Evaluation of selected contemporary biomaterials and surface treatments for soft tissue repair prosthesis

The aim of this project was to determine the best materials and surface treatments for soft tissue repair and to enhance our understanding of material / cell interactions by comparing the response of human cells growing on a selection of currently approved and novel biomaterials. This study focused on comparing the materials and also investigated the effect of modifying the surfaces using gas plasma and other treatments with the aim of enhancing cell growth. In addition, chitosan was studied to examine the reported bacteriostatic effect and promotion of human cell growth. Chitosan has many properties but this research focused on its reported acceleration of wound healing haemostatic and bacteriostatic properties. To examine the bacteriostatic properties of chitosan, a number of experimental designs were used. The bacteriostatic study led onto a selection of means to incorporate chitosan into/onto some of the biomaterials being tested. A selection of biomaterials were examined for their ability to support tissue growth in native and surface modified forms (plasma treatment/ chitosan treatment). Cells were seeded on the samples and the growth of the cells was measured at weekly intervals. The outcome of this research was that the optimal material for soft tissue repair was found to be polyurethane with an ammonia plasma treatment. This can be made into a mesh prosthesis for hernia repair and can be coated with chitosan to inhibit bacterial colonisation if required

Mid-Late miocene climate constrained by a new laser ablation ICP-MS set up

The unipolar icehouse world of the mid-late Miocene is a poorly understood interval in the evolution of Cenozoic climate. Widespread dissolution and poor preservation of carbonates in deep marine settings has resulted in large uncertainties in proxy-based climate reconstructions through the interval. Furthermore, models struggle to simulate the decoupling of low atmospheric CO2 (~250-350ppm) forcing in a warmer than modern world. This thesis uses the Sunbird-1 core, a clay-dominated sedimentary sequence from offshore East Africa, to improve the constraints on the global climate state of the mid-late Miocene. Prior to ~12 Ma, the Sunbird-1 site lay in a region of high productivity, with restricted, surface waters and an elevated supply of detrital organic matter invigorating carbon remineralisation in the water column. The redox environments associated with this high productivity setting resulted in the precipitation of diagenetic outer coatings on foraminifera, overprinting the primary Mg/Ca signal required for palaeotemperature reconstructions. The influence of these coatings decreased up-section, as the site subsided and experienced more open ocean conditions. This thesis develops and optimises a series of ablation parameters on the new Laser Ablation (LA-) ICP-MS system at Cardiff University. Employing medium to low fluences and repetition rates (3.5 Jcm-2 and 2.0 Hz) enables the collection of highly spatially resolved foraminiferal depth profiles suitable for assessing intra-test trace metal variability. By implementing the optimised LA-ICP-MS system this thesis reconstructs absolute sea surface temperature (SST) from Sunbird-1, indicating that applying a careful microanalytical approach can reconstruct palaeotemperatures from diagenetically altered foraminifera. This record suggests that tropical sea surface temperature remained relatively stable at 27-29⁰C from 13.3-9.4 Ma, presenting the mid-late Miocene as a key interval of increasing latitudinal temperature gradients towards that of the modern day climate state. These improved absolute sea surface temperature estimates, and the planktic foraminifera δ18O record, suggest a 39-48 m sea level equivalent increase in global ice volume through this interval. Furthermore, the planktic foraminiferal seawater δ18O record indicates that similar amplitude, short duration, fluctuations in global ice volume persisted through the mid-late Miocene. This implies that the East Antarctic Ice Sheet behaved dynamically following its expansion to a dry, land-based ice sheet during the Mid Miocene Climate Transition

Charge Screening by Internal pH and Polyvalent Cations as a Mechanism for Activation, Inhibition, and Rundown of TRPM7/MIC Channels

The Mg2+-inhibited cation (MIC) current, believed to represent activity of TRPM7 channels, is found in lymphocytes and mast cells, cardiac and smooth muscle, and several other eukaryotic cell types. MIC current is activated during whole-cell dialysis with divalent-free internal solutions. Millimolar concentrations of intracellular Mg2+ (or other divalent metal cations) inhibit the channels in a voltage-independent manner. The nature of divalent inhibition and the mechanism of channel activation in an intact cell remain unknown. We show that the polyamines (spermine, spermidine, and putrescine) inhibit the MIC current, also in a voltage-independent manner, with a potency that parallels the number of charges. Neomycin and poly-lysine also potently inhibited MIC current in the absence of Mg2+. These same positively charged ions inhibited IRK1 current in parallel with MIC current, suggesting that they probably act by screening the head group phosphates on PIP2 and other membrane phospholipids. In agreement with this hypothesis, internal protons also inhibited MIC current. By contrast, tetramethylammonium, tetraethylammonium, and hexamethonium produced voltage-dependent block but no inhibition. We show that inhibition by internal polyvalent cations can be relieved by alkalinizing the cytosol using externally applied ammonium or by increasing pH in inside-out patches. Furthermore, in perforated-patch and cell-attached recordings, when intracellular Mg2+ is not depleted, endogenous MIC or recombinant TRPM7 currents are activated by cytosolic alkalinization and inhibited by acidification; and they can be reactivated by PIP2 following rundown in inside-out patches. We propose that MIC (TRPM7) channels are regulated by a charge screening mechanism and may function as sensors of intracellular pH

Triplex targeted genomic crosslinks enter separable deletion and base substitution pathways

We have synthesized triple helix forming oligonucleotides (TFOs) that target a psoralen (pso) interstrand crosslink to a specific chromosomal site in mammalian cells. Mutagenesis of the targeted crosslinks results in base substitutions and deletions. Identification of the gene products involved in mutation formation is important for developing practical applications of pso-TFOs, and may be informative about the metabolism of other interstrand crosslinks. We have studied mutagenesis of a pso-TFO genomic crosslink in repair proficient and deficient cells. Deficiencies in non homologous end joining and mismatch repair do not influence mutation patterns. In contrast, the frequency of base substitutions is dependent on the activity of ERCC1/XPF and polymerase ζ, but independent of other nucleotide excision repair (NER) or transcription coupled repair (TCR) genes. In NER/TCR deficient cells the frequency of deletions rises, indicating that in wild-type cells NER/TCR functions divert pso-TFO crosslinks from processes that result in deletions. We conclude that targeted pso-TFO crosslinks can enter genetically distinct mutational routes that resolve to base substitutions or deletions

'Mindless markers of the nation': The routine flagging of nationhood across the visual environment

The visual environment has increasingly been used as a lens with which to understand wider processes of social and economic change with studies employing in-depth qualitative approaches to focus on, for example, gentrification or trans-national networks. This exploratory paper offers an alternative perspective by using a novel method, quantitative photo mapping, to examine the extent to which a particular socio-cultural marker, the nation, is ‘flagged’ across three contrasting sites in Britain. As a multi-national state with an increasingly diverse population, Britain offers a particularly fruitful case study, drawing in debates around devolution, European integration and Commonwealth migration. In contributing to wider debates around banal nationalism, the paper notes the extent to which nations are increasingly articulated through commerce, consumption and market exchange and the overall significance of everyday markers (signs, objects, infrastructure) in naturalising a national view of the world

In the dedicated pursuit of dedicated capital: restoring an indigenous investment ethic to British capitalism

Tony Blair’s landslide electoral victory on May 1 (New Labour Day?) presents the party in power with a rare, perhaps even unprecedented, opportunity to revitalise and modernise Britain’s ailing and antiquated manufacturing economy.* If it is to do so, it must remain true to its long-standing (indeed, historic) commitment to restore an indigenous investment ethic to British capitalism. In this paper we argue that this in turn requires that the party reject the very neo-liberal orthodoxies which it offered to the electorate as evidence of its competence, moderation and ‘modernisation’, which is has internalised, and which it apparently now views as circumscribing the parameters of the politically and economically possible

A Place to Call Home: Amphibian Use of Created and Restored Wetlands

Loss and degradation of wetland habitats are major contributing factors to the global decline of amphibians. Creation and restoration of wetlands could be a valuable tool for increasing local amphibian species richness and abundance. We synthesized the peer-reviewed literature addressing amphibian use of created and restored wetlands, focusing on aquatic habitat, upland habitat, and wetland connectivity and configuration. Amphibian species richness or abundance at created and restored wetlands was either similar to or greater than reference wetlands in 89% of studies. Use of created and restored wetlands by individual species was driven by aquatic and terrestrial habitat preferences, as well as ability to disperse from source wetlands. We conclude that creating and restoring wetlands can be valuable tools for amphibian conservation. However, the ecological needs and preferences of target species must be considered to maximize the potential for successful colonization and long-term persistence

Not all waits are equal: An investigation of emergency care patient pathway.

Abstract Background: Increasing pressure in the United Kingdom (UK) urgent care system has led to Emergency Departments (EDs) failing to meet the national requirement that 95% of patients are admitted, discharged or transferred within 4-h of arrival. Despite the target being the same for all acute hospitals, individual Trusts organise their services in different ways. The impact of this variation on patient journey time and waiting is unknown. Our study aimed to apply the Lean technique of Value Stream Mapping (VSM) to investigate care processes and delays in patient journeys at four contrasting hospitals. Methods: VSM timing data were collected for patients accessing acute care at four hospitals in South West England. Data were categorised according to waits and activities, which were compared across sites to identify variations in practice from the patient viewpoint. We included Public and Patient Involvement (PPI) to fully interpret our findings; observations and initial findings were considered in a PPI workshop. Results: One hundred eight patients were recruited, comprising 25,432 min of patient time containing 4098 episodes of care or waiting. The median patient journey was 223 min (3 h, 43 min); just within the 4-h target. Although total patient journey times were similar between sites, the stage where the greatest proportion of waiting occurred varied. Reasons for waiting were dominated by waits for beds, investigations or results to be available. From our sample we observed that EDs without a discharge/clinical decision area exhibited a greater proportion of waiting time following an admission or discharge decision. PPI interpretation indicated that patients who experience waits at the beginning of their journey feel more anxious because they are ‘not in the system yet’. Conclusions: The novel application of VSM analysis across different hospitals, coupled with PPI interpretation, provides important insight into the impact of care provision on patient experience. Measures that could reduce patient waiting include automatic notification of test results, and the option of discharge/clinical decision areas for patients awaiting results or departure. To enhance patient experience, good communication with patients and relatives about reasons for waits is essential. Keywords: Health service research, Acute care, Emergency admissions, Patient care, Value stream mapping, Emergency department, Patient public involvemen

The United Kingdom and British Empire: A Figurational Approach

Drawing upon the work of Norbert Elias and the process [figurational] sociology perspective, this article examines how state formation processes are related to, and, affected by, expanding and declining chains of international interdependence. In contrast to civic and ethnic conceptions, this approach focuses on the emergence of the nation/nation-state as grounded in broader processes of historical and social development. In doing so, state formation processes within the United Kingdom are related to the expansion and decline of the British Empire. That is, by focusing on the functional dynamics that are embedded in collective groups, one is able to consider how the UK’s ‘state’ and ‘imperial’ figurations were interdependently related to changes in both the UK and the former British Empire. Consequently, by locating contemporary UK relations in the historical context of former imperial relationships, nationalism studies can go ‘beyond’ the nation/nation-state in order to include broader processes of imperial expansion and decline. Here, the relationship between empire and nationalism can offer a valuable insight into contemporary political movements, especially within former imperial groups