The development of language acquisition in a mature learner

The primary objective of this study is to provide insight into the advancement of my knowledge and understanding of Spanish and of the process of language acquisition in a mature learner. While learning Spanish as a beginner, I kept a diary for two-and-a-half-years in which I recorded detailed, reflective responses to my language acquisition experiences. The diary data was recorded under prompt headings. At the end of the learning period, I approached the data from different perspectives. I summarised the content of the diary in the form of four different charts. Then I analysed the contents of the charts and the whole diary and these analyses indicated salient themes that emerged during my observations of the language acquisition process. A first quantitative preliminary study of the entries under the prompt headings in the charts indicated most frequently mentioned phenomena. A second, closer analysis of the content of the diary entries re-interpreted the entries under the prompt headings to reveal specific aspects of these phenomena that were incorporated in the process of my language acquisition. In the third interpretive analysis, I ignored the prompt headings and looked at the entries individually in terms of implicit and explicit phenomena indicated. This analysis revealed four main phenomena involved in the development of my language acquisition: language source material, method of learning, my attitude as the learner and memory. In the fourth and final analysis, I interpreted the individual entries of the whole diary in terms of the insight they gave to a detailed description of the nature of the advancement of my knowledge and understanding of Spanish and of the process of my language acquisition. Finally, the study revealed the significance of the language acquisition process itself in contrast to the products of language acquisition which currently form a major part of language acquisition theory. Although this study concerns an individual, and the language development of this individual is unique, the insight into the process of the development of acquisition involved in this individual has significant implications for further research into the development of the language acquisition in other learners of similar age and background

Pharmacies as potential providers of harm reduction services: A preliminary online survey

Background Recreational drug use is a major cause of disease, injury, physical and mental impairment and death in developed countries such as the United Kingdom and the United States. Alcohol, tobacco, cannabis, 3,4-methylenedioxymethamphetamine (MDMA) and psilocybe mushrooms are recreational drugs with capacity to cause harm. Cannabis, MDMA and psilocybin have reported therapeutic applications. Objectives The primary purpose of this study was to determine which of the three types of vendor (pharmacy, shop and the black market) are perceived to be the most suitable for selling the substances discussed according to a general population sample. Methods A sample of 105 UK nationals was selected for the survey. Participants were presented information regarding reported relative dangers of alcohol, tobacco, cannabis, MDMA and psilocybin and potential therapeutic applications. Participants were then asked to review harm reduction strategies. Results It was found that participants concluded that pharmacists with available NHS support from GPs and mental health workers are the most suitable vendors of cannabis, MDMA and psilocybin as opposed to regulated shops or the black market (p &lt; 0.001). There was a high level of support for selling cannabis in pharmacies both for therapeutic use and for harm reduction purposes with a mean score of 7.0 out of 10. Participants (60) with a university education were found to be more in favour of the substances being sold primarily in pharmacies (alcohol 5.6, tobacco 6.7, cannabis 7.6, MDMA 6.5 and psilocybin 6.5) than participants (45) with no university qualification (alcohol 5.0, tobacco 4.8, cannabis 6.3, MDMA 5.0 and psilocybin 5.1). Conclusions The data suggest that the university-educated participants are supportive of treating recreational drug use as a health issue with GPs, mental health workers and pharmacists taking on roles. </jats:sec

Radical ideas of political practice in 1780s and 1790s Britain

This thesis examines ideas about political tactics in 1780s and 1790s Britain. Edmund Burke characterised radicals in the aftermath of the French Revolution as speculative thinkers with no understanding of political action. This rhetorical strategy obscured the ideas of reformers who were frustrated with the rationalist bent of their movement and who, inspired by Scottish philosophy and events in Ireland, tried to work out what was to be done. James Mackintosh and Samuel Parr responded to Burke by arguing that theory could apply to practice, while David Williams outlined how political theory could direct reformers to the means to harness the general will and enact it through the sovereign. Interest in arming the people led David Steuart Erskine, Robert Watson, and John Cartwright to invoke the ideas of Andrew Fletcher. This interest in a militia was not purely theoretical; in Ireland from 1778 the Volunteers used a combination of arms and sumptuary rules to win legislative and trading rights. Francis Dobbs, Joseph Pollock and Henry Flood examined this movement to learn about political tactics. Lord George Gordon advocated for Francis Dobbs in the House of Commons and was imprisoned for his attempts to derail the Anglo-French Commercial Treaty, an issue that once again brought together Irish politics and discussions of commerce and luxury. In the 1790s, United Irishmen linked their understanding of the anti-luxury practice of the Volunteers with knowledge of the constitution they had learned from John Millar at Glasgow University. Meanwhile, Lord Buchan was using an unlikely tactic, the practice of history, to stir the Scots to pay attention to their Buchananite heritage. The tactical thought of British radicals in the 1790s was rarely concerned with discussions of the rights of man, but instead referred to ideas of arms, kings, commerce, and history

Repurposing old carbon monoxide-releasing molecules towards the anti-angiogenic therapy of triple-negative breast cancer

Triple-negative breast cancer (TNBC) is defined by the lack of expression of the oestrogen and progesterone receptors and HER-2. Recently, carbon monoxide (CO) was found to behave as an important endogenous signalling molecule and to suppress VEGF receptor-2 (VEGFR-2) and protein kinase B phosphorylation. Given that anti-angiogenic drugs exist as one of the few available targeted therapies against TNBC, the aim of this project was to study the effects of CO-releasing molecules (CORMs) on TNBC cell lines and the associated endothelial cells and characterise their anti-angiogenic properties that can be used for the reduction of cancer-driven angiogenesis. Four commercially available CORMs were screened for their cytotoxicity, their effects on cell metabolism, migration, VEGF expression, tube formation and VEGFR-2 activation. The most important result was the reduction in VEGF levels expressed by CORM-treated TNBC cells, along with the inhibition of phosphorylation of VEGFR2 and downstream proteins. The migration and tube formation ability of endothelial cells was also decreased by CORMs, justifying a potential re-purposing of old CORMs towards the anti-angiogenic therapy of TNBC. The additional favourable low cytotoxicity, reduction in the glycolysis levels and downregulation of haem oxygenase-1 in TNBC cells enhance the potential of CORMs against TNBC. In this study, CORM-2 remained the most effective CORM and we propose that CORM-2 may be pursued further as an additional agent in combination with existing anti-angiogenic therapies for a more successful targeting of malignant angiogenesis in TNBC

Radiosynthesis of [ 18 F]-Labelled Pro-Nucleotides (ProTides)

Phosphoramidate pro-nucleotides (ProTides) have revolutionized the field of anti-viral and anti-cancer nucleoside therapy, overcoming the major limitations of nucleoside therapies and achieving clinical and commercial success. Despite the translation of ProTide technology into the clinic, there remain unresolved in vivo pharmacokinetic and pharmacodynamic questions. Positron Emission Tomography (PET) imaging using [18F]-labelled model ProTides could directly address key mechanistic questions and predict response to ProTide therapy. Here we report the first radiochemical synthesis of [18F]ProTides as novel probes for PET imaging. As a proof of concept, two chemically distinct radiolabelled ProTides have been synthesized as models of 3′- and 2′-fluorinated ProTides following different radiosynthetic approaches. The 3′-[18F]FLT ProTide was obtained via a late stage [18F]fluorination in radiochemical yields (RCY) of 15−30% (n = 5, decay-corrected from end of bombardment (EoB)), with high radiochemical purities (97%) and molar activities of 56 GBq/μmol (total synthesis time of 130 min.). The 2′-[18F]FIAU ProTide was obtained via an early stage [18F]fluorination approach with an RCY of 1−5% (n = 7, decay-corrected from EoB), with high radiochemical purities (98%) and molar activities of 53 GBq/μmol (total synthesis time of 240 min)

The Role of Personal Meaning for Alcoholics in Achieving and Successfully Maintaining Sobriety

The aim of this study is to gain a greater understanding of the role of personal meaning in the lives of people previously deemed as alcoholics who have now successfully achieved and continue to maintain sobriety, including longer-term sobriety. Existing research studies have addressed the early stages of achieving sobriety but very few have discussed the issues involved in the long-term maintenance of change. This research study aims to make an original contribution by not only addressing the early stages of change but also the maintenance of these changes and maintaining them over the longer term. The study aims to add to the existing understanding of personal change, specifically in relation to alcoholism, through a focus on the role of personal meaning in change for alcoholics. The research adopted a qualitative interpretive methodology and used Personal Construct Psychology (PCP) as its theoretical framework. The constructivist approach of PCP considers behaviour as being shaped by the personal meaning that events and experiences hold for people. Eighteen semi-structured interviews were completed. Seven women and eleven men attending an alcoholism self-help group based in the North of England were interviewed in depth about their experiences of becoming sober and maintaining sobriety. At the time of the interviews all the participants had remained sober for between two and ten years. The study examined their perceptions of becoming sober and how they had managed to maintain this change. The interviews were analysed using Template Analysis and the findings have been interpreted within a PCP theoretical framework. The key findings to emerge from the analysis include the importance of the PCP theoretical concept of validation, which is a particular form of support from others and the involvment of families and friends in both helping and hindering recovery and its maintainence. The participants reported the use of imagination in order to rehearse the anticipated changes they needed to make before the changes were made in the ‘real world’. In addition, the participants spoke of imagining and anticipating a new sense of self, a sober self and what this new self meant to them. There was also evidence that the participants had reconstrued both themselves and others and now had new perceptions of both. It is hoped that the findings will inform interventions that may help more alcoholics to successfuly achieve and maintain change

The discovery of new and more potent chloropyramine (C4) analogues for the potential treatment of invasive breast cancer

Breast cancer is the second most common cancer worldwide, accounting for 25% of all female cancers. Although the survival rate has increased significantly in the past few decades, patients who develop secondary site metastasis as well as those diagnosed with triple negative breast cancer still represent a real unmet medical challenge. Previous studies have shown that chloropyramine (C4) inhibits FAK-VEGFR3 signalling. More recently, C4 is reported to have SASH1 inducing properties. However, C4 exerts its antitumour and antiangiogenic effects at high micromolar concentrations (>100 μm) that would not be compatible with further drug development against invasive breast cancer driven by FAK signalling. In this study, molecular modelling guided structural modifications have been introduced to the chloropyramine C4 scaffold to improve its activity in breast cancer cell lines. Seventeen compounds were designed and synthesized, and their antiproliferative activity was evaluated against three human breast cancer lines (MDA-MB-231, BT474 and T47D). Compound 5c was identified to display an average activity of IC50 = 23.5–31.3 μm, which represents a significant improvement of C4 activity in the same assay model. Molecular modelling and pharmacokinetic studies provided more promising insights into the mechanistic features of this new series