Smoking is a deep-rooted and complex psychological, behavioural, social and physiological practice. Smoking is reinforced by positive reinforcement outcomes and negative withdrawals symptoms experienced during abstinence (Marks et al., 2006). Furthermore smoking is a primary contributing factor in health inequality (Raw, McNeill, & West, 1998). Current data suggests that smoking rates in England have fallen to their lowest rate in over eighty years (Brown & West, 2014). Despite the downwards trend in smoking prevalence, smoking remains the UK’s biggest preventable cause of premature mortality (Twigg, Moon, & Walker, 2004). It has been acknowledged that the specialist Stop Smoking support programmes provided by the NHS have helped reduce smoking prevalence (Bauld, Bell, McCullough, Richardson, & Greaves, 2010). Whilst there has been a vast amount of research investigating the most effective behavioural and pharmacological support models (Lancaster, Stead, Silagy, & Sowden, 2000) there has been little research on the impact of smoking cessation advisor smoking status and clinical effectiveness (Lindson-Hawley, Begh, McDermott, McEwen, & Lycett, 2013). This study aimed to identify factors that contribute to NHS Stop Smoking advisor performance. Factors analysed included: advisor smoking status (historic and present); attitudes and beliefs towards smoking; level of training; proportion of time spent supporting patients; and number of patients supported. This study implemented a quantitative cross-sectional design. An online survey was used which consisted of three standardised questionnaires. The sample consisted of Stop Smoking advisors (n=159) from 24 London boroughs. The results were analysed using an ordinal logistic regression. The regression model showed no significant impact on the majority of the variables investigated. The non-contributing variables included: level of training; years practiced; level of advisor education; and number of patients supported in a given year. The model did however show that proportion of time spent delivering smoking cessation support significantly influenced quit rate. The results reinforce previous literature by Lindson-Hawley et al. (2013) which suggests smoking status does not significantly influence smoking practitioners’ outcomes or attitudes towards smoking. Proportion of time spent providing support was found to be a significant factor in predicting quit rate. These results suggest that these factors should be considered when recruiting, commissioning and training new smoking cessation advisors or provider organisations.

Microvesicles are heterogeneous population of micro-particles released constitutively and upon induction from healthy and unhealthy cells. The role of cancer cell derived-MV in intercellular communication gains an intensive aria of research. The influence of leukaemia cell derived-MVs in this study was determined on normal prostate epithelial cell lines. PNT2 cells were treated with Jurkat cell derived-MVs lost epithelial characteristic (decreased epithelial marker E-cadherin) and gained mesenchymal phenotype (increased expression of mesenchymal marker Vimentin). TGF-β and intracellular Ca2+ concentration were partially involved in Epithelial Mesenchymal Transition (EMT) process. PNT2 cells acquire mesenchymal characteristic produced high level of resistances against apoptotic signals after exposed to serum starvation and anti-cancer drug docetaxel, produce excessive level of MMP-9 and 2/3 of total TPNT2 cell population were arrested in the G2/M phase of the cell cycle, and halts cell proliferation. The influence of carcinoma cell derived-MVs on tumour microenvironment was examined through use of Non-small lung cancer cells (A549) derived-MVs on primary lung fibroblasts (MRC5). MRC5 cells were treated with A549 cell derived-MV produced significantly high level of myofibroblasts marker alpha-smooth muscle actin (α-SMA) cytoskeleton protein and FGF. MVs were isolated from the myofibroblasts were enriched with α-SMA protein. Primary fibroblasts were treated with MVs released myofibroblasts expressed high level of α-MSA protein. Elements present in the CGM cause aggregation of cancer cell MVs and significantly reduced the effects of MVs on the target cells.

Protein calorie malnutrition (PCM) is one of the most serious public health problems in the developing world, including Sudan. This condition was investigated through studies which examined three main areas: prevalence and seasonal variation, influencing demographic factors and impact on brain function with use of electroencephalogram (EEG) assessment before and after clinical and nutritional interventions. All 466 children admitted to the Khartoum Teaching Hospital and Ibn Oaf Children Emergency Hospital during July to September 2009 (the wet season) and during February to April 2010 (the dry season) were eligible for the study on the prevalence, seasonal variation and demographic factors influencing which influence the incidence of PCM. Questionnaires were employed to collect pertinent demographic, nutritional and anthropometric data. The impact of PCM on brain function were examined through a case-control study of 48 children admitted to the Ibn oaf Children Hospital in Khartoum between July 2011 to July 2012 (16 underweight, 16 with kwashiorkor, and 16 with marasmus), The data obtained were compared with those of 12 healthy and well-nourished children. EEGs, clinical and neuropsychological assessment were performed on admission and at two time points after discharge (week 4 and 12). The overall prevalence of PCM was 1.15%, and the distribution of marasmus, kwashiorkor and marasmic kwashiorkor 67.0, 23.0 and 10.0% respectively. Analysis of the 24-hour dietary recall revealed that the protein (p= 0.001), fat (p= 0.020), carbohydrates (p= 0.005) and energy (p=0.0028) consumption were statistically significantly lower than the recommended daily allowances. The coefficient of interaction between seasons and cofactors indicated that the wet season influenced significantly (p<0.0001) the incidence of PCM when the length of residence, paternal education, and sugar consumption were taken into consideration individually. In terms of demographic factors, mothers who delivered their first baby before they were 18 years old, mothers with a BMI of less than 18.5 Kg /m2 , a birth interval of less than 2 years, children aged 6-11 months (for marasmus), children aged 12-23 months (for kwashiorkor), children whose mid-upper arm circumference was less than 12.5cm and the number of children in a family were all highly associated with the incidence of PCM (p<0.001). Neuro-cognitive investigation of the children showed that 70.8% had abnormal EEG patterns and 50-70% neuropsychological abnormalities. However, after four weeks treatment, 84.4% of the protein calorie malnourished children exhibited normal EEG patterns. In conclusion, this study has revealed a high prevalence of PCM in Sudanese children with more cases during the wet season than the dry season. In addition, it has identified a number of predisposing demographic factors which must be addressed in order to help reduce the prevalence the disorder. Clinical and nutritional treatment of the children improved considerably clinical, neuropsychological and EEG outcomes. A more promising strategy to improve PCM outcomes may be to tackle the major risk factors for PCM: seasonality and demographic factors. It is envisaged that earlier intervention with the treatments would be beneficial. Future programmes should investigate the long-term impact of PCM on cognitive function including school performance. This study has generated important information about the prevalence of protein calorie malnutrition and pre-disposing socio-economic factors. Nevertheless it has some limitations. The main limitations are: first, there is potential recall bias among respondents answering questions relating to household food consumption, and events happening in the past, such as the child’s history of illness and breastfeeding patterns immediately after birth and then after. Second, information on some important confounding variables such as infection was not collected which could cause problems in interpreting the results. Third, the non-truly statement of the subjects regarding income which may cause bias was another limitation. Lastly, Lack of an address system limited follow-up with some patients. Overall, the findings have important implications for research policy and programme efforts towards improved growth monitoring and designing of interventions to mitigate protein calorie malnutrition and its determinants.

Aims There is a lack of sufficient knowledge about the stress experience in counselling psychology training. Previous research suffered methodological issues and there was a specific lack of qualitative studies. This research aims to contribute towards the topic as it explores the experience of stress in counselling psychology training from the perspective of young final year female trainees. Design Semi-structured interviews were conducted with eight final year female trainees (aged between 25 and 30) in order to explore their experiences of stress and major stressors in counselling psychology doctoral training. Method Interpretative phenomenological analysis was used to analyse the verbatim transcripts of interviews. Findings The process of analysis identified three superordinate themes: ‘identifying ambivalence in training’ (refers to the trainees’ mixed views about stress in training); ‘the impact of training on self and self-and-other’ (refers to the perceived lack of life outside of the training and high risk of failure); and ‘managing the lack of boundaries in training’ (refers to the process of merging with training and being forced to age). The themes are considered in relation to relevant existing literature. Conclusions Findings imply that young female trainees perceive stress as an integral element of training, which is both destructive and promoting their growth. It is suggested that training programmes should consider developing targeted interventions to support these trainees. Evaluation of the current study is followed by recommendations for future research.

Background: The Marlatt model of alcohol treatment (Marlatt & Gordon, 1986) is widespread. A key component of that model is alcohol expectancies. Alcohol expectancies refer to the effects of alcohol use anticipated by individuals. Metacognitive beliefs about alcohol are considered to be a specific form of alcohol expectancy (Spada, Moneta, & Wells). The present study argues that development of a triphasic metacognitive formulation for problematic drinking (Spada, Caselli, & Wells, 2012) represents the single most important advance in alcohol treatment since the advent of the Marlatt model. The formulation postulates that a reduction in positive and negative alcohol metacognitive beliefs leads to a reduction in alcohol use. A crucial element of the metacognitive formulation is attention allocation (Steele & Josephs, 1990). Internally generated conflict, such as gender role conflict (O’Neil, 1981), it is hypothesised, can disrupt attention allocation thereby reducing efficacy of metacognitive treatment. Method: A clinical sample of 102 (male, 74; female, 28) completed the Positive Alcohol Metacognitions Scale (PAM), Negative Alcohol Metacognitions Scale (NAM), Gender Role Conflict Scale (GRCS) and the Alcohol Use Disorders Identification Test (AUDIT). Results: Regression analysis indicated that gender role conflict moderated the relationship between positive alcohol metacognitions and alcohol use in men but not in women. Similar results were obtained for the GRCS subscale ‘Restricted Emotionality’. Conclusions: Findings have implications for gender sensitive interventions in both the Marlatt model generally and metacognitive therapy specifically.

Hyperlipidemia is defined by abnormally elevated levels of one or more lipids such as cholesterol or triglycerides in the bloodstream. It also involves elevated levels of lipoproteins especially LDL-cholesterol and this is the most common form of dyslipidemia. Hyperlipidemia is the result of complex interactions between environmental and genetic factors. Hyperlipidemia is the main cause of congestive heart diseases in adulthood. It is also the main cause of atherosclerosis which is the pathophysiological cause of vascular diseases such as angina pectoris, myocardial infarction, and stroke. It occurs due to disorders in lipid metabolism including elevation in cholesterol, low density lipoprotein, or triglyceride, or due to low levels of high density lipoprotein. Lifestyle is the main factor in prevention of hyperlipidemia. If lifestyle is not beneficial in the treatment or prevention of hyperlipidemia, drug therapy is required. Statins, fibrates, nicotinic acid bile acid sequestrants, and ezetimibe are approved drugs for the treatment of hyperlipidemia. Because of the tolerability problems, side effects, and low effectiveness of some of these drugs, discovery of new drugs is explored and investigated. Herbal products are not well explored as an alternative treatment for the treatment of hyperlipidemia. Ilex latifolia is a traditional Chinese medicine which has been used for decades for the treatment of hyperlipidemia and for weight loss. Prunella vulgaris, Rheum palmatum, and Panax notoginseng have been also used in traditional Chinese medicine. Very little work has been published about the effect of Ilex latifolia on hyperlipidemia. In this research project, Ilex latifolia hypolipidemic effect was compared to several herbs effects by assaying the effect of the extracts on pancreatic lipase. Ilex latifolia was the most active, and the other parts of the project focused on its effect on HMG-CoA reductase expression, and on LDL receptor expression in HepG2 and AML-12 hepatocytes. Ilex latifolia effect on mitochondrial metabolism, and glucose uptake was assayed in HepG2 and AML-12 hepatocytes. Chapter I is an introduction to hyperlipidemia, its types, causes, and treatment. A review of the literature relating to Ilex latifolia and other herbs and herbal compounds is given. Chapter II describes the assay of extracts from several herbs, and herbal compounds, for their inhibitory effect on pancreatic lipase, using orlistat as a positive control. It also shows that HPLC is more sensitive and accurate than a spectrophotometric assay of lipase. Ilex latifolia showed the most inhibition activity on pancreatic lipase compared to other herbs. Chapter III describes the fractionation of Ilex latifolia and pancreatic lipase inhibition activity of each fraction. Chapter IV describes the effect of Ilex latifolia extract on HMG-CoA reductase expression in HepG2 cells and the effect of Ilex latifolia extract on LDL receptors expression in HepG2 and AML-12 cells. Chapter V describes the effect of Ilex latifolia extracts on cell growth, mitochondrial toxicity, and glucose uptake in HepG2 and AML-12 cells. It also describes the effect of Ilex latifolia extract on ATP production in HepG2 cells. This study has demonstrated for the first time that Ilex latifolia can play a role in the treatment of hyperlipidemia through pancreatic lipase inhibition. Effects on HMG-CoA reductase inhibition and mitochondrial inhibition were not marked, but under some circumstances glucose uptake can be significantly affected. It remains to be seen, using animal studies and other cell culture models, whether inhibition of pancreatic lipase can wholly account for the hypolipidemic activity of Ilex latifolia, or whether other mechanisms may be involved.

Background: In view of the estimation that around one fifth of individuals abused in childhood will develop psychological difficulties which require professional input there is a high chance that counselling psychology trainees will encounter adult survivors in their practice. Counselling psychology trainees are continuously faced with philosophical and practical challenges when they seek to integrate psychological models into their practice. The critical literature review discusses the contentions regarding the most appropriate therapeutic approach when working with this client group, alongside maintaining the focus of therapeutic relationship. The review also explores the risk to clients of re-traumatisation through poorly conducted therapeutic interventions. In addition, potential risks to trainees have also been discussed such as difficult affective reactions or vicarious traumatisation. Aims: A lack of research was identified with regards to exploration of trainees’ internal experiences of working with this client group leading to the research question: How do counselling psychology trainees experience working with adult survivors of childhood sexual abuse? Methodology: Semi-structured interviews were conducted with six trainee counselling psychologists enrolled on BPS Accredited Counselling Psychology Doctoral courses, who had experience of working with adult survivors of CSA. The transcripts of the interviews were analysed using Interpretative Phenomenological Analysis (IPA). Results: From the analysis the following three key super-ordinate themes were developed: balancing the power dynamic in therapeutic relationship; management of vicarious emotional state of self; questioning competent versus incompetent self as therapist. Findings: The study identified clinical implications to develop further understanding and requirements for trainee counselling psychologists in relation the superordinate themes. Furthermore, an important limitation from the study was identified with regards to the inclusion of only one male participant. This highlighted the issue of gender differences between client and therapist; however, it underlined an important area requiring further study.

This qualitative research study explored the therapeutic relationship in online therapy from a counselling psychology perspective. An overview of the different types of online therapy and a brief history of the field were given and the existing literature surrounding online therapy and the therapeutic relationship was critically reviewed. Through this, a need was identified for an understanding of how therapeutic relationships are established in online therapy, with a particular focus on therapy via instant messaging. Semi-structured interviews were conducted asking online therapy practitioners about their experiences of therapeutic relationships. The resulting data were analysed using the grounded theory method and a tentative model of the processes that influence the formation of a therapeutic relationship online was created. An important factor in the model was therapists’ development of skills in online communication, which serve to overcome the lack of a physical presence and non-verbal communication that hinder text-based interactions. Another key influence was the management of the therapeutic frame, which is challenged by the nature of the online setting. Also significant was a client’s rationale for choosing online therapy, which influences their ability to engage in a therapy relationship online. The implications of the findings for counselling psychology professional practice, training and research were discussed.

Chronic Spontaneous Urticaria (CU) is a pruritic skin disorder that affects 0.8% of the population. As its aetiology is not fully understood the aim is to control symptoms through medicines to improve quality of life (QoL). Demographic and clinical factors have been inconsistent and poorly predict QoL but one modifiable factor that has gained credence is ones illness representations. The Common-Sense Model (Leventhal, Meyer and Nerenz, 1980) postulates that these guide coping procedures that impact outcomes. The aim of the thesis was to examine whether CU representations (mediated by coping) predicted QoL and whether both representations and QoL in CU were amenable to change via intervention. Preliminary studies undertaken validated CSM measures in CU and confirmed key reference values for CU-related QoL and its measurement. CU was seen as uncontrollable, emotionally arousing, chronic, cyclical, caused by stress and immunity with serious consequences and has a moderate impact on QoL (n=78). The necessity to take CU medicines equalled concerns about side effects. Cognitive representations were the strongest predictors of QoL explaining 35.0-60.6% of the variance independent of coping. Qualitative analyses presented CU as unsightly, uncontrollable and difficult to comprehend and self-regulate. Fifteen participants undertook psych-education and action plans to change CU representations. Multivariate analyses found a strong within-group main effect on QoL outcomes (p < .001) and for aspects of outcome over time (all p < .001). Correlation based change analysis further inferred that targeting CU cognitions resulted in changing QoL outcomes over time. In summary the thesis supported that: poor QoL is prevalent in individuals experiencing CU. Not only do CU representations predict QoL outcomes, they are amenable to change via intervention as are QoL outcomes. Such findings have implications for CU-related QoL research and how health psychology-dermatology collaborations maybe instrumental to improving outcome through psycho-education interventions in routine care to facilitate better CU self-management.

The lack of age-appropriate (paediatric) authorised medicines is a long-standing problem amongst regulatory authorities, patients, parents and prescribers. This is driven by the paucity of information on clinical efficacy, deficiency in safety data (i.e. biopharmaceutics) and the lack of quality information such as palatability and acceptability data in children. To counteract this deficiency bespoke, unlicensed formulations are formulated by contract manufacturers, hospitals and dispensing pharmacists using a variety of ‘recipes’ and differing manufacturing protocols. In this work, Morphological Analysis as a problem structuring method is deployed using key stakeholders of the problem complex. This method, developed from operational research and design thinking sectors, has the ability to structure and parameterise a complex problem to isolate a smaller subset of an internally consistent solution space for the design of experiments. Hence, Morphological Analysis is used experimentally to decide which pharmaceutical dosage forms of furosemide would be selected as a solution space for paediatric patients with low cardiac output syndrome. Morphological Analysis application resulted in the selection of two different dosage forms for further work (Microemulsion oral liquid dosage form and an Orodispersible Mini-tablet). The furosemide microemulsion formulation was developed using ternary phase diagrams to isolate the efficient self-emulsification regions. A range of experimental techniques and instruments were used to characterise the system such as HPLC, phase stability studies, droplet size determination, surface tension measurement, drug-excipient compatibility studies using FTIR and NMR, viscosity determination, thermodynamic stability assessment and determination of shelf-life via accelerated and long-term stability studies. The optimum composition of the furosemide microemulsion consisted of: MCT Oil 14%, Labrasol 60%-Transcutol-HP 20% (3:1) and Water 6%. A furosemide oro-dispersible mini-tablet formulation (ODMT) was also developed and analysed for quality assessment. The development approach for ODMT used factorial design at two levels with four factors. Pre-formulation studies included drug-excipient compatibility assessment using differential scanning calorimetry and powder flowability evaluation using angle of repose and Hausner’s ratio techniques. For that, sixteen batches of ODMTs were manufactured using a Manesty F3 tablet press; Post-compression testing and characterisation processes were performed and this involved testing for weight variation, hardness assessment, friability, in vitro disintegration, wetting time, drug content analysis, dissolution time and stability of ODMTs under ICH conditions. The optimum composition of furosemide ODMT was found to be (ludiflash excipient + 0.6% magnesium stearate lubricant + 1mg/tablet furosemide API) with 10 minutes mixing time at value 19 compression force.