Knee osteoarthritis (OA) is the commonest form of lower limb OA with a lifetime risk of over 40%. It is a disease characterised by symptoms such as pain and loss of function. In addition there are typical structural features on both radiographs and MRI. Knee OA represents a spectrum of disease, ranging from early preclinical cartilage change to established full thickness disease. Anteromedial knee OA is a particular phenotype of knee OA where disease is confined to the medial compartment. Whilst end stage arthritis is treated reliably with joint arthroplasty, those with early stage disease are treated with a variety of non- surgical interventions with varying success. This thesis is concerned with understanding the disease of patients that have early radiographic changes but symptoms not controlled by conservative measures. Up to 150 of these patients a year present to the Nuffield Orthopaedic Centre, Oxford. They have been described as being in the “Treatment Gap”. A series of validation studies were performed to determine the optimal method for diagnosing cartilage defects within the knee. The three commonest diagnostic methods were examined for their validity. Arthroscopic assessments of cartilage lesions demonstrated a moderate level of intra and inter observer reliability. In contrast, radiographs and MRI demonstrated high levels of reliability. When using MRI as a criterion standard, both radiographs and arthroscopic assessment were found to have poor accuracy. Based on the work in this thesis a formal definition of the cartilage changes exhibited in early knee OA was proposed. A cross sectional cohort of 100 patients with the symptoms and radiological features of early knee OA were identified. Their pain and function profile was compared to two comparison groups of patients at the end stage of knee OA (defined by the need for partial or total arthroplasty). In up to 78% of individual cases those with early OA had pain and function profiles as bad as those with end stage disease. The cross sectional symptoms of early knee OA demonstrate a marked discordance with their mild radiographic changes. The same cohort was extended to 125 patients. They were followed over one year with monthly PROM assessments to determine how symptoms change over time. 43% of patients experience a clinical improvement over 12 months, 31% experience a clinical deterioration and 26% remain unchanged. The range in OKS variation over 12 months was on average 12 points, with clinically relevant variation occurring on 45% of monthly measurements. Patients with early knee OA can expect to experience considerable variation in their symptoms over 12 months and this must be considered when planning interventions. A number of patients with early knee OA were noticed to demonstrate medial meniscal extrusion. Using data from the Osteo Arthritis Initiative (OAI) a nested case control study was designed to determine how the presence of meniscal extrusion in an otherwise normal knee affects the risk of developing knee OA over the next 48 months. This demonstrated an Odds Ratio of 3.5, suggesting that meniscal extrusion is a considerable risk factor for the development of OA. The presence of a knee injury or operative intervention to the index meniscus was shown to increase this risk. Many phenotypes of OA are known to demonstrate familial aggregation. In an attempt to determine where the earliest structural changes occur in medial compartment knee OA, a cohort of patients selected only for their family history of the disease were developed. This cohort was compared to spouse controls for the presence of knee OA, as well as meniscal extrusion and long leg alignment. In addition, a functional analysis of their cartilage was performed. This cohort was not shown to be at increased risk of disease compared to controls. Discussion of the possible reasons for this finding is presented. Early knee osteoarthritis is a considerable clinical problem. This thesis has aided the understanding of the condition by firstly defining the radiological description of these patients. Secondly, their cross sectional and longitudinal symptom profile have been described for the first time. In addition, the presence of an extruded meniscus has been demonstrated as a substantial risk factor for the disease. Finally, family history has not been demonstrated as a risk factor for the disease within the limits of the study described here. Future work has been proposed.

Alcohol and drug abuse are strong predictors of suicide. While screening methods have proven effective at identifying and treating substance abuse in non-treatment-seeking users (e.g., screening and brief intervention [SBI]), less attention has been given to the co-occurrence of suicidality among this population, including its correlates and etiology. The current study addresses this gap by presenting data from early adult emergency department (ED) patients (mean age = 27; N = 505), screened for substance abuse and suicidal ideation. Prevalence of past year ideation was high (15%). Results demonstrated a significant and positive indirect effect of cocaine use severity on likelihood of suicidal ideation, mediated through family support. The implications for SBI practices in the ED and suicide etiology among non-treatment-seeking substance abusers are discussed.

People who work in occupations that involve intensive near work are thought to have a higher chance of developing myopia than other people. For example, microscopists in the United Kingdom have a higher prevalence of myopia than that of the general community. The prevalence of myopia in Hong Kong is extremely high (71 %) and Hong Kong Chinese people are particularly susceptible to myopia development and progression due to environmental factors. It is possible that this environmental susceptibility may lead to Hong Kong Chinese microscopists developing even greater levels of myopia. We found that the prevalence of myopia in Hong Kong microscopists (n=47, mean age=31 years) was higher than that of United Kingdom microscopists (87 % c.f. 71 %) and similar aged people within the general Hong Kong population (87 % c.f. 71 %; −4.45 D c.f. -3.00 D). However, while in most microscopists (83 % of 36 microscopists followed for a two-year period) the amount of myopia and vitreous chamber depth increased over a two year monitoring period (−0.11 D, 0.06 mm), the increase was not clinically significant. We hypothesised that the slower myopia progression rate in Hong Kong microscopists may be the result of their older average age (Hong Kong microscopists: 31.7 years c.f. United Kingdom microscopists: 29.7 years). When a person looks into a microscope, excessive accommodation occurs even though the microscope is designed to render the magnified image at optical infinity (zero accommodation and vergence demand). This over accommodation is called instrument myopia. It is possible that this over accommodation is linked to the myopia development and progression that occurs in users of these instruments. We found that instrument myopia remained consistent with different viewing conditions and microscope settings (inexperienced microscopists, n=20, mean age: 24.1 years, mean spherical refractive error: −2.83 D). The magnitude of instrument myopia was not correlated with either the age or refractive error of the microscope user, while it was lower in those users with greater experience (inexperienced microscopists: 1.03 D c.f. experienced microscopists: 0.43 D). As the Hong Kong microscopists (n=10, mean age: 31.2 years, mean spherical refractive error: −3.39 D) who partook in this study were experienced (6.3 years spent working in this field), this may have contributed to the lower myopia progression that was observed. Studies to determine the main contribution to the phenomena of instrument myopia were also conducted. Instrument myopia was not correlated with convergence when looking into microscope (r= −0.224, p=0.342), near phoria (r=0.351, p=0.129), AC/A ratio (r= −0.135, p=0.571), the convergence induced by the excessive accommodative response (r= −0.028, p=0.906), lag of accommodation (r=0.065, p=0.785) and tonic accommodation (r=0.142, p=0.551). We suggest that the main contribution to instrument myopia during microscopy is proximal accommodation due to the awareness of the closeness, caused by the height of the microscope (i.e. the distance between the viewer and the table where the microscope is placed), during microscopy. For example, we found that the magnitude of instrument myopia increased significantly (from 0.64 D to 1.16 D) when the height of the microscope decreased from 50 cm to 35 cm. In conclusion we have added, through direct observation, to the understanding of the characteristics of instrument myopia. Guidelines for new microscopists aimed at minimising the amount of instrument myopia that is experienced have been developed. This information might help to reduce the amount of myopia progression in commencing microscopists.

The topic of this thesis is study abroad. The theoretical part presents knowledge about the process of adaptation in a new country and its culture; then it deals with acculturative and coping strategies, culture shock and its determinants and also reverse culture shock, which takes place after arrival home form a foreign country. It also introduces the age group of participants on study abroad (21 {--} 26 years old) from the developmental psychology point of view. Then it describes the already known correlation relationships between personality characteristics and some aspects of long term stays abroad. Finally, it outlines a personality profile of the ideal person for a long term study abroad. The research part informs the reader about knowledge we have found out from 3 research questionnaires that were completed by students before, during and after the experience of study abroad, and also knowledge we have gained thanks to interviews with the students. The main research areas are the following: the personality profile, changes of chosen characteristics that have taken place due to the experience of the study abroad, motivation, expectations and their fulfillment, process of culture shock and reverse culture shock.