturning in the region where overwash is generated, and that the overwash develops into fast-travelling bores. The mathematical model is shown to predict bore heights and velocities that agree with the CFD model, despite neglecting the complicated dynamics where the overwash is generated. Evidence is provided to explain the agreement in terms of the underlying agreement of mass and energy fluxes.