511 research outputs found
The Relational Geographies of Policing and Security
This paper considers the roles of policing and security in the geographies of everyday public and semi-public space. We contend that while security is concerned with territory, policing relates to place. We consider the relationship between security and territory before examining the relationship between policing and place. In the final section, we argue that a relational view of space is needed to understand how practices of policing and security shape space and, in turn, the lives of people using it
Phosphorylation of ezrin on Thr567 is required for the synergistic activation of cell spreading by EPAC1 and protein kinase A in HEK293T cells
Recent studies have demonstrated that the actin binding protein, ezrin, and the cAMP-sensor, EPAC1, cooperate to induce cell spreading in response to elevations in intracellular cAMP. To investigate the mechanisms underlying these effects we generated a model of EPAC1-dependent cell spreading based on the stable transfection of EPAC1 into HEK293T (HEK293T–EPAC1) cells. We found that direct activation of EPAC1 with the EPAC-selective analogue, 8-pCPT-2′-O-Me-cAMP (007), promoted cell spreading in these cells. In addition, co-activation of EPAC1 and PKA, with a combination of the adenylate cyclase activator, forskolin, and the cAMP phosphodiesterase inhibitor, rolipram, was found to synergistically enhance cell spreading, in association with cortical actin bundling and mobilisation of ezrin to the plasma membrane. PKA activation was also associated with phosphorylation of ezrin on Thr567, as detected by an electrophoretic band mobility shift during SDS-PAGE. Inhibition of PKA activity blocked ezrin phosphorylation and reduced the cell spreading response to cAMP elevation to levels induced by EPAC1-activation alone. Transfection of HEK293T–EPAC1 cells with inhibitory ezrin mutants lacking the key PKA phosphorylation site, ezrin-Thr567Ala, or the ability to associate with actin, ezrin-Arg579Ala, promoted cell arborisation and blocked the ability of EPAC1 and PKA to further promote cell spreading. The PKA phospho-mimetic mutants of ezrin, ezrin-Thr567Asp had no effect on EPAC1-driven cell spreading. Our results indicate that association of ezrin with the actin cytoskeleton and phosphorylation on Thr567 are required, but not sufficient, for PKA and EPAC1 to synergistically promote cell spreading following elevations in intracellular cAMP
Group A streptococcal vaccine delivery by immunization with a self-adjuvanting M protein-based lipid core peptide construct
Background & objectives: To develop a broad strain coverage GAS vaccine, several strategies have been investigated which included multi-epitope approaches as well as targeting the M protein conserved C-region. These approaches, however, have relied on the use of adjuvants that are toxic for human application. The development of safe and effective adjuvants for human use is a key issue in the development of effective vaccines. In this study, we investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting GAS vaccine delivery approach. Methods: An LCP-GAS construct was synthesised incorporating multiple copies of a protective peptide epitope (J8) from the conserved carboxy terminal C-repeat region of the M protein. B10.BR mice were immunized parenterally with the LCP-J8 construct, with or without conventional adjuvant, prior to the assessment of immunogenicity and the induction of serum opsonic antibodies. Results: Our data demonstrated immunogenicity of LCP-J8 when coadministered in complete Freund's adjuvant (CFA), or administered in the absence of conventional adjuvant. In both cases, immunization led to the induction of high-titre J8 peptide-specific serum IgG antibody responses, and the induction of heterologous opsonic antibodies that did not cross-react with human heart tissue proteins. Interpretation & conclusion: These data indicated the potential of a novel self-adjuvanting LCP vaccine delivery system incorporating a synthetic GAS M protein C-region peptide immunogen in the induction of broadly protective immune responses, and pointed to the potential application of this system in human vaccine development against infectious diseases
Implementation of a novel antimicrobial stewardship strategy for rural facilities utilising telehealth
A significant portion of healthcare takes place in small hospitals, and many are located in rural and regional areas. Facilities in these regions frequently do not have adequate resources to implement an onsite antimicrobial stewardship programme and there are limited data relating to their implementation and effectiveness. We present an innovative model of providing a specialist telehealth antimicrobial stewardship service utilising a centralised service (Queensland Statewide Antimicrobial Stewardship Program) to a rural Hospital and Health Service. Results of a 2-year post-implementation follow-up showed an improvement in adherence to guidelines [33.7% (95% CI 27.0–40.4%) vs. 54.1% (95% CI 48.7–59.5%)] and appropriateness of antimicrobial prescribing [49.0% (95% CI 42.2–55.9%) vs. 67.5% (95% CI 62.7–72.4%) (P < 0.001). This finding was sustained after adjustment for hospitals, with improvement occurring sequentially across the years for adherence to guidelines [adjusted odds ratio (aOR) = 2.44, 95% CI 1.70–3.51] and appropriateness of prescribing (aOR = 2.48, 95% CI 1.70–3.61). There was a decrease in mean total antibiotic use (DDDs/1000 patient-days) between the years 2016 (52.82, 95% CI 44.09–61.54) and 2018 (39.74, 95% CI 32.76–46.73), however this did not reach statistical significance. Additionally, there was a decrease in mean hospital length of stay (days) from 2016 (3.74, 95% CI 3.08–4.41) to 2018 (2.55, 95% CI 1.98–3.12), although this was not statistically significant. New telehealth-based models of antimicrobial stewardship can be effective in improving prescribing in rural areas. Programmes similar to ours should be considered for rural facilities
The Lore of Low Methane Livestock:Co-Producing Technology and Animals for Reduced Climate Change Impact
Methane emissions from sheep and cattle production have gained increasing profile in the context of climate change. Policy and scientific research communities have suggested a number of technological approaches to mitigate these emissions. This paper uses the concept of co-production as an analytical framework to understand farmers’ evaluation of a 'good animal’. It examines how technology and sheep and beef cattle are co-produced in the context of concerns about the climate change impact of methane. Drawing on 42 semi-structured interviews, this paper demonstrates that methane emissions are viewed as a natural and integral part of sheep and beef cattle by farmers, rather than as a pollutant. Sheep and beef cattle farmers in the UK are found to be an extremely heterogeneous group that need to be understood in their specific social, environmental and consumer contexts. Some are more amenable to appropriating methane reducing measures than others, but largely because animals are already co-constructed from the natural and the technical for reasons of increased production efficiency
Research on the Geography of Agricultural Change: Redundant or Revitalized?
Future research directions for agricultural geography were the subject of debate in Area in the late 1980s. The subsequent application of political economy ideas undoubtedly revived interest in agricultural research. This paper argues that agricultural geography contains greater diversity than the dominant political economy discourse would suggest. It reviews ‘other’ areas of agricultural research on policy, post-productivism, people, culture and animals, presenting future suggestions for research. They should ensure that agricultural research continues revitalized rather than redundant into the next millennium
Strengthening HPV vaccination delivery: findings from a qualitative service evaluation of the adolescent girls' HPV vaccination programme in England.
BACKGROUND: In 2014, the number of HPV vaccine doses given to adolescent girls as part of the English school-based immunization programme was reduced from three to two. This was based on evidence that a two-dose schedule provides long-lasting protection against HPV infection. In 2015/16 a small decline in HPV vaccination coverage in adolescent girls was noted; from 86.7% for the three-dose schedule in 2013/14 to 85.1% for the two-dose schedule. This evaluation examined whether service-related factors contributed to this decline. METHODS: In May-August 2017, we conducted semi-structured qualitative interviews with 39 participants responsible for commissioning or delivering immunization programmes in six local authorities in the South West, North Central Midlands and South Central Midlands, England. RESULTS: Effective planning and data management were key for successful service provision of HPV vaccination, as well as close collaboration between commissioners, service providers and data system managers, a team skill mix with experienced staff, pro-active engagement with schools and service providers equipped to respond to parental concerns. CONCLUSIONS: To maintain and improve the high HPV adolescent girls' vaccine coverage rates achieved in England, in the context of an expanding school-based immunization programme, it is essential to strengthen the organizational capacity of the delivery system
The role of healthcare providers in HPV vaccination programs - A meeting report
The Human Papillomavirus (HPV) Prevention and Control Board convened a meeting in Bucharest, Romania (May 2018), to discuss the role of healthcare providers (HCPs) in prevention programs, with a focus on HPV vaccination and cervical cancer screening. International and local experts discussed the role that HCPs can play to increase the uptake of HPV vaccine and screening. Experts recommended: 1) increasing HCP norms of getting vaccinated; 2) training providers to make effective recommendations; 3) making culturally appropriate materials available, in local languages; and 4) centralizing and coordinating education and information material, to direct both HCPs and the general public to the best material available
Community perspectives on the benefits and risks of technologically enhanced communicable disease surveillance systems: a report on four community juries
BACKGROUND:Outbreaks of infectious disease cause serious and costly health and social problems. Two new technologies - pathogen whole genome sequencing (WGS) and Big Data analytics - promise to improve our capacity to detect and control outbreaks earlier, saving lives and resources. However, routinely using these technologies to capture more detailed and specific personal information could be perceived as intrusive and a threat to privacy. METHOD:Four community juries were convened in two demographically different Sydney municipalities and two regional cities in New South Wales, Australia (western Sydney, Wollongong, Tamworth, eastern Sydney) to elicit the views of well-informed community members on the acceptability and legitimacy of: making pathogen WGS and linked administrative data available for public health researchusing this information in concert with data linkage and machine learning to enhance communicable disease surveillance systems Fifty participants of diverse backgrounds, mixed genders and ages were recruited by random-digit-dialling and topic-blinded social-media advertising. Each jury was presented with balanced factual evidence supporting different expert perspectives on the potential benefits and costs of technologically enhanced public health research and communicable disease surveillance and given the opportunity to question experts. RESULTS:Almost all jurors supported data linkage and WGS on routinely collected patient isolates for the purposes of public health research, provided standard de-identification practices were applied. However, allowing this information to be operationalised as a syndromic surveillance system was highly contentious with three juries voting in favour, and one against by narrow margins. For those in favour, support depended on several conditions related to system oversight and security being met. Those against were concerned about loss of privacy and did not trust Australian governments to run secure and effective systems. CONCLUSIONS:Participants across all four events strongly supported the introduction of data linkage and pathogenomics to public health research under current research governance structures. Combining pathogen WGS with event-based data surveillance systems, however, is likely to be controversial because of a lack of public trust, even when the potential public health benefits are clear. Any suggestion of private sector involvement or commercialisation of WGS or surveillance data was unanimously rejected.Chris Degeling, Stacy M. Carter, Antoine M. van Oijen, Jeremy McAnulty, Vitali Sintchenko, Annette Braunack-Mayer ... et al
A novel metabolomic approach used for the comparison of Staphylococcus aureus planktonic cells and biofilm samples
Introduction:
Bacterial cell characteristics change significantly during differentiation between planktonic and biofilm states. While established methods exist to detect and identify transcriptional and proteomic changes, metabolic fluctuations that distinguish these developmental stages have been less amenable to investigation.
Objectives:
The objectives of the study were to develop a robust reproducible sample preparation methodology for high throughput biofilm analysis and to determine differences between Staphylococcus aureus in planktonic and biofilm states.
Methods:
The method uses bead beating in a chloroform/methanol/water extraction solvent to both disrupt cells and quench metabolism. Verification of the method was performed using liquid-chromatography-mass spectrometry. Raw mass-spectrometry data was analysed using an in-house bioinformatics pipe-line incorporating XCMS, MzMatch and in-house R-scripts, with identifications matched to internal standards and metabolite data-base entries.
Results:
We have demonstrated a novel mechanical bead beating method that has been optimised for the extraction of the metabolome from cells of a clinical Staphylococcus aureus strain existing in a planktonic or biofilm state. This high-throughput method is fast and reproducible, allowing for direct comparison between different bacterial growth states. Significant changes in arginine biosynthesis were identified between the two cell populations.
Conclusions:
The method described herein represents a valuable tool in studying microbial biochemistry at a molecular level. While the methodology is generally applicable to the lysis and extraction of metabolites from Gram positive bacteria, it is particularly applicable to biofilms. Bacteria that exist as a biofilm are shown to be highly distinct metabolically from their ‘free living’ counterparts, thus highlighting the need to study microbes in different growth states. Metabolomics can successfully distinguish between a planktonic and biofilm growth state. Importantly, this study design, incorporating metabolomics, could be optimised for studying the effects of antimicrobials and drug modes of action, potentially providing explanations and mechanisms of antibiotic resistance and to help devise new antimicrobials
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