Assessment of coupled Zn concentration and natural stable isotope analyses of urine as a novel probe of Zn status

Zinc is a common trace metal in the human body, present in about 10% of proteins. Despite numerous roles of Zn in health and disease, there is still a need for a robust biomarker of Zn status. Many parameters have been proposed, with varying levels of success, with plasma Zn often favoured. This study investigates if Zn status can be assessed from the natural stable Zn isotope composition of urine. To this end, 60 urine samples were analysed from ten healthy participants. Remarkably, samples with lower Zn concentrations are systematically enriched in heavy Zn isotopes. Most of the low-Zn urine originated from individuals who omitted dairy, meat or both from their diets. When data for blood serum from age-matched, healthy individuals are compared with the urine results, the former plot at the extension of the urine trend at higher Zn concentrations and lighter isotope compositions. The observed co-variation of Zn isotope compositions with concentrations is indicative of an isotope fractionation system where both properties are controlled by the same processes. It is interpreted as arising from filtration and/or reabsorption processes within the kidney, which are associated with absorbed dietary Zn. The data suggest that the Zn in blood serum that is bound to low molecular weight molecules has an isotope composition distinct from total serum, due to the different affinities of molecular Zn-binding residues to heavy and light Zn isotopes. This technique provides additional information into an individual's Zn status compared to urine or plasma Zn levels alone

High precision zinc stable isotope measurement of certified biological reference materials using the double spike technique and multiple collector-ICP-MS

Biological reference materials with well-characterized s table isotope compositions are lacking in the field of ‘isotope biochemistry’, which seeks to understand bodily processes that rely on essential metals by determining metal stable isotope ratios. Here, we present Zn stable isotope data for six biological reference materials with certified trace metal concentrations, fish muscle, bovine muscle, pig kidney, human hair, human blood serum and human urine. Replicate analyses of multiple aliquots of each material achieved reproducibilities (2sd) of 0.04-0.13 ‰ for δ66/64Zn 22 (which denotes the deviation of the 66 Zn/64Zn ratio of a sample from a pure Zn reference material in parts per 1000). This implies only very minor isotopic heterogeneities within the samples, rendering them suitable as quality control materials for Zn isotopeanalyses. This endorsement is reinforced by (i) the close agreement of our Zn isotope data for two of the samples (bovine 2 muscle and human blood serum) to previously published results for different batches of the same material and (ii) the similarity of the isotopic data for the samples (δ66/64Zn≈ –0.8 to 0.0 ‰) to previously published Zn isotope results for similar biological materials. Further tests revealed that the applied Zn separation procedure is sufficiently effective to enable accurate data acquisition even at low mass resolving power (M/ΔM ≈ 400), as measurements and analyses conducted at much higher mass resolution (M/ΔM ≈ 8500) delivered essentially identical results

The multilevel voter: Identity, territory and electoral behaviour

This thesis is concerned with sub-state politics and the influence it has on political behaviour and attitudes. Parting company with much of the existing literature that examines elections in multilevel systems, I argue that it is incorrect to assume that factors at the statewide level determine electoral behaviour and attitudes at the sub-state level. Rather, elections at the statewide and sub-state level should be seen as interdependent. Chapter 1 serves as an introduction to the thesis and sets up the analytic framework upon which my research is based. I also give a broad discussion of my method and explain why I choose Scotland and Wales as cases in my argument. In Chapter 2, I outline and describe my primary data sources – the devolved election studies – by detailing their origins and design. Chapter 3 examines what voters know about sub-state politics. I examine data from 10 election studies in total and introduce a unique new dataset of press coverage of the NHS to examine policy attribution. I find that considerable proportions of citizens have little knowledge of sub-state political issues. Chapter 4 focuses on the role that national identities play in vote choice at sub-state and statewide elections. I also introduce the concept of party blocs in Scotland and Wales. Results indicate that national identity is a substantial predictor of bloc vote choice. In Chapter 5 I examine how sub-state identities influence how voters cast their ballots at elections to different levels of government. My results indicate that vote switching is more prevalent among those who identify with a sub-state identity (instead of a statewide identity). Chapter 6 tests whether split-ticket voting at devolved elections is driven by strategic motivations. While voters appear to understand when it is in their interests to cast a strategic vote in their constituency, there is no evidence suggesting they do in the list vote. In the final chapter, I conclude by highlighting the findings of this thesis and remarking on the importance of this work for future analyses of elections in multilevel systems

Free versus total serum 25-hydroxyvitamin D in a murine model of colitis

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease have been linked to vitamin D-deficiency. Using a dextran sodium sulphate (DSS)-induced model of IBD we have shown previously that mice raised on vitamin D-deficient diets from weaning have lower serum 25-hydroxyvitamin D (25OHD) levels and develop more severe colitis compared to vitamin D-sufficient counterparts. We have also shown in vitro that immune responses to 25OHD may depend on 'free' rather than total serum concentrations of 25OHD. To investigate the possible effects of free versus total 25OHD on anti-inflammatory immune responses in vivo we have studied DSS-induced colitis in wild type C57BL/6 mice raised from weaning on diets containing vitamin D2 (D2) or vitamin D3 (D3) only (both 1000 IU/kg feed). 25OHD2 has lower binding affinity for the vitamin D binding protein than 25OHD3 which results in higher levels of free 25OHD2 relative to free 25OHD3 in mice raised on a D2-only diet. Total serum 25OHD concentrations, measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), showed that D2 mice had significantly lower levels of 25OHD than D3 mice (6.85 ± 2.61 nmol/L vs. 49.16 ± 13.8 nmol/L for D2 and D3 respectively). Despite this, direct ELISA measurement showed no difference in free serum 25OHD levels between D2 and D3 mice (13.62 ± 2.26 pmol/L vs. 14.11 ± 2.24 pmol/L for D2 and D3 respectively). Analysis of DSS-induced colitis also showed no difference in weight loss or disease progression between D2 and D3 mice. These data indicate that despite D2-fed mice being vitamin D-deficient based on serum total 25OHD concentrations, these mice showed no evidence of increased inflammatory colitis disease relative to vitamin D-sufficient D3 mice. We therefore propose that free, rather than total serum 25OHD, may be a better marker of immune responses to vitamin D in vivo

Computed tomography-based anatomic assessment overestimates local tumor recurrence in patients with mass-like consolidation after stereotactic body radiotherapy for early-stage non-small cell lung cancer.

PURPOSE: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. METHODS AND MATERIALS: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. RESULTS: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade ≥ 2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). CONCLUSION: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will increase the likelihood of correctly identifying patients with progressive disease after lung SBRT

Thinking beyond the hybrid:“actually-existing” cities “after neoliberalism” in Boyle <i>et al.</i>

In their article, ‘The spatialities of actually existing neoliberalism in Glasgow, 1977 to present’, Mark Boyle, Christopher McWilliams and Gareth Rice (2008) usefully problematise our current understanding of neoliberal urbanism. Our response is aimed at developing a sympathetic but critical approach to Boyle et al's understanding of neoliberal urbanism as illustrated by the Glasgow example. In particular, the counterposing by Boyle et al of a 'hybrid, mutant' model to a 'pure' model of neoliberalism for us misrepresents existing models of neoliberalism as a perfectly finished object rather than a roughly mottled process. That they do not identify any ‘pure’ model leads them to create a straw construct against which they can claim a more sophisticated, refined approach to the messiness of neoliberal urbanism. In contrast, we view neoliberalism as a contested and unstable response to accumulation crises at various scales of analysis

The open source guild: creating more sustainable enterprise?

© 2017, © Emerald Publishing Limited. Purpose: The purpose of this paper is to report on an action research project with two emergent micro-businesses that explored how their business model connected with the principles of open source. Design/methodology/approach: The authors first gained initial qualitative data to establish the core values of each micro-business, which the authors then explored in the context of open source and business models in two design workshops with each organisation. Findings: The authors developed the open source guild business model, which has the elements of: building a focal micro-business with resources secured through the guild, promoting learning and development through apprenticeship, promoting shared values through a commons of experience and capturing value by protecting key intellectual property. Research limitations/implications: This research was undertaken with two emergent micro-businesses in the North West of England. Further research will be needed to establish the wider applicability of the open source guild model. Practical implications: The open source guild model can be a mechanism for an emergent micro-business to create a community around their values and grow their business without conventional external investment of resources. Originality/value: This research contributes to the literature on business models based on open source and how these models can be sustainable in terms of the quadruple bottom line, which extends the triple bottom line to include personal values and meaning