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(2023)ThesisSensory signals informing about frictional properties of a surface are used both for perception to experience material properties and for motor control to be able to handle objects using adequate manipulative forces. There are fundamental differences between these two purposes and scenarios, how sensory information typically is obtained. This thesis aims to explore the mechanisms involved in the perception of frictional properties of the touched surfaces under conditions relevant for object manipulation. Firstly, I show that in the passive touch condition, when the surface is brought in contact with immobilised finger, humans are unable to use existing friction-related mechanical cues and perceptually associate them with frictional properties. However, a submillimeter range lateral movement significantly improved the subject's ability to evaluate the frictional properties of two otherwise identical surfaces. It is demonstrated that partial slips within the contact area and fingertip tissue deformation create very potent sensory stimuli, enabling tactile afferents to signal friction-dependent mechanical effects translating into slipperiness (friction) perception. Further, I demonstrate that natural movement kinematics facilitate the development of such small skin displacements within the contact area and may play a central role in enabling the perception of surface slipperiness and adjusting grip force to friction when manipulating objects. This demonstrates intimate interdependence between the motor and sensory systems. This work significantly extends our understanding of fundamental tactile sensory processes involved in friction signaling in the context of motor control and dexterous object manipulation tasks. This knowledge and discovered friction sensing principles may assist in designing haptic rendering devices and artificial tactile sensors as well as associated control algorithms to be used in robotic grippers and hand prostheses.
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(2022)ThesisCardiovascular disease (CVD) is the leading cause of global mortality. Two forms of CVD are acute coronary syndromes (ACS) and heart failure (HF). Patients with either are prone to repeat hospitalisations, which are detrimental to both patients and the healthcare system. Traditional care models are suboptimal in preventing readmissions. Mobile health interventions (MHIs) are attractive due to the computing power and convenience of the smartphone. Firstly, the literature regarding MHIs in CVD is systematically reviewed and meta-analysed. MHIs improved medication adherence in ACS patients and hospitalisation rates in HF patients. The review noted limitations of published trials and identified features of successful MHIs, which were incorporated into the design of a novel smartphone app-based model of care (TeleClinical Care, TCC). TCC allows home measurement of blood pressure, heart rate and weight by patients. The readings are automatically transmitted to a central server, where clinicians can identify abnormalities and intervene accordingly. A pilot RCT comparing TCC and usual care (UC) to UC alone was performed (n=164). Patients using TCC had fewer readmissions at 6 months (41 vs. 21, hazard ratio 0.51, P= 0.015), and were more likely to be adherent with medications (75% vs. 50%, P= 0.001) and complete cardiac rehabilitation (39% vs. 18%, odds ratio 2.9, P= 0.02) compared to patients in the control arm. A process evaluation of the RCT was subsequently undertaken, which identified several contributory factors to TCC’s success, such as a helpful orientation protocol for team members, and high background rates of HF outreach service and cardiologist follow-up in both trial arms. Via a series of interviews, methods to improve the future delivery of TCC were identified, particularly relating to its integration into mainstream healthcare. Patterns of smartphone ownership among cardiac inpatients were also examined. Age, sex, diagnosis, and private health insurance subscription influenced smartphone ownership. These data will help identify patients who may be excluded from MHIs. The thesis contains a cost-effectiveness model of TCC if applied widely. When enrolment exceeds 237 patients, TCC will reduce healthcare costs relative to UC, resultant to readmission prevention. Enrolment of 500 patients is projected to save $100,000 annually. In conclusion, TCC is demonstrated as a feasible, beneficial, safe, and cost-effective intervention for patients with CVD.
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(2023)ThesisDepression is among the most prevalent mental disorders in middle-aged and older adults, with a global prevalence of up to 11%. Effective preventive measures for depression are often costly and labour-intensive and therefore require risk screenings to be practical. Recent studies suggested that clinically measured walking speed is a risk factor for depression, while little is known about whether other aspects of mobility are also predictive. To explore the temporal association between mobility, in particular daily-life mobility, and incident depression in older adults, one systematic review, one study on method development and validation, and three large-scale cohort studies were conducted. Significant findings include: • The Timed Up and Go Test, which incorporates multiple aspects of mobility (i.e., gait initiation, turning, and sit-to-stand time), is more predictive of depressive trajectories than the Six-Metre Walk Test and Five Times Sit to Stand Test. • Duration of the longest daily walking bout, measured with a waist-worn sensor, independently and significantly predicts incident depression over two years. • Daily-life walking speed, quality, quantity, and distribution can be reliably and validly measured with a wrist-worn sensor. • Daily-life gait quality and quantity, measured with a wrist-worn sensor, independently and significantly predict incident depression over nine years of follow-up. These findings add to the understanding of the association between human locomotion and depression. Gait quality and daily-life gait performances are independent and potentially modifiable predictors of depression. These measures, therefore, may have value for upcoming screening program development. Future research should investigate whether interventions addressing daily-life gait can play a role in preventing depression in middle-aged and older adults.
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(2023)ThesisLittle is known about human muscle growth in children with and without cerebral palsy (CP). The MUGgLE study aims to investigate growth-related changes in the three-dimensional (3D) architecture of lower leg muscles (muscle volume, physiological cross-sectional area (PCSA), fascicle length, and pennation angle) in 320 infants and children with and without CP aged < 3 months and 5 to 15 years. Infants have one leg scan (anatomical magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) images), while children have three scans over three years. The MUGgLE study is ongoing. This thesis presents data derived from the first scan conducted on each of 208 typically developing (TD) infants and children. Chapter 2 provides muscle volumes of ten muscle groups in infants, and the architecture and moment arms of the medial (MG) and lateral gastrocnemius (LG) muscles. By comparing these data to data obtained from adults, it was shown that MG muscle fascicles grow primarily in cross-section rather than in length from birth to adulthood. Chapter 3 determines if lower leg muscles grow synchronously from birth to 15 years. The data show that muscle volumes, normalised to total lower leg volume, vary with age, indicating asynchronous growth. The soleus and MG muscles grow disproportionately faster. Chapter 4 determines muscle-, age-, and sex-conditional distributions of MG and tibialis anterior (TA) muscle architecture from birth to 15 years. Up to age 15 years, both muscles grow nonlinearly in volume, PCSA, and fascicle length, while the pennation angles remain nearly constant. The MG and TA muscle fascicles grow primarily transversely rather than longitudinally over this period. Chapter 5 explores the development and evaluation of a portable dynamometer used to estimate the passive length-tension curves of the gastrocnemius muscles in children. The evaluation shows that the dynamometer requires further methodological refinements to be reliable enough for clinical and research use. This thesis contributes to the fields of biomechanics, muscle physiology, and human anatomy, providing the largest high-resolution 3D dataset of muscle architecture in children to date. Biomechanists can use the data to build more effective structure-function models of children’s muscles, clinicians can use the data to investigate disordered muscle growth in children and inform early interventions and treatments, and academics can use the data to teach muscle and bone anatomy.
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(2022)ThesisSecreted by pancreatic β-cells, insulin is the major anabolic hormone, regulating the metabolism of fats, proteins, and carbohydrates. Defects in insulin production or action can lead to diabetes characterized by derangements in glucose handling and metabolic disease. Diabetes affects 420 million people worldwide, increasing morbidity, mortality and placing a burden on healthcare of nations. There is a need for rapid and accurate monitoring of insulin levels to optimize diabetes management and facilitate early diagnosis of insulin related chronic diseases. Conventional strategies such as HPLC, MALDI-TOF, ELISA, etc. used for insulin detection are not suitable for point-of-care testing (POCT) as they are expensive, and require sample preparation, sophisticated instruments, and skilled personnel. Our goal was to develop techniques to allow POCT for insulin in real time. In this study we developed two lateral flow assays (LFAs) based POCT platforms using aptamers as the biorecognition molecules for colorimetric and fluorescent detection of insulin. A range of conditions were tested such as concentrations of aptamers, reporter molecules used, volume of sample required, and assay time to obtain quantify insulin levels using a standard LFA reader. The colorimetric LFAs had linear detection range of 0.01-1 ng.mL-1 and LOD of 0.01 ng.mL-1. The fluorescent LFAs exhibited a linear detection range of 0-4 ng.mL-1 and 0.1 ng.mL-1 LOD. Various signal amplification strategies were incorporated, ie., gold-silver amplification technique and rolling circular amplification (RCA) to further enhance the signal. The developed colorimetric LFAs were successfully used for insulin quantification in rat blood, human blood, and human saliva samples. Although insulin levels were quantified within 12 min, some issues arose such as coagulation, need for dilution, and non-uniform flow through the test strips. Further work is required to optimize blood handling to progress an insulin POCT in real time. Future work could develop a multiplexed strip for detection of different analytes such as HbA1c, glucose, and C-peptide for better management of diabetes, along with a smartphone reader App. This research goes some way to addressing the challenge of providing a reliable and rapid approach for highly sensitive and specific detection of insulin for POCT applications.