Regulation as an opportunity for learning and small business development: The case of Environmental Health inspections and good learning behaviours

The impact of regulation on small business has been subject to much debate and contestation by industry, government, and academics. Small businesses pose particular challenges in meeting legislative obligations, often due to lack of awareness and misinterpretations. The role of Environmental Health inspectors has historically been focussed on assessing compliance to protect public health. This research investigates the role of inspectors as educators, adding a new dimension to existing knowledge and theory bringing together the literature about regulatory compliance and learning and explores the interactions between actors to determine the outcomes of this interface and the potential for learning. A focus group of inspectors identified a set of good learning behaviours (GLB’s) which were used in this qualitative study of 6 case studies each made up of an inspector and a small business operator. Observations of visits were carried out to identify evidence of GLB’s, followed by semi-structured interviews with both parties to identify evidence of learning, responses between individuals and exploration of the supportive and prohibitive factors for learning. The key finding is that learning often does take place during regulatory interactions, this can be a two-way process, and certain conditions are particularly supportive of learning. Timing of the visit and the first introductory phase are critical, and two-way dialogue which includes a number of factors, is key to effective learning. These findings enabled the construction of a conceptual framework and development of a model that can be applied to Environmental Health regulatory activities to promote better learning outcomes in small businesses. These findings are of significance to small business operators and Local Authority Environmental Health departments and their overarching bodies who have the ability to influence how regulatory interventions are carried out in the future. There is a particular gap in inspector training, with a need to focus more on understanding small businesses and how they operate, to better meet their needs

Physiological and Evolutionary Implications of the Pattern of Expression of Oxygen-Binding Hemoproteins in Antarctic Notothenioid Fishes

Antarctic icefish do not express hemoglobin (Hb). Icefishes possess cardiovascular modifications including increased densities of blood vessels, larger ventricles and increased blood volume compared to red-blooded relatives. In addition to delivering oxygen to tissues, Hb degrades nitric oxide (NO), a small signaling molecule. To investigate the mechanism driving development of icefish cardiovascular characteristics, I present and test the hypothesis that loss of Hb results in increased steady-state levels of NO, triggering downstream signaling pathways such as angiogenesis. I measured NO breakdown products, as a proxy for NO, and found that icefish have higher steady-state levels of NO metabolites in their plasma compared to red-blooded notothenioids. Expression of angiogenesis genes (HIF-1α, PHD2, and VEGF) did not differ significantly between red- and white-blooded notothenioids indicating that, while NO levels are higher in adult icefish, angiogenesis is not active. To investigate whether loss of Hb directly can increase NO and stimulate angiogenesis, hematocrit of red-blooded N. coriiceps was severely reduced using the hemolytic agent, phenylhydrazine HCl. Anemic fish exhibited a significantly higher concentration of NO metabolites in the plasma than did control fish, indicating an increase in NO. Expression of HIF-1α, PHD2, and VEGF mRNA was higher in anemic animals compared to control N. coriiceps, suggesting a causative relationship between loss of Hb and induction of angiogenesis that likely is mediated via NO signaling. In addition to lacking Hb, several species of icefish have lost ability to express myoglobin (Mb), an oxygen-binding protein expressed in the ventricle of most notothenioids. Previous studies have indicated Mb expression was lost on four separate occasions during evolution of the icefish family. Sequencing of the Mb gene from D. hunteri identified a duplicated TATA box previously proposed as the mechanism responsible for loss of Mb in C. aceratus. Sequencing of Mb from all 16 species of icefish identified the duplicated TATA box is present in all but two icefish species. The presence of the duplicated TATA box in Mb-expressing icefish suggests that the loss of Mb in C. aceratus and D. hunteri may occur by a mechanism independent of the duplicated TATA box

A reflection on the current local authority-led regulation model: views from small-and medium-sized businesses

Background Health and safety regulation has been identified by the UK government as an area of over-regulation; a burden to business; and hindering economic growth. In response recommendations have been made to government to reduce this regulation1-3. Whilst this seems to be the view held by government, many sources indicate that health and safety regulation has a role to play in supporting business4-6 and that ‘good regulation’ can actually help businesses and aid in their growth and economic prosperity. Guidance issued by the Health and Safety Executive (HSE) to Local Authorities has left Local Authority regulatory departments unable to undertake proactive inspections in medium and low risk workplaces, relying on intelligence to trigger reactive investigative visits. Such visits effectively only allow the prevention of future repetitions rather than preventing harm in the first place. At the same time spending cuts have seen reductions of 28% to Local Authority funding which has forced a re-examination of how to deliver services including health and safety regulation. Method An empirical qualitative methodology was applied to test the health and safety compliance advice required by SMEs. Semi-structured interviews (n-10) were carried out with selected SME owners/managers across a range of sectors with varying exposures to health and safety regulatory interventions, in the City of Peterborough. The interviews were conducted face-to-face at the business premises, recorded and transcribed. The data was coded in order to establish themes which were used to develop emergent theory. Results Ten themes emerged from the data. The strongest themes that emerged were that businesses did not feel that deregulation or reduced inspections would be beneficial either at the individual business level or across the sector. Of significant note was that participants wanted to continue to have inspections on a frequent basis. They felt that fewer inspections would lead to lower compliance levels and increased accidents. In addition, SMEs indicated that they do not have the skills or capacity to self-regulate and thus wish for tailored business advice to aid in protecting their workforce. Recommendations The presumption that regulatory visits are negative is questioned by the research and indeed all interviewees welcomed the support they gain from such visits. With this in mind it is suggested that a more business advisory approach is adopted to meet SME needs and aid growth while still protecting the workforce. A number of recommendations are made including a risk based proactive intervention strategy based on responsive regulation principles, improvement of communication and business engagement and focus on advice provision for SMEs. The recommendations are designed to meet businesses needs and also to contribute to business growth

The discovery and evaluation of treatment stratification biomarkers in epithelial ovarian cancer

Background: Epithelial ovarian cancer (EOC) has the poorest survival outcomes for all gynaecological malignancies. Despite emerging knowledge on the heterogeneity of the disease the majority of patients are initially treated the same. Biomarkers which could predict treatment response would greatly enhance patient care. Results: Differential DNA methylation analysis of serous EOC tumours identified 180 loci significantly associated with residual disease status (n=297, p<0.05, FDR <5%), with 23 corresponding genes also significantly associated in gene expression array analysis (p<0.05, FDR <10%). Differential DNA methylation of 27 loci were significantly associated with overall survival in patients receiving optimal debulking (n=78, p<0.05). Patients optimally debulked but with poor prognosis markers were found to have the same survival as those suboptimally debulked suggesting that supraradical surgery is not beneficial in these patients. Hypomethylation at intragenic regions of the homeobox gene MSX1 was associated with primary platinum resistance significantly (n=61, p<0.05, FDR<5%) and these findings were validated in an independent dataset (n=252, p<0.05). DNA methylation was also significantly correlated to gene expression. Platinum resistant ovarian cancer cell lines demonstrated significantly lower gene expression of MSX1 compared to sensitive pairs. Proliferation and apoptosis cell-line assays demonstrated sensitisation to cisplatin when cisplatin resistant A2780/CP70 cells re-expressed MSX1 following gene transfection. An increase in p53 downstream transcripts, CDKN1A (p21) and BAX was also demonstrated in these MSX1 transfectants. The detection of disease at 5 distinct anatomical sites determined by preoperative computed tomography was significantly associated with surgical debulking outcomes in a test (n=111) and validation (n=70) cohort of patients with EOC (sensitivity 64.7-69.2%, specificity 67.9-71.4%, AUC 0.721-0.749). Conclusions: DNA methylation is a potential rich source of biomarkers predicting cytoreductive outcome and survival. The discovery and validation of a novel DNA methylation biomarker of chemotherapy resistance is demonstrated with exciting findings related to its biological function in cisplatin sensitive assays.Open Acces

Leakage after surgery for rectum cancer; inconsistency in reporting to the Danish Colorectal Cancer Group?

Purpose. Anastomotic leakage accounts for up to 1/3 of all fatalities after rectal cancer surgery. Evidence suggests that anastomotic leakage has a negative prognostic impact on local cancer recurrence and long-term cancer specific survival. The reported leakage rate in 2011 in Denmark varied from 7 to 45 percent. The objective was to clarify if the reporting of anastomotic leakage to the Danish Colorectal Cancer Group was rigorous and unequivocal. Methods. An Internet-based questionnaire was e-mailed to all Danish surgical departments, who reported to Danish Colorectal Cancer Group (DCCG) in 2011. There were 23 questions. Four core questions were whether pelvic collection, fecal appearance in a pelvic drain, rectovaginal fistula, and “watchfull” waiting patients were reported as anastomotic leakage. Results. Fourteen out of 17 departments, who in 2011 according to DDCG performed rectal cancer surgery, answered the questionnaire. This gave a response rate of 82%. In three of four core questions there was disagreement in what should be reported as anastomotic leakage. Conclusion. The reporting of anastomotic leakage to the Danish Colorectal Cancer Group was not rigorous and unequivocal. The reported anastomotic leakage rate in Danish Colorectal Cancer Group should be interpreted with caution

Kingdom of Fear: A Dark Fantasy Novel

This project is the first draft of a novel written over the course of half a year. It is a dark fantasy novel about three strangers who must stop a mage with the power to use peoples\u27 fear to turn them into monsters. The novel in question is intended to be published at a later date, and so only the first chapter is available in the archive. Additionally, presentation slides are included that describe the process of brainstorming, outlining, and drafting the novel, as well as plans for future edits and publishing

The uptake of vitamin B12 by unicellular algae

Vitamin B12 binding and uptake by two unicellular, marine algae, the autotrophic Dunaliella primolecta and the auxotrophic Pavlova lutheri, has been studied. Features of the extracellular binders found in the culture medium of micro-algae were examined to elucidate their role. The B12 binding capacity of these proteins was shown to be proportional to cell density, and they were relatively stable for at least one month. Nevertheless, cells bind the majority of vitamin until stationary phase. Membrane-bound and intracellular cytosolic binders have also been isolated, representing around 49 and 16 % respectively of the total B12 binding capacity of cultures, 35% typically being associated with the extracellular fraction. To discover the relationship between these proteins and the nature of the uptake process, characterisation was pursued. An affinity chromatography-based purification scheme was developed for the binders, and small quantities of these proteins were purified from all three phases. Gel filtration showed uniform molecular weights in excess of 500,000, and amino acid analyses revealed similar compositions. The identification of carbohydrate components was investigated using a lectin-binding assay. However, it was not found to be possible to determine sub-unit molecular weight by SDS gelelectrophoresis, and attempts at localisation of the cellular B12 binding sites using fluorescence microscopy and electron probe micro-analysis were unsuccessful. Interestingly though, similar vitaminbinding characteristics were demonstrated for isolatedchloroplasts and intact cells of D. primolecta.Aspects of B12 and its uptake by micro-algae arereviewed, and an explanation for extracellular B12 binding proteins involving non-specific release issuggested. A general model of two-stage uptake of the vitamin by micro-algae, with a primary stage of binding to a receptor protein in the plasma membrane and a secondary phase of energy-dependent internalisation, is also proposed.<p