Development of techniques for high-resolution spatially-resolved elemental analysis in materials of interest in luminescence dating

A series of analytical techniques have been developed to characterise the surface distribution of elements in a number of materials of archaeological interest, in support of current and future research in luminescence dating techniques. Under certain circumstances, sample heterogeneity, with respect to naturally occurring radionuclides, may significantly reduce the levels of accuracy associated with experimentally determined luminescence dates. The aim of this thesis is to develop a series of high-resolution, spatially resolved techniques to assess and quantify the degree of matrix (material fabric) radionuclide heterogeneity present in a number of archaeological materials. Digital analysis and mineralogical staining techniques were combined to provide initial data regarding matrix heterogeneity and the distribution patterns of potassium-bearing minerals and in some cases, provided data that were comparable to those derived from SEM-EDX analyses. Alpha autoradiographic techniques using solid state nuclear track detectors (CR-39) were applied initially to map localised differences in surface alpha activity, and were subsequently developed to provide semi-quantitative data about the concentration of alpha emitters present, and by association, the likely concentrations of uranium and thorium. Micro-sampling techniques were developed to produce material for instrumental analysis (ICP-MS and AAS), to provide quantitative information about the concentrations of uranium, thorium and potassium in the areas of interest, highlighted by the application of the aforementioned techniques. The techniques were successfully applied in a number of case studies, providing both quantitative and qualitative information relating to material characteristics with respect to luminescence dating techniques

Effectively Measuring Exercise-Related Variations in T1ρ and T2 Relaxation Times of Healthy Articular Cartilage.

BACKGROUND: Determining the compositional response of articular cartilage to dynamic joint-loading using MRI may be a more sensitive assessment of cartilage status than conventional static imaging. However, distinguishing the effects of joint-loading vs. inherent measurement variability remains difficult, as the repeatability of these quantitative methods is often not assessed or reported. PURPOSE: To assess exercise-induced changes in femoral, tibial, and patellar articular cartilage composition and compare these against measurement repeatability. STUDY TYPE: Prospective observational study. POPULATION: Phantom and 19 healthy participants. FIELD STRENGTH/SEQUENCE: 3T; 3D fat-saturated spoiled gradient recalled-echo; T1ρ - and T2 -prepared pseudosteady-state 3D fast spin echo. ASSESSMENT: The intrasessional repeatability of T1ρ and T2 relaxation mapping, with and without knee repositioning between two successive measurements, was determined in 10 knees. T1ρ and T2 relaxation mapping of nine knees was performed before and at multiple timepoints after a 5-minute repeated, joint-loading stepping activity. 3D surface models were created from patellar, femoral, and tibial articular cartilage. STATISTICAL TESTS: Repeatability was assessed using root-mean-squared-CV (RMS-CV). Using Bland-Altman analysis, thresholds defined as the smallest detectable difference (SDD) were determined from the repeatability data with knee repositioning. RESULTS: Without knee repositioning, both surface-averaged T1ρ and T2 were very repeatable on all cartilage surfaces, with RMS-CV SDD) average exercise-induced in T1ρ and T2 of femoral (-8.0% and -5.3%), lateral tibial (-6.9% and -5.9%), medial tibial (+5.8% and +2.9%), and patellar (-7.9% and +2.8%) cartilage were observed. DATA CONCLUSION: Joint-loading with a stepping activity resulted in T1ρ and T2 changes above background measurement error. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1 J. MAGN. RESON. IMAGING 2020;52:1753-1764.GlaxoSmithKline National Institute of Health Research (NIHR) Cambridge Biomedical Research Centr

The host immune response to gastrointestinal nematode infection in sheep

non peer reviewedGastrointestinal nematode infection represents a major threat to the health, welfare and productivity of sheep populations worldwide. Infected lambs have a reduced ability to absorb nutrients from the gastrointestinal tract, resulting in morbidity and occasional mortality. The current chemo-dominant approach to nematode control is considered unsustainable due to the increasing incidence of anthelmintic resistance. In addition there is growing consumer demand for food products from animals not subjected to chemical treatment. Future mechanisms of nematode control must rely on alternative, sustainable strategies such as vaccination or selective breeding of resistant animals. Such strategies take advantage of the host's natural immune response to nematodes. The ability to resist gastrointestinal nematode infection is considered to be dependent on the development of a protective acquired immune response; although the precise immune mechanisms involved in initiating this process remain to be fully elucidated. In this paper current knowledge on the innate and acquired host immune response to gastrointestinal nematode infection in sheep and the development of immunity is reviewed.We gratefully acknowledge funding support for the research in our laboratories from the Teagasc Walsh Fellowship Programme, the Allan and Grace Kay Overseas Scholarship and the EC-funded FP7 Programme. We also thank the BBSRC Animal Health Research Club for funding part of this research (grant BB/l004070/1

"Author! Author!" : Shakespeare and biography

Original article can be found at: http://www.informaworld.com/smpp/title~content=t714579626~db=all Copyright Informa / Taylor & Francis Group. DOI: 10.1080/17450910902764454Since 1996, not a year has passed without the publication of at least one Shakespeare biography. Yet for many years the place of the author in the practice of understanding literary works has been problematized, and even on occasions eliminated. Criticism reads the “works”, and may or may not refer to an author whose “life” contributed to their meaning. Biography seeks the author in the works, the personality that precedes the works and gives them their characteristic shape and meaning. But the form of literary biography addresses the unusual kind of “life” that puts itself into “works”, and this is particularly challenging where the “works” predominate massively over the salient facts of the “life”. This essay surveys the current terrain of Shakespeare biography, and considers the key questions raised by the medium: can we know anything of Shakespeare's “personality” from the facts of his life and the survival of his works? What is the status of the kind of speculation that inevitably plays a part in biographical reconstruction? Are biographers in the end telling us as much about themselves as they tell us about Shakespeare?Peer reviewe

Sunyaev-Zel'dovich observations of galaxy clusters out to the virial radius with the Arcminute Microkelvin Imager

We present observations using the Small Array of the Arcminute Microkelvin Imager (AMI; 14-18 GHz) of four Abell and three MACS clusters spanning 0.171-0.686 in redshift. We detect Sunyaev-Zel'dovich (SZ) signals in five of these without any attempt at source subtraction, although strong source contamination is present. With radio-source measurements from high-resolution observations, and under the assumptions of spherical $\beta$-model, isothermality and hydrostatic equilibrium, a Bayesian analysis of the data in the visibility plane detects extended SZ decrements in all seven clusters over and above receiver noise, radio sources and primary CMB imprints. Bayesian evidence ratios range from 10^{11}:1 to 10^{43}:1 for six of the clusters and 3000:1 for one with substantially less data than the others. We present posterior probability distributions for, e.g., total mass and gas fraction averaged over radii internal to which the mean overdensity is 1000, 500 and 200, r_200 being the virial radius. Reaching r_200 involves some extrapolation for the nearer clusters but not for the more-distant ones. We find that our estimates of gas fraction are low (compared with most in the literature) and decrease with increasing radius. These results appear to be consistent with the notion that gas temperature in fact falls with distance (away from near the cluster centre) out to the virial radius.Comment: 18 pages, 10 figures, submitted to MNRAS (updated authors and fixed Figure 1

Detailed SZ study of 19 LoCuSS galaxy clusters: masses and temperatures out to the virial radius

We present 16-GHz AMI SZ observations of 19 clusters with L_X >7x10^37 W (h50=1) selected from the LoCuS survey (0.142<z<0.295) and of A1758b, in the FoV of A1758a. We detect 17 clusters with 5-23sigma peak surface brightnesses. Cluster parameters are obtained using a Bayesian cluster analysis. We fit isothermal beta-models to our data and assume the clusters are virialized (with all the kinetic energy in gas internal energy). Our gas temperature, T_AMI, is derived from AMI SZ data, not from X-ray spectroscopy. Cluster parameters internal to r500 are derived assuming HSE. We find: (i) Different gNFW parameterizations yield significantly different parameter degeneracies. (ii) For h70 = 1, we find the virial radius r200 to be typically 1.6+/-0.1 Mpc and the total mass M_T(r200) typically to be 2.0-2.5xM_T(r500).(iii) Where we have found M_T X-ray (X) and weak-lensing (WL) values in the literature, there is good agreement between WL and AMI estimates (with M_{T,AMI}/M_{T,WL} =1.2^{+0.2}_{-0.3} and =1.0+/-0.1 for r500 and r200, respectively). In comparison, most Suzaku/Chandra estimates are higher than for AMI (with M_{T,X}/M_{T,AMI}=1.7+/-0.2 within r500), particularly for the stronger mergers.(iv) Comparison of T_AMI to T_X sheds light on high X-ray masses: even at large r, T_X can substantially exceed T_AMI in mergers. The use of these higher T_X values will give higher X-ray masses. We stress that large-r T_SZ and T_X data are scarce and must be increased. (v) Despite the paucity of data, there is an indication of a relation between merger activity and SZ ellipticity. (vi) At small radius (but away from any cooling flow) the SZ signal (and T_AMI) is less sensitive to ICM disturbance than the X-ray signal (and T_X) and, even at high r, mergers affect n^2-weighted X-ray data more than n-weighted SZ, implying significant shocking or clumping or both occur even in the outer parts of mergers.Comment: 45 pages, 33 figures, 13 tables Accepted for publication in MNRA

A blind detection of a large, complex, Sunyaev--Zel'dovich structure

We present an interesting Sunyaev-Zel'dovich (SZ) detection in the first of the Arcminute Microkelvin Imager (AMI) 'blind', degree-square fields to have been observed down to our target sensitivity of 100{\mu}Jy/beam. In follow-up deep pointed observations the SZ effect is detected with a maximum peak decrement greater than 8 \times the thermal noise. No corresponding emission is visible in the ROSAT all-sky X-ray survey and no cluster is evident in the Palomar all-sky optical survey. Compared with existing SZ images of distant clusters, the extent is large (\approx 10') and complex; our analysis favours a model containing two clusters rather than a single cluster. Our Bayesian analysis is currently limited to modelling each cluster with an ellipsoidal or spherical beta-model, which do not do justice to this decrement. Fitting an ellipsoid to the deeper candidate we find the following. (a) Assuming that the Evrard et al. (2002) approximation to Press & Schechter (1974) correctly gives the number density of clusters as a function of mass and redshift, then, in the search area, the formal Bayesian probability ratio of the AMI detection of this cluster is 7.9 \times 10^4:1; alternatively assuming Jenkins et al. (2001) as the true prior, the formal Bayesian probability ratio of detection is 2.1 \times 10^5:1. (b) The cluster mass is MT,200 = 5.5+1.2\times 10^14h-1M\odot. (c) Abandoning a physical model with num- -1.3 70 ber density prior and instead simply modelling the SZ decrement using a phenomenological {\beta}-model of temperature decrement as a function of angular distance, we find a central SZ temperature decrement of -295+36 {\mu}K - this allows for CMB primary anisotropies, receiver -15 noise and radio sources. We are unsure if the cluster system we observe is a merging system or two separate clusters.Comment: accepted MNRAS. 12 pages, 9 figure

Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study protocol for a randomized controlled trial.

Background: Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain. Methods/design: HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis. Discussion: The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting

Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study protocol for a randomized controlled trial

Background Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain. Methods/design HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis. Discussion The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting. Trial registration ISRCTN91859104