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Serosal pathologies including malignant mesothelioma (MM) can show features of osseous and/or cartilaginous differentiation although the mechanism for its formation is unknown. Mesothelial cells have the capacity to differentiate into cells with myofibroblast, smooth muscle and endothelial cell characteristics. Whether they can differentiate into other cell types is unclear. This study tests the hypothesis that mesothelial cells can differentiate into cell lineages of the embryonic mesoderm including osteoblasts and adipocytes. To examine this, a functional assay of bone formation and an adipogenic assay were performed in vitro with primary rat and human mesothelial cells maintained in osteogenic or adipogenic medium (AM) for 0–26 days. Mesothelial cells expressed increasing levels of alkaline phosphatase, an early marker of the osteoblast phenotype, and formed mineralized bone‐like nodules. Mesothelial cells also accumulated lipid indicative of a mature adipocyte phenotype when cultured in AM. All cells expressed several key osteoblast and adipocyte markers, including osteoblast‐specific runt‐related transcription factor 2, and demonstrated changes in mRNA expression consistent with epithelial‐to‐mesenchymal transition. In conclusion, these studies confirm that mesothelial cells have the capacity to differentiate into osteoblast‐ and adipocyte‐like cells, providing definitive evidence of their multipotential nature. These data strongly support mesothelial cell differentiation as the potential source of different tissue types in MM tumours and other serosal pathologies, and add support for the use of mesothelial cells in regenerative therapies.

The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care. Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in 15 UK paediatric intensive care units (PICUs). Children admitted as an emergency, who were older than 38 weeks corrected gestational age and younger than 16 years receiving invasive ventilation and supplemental oxygen were randomly allocated in a 1:1 ratio via a concealed, central, web-based randomisation system to conservative peripheral oxygen saturations ([SpO2] 88–92%) or liberal (SpO2 >94%) targets. The primary outcome was the duration of organ support at 30 days following random allocation, a rank-based endpoint with death either on or before day 30 as the worst outcome (a score equating to 31 days of organ support), with survivors assigned a score between 1 and 30 depending on the number of calendar days of organ support received. The primary effect estimate was the probabilistic index, a value greater than 0·5 indicating more than 50% probability that conservative oxygenation is superior to liberal oxygenation for a randomly selected patient. All participants in whom consent was available were included in the intention-to-treat analysis. The completed study was registered with the ISRCTN registry (ISRCTN92103439). Between Sept 1, 2020, and May 15, 2022, 2040 children were randomly allocated to conservative or liberal oxygenation groups. Consent was available for 1872 (92%) of 2040 children. The conservative oxygenation group comprised 939 children (528 [57%] of 927 were female and 399 [43%] of 927 were male) and the liberal oxygenation group included 933 children (511 [56%] of 920 were female and 409 [45%] of 920 were male). Duration of organ support or death in the first 30 days was significantly lower in the conservative oxygenation group (probabilistic index 0·53, 95% CI 0·50–0·55; p=0·04 Wilcoxon rank-sum test, adjusted odds ratio 0·84 [95% CI 0·72–0·99]). Prespecified adverse events were reported in 24 (3%) of 939 patients in the conservative oxygenation group and 36 (4%) of 933 patients in the liberal oxygenation group. Among invasively ventilated children who were admitted as an emergency to a PICU receiving supplemental oxygen, a conservative oxygenation target resulted in a small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target. Widespread adoption of a conservative oxygenation saturation target (SpO2 88–92%) could help improve outcomes and reduce costs for the sickest children admitted to PICUs. UK National Institute for Health and Care Research Health Technology Assessment Programme.

PurposeGlobal talent shortages, new skill demand and rising numbers of unfilled posts are fuelling an increasingly challenging job market, exacerbated by economic uncertainty and transformational digital change. Seeking creative solutions in response, the authors examine talent management’s (TM) theoretical and conceptual foundations, specifically the identification and selection of talent and TM programme design to explore the challenges and benefits of side-of-desk projects as interventions.Design/methodology/approachTaking an inductive qualitative approach, questionnaires, focus groups and semi-structured interviews gathered data from three employee groups in a UK digital communications organisation.FindingsThe authors reveal inconsistencies in the definition and selection of talent, highlighting programme quality challenges to expose a direct correlation between participant experience and motivation and retention, along with the longer-term challenges of balancing talented human capital, shareholder expectations and sustainable workforce resourcing.Originality/valueThe authors' research extends existing knowledge concerning the effect of organisational culture, context and workforce demands upon TM programmes, providing theoretical and practical implications for leaders and policymakers in designing enrichment activities to motivate, develop and retain talent. The authors make recommendations to inform the future design of TM programmes, revealing new opportunities to develop hidden talent and presenting a realistic and sustainable toolkit for future practice in the form of an organisational logic model.

ContextPatient safety is a priority for healthcare organisations worldwide and is a key factor in providing high quality healthcare. Prescribing medications correctly is critical to ensuring safety, especially in the setting of a Paediatric Intensive Care Unit (PICU) where patients are vulnerable to being exposed to incidents due to highly complex care and illness severity. In our 21 bedded PICU, any prescribing errors detected by critical care pharmacists are recorded on a prescribing error database each day (Microsoft Access). Information inputted includes the drug involved in the error, the route of administration, prescriber identifier number, type of error and category of error based on the NCC MERP1 classification system. Information is extracted monthly from this database to further populate a prescribing errors dashboard, highlighting the total number of prescribing errors each month and sub-categorising the number of errors according to drug cause and error type.Data collected in 2021 was analysed by our Trust’s Quality Improvement (QI) Team who generated pareto charts for the highest reported prescribing errors according to drug and error type. Although pharmacist data showed that many drugs were responsible for prescribing errors, pareto analysis by the QI team identified that Teicoplanin, Heparin, Fentanyl, Chloral Hydrate and Octenisan® were the drugs associated with the most frequent number of errors and causing the biggest cumulative impact on our prescribing error data. In terms of error type, pareto analysis identified that 80% of our cumulative errors were attributed to the wrong route, wrong dose or missing route of administration.ConclusionA pareto chart is a graph that indicates the frequency of defects as well as their cumulative impact. By applying this statistical control process to PICU prescribing error data for 2021, we were able to identify the drugs and error types responsible for the majority of our cumulative errors. Using the ‘Brilliant Basics’ methodology,2 we followed a two-step approach in dissecting our data. For step one, we analysed the data that we had and then in step two, using this analysis, we were able to agree and introduce measures to our prescribing systems in order to mitigate the risk of the errors re-occurring. These measures have included redesigning our PICU prescription to add or adapt prescribing recommendations for Teicoplanin, Heparin and Fentanyl, updating prescribing advice in our PICU electronic drugs formulary for Chloral Hydrate and placing an additional daily task on our nurses’ electronic task list to ensure Octenisan® is used. In terms of error type, we have raised awareness of the prevalence of the errors causing the biggest impact on reported prescribing errors, through the medium of pharmacy newsletters, which are disseminated to all PICU staff and by educating new PICU prescribers as part of their induction to the unit. To assess whether the above changes have contributed to an improvement in our reported errors by drug and type, we will continue to perform statistical analysis on prescribing data collected throughout 2022.ReferencesNational Coordinating Council for Medication Error Reporting and Prevention. 2001. http://www.nccmerp.org/types-medication-errors Accessed 14 June 2022.A Catalyst for Better Health Strategy 2019/22. NHS Business Services Authority (V1) 03 2019. https://www.nhsbsa.nhs.uk/sites/default/files/2019-04/Strategy%202019-22%20%28V1%29%2003.2019.pdf

AimBreast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment.MethodsExpression of five proliferation gene mRNAs; Ki-67, STK 15, CCNB1, CCND1 and MYBL2, was quantified in 27 breast carcinomas and compared with Ki-67 proliferation index (PI) and Nottingham mitotic score.ResultsExpression of Ki-67, STK15 and MYBL2 mRNA showed moderate Spearman's correlation with Ki-67 PI (p<0.01), but CCND1 and CCNB1 showed weak, non-significant correlation. Individual gene expression did not associate with mitotic score but combined mRNA expression correlated with both Ki-67 PI (p=0.018) and mitotic score (p=0.03; 0.007).ConclusionsThis study confirms mRNA analysis in breast carcinoma formalin-fixed, paraffin-embedded samples is feasible and suggests gene expression profiling, using a small set of five proliferation genes, has potential in aiding histological grading or assessment of proliferative activity of breast cancers. To fully evaluate the clinical applicability of this approach, a larger cohort study with long-term follow-up data is required.

Implicit racial bias is a prominent concern in today’s academic and popular discussions. The negative effects of implicit racial bias have been seen in both private and public forums. Society and, in particular, the workplace, is approaching a significant racial demographic transformation; however, as yet there are no effective approaches to mitigating the negative effects of implicit racial bias. This study examined how ethnocultural empathic response, as a psychological process capable of development, relates to the negative effects of implicit racial bias in the workplace. By means of a mixed-methods, phenomenological approach, this study’s 146 participants completed 2 online surveys and, of those 8 qualitative interviews were used to triangulate results. These online surveys are 1) The Scale of Ethnocultural Empathy—SEE, which measures ethnocultural empathic response, and 2) the Implicit Association Test (IAT), which measures implicit racial bias. Four key findings emerged from this study: 1) Ethnocultural empathy is a psychological phenomenon that contributes to an individual’s level of implicit racial bias; 2) Implicit racial bias in the workplace is perceived to be happening predominantly to other people, the result of other people’s actions, and having no lasting impact on those who observe it; 3) Ethnocultural empathy in the workplace is perceived to be demonstrated predominantly through appreciating cultural difference. 4) Significant relationships in 3 factors of ethnocultural empathy are related to implicit racial bias. This study offers an increased awareness of the aspects of ethnocultural empathy and contributes to an understanding of psychosocial factors, capable of development, that can mitigate the negative effects of implicit racial bias.

Early Middle English is a vernacular of England that evolves from Old English a hundred years after the Norman Conquest of 1066 (c.1150–1300). The literature of this period is diverse, ranging from homilies to debate poetry and more, but traditional academic categories have failed to understand the nature of this diversity, which, in turn, fails to understand the literature of the late twelfth century. By approaching the period and specifically two works, the Ormulum and Poema Morale, from the perspective of Deleuze and Guattari’s rhizome—an always expanding multiplicity made up of other multiplicities, all interconnected—we can better understand the innovative synthesis at work. The Ormulum is a collection of verse-homilies in strict septenary meter that paraphrase and explicate the Gospels; however, its organization is more akin to a gospel harmony while its explication is similar to a biblical commentary. Poema Morale is a devotional poem in a less stable septenary meter with rhyming couplets and exhorts Christian living in preparation for Judgment Day. Its transmission history, though, begins with a seemingly homiletic context. We must return to the manuscript as our starting point because both the text and the manuscripts in which they survive reveal the extent to which writers synthesized vernacular and Latin form and content, resulting not only in new English devotional material and the appearance thereof, but also in a new English verse form, the septenary. Therefore, the origins of the English septenary arise from a synthesis of Latin meter and the Old English rhythmical prose style that was famously used by Abbot Ælfric of Eynsham and Archbishop Wulfstan of York. The writers, then, are culturally redeeming, or remediating, the English language and its redemptive material just as I hope to redeem Early Middle English literature in modern scholarship.

The Joint Commission (TJC) sets standards to assist healthcare organizations in improving performance. The hospital for which this project was developed did not meet national TJC benchmarks for patient satisfaction and nurse retention. Based on direct observation, discussion with staff, and results of the Multifactorial Leadership Questionnaire given to 39 staff nurses before this project was chosen, evidence suggested that the leadership style of the charge nurses was transactional, which is less effective than transformational leadership (TFL). Framed within the Plan, Do, Study, Act model, the purpose of this quality improvement project was to design an educational curriculum including didactic and competencies on TFL for unit charge nurses. A team approach was used for the project. Incorporating the American Organization of Nurse Executives recommendations on effective leadership, the curriculum encompassed the importance and management of TFL intertwined with the power, motivation, and characteristics of the transformational leader. Competencies governing TFL in practice were a significant part of the curriculum. The curriculum was evaluated by 4 content experts using a 12-item yes or no response for each of the criteria. One of the criteria was answered no in the learning objectives section and the design of the criteria was revised All other criteria were met. A recommendation was made for a change to the evaluation format for the leadership style identification portion of the curriculum. This project has important implications for social change as unit charge nurses strive to act on best practices in leadership, thus positively impacting the well-being and satisfaction of their patients and fellow nurses.

Purpose: A challenge in ocular preventive medicine is identification of patients with early pathological retinal damage that might benefit from nutritional intervention. The purpose of this study is to evaluate retinal thinning (RT) in early atrophic age-related macular degeneration (AMD) against visual function data from the Zeaxanthin and Visual Function (ZVF) randomized double masked placebo controlled clinical trial (FDA IND #78973). Methods: Retrospective, observational case series of medical center veterans with minimal visible AMD retinopathy (AREDS Report #18 simplified grading 1.4/4.0 bilateral retinopathy). Foveal and extra-foveal four quadrant SDOCT RT measurements were evaluated in n = 54 clinical and ZVF AMD patients. RT by age was determined and compared to the OptoVue SD OCT normative database. RT by quadrant in a subset of n = 29 ZVF patients was correlated with contrast sensitivity and parafoveal blue cone increment thresholds. Results: Foveal RT in AMD patients and non-AMD patients was preserved with age. Extrafoveal regions, however, showed significant slope differences between AMD patients and non-AMD patients, with the superior and nasal quadrants most vulnerable to retinal thinning (sup quad: −5.5 μm/decade thinning vs. Non-AMD: −1.1 μm/decade, P < 0.02; nasal quad: −5.0 μm/decade thinning vs. Non-AMD: −1.0 μm/decade, P < 0.04). Two measures of extrafoveal visual deterioration were correlated: A significant inverse correlation between % RT and contrast sensitivity (r = −0.33, P = 0.01, 2 Tailed Paired T) and an elevated extrafoveal increment blue cone threshold (r = +0.34, P = 0.01, 2 Tailed T). Additional SD OCT RT data for the non-AMD oldest age group (ages 82–91) is needed to fully substantiate the model. Conclusion: A simple new SD OCT clinical metric called “% extra-foveal RT” correlates well with functional visual loss in early AMD patients having minimal visible retinopathy. This metric can be used to follow the effect of repleting ocular nutrients, such as zinc, antioxidants, carotenoids, n-3 essential fats, resveratrol and vitamin D.

Dietary iron is present in the intestine as Fe(II) and Fe(III). Since enterocytes take up Fe(II) by the divalent metal transporter (DMT1), Fe(III) must be reduced. Whether other Fe(III) transport processes are present is unknown. Release of iron from the enterocyte into the plasma involves the iron-regulated transporter-1/metal transporter protein-1 (IREG-1/MTP-1, ferroportin) but ferroportin is also found on the apical membrane. We compared the uptake of iron from Fe(II):ascorbate and Fe(III):citrate using the rat intestinal enterocyte cell line-6 (IEC-6), in the presence of ferrous chelators, a blocking antibody to ferroportin, at different pH and during the over-expression of DMT1. Firstly, surface ferrireduction was absent. Secondly, blocking ferroportin partly and totally reduced Fe(II) and Fe(III) uptake, respectively. Thirdly, optimal Fe(II) uptake occurred at pH 5.5 but Fe(III) uptake was unaffected by pH and, fourthly, over-expression of DMT1 increased uptake of Fe(II) and Fe(III). This indicates that an increased extracellular H+ concentration facilitates DMT1-mediated Fe(II) uptake at the cell membrane. However, since Fe(III) uptake required DMT1, but not cell surface ferrireduction, and was independent of variations in extracellular pH, it appears that Fe(III) is internalised before ferrireduction and transport by DMT1. Ferroportin may function as a modulator of DMT1 activity and play a role in Fe(III) uptake, possibly by affecting the number or affinity of citrate binding sites.