Medicine & Health

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  • (2023) Zillur Rahman, Kazi Mohammad
    Thesis
    Current healthcare infection surveillance rarely monitors the distribution of antimicrobial resistance (AMR) in bacteria beyond clinical settings in Australia and overseas. This results in a significant gap in our ability to fully understand and manage the spread of AMR in the general community. This thesis explores whether wastewater-based monitoring could reveal geospatial-temporal and demographic trends of antibiotic-resistant bacteria in the urban area of Greater Sydney, Australia. Untreated wastewater from 25 wastewater treatment plants sampled between 2017 and 2019 consistently contained extended-spectrum β-lactamases-producing Enterobacteriaceae (ESBL-E) isolates, suggesting its endemicity in the community. Carbapenem-resistant Enterobacteriaceae (CRE), vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA) isolates were occasionally detected. Demographic and healthcare infection-related factors correlated with the ESBL-E load, and demographic variables influenced the VRE load. In contrast, the healthcare infection-related factor mainly drove the CRE load. These findings demonstrate the potential of wastewater-based surveillance to understand the factors driving AMR distribution in the community. The subsequent thesis work covers the genomic characterisation of selected ESBL-E and CRE wastewater isolates to reveal their nature, origin, and underlying resistance mechanisms. Phylogenetic analysis showed that Escherichia coli isolates were related to high-risk human-associated pandemic clones and non-human-associated clones. The Klebsiella pneumoniae and K. variicola isolates were related to globally disseminated and emerging human-associated clones, and some were detected for the first time in Australia. Genomic analysis also indicated novel resistance mechanisms against nitrofurantoin in E. coli, and against piperacillin/tazobactam and ticarcillin/clavulanic acid in Klebsiella isolates. The virulence gene content indicated that some E. coli and Klebsiella isolates were likely associated with infections, while the asymptomatic carriage was suggested for other isolates. These results demonstrate a clear potential for wastewater-based surveillance to monitor the emergence and dissemination of resistance in non-clinical isolates, and in particular, isolates from the community and non-human sources. The findings of this study can complement healthcare infection surveillance to inform management strategies to mitigate the emergence and dissemination of AMR and important human pathogens in the general community.

  • (2023) Chan, Lloyd
    Thesis
    Depression 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.