The provision of fire services in rural areas

Fire services have been neglected in discussions of public service provision in rural areas. The way in which they are provided has a broader significance in terms of current debates about risk management. Fire service policy was transferred away from the Home Office, but the Bain Report provided the major stimulus to change. Early central government attempts to stimulate fire service provision in rural area were hampered by a lack of cooperation between local authorities. Rates of death from fire are influenced by attendance times and are particularly high in remote rural areas. The development of national standards of fire cover was focused on protecting property rather than saving lives with disproportionate funding being provided for urban areas. Social changes in rural areas have made it more difficult to secure sufficient numbers of retained fire fighters. It has proved particularly difficult to provide an adequate service in remote rural areas such as the Highlands and Islands of Scotland, despite recent policy initiatives there. Problems of providing fire cover are particularly acute on isolated islands. The development of integrated risk management plans should offer a more fine grained approach to providing fire cover. However, they may be too sophisticated for the task in rural areas and more traditional democratic mechanisms for expressing perceived community needs may have a greater relevance

The Cavendish Living lab - a multidisciplinary, vertically integrated project focused on sustainability

Colleagues from the School of Life Sciences will present findings from The Cavendish Living Lab’: a 2 year vertically integrated project (VIP) that focuses on co-creating sustainable solutions with the student participants from various disciplines and levels. Through applied research and learning within an authentic setting, the ‘Living Lab’ approach uses our university campus as the laboratory, and a platform for the students to partner with various stakeholders to address real world issues and develop innovative, sustainable solutions to problems such as food waste, plastic waste, and waste water

Controlled Delivery of Pan-PAD-Inhibitor Cl-Amidine Using Poly(3-Hydroxybutyrate) Microspheres.

This study deals with the process of optimization and synthesis of Poly(3-hydroxybutyrate) microspheres with encapsulated Cl-amidine. Cl-amidine is an inhibitor of peptidylarginine deiminases (PADs), a group of calcium-dependent enzymes, which play critical roles in a number of pathologies, including autoimmune and neurodegenerative diseases, as well as cancer. While Cl-amidine application has been assessed in a number of in vitro and in vivo models; methods of controlled release delivery remain to be investigated. P(3HB) microspheres have proven to be an effective delivery system for several compounds applied in antimicrobial, wound healing, cancer, and cardiovascular and regenerative disease models. In the current study, P(3HB) microspheres with encapsulated Cl-amidine were produced in a size ranging from ~4-5 µm and characterized for surface morphology, porosity, hydrophobicity and protein adsorption, in comparison with empty P(3HB) microspheres. Cl-amidine encapsulation in P(3HB) microspheres was optimized, and these were found to be less hydrophobic, compared with the empty microspheres, and subsequently adsorbed a lower amount of protein on their surface. The release kinetics of Cl-amidine from the microspheres were assessed in vitro and expressed as a function of encapsulation efficiency. There was a burst release of ~50% Cl-amidine in the first 24 h and a zero order release from that point up to 16 days, at which time point ~93% of the drug had been released. As Cl-amidine has been associated with anti-cancer effects, the Cl-amidine encapsulated microspheres were assessed for the inhibition of vascular endothelial growth factor (VEGF) expression in the mammalian breast cancer cell line SK-BR-3, including in the presence of the anti-proliferative drug rapamycin. The cytotoxicity of the combinatorial effect of rapamycin with Cl-amidine encapsulated P(3HB) microspheres was found to be 3.5% more effective within a 24 h period. The cells treated with Cl-amidine encapsulated microspheres alone, were found to have 36.5% reduction in VEGF expression when compared with untreated SK-BR-3 cells. This indicates that controlled release of Cl-amidine from P(3HB) microspheres may be effective in anti-cancer treatment, including in synergy with chemotherapeutic agents. Using controlled drug-delivery of Cl-amidine encapsulated in Poly(3-hydroxybutyrate) microspheres may be a promising novel strategy for application in PAD-associated pathologies

Integration of copy number and transcriptomics provides risk stratification in prostate cancer : a discovery and validation cohort study

Study data are deposited in NCBI GEO (unique identifier number GSE70770).Background : Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. Methods : In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. Findings : We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer ( MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. Interpretation : For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.Peer reviewe

Toward a Closed Loop, Integrated Biocompatible Biopolymer Wound Dressing Patch for Detection and Prevention of Chronic Wound Infections

Chronic wound infections represent a significant burden to healthcare providers globally. Often, chronic wound healing is impeded by the presence of infection within the wound or wound bed. This can result in an increased healing time, healthcare cost and poor patient outcomes. Thus, there is a need for dressings that help the wound heal, in combination with early detection of wound infections to support prompt treatment. In this study, we demonstrate a novel, biocompatible wound dressing material, based on Polyhydroxyalkanoates, doped with graphene platelets, which can be used as an electrochemical sensing substrate for the detection of a common wound pathogen, Pseudomonas aeruginosa. Through the detection of the redox active secondary metabolite, pyocyanin, we demonstrate that a dressing can be produced that will detect the presence of pyocyanin across clinically relevant concentrations. Furthermore, we show that this sensor can be used to identify the presence of pyocyanin in a culture of P. aeruginosa. Overall, the sensor substrate presented in this paper represents the first step toward a new dressing with the capacity to promote wound healing, detect the presence of infection and release antimicrobial drugs, on demand, to optimized healing

Esterase Cleavable 2D Assemblies of Magnetic Iron Oxide Nanocubes: Exploiting Enzymatic Polymer Disassembling to Improve Magnetic Hyperthermia Heat Losses

Here, we report a nanoplatform based on iron oxide nanocubes (IONCs) coated with a bioresorbable polymer that, upon exposure to lytic enzymes can be disassembled increasing the heat performances in comparison with the initial clusters. We have developed bi-dimensional (2D) clusters by exploiting benchmark iron oxide nanocubes as heat mediators for magnetic hyperthermia and a polyhydroxyalkanoate (PHA) copolymer, a biodegradable polymer produced by bacteria that can be digested by intracellular esterase enzymes. The comparison of magnetic heat performance of the 2D assemblies with 3D centro-symmetrical assemblies or single iron oxide nanocubes emphasize the benefit of the 2D assembly. On one hand, the heat losses of 2D assemblies dispersed in water are better than the 3D assemblies, but worse than for single nanocubes. On the other hand, when the bi-dimensional magnetic beads (2D-MNBs) are incubated with the esterase enzyme at a physiological temperature, their magnetic heat performances began to progressively increase. After 2 hours of incubation, specific absorption rate values of the 2D assembly double the ones of individually coated nanocubes. Such an increase can be mainly correlated to the splitting of the 2D-MNBs into smaller size clusters with a chain- like configuration containing few nanocubes. Moreover, 2D-MNBs exhibited non-variable-heat performances even after intentionally inducing their aggregation. Magnetophoresis measurements indicate a comparable response of 3D and 2D clusters to external magnets (0.3T) that is by far faster than that of single nanocubes. This feature is crucial for a physical accumulation of magnetic materials in the presence of magnetic field gradients. This system is the first example of a nanoplatform that, upon exposure to lytic enzymes, such as those present in a tumor environment, can be disassembled from the initial 2D-MNB organization to chain-like assemblies with clear improvement of the heat magnetic losses resulting in better heat dissipation performances. The potential application of 2D nano-assemblies based on the cleavable PHAs for preserving their magnetic losses inside cells will benefit hyperthermia therapies mediated by magnetic nanoparticles under alternating magnetic fields

Improving Suicide Crisis Support: A Mixed-Methods Evaluation of the Martin Gallier Project in Partnership with the NHS

This evaluation assesses the impact and effectiveness of The Martin Gallier Project (MGP) in supporting individuals experiencing suicidal crisis, with a particular focus on those referred via the Cheshire and Wirral Partnership (CWP) NHS Foundation Trust. MGP offers a unique, non-clinical, community-based intervention model that provides rapid, high-street access to suicide intervention specialists without eligibility restrictions or waiting lists. The evaluation draws on a mixed-methods approach, combining quantitative data from 9801 clients between February 23, 2019 (when the service began operating) and August 5, 2025, and qualitative insights from 50 semi-structured interviews with clients, carers, staff, and referrers

Making nonwoven fibrous poly(epsilon-caprolactone) constructs for antimicrobial and tissue engineering applications by pressurized melt gyration

A pressurized melt gyration process has been used for the first time to generate poly(ε-caprolactone) (PCL) fibers. Gyration speed, working pressure, and melt temperature are varied and these parameters influence the fiber diameter and the temperature enabled changing the surface morphology of the fibers. Two types of nonwoven PCL fiber constructs are prepared. First, Ag-doped PCL is studied for antibacterial activity using Gram-negative Escherichia coli and Pseudomonas aeruginosa microorganisms. The melt temperature used to make these constructs significantly influences antibacterial activity. Neat PCL nonwoven scaffolds are also prepared and their potential for application in muscular tissue engineering is studied with myoblast cells. Results show significant cell attachment, growth, and proliferation of cells on the scaffolds