Beyond ‘single customer view’:Player tracking’s potential role in understanding and reducing gambling-related harm

Background: Usage of electronic gaming machines (EGMs) and on-line gambling is strongly associated with gambling-related harm. Player-tracking systems can monitor a gambler’s activity across multiple sessions and/or operators, providing a clearer picture of the person’s risk of harm with respect to these gambling formats and enabling harmreduction efforts. The Finnish and Norwegian state monopolies have player-tracking systems in place, while the United Kingdom is implementing an operator-led system called ‘single customer view’ for on-line gambling, and Australian states are proposing similar ‘player cards’ for land-based EGMs.Argument: Player tracking can advance harm reduction efforts in three ways. First, player tracking improves our understanding of gambling-related harm by providing data on how the population gambles, which can potentially be linked with operator, government and/or prevalence data sets. Secondly, player tracking can be used to implementharm reduction measures such as expenditure limits, self-exclusion and age verification. Thirdly, player tracking can provide a platform to evaluate harm reduction measures via gold-standard field trials. These potential benefits need to be weighed against various practical and ethical issues.Conclusions: The potential benefits of player-tracking systems would be maximized via systems administered independently of the gambling industry and implemented universally across all gambling in a given jurisdiction

Gambling-related consumer credit use and debt problems: a brief review

People experiencing problems with gambling may use consumer credit to cover expenses and/or continue gambling. This may contribute to debt problems and psychological distress, both of which may have pre-existed (and potentially motivated) their gambling. This review found little empirical investigation of patterns of consumer credit use by gamblers, despite borrowing money being a diagnostic criterion for gambling disorder and financial harms being one of the most commonly reported problems. Research suggests that consumer credit use and debt problems increase with problem gambling severity. Gambling-related debt problems increase the likelihood of experiencing poor psychosocial functioning, including psychological distress, substance use, adverse family impacts, crime, and suicidality. Communities and governments are calling for more socially responsible conduct by financial institutions, which increasingly recognise the potentially harmful impacts of credit provision on the well-being of customers experiencing gambling problems. Policies and interventions are needed relating to consumer credit, debt, and gambling to enhance customers’ financial and psychosocial well-being.This work was partially funded by the Commonwealth Bank of Australia and University of Sydney Industry Seed Funding and an Australian Research Council Discovery Early Career Researcher Award [DE1060100459] awarded to Associate Professor Sally Gainsbury. The funding bodies had no involvement in the research, including but not limited to: the conceptualisation of the manuscript; collection, analysis, and interpretation of the data; the writing of the manuscript; or the decision to submit the article for publication

The role of financial institutions in gambling

Financial institutions have corporate social responsibility to assist customers in enhancing their financial well-being, and to make a positive contribution to society given the considerable role that they play in customers’ everyday lives. Financial institutions are involved in gambling through facilitating gambling transactions, including provision of credit to customers potentially experiencing gambling-related harms. As financial institutions have an overview of customers’ income, spending and debt, this potentially allows for the identification of excessive expenditure on specific activities. This article reviewed the role of financial institutions in gambling with the aim of considering ways in which policies and practices could enhance customer well-being. The Australian-focused review found limited evidence of gambling-specific bank policies despite increasing recognition of the impact of gambling-related harms. Behavioral economics and psychological approaches may be promising frameworks to guide the development of policies to assist customers in limiting their gambling to affordable levels. Financial institutions could implement products and resources for customers to enhance management of gambling expenditure. Government and community scrutiny over the role of financial institutions in gambling will likely increase given growing recognition of harms. A proactive effort to enhance customer well-being could have broad positive outcomes for financial institutions’ social licence to operate.This work was supported by the Discovery Early Career Research Award, awarded to Dr Sally Gainsbury; Australian Research Council [DE1060100459]

Problematic risk-taking involving emerging technologies: A stakeholder framework to minimize harms

Background and aims Despite the many benefits of technological advancements, problematic use of emerging technologies may lead to consumers experiencing harms. Substantial problems and behavioral addictions, such as gambling and gaming disorders, are recognized to be related to Internet-based technologies, including the myriad of new devices and platforms available. This review paper seeks to explore problematic risk-taking behaviors involving emerging technologies (e.g., online gambling and gaming, online sexual behaviors, and oversharing of personal information via social networking sites) that have the potential to lead to problematic outcomes for individuals. Results and discussion Previous research has focused on policy frameworks for responding to specific issues (e.g., online gambling), but a broader framework is needed to address issues as they emerge, given lags in governments and regulators responding to dynamically evolving technological environments. In this paper, key terms and issues involved are identified and discussed. We propose an initial framework for the relative roles and responsibilities of key stakeholder groups involved in addressing these issues (e.g., industry operators, governments and regulators, community groups, researchers, treatment providers, and individual consumers/end users). Conclusion Multidisciplinary collaboration can facilitate a comprehensive, unified response from all stakeholders that balances individual civil liberties with societal responsibilities and institutional duty of care.This work was supported by an Australian Research Council Discovery Early Career Research Award (DE1060100459) awarded to Associate Professor Sally Gainsbury

Refphase: Multi-Sample Phasing Reveals Haplotype-Specific Copy Number Heterogeneity

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient\u27s disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample phasing. We demonstrate Refphase\u27s ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours

Refphase: Multi-sample phasing reveals haplotype-specific copy number heterogeneity

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient’s disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample phasing. We demonstrate Refphase’s ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours

MEDICC2: whole-genome doubling aware copy-number phylogenies for cancer evolution

Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution and provide information for the complex task of phylogenetic inference. We present MEDICC2, a method for inferring evolutionary trees and WGD using haplotype-specific somatic copy-number alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as the infinite sites assumption, allowing multiple mutations and parallel evolution, and does not treat adjacent loci as independent, allowing overlapping copy-number events. Using simulations and multiple data types from 2780 tumors, we use MEDICC2 to demonstrate accurate inference of phylogenies, clonal and subclonal WGD, and ancestral copy-number states

Genomic-Transcriptomic Evolution in Lung Cancer and Metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study2,3. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic-transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary-metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Evolutionary Characterization of Lung Adenocarcinoma Morphology in TRACERx

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and \u27tumor spread through air spaces\u27 were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk

The evolution of non-small cell lung cancer metastases in TRACERx.

Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse