Applying lead (Pb) isotopes to explore mobility in humans and animals.

Lead (Pb) isotopes provide a complementary method to other provenance tools for tracking the origin and movement of humans and animals. The method is founded in the geographic distribution of Pb isotope ratios. However, unlike the Sr isotope method that is closely linked to the lithology of underlying rocks, Pb more closely reflects the tectonic regimes. This makes it particularly pertinent to use in Britain as there is major tectonic boundary (the Iapetus Suture) that runs between Berwick-upon-Tweed and the Solway Firth providing a compositional boundary in Pb isotope domains that approximates to the geographic areas of Scotland versus England and Wales. Modern pollution makes it difficult to use modern floral or faunal samples to characterize biosphere variation, and so we use geological datasets to define isoscape variation and present the first Pb isotope map of Britain. We have validated the use of these data form biosphere studies using well provenanced samples. Reference fields of diagnostic compositions, are created in µ-T space and these have been used in a test case to assess the geographic origins of Neolithic animals in Great Britain.

Intestinal parasites in the Neolithic population who built Stonehenge (Durrington Walls, 2500 BCE).

Durrington Walls was a large Neolithic settlement in Britain dating around 2500 BCE, located very close to Stonehenge and likely to be the campsite where its builders lived during its main stage of construction. Nineteen coprolites recovered from a midden and associated pits at Durrington Walls were analysed for intestinal parasite eggs using digital light microscopy. Five (26%) contained helminth eggs, 1 with those of fish tapeworm (likely Dibothriocephalus dendriticus) and 4 with those of capillariid nematodes. Analyses of bile acid and sterol from these 5 coprolites show 1 to be of likely human origin and the other 4 to likely derive from dogs. The presence of fish tapeworm reveals that the Neolithic people who gathered to feast at Durrington Walls were at risk of infection from eating raw or undercooked freshwater fish. When the eggs of capillariids are found in the feces of humans or dogs it normally indicates that the internal organs (liver, lung or intestines) of animals with capillariasis have been eaten, and eggs passed through the gut without causing disease. Their presence in multiple coprolites provides new evidence that internal organs of animals were consumed. These novel findings improve our understanding of both parasitic infection and dietary habits associated with this key Neolithic ceremonial site.

Care in Europe after presenting to the emergency department with a seizure; position paper and insights from the European Audit of Seizure Management in Hospitals.

BACKGROUND AND PURPOSE: This position paper makes recommendations following an audit of care provided to people presenting with a seizure to emergency departments (EDs) in Europe. METHODS: Participating countries were asked to include five hospitals agreeing to identify 50 consecutive seizure patients presenting to their ED between 1 August 2016 and 31 August 2017. Anonymous data were collected to a web database. Where quoted, percentages are mean site values and ranges are the 10th-90th centile. RESULTS: Data were collected on 2204 ED visits (47 sites, up to six per country, across 15 countries): 1270 (58%) known epilepsy, 299 (14%) previous blackouts but no epilepsy diagnosis, 634 (29%) with a first seizure. Wide variability was identified for most variables. Of those with known epilepsy, 41.2% (range 26.2%-59.6%) attended the ED in the previous 12 months, but only 64.7% (range 37.2%-79.8%) had seen an epilepsy specialist in the previous 12 months. 67.7% (range 34.0%-100%) were admitted, 53.1% to a neurology ward (range 0.0%-88.9%). Only 37.5% first seizure patients (range 0.0%-71.4%) were given advice about driving. CONCLUSIONS AND RECOMMENDATIONS: It is recommended that in Europe guidance is agreed on the management and onward referral of those presenting to the ED with a seizure; a referral process is created that can be easily implemented; it is ensured that the seizure services receive referrals and see the patients within a short time period; and a simple system is developed and implemented to allow continuous monitoring of key indices of epilepsy care.

Clinical Impact of the Predict Prostate Risk Communication Tool in Men Newly Diagnosed with Nonmetastatic Prostate Cancer: A Multicentre Randomised Controlled Trial.

BACKGROUND: Predict Prostate is a freely available online personalised risk communication tool for men with nonmetastatic prostate cancer. Its accuracy has been assessed in multiple validation studies, but its clinical impact among patients has not hitherto been assessed. OBJECTIVE: To assess the impact of the tool on patient decision-making and disease perception. DESIGN, SETTING, AND PARTICIPANTS: A multicentre randomised controlled trial was performed across eight UK centres among newly diagnosed men considering either active surveillance or radical treatment. A total of 145 patients were included between 2018 and 2020, with median age 67 yr (interquartile range [IQR] 61-72) and prostate-specific antigen 6.8 ng/ml (IQR 5.1-8.8). INTERVENTION: Participants were randomised to either standard of care (SOC) information or SOC and a structured presentation of the Predict Prostate tool. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Validated questionnaires were completed by assessing the impact of the tool on decisional conflict, uncertainty, anxiety, and perception of survival. RESULTS AND LIMITATIONS: Mean Decisional Conflict Scale scores were 26% lower in the Predict Prostate group (mean = 16.1) than in the SOC group (mean = 21.7; p = 0.027). Scores on the "support", "uncertainty", and "value clarity" subscales all favoured Predict Prostate (all p < 0.05). There was no significant difference in anxiety scores or final treatment selection between the two groups. Patient perception of 15-yr prostate cancer-specific mortality (PCSM) and overall survival benefit from radical treatment were considerably lower and more accurate among men in the Predict Prostate group (p < 0.001). In total, 57% of men reported that the Predict Prostate estimates for PCSM were lower than expected, and 36% reported being less likely to select radical treatment. Over 90% of patients in the intervention group found it useful and 94% would recommend it to others. CONCLUSIONS: Predict Prostate reduces decisional conflict and uncertainty, and shifts patient perception around prognosis to be more realistic. This randomised trial demonstrates that Predict Prostate can directly inform the complex decision-making process in prostate cancer and is felt to be useful by patients. Future larger trials are warranted to test its impact upon final treatment decisions. PATIENT SUMMARY: In this national study, we assessed the impact of an individualised risk communication tool, called Predict Prostate, on patient decision-making after a diagnosis of localised prostate cancer. Men were randomly assigned to two groups, which received either standard counselling and information, or this in addition to a structured presentation of the Predict Prostate tool. Men who saw the tool were less conflicted and uncertain in their decision-making, and recommended the tool highly. Those who saw the tool had more realistic perception about their long-term survival and the potential impact of treatment upon this. TAKE HOME MESSAGE: The use of an individualised risk communication tool, such as Predict Prostate, reduces patient decisional conflict and uncertainty when deciding about treatment for nonmetastatic prostate cancer. The tool leads to more realistic perceptions about survival outcomes and prognosis.

Petrological and geochemical characterisation of the sarsen stones at Stonehenge.

Little is known of the properties of the sarsen stones (or silcretes) that comprise the main architecture of Stonehenge. The only studies of rock struck from the monument date from the 19th century, while 20th century investigations have focussed on excavated debris without demonstrating a link to specific megaliths. Here, we present the first comprehensive analysis of sarsen samples taken directly from a Stonehenge megalith (Stone 58, in the centrally placed trilithon horseshoe). We apply state-of-the-art petrographic, mineralogical and geochemical techniques to two cores drilled from the stone during conservation work in 1958. Petrographic analyses demonstrate that Stone 58 is a highly indurated, grain-supported, structureless and texturally mature groundwater silcrete, comprising fine-to-medium grained quartz sand cemented by optically-continuous syntaxial quartz overgrowths. In addition to detrital quartz, trace quantities of silica-rich rock fragments, Fe-oxides/hydroxides and other minerals are present. Cathodoluminescence analyses show that the quartz cement developed as an initial <10 µm thick zone of non-luminescing quartz followed by ~16 separate quartz cement growth zones. Late-stage Fe-oxides/hydroxides and Ti-oxides line and/or infill some pores. Automated mineralogical analyses indicate that the sarsen preserves 7.2 to 9.2 area % porosity as a moderately-connected intergranular network. Geochemical data show that the sarsen is chemically pure, comprising 99.7 wt. % SiO2. The major and trace element chemistry is highly consistent within the stone, with the only magnitude variations being observed in Fe content. Non-quartz accessory minerals within the silcrete host sediments impart a trace element signature distinct from standard sedimentary and other crustal materials. 143Nd/144Nd isotope analyses suggest that these host sediments were likely derived from eroded Mesozoic rocks, and that these Mesozoic rocks incorporated much older Mesoproterozoic material. The chemistry of Stone 58 has been identified recently as representative of 50 of the 52 remaining sarsens at Stonehenge. These results are therefore representative of the main stone type used to build what is arguably the most important Late Neolithic monument in Europe.

Redevelopment of the Predict: Breast Cancer website and recommendations for developing interfaces to support decision-making.

OBJECTIVES: To develop a new interface for the widely used prognostic breast cancer tool: Predict: Breast Cancer. To facilitate decision-making around post-surgery breast cancer treatments. To derive recommendations for communicating the outputs of prognostic models to patients and their clinicians. METHOD: We employed a user-centred design process comprised of background research and iterative testing of prototypes with clinicians and patients. Methods included surveys, focus groups and usability testing. RESULTS: The updated interface now caters to the needs of a wider audience through the addition of new visualisations, instantaneous updating of results, enhanced explanatory information and the addition of new predictors and outputs. A programme of future research was identified and is now underway, including the provision of quantitative data on the adverse effects of adjuvant breast cancer treatments. Based on our user-centred design process, we identify six recommendations for communicating the outputs of prognostic models including the need to contextualise statistics, identify and address gaps in knowledge, and the critical importance of engaging with prospective users when designing communications. CONCLUSIONS: For prognostic algorithms to fulfil their potential to assist with decision-making they need carefully designed interfaces. User-centred design puts patients and clinicians needs at the forefront, allowing them to derive the maximum benefit from prognostic models.

A changing estuary: Understanding historical patterns in salinity and fecal coliform levels in the May River, SC.

The May River, South Carolina watershed has undergone rapid increases in population and development from 1999 to 2017. This study aimed to understand the factors that influence salinity and fecal coliform levels in this estuary and how these levels changed from 1999 to 2017. This analysis revealed that salinity levels decreased in the headwaters, while variability increased. Additionally, fecal coliform increased from 1999 to 2017 throughout the hydrological network, with drastic changes occurring in the headwaters. Salinity and fecal coliform were influenced by spatial (distance from the mouth of the river), temporal (year, season, and tidal cycles), environmental (El Niño Southern Oscillation and rainfall), and anthropogenic parameters (population). This analysis suggests that the synergistic nature of climate change, resulting in more intense and frequent El Niño events, and watershed development may lead to further decreases in salinity and increases in fecal coliform levels in the May River estuary.

Implementation of a computer-guided consultation in the assessment of suspected obstructive sleep apnoea syndrome.

BACKGROUND: We describe implementation of a clinical decision support system, a computer-guided consultation (CGC), in the assessment of subjects referred with suspected obstructive sleep apnoea syndrome (OSAS). METHODS: Two cohorts of patients were assessed. The first 100 cases had data collected with the CGC by a specialist sleep physician (stage1). A further 100 cases were assessed by a nonspecialist using the CGC (stage 2). For each case, the diagnosis suggested by the CGC was compared with the final diagnosis made by a second specialist sleep physician blinded to the CGC diagnosis. RESULTS: Stage 1: of 100 people evaluated, a final diagnosis of OSAS was made by both the sleep specialist and CGC in 88% of cases. In 7 of the remaining 12 cases, both agreed there was "No evidence of OSAS"; in 5 cases the CGC did not reach a final diagnosis instead prompting specialist referral. Stage 2: 100 people were evaluated; 95% were evaluable. Both CGC and the sleep specialist made a diagnosis of OSAS in 83 cases (87%), in 5 cases both agreed there was no OSAS, whereas in 7 cases the CGC prompted a specialist review due to unexplained symptoms. The CGC was concordant with the final diagnosis in 95% and 93% of cases in the two cohorts, respectively and where there was doubt, prompted for clinical review. No OSAS cases were overlooked by the CGC. CONCLUSION: An intelligent CGC program creates opportunities in sleep medicine management pathways to safely yet effectively utilise nonspecialists working under specialist supervision.

Origins of the sarsen megaliths at Stonehenge.

The sources of the stone used to construct Stonehenge around 2500 BCE have been debated for over four centuries. The smaller "bluestones" near the center of the monument have been traced to Wales, but the origins of the sarsen (silcrete) megaliths that form the primary architecture of Stonehenge remain unknown. Here, we use geochemical data to show that 50 of the 52 sarsens at the monument share a consistent chemistry and, by inference, originated from a common source area. We then compare the geochemical signature of a core extracted from Stone 58 at Stonehenge with equivalent data for sarsens from across southern Britain. From this, we identify West Woods, Wiltshire, 25 km north of Stonehenge, as the most probable source area for the majority of sarsens at the monument.

Reducing variation in hospital mortality for alcohol-related liver disease in North West England.

BACKGROUND: Variations in emergency care quality for alcohol-related liver disease (ARLD) have been highlighted. AIM: To determine whether introduction of a regional quality improvement (QI) programme was associated with a reduction in potentially avoidable inpatient mortality. METHOD: Retrospective observational cohort study using hospital administrative data spanning a 1-year period before (2014/2015) and 3 years after a QI initiative at seven acute hospitals in North West England. The intervention included serial audit of a bundle of process metrics. An algorithm was developed to identify index ("first") emergency admissions for ARLD (n = 3887). We created a standardised mortality ratio (SMR) to compare relative mortality and regression models to examine risk-adjusted odds of death. RESULTS: In 2014/2015, three of seven hospitals had an SMR above the upper control limit ("outliers"). Adjusted odds of death for patients admitted to outlier hospitals was higher than non-outliers (OR 2.13, 95% CI 1.32-3.44, P = 0.002). Following the QI programme there was a step-wise reduction in outliers (none in 2017/2018). Odds of death was 67% lower in 2017/2018 compared to 2014/2015 at original outlier hospitals, but unchanged at other hospitals. Process audit performance of outliers was worse than non-outliers at baseline, but improved after intervention. CONCLUSIONS: There was a reduction in unexplained variation in hospital mortality following the QI intervention. This challenges the pessimism that is prevalent for achieving better outcomes for patients with ARLD. Notwithstanding the limitations of an uncontrolled observational study, these data provide hope that co-ordinated efforts to drive adoption of evidence-based practice can save lives.

Nationwide improvement in outcomes of emergency admission for ulcerative colitis in England, 2005-2013.

BACKGROUND: The UK IBD Audit Programme reported improved inpatient care processes for ulcerative colitis (UC) between 2005 and 2013. There are no independent data describing national or institutional trends in patient outcomes over this period. AIM: To assess the association between the outcome of emergency admission for UC and year of treatment. METHODS: Retrospective analysis of hospital administrative data, focused on all emergency admissions to English public hospitals with a discharge diagnosis of UC. We extracted case mix factors (age, sex, co-morbidity, emergency bed days in last year, deprivation status), outcomes of index admission (death and first surgery), 30-day emergency readmissions (all-cause, and selected causes) and outcome of readmission. RESULTS: There were 765 deaths and 3837 unplanned first operations in 44 882 emergency admissions, with 5311 emergency readmissions (with a further 171 deaths and 517 first operations). Case mix adjusted odds of death for any given year were 9% lower (OR 0.91, 95% CI: 0.89-0.94), and that for emergency surgery 3% lower (OR 0.97, 95% CI: 0.95-0.98) than the preceding year. Results were robust to sensitivity analysis (admissions lasting ≥4 days). There was no reduction in odds for all-cause readmission, but rates for venous thromboembolism declined significantly. Analysis of institutional-level metrics across 136 providers showed a stepwise reduction in outliers for mortality and unplanned surgery. CONCLUSIONS: Risk of death and unplanned surgery for UC patients admitted as emergencies declined consistently, as did unexplained variation between hospitals. Risk of readmission was unchanged (over 1 in 10). Multiple factors are likely to explain these nationwide trends.

Author Correction: Ancient genomes indicate population replacement in Early Neolithic Britain.

In the version of this Article originally published, there were errors in the colour ordering of the legend in Fig. 5b, and in the positions of the target and surrogate populations in Fig. 5c. This has now been corrected. The conclusions of the study are in no way affected. The errors have been corrected in the HTML and PDF versions of the article.

Ancient genomes indicate population replacement in Early Neolithic Britain.

The roles of migration, admixture and acculturation in the European transition to farming have been debated for over 100 years. Genome-wide ancient DNA studies indicate predominantly Aegean ancestry for continental Neolithic farmers, but also variable admixture with local Mesolithic hunter-gatherers. Neolithic cultures first appear in Britain circa 4000 BC, a millennium after they appeared in adjacent areas of continental Europe. The pattern and process of this delayed British Neolithic transition remain unclear. We assembled genome-wide data from 6 Mesolithic and 67 Neolithic individuals found in Britain, dating 8500-2500 BC. Our analyses reveal persistent genetic affinities between Mesolithic British and Western European hunter-gatherers. We find overwhelming support for agriculture being introduced to Britain by incoming continental farmers, with small, geographically structured levels of hunter-gatherer ancestry. Unlike other European Neolithic populations, we detect no resurgence of hunter-gatherer ancestry at any time during the Neolithic in Britain. Genetic affinities with Iberian Neolithic individuals indicate that British Neolithic people were mostly descended from Aegean farmers who followed the Mediterranean route of dispersal. We also infer considerable variation in pigmentation levels in Europe by circa 6000 BC.

Strontium isotope analysis on cremated human remains from Stonehenge support links with west Wales.

Cremated human remains from Stonehenge provide direct evidence on the life of those few select individuals buried at this iconic Neolithic monument. The practice of cremation has, however, precluded the application of strontium isotope analysis of tooth enamel as the standard chemical approach to study their origin. New developments in strontium isotopic analysis of cremated bone reveal that at least 10 of the 25 cremated individuals analysed did not spend their lives on the Wessex chalk on which the monument is found. Combined with the archaeological evidence, we suggest that their most plausible origin lies in west Wales, the source of the bluestones erected in the early stage of the monument's construction. These results emphasise the importance of inter-regional connections involving the movement of both materials and people in the construction and use of Stonehenge.

Understanding Children's Heart Surgery Data: A Cross-Disciplinary Approach to Codevelop a Website.

Risk-adjusted survival statistics after children's heart surgery are published annually in the United Kingdom. Interpreting these statistics is difficult, and better resources about how to interpret survival data are needed. Here we describe how a multidisciplinary team of mathematicians, psychologists, and a charity worked with parents of heart surgery children and other users to codevelop online resources to present survival outcomes. Early and ongoing involvement of users was crucial and considerably changed the content, scope, and look of the website, and the formal psychology experiments provided deeper insight. The website http://childrensheartsurgery.info/ was launched in June 2016 to very positive reviews.

Paramedics' views on their seizure management learning needs: a qualitative study in England.

INTRODUCTION: The UK ambulance service often attends to suspected seizures. Most persons attended to will not require the facilities of a hospital emergency department (ED) and so should be managed at scene or by using alternative care pathways. Most though are transported to ED. One factor that helps explain this is paramedics can have low confidence in managing seizures. OBJECTIVES: With a view to ultimately developing additional seizure management training for practicing paramedics, we explored their learning needs, delivery preferences and potential drivers and barriers to uptake and effectiveness. DESIGN AND SETTING: Semistructured interviews were conducted with a purposive sample of paramedics from the English ambulance service. Interviews were transcribed and thematically analysed. PARTICIPANTS: A diverse sample of 19 professionals was recruited from 5 different ambulance NHS trusts and the College of Paramedics. RESULTS: Participants said seizure management was neglected within basic and postregistration paramedic training. Most welcomed additional learning opportunities and identified gaps in knowledge. This included how to differentiate between seizure types and patients that do and do not need ED. Practical, interactive e-learning was deemed the most preferable delivery format. To allow paramedics to fully implement any increase in skill resulting from training, organisational and structural changes were said to be needed. This includes not penalising paramedics for likely spending longer on scene. CONCLUSIONS: This study provides the first evidence on the learning needs and preferences of paramedics regarding seizures. It can be used to inform the development of a bespoke training programme for paramedics. Future research should develop and then assess the benefit such training has on paramedic confidence and on the quality of care they offer to seizure patients.

Tooth enamel oxygen "isoscapes" show a high degree of human mobility in prehistoric Britain.

A geostatistical model to predict human skeletal oxygen isotope values (δ18Op) in Britain is presented here based on a new dataset of Chalcolithic and Early Bronze Age human teeth. The spatial statistics which underpin this model allow the identification of individuals interpreted as 'non-local' to the areas where they were buried (spatial outliers). A marked variation in δ18Op is observed in several areas, including the Stonehenge region, the Peak District, and the Yorkshire Wolds, suggesting a high degree of human mobility. These areas, rich in funerary and ceremonial monuments, may have formed focal points for people, some of whom would have travelled long distances, ultimately being buried there. The dataset and model represent a baseline for future archaeological studies, avoiding the complex conversions from skeletal to water δ18O values-a process known to be problematic.

Qualitative study of paramedics' experiences of managing seizures: a national perspective from England.

OBJECTIVES: The UK ambulance service is expected to now manage more patients in the community and avoid unnecessary transportations to hospital emergency departments (ED). Most people it attends who have experienced seizures have established epilepsy, have experienced uncomplicated seizures and so do not require the full facilities of an ED. Despite this, most are transported there. To understand why, we explored paramedics' experiences of managing seizures. DESIGN AND SETTING: Semistructured interviews were conducted with a purposive sample of paramedics from the English ambulance service. Interviews were transcribed and thematically analysed. PARTICIPANTS: A diverse sample of 19 professionals was recruited from 5 different ambulance NHS trusts and the College of Paramedics. RESULTS: Participants' confirmed how most seizure patients attended to do not clinically require an ED. They explained, however, that a number of factors influence their care decisions and create a momentum for these patients to still be taken. Of particular importance was the lack of access paramedics have to background medical information on patients. This, and the limited seizure training paramedics receive, meant paramedics often cannot interpret with confidence the normality of a seizure presentation and so transport patients out of precaution. The restricted time paramedics are expected to spend 'on scene' due to the way the ambulance services' performance is measured and that are few alternative care pathways which can be used for seizure patients also made conveyance likely. CONCLUSIONS: Paramedics are working within a system that does not currently facilitate non-conveyance of seizure patients. Organisational, structural, professional and educational factors impact care decisions and means transportation to ED remains the default option. Improving paramedics access to medical histories, their seizure management training and developing performance measures for the service that incentivise care that is cost-effective for all of the health service might reduce unnecessary conveyances to ED.

National Audit of Seizure management in Hospitals (NASH): results of the national audit of adult epilepsy in the UK.

OBJECTIVES: About 100,000 people present to hospitals each year in England with an epileptic seizure. How they are managed is unknown; thus, the National Audit of Seizure management in Hospitals (NASH) set out to assess prior care, management of the acute event and follow-up of these patients. This paper describes the data from the second audit conducted in 2013. SETTING: 154 emergency departments (EDs) across the UK. PARTICIPANTS: Data from 4544 attendances (median age of 45 years, 57% men) showed that 61% had a prior diagnosis of epilepsy, 12% other neurological problems and 22% were first seizure cases. Each ED identified 30 consecutive adult cases presenting due to a seizure. PRIMARY AND SECONDARY OUTCOME MEASURES: Details were recorded of the patient's prior care, management at hospital and onward referral to neurological specialists onto an online database. Descriptive results are reported at national level. RESULTS: Of those with epilepsy, 498 (18%) were on no antiepileptic drug therapy and 1330 (48%) were on monotherapy. Assessments were often incomplete and witness histories were sought in only 759 (75%) of first seizure patients, 58% were seen by a senior doctor and 57% were admitted. For first seizure patients, advice on further seizure management was given to 264 (27%) and only 55% were referred to a neurologist or epilepsy specialist. For each variable, there was wide variability among sites that was not explicable. For the sites who partook in both audits, there was a trend towards better care in 2013, but this was small and dwarfed by the intersite variability. CONCLUSIONS: These results have parallels with the Sentinel Audit of Stroke performed a decade earlier. There is wide intersite variability in care covering the entire care pathway, and a need for better organised and accessible care for these patients.