Transcatheter Heart Valve Leaflet Assembly Tooling Improvement Final Design Report

Statement of Confidentiality: The complete senior project report was submitted to the project advisor and sponsor. The results of this project are of a confidential nature and will not be published at this time

Quantifying the UK's carbon dioxide flux: An atmospheric inverse modelling approach using a regional measurement network

We present a method to derive atmosphericobservation-based estimates of carbon dioxide (CO 2 ) fluxes at the national scale, demonstrated using data from a network of surface tall-tower sites across the UK and Ireland over the period 2013-2014. The inversion is carried out using simulations from a Lagrangian chemical transport model and an innovative hierarchical Bayesian Markov chain Monte Carlo (MCMC) framework, which addresses some of the traditional problems faced by inverse modelling studies, such as subjectivity in the specification of model and prior uncertainties. Biospheric fluxes related to gross primary productivity and terrestrial ecosystem respiration are solved separately in the inversion and then combined a posteriori to determine net ecosystem exchange of CO 2 . Two different models, Data Assimilation Linked Ecosystem Carbon (DALEC) and Joint UK Land Environment Simulator (JULES), provide prior estimates for these fluxes. We carry out separate inversions to assess the impact of these different priors on the posterior flux estimates and evaluate the differences between the prior and posterior estimates in terms of missing model components. The Numerical Atmospheric dispersion Modelling Environment (NAME) is used to relate fluxes to the measurements taken across the regional network. Posterior CO2 estimates from the two inversions agree within estimated uncertainties, despite large differences in the prior fluxes from the different models. With our method, averaging results from 2013 and 2014, we find a total annual net biospheric flux for the UK of 8±79 TgCO 2 yr -1 (DALEC prior) and 64±85 TgCO 2 yr -1 (JULES prior), where negative values represent an uptake of CO 2 . These biospheric CO 2 estimates show that annual UK biospheric sources and sinks are roughly in balance. These annual mean estimates consistently indicate a greater net release of CO 2 than the prior estimates, which show much more pronounced uptake in summer months

Serendipitous discovery of a dying Giant Radio Galaxy associated with NGC 1534, using the Murchison Widefield Array

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2015 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.Recent observations with the Murchison Widefield Array at 185~MHz have serendipitously unveiled a heretofore unknown giant and relatively nearby ($z = 0.0178$) radio galaxy associated with NGC\,1534. The diffuse emission presented here is the first indication that NGC\,1534 is one of a rare class of objects (along with NGC\,5128 and NGC\,612) in which a galaxy with a prominent dust lane hosts radio emission on scales of $\sim$700\,kpc. We present details of the radio emission along with a detailed comparison with other radio galaxies with disks. NGC1534 is the lowest surface brightness radio galaxy known with an estimated scaled 1.4-GHz surface brightness of just 0.2\,mJy\,arcmin$^{-2}$. The radio lobes have one of the steepest spectral indices yet observed: $\alpha=-2.1\pm0.1$, and the core to lobe luminosity ratio is $Peer reviewe

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

An Orally Bioavailable, Indole-3-glyoxylamide Based Series of Tubulin Polymerization Inhibitors Showing Tumor Growth Inhibition in a Mouse Xenograft Model of Head and Neck Cancer.

A number of indole-3-glyoxylamides have previously been reported as tubulin polymerization inhibitors, although none has yet been successfully developed clinically. We report here a new series of related compounds, modified according to a strategy of reducing aromatic ring count and introducing a greater degree of saturation, which retain potent tubulin polymerization activity but with a distinct SAR from previously documented libraries. A subset of active compounds from the reported series is shown to interact with tubulin at the colchicine binding site, disrupt the cellular microtubule network, and exert a cytotoxic effect against multiple cancer cell lines. Two compounds demonstrated significant tumor growth inhibition in a mouse xenograft model of head and neck cancer, a type of the disease which often proves resistant to chemotherapy, supporting further development of the current series as potential new therapeutics

Galaxy and Mass Assembly (GAMA): Variation in Galaxy Structure Across the Green Valley

Using a sample of 472 local Universe (z < 0.06) galaxies in the stellar mass range 10.25 < log M*/MG < 10.75, we explore the variation in galaxy structure as a function of morphology and galaxy colour. Our sample of galaxies is sub-divided into red, green and blue colour groups and into elliptical and non-elliptical (disk-type) morphologies. Using KiDS and VIKING derived postage stamp images, a group of eight volunteers visually classified bars, rings, morphological lenses, tidal streams, shells and signs of merger activity for all systems. We find a significant surplus of rings (2.3σ) and lenses (2.9σ) in disk-type galaxies as they transition across the green valley. Combined, this implies a joint ring/lens green valley surplus significance of 3.3σ relative to equivalent disk-types within either the blue cloud or the red sequence. We recover a bar fraction of ∼ 44% which remains flat with colour, however, we find that the presence of a bar acts to modulate the incidence of rings and (to a lesser extent) lenses, with rings in barred disk-type galaxies more common by ∼ 20 − 30 percentage points relative to their unbarred counterparts, regardless of colour. Additionally, green valley disk-type galaxies with a bar exhibit a significant 3.0σ surplus of lenses relative to their blue/red analogues. The existence of such structures rules out violent transformative events as the primary end-of-life evolutionary mechanism, with a more passive scenario the favoured candidate for the majority of galaxies rapidly transitioning across the green valley. Key words: galaxies: elliptical and lenticular, cD – galaxies: spiral – galaxies: evo- lution – galaxies: star formation – galaxies: statistics – galaxies: structur

Multi-campaign ship and aircraft observations of marine cloud condensation nuclei and droplet concentrations

In-situ marine cloud droplet number concentrations (CDNCs), cloud condensation nuclei (CCN), and CCN proxies, based on particle sizes and optical properties, are accumulated from seven field campaigns: ACTIVATE; NAAMES; CAMP2EX; ORACLES; SOCRATES; MARCUS; and CAPRICORN2. Each campaign involves aircraft measurements, ship-based measurements, or both. Measurements collected over the North and Central Atlantic, Indo-Pacific, and Southern Oceans, represent a range of clean to polluted conditions in various climate regimes. With the extensive range of environmental conditions sampled, this data collection is ideal for testing satellite remote detection methods of CDNC and CCN in marine environments. Remote measurement methods are vital to expanding the available data in these difficult-to-reach regions of the Earth and improving our understanding of aerosol-cloud interactions. The data collection includes particle composition and continental tracers to identify potential contributing CCN sources. Several of these campaigns include High Spectral Resolution Lidar (HSRL) and polarimetric imaging measurements and retrievals that will be the basis for the next generation of space-based remote sensors and, thus, can be utilized as satellite surrogates

Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant