Sulphur-isotope compositions of pig tissues from a controlled feeding study

Sulphur-isotope determinations are becoming increasingly useful for palaeodietary reconstruction, but knowledge of isotopic discrimination between diet and various tissues remains inadequate. In this study, we explore the sensitivity of δ34Stissue values to changes in δ34Sdiet values, sulphur isotopic discrimination between diet and consumer, and the potential impact of terrestrial vs. marine protein consumption on these discrimination offsets. We present new δ34S values of bone collagen, muscle, liver, hair, milk and faeces from ten mature sows, ten piglets and fifteen adolescent pigs from a controlled feeding study. The δ34Stissue values were found to co-vary with the δ34Sdiet values, the δ34Stissue – δ34Sdiet isotopic offsets (Δ34Stissue-diet) are small but consistent, and dietary protein source does not systematically alter the Δ34Stissue-diet isotopic discrimination. The outcomes of this study are of particular relevance to questions that are difficult to resolve using carbon and nitrogen stable isotopes alone, and will also be useful in regions where terrestrial, freshwater, and marine resources could have all potentially contributed to human diet

Mathematical modelling of a magnetic immunoassay

© The authors 2017. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved. A mathematical model is developed to describe the action of a novel form of fluidic biosensor that uses paramagnetic particles (PMPs) that have been pre-coated with target-specific antibodies. In an initial phase the particles are introduced to a sample solution containing the target which then binds to the particles via antigen-antibody reactions. During the test phase a magnet is used to draw the PMPs to the sensor surface which is similarly coated with specific antibodies. During this process, cross-links are formed by the antigens thereby binding the PMPs to the sensor surface. After the magnetic field is removed, a voltage change across an inductor below the sensor surface is recorded, which is deemed to depend on the number of magnetic particles that have been bound to the sensor surface. The fundamental question addressed is to explain the range of experimentally observed dose-response curves, and how this depends on the various parameters of the problem. In particular, observations have shown both rising and falling dose-response curves, as well as 'hooked' dose-response curves possessing local maxima. Initially a particle-dynamics computational model is produced to determine the time scales of the key processes involved, but is shown to be unable to produce differently shaped dose-response curves. The computational model suggests spatio-temporal effects are unimportant, therefore a homogenized rateequation model is developed for each of the key phases of the immunoassay process. Binding rates are shown to depend on various geometric factors related to the diameter of the PMPs and the size of the sensor surface. The dose-response is shown to depend crucially on various saturation effects during each phase, and conditions can be derived, in some cases analytically, for each of the three qualitatively different curve types. Furthermore, non-dimensionalization reveals 5 key dimensionless parameters and the dependence of these curve shapes on each is revealed. The results point to future quantitative approaches to sensor design and calibration

Galaxy redshift surveys selected by neutral hydrogen using FAST

We discuss the possibility of performing a substantial spectroscopic galaxy redshift survey selected via the 21cm emission from neutral hydrogen using the Five-hundred metre Aperture Spherical Telescope (FAST) to be built in China. We consider issues related to the estimation of the source counts and optimizations of the survey, and discuss the constraints on cosmological models that such a survey could provide. We find that a survey taking around two years could detect ~10^7 galaxies with an average redshift of ~0.15 making the survey complementary to those already carried out at optical wavelengths. These conservative estimates have used the z=0 HI mass function and have ignored the possibility of evolution. The results could be used to constrain Gamma = (Omega_m h) to 5 per cent and the spectral index, n_s, to 7 per cent independent of cosmic microwave background data. If we also use simulated power spectra from the Planck satellite, we can constrain w to be within 5 per cent of -1.Comment: 13 pages, 15 figures, Accepted by MNRAS, minor correction

Music Information Technology and Professional Stakeholder Audiences: Mind the Adoption Gap

The academic discipline focusing on the processing and organization of digital music information, commonly known as Music Information Retrieval (MIR), has multidisciplinary roots and interests. Thus, MIR technologies have the potential to have impact across disciplinary boundaries and to enhance the handling of music information in many different user communities. However, in practice, many MIR research agenda items appear to have a hard time leaving the lab in order to be widely adopted by their intended audiences. On one hand, this is because the MIR field still is relatively young, and technologies therefore need to mature. On the other hand, there may be deeper, more fundamental challenges with regard to the user audience. In this contribution, we discuss MIR technology adoption issues that were experienced with professional music stakeholders in audio mixing, performance, musicology and sales industry. Many of these stakeholders have mindsets and priorities that differ considerably from those of most MIR academics, influencing their reception of new MIR technology. We mention the major observed differences and their backgrounds, and argue that these are essential to be taken into account to allow for truly successful cross-disciplinary collaboration and technology adoption in MIR

Measurement of retinal vessels as a biomarker of cerebrovascular ageing in older HIV positive men compared to controls

Background: To compare retinal vascular measurements, biomarkers of cerebral small vessel disease (SVD), in HIV positive men aged 50 years and above with similarly-aged HIV negative men and younger HIV positive men. Methods: We recruited white, non-diabetic men to a cross-sectional substudy of a larger cohort including three demographically-matched groups. Optic disc centred 45° colour fundus photographs were used to calculate central retinal arterial and venous calibre and the arterial- venous ratio (AVR). We used univariate and multivariable linear regression to compare retinal vessel measurements in the three groups and to identify factors associated with AVR. Results: All HIV positive men were virologically suppressed. In a multivariable model, study group was not associated with AVR (adjusted β 0.010 for HIV positive men 50 years [n=120], 95% CI -0.018 to 0.038, p=0.47; adjusted β 0.00002 for HIV negative men >50 years [n=52], 95% CI -0.022 to 0.022, p=0.99). Factors associated with lower AVR were systolic BP (adjusted β -0.009 per +10 mmHg, 95% CI - 0.015 to -0.003, p=0.002), history of stroke or transient ischemic attack (adjusted β -0.070, 95% CI -0.12 to -0.015, p=0.01), and recent recreational drug use (adjusted β -0.037, 95% CI -0.057 to -0.018, p=0.0002). Conclusion: There were no differences in retinal vascular indices between HIV positive men aged >50 years and HIV negative men aged >50 years or HIV positive men aged <50 years, suggesting that HIV is not associated with an increased burden of cerebral SVD

Magnetic Resonance Imaging Is More Sensitive Than PET for Detecting Treatment-Induced Cell Death-Dependent Changes in Glycolysis.

Metabolic imaging has been widely used to measure the early responses of tumors to treatment. Here, we assess the abilities of PET measurement of [18F]FDG uptake and MRI measurement of hyperpolarized [1-13C]pyruvate metabolism to detect early changes in glycolysis following treatment-induced cell death in human colorectal (Colo205) and breast adenocarcinoma (MDA-MB-231) xenografts in mice. A TRAIL agonist that binds to human but not mouse cells induced tumor-selective cell death. Tumor glycolysis was assessed by injecting [1,6-13C2]glucose and measuring 13C-labeled metabolites in tumor extracts. Injection of hyperpolarized [1-13C]pyruvate induced rapid reduction in lactate labeling. This decrease, which correlated with an increase in histologic markers of cell death and preceded decrease in tumor volume, reflected reduced flux from glucose to lactate and decreased lactate concentration. However, [18F]FDG uptake and phosphorylation were maintained following treatment, which has been attributed previously to increased [18F]FDG uptake by infiltrating immune cells. Quantification of [18F]FDG uptake in flow-sorted tumor and immune cells from disaggregated tumors identified CD11b+/CD45+ macrophages as the most [18F]FDG-avid cell type present, yet they represented <5% of the cells present in the tumors and could not explain the failure of [18F]FDG-PET to detect treatment response. MRI measurement of hyperpolarized [1-13C]pyruvate metabolism is therefore a more sensitive marker of the early decreases in glycolytic flux that occur following cell death than PET measurements of [18F]FDG uptake. SIGNIFICANCE: These findings demonstrate superior sensitivity of MRI measurement of hyperpolarized [1-13C]pyruvate metabolism versus PET measurement of 18F-FDG uptake for detecting early changes in glycolysis following treatment-induced tumor cell death

The Development and Use of Sustainability Criteria in SuRF-UK’s Sustainable Remediation Framework

Sustainability considerations have become widely recognised in contaminated land management and are now accepted as an important component of remediation planning and implementation around the world. The Sustainable Remediation Forum for the UK (SuRF-UK) published guidance on sustainability criteria for consideration in drawing up (or framing) assessments, organised across 15 &ldquo;headline&rdquo; categories, five for the environment element of sustainability, five for the social, and five for the economic. This paper describes how the SuRF-UK indicator guidance was developed, and the rationale behind its structure and approach. It describes its use in remediation option appraisal in the UK, and reviews the international papers that have applied or reviewed it. It then reviews the lessons learned from its initial use and the opinions and findings of international commentators, and concludes with recommendations on how the indicator categories might be further refined in the future. The key findings of this review are that the SuRF-UK framework and indicator guidance is well adopted into practice in the UK. It is widely recognised as the most appropriate mechanism to support sustainability-based decision making in contaminated land decision making. It has influenced the development of other national and international guidance and standards on sustainable remediation. However, there is room for some fine tuning of approach based on the lessons learned during its application

Nasal Administration and Plasma Pharmacokinetics of Parathyroid Hormone Peptide PTH 1-34 for the Treatment of Osteoporosis

Nasal delivery of large peptides such as parathyroid 1-34 (PTH 1-34) can benefit from a permeation enhancer to promote absorption across the nasal mucosa into the bloodstream. Previously, we have published an encouraging bioavailability (78%), relative to subbcutaneous injection in a small animal preclinical model, for a liquid nasal spray formulation containing the permeation enhancer polyethylene glycol (15)-hydroxystearate (Solutol® HS15). We report here the plasma pharmacokinetics of PTH 1-34 in healthy human volunteers receiving the liquid nasal spray formulation containing Solutol® HS15. For comparison, data for a commercially manufactured teriparatide formulation delivered via subcutaneous injection pen are also presented. Tc-99m-DTPA gamma scintigraphy monitored the deposition of the nasal spray in the nasal cavity and clearance via the inferior meatus and nasopharynx. The 50% clearance time was 17.8 min (minimum 10.9, maximum 74.3 min). For PTH 1-34, mean plasma Cmax of 5 pg/mL and 253 pg/mL were obtained for the nasal spray and subcutaneous injection respectively; relative bioavailability of the nasal spray was 1%. Subsequently, we investigated the pharmacokinetics of the liquid nasal spray formulation as well as a dry powder nasal formulation also containing Solutol® HS15 in a crossover study in an established ovine model. In this preclinical model, the relative bioavailability of liquid and powder nasal formulations was 1.4% and 1.0% respectively. The absolute bioavailability of subcutaneously administered PTH 1-34 (mean 77%, range 55–108%) in sheep was in agreement with published human data for teriparatide (up to 95%). These findings have important implications in the search for alternative routes of administration of peptides for the treatment of osteoporosis, and in terms of improving translation from animal models to humans