High-resolution sub-ice-shelf seafloor records of 20th-century ungrounding and retreat of Pine Island Glacier, West Antarctica.

Pine Island Glacier Ice Shelf (PIGIS) has been thinning rapidly over recent decades, resulting in a progressive drawdown of the inland ice and an upstream migration of the grounding line. The resultant ice loss from Pine Island Glacier (PIG) and its neighboring ice streams presently contributes an estimated ∼10% to global sea level rise, motivating efforts to constrain better the rate of future ice retreat. One route toward gaining a better understanding of the processes required to underpin physically based projections is provided by examining assemblages of landforms and sediment exposed over recent decades by the ongoing ungrounding of PIG. Here we present high-resolution bathymetry and sub-bottom-profiler data acquired by autonomous underwater vehicle (AUV) surveys beneath PIGIS in 2009 and 2014, respectively. We identify landforms and sediments associated with grounded ice flow, proglacial and subglacial sediment transport, overprinting of lightly grounded ice-shelf keels, and stepwise grounding line retreat. The location of a submarine ridge (Jenkins Ridge) coincides with a transition from exposed crystalline bedrock to abundant sediment cover potentially linked to a thick sedimentary basin extending upstream of the modern grounding line. The capability of acquiring high-resolution data from AUV platforms enables observations of landforms and understanding of processes on a scale that is not possible in standard offshore geophysical surveys

Osteoporosis and fracture risk - a linked data study in Wales

Introduction Osteoporosis is a global disease with a 30-40% lifetime fracture risk according to the World Health Organisation. Over half a million people receive treatment for fragility fractures annually in the UK. Osteoporosis incidence is rising with aging populations; however, medical secondary prevention treatment may reduce fracture risk. Objectives and Approach Primary aims were to investigate if secondary medical prevention treatment following an index fracture was associated with survival and subsequent fracture risk, evaluated using a pseudonymised population based e-cohort study design. Patients aged ≥60 years with an index fragility fracture at any anatomical location were identified from the Secure Anonymised Information Linkage (SAIL) databank. Fracture data were identified from secondary care datasets (emergency department and inpatient) and the National Hip Fracture Register data. In addition linkages were made to primary care datasets for medical prescription and Office for National Statistics records for mortality, supplementing data on demographic characteristics and co-morbidity. Results The cohort comprised 81,252 cases between April 2009 and December 2016 of median age 78 years (range 60-109) and 22,896 (28%) males. Medical secondary prevention treatment was received by 29,393 cases (36%). Subsequent fractures were reported for 10,907 cases (14%) and 29,026 cases (36%) died during the study period. For those that received medical prevention, the subsequent fracture and mortality rates were 15% and 28% respectively compared to 12% and 31% for those that did not receive the prevention treatment. Further analyses will include a discrete time competing risks model. Conclusion/Implications A population based e-cohort was successfully created by linking data across multiple datasets. Preliminary findings identified that <50% of eligible patients receive secondary medical prevention treatment after an index fragility fracture. These findings may help inform and unify treatment pathways for those at risk of fragility fractures

Cohort study of osteoporosis and fracture risk in Wales: does secondary prevention achieve any benefit?

Background Osteoporosis is a global disease with a 30-40% lifetime fracture risk according to the World Health Organisation. Incidence is rising with aging populations; however, medical secondary prevention treatment may reduce fracture risk. Objectives The primary aim was to investigate if secondary medical prevention treatment following an index fracture was associated with survival and subsequent fracture risk. Methods Patients aged ≥60 years with an index fragility fracture at any anatomical location were identified from the Secure Anonymised Information Linkage (SAIL) databank. A population based e-cohort was created by linking fracture data identified from secondary care datasets and the National Hip Fracture Register data, with linkages to primary care datasets for medical prescription and Office for National Statistics records for mortality. Findings The cohort comprised 81,252 cases between April 2009 and December 2016 of median age 78 years and 22,896 (28%) males. Medical secondary prevention treatment was received by 29,393 cases (36%). Subsequent fractures were reported for 10,907 cases (13%) and 29,026 cases (36%) died during the study period. Conclusions Preliminary findings identified that <50% of eligible patients receive secondary medical prevention treatment after an index fragility fracture. These findings may help inform and unify treatment pathways for those at risk of fragility fractures

Cognitive development Respiratory Tract Illness and Effects of eXposure (CORTEX) project: Data processing challenges in combining high spatial resolution pollution level data with individual level health and education data

Background and Objectives: There is a lack of evidence of the adverse effects of air pollution and pollen on cognition for people with air quality-related health conditions. The CORTEX project combined routinely collected health and education data, high spatial resolution air pollution modelling, and daily pollen measurements for 18,241 pupils living in Cardiff, UK, between 2009 and 2015, to investigate the acute effects of air quality and respiratory conditions on education attainment. Datasets: Air pollutants PM2.5, PM10, NO2, and ozone levels were modelled for 157,361 home and school locations, anonymised into the Secure Anonymised Information Linkage (SAIL) Databank, and summarised into minimum, average and maximum readings for 4 daily time periods reflecting pupil home/school exposure. Adding a unique Residential Anonymised Linking Field (RALF) allowed linkage of pollution estimates to individual level data. Annual pollution datasets contained 369 columns and 472,083-rows, with one column per location, pollutant, daily time-period and day of year. Dataset transformation produced a 5 column, 3,446,205,900-row matrix per year. Methods and Conclusions: An algorithm using Structured Query Language (SQL) to manage data held within a relational database management system, was designed to reduce dimensionality from 24 billion to 18,241 rows of data. The algorithm calculated average means for each pollutant (PM2.5, PM10, NO2, and ozone levels) over the revision and examination periods, and summarised data into one row per pupil. The algorithm adjusted for weekends, school, and bank holidays, it calculated daily pollutant exposure for each pupil, and successfully linked 95% of pupil pollution exposures to their health and education data

N-3 fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD

Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults and at present no licensed medication has been approved. Despite its complex patho-physiology, dietary strategies aiming at delaying or preventing NAFLD have taken a reductionist approach, examining the impact of single components. Accumulating evidence suggests that n-3 LC-PUFAs are efficacious in regulating lipogenesis and fatty acid oxidation. In addition, plant derived flavonoids are also emerging as a dietary strategy for NAFLD prevention, with efficacy attributed to their insulin sensitising and indirect antioxidant effects. Based on knowledge of their complementary molecular targets, we aimed to demonstrate that the combination of n-3 LC-PUFA (n-3) and flavan-3-ols (FLAV) prevents NAFLD. In a high-fat high-fructose (HF/HFr) fed C57Bl/6 J mouse model, the independent and interactive impact of n-3 and FLAV on histologically defined NAFLD, insulin sensitivity, weight gain, intestinal and hepatic gene expression, intestinal bile acids were examined. Only the combination of FLAV and n-3 (FLAVn-3) prevented steatosis as evidenced by a strong reduction in hepatocyte ballooning. While FLAV reduced body (− 28–30%), adipose tissue (− 45–50%) weights and serum insulin (− 22–25%) as observed following an intra-peritoneal glucose tolerance test, n-3 downregulated the expression of Srebf1 and the lipogenic genes (Acaca, Fasn). Significant impacts of interventions on intestinal bile acid metabolism, farnesoid X receptor (Fxr) signalling in the intestine and liver, and hepatic expression of fatty acid transporters (Fabp4, Vldlr, Cd36) were also evident. FLAVn-3 may be a novel intervention for NAFLD. Future research should aim to demonstrate its efficacy in the prevention and treatment of human NAFLD

Hydrolytic Reactivity Trends among Potential Prodrugs of the O2-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity

Glycosylated diazeniumdiolates of structure R2NN(O)dNO-R ′ (R ′ ) a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R2NN(O)dNO- ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R2NN(O)dNO-GlcNAc (where R2N) diethylamino or pyrrolidin-l-yl and GlcNAc) N-acetylglucosamin-l-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity

Is educational attainment associated with acute exposure to air pollution and pollen, and is it worse for pupils with asthma and seasonal allergic rhinitis?

Introduction There is a lack of evidence of the adverse effects of air pollution and pollen on cognition for people with air quality related health conditions. This study explored the effects of air quality and respiratory health conditions on educational attainment for 18,241 pupils across the city of Cardiff, United Kingdom. Objectives and Approach Anonymised, routinely collected health and education data were linked at the household and school level with modelled high spatial resolution pollution data, and daily pollen measurements using the Secure Anonymised Information Linkage (SAIL) databank. This created 7 repeated cross-sectional cohorts (2009-2015). Multilevel linear regression analysis examined whether exam performance was associated with health status and/or air quality levels averaged at school and home locations during revision and examination periods. We also investigated the combined effects of air quality and associations with educational attainment for pupils who were treated for asthma and/or Severe Allergic Rhinitis (SAR), and those who were not. Results The cohort contained 9337 males and 8904 female pupils. There were 871 treated for asthma, 2091 for SAR, and 634 treated for both. Asthma was not associated with exam performance (p=0.700). However, SAR was positively associated with exam performance (p 2) was negatively associated with educational attainment (p = 0.002). Other indicators of air quality (pollutants: Ozone, Particulate Matter - PM2.5, and pollen) were not associated with educational attainment (p> 0.05). Exposure to NO2 was negatively associated with educational attainment irrespective of treatment for asthma or SAR. There was no combined effect of air quality on the variation in educational attainment between those who are treated for asthma and/or SAR and those who were not. Conclusion/Implications Irrespective of health status, exposure to NO2 was negatively associated with educational attainment. Treatment seeking behaviour may be a possible explanation for the positive association between SAR and educational attainment. For a more accurate reflection of health status, health outcomes not subject to treatment seeking behaviour should be investigated

Are children who are treated for asthma and seasonal allergic rhinitis disadvantaged in their educational attainment when acutely exposed to air pollution and pollen? A feasibility study

Background There is a lack of evidence of the adverse effects which air quality has on cognition for people with air quality-related health conditions, these are not widely documented in the literature. Educational attainment, as a proxy for cognition, may increase with improved air quality. Objectives Prepare individual and household level linked environmental and health data for analysis within an anonymised safe haven; analyse the linked dataset for our study investigating: Cognition, Respiratory Tract illness and Effects of eXposure (CORTEX). Methods Anonymised, routinely collected health and education data were linked with high spatial resolution pollution measurements and daily pollen measurements to provide repeated cross-sectional cohorts (2009-2015) on 18,241 pupils across the city of Cardiff, using the SAIL databank. A fully adjusted multilevel linear regression analysis examined associations between health status and/or air quality. Cohort, school and individual level confounders were controlled for. We hope that using individual-level multi-location daily exposure assessment will help to clarify the role of traffic and prevent potential community-level confounding. Combined effects of air quality on variation in educational attainment between those treated for asthma and/or Severe Allergic Rhinitis (SAR), and those not treated, was also investigated. Findings Asthma was not associated with exam performance (p=0.7). However, SAR was positively associated with exam performance (p<0.001). Exposure to air pollution was negatively associated with educational attainment regardless of health status. Conclusions Irrespective of health status, air quality was negatively associated with educational attainment. Treatment seeking behaviour may explain the positive association between SAR and educational attainment. For a more accurate reflection of health status, health outcomes not subject to treatment seeking behaviours, such as emergency hospital admission, should be investigated

Creating individual level air pollution exposures in an anonymised data safe haven: a platform for evaluating impact on educational attainment

Introduction: There is a lack of evidence on the adverse effects of air pollution on cognition for people with air quality-related health conditions. We propose that educational attainment, as a proxy for cognition, may increase with improved air quality. This study will explore whether asthma and seasonal allergic rhinitis, when exacerbated by acute exposure to air pollution, is associated with educational attainment. Objective: To describe the preparation of individual and household-level linked environmental and health data for analysis within an anonymised safe haven. Also to introduce our statistical analysis plan for our study: COgnition, Respiratory Tract illness and Effects of eXposure (CORTEX). Methods: We imported daily air pollution and aeroallergen data, and individual level education data into the SAIL databank, an anonymised safe haven for person-based records. We linked individual-level education, socioeconomic and health data to air quality data for home and school locations, creating tailored exposures for individuals across a city. We developed daily exposure data for all pupils in repeated cross sectional exam cohorts (2009-2015). Conclusion: We have used the SAIL databank, an innovative, data safe haven to create individual-level exposures to air pollution and pollen for multiple daily home and school locations. The analysis platform will allow us to evaluate retrospectively the impact of air quality on attainment for multiple cross-sectional cohorts of pupils. Our methods will allow us to distinguish between the pollution impacts on educational attainment for pupils with and without respiratory health conditions. The results from this study will further our understanding of the effects of air quality and respiratory-related health conditions on cognition. Highlights: This city-wide study includes longitudinal routinely-recorded educational attainment data for all pupils taking exams over seven years;High spatial resolution air pollution data were linked within a privacy protected databank to obtain individual exposure at multiple daily locations;This study will use health data linked at the individual level to explore associations between air pollution, related morbidity, and educational attainment

Vaccinia extracellular virions enter cells by macropinocytosis and acid-activated membrane rupture

Double membrane-bound vaccinia extracellular virions actively promote their own macropinocytosis. This, followed by acid-induced rupture of the outer membrane in endocytic vesicles, exposes the inner membrane for fusion with the endocytic membrane and release into the cytosol