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Induced pluripotent stem cells (iPSCs) have emerged as a revolutionary tool in cell therapies due to their ability to differentiate into various cell types, unlimited supply, and potential as off-the-shelf cell products. New advances in iPSC-derived immune cells have generated potent iNK and iT cells which showed robust killing of cancer cells in animal models and clinical trials. With the advent of advanced genome editing technologies that enable the development of highly engineered cells, here we outline 12 strategies to engineer iPSCs to overcome limitations and challenges of current cell-based immunotherapies, including safety switches, stealth edits, avoiding graft-versus-host disease (GvHD), targeting, reduced lymphodepletion, efficient differentiation, increased in vivo persistence, stemness, metabolic fitness, homing/trafficking, and overcoming suppressive tumor microenvironment and stromal cell barrier. With the development of advanced genome editing techniques, it is now possible to insert large DNA sequences into precise genomic locations without the need for DNA double strand breaks, enabling the potential for multiplexed knock out and insertion. These technological breakthroughs have made it possible to engineer complex cell therapy products at unprecedented speed and efficiency. The combination of iPSC derived iNK, iT and advanced gene editing techniques provides new opportunities and could lead to a new era for next generation of cell immunotherapies.

Objective The aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London.Design Observational cohort study.Setting London North West Healthcare NHS Trust (LNWH).Participants Patients tested and/or admitted for COVID-19 at LNWH during March and April 2020Main outcome measures Descriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19.Results The outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p

Intimal sarcoma (IS) is a rare malignancy arising in the great vessels or heart, most commonly in the pulmonary artery, primarily treated with surgical intervention. We report a case of IS of the pulmonary artery diagnosed after an endarterectomy to remove a suspected pulmonary embolism. The tumor could not be entirely resected and showed interval growth at post-operative follow up. Neoadjuvant radiotherapy was then delivered to improve resectability. Imaging confirmed decreased tumor size, and a surgical resection with pulmonary artery reconstruction and right upper lobectomy was then successfully performed. Adjuvant gemcitabine and docetaxel was later initiated. Four months post-operatively, the patient is alive without disease recurrence. While prior reports in the literature document use of adjuvant chemotherapy and radiotherapy for treatment of IS of the pulmonary artery, no prior experience has documented utility of neoadjuvant radiotherapy for improvement of resectability. Our experience suggests that neoadjuvant radiation should be considered to improve resectability in cases of borderline resectable IS of the pulmonary artery.

BackgroundBeverages, especially sugar-sweetened beverages (SSBs), have been increasingly subject to policies aimed at reducing their consumption as part of measures to tackle obesity. However, precision targeting of policies is difficult as information on what types of consumers they might affect, and to what degree, is missing. We fill this gap by creating a typology of beverage consumers in Great Britain (GB) based on observed beverage purchasing behaviour to determine what distinct types of beverage consumers exist, and what their socio-demographic (household) characteristics, dietary behaviours, and weight status are.Methods and findingsWe used cross-sectional latent class analysis to characterise patterns of beverage purchases. We used data from the 2016 GB Kantar Fast-Moving Consumer Goods (FMCG) panel, a large representative household purchase panel of food and beverages brought home, and restricted our analyses to consumers who purchase beverages regularly (i.e., >52 l per household member annually) (n = 8,675). Six categories of beverages were used to classify households into latent classes: SSBs; diet beverages; fruit juices and milk-based beverages; beer and cider; wine; and bottled water. Multinomial logistic regression and linear regression were used to relate class membership to household characteristics, self-reported weight status, and other dietary behaviours, derived from GB Kantar FMCG. Seven latent classes were identified, characterised primarily by higher purchases of 1 or 2 categories of beverages: 'SSB' (18% of the sample; median SSB volume = 49.4 l/household member/year; median diet beverage volume = 38.0 l), 'Diet' (16%; median diet beverage volume = 94.4 l), 'Fruit & Milk' (6%; median fruit juice/milk-based beverage volume = 30.0 l), 'Beer & Cider' (7%; median beer and cider volume = 36.3 l; median diet beverage volume = 55.6 l), 'Wine' (18%; median wine volume = 25.5 l; median diet beverage volume = 34.3 l), 'Water' (4%; median water volume = 46.9 l), and 'Diverse' (30%; diversity of purchases, including median SSB volume = 22.4 l). Income was positively associated with being classified in the Diverse class, whereas low social grade was more likely for households in the classes SSB, Diet, and Beer & Cider. Obesity (BMI > 30 kg/m2) was more prevalent in the class Diet (41.2%, 95% CI 37.7%-44.7%) despite households obtaining little energy from beverages in that class (17.9 kcal/household member/day, 95% CI 16.2-19.7). Overweight/obesity (BMI > 25 kg/m2) was above average in the class SSB (66.8%, 95% CI 63.7%-69.9%). When looking at all groceries, households from the class SSB had higher total energy purchases (1,943.6 kcal/household member/day, 95% CI 1,901.7-1,985.6), a smaller proportion of energy from fruits and vegetables (6.0%, 95% CI 5.8%-6.3%), and a greater proportion of energy from less healthy food and beverages (54.6%, 95% CI 54.0%-55.1%) than other classes. A greater proportion of energy from sweet snacks was observed for households in the classes SSB (18.5%, 95% CI 18.1%-19.0%) and Diet (18.8%, 95% CI 18.3%-19.3%). The main limitation of our analyses, in common with other studies, is that our data do not include information on food and beverage purchases that are consumed outside the home.ConclusionsAmongst households that regularly purchase beverages, those that mainly purchased high volumes of SSBs or diet beverages were at greater risk of obesity and tended to purchase less healthy foods, including a high proportion of energy from sweet snacks. These households might additionally benefit from policies targeting unhealthy foods, such as sweet snacks, as a way of reducing excess energy intake.

Over 60 years of scholarship have been dedicated to describing meaning-making processes through which organisational learning occurs. Recently, researchers have considered the creation of shared meaning-making through prolonged and co-located interactions situated in the context of a community. The spread of hybrid working has had an adverse impact on several of these meaning-making processes, disrupting knowledge-sharing ecosystems and organisational learning overall. In this article, we explore ways of facilitating knowledge-sharing against such disruption. To maximise the efficiency of verbal communication, we introduce Basil Bernstein's socio-linguistic approach of learning as the emergence and consolidation of verbal codes. We trial the LEGO® SERIOUS PLAY® method as a means of facilitating the emergence and consolidation of such verbal codes in five online workshops with manufacturing businesses. We find that the emergence of verbal codes can be facilitated through the use of the LEGO® SERIOUS PLAY® method. We also find that code consolidation is a much more spontaneous process, and we observe this in the final reflection stage of the workshops. Our study offers insights into the process of meaning-making in online exchanges and has implications for organisations seeking to manage hybrid or fully remote workforces, as well as the wider field of organisational learning. [ABSTRACT FROM AUTHOR]