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BackgroundAnalysis of mixed microbial communities using metagenomic sequencing experiments requires multiple preprocessing and analytical steps to interpret the microbial and genetic composition of samples. Analytical steps include quality control, adapter trimming, host decontamination, metagenomic classification, read assembly, and alignment to reference genomes.ResultsWe present a modular and user-extensible pipeline called Sunbeam that performs these steps in a consistent and reproducible fashion. It can be installed in a single step, does not require administrative access to the host computer system, and can work with most cluster computing frameworks. We also introduce Komplexity, a software tool to eliminate potentially problematic, low-complexity nucleotide sequences from metagenomic data. Unique components of the Sunbeam pipeline include direct analysis of data from NCBI SRA and an easy-to-use extension framework that enables users to add custom processing or analysis steps directly to the workflow. The pipeline and its extension framework are well documented, in routine use, and regularly updated.ConclusionsSunbeam provides a foundation to build more in-depth analyses and to enable comparisons in metagenomic sequencing experiments by removing problematic low complexity reads and standardizing post-processing and analytical steps. Sunbeam is written in Python using the Snakemake workflow management software and is freely available at github.com/sunbeam-labs/sunbeam under the GPLv3.

This thesis investigates the implications of falls in residential aged care and provides evidence for exercise as a clinically and cost-effective intervention. The opening chapters present gaps in evidence and form the rationale for the studies undertaken. The first is a cluster randomised controlled trial to test the effectiveness of the Sunbeam Program which was designed to incorporate the key components of effective exercises for falls prevention in community dwellers. Falls rate was the primary outcome measure, a range of secondary outcomes were taken including; quality of life, physical performance, functional mobility, fear of falling and cognition. The trial included 16 clusters and 221 residents, 8 clusters were randomly allocated to receive the program and 8 continued usual care. Progressive resistance and balance training was individually prescribed and upgraded over 50 one- hour sessions provided twice weekly for 25 weeks in a group setting. At 12-months, there was a significant reduction of 55% in the rate of falls for those in the Sunbeam Program (incidence rate ratio = 0.45 (95% confidence interval 0.17 - 0.74). These findings are important as this is the first trial that provides strong evidence for exercise as an effective counter measure to falls in this setting. A significant improvement was also demonstrated in physical performance (p = 0‧02). The Sunbeam Program cost $AUD 463 per person to deliver and the incremental cost effectiveness ratio per fall avoided was $AUD 22. These outcomes are compared to other falls prevention programs and demonstrate cost effectiveness. These studies have important implications for residents of aged care as the intervention is relatively simple to scale with the potential to improve health outcomes as well as reduce healthcare costs.