Academic literature on the topic 'RC Internal medicine'

Purpose: To adapt the Rotator Cuff Quality of Life (RC-QOL) questionnaire into traditional Chinese (Chi-RC-QOL) and to evaluate the validity and reliability in patients suffering from rotator cuff pathologies in Hong Kong. Methods: The Chi-RC-QOL will be constructed using the forward-translation followed by the backward-translation method. Thirty consecutive patients with clinically and radiologically confirmed rotator cuff pathology were recruited. Descriptive statistics will be followed by validity assessment using comparison with the Constant Shoulder (CS) score, University of California Los Angeles (UCLA) Shoulder Rating Scale, and Western Ontario Rotator Cuff (WORC) score. Parametric data will be tested using Pearson’s correlation coefficient for the total scores. Reliability was assessed using a test–retest interval of 30 min. The Cronbach’s α and intraclass correlation coefficient were calculated. Results: Cronbach’s α and internal consistency scores were high for all parts of the Chi-RC-QOL, with Cronbach’s α ranging between 0.89 and 0.98. Internal consistency scores range from 0.82 to 0.92, which can be regarded as an excellent correlation. Test–retest reliability was excellent for all parts of the Chi-RC-QOL with good absolute reliability. Chi-RC-QOL correlates well with the CS score, UCLA Shoulder Rating Scale, and the WORC score, with all being statistically significant. Conclusions: The current study adapted the RC-QOL to traditional Chinese version. The analysis confirmed the validity and reliability of the Chi-RC-QOL questionnaire. Level of Evidence: III.

The main aim of the study was to perform selection procedure in order to find the optimal predictors for the shear strength of fibre reinforced polymers (FRP) used as internal reinforcement for reinforced concrete (RC) beams. The procedure was performed by adaptive neuro fuzzy inference system (ANFIS) and all available parameters are included. The ANFIS model could be used as simplification of the shear strength analysis of the FRP-RC beams. MATLAB software was used for the ANFIS application for the shear strength prediction of the FRP-RC beams. The results from the searching procedure indicated that ?beam width? and ?effective depth? form the optimal combination of two input attributes or two predictors for the shear strength prediction of the FRP-RC beams. This selected two predictors could be used effectively to estimate the strength of the FRP-RC beams.

The use of a protective cervical barrier (PCB) is very well established to perform a safe internal bleaching; however, there is still no consensus on which material has the best sealing ability. Objective: This in vitro study aimed to evaluate the apical and linear sealing of different PCB materials placed during internal bleaching. Material and methods: This study had two study factors: PCB positioning, divided at two levels (cement-enamel junction [CEJ] and 1mm above the cement enamel junction [CEJ+1]); and PCB material, divided at eight levels (resin composite [RC], glass ionomer cement [GIC], resin-modified glass ionomer cement liner [LRGIC], restorative resin-modified glass ionomer cement [RRGIC], zinc phosphate cement [ZPC], eugenol-free zinc oxide cement [ZOC], provisional filling resin [PFR] and gutta-percha as control [GUT]). Response variables were apical and linear sealing obtained through dye penetration and analyzed with a digital microscope. Data were subjected to two-way analysis of variance followed by Tukey test (p<0.05). Results: The main factor for both apical and linear sealing was the type of material (p<0.01) regardless of their position. RC and ZPC presented the worst sealing values (p<0.05). The Spearman rank correlation coefficient revealed a positive correlation between the apical and linear leakage. Conclusion: The results suggest that RC and ZPC must be avoided as a PCB during internal bleaching procedures.

IntroductionBladder cancer (BC) is a common malignancy and one of the most expensive to manage. Radical cystectomy (RC) with pelvic lymphadenectomy is a gold standard treatment for high-risk BC. Reductions in morbidity and mortality from RC may be achieved through robot-assisted RC (RARC). Prospective comparisons between open RC (ORC) and RARC have been limited by sample size, use of extracorporeal reconstruction and use of outcomes important for ORC. Conversely, while RARC is gaining in popularity, there is little evidence to suggest it is superior to ORC. We are undertaking a prospective randomised controlled trial (RCT) to compare RARC with intracorporeal reconstruction (iRARC) and ORC using multimodal outcomes to explore qualitative and quantitative recovery after surgery.Methods and analysisiROC is a multicentre prospective RCT in English National Health Service (NHS) cancer centres. We will randomise 320 patients undergoing RC to either iRARC or ORC. Treatment allocation will occur after trial entry and consent. The primary outcome is days alive and out of hospital within the first 90 days from surgery. Secondary outcomes will measure functional recovery (activity trackers, chair-to-stand tests and health related quality of life (HRQOL) questionnaires), morbidity (complications and readmissions), cost-effectiveness (using EuroQol-5 Domain-5 levels (EQ-5D-5L) and unit costs) and surgeon fatigue. Patients will be analysed according to intention to treat. The primary outcome will be transformed and analysed using regression. All statistical assumptions will be investigated. Secondary outcomes will be analysed using appropriate regression methods. An internal feasibility study of the first 30 patients will evaluate recruitment rates, acceptance of randomised treatment choice, compliance outcome collection and to revise our sample size.Ethics and disseminationThe study has ethical approval (REC reference 16/NE/0418). Findings will be made available to patients, clinicians, funders and the NHS through peer-reviewed publications, social media and patient support groups.Trial registration numbersISRCTN13680280andNCT03049410.

Due to the high prevalence of cardiovascular diseases and better treatment strategies, with increased survival, heart failure is a condition with increasing prevalence, especially in developed countries. Heart failure patients often present electrolytic disorders, the most frequent one being hyponatremia. The objective of the study was to evaluate the frequency of hyponatremia in patients with chronic heart failure hospitalized in the Internal Medicine Clinic of the Clinical Emergency Hospital of Bucharest and to assess the clinical and paraclinical correlations, as well as prognostic implications of hyponatremia in these patients. We performed an observational retrospective study on 400 chronic heart failure patients hospitalized between January 1st 2014 and August 31st 2015. From these patients, 60 patients have been diagnosed with hyponatremia (defined as a serum natrium [135 mEq/L) and represented our group of study. The values of the serum natrium at admission in the study group ranged between 110-132 mmol/L. Most patients had advanced heart failure, according to NYHA classes� classification. The proportion of patients discharged with persistent hyponatremia was 48.33%, lower than the patients discharged with corrected serum sodium (51.67%), indicating an effective treatment of hyponatremia during hospitalization. The mortality rate during hospitalization in patients with corrected hyponatremia was 8.33%, smaller than the mortality rate in patients with persistent hyponatremia despite the correct administration of hydroelectrolytic rebalancing treatment (18.33%). Persistent hyponatremia may be considered a marker of a poor prognosis in hospitalized heart failure patients.

Developing molecular generative models for directly generating 3D conformation has recently become a hot research area. Here, an autoencoder based generative model was proposed for molecular conformation generation. A unique feature of our method is that the graph information embedded relative coordinate (GIE-RC), satisfying translation and rotation invariance, was proposed as a novel way for encoding molecular three-dimensional structure. Compared with commonly used Cartesian coordinate and internal coordinate, GIE-RC is less sensitive on errors when decoding latent variables to 3D coordinates. By using this method, a complex 3D generation task can be turned into a graph node feature generation problem. Examples were shown that the GIE-RC based autoencoder model can be used for both ligand and peptide conformation generation. Additionally, this model was used as an efficient conformation sampling method to augment conformation data needed in the construction of neural network-based force field.

Risk calculator (RC) combining PSA with other clinical information can help to better select patients at risk of prostate cancer (PCa) for prostate biopsy. The present study aimed to develop a new Pca RC, including MRI and bladder outlet obstruction parameters (BOOP). The ability of these parameters in predicting PCa and clinically significant PCa (csPCa: ISUP GG≥2) was assessed by binary logistic regression. A total of 728 patients were included from two institutions. Of these, 395 (54.3%) had negative biopsies and 161 (22.11%) and 172 (23.6%) had a diagnosis of ISUP GG1 PCa and csPCa. The two RC ultimately included age, PSA, DRE, prostate volume (pVol), post-voided residual urinary volume (PVR), and PIRADS score. Regarding BOOP, higher prostate volumes (csPCa: OR 0.98, CI 0.97,0.99) and PVR ≥ 50 mL (csPCa: OR 0.27, CI 0.15,0.47) were protective factors for the diagnosis of any PCa and csPCa. AUCs after internal validation were 0.78 (0.75, 0.82) and 0.82 (0.79, 0.86), respectively. Finally, decision curves analysis demonstrated higher benefit compared to the first-generation calculator and MRI alone. These novel RC based on MRI and BOOP may help to better select patient for prostate biopsy after prostate MRI.

In many seismically active regions worldwide, massive reinforced concrete (RC) structures built before the 1970s existed. These older RC buildings, in countries having seismic history, were designed for gravity loads only. Anyway, the beam-column connections influence the structures where the functions of connection shortage by transport the forces like shear, moment, and torsion through the beam to the column. Also, it could behave in a ductile manner to help the structure resist the seismic, as simulate the seismic loading by high and low cyclic loading. Due to the failure of external joints more than the internal beam-column joints, this review focuses on the behavior of exterior beam-column joints under cyclic loading, consequently simulated the behavior under an earthquake and the reinforcement detailed.

The development of psychotropic chemotherapy with widespread use in the psychiatric clinic for its anxiolytic, hypnotic, antidepressant, psychostimulant or psycho-destructive sedative effects has given rise to a new pathology secondary to increased abuse and accessibility. Their neurotropism is generally exerted on the central nervous system at the level of the complex meso-diencephalo-striate structures, influencing the elementary psychic functions, but also the activity of the whole organism through the neuro-humoral system. The clinical investigation of the patient must be interdisciplinary in nature, as human beings are characterized by a bio-psycho-social unit, in which the various biological and psychological components, influenced to a greater or lesser extent by the social environment, are involved in a special way, which gives an original personality to everyone. There are five fundamental axes, which are usually evaluated: thinking, memory, attention, emotion and behavior. A disorder in any of these axes, intense enough to interrupt the normal activity in more than one operating field over a sufficiently long period of time, is diagnosable as a mental disorder. There is an indication borrowed from internal medicine regarding the acute character (weeks), subacute character (months) and chronic character (years), which is attached to the diagnosis. A small part of the entire psychiatric population suffers from severe conditions, which involve intermittent episodes of severe disinhibition, aggressive behavior and self- or hetero-directed violence. In most cases, we talk about conditions such as depression or anxiety disorders (panic disorder, phobias, obsessive-compulsive disorder), which do not make him a social predator, although they cause enormous suffering to the individual. This study includes 67 patients with mental illness. While conducting the study, we took into account that the first contact with the patient is essential for the results of the anamnesis, oral examination, risk assessment and provisional treatment plan. In the 67 cases there were performed mycological analyses. It is necessary that dentists have certain knowledge of psychology and psychopathology, in order to understand the mechanism of psychopathological reactions and avoid them.

The purpose of this paper is to point out the value of OPG exam in pre and postoperative diagnosis assessment of maxillary inflammatory and atrophic lesions with the very full appreciation of surgical solutions and local integration of heterolog membranes and materials together with metallic implants used to repair the osseous defects and rehabilitate the dental status. There were statistically retrospective evaluated the pre and postoperative results of OPG exams of 47 patients with maxillary inflammatory and atrophic lesions clinically and biologically assessed, treated and dental rehabilitated by metallic implants at ESTETIQDENT, a dental medicine practice from Petrosani. In all cases we proceeded to surgical extraction of the non-vital teeth and ultrasonic plaques remove. In the presence of inflammatory radicular cysts, surgical radicular cysts removement and curettage of the periradicular granuloma were the elected choice together with heterolog membranes and materials repair of the osseous defects. When it was necessary, the existent prosthesis works were removed and in order to obtain the bone support, internal or external sinus lift and regional bone addition were performed for dental status rehabilitation through metallic implants. The OPG preoperative exams clearly showed the extent, the morphological characteristics and the topoanatomic reports, in all cases of maxillary inflammatory and atrophic lesions together with regional endodontic status. The postoperative OPG revealed the very local results of surgery procedures and the integration of heterolog membranes and materials used to repair the osseous defects and the dental status rehabilitation by metallic implants. The OPG exam is the imaging method of choice in pre and postoperative diagnosis assessment of maxillary inflammatory and atrophic lesions with the full appreciation of surgical solutions and local integration of heterolog membranes and materials together with metallic implants used to repair the osseous defects and rehabilitate the dental status, due to highly specific abilities in bone tissue evaluation of all maxillary skeletal and dental segments.

This thesis investigates the application of classical and contemporary statistical methods in medical research attempting to bridge the gap between statistics and clinical medicine. The importance of using simple and advanced statistical methods in constructing and assessing risk models in medicine will be demonstrated by empirical studies related to vascular complications: namely abdominal aortic aneurysm and diabetic retinopathy. First, data preprocessing and preliminary statistical analysis are examined and their application is investigated using data on abdominal aortic aneurysm. We illustrate that when dealing with missing data, the co-operation between statisticians and clinicians is necessary. Also, we show advantages and disadvantages of exploratory analysis. Second, we describe and compare classification models for AAA selective screening. Tow logistic regression models are proposed. We also show that it is important to assess the performance of classifiers by cross-validation and bootstrapping. We also examine models that include other definitions of abnormality, weighted classification and multiple class models. Third, we consider the application of graphical models. We look at different types of graphical models that can be used for classification and for identifying the underlying data structure. The use of Naïve Bayes classifier (NBC) is shown and subsequently we illustrate the Occam’s window model selection in a statistical package for Mixed Interactions Modelling (MIM). The EM-algorithm and multiple imputation method are used to deal with inconsistent entries in the dataset. Finally, modelling mixture of Normal components is investigated by graphical modelling and compared with an alternative minimisation procedure. Finally, we examine risk factors of diabetic sight threating retinopathy (STR). We show the complexity of data preparation and preliminary analysis as well as the importance of using the clinicians’ opinion on selecting appropriate variables. Blood pressure measurements have been examined as predictors of STR. The fundamental role of imputation and its influence on the conclusions of the study are demonstrated. From this study, we conclude that the application of statistics in medicine is an optimisation procedure where both the statistical and the clinical validity need to be taken into account. Also, the combination of simple and advanced methods should be used as it provides additional information. Data, software and time limitations should be considered before and during statistical analysis and appropriate modifications might be implemented to avoid compromising the quality of the study. Finally, medical research should be regarded for statisticians and clinicians as part of a learning process.

Chronic hypoxia, in animals and man, results in remodelling of the pulmonary vasculature with consequent pulmonary hypertension. The pulmonary artery fibroblast (PAF) has been shown to play an early and important role in hypoxia-induced pulmonary vascular remodelling. In acute and chronic hypoxia there is excess proliferation of PAFs. Morevoer, it is likely that cell-cell interactions between hypoxia-stimulated PAFs and other vascular cells – particularly smooth muscle cells - initiates and progresses the changes that occur in pulmonary vascular remodelling in the other vessel compartments. Although hypoxic proliferation of PAFs has been shown to be circulation specific and dependant on phosphorylation of p38 mitogen-activated protein (MAP) kinase, the cell signalling pathway(s)underlying this are incompletely characterised. Hypoxic activation of PAFs is a potential therapeutic target but, as p38 MAP kinase inhibitors are not established for clinical use, work was proposed to better characterise this pathway and identify agent(s) which may inhibit p38 MAPK indirectly. The HMG-CoA reductase inhibitor simvastatin was recently shown to inhibit hypoxic pulmonary vascular remodelling in rats, but the applicability of this finding to clinical practice is incompletely established and the mechanism of action of the statin is unclear. Statins have been shown to influence MAP kinase pathways in other cell types and, as their modes of action are well established, they can be used to interrogate uncharacterised upstream cell signalling pathways. On this basis, the aims of this study were firstly to determine whether statins had a therapeutically useful inhibitory effect on hypoxia-induced, p38 MAP kinase-mediated PAF proliferation. A second aim was to exploit the known effects of statins to better characterise hypoxic cell signalling upstream of p38 MAP kinase in PAFs. Lastly, comparison of the effects of statins with established pulmonary hypertension therapeutics and a preliminary assessment – also using statins as an experimental tool - of cell-cell interactions between PAFs and pulmonary artery smooth muscle cells (PASMCs) was proposed. 1μM of fluvastatin was found to selectively inhibit acute and chronic hypoxia-induced p38 MAP kinase phosphorylation and proliferation in rat PAFs. At this dose, fluvastatin had no effect on serum-induced proliferation in PAFs, no effect on systemic adventitial fibroblast proliferation, and no effect on the phosphorylation status of other MAP kinases. Selective use of mediators and inhibitors related to the HMG-CoA pathway indicated that a geranylgeranylated protein, probably Rac1, had an obligatory role upstream of p38 MAPK, in this signalling pathway. Co-culture and conditioned media experiments with bovine PAFs and PASMCs demonstrated the release of PASMC mitogens from hypoxic PAFs. 1μM fluvastatin and the p38 MAP kinase inhibitor SB203580 selectively blocked the hypoxic PAF-PASMC interaction. Results with hypoxic PAF proliferation with the prostacyclin analogue treprostinil, the phosphodiesterase-5 inhibitor sildenafil and the endothelin-1 antagonist bosentan were negative. Bosentan, however, inhibited the hypoxic PAF-PASMC interaction, suggesting endothelin-1 release by hypoxic PAFs, with proproliferative effects on PASMCs. The results reported in this thesis provide new information on hypoxic signalling,PAF proliferation and PAF cell-cell interactions in hypoxic states. A circulation and stimulus specific anti-proliferative effect of fluvastatin on PAFs was identified and this may be of clinical relevance in hypoxia-associated pulmonary hypertension.

Cardiovascular disease is the leading cause of morbidity and mortality in the Western world, mainly through cerebrovascular and coronary artery related events. Cardiovascular disease is a chronic progressive disease with different stages. These stages can be assessed by a variety of biomarkers. Biomarker quantification can be used for different purposes: screening, prediction of disease recurrence, therapeutic monitoring, diagnosis and prognostication. Noninvasive, inexpensive diagnostic tests currently applied in clinical practice have a relative high rate of false positive and false negative results. Therefore further refinement of the diagnostic process could improve clinical care. Regarding prognostication the need for improvement also remains as current risk models only predict a small quantity of occurring cardiovascular events. The concept of the cardiovascular continuum postulates that cardiovascular disease consists of a chain of events, is initiated by numerous cardiovascular risk factors and subsequently progresses through pathophysiological processes, ultimately leading to end-stage heart failure. For that reason cardiovascular diseases are chronic progressive conditions and can be divided into different stages, such as early tissue dysfunction or subclinical atherosclerosis prior to development of clinically overt disease. Biomarkers suitable for prognostication and diagnosis can differ at each stage. The general aim of this thesis was therefore the investigation of a variety of biomarkers in diagnosis and prediction of cardiovascular disease at different stages of the cardiovascular continuum, as covered by three different study cohorts contributing to this thesis. This included several approaches: the comparison of central and peripheral pulse pressure in middle aged hypertensive patients in regards of their prognostic potential; the application of established circulating, functional and structural biomarkers to the diagnostic process of coronary artery disease in stable angina patients; the development/refinement of a urinary proteomic biomarker for coronary artery disease and the examination of its diagnostic potential in stable angina patients. Biomarkers successful in the diagnosis of coronary artery disease were included in multiple biomarker models. Aside from biomarker development for the general population, investigations of specific cohorts, such as patients with certain diseases and belonging to certain age groups or sharing specific biochemical features provided advances in the past. To estimate the potential of a biomarker in risk prediction association studies with surrogate biomarkers are applicable. We collected a cohort of middle-aged hypertensive patients to assess if central pulse pressure, derived from non-invasive assessment of arterial stiffness, could improve risk prediction. Central pulse pressure has been previously shown to have prognostic value in populations with end-stage renal failure, coronary artery disease and high prevalence of diabetes mellitus. Considering the prognostic information of peripheral pulse pressure in the elderly, the hypothesis that central pulse pressure could improve risk prediction is comprehensive and was investigated as part of this thesis. This was accomplished by comparing the strength of correlation between central or peripheral pulse pressure and these surrogate biomarkers. When compared to peripheral pulse pressure, central pulse pressure had stronger associations with aortic pulse wave velocity, carotid intima-media thickness, and left ventricular mass index, but equal association with the albumin:creatinine ratio. In contrast, after adjustment for age, mean arterial pressure, heart rate and hypertension status there was no significant difference between central and peripheral pulse pressure for prediction of listed surrogate biomarkers in multivariate analysis. These results suggested that central pulse pressure is unlikely to provide more prognostic information than peripheral pulse pressure in middle-aged hypertensive patients. The diagnosis of coronary artery disease is clinically relevant in symptomatic patients, either acute or stable. The diagnosis of stable flow limiting coronary artery disease is especially challenging as non-cardiac as well as other cardiac conditions can mimic symptoms. Non-invasive diagnostic tools have either moderate sensitivities or specificities, or are not widely available. Therefore new biomarkers for the diagnosis of flow limiting coronary artery disease have the potential to improve current diagnostic strategies. This could be accomplished adjacent to existing biomarkers or by replacement of such, due to cost effectiveness, better discriminatory etc. As part of this thesis, a biomarker identification and validation study was conducted into urinary proteomics of coronary artery disease. First we tried to replicate a study conducted by our research group in the past. Therein, an established coronary artery disease specific polypeptide pattern was unable to differentiate between patients with severe coronary artery disease and healthy controls despite strong cohort similarities to the original study. We therefore recalibrated the urinary polypeptide pattern using an enlarged biomarker discovery cohort and adjusted the pattern for lipid lowering and angiotensin converting enzyme inhibitor treatment effects. We calculated a score from the resulting polypeptide pattern, which identified coronary artery disease patients with a sensitivity of 79% and a specificity of 88% in a biomarker validation cohort. As the next step of biomarker development we performed a diagnostic validation study. The investigated clinical cohort consisted of stable angina patients with or without coronary artery disease. The new polypeptide pattern score was unable to differentiate between these two groups. The score however correlated strongly with coronary artery disease extent as measured by the Gensini score, implying that urinary proteomics in the diagnosis of coronary artery disease is promising, yet requires further effort before clinical employment. In addition to the urinary proteomic biomarker development second diagnostic approach was selected. As coronary artery disease is a complex chronic disease, the combination of different biomarkers should result in a better discrimination between stable angina patients with or without coronary artery disease. This approach attempts to position the individual as precisely as possible on the cardiovascular continuum including serologic, functional vascular and imaging biomarkers of subclinical atherosclerosis. Serologic markers thereby present a plasma proteomic approach covering pathophysiological processes with known correlation or causative for coronary artery disease. Functional and structural changes of the peripheral vasculature resemble the coronary artery system. We investigated circulating biomarkers and vascular biomarkers separately. A variety of circulating biomarkers differentiated patients with severe coronary artery disease from healthy control subjects. When patients with stable angina and with or without coronary artery disease as diagnosed by coronary angiography were investigated no statistically significant differences could be detected for circulating biomarkers. In the same study a microvascular biomarker, the reactive hyperaemia index, and a macrovascular biomarker, the carotide plaque score, were able to differentiated between cases and controls. Both markers either added separately or together improved the risk classification of exercise treadmill test results. This suggests that a multiple biomarker approach in the diagnosis of coronary artery disease in stable angina patients could be successful. Different aspects of the cardiovascular continuum can be applied to diagnosis and prognostication of cardiovascular disease.

Cardiovascular disease is multifactorial. The main risk factors for developing cardiovascular disease (age, sex, smoking, diabetes, hyperlipidaemia and hypertension) do not explain its development in everyone. New risk factors are continually being sought in order to better understand and treat the disease process. In recent years homocysteine has been proposed as a risk factor for the development of premature cardiovascular disease as a consequence of the accelerated arterial and venous thrombotic disease seen in homocystinuria as a result of a single gene defect. This theory has been difficult to test because patients with premature cardiovascular disease are thankfully rare and because of the difficulties in measuring homocysteine itself. We propose that, if homocysteine is a causative risk factor for atherothrombosis, it will be involved in the development of cardiovascular disease regardless of age and have therefore studied affected patients from routine hospital clinics. Homocysteine analysis has become easier over the past decade with the development of HPLC methods utilising fluorescent detection, but these methods involve toxic chemicals and suffer from high background fluoresence. I have developed an HPLC method more suited to a routine hospital laboratory utilising coulometric detection for measuring plasma total homocysteine and used it to investigate the relationship between homocysteine levels and both micro- and macro-vascular atherothrombotic disease.

Trichotillomania (TTM) is a body focussed repetitive behaviour (BFRB) characterised by the repetitive pulling out of one’s hair. It is a moderately new disorder having only been classified in 1987 and it is under-researched relative to other psychological disorders. This thesis investigates TTM by presenting a series of experiments designed to further understand attitudes towards, and attentional biases in, TTM. The experiments in this thesis address 3 central issues: stigmatising attitudes towards TTM; attentional bias pertaining to the experience of shame in TTM; and attentional bias towards hair-related stimuli in TTM. Experiment 1 investigated differences in ratings of stigma towards perceived controllable (TTM, compulsive skin-picking) and perceived uncontrollable (alopecia, psoriasis) hair-loss and skin-lesioning conditions in a TTM and control group. The main findings indicated that stigma ratings varied as a function of group: the public rated perceived controllable conditions with higher stigma than perceived uncontrollable conditions while TTM participants rated these conditions equally. Experiment 2 used a modified emotional Stroop task using shame-related words to investigate the affective correlate of shame in individuals with TTM and a control group. TTMs did not demonstrate different response latencies to shame-related words, relative to other word types or the control group, indicating no evidence of attentional bias towards shame-related linguistic stimuli. Experiments 3, 4 and 5 focussed specifically on disorder-stimuli (i.e., hair-related) linguistic stimuli in a series of lexical paradigms. Experiment 3 was a lexical decision task and Experiment 4 was a modified Stroop task: these paradigms investigated response latencies towards hair-related words in TTMs and a control group. The main findings for both experiments showed that TTMs do not demonstrate an attentional bias towards hair-related words, relative to other word types and the control group. Experiment 5 investigated higher-level judgements of hair-related words in a word rating task. The findings revealed a group-by-word-type interaction for arousal ratings: TTMs rated hair-related words higher in arousal than body image and neutral words, and these ratings were higher than those of the control group for hair-related words. No group-by-word-type interaction for valence ratings was found. This indicates that TTMs rate hair-related words as more arousing but not more positive or negative, than other word types, relative to individuals without TTM. Finally, Experiment 6 utilised a modified dot probe paradigm to investigate attentional bias towards hair-related images. Our findings showed that TTMs disengage more slowly from hair-related images at a longer stimulus duration compared to neutral images, relative to control participants. This evidence is consistent with an attentional bias characterised by maintained attention towards hair-related stimuli in individuals with TTM. In conclusion, this thesis has presented evidence indicating that TTM (and other BFRBs) are associated with higher public stigma ratings than comparable perceived uncontrollable conditions. Results have also shown an attentional bias towards hair-related images but not words. This represents an important contribution towards the understanding of the processing of disorder-related stimuli in TTM. This may have implications for the maintenance mechanisms potentially involved in the hair-pulling condition.

Poor sleep and high levels of anxiety have a detrimental effect on cognitive functioning. However, very little is known about what cognitive functions are affected by poor sleep or high levels of anxiety and if some are more affected than others. This thesis informs the understanding of poor sleep and anxiety with a focus on generalised anxiety disorder and how they affect specific cognitive functioning namely Attention and Working Memory. Chapter one is a systematic literature review of the qualitative research exploring how sleep deprivation impacts on the cognitive functioning of people with Autistic Spectrum Conditions (ASC) and the principal challenges associated with trying to study the impact of sleep deprivation in people with ASC. Following both database and manual searches, fifteen studies were included and reviewed. The review highlights the suggestions that poor sleep has a detrimental effect on the cognitive functioning of people with ASC. Also, the use of objective and subjective measures of sleep was discussed to help in the early detection of these problems and considerations of carers and families was reviewed. Future research/clinical implications are discussed. Chapter two is a quantitative research study that investigated the combined effects of GAD and poor sleep on Attention and Working Memory. Sleep quality and quantity were assessed using subjective and objective measures of sleep. Attention and Working Memory was measured using various neuropsychological measures. Groups were compared for differences in cognitive scores using a non-parametric test. Relationships between GAD-7 scores, sleep quality/quantity and cognition scores were investigated using correlation analyses. Implications for future research and clinical implications are discussed. Chapter three is a reflective account, exploring the role of reflexivity in personal and professional development during the research process.

Treating people living with severe health conditions has, and always will be, a fundamental part of the National Health Service. Given the complex nature of conditions such as Huntington's Disease and Cancer, research exploring the impact severe health conditions can have on those affected is of paramount importance. Chapter one is a systematic review utilising a meta-ethnographic approach to explore qualitative research portraying people's experiences of genetic testing for Huntington's Disease (HD). Electronic databases cataloguing relevant research were searched which, combined with manual searches, resulted in eleven studies suitable for inclusion. Three meta-themes were identified, highlighting the complex and individual nature of undergoing genetic testing, together with the potential emotional and behavioural consequences. The implications of such findings, together with clinical recommendations are considered. There is a dearth of research exploring what it is like to live with cancer as a young person in the United Kingdom. Chapter two is a qualitative research study that explored the lived experiences of young people (13-24 years) who had recently been diagnosed with cancer. Utilising an interpretative phenomenological approach, emergent findings related to the adversarial nature of being diagnosed with cancer, with young people speaking to the unjust nature of battling this disease at such a youthful age, questioning their identity and having to navigate a new, and at times, uncertain world. The clinical and service implications of these findings are discussed, alongside areas of future research. Chapter three represents the author's reflective account of conducting this research. From exploring initial motivations, to evaluating the role of "insider" and "outsider" perspectives, the author explores the reciprocal nature of conducting qualitative research, particularly in relation to the mutuality felt between himself and his participants.

Chronic liver disease is a highly prevalent condition associated with significant morbidity and mortality. There is need for clinicians to stratify chronic liver disease and for researchers to define meaningful study endpoints. Currently this is often reliant on liver biopsy histology, which is known to be a flawed gold standard. There is a need to develop novel, non-invasive techniques for the evaluation of chronic liver disease that are accurate and reliable. In this thesis I have demonstrated that multiparametric MRI can stage hepatic fibrosis in an unselected cohort with performance comparable to existing non-invasive fibrosis markers. The assessment of fibrosis is however confounded by inflammation. The sensitivity of multiparametric MRI to inflammation allows the differentiation of simple steatosis and NASH but in a non-alcoholic fatty liver disease (NAFLD) cohort, multiparametric MRI fails to predict fibrosis stage. Evaluating NAFLD with magnetic resonance spectroscopy has shown that this technique is feasible and that lipidomic differences can be demonstrated in patients with NAFLD. Exploring the role of multiparametric MRI in primary sclerosing cholangitis (PSC) has demonstrated a characteristic pattern in the distribution of corrected Tl in PSC suggesting that multiparametric MRI may have a role in its diagnosis and evaluation.

Antibiotic resistance is a major problem estimated to cost $100 trillion and cause 10 million deaths per year by 2050. Despite novel molecules targeting Gram-positive bacteria, there are no new antibiotics active against Gram-negatives. To prolong use of current drugs, we need to understand mechanisms of resistance to inform prescribing practices and drug discovery. Quinolone resistance is primarily conferred by mutations in the target loci: DNA gyrase (gyrA) and topoisomerase IV. Quinolone resistance arising from gyrA mutations has also been shown to confer a low level of protection against a range of non-quinolone drugs. This thesis investigated the hypotheses that altered supercoiling levels, resulting from gyrA mutations, alter expression of stress response genes and confer a generic protective effect against other antibiotics and chemicals. The effects of equivalent gyrA mutations in Salmonella and E. coli upon supercoiling were analysed. Both GyrA Ser83Phe and GyrA Asp87Gly substitutions resulted in altered topoisomer profiles, although these were different between the species. When exposed to stresses, Salmonella gyrA mutants maintain supercoiling in a relatively fixed manner, providing a degree of antimicrobial protection but possibly limiting flexibility in response to environmental change. Fluorescent reporter assays showed a modest elevation of stress responses in Salmonella GyrA Asp87Gly cells, but highly upregulated stress responses in E. coli GyrA Asp87Gly cells. This correlated with a competitive fitness benefit of E. coli GyrA Asp87Gly cells vs the parent in the presence of low levels of triclosan. The elevated stress responses likely result from supercoiling-induced changes in promoter accessibility, and are probably responsible for the generic protective effect gyrA mutation confers against other chemicals and antibiotics. Non-quinolone antimicrobials can provide a selective pressure that favours gyrA mutants, although this is highly dependent on condition and species.

Advancements in burn care have improved immediate outcome, however, the prevalence of sepsis and multiple organ failure (MOF) remain significant. Although well characterised the mechanisms responsible for the pathogenesis of MOF and increased propensity to infection are poorly understood. Neutrophil extracellular traps (NETs) provide protection against invading pathogens but also contribute to thrombosis. Sepsis is required for NET generation following severe thermal injury. Quantification of circulating NET biomarkers shows good discriminatory power for diagnosis of sepsis. Interestingly, neutrophils isolated from 24 patients with severe thermal injuries, ≥ 15% total body surface area, had a significantly reduced ability to form NETs ex vivo, potentially mediated by phenotypical changes of neutrophils and inhibitory effects of formyl peptides. This thesis identified a major biological mechanism driving MOF after severe thermal injury, namely the compromise to the actin scavenging system which leads to reduced DNAse activity and a build-up of circulating DNA. Preliminary analysis suggests that DNAse activity can be restored by prehospital use of fresh frozen plasma following major trauma. Thus, administration of blood products or manipulation of the actin scavenging system is a potential therapeutic target. This thesis has identified a number of novel mechanisms responsible for the regulation of NETs following severe thermal injuries and their implications for sepsis and MOF.