How much of a problem is problem gambling?

Problem gambling is conventionally defined by the score in a specific questionnaire exceeding some critical value and data suggests is that 0.7% of adults in the UK could be afflicted. However, the literature has not evaluated the size of the harm associated with such an affliction and this research evaluates the effect of problem gambling on self-reported well-being which, together with a corresponding effect of income on well-being, allows us to construct a money-metric of the (self) harm associated with being a problem gambler. Our estimates suggest that problem gambling imposes a very large reduction in individual well-being

The economics of gambling:a collection of essays

Chapter 2 examines the harm associated with being a problem gambler. Problem gambling is conventionally determined by having a score in a questionnaire screen that exceeds some critical value. The UK is fortunate in having large representative sample surveys that embed such questions, and our estimate from the 2010 survey is that several hundred thousand people in the UK could be afflicted by PG. However, existing literature has not evaluated the size of the harm associated with being a problem gambler and this chapter uses this individual level survey data to evaluate the effect of problem gambling on self-reported well-being. Together with a corresponding effect of income on well-being a money-metric of the harm associated with being a problem gambler is derived. An important methodological challenge is that well-being and the harm experienced may be simultaneously determined. Nonetheless, instrumental variable estimates suggest that problem gambling imposes an even larger reduction in well-being than least squares would suggest. The role of gambling expenditures in the transmission between problem gambling and well-being is considered, distinguishing between draw-based games, such as lotto, from scratchcards, and from other forms of gambling. Chapter 3 investigates the price elasticity of demand for the UK National Lottery – a state-licensed, draw-based lotto game. Little is known about the price elasticity of demand for gambling products because the “price” is typically hard to define. The exception is “lotto” where an economics literature has focused on the response of sales to variations in the prize distribution. Existing literature has used these responses make inferences about the price elasticity of demand, where price is defined as the cost of entry minus the expected winnings. In particular, the variation in the value of the jackpot prize pool, due to rollovers that are a feature of lotto, has been used as an instrument for price. This chapter argues that rollovers do not make valid instruments, because of their correlation with lagged sales, and propose an alternative identification strategy which exploits two arcane features of lotto. Finally, this chapter evaluates whether changes to the design of the UK National Lottery in 2013 and 2015 had a positive effect on the sales figures. Chapter 4 investigates the extent to which the large, flat-rate tax imposed on the UK National Lottery is regressive. This chapter evaluates a Working-Leser demand model for lotto tickets using both Heckman’s selection model and Cragg’s double hurdle estimator using household-level data. A unique strategy is employed to identify these two-stage routines by exploiting exogenous differences in consumer preference arising from religious practice. The income elasticity of lottery tickets is found to be significantly lower than previous estimates, suggesting that lottery tickets are inferior goods and that the (high) flat-rate tax imposed on lotto tickets is more regressive than previously thought. Whilst the three chapters are stand-alone essays, they are linked by the use of modern statistical techniques and the use of the best possible data. Together, they address key issues on the economics of gambling and the results are new to their respective literatures and of interest to academics and policy makers alike

The Decline and Fall of UK Lotto

UK lotto sales have fallen by 60% from its heyday in 1996 (just two years after the introduction of the game) when weekly sales were close to £100m, to £40m per week in nominal terms by 2013 (and, with inflation averaging 2.9%, the real fall in sales revenue was approximately 75%). The aim of this paper is to estimate the demand for lotto - so as to understand the fall in lotto sales revenue, and to evaluate attempts since 2013 to arrest the fall

Hsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans

We thank Karim Gharbi and Urmi Trivedi for their assistance with RNA sequencing, carried out in the GenePool genomics facility (University of Edinburgh). We also thank Susan Fairley and Eduardo De Paiva Alves (Centre for Genome Enabled Biology and Medicine, University of Aberdeen) for help with the initial bioinformatics analysis. We thank Aaron Mitchell for kindly providing the ALS3 mutant, Julian Naglik for the gift of TR146 cells, and Jon Richardson for technical assistance. We thank the Genomics and Bioinformatics core of the Faculty of Health Sciences for Next Generation Sequencing and Bioinformatics support, the Information and Communication Technology Office at the University of Macau for providing access to a High Performance Computer and Jacky Chan and William Pang for their expert support on the High Performance Computer. Finally, we thank Amanda Veri for generating CaLC2928. M.D.L. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072), R.A.F. by a Wellcome Trust-Massachusetts Institute of Technology (MIT) Postdoctoral Fellowship, L.E.C. by a Canada Research Chair in Microbial Genomics and Infectious Disease and by Canadian Institutes of Health Research Grants MOP-119520 and MOP-86452, A.J. P.B. was supported by the UK Biotechnology and Biological Sciences Research Council (BB/F00513X/1) and by the European Research Council (ERC-2009-AdG-249793-STRIFE), KHW is supported by the Science and Technology Development Fund of Macau S.A.R (FDCT) (085/2014/A2) and the Research and Development Administrative Office of the University of Macau (SRG2014-00003-FHS) and R.T.W. by the Burroughs Wellcome fund and NIH R15AO094406. Data availability RNA-sequencing data sets are available at ArrayExpress (www.ebi.ac.uk) under accession code E-MTAB-4075. ChIP-seq data sets are available at the NCBI SRA database (http://www.ncbi.nlm.nih.gov) under accession code SRP071687. The authors declare that all other data supporting the findings of this study are available within the article and its supplementary information files, or from the corresponding author upon request.Peer reviewedPublisher PD

Research priorities for mitochondrial disorders: Current landscape and patient and professional views

Primary mitochondrial disorders encompass a wide range of clinical presentations and a spectrum of severity. They currently lack effective disease-modifying therapies and have a high mortality and morbidity rate. It is therefore essential to know that competitively-funded research designed by academics meets core needs of people with mitochondrial disorders and their clinicians. The Priority Setting Partnerships are an established collaborative methodology that brings patients, carers and families, charity representatives and clinicians together to try to establish the most pressing and unanswered research priorities for a particular disease. We developed a web-based questionnaire, requesting all patients affected by primary mitochondrial disease, their carers, and clinicians to pose their research questions. This yielded 709 questions from 147 participants. These were grouped into overarching themes including basic biology, causation, health services, clinical management, social impacts, prognosis, prevention, symptoms, treatment, and psychological impact. Following the removal of 'answered questions' the process resulted in a list of 42 discrete, answerable questions. This was further refined by web-based ranking by the community to 24 questions. These were debated at a face-to-face workshop attended by a diverse range of patients, carers, charity representatives and clinicians to create a definitive 'Top Ten of unanswered research questions for primary mitochondrial disorders'. These Top Ten questions related to understanding biological processes, including triggers of disease onset, mechanisms underlying progression and reasons for differential symptoms between individuals with identical genetic mutations; new treatments; biomarker discovery; psychological support; and optimal management of stroke-like episodes and fatigue

Research priorities for mitochondrial disorders: current landscape and patient and professional views

Primary mitochondrial disorders encompass a wide range of clinical presentations and a spectrum of severity. They currently lack effective disease-modifying therapies and have a high mortality and morbidity rate. It is therefore essential to know that competitively-funded research designed by academics meets core needs of people with mitochondrial disorders and their clinicians. The Priority Setting Partnerships are an established collaborative methodology that brings patients, carers and families, charity representatives and clinicians together to try to establish the most pressing and unanswered research priorities for a particular disease. We developed a web-based questionnaire, requesting all patients affected by primary mitochondrial disease, their carers, and clinicians to pose their research questions. This yielded 709 questions from 147 participants. These were grouped into overarching themes including basic biology, causation, health services, clinical management, social impacts, prognosis, prevention, symptoms, treatment, and psychological impact. Following the removal of ‘answered questions’ the process resulted in a list of 42 discrete, answerable questions. This was further refined by web-based ranking by the community to 24 questions. These were debated at a face-to-face workshop attended by a diverse range of patients, carers, charity representatives and clinicians to create a definitive ‘Top Ten of unanswered research questions for primary mitochondrial disorders’. These Top Ten questions related to understanding biological processes, including triggers of disease onset, mechanisms underlying progression and reasons for differential symptoms between individuals with identical genetic mutations; new treatments; biomarker discovery; psychological support; and optimal management of stroke-like episodes and fatigue

New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms

Background: Hyperekplexia mutations have provided much information about glycine receptor structure and function. Results: Weidentified and characterized nine new mutations. Dominant mutations resulted in spontaneous activation, whereas recessive mutations precluded surface expression. Conclusion: These data provide insight into glycine receptor activation mechanisms and surface expression determinants. Significance: The results enhance our understanding of hyperekplexia pathology and glycine receptor structure-function. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant