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

COMPARISON OF TWO ELLIPTICAL MOTION RUNNING MACHINES AND TREADMILL RUNNING

INTRODUCTION: One of the major problems associated with rehabilitation from impact- associated running injuries is maintaining cardiovascular fitness. Recently, elliptical motion exercise machines have been developed in an attempt to simulate running while minimizing impact forces. These machines have been shown to maintain cardiovascular fitness. However, they have not yet been shown to truly simulate the running motion. The purpose of this study was to provide a quantitative comparison of two elliptical motion exercise machines (C1 and C2) and treadmill running (C3). METHODS: Both of the elliptical motion machines fixed stride length, although one allowed a greater stride length (C1). Eight subjects were tested in each of three submaximal exercise conditions during a 15 minute bout. Subjects performed at a stride frequency that resulted in a heart rate of 65% of their age-predicted maximum heart rate. Five 60 Hz digital cameras were used to collect lower extremity kinematic data. Pre-amplified surface electrodes measured the muscle activity of seven lower extremity muscles. Impact forces were assessed using a 1.7g PCB accelerometer placed on the distal medial aspect of the tibia. Both the accelerometer and EMG data were collected concurrently on a microcomputer sampling at 600 Hz. Lower extremity joint and segment parameters, onset and offset of muscles during stride, peak impact force and time to peak impact force were calculated. An analysis of variance was used to compare the measured parameters between each machine condition and to identify whether the duration of the exercise bout had an effect. RESULTS: There were no significant differences in stride duration with controlled stride frequency. The results of the analysis of the kinematic data showed that the majority of the differences between the machines and treadmill running occurred at the ankle and knee joints. At the ankle and knee joints, the touchdown angle was greater for the two machines (C1 and C2) than for treadmill running (ankle: 11.97 o and 22.14 o versus 2.23o; knee: 34.94 o and 33.89 o versus 12.05 o). At the ankle joint, the maximum plantar flexion angle was greatest in treadmill running, while there were no significant differences in any knee angles subsequent to touchdown. There were no differences in any of the hip angles at any time in the stride. Impact values on the two machines were 30% of those measured during treadmill running, and the time of occurrence of the impact was substantially longer into the stride. The results of the EMG data showed that the duration of muscle activity throughout the stride was different in the triceps surae, rectus femoris and vastus lateralis. In each case, the duration of the stride in which these muscles were active was least in treadmill running. CONCLUSIONS: In conclusion, while there are a few differences between the elliptical machines and running, it appears that the machines could be considered representative of running with distinctly less impact. Thus, these machines could be used as rehabilitation tools for runners recovering from impact-related injuries

Improving your target-template alignment with MODalign

Summary: MODalign is an interactive web-based tool aimed at helping protein structure modelers to inspect and manually modify the alignment between the sequences of a target protein and of its template(s). It interactively computes, displays and, upon modification of the target-template alignment, updates the multiple sequence alignments of the two protein families, their conservation score, secondary structure and solvent accessibility values, and local quality scores of the implied three-dimensional model(s). Although it has been designed to simplify the target-template alignment step in modeling, it is suitable for all cases where a sequence alignment needs to be inspected in the context of other biological information

A randomised double-blind control study of early intracoronary autologous bone marrow cell infusion in acute myocardial infarction (REGENERATEAMI)

This article has been accepted for publication in European Heart Journal Published by Oxford University Press.UK Stem Cells Foundation, the Heart Cells Foundation, and Barts and the London Charity. Funding to pay the Open Access publication charges for this article was provided by the Barts Cardiovascular Biomedical Research Unit (CVBRU)

Displaced but not replaced: the impact of e-learning on academic identities in higher education.

Challenges facing universities are leading many to implement institutional strategies to incorporate e-learning rather than leaving its adoption up to enthusiastic individuals. Although there is growing understanding about the impact of e-learning on the student experience, there is less understanding of academics’ perceptions of e-learning and its impact on their identities. This paper explores the changing nature of academic identities revealed through case study research into the implementation of e-learning at one UK university. By providing insight into the lived experiences of academics in a university in which technology is not only transforming access to knowledge but also influencing the balance of power between academic and student in knowledge production and use, it is suggested that academics may experience a jolt to their ‘trajectory of self’ when engaging with e-learning. The potential for e-learning to prompt loss of teacher presence and displacement as knowledge expert may appear to undermine the ontological security of their academic identity

Implementation of a quantum algorithm to solve Bernstein-Vazirani's parity problem without entanglement on an ensemble quantum computer

Bernstein and Varizani have given the first quantum algorithm to solve parity problem in which a strong violation of the classical imformation theoritic bound comes about. In this paper, we refine this algorithm with fewer resource and implement a two qubits algorithm in a single query on an ensemble quantum computer for the first time

Differential spatial repositioning of activated genes in Biomphalaria glabrata snails infected with Schistosoma mansoni

Copyright @ 2014 Arican-Goktas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.NIH and Sandler Borroughs Wellcome Travel Fellowshi

The Use of Novel Oral Anti-Coagulant's (NOAC) compared to Vitamin K Antagonists (Warfarin) in patients with Left Ventricular thrombus after Acute Myocardial Infarction (AMI).

This is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal - Cardiovascular Pharmacotherapy following peer review. The version of record: Daniel A Jones, Paul Wright, Momin A Alizadeh, Sadeer Fhadil, Krishnaraj S Rathod, Oliver Guttmann, Charles Knight, Adam Timmis, Andreas Baumbach, Andrew Wragg, Anthony Mathur, Sotiris Antoniou, The Use of Novel Oral Anti-Coagulant’s (NOAC) compared to Vitamin K Antagonists (Warfarin) in patients with Left Ventricular thrombus after Acute Myocardial Infarction (AMI), European Heart Journal - Cardiovascular Pharmacotherapy, pvaa096, https://doi.org/10.1093/ehjcvp/pvaa096AIM: Current guidelines recommend the use of Vitamin K Antagonist (VKA) for up to 3 - 6 months for treatment of LV thrombus post-acute myocardial infarction (AMI). However, based on evidence supporting non-inferiority of Novel Oral Anti-Coagulant's (NOAC) compared to VKA for other indications such as DVT, PE and thrombo-embolic prevention in atrial fibrillation, NOACs are being increasingly used off licence for the treatment of LV thrombus post AMI. In this study we investigated the safety and effect of NOACs compared to VKA on LV thrombus resolution in patients presenting with AMI. METHODS AND RESULTS: This was an observational study of 2,328 consecutive patients undergoing Coronary Angiography +/- Percutaneous Coronary Intervention (PCI) for AMI between May 2015- December 2018, at a UK cardiac centre. Patients' details were collected from the hospital electronic database. The primary end-point was rate of LV thrombus resolution with bleeding rates a secondary outcome.Left ventricular (LV) thrombus was diagnosed in 101 (4.3%) patients. Sixty patients (59.4%) were started on VKA and 41 patients (40.6%) on NOAC therapy (rivaroxaban: 58.5%, apixaban, 36.5% and edoxaban: 5.0%). Both groups were well matched in terms of baseline characteristics including age, previous cardiac history (Previous MI, PCI, CABG), and cardiovascular risk factors (Hypertension, Diabetes, Hypercholesterolaemia).Over the follow up period (median 2.2 years), overall rates of LV thrombus resolution were 86.1%. There was greater and earlier LV thrombus resolution in the NOAC group compared to patients treated with warfarin (82% vs 64.4%, p = 0.0018, at 1 year), which persisted after adjusting for baseline variables (OR 1.8 95% CI 1.2-2.9). Major bleeding events during the f/u period were lower in the NOAC group, compared with VKA group (0% vs 6.7%, p = 0.030) with no difference in rates of systemic thromboembolism (5% vs 2.4%, p = 0.388). CONCLUSION: This data suggests improved thrombus resolution in post ACS LV thrombosis in patients treated with NOACs compared to vitamin K antagonists. This improvement in thrombus resolution was accompanied with a better safety profile for NOAC patients' vs VKA treated patients. Thus, provides data to support a randomised trial to answer this question

Directed vaccination against pneumococcal disease

Immunization strategies against commensal bacterial pathogens have long focused on eradicating asymptomatic carriage as well as disease, resulting in changes in the colonizing microflora with unknown future consequences. Additionally, current vaccines are not easily adaptable to sequence diversity and immune evasion. Here, we present a "smart" vaccine that leverages our current understanding of disease transition from bacterial carriage to infection with the pneumococcus serving as a model organism. Using conserved surface proteins highly expressed during virulent transition, the vaccine mounts an immune response specifically against disease-causing bacterial populations without affecting carriage. Aided by a delivery technology capable of multivalent surface display, which can be adapted easily to a changing clinical picture, results include complete protection against the development of pneumonia and sepsis during animal challenge experiments with multiple, highly variable, and clinically relevant pneumococcal isolates. The approach thus offers a unique and dynamic treatment option readily adaptable to other commensal pathogens