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Crises spur reflection and re-evaluation of what matters and what is valued. The impacts of the 2008 global financial crisis, COVID-19 pandemic and climate emergency are reigniting debates about the nature of economic development approaches and what they aim to achieve in urban settings. Addressing a substantive gap in contemporary debates by helping to navigate a burgeoning and diverse field, this paper provides a critical and comparative assessment of five leading agendas that have been positioned as alternative and progressive policy responses to urban economic change: inclusive growth; the wellbeing economy; community wealth building; doughnut economics; and the foundational economy. Taking an international perspective, the paper provides a comparative review of their stated visions, mechanisms for change, and the spatial scales through which they are led and implemented. Our argument is that these alternative approaches to urban economic development are shaping creative, innovative and progressive responses to longstanding urban problems within policy and practice communities but require on-going scrutiny and evaluation to realise their potential to meaningfully achieve transformative change. [ABSTRACT FROM AUTHOR]

City leaders around the world are setting ambitious targets for emissions reductions. Yet the pathway to achieving this remains largely unspecified. Starting with this objective, the paper explores the merits of deploying a mission-oriented framework within the context of a 'wicked problem' by looking at a mid-sized city, Glasgow, which has a target for net zero by 2030. Focusing on themes drawn from one high-emitting sector – transport – the paper points to the real-world policy implications that stem from such a mission-oriented approach to suggest aspects of the approach that may be usefully developed further. The latter hinges on a-priori considerations given to: agency, boundaries and inter-temporality, leading to questions about the nature and scope of wickedness and argues that core issues of wickedness – uncertainty, contestation and complexity – can be amplified in local and multi-layered policy making contexts. Key policy insights Many cities are looking to reduce emissions including establishing net zero targets and a mission-oriented framework – 'concrete targets within a challenge that act as frames and stimuli for innovation' (Mazzucato and Dibb, 2019) – has been a popular framing vehicle. Such a framework reveals challenges inherent in such a 'wicked problem' at urban scales, which are interwoven with regional and national issues, institutions and influences. Exploring these for Glasgow, which hosted COP26, we highlight the policy 'problem' and 'solution' space for mid-sized cities more generally. We highlight three dimensions that reflect the nature of the urban decarbonization challenge: agency – the responsibilities of various actors in delivering change; boundaries – the interactions between actions to reduce emissions alongside wider policy ambitions such as a 'Just Transition' and 'green jobs'; and intertemporal issues – including how ambitions for rapid change might interact with the glacial progress of structural policy change. [ABSTRACT FROM AUTHOR]

To protect New Zealand's unique ecosystems and primary industries, imported plant materials must be constantly monitored at the border for high-threat pathogens. Techniques adopted for this purpose must be robust, accurate, rapid, and sufficiently agile to respond to new and emerging threats. Polymerase chain reaction (PCR), especially real-time PCR, remains an essential diagnostic tool but it is now being complemented by high-throughput sequencing using both Oxford Nanopore and Illumina technologies, allowing unbiased screening of whole populations. The demand for and value of Point-of-Use (PoU) technologies, which allow for in situ screening, are also increasing. Isothermal PoU molecular diagnostics based on recombinase polymerase amplification (RPA) and loop-mediated amplification (LAMP) do not require expensive equipment and can reach PCR-comparable levels of sensitivity. Recent advances in PoU technologies offer opportunities for increased specificity, accuracy, and sensitivities which makes them suitable for wider utilization by frontline or border staff. National and international activities and initiatives are adopted to improve both the plant virus biosecurity infrastructure and the integration, development, and harmonization of new virus diagnostic technologies. [ABSTRACT FROM AUTHOR]

The field of biosecurity has greatly benefited from the widespread adoption of high-throughput sequencing technologies, for its ability to deeply query plant and animal samples for pathogens for which no tests exist. However, the bioinformatics analysis tools designed for rapid analysis of these sequencing datasets are not developed with this application in mind, limiting the ability of diagnosticians to standardise their workflows using published tool kits. We sought to assess previously published bioinformatic tools for their ability to identify plant- and animal-infecting viruses while distinguishing from the host genetic material. We discovered that many of the current generation of virus-detection pipelines are not adequate for this task, being outperformed by more generic classification tools. We created synthetic MinION and HiSeq libraries simulating plant and animal infections of economically important viruses and assessed a series of tools for their suitability for rapid and accurate detection of infection, and further tested the top performing tools against the VIROMOCK Challenge dataset to ensure that our findings were reproducible when compared with international standards. Our work demonstrated that several methods provide sensitive and specific detection of agriculturally important viruses in a timely manner and provides a key piece of ground truthing for method development in this space. [ABSTRACT FROM AUTHOR]

Why some cities have been able to sustain economic growth more than others, and how particular technological or sectoral break points shift a city's economic performance favourably (or unfavourably), present ongoing conundrums. Whilst single factor accounts – such as the skilled city and the creative city – have the appeal of analytical parsimony, economic geographers suggest that a multiplicity of structures, processes and events typically sit behind how growth originates and is subsequently shaped. Given such complexity, how can we develop appropriate approaches to theorising causality within urban economic systems? This paper presents the case that critical realism may perform a useful ground-clearing role. With a layered ontology at its core, coupled with recent literature providing greater guidance for empirical application, it is argued that critical realism may present a complementary explanatory perspective. [ABSTRACT FROM AUTHOR]

• Stability of levothyroxine sodium in solution for 24 hours was evaluated using different solvents and stabilisers. • Results suggested that bovine serum albumin is capable of stabilising levothyroxine sodium in solution for up to 14 days. • An HPLC method to separate the protein from levothyroxine sodium was developed and validated following ICH guidelines. • The developed HPLC method was tested to evaluate levothyroxine release from a long acting drug delivery implant. Deficiency of thyroid hormones (hypothyroidism) is treated with oral levothyroxine (LEVO). However, the effectiveness of oral administration is highly dependent on the co-administration of food and other drugs. This factor, in combination with the chronic nature of this condition, mean that there are concerns with patient compliance. Development of long acting formulations to treat hypothyroidism could potentially solve this problem. However, LEVO instability in solution could be problematic. In order to develop long acting LEVO delivery systems in vitro drug release experiments should be carried out. However, short term LEVO stability in aqueous solution will prevent this. BSA was used as a stabiliser for LEVO; extending the stability of the drug in aqueous solutions from a few hours to 2 weeks. In order to achieve this, the required concentration of the protein was 0.1% w/v. Subsequently, an HPLC method capable of separating LEVO from the protein was developed and validated following ICH guidelines. The analysis was carried out using a reverse phase HPLC method on an Agilent 1220 Infinity II LC system. The column used to achieve separation was a Zorbax Eclipse plus C18 (95 Å pore size, 250 mm length x 4.6 mm internal diameter; 5 μm particle size). The mobile phase used was composed of acetonitrile and 0.1% trifluoroacetic acid at a ratio of 50:50% v/v. UV detection of LEVO sodium was carried out at 225 nm. The retention time for the drug was 6.6 minutes. The method showed a limit of detection of 0.03 μg/mL and a limit of quantification of 0.09 μg/mL. Finally, this method was used to evaluate the release from implants containing 20% w/w of LEVO. These devices were prepared using a solvent casting method with poly(caprolactone) and LEVO. These devices showed an initial burst release over the first 3 days. Subsequently, they were capable of providing a linear release rate over the following 25 days. [ABSTRACT FROM AUTHOR]

The adoption of Oxford Nanopore Technologies (ONT) sequencing as a tool in plant virology has been relatively slow despite its promise in more recent years to yield large quantities of long nucleotide sequences in real time without the need for prior amplification. The portability of the MinION and Flongle platforms combined with lowering costs and continued improvements in read accuracy make ONT an attractive method for both low- and high-scale virus diagnostics. Here, we provide a detailed step-by-step protocol using the ONT Flongle platform that we have developed for the routine application on a range of symptomatic post-entry quarantine and domestic surveillance plant samples. The aim of this methods paper is to highlight ONT's feasibility as a valuable component to the diagnostician's toolkit and to hopefully stimulate other laboratories towards the eventual goal of integrating high-throughput sequencing technologies as validated plant virus diagnostic methods in their own right. [ABSTRACT FROM AUTHOR]

Purpose: Age-related macular degeneration is a vision-threatening disorder affecting the posterior segment of the eye. Drug delivery to the posterior segment is challenging owing to the complex anatomical and physiological structure, necessitating monthly injections of antivascular endothelial growth factors. Thermoresponsive hydrogels provide sustained drug delivery and ease of injection, due to their sol-gel transition. Poly (N-isopropyl acrylamide) (PNIPAAm) is a widely researched thermoresponsive hydrogel; however, insufficient wet strength and a wide mesh network make it inept for the entrapment of small molecules. Methods: A novel approach of grafting PNIPAAm with chitosan is exploited. A chitosan concentration altered in 10%, 30%, and 50% compared to PNIPAAm is investigated for entrapment of a small-molecular weight, hydrophilic drug, sunitinib (SUN), a multiple tyrosine kinase receptor inhibitor. Furthermore, these hydrogels were characterized using 1H-NMR, FTIR, differential scanning calorimetry (DSC), and thermogravimetric analysis for chemical characterization and viscosity, swellability, syringeability, degradation, and In-vitro permeation using Franz-diffusion cell. Results:In-vitro drug release kinetics suggested that the release of SUN could be controlled with the percentage of chitosan grafting; however, gel strength (3%-5% w/v) of 30% Cs-g-PNIPAAm did not significantly affect percentage drug release. Sustained release of SUN was observed for 1 month. In-vitro permeation studies on porcine sclera suggested that a thermoresponsive gel of chitosan grafted PNIPAAm (Cs-g-PNIPAAm) was able to sustain the drug release by 40%, compared to SUN solution. Conclusions: The study indicates that the synthesized Cs-g-NIPAAm hydrogel has the potential to serve as a tailorable injectable platform for intrascleral drug delivery applications. [ABSTRACT FROM AUTHOR]

The role of Staphylococcus aureus in the pathogenesis of the chronic sinonasal disease chronic rhinosinusitis (CRS), has not been definitively established. Comparative analyses of S. aureus isolates from CRS with those from control participants may offer insight into a possible pathogenic link between this organism and CRS. The intra- and inter-subject S. aureus strain-level diversity in the sinuses of patients with and without CRS were compared in this cross-sectional study. In total, 100 patients (CRS = 64, control = 36) were screened for S. aureus carriage. The overall carriage prevalence of S. aureus in this cohort was 24% (CRS n = 13, control n = 11). Cultured S. aureus isolates from 18 participants were strain-typed using spa gene sequencing. The bacterial community composition of the middle meatus was assessed using amplicon sequencing targeting the V3V4 hypervariable region of the bacterial 16S rRNA gene. S. aureus isolates cultured from patients were grown in co-culture with the commensal bacterium Dolosigranulum pigrum and characterised. All participants harboured a single S. aureus strain and no trend in disease-specific strain-level diversity was observed. Bacterial community analyses revealed a significant negative correlation in the relative abundances of S. aureus and D. pigrum sequences, suggesting an antagonistic interaction between these organisms. Co-cultivation experiments with these bacteria, however, did not confirm this interaction in vitro. We saw no significant associations of CRS disease with S. aureus strain types. The functional role that S. aureus occupies in CRS likely depends on other factors such as variations in gene expression and interactions with other members of the sinus bacterial community. [ABSTRACT FROM AUTHOR]

[Display omitted] Treatment of neovascular ocular diseases involves intravitreal injections of therapeutic proteins using conventional hypodermic needles every 4–6 weeks. Due to the chronic nature of these diseases, these injections will be administrated to patients for the rest of their lives and their frequent nature can potentially pose a risk of sight-threatening complications and poor patient compliance. Therefore, we propose to develop nanoparticle (NP)-loaded bilayer dissolving microneedle (MN) arrays, to sustain delivery of protein drugs in a minimally invasive manner. In this research, a model protein, ovalbumin (OVA)-encapsulated PLGA NPs were prepared and optimised using a water-in-oil-in-water (W/O/W) double emulsion method. The impact of stabilisers and primary sonication time on the stability of encapsulated OVA was evaluated using an enzyme-linked immunosorbent assay (ELISA). Results showed that the lower primary sonication time was capable of sustaining release (77 days at 28.5% OVA loading) and improving the OVA bioactivity. The optimised NPs were then incorporated into a polymeric matrix to fabricate bilayer MNs and specifically concentrated into MN tips by high-speed centrifugation. Optimised bilayer MNs exhibited good mechanical and insertion properties and rapid dissolution kinetics (less than 3 min) in excised porcine sclera. Importantly, ex vivo transscleral distribution studies conducted using a multiphoton microscope confirmed the important function of MN arrays in the localisation of proteins and NPs in the scleral tissue. Furthermore, the polymers selected to prepare bilayer MNs and OVA NPs were determined to be biocompatible with retinal cells (ARPE-19). This delivery approach could potentially sustain the release of encapsulated proteins for more than two months and effectively bypass the scleral barrier, leading to a promising therapy for treating neovascular ocular diseases. [ABSTRACT FROM AUTHOR]

Organoheterotrophs are the dominant bacteria in most soils worldwide. While many of these bacteria can subsist on atmospheric hydrogen (H2), levels of this gas are generally insufficient to sustain hydrogenotrophic growth. In contrast, bacteria residing within soil-derived termite mounds are exposed to high fluxes of H2 due to fermentative production within termite guts. Here, we show through community, metagenomic, and biogeochemical profiling that termite emissions select for a community dominated by diverse hydrogenotrophic Actinobacteriota and Dormibacterota. Based on metagenomic short reads and derived genomes, uptake hydrogenase and chemosynthetic RuBisCO genes were significantly enriched in mounds compared to surrounding soils. In situ and ex situ measurements confirmed that high- and low-affinity H2-oxidizing bacteria were highly active in the mounds, such that they efficiently consumed all termite-derived H2 emissions and served as net sinks of atmospheric H2. Concordant findings were observed across the mounds of three different Australian termite species, with termite activity strongly predicting H2 oxidation rates (R2 = 0.82). Cell-specific power calculations confirmed the potential for hydrogenotrophic growth in the mounds with most termite activity. In contrast, while methane is produced at similar rates to H2 by termites, mounds contained few methanotrophs and were net sources of methane. Altogether, these findings provide further evidence of a highly responsive terrestrial sink for H2 but not methane and suggest H2 availability shapes composition and activity of microbial communities. They also reveal a unique arthropod-bacteria interaction dependent on H2 transfer between host-associated and free-living microbial communities. [ABSTRACT FROM AUTHOR]

[Display omitted] Implantable drug delivery systems (IDDS) are an attractive alternative to conventional drug administration routes. Oral and injectable drug administration are the most common routes for drug delivery providing peaks of drug concentrations in blood after administration followed by concentration decay after a few hours. Therefore, constant drug administration is required to keep drug levels within the therapeutic window of the drug. Moreover, oral drug delivery presents alternative challenges due to drug degradation within the gastrointestinal tract or first pass metabolism. IDDS can be used to provide sustained drug delivery for prolonged periods of time. The use of this type of systems is especially interesting for the treatment of chronic conditions where patient adherence to conventional treatments can be challenging. These systems are normally used for systemic drug delivery. However, IDDS can be used for localised administration to maximise the amount of drug delivered within the active site while reducing systemic exposure. This review will cover current applications of IDDS focusing on the materials used to prepare this type of systems and the main therapeutic areas of application. [ABSTRACT FROM AUTHOR]