Targeting of Rac GTPases blocks the spread of intact human breast cancer

High expression of Rac small GTPases in invasive breast ductal carcinoma is associated with poor prognosis, but its therapeutic value in human cancers is not clear. The aim of the current study was to determine the response of human primary breast cancers to Rac-based drug treatments ex vivo. Three-dimensional organotypic cultures were used to assess candidate therapeutic avenues in invasive breast cancers. Uniquely, in these primary cultures, the tumour is not disaggregated, with both epithelial and mesenchymal components maintained within a three-dimensional matrix of type I collagen. EHT 1864, a small molecule inhibitor of Rac GTPases, prevents spread of breast cancers in this setting, and also reduces proliferation at the invading edge. Rac1+ epithelial cells in breast tumours also contain high levels of the phosphorylated form of the transcription factor STAT3. The small molecule Stattic inhibits activation of STAT3 and induces effects similar to those seen with EHT 1864. Pan-Rac inhibition of proliferation precedes down-regulation of STAT3 activity, defining it as the last step in Rac activation during human breast cancer invasion. Our data highlights the potential use of Rac and STAT3 inhibition in treatment of invasive human breast cancer and the benefit of studying novel cancer treatments using three-dimensional primary tumour tissue explant cultures

Reward Reactivity and Dark Flow in Slot-Machine Gambling: “Light” and “Dark” Routes to Enjoyment

Background and aims: Slot machines are a very popular form of gambling. In this study, we look at two different routes to enjoying slots play. One route involves the degree to which players react to rewards. The other route involves what we call dark flow – a pleasurable, but maladaptive state where players become completely engrossed in slots play, providing an escape from the depressing thoughts that characterize their everyday lives. Methods: One hundred and twenty-nine high-frequency slots players were tested on slot-machine simulators set up in the lobby of a casino. We measured reward reactivity using post-reinforcement pauses (PRPs) and the force with which players pressed the spin button following different slot-machine outcomes. For each player, we calculated the slopes of PRPs and force as a function of credit gains. We also assessed players’ slots game enjoyment and their experience of dark flow, depression, and problem gambling. Results: Both the PRP and the force measures of reward reactivity were significantly correlated with players’ enjoyment of the slots session, but neither measure was correlated with either problem gambling or depression. Ratings of dark flow were strongly correlated with slots enjoyment (which accounted for far more positive affect variance than the reward reactivity measures) and were correlated with both problem gambling scores and depression. Discussion and conclusions: Our results suggest that of these two routes to enjoying slot-machine play, the dark flow route is especially problematic. We contend that the dark flow state may be enjoyable because it provides escape from the negative thoughts linked to depression

Cross-Cultural Studies Into Gambling Consumption Behavior: Eyeing Eye-Tracking Measures

“Every man's ability may be strengthened or increased by culture”—John Abbot (Textappeal, 2017). While data aggregated from gambling operators have shown cross-cultural differences in the behavior of their customers (CasinoBeats, 2020), in recent years research into gambling consumption has been strengthened and enriched by studies uncovering the roles of culture in shaping gambling relevant phenomena (Oei et al., 2019). These studies were commonly based on data collected through survey questionnaires (e.g., Rinker et al., 2016; Calado et al., 2020) or interviews (e.g., Radermacher et al., 2016; Egerer and Marionneau, 2019). In the present opinion paper, it is argued that eye-tracking measurements should also be adopted in cross-cultural gambling research, particularly given the systematic differences in visual attentional patterns that potentially exist among gambling product consumers from different cultures

‘Question Moments’: A Rolling Programme of Question Opportunities in Classroom Science

This article has been made available through the Brunel Open Access Publishing Fund.This naturalistic study integrates specific 'question moments' into lesson plans to increase pupils' classroom interactions. A range of teaching tools has explored students' ideas through opportunities to ask and write questions. Their oral and written outcomes provide data on individual and group misunderstandings. Changes to the schedule of lessons were introduced to discuss these questions and solve disparities. Flexible lesson planning over fourteen lessons across a four-week period of highschool chemistry accommodated students' contributions and increased student participation, promoted inquiring and individualised teaching, with each teaching strategy feeding forward into the next

Unclaimed Prize Information Increases the Appeal of Scratch Card Games

This is an Accepted Manuscript of an article published by Taylor & Francis in International Gambling Studies on 03 Nov 2020, available online:https://www.tandfonline.com/doi/full/10.1080/14459795.2020.1826558.Previous research suggests that intuitively appealing, yet uninformative unclaimed prize information is capable of biasing gambling-related judgments when people compare scratch cards that vary in the number of unclaimed prizes. However, it is unknown if the mere presence of unclaimed prize information alters a game’s attractiveness. Using an online crowdsourcing platform, we recruited 402 U.S. residents to participate in an online study. In a within-subjects design, participants made four gambling-related judgments (likelihood of winning, excitement to play, urge to gamble, and hypothetical card purchasing) for scratch cards presented with and without unclaimed prize information. Compared to cards presented without unclaimed prize information, those with unclaimed prize information were judged as more likely to win, produced more excitement to play, a greater urge to gamble, and were chosen more often during a hypothetical purchasing task. Therefore, unclaimed prize information increases the appeal of scratch card games, and may be an important aspect of the scratch card gambling environment to consider from a harm reduction perspective.Natural Sciences and Engineering Research Council of Canada (NSERC

Exploring relationships between problem gambling, scratch card gambling, and individual differences in thinking style

Background and aims: Scratch cards are a popular form of lottery gambling available in many jurisdictions. However, there is a paucity of research that examines associations between individual differences in thinking style, participation in scratch card gambling, and problem gambling severity. Methods: In three studies, we sought to examine the relationships among these variables in large, online samples of participants. Participants completed the Cognitive Reflection Test (CRT), the Problem Gambling Severity Index (PGSI), the Actively Open-Minded Thinking Scale, and self-reported their frequency of scratch card gambling. Results: Throughout all three studies, specific associations were reliably established. Specifically, negative associations were observed between participants’ CRT and PGSI scores, as well as between participants’ CRT scores and scratch card gambling frequency. In addition, we found a positive association between problem gambling severity and scratch card gambling frequency. Finally, problem gambling severity was shown to correlate positively with participants’ willingness to pay for irrelevant information in a scratch card gambling scenario. Discussion and conclusions: Overall, we observed that problem gambling severity is associated with an individuals’ thinking style and scratch card gambling behavior. This study adds to the existing literature examining problem gambling, and highlights the role of thinking style in understanding gambling behavior and problematic gambling

Increasing Short-Stay Unplanned Hospital Admissions among Children in England; Time Trends Analysis '97-'06

BACKGROUND: Timely care by general practitioners in the community keeps children out of hospital and provides better continuity of care. Yet in the UK, access to primary care has diminished since 2004 when changes in general practitioners' contracts enabled them to 'opt out' of providing out-of-hours care and since then unplanned pediatric hospital admission rates have escalated, particularly through emergency departments. We hypothesised that any increase in isolated short stay admissions for childhood illness might reflect failure to manage these cases in the community over a 10 year period spanning these changes. METHODS AND FINDINGS: We conducted a population based time trends study of major causes of hospital admission in children 2 days. By 2006, 67.3% of all unplanned admissions were isolated short stays <2 days. The increases in admission rates were greater for common non-infectious than infectious causes of admissions. CONCLUSIONS: Short stay unplanned hospital admission rates in young children in England have increased substantially in recent years and are not accounted for by reductions in length of in-hospital stay. The majority are isolated short stay admissions for minor illness episodes that could be better managed by primary care in the community and may be evidence of a failure of primary care services

Resource-Bound Quantification for Graph Transformation

Graph transformation has been used to model concurrent systems in software engineering, as well as in biochemistry and life sciences. The application of a transformation rule can be characterised algebraically as construction of a double-pushout (DPO) diagram in the category of graphs. We show how intuitionistic linear logic can be extended with resource-bound quantification, allowing for an implicit handling of the DPO conditions, and how resource logic can be used to reason about graph transformation systems