The enemy within:designing a cell-based gameplay system for cancer education

This paper outlines the design and preliminary evaluation of The Enemy Within, a browser-based game produced to raise awareness of the nature of cancer as a progressive disease. Aimed at high school and young adult audiences, the ambition with the game is to make visible to players the myriad ways in which healthy cells can mutate and ultimately inherit hallmarks of cancer, whilst also demonstrating how both real-world behaviours and underlying genetics impact both positively and negatively on cell health

Case report: Severe mercuric sulphate poisoning treated with 2,3-dimercaptopropane-1-sulphonate and haemodiafiltration

INTRODUCTION: Inorganic mercury poisoning is uncommon, but when it occurs it can result in severe, life-threatening features and acute renal failure. Previous reports on the use of extracorporeal procedures such as haemodialysis and haemoperfusion have shown no significant removal of mercury. We report here the successful use of the chelating agent 2,3-dimercaptopropane-1-sulphonate (DMPS), together with continuous veno-venous haemodiafiltration (CVVHDF), in a patient with severe inorganic mercury poisoning. CASE REPORT: A 40-year-old man presented with haematemesis after ingestion of 1 g mercuric sulphate and rapidly deteriorated in the emergency department, requiring intubation and ventilation. His initial blood mercury was 15 580 μg/l. At 4.5 hours after ingestion he was started on DMPS. He rapidly developed acute renal failure and so he was started on CVVHDF for renal support and in an attempt to improve mercury clearance; CVVHDF was continued for 14 days. METHODS: Regular ultradialysate and pre- and post-filtrate blood samples were taken and in addition all ultradialysate generated was collected to determine its mercury content. RESULTS: The total amount of mercury in the ultrafiltrate was 127 mg (12.7% of the ingested dose). The sieving coefficient ranged from 0.13 at 30-hours to 0.02 at 210-hours after ingestion. He developed no neurological features and was discharged from hospital on day 50. Five months after discharge from hospital he remained asymptomatic, with normal creatinine clearance. DISCUSSION: We describe a patient with severe inorganic mercury poisoning in whom full recovery occurred with the early use of the chelating agent DMPS and CVVHDF. There was removal of a significant amount of mercury by CVVHDF. CONCLUSION: We feel that CVVHDF should be considered in patients with inorganic mercury poisoning, particularly those who develop acute renal failure, together with meticulous supportive care and adequate doses of chelation therapy with DMPS

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

A case of severe mercuric sulphate ingestion treated with 2,3-kimercaptopropane 1 sulphonate (DMPD) and hi-flow hemodiafiltration

Objective: Our training program uses senior emergency medicine residents (SEMRs) as toxicology consultants, with the back-up of the physician toxicologist on-call. We assessed health care practitioner (HCP) satisfaction with this toxicology consulting service. Methods: For 5 months, HCPs who spoke to a toxicology consultant (SEMR or attending on-call toxicologist) were contacted by telephone and a 12 question survey was implemented. Results: 48 toxicology consultant cases were identified. 9 HCPs did not respond to initial or 3 follow-up calls. 3 surveys were eliminated because they were incomplete. Of the 36 completed surveys, 21 used the SEMR as consultant, and 15 used attending toxicologists. 92% (33/36) felt the response time of the consultant was very quick and 100% felt that advice given was relevant to the poisoning case. 94% (34/36) followed the advice given by the consultant. 83% (30/36) felt that his/her knowledge base was expanded by discussion with the consultant. 94% (34/36) felt that all of his/her questions were answered. 92% (33/36) said they could access the consultant easily if needed again. 80% (29/36) had used the service before, and 100% stated they would use it again. When asked to rate the service on a scale of 1-5 (5 = extremely valuable), the median score was 5 (range 4-5). When asked for comments, 13 had no comments, 3 had negative comments, 6 had suggestions for improvement, and the remaining 14 had praise for the service. When SEMR survey results were compared to those of the toxicologist, no differences were noted. Conclusion: The poison center consultation service meets with high satisfaction and is well received. Use of SEMRs as toxicology consultants in the poison center compared favorably to the use of attending toxicologists

The representativeness of observational samples of different durations.

The representativeness of behavioral observation samples with durations of less than the whole time of interest was investigated. A real-time recording system was developed to quantify the behavior of 5 profoundly mentally retarded physically handicapped adult students in an institutional training setting. Behavior was observed using six mutually exclusive and exhaustive categories during 2.5-hr observation sessions. Sample observation sessions with durations ranging from 15 to 135 min were computer simulated from the whole-session (150-min) records. It was found that the representativeness of these samples, when compared to whole-session records, was a function of the relative duration of the behavioral categories and of sample duration. The occurrence of relatively high-duration behaviors (lasting for more than 50% of the session) was estimated to within 20% error by samples of less than 60 min, but low-duration behaviors (1 to 3% of the session) were inadequately quantified even from 135-min samples. Increasing irregularity of bouts of behavior in the low-duration behaviors is suggested as the cause of the functions obtained. Implications of the findings for applied behavior analysis are discussed, with the recommendation that the adequacy of observational session durations be empirically assessed routinely

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19. Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24). Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research