Opening the Woods: Towards a Quantification of Neolithic Clearance Around the Somerset Levels and Moors

Environmental reconstructions from pollen records collected within archaeological landscapes have traditionally taken a broadly narrative approach, with few attempts made at hypothesis testing or formal assessment of uncertainty. This disjuncture between the traditional interpretive approach to palynological data and the requirement for detailed, locally specific reconstructions of the landscapes in which people lived has arguably hindered closer integration of palaeoecological and archaeological datasets in recent decades. Here we implement a fundamentally different method for reconstructing past land cover from pollen records to the landscapes of and around the Somerset Levels and Moors — the Multiple Scenario Approach (MSA) — to reconstruct land cover for a series of 200-year timeslices covering the period 4200–2000 cal BC. Modelling of both archaeological and sediment chronologies enables integration of reconstructed changes in land cover with archaeological evidence of contemporary Neolithic human activity. The MSA reconstructions are presented as a series of land cover maps and as graphs of quantitative measures of woodland clearance tracked over time. Our reconstructions provide a more nuanced understanding of the scale and timing of Neolithic clearance than has previously been available from narrative based interpretations of pollen data. While the archaeological record tends to promote a view of long-term continuity in terms of the persistent building of wooden structures in the wetlands, our new interpretation of the palynological data contributes a more dynamic and varying narrative. Our case study demonstrates the potential for further integration of archaeological and palynological datasets, enabling us to get closer to the landscapes in which people lived

Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma

RATIONALE: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. OBJECTIVES: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. METHODS: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. MEASUREMENTS AND MAIN RESULTS: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P \u3c 3.53 × 10 CONCLUSIONS: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations

Whole-genome sequencing of pharmacogenetic drug response in racially diverse children with asthma

RATIONALE: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response. OBJECTIVES: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children. METHODS: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR. MEASUREMENTS AND MAIN RESULTS: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P \u3c 3.53 × 10-7) and suggestive (P \u3c 7.06 × 10-6) loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and β-adrenergic signaling (ADAMTS3 and COX18). Functional analyses of the BDR-associated SNP in NFKB1 revealed potential regulatory function in bronchial smooth muscle cells. The SNP is also an expression quantitative trait locus for a neighboring gene, SLC39A8. The lack of other asthma study populations with BDR and whole-genome sequencing data on minority children makes it impossible to perform replication of our rare variant associations. Minority underrepresentation also poses significant challenges to identify age-matched and population-matched cohorts of sufficient sample size for replication of our common variant findings. CONCLUSIONS: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations

Beta-HPV E6 Contributes To Skin Cancer by Hindering DNA Repair

<div><p>Recent work has explored a putative role for the E6 protein from some β-human papillomavirus genus (β-HPVs) in the development of non-melanoma skin cancers, specifically β-HPV 5 and 8 E6. Because these viruses are not required for tumor maintenance, they are hypothesized to act as co-factors that enhance the mutagenic capacity of UV-exposure by disrupting the repair of the resulting DNA damage. Supporting this proposal, we have previously demonstrated that UV damage signaling is hindered by β-HPV 5 and 8 E6 resulting in an increase in both thymine dimers and UV-induced double strand breaks (DSBs). Here we show that β-HPV 5 and 8 E6 further disrupt the repair of these DSBs and provide a mechanism for this attenuation. By binding and destabilizing a histone acetyltransferase, p300, β-HPV 5 and 8 E6 reduce the enrichment of the transcription factor at the promoter of two genes critical to the homology dependent repair of DSBs (BRCA1 and BRCA2). The resulting diminished BRCA1/2 transcription not only leads to lower protein levels but also curtails the ability of these proteins to form repair foci at DSBs. Using a GFP-based reporter, we confirm that this reduced foci formation leads to significantly diminished homology dependent repair of DSBs. By deleting the p300 binding domain of β-HPV 8 E6, we demonstrate that the loss of robust repair is dependent on viral-mediated degradation of p300 and confirm this observation using a combination of p300 mutants that are β-HPV 8 E6 destabilization resistant and p300 knock-out cells. In conclusion, this work establishes an expanded ability of β-HPV 5 and 8 E6 to attenuate UV damage repair, thus adding further support to the hypothesis that β-HPV infections play a role in skin cancer development by increasing the oncogenic potential of UV exposure.</p></div

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Mastering Linked Datasets: The Future of Emergency Health Care Research

Objectives: The aim of this work is to describe routine integration of prehospital emergency health records into a health master linkage file, delivering ongoing access to integrated patient treatment and outcome information for ambulance-attended patients in Queensland. Methods: The Queensland Ambulance Service (QAS) data are integrated monthly into the Queensland Health Master Linkage File (MLF) using a linkage algorithm that relies on probabilistic matches in combination with deterministic rules based on patient demographic details, date, time and facility identifiers. Each ambulance record is assigned an enduring linkage key (unique patient identifier) and further processing determines whether each record matches with a corresponding hospital emergency department, admission or death registry record. In this study, all QAS electronic ambulance report form (eARF) records from October 2016 to December 2018 where at least 1 key linkage variable was present (n = 1,771,734) were integrated into the MLF. Results: The majority of records (n = 1,456,502; 82.2%) were for transported patients, and 90.1% (n = 1,312,176) of these transports were to public hospital facilities. Of these transport records, 93.9% (n = 1,231,951) matched to emergency department (ED) records and 59.3% (n = 864,394) also linked to admitted patient records. Of ambulance non-transport records integrated into the MLF, 23.6% (n = 74,311) matched with ED records. Conclusion: This study demonstrates robust linkage methods, quality assurance processes and high linkage rates of data across the continuum of care (prehospital/emergency department/admitted patient/death) in Queensland. The resulting infrastructure provides a high-quality linked dataset that facilitates complex research and analysis to inform critical functions such as quality improvement, system evaluation and design

Pre-hospital and emergency department pathways of care for exacerbations of chronic obstructive pulmonary disease (COPD)

Exacerbations are serious complications of chronic obstructive pulmonary disease (COPD) that often require acute care from pre-hospital and emergency department (ED) services. Despite being a frequent cause of emergency presentations, gaps remain in both literature and practice for emergency care pathways of COPD exacerbations. This review seeks to address these gaps and focuses on the literature of pre-hospital and ED systems of care and how these intersect with patients experiencing an exacerbation of COPD. The literature in this area is expanding rapidly; however, more research is required to further understand exacerbations and how they are addressed by emergency medical services worldwide. For the purpose of this review, the pre-hospital domain includes ambulance and other emergency transport services, and encompasses medical interventions delivered prior to arrival at an ED or hospital. The ED domain is defined as the area of a hospital or free-standing centre where patients arrive to receive emergent medical care prior to admission. In many studies there is a significant overlap between these two domains and frequent intersection and collaboration between services. In both of these domains, for the management of COPD exacerbations, several overarching themes have been identified in the literature. These include: the appropriate delivery of oxygen in the emergency setting; strategies to improve the provision of care in accordance with diagnostic and treatment guidelines; strategies to reduce the requirement for emergency presentations; and, technological advances including machine learning which are helping to improve emergency healthcare systems

Insights into the epidemiology of cardiopulmonary resuscitation-induced consciousness in out-of-hospital cardiac arrest

Objectives To describe the characteristics and outcomes of cardiopulmonary resuscitation (CPR)-induced consciousness patients from a large database of out-of-hospital cardiac arrest (OHCA). Methods Included were adult patients, attended between January 2007 and December 2018 by the Queensland Ambulance Service, where resuscitation was attempted by paramedics. Manual review of records was undertaken to identify CPR-induced consciousness cases. Patients exhibiting purposeful limb/body movement during CPR, with or without displaying other signs, were considered to be CPR-induced consciousness. Characteristics and outcomes of CPR-induced consciousness patients were compared to those without CPR-induced consciousness. Results A total of 23 011 OHCA patients were included; of these, 52 (0.23%) were CPR-induced consciousness. This translates into an incidence rate of 2.3 cases per 1000 adult resuscitation attempts over 12 years. Combativeness/agitation was the most common sign of CPR-induced consciousness, described in 34.6% (18/52) of patients. CPR-induced consciousness patients had numerically higher rates of return of spontaneous circulation on hospital arrival (51.9% vs 28.6%), discharge survival (46.2% vs 15.1%) and 30-day survival (46.2% vs 14.7%), than those without CPR-induced consciousness; however, CPR-induced consciousness was not found to be an independent predictor of survival. Higher proportions of CPR-induced consciousness patients had arrest witnessed by paramedics, occurring in public places, of cardiac aetiology and initial shockable rhythm, than patients without CPR-induced consciousness. Conclusions CPR-induced consciousness in OHCA appears to be associated with higher survival rates. Standardised guidelines on recognition and management of CPR-induced consciousness remain to be established

Suicide crisis calls to emergency services: Cohort profile and findings from a data linkage study in Queensland, Australia

Background and Aims: Police and paramedics play a crucial role in responding to suicide crises in the community. However, little is known about the nature, extent, precipitating factors, pathways and outcomes of a suicide-related call to emergency services and what responses will most effectively and compassionately meet the needs of those in crisis. Partners in Prevention: Understanding and Enhancing First Responses to Suicide Crisis Situations (PiP) was established to address these knowledge gaps. Methods: This article describes (1) the methodology used to construct the PiP dataset, a population-wide linked dataset that investigates the characteristics and health pathways of individuals in Queensland who were the subject of a suicide-related call to police or paramedics; and (2) preliminary findings on service demand, demographics and health services utilisation. Results: We identified 219,164 suicide-related calls to Queensland Police Service or Queensland Ambulance Service that were made over the 3-year period 1 February 2014 to 31 January 2017. A total of 70,893 individuals were identifiable via records linkage. The cohort linked to more than 7,000,000 health records. We estimated that police or paramedics in Queensland received on average 209 calls per day, with increases year on year over the study period. Analysis of demographic data highlighted the heterogeneous nature of this cohort and important demographic variations between individuals in contact with police versus ambulance services. Discussion: The PiP dataset provides a strong foundation for a multi-modal dataset that can be built on over time, both cross-sectionally and longitudinally. Further linkages to Medicare Benefits Schedule, Pharmaceutical Benefits Scheme and social care datasets are planned. Conclusion: Detailed population-level analysis that data linkage can provide is critical to improving understanding and responses to suicide crisis situations. The PiP study is a world first and provides a unique opportunity to improve responses to this public health problem.</p

The clinical journey of patients with a severe exacerbation of chronic obstructive pulmonary disease (COPD): from the ambulance to the emergency department to the hospital ward

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are acute complications that often require emergency management by ambulance, emergency department (ED) and hospital services. Given the high mortality and morbidity of exacerbations, better understanding of the epidemiology of patients with COPD presenting to EDs is needed, as well as identification of predictive factors for adverse outcomes from exacerbations. Methods: This retrospective observational study involved patients who presented to an ED in the state of Queensland and received either an ED or hospital diagnosis of COPD in 2015 and 2016. Administrative data from ambulance, ED, hospital and death registry databases were linked to provide a comprehensive picture of the emergency healthcare pathway for these patients. Results: A total of 16,166 patients (49% female, 51% male) had 29,332 presentations to an ED in Queensland and received either an ED or hospital principal diagnosis of COPD during 2015 and 2016. These patients had a significant comorbidity burden with 54% having two or more comorbidities. Sixty-nine percent of ED presentations involved ambulance transport, and most of these (74%) involved administration of oxygen therapy and/or other medications by paramedics. Prehospital oxygen administration and ≥10 comorbidities were associated with >1 admission [odds ratio (OR) 1.3, 95% confidence interval (CI) 1.1–1.5; OR 4.3, 95% CI: 3.1–5.8, respectively], greater than average lengths of stay (OR 1.5, 95% CI: 1.3–1.6; OR 22.1, 95% CI: 18.1–27.2) and mortality (OR 1.6, 95% CI: 1.5–1.8; OR 5.3, 95% CI: 4.2–6.8). Of the ambulance presentations, 90% were admitted or received ongoing care. Conclusions: COPD places considerable burden on the emergency healthcare pathway including ambulances and EDs in Queensland. Patients with COPD most commonly present to the ED by ambulance and receive extensive pre-hospital management. These patients have significant comorbidity burden and experience high rates of admission and mortality. More research is required to investigate the emergency pathway to further identify reversible factors and enhance healthcare practice and policy for COPD management.</p