Glycoprotein IIb/IIIa Inhibitors Use and Outcome after Percutaneous Coronary Intervention for Non-ST Elevation Myocardial Infarction

Aims. We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors on long-term outcomes following percutaneous coronary intervention (PCI) after non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that these agents are associated with improved short-term outcomes. However, many trials were undertaken before the routine use of P2Y12 inhibitors. Recent studies yield conflicting results and registry data have suggested that GP IIb/IIIa inhibitors may cause more bleeding than what trials indicate. Methods and Results. This retrospective observational study involves 3047 patients receiving dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all-cause mortality. Major adverse cardiac events (MACE) were a secondary outcome. Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes, multivariate analysis (including propensity scoring) showed no benefit for either survival (P=0.136) or MACE (P=0.614). GP IIb/IIIa inhibitor use was associated with an increased risk of major bleeding (P=0.021). Conclusion. Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk. After multivariate adjustment we observed no improvement in MACE or survival and an increased risk of major bleeding

Agent based modelling : initial assessment for use on soil bioaccessibility

This report describes the testing of Agent Based Modelling implementations in three different software packages: Repast-simphony, NetLogo and Insight-maker. These software have been evaluated against their capability to simulate the exposure of people as agents moving across Arsenic contaminated soils. Two of the three tested software (Repast-simphony and NetLogo) are recommended for assessment on more complex problems. An outline work plan is presented for future work

Out-of-hours primary percutaneous coronary intervention for ST-elevation myocardial infarction is not associated with excess mortality: a study of 3347 patients treated in an integrated cardiac network

OBJECTIVES: Timely delivery of primary percutaneous coronary intervention (PPCI) is the treatment of choice for ST-segment elevation myocardial infarction (STEMI). Optimum delivery of PPCI requires an integrated network of hospitals, following a multidisciplinary, consultant-led, protocol-driven approach. We investigated whether such a strategy was effective in providing equally effective in-hospital and long-term outcomes for STEMI patients treated by PPCI within normal working hours compared with those treated out-of-hours (OOHs). DESIGN: Observational study. SETTING: Large PPCI centre in London. PARTICIPANTS: 3347 STEMI patients were treated with PPCI between 2004 and 2012. The follow-up median was 3.3 years (IQR: 1.2–4.6 years). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was long-term major adverse cardiac events (MACE) with all-cause mortality a secondary endpoint. RESULTS: Of the 3347 STEMI patients, 1299 patients (38.8%) underwent PPCI during a weekday between 08:00 and 18:00 (routine-hours group) and 2048 (61.2%) underwent PPCI on a weekday between 18:00 and 08:00 or a weekend (OOHs group). There were no differences in baseline characteristics between the two groups with comparable door-to-balloon times (in-hours (IHs) 67.8 min vs OOHs 69.6 min, p=0.709), call-to-balloon times (IHs 116.63 vs OOHs 127.15 min, p=0.60) and procedural success. In hospital mortality rates were comparable between the two groups (IHs 3.6% vs OOHs 3.2%) with timing of presentation not predictive of outcome (HR 1.25 (95% CI 0.74 to 2.11). Over the follow-up period there were no significant differences in rates of mortality (IHs 7.4% vs OFHs 7.2%, p=0.442) or MACE (IHs 15.4% vs OFHs 14.1%, p=0.192) between the two groups. After adjustment for confounding variables using multivariate analysis, timing of presentation was not an independent predictor of mortality (HR 1.04 95% CI 0.78 to 1.39). CONCLUSIONS: This large registry study demonstrates that the delivery of PPCI with a multidisciplinary, consultant-led, protocol-driven approach provides safe and effective treatment for patients regardless of the time of presentation

Systematic Review of miRNA as Biomarkers in Alzheimer's Disease.

Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood. These deregulated miRNAs were cross-referenced against the miRNAs deregulated in the brain at Braak Stage III. This resulted in a panel of 10 miRNAs (hsa-mir-107, hsa-mir-26b, hsa-mir-30e, hsa-mir-34a, hsa-mir-485, hsa-mir200c, hsa-mir-210, hsa-mir-146a, hsa-mir-34c, and hsa-mir-125b) hypothesised to be deregulated early in Alzheimer's disease, nearly 20 years before the onset of clinical symptoms. After network analysis of the 10 miRNAs, they were found to be associated with the immune system, cell cycle, gene expression, cellular response to stress, neuron growth factor signalling, wnt signalling, cellular senescence, and Rho GTPases

The Jahn-Teller active fluoroperovskites ACrF3A\mathrm{CrF_3} A=Na+,K+A=\mathrm{Na^+},\mathrm{K^+}: thermo- and magneto optical correlations as function of the AA-site

Chromium (II) fluoroperovskites $A\mathrm{CrF_3}(A\mathrm{=Na^+,K^+})$ are strongly correlated Jahn-Teller active materials at low temperatures. In this paper, we examine the role that the $A$-site ion plays in this family of fluoroperovskites using both experimental methods (XRD, optical absorption spectroscopy and magnetic fields) and DFT simulations. Temperature-dependent optical absorption experiments show that the spin-allowed transitions $E_2$ and $E_3$ only merge completely for $A$= Na at 2 K. Field-dependent optical absorption measurements at 2 K show that the oscillating strength of the spin-allowed transitions in $\mathrm{NaCrF_3}$ increases with increasing applied field. Direct magneto-structural correlations which suppress the spin-flip transitions are observed for ${\rm KCrF_3}$ below its Ne\'el temperature. In ${\rm NaCrF_3}$ the spin-flip transitions vanish abruptly below 9 K revealing magneto-optical correlations not linked to crystal structure changes. This suggests that as the long range ordering is reduced local JT effects in the individual ${\rm CrF_6^{4-}}$ octahedra take control of the observed behavior. Our results show clear deviation from the pattern found for the isoelectronic $A_x{\rm MnF}_{3+x}$ system. The size of the $A$-site cation is shown to be central in dictating the physical properties and phase transitions in $A{\rm CrF}_3$, opening up the possibility of varying the composition to create novel states of matter with tuneable properties

Energy-balance models of the solar corona

Solar coronal observations have shown that the corona has a highly complex structure which presumably owes its existence to the magnetic field. Models in thermal and hydrostatic equilibrium are here calculated in order to try and explain many of these observations. Coronal holes occur where open field lines reach out into space. The model of McWhirter, et al. (1975) for the inner corona in such a configuration is generalised to allow different types and magnitudes of heating as well as different area divergences and flows. It is found that hot, fast upflows cannot always exist in thermal equilibrium. The choice of boundary conditions can appreciably alter the results, and so different choices are compared. Most of the corona, especially in active regions, appears to consist of coronal loops. Subtle relations for energy balance models of such loops are found to exist between the physical parameters of a loop's length, base density, and heat input. No solution exists at coronal temperatures in certain cases, which may explain the observations of very cool loops. The effect of a loop's geometry and field line divergence on the structure is found. Results predicted from scaling laws are compared, and the uniqueness of the solution for a loop with a fixed mass is studied. The error in the predicted emission measure through assuming uniform pressure is shown to be considerable. The life-time of a loop can often be many days, suggesting the existence of a thermally stable state. A global stability analysis is performed, and it is found that a loop's stability may depend critically upon its length. Thermally isolated loops, which are the most unstable type, can be thermally stable, provided their pressure falls off sufficiently rapidly with height (due to hydrostatic equilibrium)

Iron nutrition and possible lead toxicity: an appraisal of geophagy undertaken by pregnant women of UK Asian communities

A cultural transfer of geophagy is evident in the UK, with soils imported from Bengal being deliberately consumed mainly by pregnant Asian women. Two samples purchased from ethnic shops were subjected to a 2-part acid–alkaline in vitro physiologically based extraction test (PBET) procedure, representing the stomach and small intestine of the human digestive system respectively, to determine the bioaccessibility of elements. Despite the low bioaccessibility of Fe, with the quantity of soil consumed one sample can provide 41–54% of this mineral nutrient required by a 15–18 year old female, with the other sample providing 90–119%. Significant amounts of Ca, Cu and Mn are also supplied to the consumer, whilst further research investigating the possible effects of Pb toxicity on the geophagist would seem to be justifie

UK perspective on the changing landscape of non-invasive cardiac testing.

Objective: To document UK rates of exercise treadmill testing, functional stress testing and CT coronary angiography (CTCA). Specific aims were to determine how rates have changed in the context of changing guideline recommendations within the UK and to identify regional inequalities in the utilisation of testing modalities. Secondary objectives were to compare these trends with national data on revascularisation. Methods: 159 acute National Health Service trusts were served Freedom of Information (FOI) requests to provide total numbers of CTCA and functional imaging tests for each financial year from 2011-2012 to 2016-2017. Results: The FOI requests yielded data from 88% of Trusts, increasing from 81.9% in 2011-2012% to 92.1% in 2016-2017. Exercise treadmill tests (ETTs) were performed by over 97% of Trusts. ETT was the most commonly performed diagnostic test in the UK across the study period despite declining by 8.4%. Utilisation of non-invasive stress imaging tests increased by 80.9% during the same period. Myocardial perfusion scintigraphy and stress echocardiography increased by 25.8% and 73.9%, respectively. The 268% increase in CTCA scans was yet greater. Trends in test utilisation during the study period showed important regional differences between devolved nations. Comparably, only small changes in rates of invasive coronary angiography and revascularisation have been reported during the study period. Conclusion: Non-invasive imaging in UK Trusts has increased substantially since 2010 with only a small decline in use of the ETT and minimal changes in rates of invasive coronary angiography and revascularisation in the same time period

AmelHap: Leveraging drone whole-genome sequence data to create a honey bee HapMap

Honey bee, Apis mellifera, drones are typically haploid, developing from an unfertilized egg, inheriting only their queen’s alleles and none from the many drones she mated with. Thus the ordered combination or ‘phase’ of alleles is known, making drones a valuable haplotype resource. We collated whole-genome sequence data for 1,407 drones, including 45 newly sequenced Scottish drones, collectively representing 19 countries, 8 subspecies and various hybrids. Following alignment to Amel_HAv3.1, variant calling and quality filtering, we retained 17.4 M high quality variants across 1,328 samples with a genotyping rate of 98.7%. We demonstrate the utility of this haplotype resource, AmelHap, for genotype imputation, returning >95% concordance when up to 61% of data is missing in haploids and up to 12% of data is missing in diploids. AmelHap will serve as a useful resource for the community for imputation from low-depth sequencing or SNP chip data, accurate phasing of diploids for association studies, and as a comprehensive reference panel for population genetic and evolutionary analyses.For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. This work was supported by a grant from the CB Dennis British Beekeepers’ Research Trust awarded to MB and DW, and through strategic investment funding to the Roslin Institute from the Biotechnology and Biological Sciences Research Council (BBS/E/D/30002276). MP was supported by a Basque Government grant (IT1233-19)