Mixed Methods Research: A Comprehensive Approach for Study into the New Zealand Voluntary Carbon Market

Climate change and solutions to solving this wicked problem require a mixed methods research approach that draws on quantitative and qualitative inquiry together. The purpose of this article is to demonstrate the applicability (and effectiveness) of a mixed methods approach applied to research into the voluntary carbon market (VCM), a key path available for organisations electing to offset their carbon emissions, in New Zealand. The mixed methods approach included three unique data sets (quantitative documents, quantitative surveys, qualitative in-depth interviews), and was both explanatory (qualitative interviews built upon and contextualized the document analysis and survey results) and convergent (data sets were examined separately, then, as they represent different aspects of the same phenomenon, were combined for analysis). These complementary methods were used to gain a fuller picture of the evolution and institutional dynamics of the VCM field in order to produce a comprehensive case study

Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay

Objectives: Lead antituberculosis (anti-TB) molecules with novel mechanisms of action are urgently required to fuel the anti-TB drug discovery pipeline. The aim of this study was to validate the use of the high-throughput spot culture growth inhibition (HT-SPOTi) assay for screening libraries of compounds against Mycobacterium tuberculosis and to study the inhibitory effect of ibuprofen (IBP) and the other 2-arylpropanoic acids on the growth inhibition of M tuberculosis and other mycobacterial species. Methods: The HT-SPOTi method was validated not only with known drugs but also with a library of 47 confirmed anti-TB active compounds published in the ChEMBL database. Three over-the-counter non-steroidal anti-inflammatory drugs were also included in the screening. The 2-arylpropanoic acids, including IBP, were comprehensively evaluated against phenotypically and physiologically different strains of mycobacteria, and their cytotoxicity was determined against murine RAW264.7 macrophages. Furthermore, a comparative bioinformatic analysis was employed to propose a potential mycobacterial target. Results: IBP showed antitubercular properties while carprofen was the most potent among the 2-arylpropanoic class. A 3,5-dinitro-IBP derivative was found to be more potent than IBP but equally selective. Other synthetic derivatives of IBP were less active, and the free carboxylic acid of IBP seems to be essential for its anti-TB activity. IBP, carprofen and the 3,5-dinitro-IBP derivative exhibited activity against multidrug-resistant isolates and stationary phase bacilli. On the basis of the human targets of the 2-arylpropanoic analgesics, the protein initiation factor infB (Rv2839c) of M tuberculosis was proposed as a potential molecular target. Conclusions: The HT-SPOTi method can be employed reliably and reproducibly to screen the antimicrobial potency of different compounds. IBP demonstrated specific antitubercular activity, while carprofen was the most selective agent among the 2-arylpropanoic class. Activity against stationary phase bacilli and multidrug-resistant isolates permits us to speculate a novel mechanism of antimycobacterial action. Further medicinal chemistry and target elucidation studies could potentially lead to new therapies against TB

Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high saturation magnetization value (84.5 emu g(-1)). The surface of the IONPs could be tailored post synthesis with two different ligands which provided functionality and stability in water and phosphate buffer saline (PBS). Their potential as a magnetic resonance imaging (MRI) contrast agent was confirmed as they exhibited high r1 and r2 relaxivities of 7.95 mM(-1) s(-1) and 185.58 mM(-1) s(-1) respectively at 1.4 T. Biocompatibility and viability of IONPs in primary human mesenchymal stem cells (hMSCs) was studied and confirmed

Multicentre analysis of incidental findings on low-resolution CT attenuation correction images : an extended study

Objective: To review new incidental findings detected on low-resolution CT attenuation correction (CTAC) images acquired during single-photon emission CT-CT myocardial perfusion imaging as an extension to our initial study. Methods: CTAC images acquired as part of myocardial perfusion imaging performed using single-photon emission CT at four UK nuclear medicine centres were evaluated as part of a multicentre study. New incidental findings that were considered to be clinically significant were evaluated further. Positive-predictive value (PPV) was determined at the time of definitive diagnosis. Results: Out of 3485 patients, 962 (28%) patients had a positive finding on the CTAC image, of which 824 (24%) were new findings. 84 (2.4%) patients had findings that were considered clinically significant at the time of the CTAC report and which had not been previously diagnosed. However, only 10 (0.29%) of these had findings that were confirmed as clinically significant, with the potential to be detrimental to patient outcome, after follow-up and definitive diagnosis. Conclusion: The overall PPV from all centres over the 2-year period was 12%. Each centre achieved what we considered to be low PPVs with no significant difference between the present and initial studies. The additional data from the combined studies show that, statistically, there is no significant difference between the PPVs from any of the centres. We conclude that routine reporting of CTAC images is not beneficial. Advances in knowledge: This study combined with the previous study offers a unique evaluation of new clinically significant incidental findings on low-resolution CT images in an attempt to determine the benefit of reporting the CTAC images

Parity Violation in Proton-Proton Scattering

Measurements of parity-violating longitudinal analyzing powers (normalized asymmetries) in polarized proton-proton scattering provide a unique window on the interplay between the weak and strong interactions between and within hadrons. Several new proton-proton parity violation experiments are presently either being performed or are being prepared for execution in the near future: at TRIUMF at 221 MeV and 450 MeV and at COSY (Kernforschungsanlage Juelich) at 230 MeV and near 1.3 GeV. These experiments are intended to provide stringent constraints on the set of six effective weak meson-nucleon coupling constants, which characterize the weak interaction between hadrons in the energy domain where meson exchange models provide an appropriate description. The 221 MeV is unique in that it selects a single transition amplitude (3P2-1D2) and consequently constrains the weak meson-nucleon coupling constant h_rho{pp}. The TRIUMF 221 MeV proton-proton parity violation experiment is described in some detail. A preliminary result for the longitudinal analyzing power is Az = (1.1 +/-0.4 +/-0.4) x 10^-7. Further proton-proton parity violation experiments are commented on. The anomaly at 6 GeV/c requires that a new multi-GeV proton-proton parity violation experiment be performed.Comment: 13 Pages LaTeX, 5 PostScript figures, uses espcrc1.sty. Invited talk at QULEN97, International Conference on Quark Lepton Nuclear Physics -- Nonperturbative QCD Hadron Physics & Electroweak Nuclear Processes --, Osaka, Japan May 20--23, 199

FlgN is required for flagellum based motility by <em>Bacillus subtilis</em>

The assembly of the bacterial flagellum is exquisitely controlled. Flagellar biosynthesis is underpinned by a specialized type III secretion system that allows export of proteins from the cytoplasm to the nascent structure. Bacillus subtilis regulates flagellar assembly using both conserved and species-specific mechanisms. Here, we show that YvyG is essential for flagellar filament assembly. We define YvyG as an orthologue of the Salmonella enterica serovar Typhimurium type III secretion system chaperone, FlgN, which is required for the export of the hook-filament junction proteins, FlgK and FlgL. Deletion of flgN (yvyG) results in a nonmotile phenotype that is attributable to a decrease in hag translation and a complete lack of filament polymerization. Analyses indicate that a flgK-flgL double mutant strain phenocopies deletion of flgN and that overexpression of flgK-flgL cannot complement the motility defect of a ΔflgN strain. Furthermore, in contrast to previous work suggesting that phosphorylation of FlgN alters its subcellular localization, we show that mutation of the identified tyrosine and arginine FlgN phosphorylation sites has no effect on motility. These data emphasize that flagellar biosynthesis is differentially regulated in B. subtilis from classically studied Gram-negative flagellar systems and questions the biological relevance of some posttranslational modifications identified by global proteomic approaches

Research Handbook on Human Rights and Business

This authoritative Research Handbook brings together leading international scholars and practitioners to provide in-depth analysis of some of the most hotly debated topics and issues concerning the interface of human rights and business. Offering critical insights on prominent strands of research within the field of business and human rights, this comprehensive Research Handbook examines key challenges and potential solutions in the field

Hydrodynamic gene delivery in human skin using a hollow microneedle device

Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50 μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery