The book: production and participation

Purpose – The focus of this paper is on the benefits that may eventuate through new mechanisms of production and distribution. As we enter the twenty-first century, the nature of the book and the structure of the industry which produces it are undergoing radical transformation, as developments in information technology offer new mechanisms for production and distribution. Most of the discussion of these changes is conducted from the perspective of what has been lost through these changes. Design/methodology/approach – This paper reviews the history of the book from the perspective of the disruptive effects of the changes in production technology and impact on the roles involved in production, distribution and reading of books. Darnton’s Communication Circuit is updated to predict future limiting factors and opportunities for participation. Findings – The evolution of the book has seen successive categories of workers involved in book production supplanted by the adoption of new technology. The updated Darnton’s model suggests that the roles involved in the production and distribution of the book will, however, be supplanted in favour of authors and readers of the book in the future. Social implications – The predicted changes will alter the roles of authors and book users. Originality/value – This paper suggests a novel approach to the discussion of the future of book publication and suggests future developments

PEITC-mediated inhibition of mRNA translation is associated with both inhibition of mTORC1 and increased eIF2α phosphorylation in established cell lines and primary human leukemia cells.

Increased mRNA translation drives carcinogenesis and is an attractive target for the development of new anti-cancer drugs. In this work, we investigated effects of phenethylisothiocyanate (PEITC), a phytochemical with chemopreventive and anti-cancer activity, on mRNA translation. PEITC rapidly inhibited global mRNA translation in human breast cancer-derived MCF7 cells and mouse embryonic fibroblasts (MEFs). In addition to the known inhibitory effects of PEITC on mTORC1 activity, we demonstrate that PEITC increased eIF2α phosphorylation. PEITC also increased formation of stress granules which are typically associated with eIF2α phosphorylation and accumulation of translationally stalled mRNAs. Analysis of genetically modified MEFs demonstrated that optimal inhibition of global mRNA translation by PEITC was dependent on eIF2α phosphorylation, but not mTORC1 inhibition. We extended this study into primary leukemic B cells derived from patients with chronic lymphocytic leukaemia (CLL). CLL cells were stimulated in vitro with anti-IgM to mimic binding of antigen, a major driver of this leukemia. In CLL cells, PEITC increased eIF2α phosphorylation, inhibited anti-IgM-induced mTORC1 activation and decreased both basal and anti-IgM-induced global mRNA translation. PEITC also inhibited transcription and translation of MYC mRNA and accumulation of the MYC oncoprotein, in anti-IgM-stimulated cells. Moreover, treatment of CLL cells with PEITC and the BTK kinase inhibitor ibrutinib decreased anti-IgM-induced translation and induced cell death to a greater extent than either agent alone. Therefore, PEITC can inhibit both global and mRNA specific translation (including MYC) via effects on multiple regulatory pathways. Inhibition of mRNA translation may contribute to the chemopreventive and anti-cancer effects of PEITC

Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder

Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members. In these 57 patients we identified 49 different mutations, including six multiple exon deletions, six known mutations and 37 novel mutations (13 missense, five nonsense, 13 frame shift, four splice site and two translation initiation mutations). Clinical data were retrospectively collected from referring physicians by means of a questionnaire. Three different phenotypes were recognized: (i) the classical phenotype (84%), subdivided into early-onset (<2 years) (65%) and late-onset (18%); (ii) a non-classical phenotype, with mental retardation and movement disorder, without epilepsy (15%); and (iii) one adult case of glucose transporter-1 deficiency syndrome with minimal symptoms. Recognizing glucose transporter-1 deficiency syndrome is important, since a ketogenic diet was effective in most of the patients with epilepsy (86%) and also reduced movement disorders in 48% of the patients with a classical phenotype and 71% of the patients with a non-classical phenotype. The average delay in diagnosing classical glucose transporter-1 deficiency syndrome was 6.6 years (range 1 month-16 years). Cerebrospinal fluid glucose was below 2.5 mmol/l (range 0.9-2.4 mmol/l) in all patients and cerebrospinal fluid : blood glucose ratio was below 0.50 in all but one patient (range 0.19-0.52). Cerebrospinal fluid lactate was low to normal in all patients. Our relatively large series of 57 patients with glucose transporter-1 deficiency syndrome allowed us to identify correlations between genotype, phenotype and biochemical data. Type of mutation was related to the severity of mental retardation and the presence of complex movement disorders. Cerebrospinal fluid : blood glucose ratio was related to type of mutation and phenotype. In conclusion, a substantial number of the patients with glucose transporter-1 deficiency syndrome do not have epilepsy. Our study demonstrates that a lumbar puncture provides the diagnostic clue to glucose transporter-1 deficiency syndrome and can thereby dramatically reduce diagnostic delay to allow early start of the ketogenic die

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Building capacity for implementation—the KT Challenge

Background The KT Challenge program supports health care professionals to effectively implement evidence-based practices. Unlike other knowledge translation (KT) programs, this program is grounded in capacity building, focuses on health care professionals (HCPs), and uses a multi-component intervention. This study presents the evaluation of the KT Challenge program to assess the impact on uptake, KT capacity, and practice change. Methods The evaluation used a mixed-methods retrospective pre-post design involving surveys and review of documents such as teams’ final reports. Online surveys collecting both quantitative and qualitative data were deployed at four time points (after both workshops, 6 months into implementation, and at the end of the 2-year funded projects) to measure KT capacity (knowledge, skills, and confidence) and impact on practice change. Qualitative data was analyzed using a general inductive approach and quantitative data was analyzed using non-parametric statistics. Results Participants reported statistically significant increases in knowledge and confidence across both workshops, at the 6-month mark of their projects, and at the end of their projects. In addition, at the 6-month check-in, practitioners reported statistically significant improvements in their ability to implement practice changes. In the first cohort of the program, of the teams who were able to complete their projects, half were able to show demonstrable practice changes. Conclusions The KT Challenge was successful in improving the capacity of HCPs to implement evidence-based practice changes and has begun to show demonstrable improvements in a number of practice areas. The program is relevant to a variety of HCPs working in diverse practice settings and is relatively inexpensive to implement. Like all practice improvement programs in health care settings, a number of challenges emerged stemming from the high turnover of staff and the limited capacity of some practitioners to take on anything beyond direct patient care. Efforts to address these challenges have been added to subsequent cohorts of the program and ongoing evaluation will examine if they are successful. The KT Challenge program has continued to garner great interest among practitioners, even in the midst of dealing with the COVID-19 pandemic, and shows promise for organizations looking for better ways to mobilize knowledge to improve patient care and empower staff. This study contributes to the implementation science literature by providing a description and evaluation of a new model for embedding KT practice skills in health care settings.Other UBCNon UBCReviewedFacultyResearche

Investigation of a SARS-CoV-2 Outbreak at an Automotive Manufacturing Site in England.

Workplace-related outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to occur globally. The manufacturing sector presents a particular concern for outbreaks, and a better understanding of transmission risks are needed. Between 9 March and 24 April 2021, the COVID-19 (coronavirus disease 2019) Outbreak Investigation to Understand Transmission (COVID-OUT) study undertook a comprehensive investigation of a SARS-CoV-2 outbreak at an automotive manufacturing site in England. The site had a total of 266 workers, and 51 SARS-CoV-2 infections. Overall, ventilation, humidity, and temperature at the site were assessed to be appropriate for the number of workers and the work being conducted. The company had implemented a number of infection control procedures, including provision of face coverings, spacing in the work, and welfare areas to allow for social distancing. However, observations of worker practices identified lapses in social distancing, although all were wearing face coverings. A total of 38 workers, including four confirmed cases, participated in the COVID-OUT study. The majority of participants received COVID-19 prevention training, though 42.9% also reported that their work required close physical contact with co-workers. Additionally, 73.7% and 34.2% had concerns regarding reductions in future income and future unemployment, respectively, due to self-isolation. This investigation adds to the growing body of evidence of SARS-CoV-2 outbreaks from the manufacturing sector. Despite a layered COVID-19 control strategy at this site, cases clustered in areas of high occupancy and close worker proximity

Marking out the pitch: a historiography and taxonomy of football fiction

Football, or soccer as it is more commonly referred to in Australia and the US, is arguably the world’s most popular sport. It generates a proportionate volume of related writing. Within this landscape, works of novel-length fiction are seemingly rare. This paper establishes and maps a substantial body of football fiction works, explores elements and qualities exhibited individually and collectively. In bringing together current, limited surveys of the field, it presents the first rigorous definition of football fiction and captures the first historiography of the corpus. Drawing on distant reading methods developed in conjunction with closer textual analyses, the historiography and subsequent taxonomy represent the first articulation of relationships across the body of work, identify growth areas and establish a number of movements and trends. In advancing the understanding of football fiction as a collective body, the paper lays foundations for further research and consideration of the works in generic terms