Expositions

The first comprehensive introduction to the origins, aspirations, and evolution of live coding. Performative, improvised, on the fly: live coding is about how people interact with the world and each other via code. In the last few decades, live coding has emerged as a dynamic creative practice, gaining attention across cultural and technical fields—from music and the visual arts to computer science. Live Coding: A User's Manual is the first comprehensive introduction to the practice and a broader cultural commentary on the potential for live coding to open up deeper questions about contemporary cultural production and computational culture. This multiauthored book—by artists and musicians, software designers, and researchers—provides a practice-focused account of the origins, aspirations, and evolution of live coding, including expositions from a wide range of live coding practitioners. In a more conceptual register, the authors consider liveness, temporality, and knowledge in relation to live coding, alongside speculating on the practice's future forms

Urological Cancer 2020

This Urological Cancer 2020 collection contains a set of multidisciplinary contributions to the extraordinary heterogeneity of tumor mechanisms, diagnostic approaches, and therapies of the renal, urinary tract, and prostate cancers, with the intention of offering to interested readers a representative snapshot of the status of urological research

Applications and Experiences of Quality Control

The rich palette of topics set out in this book provides a sufficiently broad overview of the developments in the field of quality control. By providing detailed information on various aspects of quality control, this book can serve as a basis for starting interdisciplinary cooperation, which has increasingly become an integral part of scientific and applied research

Precision health approaches: ethical considerations for health data processing

This thesis provides insights and recommendations on some of the most crucial elements necessary for an effective, legally and ethically sound implementation of precision health approaches in the Swiss context (and beyond), specifically for precision medicine and precision public health. In this regard, this thesis recognizes the centrality of data in these two abovementioned domains, and the ethical and scientific imperative of ensuring the widespread and responsible sharing of high quality health data between the numerous stakeholders involved in healthcare, public health and associated research domains. It also recognizes the need to protect not only the interests of data subjects but also those of data processors. Indeed, it is only through a comprehensive assessment of the needs and expectations of each and every one regarding data sharing activities that sustainable solutions to known ethical and scientific conundrums can be devised and implemented. In addition, the included chapters in this thesis emphasize recommending solutions that could be convincingly applied to real world problems, with the ultimate objective of having a concrete impact on clinical and public health practice and policies, including research activities. Indeed, the strengths of this thesis reside in a careful and in-depth interdisciplinary assessment of the different issues at stake in precision health approaches, with the elaboration of the least disruptive solutions (as far as possible) and recommendations for an easy evaluation and subsequent adoption by relevant stakeholders active in these two domains. This thesis has three main objectives, namely (i) to investigate and identify factors influencing the processing of health data in the Swiss context and suggest some potential solutions and recommendations. A better understanding of these factors is paramount for an effective implementation of precision health approaches given their strong dependence on high quality and easily accessible health datasets; (ii) to identify and explore the ethical, legal and social issues (ELSI) of innovative participatory disease surveillance systems – also falling under precision health approaches – and how research ethics are coping within this field. In addition, this thesis aims to strengthen the ethical approaches currently used to cater for these ELSIs by providing a robust ethical framework; and lastly, (iii) to investigate how precision health approaches might not be able to achieve their social justice and health equity goals, if the impact of structural racism on these initiatives is not given due consideration. After a careful assessment, this thesis provides recommendations and potential actions that could help these precision health approaches adhere to their social justice and health equity goals. This thesis has investigated these three main objectives using both empirical and theoretical research methods. The empirical branch consists of systematic and scoping reviews, both adhering to the PRISMA guidelines, and two interview-based studies carried out with Swiss expert stakeholders. The theoretical branch consists of three chapters, each addressing important aspects concerning precision health approaches

Systematic analysis of prognostic miRNAs and isomiRs in prostate cancer

There are no reliable prognostic indicators to distinguish between indolent and aggressive prostate cancer (PCa). Consequently, 42–66% of patients with indolent PCa are over-treated. Additionally, 15-45% of patients treated with radical prostatectomy (RP) experience biochemical recurrence (BCR) within 5-years, highlighting an urgent need for reliable prognostic biomarkers. MiRNAs (miRs) and isomiRs (miR isoforms) are non-coding regulatory RNAs that hold ideal biomarker properties such as detection in circulation, tissue and tumour specific expression profiles, and correlation with PCa development and progression. I hypothesised that miR species (canonical miRs and isomiRs) can be utilised as biomarkers for reliable PCa prognostication. A novel database of prognostic PCa miRs was built by performing a systematic review of relevant publications in the PubMed database. MiRs significantly associated with BCR were also identified following a meta-analysis of six datasets. MiR-148a-3p and miR-582-4p were identified as potential biomarker candidates as they were consistently prognostic in both the review and meta-analysis. The ability of miR species to predict BCR post-RP was tested with elastic net regularisation models using The Cancer Genome Atlas PCa dataset (recurrent=61, non-recurrent=330). Models based on a combination of isomiRs and clinical markers achieved marginally greater predictive power (AUC=0.795) than the model solely based on clinical markers (AUC=0.748), demonstrating that isomiRs could contribute additional prognostic value to the clinical markers currently used. The mechanism by which miR-27a-3p, a PCa-specific putative oncomiR, promotes tumour growth was investigated using RNA-seq data from LNCaP tumour xenograft models treated with a miR-27a-3p inhibitor (n=3) and control (n=3). 11 significantly dysregulated genes involved in apoptosis and oncogenic signalling were identified as likely mir-27a-3p targets. This study has not only furthered our understanding of the importance of miRs in PCa, but also identified potential prognostic miR biomarkers and showed the inclusion of miR species increases the utility of current markers.Open Acces

Molecular and Computational Transcriptomics in Prostate Cancer

RNA-seq is a powerful new technology that allows detection of new RNA molecules, including potentially new biomarkers. For various analysis applications of such data, new or better solutions are needed. Because there is a lack of diagnostic / prognostic biomarkers for prostate cancer, one of the most common types of cancer in men, prostate cancer is an ideal model system for the development of new analysis methods. We developed new computational methods, to improve detection of fusion genes and small ncRNAs, and demonstrate how these methods can be used to find prostate cancer specific transcripts. All proposed methods were ultimately integrated into the Galaxy RNA workbench that has been made available to other researchers, free of charge

Conserving Australia's iconic marsupials; one genome at a time

In the midst of a global sixth mass extinction event, conservation initiatives are now more crucial than ever. Australia houses the most diverse range of marsupial species in the world; however, the number that are threatened is growing every year. Genetic management of threatened populations is vital in species recovery, yet incorporation of genetic data in conservation management is currently limited. International and national genome sequencing consortia are currently producing reference genomes for a large variety of species, though there is currently a gap between the creation of these genomic resources and their downstream applications, particularly in conservation contexts. One of the major drivers of this gap is due to the bioinformatic expertise and resources that are required to analyse genomic datasets and to translate the findings into conservation management. This PhD employs a variety of bioinformatic and sequencing approaches to develop genomic resources for threatened Australian Marsupials and demonstrates how these resources can be used as a tool to assist species conservation. The value of genomic data for conservation is demonstrated for a range of species under varying scenarios including: i) using existing genomic datasets for the endangered Tasmanian devil to answer new conservation questions relating to reproduction, ii) creating a reference genome for the common brown antechinus, to act as a model species for its threatened congeneric counterparts and iii) generating and uniting a suite of genomic resources to assist in the management of the vulnerable greater bilby. In addition, ten simple rules for getting started with command-line bioinformatics are presented to facilitate the use of genomic data in wildlife conservation. Bridging the research-implementation gap is essential for harnessing the power of genomic resources for the conservation of threatened species. The findings from this PhD provide crucial steps into bridging this gap

Evaluation of an MRI-based screening pathway for prostate cancer

In recent years there has been a wealth of debate regarding prostate cancer screening, with a concurrent increase in new imaging techniques for prostate cancer diagnosis. Imaging has been the technique of choice in lung and breast cancer screening programmes but has not been explored for prostate cancer screening. Herein, this thesis explores the role of magnetic resonance imaging (MRI) as a new approach to screen for prostate cancer. Following an introduction to the current screening landscape, my thesis focuses on the development and validation of a fast MRI, known as a prostagram, that could serve as a viable image-based screening test. Evaluation of this new technique is performed within a prospective, population-based, blinded, cohort study which was conducted at seven primary care practices and two imaging centres. A diverse array of performance characteristics of fast MRI are compared to PSA. These encompass biopsy rates, cancer detection rates, diagnostic accuracy and patient reported experience measures. The second half of this thesis focuses on further optimising the fast MRI protocol for screening and exploring methods of integrating it into an alternative screening pathway. The outcomes point towards a pathway which combines a low threshold PSA and a fast MRI as yielding a more acceptable balance between benefits and harms. This is followed by the development of a risk tool to address the challenges of equivocal MRI lesions. Overall my thesis provides a balanced evaluation of fast MRI as a new screening test and the final chapter highlights outstanding challenges that must be addressed for fast MRI to progress as a legitimate screening modality. There is a requirement for all new screening tests to be evaluated in robust randomised controlled trials and the thesis concludes by setting out a phased research framework for fast MRI to enable a full evaluation over the next decade.Open Acces