Predictive Models For Falls-Risk Assessment in Older People, Using Markerless Motion Capture

Falling in old age contributes to considerable misery for many people. Currently, there is a lack of practical, low cost and objective methods for identifying those at risk of falls. This thesis aims to address this need. The majority of the literature related to falls risk and balance impairment uses force plates to quantify postural sway. The use of such devices in a clinical setting is rare, mainly due to cost. However, some force-plate-based commercial products have been created, e.g. the Balance Master. To align the research in this thesis to both the literature and existing methods of assessing postural sway, a method is proposed which can generate sway metrics from the output of a low-cost markerless motion capture device (Kinect V2). Good agreement was found between the proposed method and the output of the Balance Master. A key reason for the lack of research into falls-risk using markerless motion capture, is the lack of an appropriate dataset. To address this issue, a dataset of clinical movements, recorded using markerless motion capture, was created. Named KINECAL, It contains the recordings of 90 participants, labelled by age and falls-risk. The data provided includes depth images, 3D joint positions, sway metrics and socioeconomic and health meta data. Many studies have noted that postural sway increases with age and conflate age-related changes with falls risk. However, if one examines sub-populations of older people, such as master athletes, It is clear that this is not necessarily true. The structure of KINECAL allows for the examination of age-related factors and falls-risk factors simultaneously. In addition, it includes labels of falls history, clinical impairment and comprehensive metadata. KINECAL was used to identify sway metrics most closely associated with falls risk, as distinct from the ageing process. Using the identified metrics, a model was developed that can identify those who would be classified as impaired by a range of clinical tests. Finally, a model is proposed, which can predict fallers by placing individuals on a scale of physical impairment. An autoencoder was used to model, healthy adult sit-to-stand movements. Using an anomaly detection approach, an individuals level of impairment can be plotted relative to this healthy standard. Using this model, the existence of two older populations (one with a high falls risk and one with a low falls risk) is demonstrated

Multisystem proteinopathy due to a homozygous p.Arg159His VCP mutation : a tale of the unexpected

ObjectiveTo assess the clinical, radiologic, myopathologic, and proteomic findings in a patient manifesting a multisystem proteinopathy due to a homozygous valosin-containing protein gene (VCP) mutation previously reported to be pathogenic in the heterozygous state.MethodsWe studied a 36-year-old male index patient and his father, both presenting with progressive limb-girdle weakness. Muscle involvement was assessed by MRI and muscle biopsies. We performed whole-exome sequencing and Sanger sequencing for segregation analysis of the identified p.Arg159His VCP mutation. To dissect biological disease signatures, we applied state-of-the-art quantitative proteomics on muscle tissue of the index case, his father, 3 additional patients with VCP-related myopathy, and 3 control individuals.ResultsThe index patient, homozygous for the known p.Arg159His mutation in VCP, manifested a typical VCP-related myopathy phenotype, although with a markedly high creatine kinase value and a relatively early disease onset, and Paget disease of bone. The father exhibited a myopathy phenotype and discrete parkinsonism, and multiple deceased family members on the maternal side of the pedigree displayed a dementia, parkinsonism, or myopathy phenotype. Bioinformatic analysis of quantitative proteomic data revealed the degenerative nature of the disease, with evidence suggesting selective failure of muscle regeneration and stress granule dyshomeostasis.ConclusionWe report a patient showing a multisystem proteinopathy due to a homozygous VCP mutation. The patient manifests a severe phenotype, yet fundamental disease characteristics are preserved. Proteomic findings provide further insights into VCP-related pathomechanisms

Effects of Detergent on α-Synuclein Structure: A Native MS-Ion Mobility Study

The intrinsically disordered protein α-synuclein plays a major role in Parkinson’s disease. The protein can oligomerize resulting in the formation of various aggregated species in neuronal cells, leading to neurodegeneration. The interaction of α-synuclein with biological cell membranes plays an important role for specific functions of α-synuclein monomers, e.g., in neurotransmitter release. Using different types of detergents to mimic lipid molecules present in biological membranes, including the presence of Ca2+ ions as an important structural factor, we aimed to gain an understanding of how α-synuclein interacts with membrane models and how this affects the protein conformation and potential oligomerization. We investigated detergent binding stoichiometry, affinity and conformational changes of α-synuclein taking detergent concentration, different detergent structures and charges into account. With native nano-electrospray ionization ion mobility-mass spectrometry, we were able to detect unique conformational patterns resulting from binding of specific detergents to α-synuclein. Our data demonstrate that α-synuclein monomers can interact with detergent molecules irrespective of their charge, that protein-micelle interactions occur and that micelle properties are an important factor

Students' perception of the learning environment in a distributed medical programme

Background : The learning environment of a medical school has a significant impact on students’ achievements and learning outcomes. The importance of equitable learning environments across programme sites is implicit in distributed undergraduate medical programmes being developed and implemented. Purpose : To study the learning environment and its equity across two classes and three geographically separate sites of a distributed medical programme at the University of British Columbia Medical School that commenced in 2004. Method : The validated Dundee Ready Educational Environment Survey was sent to all students in their 2nd and 3rd year (classes graduating in 2009 and 2008) of the programme. The domains of the learning environment surveyed were: students’ perceptions of learning, students’ perceptions of teachers, students’ academic self-perceptions, students’ perceptions of the atmosphere, and students’ social self-perceptions. Mean scores, frequency distribution of responses, and inter- and intrasite differences were calculated. Results : The perception of the global learning environment at all sites was more positive than negative. It was characterised by a strongly positive perception of teachers. The work load and emphasis on factual learning were perceived negatively. Intersite differences within domains of the learning environment were more evident in the pioneer class (2008) of the programme. Intersite differences consistent across classes were largely related to on-site support for students. Conclusions : Shared strengths and weaknesses in the learning environment at UBC sites were evident in areas that were managed by the parent institution, such as the attributes of shared faculty and curriculum. A greater divergence in the perception of the learning environment was found in domains dependent on local arrangements and social factors that are less amenable to central regulation. This study underlines the need for ongoing comparative evaluation of the learning environment at the distributed sites and interaction between leaders of these sites

A new process to measure postural sway using a Kinect depth camera during a Sensory Organisation Test

Posturography provides quantitative, objective measurements of human balance and postural control for research and clinical use. However, it usually requires access to specialist equipment to measure ground reaction forces, which are not widely available in practice, due to their size or cost. In this study, we propose an alternative approach to posturography. It uses the skeletal output of an inexpensive Kinect depth camera to localise the Centre of Mass (CoM) of an upright individual. We demonstrate a pipeline which is able to measure postural sway directly from CoM trajectories, obtained from tracking the relative position of three key joints. In addition, we present the results of a pilot study that compares this method of measuring postural sway to the output of a NeuroCom SMART Balance Master. 15 healthy individuals (age: 42.3 ± 20.4 yrs, height: 172 ± 11 cm, weight: 75.1 ± 14.2 kg, male = 11), completed 25 Sensory Organisation Test (SOT) on a NeuroCom SMART Balance Master. Simultaneously, the sessions were recorded using custom software developed for this study (CoM path recorder). Postural sway was calculated from the output of both methods and the level of agreement determined, using Bland-Altman plots. Good agreement was found for eyes open tasks with a firm support, the agreement decreased as the SOT tasks became more challenging. The reasons for this discrepancy may lie in the different approaches that each method takes to calculate CoM. This discrepancy warrants further study with a larger cohort, including fall-prone individuals, cross-referenced with a marker-based system. However, this pilot study lays the foundation for the development of a portable device, which could be used to assess postural control, more cost-effectively than existing equipment

Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy

Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definite-ALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function. Differences in each individual metabolite and its ratio distributions were evaluated in the entire intracranial CST and in five segments along the length of the CST (at the levels of precentral gyrus (PCG), centrum semiovale (CS), corona radiata (CR), posterior limb of internal capsule (PLIC) and cerebral peduncle (CP)). Major findings included significantly decreased NAA and increased Cho and Cho/NAA in the entire intracranial CST, with the largest differences for Cho/NAA in all the groups. Significant correlations between Cho/NAA in the entire intracranial CST and the right finger tap rate were noted. Of the ten bilateral CST segments, significantly decreased NAA in 4 segments, increased Cho in 5 segments and increased Cho/NAA in all the segments were found. Significant left versus right CST asymmetries were found only in ALS for Cho/NAA in the CS. Among the significant correlations found between Cho/NAA and the clinical assessments included the left-PCG versus FVC and right finger tap rate, left -CR versus FVC and right finger tap rate, and left PLIC versus FVC and right foot tap rate. These results demonstrate that a significant and bilaterally asymmetric alteration of metabolites occurs along the length of the entire intracranial CST in ALS, and the MRS metrics in the segments correlate with measures of disease severity and UMN function

The specialty choices of graduates from Brighton and Sussex Medical School: a longitudinal cohort study

BACKGROUND Since 2007 junior doctors in the UK have had to make major career decisions at a point when previously many had not yet chosen a specialty. This study examined when doctors in this new system make specialty choices, which factors influence choices, and whether doctors who choose a specialty they were interested in at medical school are more confident in their choice than those doctors whose interests change post-graduation. METHODS Two cohorts of students in their penultimate year at one medical school (n = 227/239) were asked which specialty interested them as a career. Two years later, 210/227 were sent a questionnaire measuring actual specialty chosen, confidence, influence of perceptions of the specialty and experiences on choice, satisfaction with medicine, personality, self-efficacy, and demographics. Medical school and post-graduation choices in the same category were deemed 'stable'. Predictors of stability, and of not having chosen a specialty, were calculated using bootstrapped logistic regression. Differences between specialties on questionnaire factors were analysed. RESULTS 50% responded (n = 105/277; 44% of the 239 Year 4 students). 65% specialty choices were 'stable'. Factors univariately associated with stability were specialty chosen, having enjoyed the specialty at medical school or since starting work, having first considered the specialty earlier. A regression found doctors who chose psychiatry were more likely to have changed choice than those who chose general practice. Confidence in the choice was not associated with stability. Those who chose general practice valued lifestyle factors. A psychiatry choice was associated with needing a job and using one's intellect to help others. The decision to choose surgical training tended to be made early. Not having applied for specialty training was associated with being lower on agreeableness and conscientiousness. CONCLUSION Medical school experiences are important in specialty choice but experiences post-graduation remain significant, particularly in some specialties (psychiatry in our sample). Career guidance is important at medical school and should be continued post-graduation, with senior clinicians supported in advising juniors. Careers advice in the first year post-graduation may be particularly important, especially for specialties which have difficulty recruiting or are poorly represented at medical school