Environmental education and the non-governmental organisation: a case study of the wildlife trusts

This thesis describes and discusses an investigation into the education provision of The Wildlife Trusts as a UK environmental non-governmental organisation (NGO), comprising 47 local Trusts. Prior to this study, The Wildlife Trusts organisation had not been examined as a whole partnership, as an NGO or as a provider of environmental education. Research questions focus upon what The Wildlife Trusts does as an organisation in terms of providing environmental education and the associated limits and potentials. Specific areas of investigation are The Wildlife Trusts' educational activities, its strengths and weaknesses and its educational culture. Such enquiry is valuable for The Wildlife Trusts itself, other NGOs, environmental educators and indeed all concerned with environmental education provision. The empirical work was conducted as a research-based case study and derives and builds upon research done for a commissioned review of The Wildlife Trusts' education provision. The thesis is influenced by Grounded Theory and draws predominantly on qualitative, but also quantitative techniques for data analysis and presentation. Interviews with Wildlife Trust personnel provided the primary source of data, supported by questionnaires, documentation obtained from Trusts and the author’s personal field notes. It is concluded that The Wildlife Trusts deliver numerous and diverse educational activities, yet neither as a unified NGO nor in sufficient partnership with other NGOs. The Wildlife Trusts is well placed to tailor activities effectively to local community audiences. It is recommended that The Wildlife Trusts overcome internally held negative attitudes towards 'education' through strengthening internal communications and developing a broader concept of 'people work'. It is argued that The Wildlife Trusts NGO has the potential to provide environmental education for all ages in both formal and informal education settings, in particular by providing outdoor and affective experiences on Trusts' reserves

Neuroglobin protects nerve cells from apoptosis by inhibiting the intrinsic pathway of cell death

In the past few years, overwhelming evidence has accrued that a high level of expression of the protein neuroglobin protects neurons in vitro, in animal models, and in humans, against cell death associated with hypoxic and amyloid insult. However, until now, the exact mechanism of neuroglobin's protective action has not been determined. Using cell biology and biochemical approaches we demonstrate that neuroglobin inhibits the intrinsic pathway of apoptosis in vitro and intervenes in activation of pro-caspase 9 by interaction with cytochrome c. Using systems level information of the apoptotic signalling reactions we have developed a quantitative model of neuroglobin inhibition of apoptosis, which simulates neuroglobin blocking of apoptosome formation at a single cell level. Furthermore, this model allows us to explore the effect of neuroglobin in conditions not easily accessible to experimental study. We found that the protection of neurons by neuroglobin is very concentration sensitive. The impact of neuroglobin may arise from both its binding to cytochrome c and its subsequent redox reaction, although the binding alone is sufficient to block pro-caspase 9 activation. These data provides an explanation the action of neuroglobin in the protection of nerve cells from unwanted apoptosis.Comment: 11 page

The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma

The cell's repertoire of transfer RNAs (tRNAs) has been linked to cancer. Recently, levels of the initiator methionine tRNA (tRNAiMet) in stromal fibroblasts have been shown to influence extracellular matrix (ECM) secretion to drive tumour growth and angiogenesis. Here we show that increased tRNAiMet within cancer cells does not influence tumour growth, but drives cell migration and invasion via a mechanism that is independent from ECM synthesis and dependent on α5β1 integrin and levels of the translation initiation ternary complex. In vivo and ex vivo migration (but not proliferation) of melanoblasts is significantly enhanced in transgenic mice which express additional copies of the tRNAiMet gene. We show that increased tRNAiMet in melanoma drives migratory, invasive behaviour and metastatic potential without affecting cell proliferation and primary tumour growth, and that expression of RNA polymerase III-associated genes (which drive tRNA expression) are elevated in metastases by comparison with primary tumours. Thus specific alterations to the cancer cell tRNA repertoire drive a migration/invasion programme that may lead to metastasis

Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region

Background: Conventional MRI fails to detect regions of glioblastoma cell infiltration beyond the contrast‐enhanced T1 solid tumor region, with infiltrating tumor cells often migrating along host blood vessels. Purpose: To quantitatively and qualitatively analyze the correlation between perfusion MRI signal and tumor cell density in order to assess whether local perfusion perturbation could provide a useful biomarker of glioblastoma cell infiltration. Study Type: Animal model. Subjects: Mice bearing orthotopic glioblastoma xenografts generated from a patient‐derived glioblastoma cell line. Field Strength/Sequences: 7T perfusion images acquired using a high signal‐to‐noise ratio (SNR) multiple boli arterial spin labeling sequence were compared with conventional MRI (T1/T2 weighted, contrast‐enhanced T1, diffusion‐weighted, and apparent diffusion coefficient). Assessment: Immunohistochemistry sections were stained for human leukocyte antigen (probing human‐derived tumor cells). To achieve quantitative MRI‐tissue comparison, multiple histological slices cut in the MRI plane were stacked to produce tumor cell density maps acting as a “ground truth.” Statistical Tests: Sensitivity, specificity, accuracy, and Dice similarity indices were calculated and a two‐tailed, paired t‐test used for statistical analysis. Results: High comparison test results (Dice 0.62–0.72, Accuracy 0.86–0.88, Sensitivity 0.51–0.7, and Specificity 0.92–0.97) indicate a good segmentation for all imaging modalities and highlight the quality of the MRI tissue assessment protocol. Perfusion imaging exhibits higher sensitivity (0.7) than conventional MRI (0.51–0.61). MRI/histology voxel‐to‐voxel comparison revealed a negative correlation between tumor cell infiltration and perfusion at the tumor margins (P = 0.0004). Data Conclusion: These results demonstrate the ability of perfusion imaging to probe regions of low tumor cell infiltration while confirming the sensitivity limitations of conventional imaging modalities. The quantitative relationship between tumor cell density and perfusion identified in and beyond the edematous T2 hyperintensity region surrounding macroscopic tumor could be used to detect marginal tumor cell infiltration with greater accuracy

Samsung and University of Edinburgh’s System for the IWSLT 2019

This paper describes the joint submission to the IWSLT 2019 English to Czech task by Samsung R&D Institute, Poland, and the University of Edinburgh. Our submission was ultimately produced by combining four Transformer systems through a mixture of ensembling and reranking

The impact of maintaining serum potassium ≥3.6 mEq/L vs ≥4.5 mEq/L on the incidence of new-onset atrial fibrillation in the first 120 hours after isolated elective coronary artery bypass grafting - study protocol for a randomised feasibility trial for the proposed Tight K randomized non-inferiority trial.

BACKGROUND: Atrial fibrillation (AF) occurs in approximately one in three patients after cardiac surgery, and is associated with increased short-term and long-term mortality, intensive care unit (ICU) and hospital stay, and increased cost of care. In an attempt to reduce AF incidence in these patients, serum potassium (K+) levels are commonly maintained at the high end of normal (4.5-5.5 mEq/L). However, such potassium supplementation is without proven benefit, and is not without negative consequences. It carries clinical risk, negatively impacts patient experience and is both time-consuming and costly. This protocol describes a randomised controlled pilot trial to assess the feasibility of a proposed randomised non-inferiority trial to investigate the impact of maintaining serum potassium ≥ 3.6 mEq/L vs ≥ 4.5 mEq/L on the incidence of new-onset atrial fibrillation in the first 120 hours after isolated elective coronary artery bypass grafting. METHODS: Design: this is a randomized feasibility trial as a pilot for a randomized non-inferiority trial. PARTICIPANTS: are 160 patients undergoing isolated coronary artery bypass grafting at two centres. Allocation: patients will be randomized (1:1) to protocols aiming to maintain serum potassium at either ≥ 3.6 mEq/L ("relaxed control") or ≥ 4.5 mEq/L ("tight control"). Primary analytic aim: was to assess the feasibility and acceptability of planning and delivering the intervention and trial methods to inform a full-scale non-inferiority trial. OUTCOME: the primary indicative efficacy outcome measures being field-tested are feasibility of participant recruitment and randomization, maintaining a protocol violation rate < 10%, and retaining 90% patient follow up 28 days after surgery. The primary clinical outcome measure of the future full "Tight K Study" will be incidence of AF after cardiac surgery. DISCUSSION: The Tight K Pilot will assess the feasibility of conducting the full trial, which is intended to confirm or refute the efficacy of current potassium management in preventing AF after cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03195647 . Registered on 23 May 2017. Last updated 19June 2017

Novel radiation and targeted therapy combinations for improving rectal cancer outcomes

Neoadjuvant radiotherapy is commonly used as standard treatment for rectal cancer. However, response rates are variable and survival outcomes remain poor, highlighting the need to develop new therapeutic strategies. Research is focused on identifying novel methods for sensitizing rectal tumours to radiotherapy to enhance responses and improve patient outcomes. This can be achieved through harnessing tumour promoting effects of radiation or preventing development of radio-resistance in cancer cells. Many of the approaches being investigated involve targeting the recently published new dimensions of cancer hallmarks. This review article will discuss key radiation and targeted therapy combination strategies being investigated in the rectal cancer setting, with a focus on exploitation of mechanisms which target the hallmarks of cancer

The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis

Summary: Expression of the initiator methionine tRNA (tRNAi Met) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi Met expression levels influence tumor progression. We have found that tRNAi Met expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi Met in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi Met contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi Met gene (2+tRNAi Met mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi Met mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi Met mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi Met significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi Metoverexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl- 3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi Met-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi Met mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi Met levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis

The Colston Statue: What next? ‘We are Bristol’ History commission - Visual short report

This version of the report contains images and presents the findings of the research in an accessable format.In the summer of 2021, the ‘We are Bristol’ History Commission consulted with the public about the future of the Colston statue and the Colston plinth. People had a chance to see the statue and learn about its history in a temporary display at the M Shed museum, as well as view the display online. Alongside the display was a survey that invited people from Bristol and beyond to share their views on a number of questions. Almost 14,000 people filled out the survey. The Mayor asked the History Commission to review the consultation and offer a number of recommendations in the light of it. This report summarizes the findings and also suggests what might happen next

A systematic review examining socioeconomic factors in trials of interventions for men that report weight as an outcome.

Funder: Australian Government Research Training Program ScholarshipWeight management interventions designed specifically for men have become more common, but the extent to which socioeconomic factors are considered in trials of these interventions is unclear. We synthesized study characteristics, methods, and reporting of interventions with a behavioral component for men that report weight as an outcome, to establish the extent to which socioeconomic factors are considered during intervention design, conduct, and reporting. A comprehensive search was conducted on Medline, Embase, PsycINFO, and CENTRAL for studies published from January 2000 to July 2021. Thirty-six trials were included. Educational attainment (n = 24) was the most frequently reported socioeconomic characteristic, followed by working status (n = 14) and area level deprivation (n = 12). Seven studies did not report any socioeconomic characteristics. Most studies (n = 20) did not mention the socioeconomic profile of their samples in relation to study strengths or limitations. Few (n = 4) consulted with men from lower socioeconomic groups during intervention design. One study examined potential differential intervention effects across socioeconomic groups, with most not powered to do so. Recent feasibility trials (n = 3) targeting specific socioeconomic groups suggest a potential nascent towards a greater consideration of factors related to equity. To best inform public health policy related to health inequalities, greater consideration of socioeconomic factors is required in trials of men's weight management interventions