2,217 research outputs found
Haemophilus influenzae type b reemergence after combination immunization
An increase in Haemophilus influenzae type b (Hib) in
British children has been linked to the widespread use of a
diphtheria/tetanus/acellular pertussis combination vaccine
(DTaP-Hib). We measured anti-polyribosyl-ribitol phos-
phate antibody concentration and avidity before and after a
Hib booster in 176 children 2–4 years of age who had
received 3 doses of DTP-Hib (either DT whole cell pertus-
sis-Hib or DTaP-Hib) combination vaccine in infancy. We
also measured pharyngeal carriage of Hib. Antibody con-
centrations before and avidity indices after vaccination
were low (geometric mean concentration 0.46μg/mL, 95%
confidence interval [CI] 0.36–0.58; geometric mean avidity
index 0.16, 95% CI 0.14–0.18) and inversely related to the
number of previous doses of DTaP-Hib (p = 0.02 and
p<0.001, respectively). Hib was found in 2.1% (95% CI
0.7%–6.0%) of study participants. Our data support an
association between DTaP-Hib vaccine combinations and
clinical Hib disease through an effect on antibody concen-
tration and avidit
C.R.I.S.T.A.L. Concurrent Repository & Information System for Tracking Assembly and production Lifecycles: A data capture and production management tool for the assembly and construction of the CMS ECAL detector
The CMS experiment will comprise several very large high resolution detectors for physics. Each detector may be constructed of well over a million parts and will be produced and assembled during the next decade by specialised centres distributed world-wide. Each constituent part of each detector must be accurately measured and tested locally prior to its ultimate assembly and integration in the experimental area at CERN. The CRISTAL project (Concurrent Repository and Information System for Tracking Assembly and production Lifecycles) [1] aims to monitor and control the quality of the production and assembly process to aid in optimising the performance of the physics detectors and to reject unacceptable constituent parts as early as possible in the construction lifecycle. During assembly CRISTAL will capture all the information required for subsequent detector calibration. Distributed instances of Object databases linked via CORBA [2] and with WWW/Java-based query processing are the main technology aspects of CRISTAL.The CMS experiment will comprise several very large high resolution detectors for physics. Each detector may be constructed of well over a million parts and will be produced and assembled during the next decade by specialised centres distributed world-wide. Each constituent part of each detector must be accurately measured and tested locally prior to its ultimate assembly and integration in the experimental area at CERN. The CRISTAL project (Concurrent Repository and Information System for Tracking Assembly and production Lifecycles) [1] aims to monitor and control the quality of the production and assembly process to aid in optimising the performance of the physics detectors and to reject unacceptable constituent parts as early as possible in the construction lifecycle. During assembly CRISTAL will capture all the information required for subsequent detector calibration. Distributed instances of Object databases linked via CORBA [2] and with WWW/Java-based query processing are the main technology aspects of CRISTAL
Measurement of inclusive D*+- and associated dijet cross sections in photoproduction at HERA
Inclusive photoproduction of D*+- mesons has been measured for photon-proton
centre-of-mass energies in the range 130 < W < 280 GeV and a photon virtuality
Q^2 < 1 GeV^2. The data sample used corresponds to an integrated luminosity of
37 pb^-1. Total and differential cross sections as functions of the D*
transverse momentum and pseudorapidity are presented in restricted kinematical
regions and the data are compared with next-to-leading order (NLO) perturbative
QCD calculations using the "massive charm" and "massless charm" schemes. The
measured cross sections are generally above the NLO calculations, in particular
in the forward (proton) direction. The large data sample also allows the study
of dijet production associated with charm. A significant resolved as well as a
direct photon component contribute to the cross section. Leading order QCD
Monte Carlo calculations indicate that the resolved contribution arises from a
significant charm component in the photon. A massive charm NLO parton level
calculation yields lower cross sections compared to the measured results in a
kinematic region where the resolved photon contribution is significant.Comment: 32 pages including 6 figure
Measurement of Jet Shapes in Photoproduction at HERA
The shape of jets produced in quasi-real photon-proton collisions at
centre-of-mass energies in the range GeV has been measured using the
hadronic energy flow. The measurement was done with the ZEUS detector at HERA.
Jets are identified using a cone algorithm in the plane with a
cone radius of one unit. Measured jet shapes both in inclusive jet and dijet
production with transverse energies GeV are presented. The jet
shape broadens as the jet pseudorapidity () increases and narrows
as increases. In dijet photoproduction, the jet shapes have been
measured separately for samples dominated by resolved and by direct processes.
Leading-logarithm parton-shower Monte Carlo calculations of resolved and direct
processes describe well the measured jet shapes except for the inclusive
production of jets with high and low . The observed
broadening of the jet shape as increases is consistent with the
predicted increase in the fraction of final state gluon jets.Comment: 29 pages including 9 figure
Serum miRNAs miR-206, 143-3p and 374b-5p as potential biomarkers for amyotrophic lateral sclerosis (ALS)
Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative condition characteris
loss of motor neurones and progressive muscle wasting. There is no diagnostic test fo
therefore robust biomarkers would not only be valuable for diagnosis, but also the
classification of disease subtypes, monitoring responses to drugs and tracking diseas
progression. As regulators of gene expression, microRNAs (miRNAs) are increasingly
for diagnostic and prognostic purposes in various disease states with increasing explo
in neurodegenerative disorders. We hypothesise that circulating blood based miRNAs
serve as biomarkers and use miRNA profiling to determine miRNA signatures from th
serum of sporadic (sALS) patients compared to healthy controls and patients with dise
that mimic ALS. A number of differentially expressed miRNAs were identified in each
patient comparisons. Validation in an additional patient cohort showed that miR-206 a
miR-143-3p were increased and miR-374b-5p was decreased compared to controls. A
continued change in miRNA expression persisted during disease progression indicatin
potential use of these particular miRNAs as longitudinal biomarkers in ALS
UK Iatrogenic Creutzfeldt-Jakob disease:Investigating human prion transmission across genotypic barriers using human tissue-based and molecular approaches
Creutzfeldt-Jakob disease (CJD) is the prototypic human prion disease that occurs most commonly in sporadic and genetic forms, but it is also transmissible and can be acquired through medical procedures, resulting in iatrogenic CJD (iCJD). The largest numbers of iCJD cases that have occurred worldwide have resulted from contaminated cadaveric pituitary-derived human growth hormone (hGH) and its use to treat primary and secondary growth hormone deficiency. We report a comprehensive, tissue-based and molecular genetic analysis of the largest series of UK hGH-iCJD cases reported to date, including in vitro kinetic molecular modelling of genotypic factors influencing prion transmission. The results show the interplay of prion strain and host genotype in governing the molecular, pathological and temporal characteristics of the UK hGH-iCJD epidemic and provide insights into the adaptive mechanisms involved when prions cross genotypic barriers. We conclude that all of the available evidence is consistent with the hypothesis that the UK hGH-iCJD epidemic resulted from transmission of the V2 human prion strain, which is associated with the second most common form of sporadic CJD
Embedding physical activity in the heart of the NHS: the need for a whole-system approach
Solutions to the global challenge of physical inactivity have tended to focus on interventions at an individual level, when evidence shows that wider factors, including the social and physical environment, play a major part in influencing health-related behaviour. A multidisciplinary perspective is needed to rewrite the research agenda on physical activity if population-level public health benefits are to be demonstrated. This article explores the questions that this raises regarding the particular role that the UK National Health Service (NHS) plays in the system. The National Centre for Sport and Exercise Medicine in Sheffield is put forward as a case study to discuss some of the ways in which health systems can work in collaboration with other partners to develop environments and systems that promote active lives for patients and staff
Persistence of immune response in heterologous COVID vaccination schedules in the Com-COV2 study - a single-blind, randomised trial incorporating mRNA, viral-vector and protein-adjuvant vaccines
BACKGROUND: Heterologous COVID vaccine priming schedules are immunogenic and effective. This report aims to understand the persistence of immune response to the viral vectored, mRNA and protein-based COVID-19 vaccine platforms used in homologous and heterologous priming combinations, which will inform the choice of vaccine platform in future vaccine development. METHODS: Com-COV2 was a single-blinded trial in which adults ≥50 years, previously immunised with single dose 'ChAd' (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or 'BNT' (BNT162b2, tozinameran, Comirnaty, Pfizer/BioNTech), were randomised 1:1:1 to receive a second dose 8-12 weeks later with either the homologous vaccine, or 'Mod' (mRNA-1273, Spikevax, Moderna) or 'NVX' (NVX-CoV2373, Nuvaxovid, Novavax). Immunological follow-up and the secondary objective of safety monitoring were performed over nine months. Analyses of antibody and cellular assays were performed on an intention-to-treat population without evidence of COVID-19 infection at baseline or for the trial duration. FINDINGS: In April/May 2021, 1072 participants were enrolled at a median of 9.4 weeks after receipt of a single dose of ChAd (N= 540, 45% female) or BNT (N=532, 39% female) as part of the national vaccination programme. In ChAd-primed participants, ChAd/Mod had the highest anti-spike IgG from day 28 through to 6 months, although the heterologous vs homologous geometric mean ratio (GMR) dropped from 9.7 (95%CI: 8.2,11.5) at D28 to 6.2 (95%CI: 5.0, 7.7) at D196. The heterologous/homologous GMR for ChAd/NVX similarly dropped from 3.0 (95%CI:2.5-3.5) to 2.4 (95%CI:1.9-3.0). In BNT-primed participants, decay was similar between heterologous and homologous schedules with BNT/Mod inducing the highest anti-spike IgG for the duration of follow-up. The aGMR for BNT/Mod compared with BNT/BNT increased from 1.36 (95%CI: 1.17, 1.58) at D28 to 1.52 (95%CI: 1.21, 1.90) at D196, whilst for BNT/NVX this aGMR was 0.55 (95%CI: 0.47, 0.64) at day 28 and 0.62 (95%CI: 0.49, 0.78) at day 196. Heterologous ChAd-primed schedules produced and maintained the largest T-cell responses until D196. Immunisation with BNT/NVX generated a qualitatively different antibody response to BNT/BNT, with the total IgG significantly lower than BNT/BNT during all follow-up time points, but similar levels of neutralising antibodies. INTERPRETATION: Heterologous ChAd-primed schedules remain more immunogenic over time in comparison to ChAd/ChAd. BNT-primed schedules with a second dose of either mRNA vaccine also remain more immunogenic over time in comparison to BNT/NVX. The emerging data on mixed schedules using the novel vaccine platforms deployed in the COVID-19 pandemic, suggest that heterologous priming schedules might be considered as a viable option sooner in future pandemics. ISRCTN: 27841311 EudraCT:2021-001275-16 FUNDING: UK Vaccine Task Force (VTF), Coalition for Epidemic Preparedness Innovations (CEPI) and National Institute for Health and Carte Research (NIHR). NVX was supplied for trial use by Novavax, Inc
Insulin and IGF1 signalling pathways in human astrocytes <i>in vitro</i> and <i>in vivo</i>; characterisation, subcellular localisation and modulation of the receptors.
Background
The insulin/IGF1 signalling (IIS) pathways are involved in longevity regulation and are dysregulated in neurons in Alzheimer’s disease (AD). We previously showed downregulation in IIS gene expression in astrocytes with AD-neuropathology progression, but IIS in astrocytes remains poorly understood. We therefore examined the IIS pathway in human astrocytes and developed models to reduce IIS at the level of the insulin or the IGF1 receptor (IGF1R).
Results
We determined IIS was present and functional in human astrocytes by immunoblotting and showed astrocytes express the insulin receptor (IR)-B isoform of Ir. Immunocytochemistry and cell fractionation followed by western blotting revealed the phosphorylation status of insulin receptor substrate (IRS1) affects its subcellular localisation. To validate IRS1 expression patterns observed in culture, expression of key pathway components was assessed on post-mortem AD and control tissue using immunohistochemistry. Insulin signalling was impaired in cultured astrocytes by treatment with insulin + fructose and resulted in decreased IR and Akt phosphorylation (pAkt S473). A monoclonal antibody against IGF1R (MAB391) induced degradation of IGF1R receptor with an associated decrease in downstream pAkt S473. Neither treatment affected cell growth or viability as measured by MTT and Cyquant® assays or GFAP immunoreactivity.
Discussion
IIS is functional in astrocytes. IR-B is expressed in astrocytes which differs from the pattern in neurons, and may be important in differential susceptibility of astrocytes and neurons to insulin resistance. The variable presence of IRS1 in the nucleus, dependent on phosphorylation pattern, suggests the function of signalling molecules is not confined to cytoplasmic cascades. Down-regulation of IR and IGF1R, achieved by insulin + fructose and monoclonal antibody treatments, results in decreased downstream signalling, though the lack of effect on viability suggests that astrocytes can compensate for changes in single pathways. Changes in signalling in astrocytes, as well as in neurons, may be important in ageing and neurodegeneration
Measurement of the F2 structure function in deep inelastic ep scattering using 1994 data from the ZEUS detector at HERA
We present measurements of the structure function \Ft\ in e^+p scattering at HERA in the range 3.5\;\Gevsq < \qsd < 5000\;\Gevsq. A new reconstruction method has allowed a significant improvement in the resolution of the kinematic variables and an extension of the kinematic region covered by the experiment. At \qsd < 35 \;\Gevsq the range in x now spans 6.3\cdot 10^{-5} < x < 0.08 providing overlap with measurements from fixed target experiments. At values of Q^2 above 1000 GeV^2 the x range extends to 0.5. Systematic errors below 5\perc\ have been achieved for most of the kinematic urray, W
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