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’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

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Trade and Exchange in Anglo-Saxon Wessex, AD 600-780

This paper assesses the provenance and general distribution of coins of the period c 600–c 780 found in the west of Anglo‐Saxon Wessex. It shows that the distribution of coin finds is not a function of the habits of metal detectorists, but a reflection of the real pattern of losses. In the second part of the paper, an analysis of the observed distributions is presented which reveals that the bulk of trade, of which the coins are a sign, was carried on through local ports and that foreign trade was not mediated through Hamwic, but came directly from the continent. The distribution of coin finds also suggests an important export trade, probably in wool and woollen goods, controlled from major local centres. There are also hints of a potentially older trade system in which hillforts and other open sites were important

Induction of APOBEC3 exacerbates DNA replication stress and chromosomal instability in early breast and lung cancer evolution

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast DCIS, and in pre-invasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx pre-invasive to invasive NSCLC lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models, revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in pre-invasive disease, providing fuel for selection early in cancer evolution

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+) tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non–small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy–induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens