Pixel Detectors

Results of the characterisation of three different pixel detectors are presented. The first is an energy resolving detector (ERD1) which has been characterised using laboratory sources and the synchrotron radiation source (SRS) at Daresbury. The ERD1 is a 16 by 16 array of 300 mum by 300 mum square pixels, the detector is 300 mum thick Si and is bump-bonded using gold studs to the RAL PAC5 read out. Energy spectra and diffraction lines acquired at the SRS are presented and show the imaging and simultaneous spectroscopic capabilities of the ERD1. The energy resolution was investigated using X- rays of energies between 6 and 60 keV from laboratory sources. The achieved full-width-at-half-maximum (FWHM) of the photo peaks is in the range of 300 eV to 500 eV with an electronic noise of 227 +/-43 eV. Charge sharing was investigated for different energy X-rays and is shown to be significant with up to around 10% of events sharing some charge. The second detector is a large area detector (LAD1). It is based on single photon counting and is designed for imaging in synchrotron radiation applications. Results of tests performed with a single chip module at the Daresbury SRS are presented. The detector is 300 mum thick Si with 150 mum by 150 mum pixels bump-bonded to an (RAL ALADIN) array of 64 by 64 read out channels. The spatial resolution was determined using the modulation transfer function (MTF) with a result of (5.1 +/- 0.1) 1p/mm at an MTF value of 0.3. Theoretical studies of the spatial resolution predict a value of 5.3 1p/mm. The image noise in photon counting systems is investigated theoretically and experimentally and is shown to be given by Poisson statistics. The rate capability of the LAD1 was measured to be 250 kHz per pixel. Theoretical and experimental studies of the difference in contrast for ideal charge integrating and photon counting imaging systems were carried out. It is shown that the contrast differs and that for the conventional definition (contrast = (background - signal)/background) the photon counting device will, in some cases, always give a better contrast than the integrating system. Simulations in MEDICI are combined with analytical calculations to investigate charge collection efficiencies (CCE) in semiconductor detectors. Different pixel sizes and biasing conditions are considered. The results show charge sharing due to the limited mean free drift lengths of the charge carriers, the improvement of the CCE in unipolar detectors with decreasing pixel size and the "small pixel effect" which shows the improved CCE of the photo peak with smaller pixels. The third detector is a graphite pixel detector for ion beam profiling. The system was tested in the ion implanters at the University of Salford and Surrey. Results are presented showing real time profiling of the ion beam and the measurement of the beam current. The secondary electron emission was qualitatively measured for different beam energies and different positions on the detector. The loss of secondary electrons follows the profile of the detector and increases with higher energy ions

Mep72, a metzincin protease that is preferentially secreted by biofilms of Pseudomonas aeruginosa.

In this work, we compared the profile of proteins secreted by planktonic and biofilm cultures of Pseudomonas aeruginosa using two-dimensional difference gel electrophoresis (2D-DiGE). This revealed that a novel metzincin protease, Mep72, was secreted during biofilm growth. Subsequent Western blotting and reverse transcription-PCR (RT-PCR) analyses demonstrated that Mep72 was expressed only during biofilm growth. Mep72 has a tridomain structure comprised of a metzincin protease-like domain and two tandem carbohydrate-binding domains. Unlike the only other metzincin (alkaline protease; AprA) in P. aeruginosa, Mep72 is secreted through the type II pathway and undergoes processing during export. During this processing, the metzincin domain is liberated from the carbohydrate-binding domains. This processing may be self-catalyzed, since purified Mep72 autodegraded in vitro. This autodegradation was retarded in the presence of alginate (an extracellular matrix component of many P. aeruginosa biofilms). The expression of full-length mep72 in Escherichia coli was toxic. However, this toxicity could be alleviated by coexpression of mep72 with the adjacent gene, bamI. Mep72 and BamI were found to form a protein-protein complex in vitro. 2D-DiGE revealed that the electrophoretic mobility of several discrete protein spots was altered in the biofilm secretome of an mep72 mutant, including type III secretion proteins (PopD, PcrV, and ExoS) and a flagellum-associated protein (FliD). Mep72 was found to bind directly to ExoS and PcrV and to affect the processing of these proteins in the biofilm secretome. We conclude that Mep72 is a secreted biofilm-specific regulator that affects the processing of a very specific subset of virulence factors.This study was funded by the BBSRC, the Isaac Newton Trust (Cambridge), and a grant from the Japanese Society for Acute Infection to K.N.The paper was originally published by the American Society for Microbiology in the Journal of Bacteriology with a CC-BY licence (IJ Passmore, K Nishikawa, KS Lilley, SD Bowden, JCS Chung, M Welch, Journal of Bacteriology 2015, 197, 762–773

Systematic Review of Prognostic Factors for Return to Work in Workers with Sub Acute and Chronic Low Back Pain

Morgan, John (2012)Teaching Secondary Geography as if the Planet MattersLondres: Routledge, 165 p.ISBN 978-0-415-56387-1Morgan, John (2012)Teaching Secondary Geography as if the Planet MattersLondres: Routledge, 165 p.ISBN 978-0-415-56387-1Morgan, John (2012)Teaching Secondary Geography as if the Planet MattersLondres: Routledge, 165 p.ISBN 978-0-415-56387-1Morgan, John (2012)Teaching Secondary Geography as if the Planet MattersLondres: Routledge, 165 p.ISBN 978-0-415-56387-

Blood type gene locus has no influence on ACE association with Alzheimer's disease

The ABO blood group locus was recently found to contribute independently as well as via interactions with ACE gene variation to plasma levels of angiotensin converting enzyme (ACE). Variation in ACE has also previously been implicated as conferring susceptibility for Alzheimer’s disease (AD), but has also been proposed to confer risk via interactions with other as yet unknown genes. More recently, larger studies have not supported ACE as a risk factor for AD, while the role of ACE pathway in AD has come under increased levels of scrutiny with respect to various aspects of AD pathology and possible therapies. We explored the potential combined involvement of ABO and ACE variation in the genetic susceptibility of 2067 AD cases compared to 1376 non-demented elderly. Including the effects of ABO haplotype did not provide any evidence for the genetic association of ACE with AD

Knowledge Transfer within the Canadian Chiropractic Community. Part 1: Understanding Evidence-Practice Gaps

The article presents an overview of the concept of knowledge transfer (KT) and discusses the process of KT and its role in optimizing health care delivery and integrating available and new knowledge into practice and policy. A discussion of several barriers to KT, including those that are common to most health care disciplines, and of those that are of relevance to the chiropractic profession, is presented

Replication of EPHA1 and CD33 associations with late-onset Alzheimer's disease: a multi-centre case-control study

<p>Abstract</p> <p>Background</p> <p>A recently published genome-wide association study (GWAS) of late-onset Alzheimer's disease (LOAD) revealed genome-wide significant association of variants in or near <it>MS4A4A, CD2AP, EPHA1 </it>and <it>CD33</it>. Meta-analyses of this and a previously published GWAS revealed significant association at <it>ABCA7 </it>and <it>MS4A</it>, independent evidence for association of <it>CD2AP, CD33 </it>and <it>EPHA1 </it>and an opposing yet significant association of a variant near <it>ARID5B</it>. In this study, we genotyped five variants (in or near <it>CD2AP, EPHA1, ARID5B</it>, and <it>CD33</it>) in a large (2,634 LOAD, 4,201 controls), independent dataset comprising six case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and tested for association using logistic regression adjusted by age-at-diagnosis, gender, and <it>APOE ε4 </it>dosage.</p> <p>Results</p> <p>We found no significant evidence of series heterogeneity. Associations with LOAD were successfully replicated for <it>EPHA1 </it>(rs11767557; OR = 0.87, p = 5 × 10^-4) and <it>CD33 </it>(rs3865444; OR = 0.92, p = 0.049), with odds ratios comparable to those previously reported. Although the two <it>ARID5B </it>variants (rs2588969 and rs494288) showed significant association with LOAD in meta-analysis of our dataset (p = 0.046 and 0.008, respectively), the associations did not survive adjustment for covariates (p = 0.30 and 0.11, respectively). We had insufficient evidence in our data to support the association of the <it>CD2AP </it>variant (rs9349407, p = 0.56).</p> <p>Conclusions</p> <p>Our data overwhelmingly support the association of <it>EPHA1 </it>and <it>CD33 </it>variants with LOAD risk: addition of our data to the results previously reported (total n > 42,000) increased the strength of evidence for these variants, providing impressive p-values of 2.1 × 10^-15(<it>EPHA1</it>) and 1.8 × 10^-13(<it>CD33</it>).</p

Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

Background 1Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset. Principal Findings We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD. Significance Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches

Abstracts from the NIHR INVOLVE Conference 2017

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