Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2

Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis

In situ phase behaviour of a high capacity LiCoPO4 electrode during constant or pulsed charge of a lithium cell

The phase changes that occur during lithium extraction from LiCoPO4 in lithium half-cells were studied using synchrotron X-ray diffraction. The existence of two two-phase regions with an intermediate phase present was observed. Significant variations in the composition of the phases of nominal stoichiometry LiCoPO4, Li2/3CoPO4 and CoPO4 resulted in unit cell volume variations. On current pulsing, lattice parameter shifts and phase recovery were directly observed

Loot box engagement: relationships with educational attainment, employment status and earnings in a cohort of 16 000 United Kingdom gamers

© 2022 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/add.15837Background and Aims: Loot boxes are purchasable randomised rewards in video games that share structural and psychological similarities with gambling. Systematic review evidence has established reproducible associations between loot box purchasing and both problem gambling and problem video gaming. We aimed to measure the association between loot box engagement and socioeconomic correlates. Design: The study was a cross-sectional online survey using the recruitment platform, Prolific. Setting: United Kingdom (UK). Participants: A cohort of 16 196 UK adults (18 + years) self-reporting as video gamers. Measurements: Respondents were asked about their game-related purchasing behaviour (including loot boxes), recent monthly spend on loot boxes and gambling engagement (gambling in any form; gambling online; playing ‘social casino’ games). A range of demographic variables were simultaneously captured, including age, sex, ethnicity, earnings, employment and educational attainment. Findings: Overall, 17.16% of gamers in our cohort purchased loot boxes, with a mean self-reported monthly spend of £29.12. These loot box purchasers are more likely to gamble (45.97% gamble) than people who make other types of game-related purchases (on aggregate, 28.13% of non-loot box purchasers gamble), and even greater still than those who do not make any game related purchases (24.38% gamble P < 0.001). Loot box engagement (as binary yes/no or as monthly spend normalised to earnings) was significantly associated with younger age (P < 0.001 and P < 0.001; respectively, for binary yes/no and monthly spend, adjusted for false discovery rate correction), male sex (P < 0.001 and P = 0.025), non-university educational attainment (P < 0.001 and P < 0.001) and unemployment (P = 0.003 and P = < 0.001). Lower earners spent a higher proportion of monthly earnings on loot boxes (P < 0.001). Conclusions: The demographic associations of video game loot box engagement (younger age, male sex, non-university educational attainment and unemployment) mirror those of other addictive and problematic behaviours, including disordered gambling, drug and alcohol misuse.Gamble Aware.Published versio

ACE2-independent interaction of SARS-CoV-2 spike protein with human epithelial cells is inhibited by unfractionated heparin

Coronaviruses such as SARS-CoV-2, which is responsible for COVID-19, depend on virus spike protein binding to host cell receptors to cause infection. The SARS-CoV-2 spike protein binds primarily to ACE2 on target cells and is then processed by membrane proteases, including TMPRSS2, leading to viral internalisation or fusion with the plasma membrane. It has been suggested, however, that receptors other than ACE2 may be involved in virus binding. We have investigated the interactions of recombinant versions of the spike protein with human epithelial cell lines that express low/very low levels of ACE2 and TMPRSS2 in a proxy assay for interaction with host cells. A tagged form of the spike protein containing the S1 and S2 regions bound in a temperature-dependent manner to all cell lines, whereas the S1 region alone and the receptor-binding domain (RBD) interacted only weakly. Spike protein associated with cells independently of ACE2 and TMPRSS2, while RBD required the presence of high levels of ACE2 for interaction. As the spike protein has previously been shown to bind heparin, a soluble glycosaminoglycan, we tested the effects of various heparins on ACE2-independent spike protein interaction with cells. Unfractionated heparin inhibited spike protein interaction with an IC50 value of <0.05 U/mL, whereas two low-molecular-weight heparins were less effective. A mutant form of the spike protein, lacking the arginine-rich putative furin cleavage site, interacted only weakly with cells and had a lower affinity for unfractionated and low-molecular-weight heparin than the wild-type spike protein. This suggests that the furin cleavage site might also be a heparin-binding site and potentially important for interactions with host cells. The glycosaminoglycans heparan sulphate and dermatan sulphate, but not chondroitin sulphate, also inhibited the binding of spike protein, indicating that it might bind to one or both of these glycosaminoglycans on the surface of target cells

Gambling and gaming in the United Kingdom during the COVID-19 lockdown

© 2022 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/covid2020007During the first UK national COVID-19 lockdown, there were fears that increased online gaming and gambling could negatively impact wellbeing. Using a cross-sectional retrospective change survey of 631 UK adult gamers and/or gamblers during the week the UK lockdown was partially lifted (June 2020), we investigated participation in gaming/gambling and relationships with problem gaming, problem gambling and wellbeing (using the following previously validated scales: the Internet Gaming Disorder Short Form; a short-form version of the Problem Gambling Severity Index; a short-form of the Warwick–Edinburgh Mental Well-Being Scale). Results indicated a near-doubling in gaming activity during lockdown and significant increases in problem gaming scores, but not in numbers of disordered gamers. Aggregate changes to gambling participation and problem gambling were negligible: decreases in offline and sports gambling were balanced by increases in online gambling. Wellbeing scores decreased during lockdown across the sample, particularly amongst women, and path analysis revealed moderate correlations between increases in problem gaming and gambling scores and reductions in wellbeing. We conclude that for some, maladaptive gaming/gambling coping strategies during the lockdown may have exacerbated its negative effects.This work was funded by the University of Plymouth School of Psychology. J.C., S.S., H.L., L.L.N. and J.L. were further supported by funding from GambleAware.Published onlin

Loot boxes and problem gambling: Investigating the “gateway hypothesis”

Loot boxes are purchasable items in video games with a chance-based outcome. They have attracted substantial attention from academics and legislators over recent years, partly because of associations between loot box engagement and problem gambling. Some researchers have suggested that loot boxes may act as a gateway into subsequent gambling and/or problem gambling. However, such “gateway effects” have not been formally investigated. Using a survey of 1102 individuals who both purchase loot boxes and gamble, we found that 19.87% of the sample self reported either “gateway effects” (loot boxes causally influencing subsequent gambling) or “reverse gateway effects” (gambling causally influencing subsequent loot box engagement). Both subsets of participants had higher scores for problem gambling, problem video gaming, gambling-related cognitions, risky loot boxes engagement, and impulsivity. These individuals also had a tendency for higher loot box and gambling spend; suggesting that potential gateway effects are related to measurable risks and harms. Moreover, the majority of participants reporting gateway effects were under 18 when they first purchased loot boxes. Content analysis of free text responses revealed several reasons for self-reported gateway effects, the most frequent of which were sensation-seeking, normalisation of gambling-like behaviours, and the addictive nature of both activities. Whilst the cross-sectional nature of our findings cannot conclusively establish directions of causality, thus highlighting the need for longitudinal research, we conclude that there is a case for legislation on loot boxes for harm minimisation purposes

Loot boxes, problem gambling, and problem video gaming: a systematic review and meta-synthesis

This is an accepted manuscript of an article published by SAGE in New Media & Society on 17 July 2021. doi:10.1177/14614448211027175 The accepted version of the publication may differ from the final published version.Loot boxes are video game-related purchases with a chance-based outcome. Due to similarities with gambling, they have come under increasing scrutiny from media, academics and policymakers alike. Initial evidence suggested that loot box (LB) engagement might be associated with both problem gambling (PG) and problem video gaming (PVG). We therefore conducted a systematic review of the evidence for associations between LB purchasing, PG and PVG. For LB/PG, 12 of 13 publications reported a positive relationship, with a moderately sized mean effect of r = 0.27. For LB/PVG, the mean effect was r = 0.40, although this finding was drawn from only six surveys in total. For PG/PVG, the mean effect was r = 0.21, with only 11 of 20 studies reporting significant effects. Whilst further evidence is required to determine direction of causality, the strength of relationships suggests that policy action on loot boxes may have benefits for harm minimisation

Experimental investigation of air–water two-phase flow through vertical 90° bend

The behaviour of two-phase air–water mixture flowing from the horizontal to the vertical through a 90° bend has been investigated experimentally. Cross sectional void fraction at nine positions, three upstream and six downstream of the bend have been measured using a conductance probe technique. The bend, manufactured from transparent acrylic resin has a diameter of 34 mm and a curvature (R/D) equal to 5. The superficial velocity of the air was varied between 0.3 and 4 m/s and that for the water between 0.21 and 0.91 m/s. The characteristics signatures of Probability Density Function (PDF), the Power Spectral Density (PSD) of the time series of cross sectionally average void fraction and visual observations have been used to characterise the flow behaviour. For the experimental conditions, plug, slug and stratified wavy flow pattern occurred in the horizontal pipe while slug and churn flow patterns were present in the vertical pipe. The void fraction increased with the gas superficial velocity. The correlation of Nicklin et al. predicted the structure velocity for the slug flow in both horizontal and vertical pipes reasonably accurately. With regards to the frequency of the periodic structures present, some conditions showed little change from upstream to downstream the bend whilst others showed an increasing in the structure frequency from horizontal to vertical pipe. The slug length increased by passing through the vertical bend

Loot boxes and problem gambling: Investigating the “gateway hypothesis”

© 2022 The Authors. Published by Elsevier. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.addbeh.2022.107327Loot boxes are purchasable items in video games with a chance-based outcome. They have attracted substantial attention from academics and legislators over recent years, partly because of associations between loot box engagement and problem gambling. Some researchers have suggested that loot boxes may act as a gateway into subsequent gambling and/or problem gambling. However, such “gateway effects” have not been formally investigated. Using a survey of 1102 individuals who both purchase loot boxes and gamble, we found that 19.87% of the sample self-reported either “gateway effects” (loot boxes causally influencing subsequent gambling) or “reverse gateway effects” (gambling causally influencing subsequent loot box engagement). Both subsets of participants had higher scores for problem gambling, problem video gaming, gambling-related cognitions, risky loot boxes engagement, and impulsivity. These individuals also had a tendency for higher loot box and gambling spend; suggesting that potential gateway effects are related to measurable risks and harms. Moreover, the majority of participants reporting gateway effects were under 18 when they first purchased loot boxes. Content analysis of free text responses revealed several reasons for self-reported gateway effects, the most frequent of which were sensation-seeking, normalisation of gambling-like behaviours, and the addictive nature of both activities. Whilst the cross-sectional nature of our findings cannot conclusively establish directions of causality, thus highlighting the need for longitudinal research, we conclude that there is a case for legislation on loot boxes for harm minimisation purposes.This project was funded by the charity GambleAware, with additional funding from the University of Plymouth School of Psychology. S. G. Spicer was additionally supported by the National Institute for Health Research Applied Research Collaboration South West Peninsula. The views expressed in this publication are those of the authors and not necessarily those of the funder/supporter organisations.Accepted versio

Initial lists of AMMA-2050 user-relevant climate metrics

AMMA-2050 (African Monsoon Multi-disciplinary Analysis 2050) will improve understanding of how the West African monsoon will be affected by climate change in the coming decades – and help West African societies prepare and adapt