Coming and going: A narrative review exploring the push-pull factors during nurses' careers.

BACKGROUND: Shortages of nurses are one of the biggest challenges healthcare systems face around the world. Given the wide range of contexts and individuals working in nursing, a 'one-size-fits-all' retention strategy is unlikely to be effective. Knowing what matters most to nurses at different career stages would help employers and policy-makers who want to enhance nurse retention to design tailored strategies. OBJECTIVE: To review and synthesise findings from recently published literature on the push-pull factors influencing nurses' decisions at the micro level, to enter and stay (or leave) at key career stages (i.e. pre-career, training, early-, mid- and late-career, and return to practice). METHODS: We undertook a set of structured searches of the literature and a narrative synthesis to explore factors that motivate individuals to enter the nursing profession and the push-pull factors influencing nurse retention at different career stages. Electronic databases CINAHL, Medline, Scopus and Embase were searched in December 2022 (and updated in November 2023) for English language publications. Additional health workforce sources, such as King's Fund and Nuffield Trust, were also searched. RESULTS: 227 articles met the criteria for inclusion in the narrative review. Some push-pull factors were common to nurses across all career stages, including workplace support, flexible schedule patterns, opportunities for career advancement, fair treatment and salaries. In contrast, some challenges and push-pull factors were unique to each career stage. Students experienced difficulty in adjusting and balancing education and life; early-career nurses experienced transition shocks; mid-career nurses were frustrated by the lack of career advancement; late-career nurses desired more recognition; nurses returning to practice were discouraged by their lack of confidence and the cost of return-to-practice courses. CONCLUSION: Our findings reinforce the view that factors influencing nurses' choices about whether to enter, continue or leave nursing jobs are multi-factorial and multi-dimensional. Policy and employment practices should be informed by research that has a more nuanced insight into what matters most to whom and at what career stage. TWEETABLE ABSTRACT: Nuanced insight into motivations is needed to attract and retain a mix of nurse throughout their careers @ZEjebu @julia_philippou @JaneEball.

Association between preoperative right heart catheterization parameters and outcomes in patients undergoing isolated coronary artery bypass grafting.

Right ventricular catheterization may capture information that can help define prognosis before coronary artery bypass grafting (CABG). In this study, we evaluate the association between preoperative right heart catheterization parameters and outcomes of patients undergoing isolated CABG. All patients undergoing isolated CABG at our institution from 2013 to 2021 who also underwent preoperative right heart catheterization <14 days prior to isolated CABG were retrospectively queried. A total of 2343 patients underwent isolated CABG of whom 78 patients [20 (25.6%) female] were included in the final analysis. On multivariable regression, central venous pressure was significantly associated with operative mortality (odds ratio 1.14, 95% confidence interval 1.02-1.27, P = 0.024). Preoperative cardiac index was significantly inversely associated with intensive care unit length of stay (odds ratio 0.72, 95% confidence interval 0.62-0.84, P < 0.001) and duration of inotropic support (odds ratio 0.76, 95% confidence interval 0.63-0.92, P < 0.01). Assessment of preoperative cardiac function by right heart catheterization should be considered in high-risk patient populations, particularly those who have significant left ventricular dysfunction on preoperative echocardiography that would make them candidate for percutaneous coronary intervention, left ventricular assist device or heart transplantation. Further, right heart catheterization can help to guide preoperative optimization and intra-/postoperative decision-making.

Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection.

Current influenza vaccine strategies have yet to overcome significant obstacles, including rapid antigenic drift of seasonal influenza viruses, in generating efficacious long-term humoral immunity. Due to the necessity of germinal center formation in generating long-lived high affinity antibodies, the germinal center has increasingly become a target for the development of novel or improvement of less-efficacious vaccines. However, there remains a major gap in current influenza research to effectively target T follicular helper cells during vaccination to alter the germinal center reaction. In this study, we used a heterologous infection or immunization priming strategy to seed an antigen-specific memory CD4+ T cell pool prior to influenza infection in mice to evaluate the effect of recalled memory T follicular helper cells in increased help to influenza-specific primary B cells and enhanced generation of neutralizing antibodies. We found that heterologous priming with intranasal infection with acute lymphocytic choriomeningitis virus (LCMV) or intramuscular immunization with adjuvanted recombinant LCMV glycoprotein induced increased antigen-specific effector CD4+ T and B cellular responses following infection with a recombinant influenza strain that expresses LCMV glycoprotein. Heterologously primed mice had increased expansion of secondary Th1 and Tfh cell subsets, including increased CD4+ TRM cells in the lung. However, the early enhancement of the germinal center cellular response following influenza infection did not impact influenza-specific antibody generation or B cell repertoires compared to primary influenza infection. Overall, our study suggests that while heterologous infection or immunization priming of CD4+ T cells is able to enhance the early germinal center reaction, further studies to understand how to target the germinal center and CD4+ T cells specifically to increase long-lived antiviral humoral immunity are needed.

A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine.

Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0-36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.

Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy.

Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with inferior overall survival after ICB. Mechanistically, these phenotypes are at least partially explained by ARF6-dependent recycling, which controls plasma membrane density of the interferon-gamma receptor. Collectively, our findings reveal the importance of endomembrane trafficking in outfitting tumour cells with the ability to shape their immune microenvironment and respond to immunotherapy.

Testing times: disentangling admixture histories in recent and complex demographies using ancient DNA.

Our knowledge of human evolutionary history has been greatly advanced by paleogenomics. Since the 2020s, the study of ancient DNA has increasingly focused on reconstructing the recent past. However, the accuracy of paleogenomic methods in resolving questions of historical and archaeological importance amidst the increased demographic complexity and decreased genetic differentiation remains an open question. We evaluated the performance and behavior of two commonly used methods, qpAdm and the f3-statistic, on admixture inference under a diversity of demographic models and data conditions. We performed two complementary simulation approaches-firstly exploring a wide demographic parameter space under four simple demographic models of varying complexities and configurations using branch-length data from two chromosomes-and secondly, we analyzed a model of Eurasian history composed of 59 populations using whole-genome data modified with ancient DNA conditions such as SNP ascertainment, data missingness, and pseudohaploidization. We observe that population differentiation is the primary factor driving qpAdm performance. Notably, while complex gene flow histories influence which models are classified as plausible, they do not reduce overall performance. Under conditions reflective of the historical period, qpAdm most frequently identifies the true model as plausible among a small candidate set of closely related populations. To increase the utility for resolving fine-scaled hypotheses, we provide a heuristic for further distinguishing between candidate models that incorporates qpAdm model P-values and f3-statistics. Finally, we demonstrate a significant performance increase for qpAdm using whole-genome branch-length f2-statistics, highlighting the potential for improved demographic inference that could be achieved with future advancements in f-statistic estimations.

Ancient genomes reveal over two thousand years of dingo population structure.

Dingoes are culturally and ecologically important free-living canids whose ancestors arrived in Australia over 3,000 B.P., likely transported by seafaring people. However, the early history of dingoes in Australia-including the number of founding populations and their routes of introduction-remains uncertain. This uncertainty arises partly from the complex and poorly understood relationship between modern dingoes and New Guinea singing dogs, and suspicions that post-Colonial hybridization has introduced recent domestic dog ancestry into the genomes of many wild dingo populations. In this study, we analyzed genome-wide data from nine ancient dingo specimens ranging in age from 400 to 2,746 y old, predating the introduction of domestic dogs to Australia by European colonists. We uncovered evidence that the continent-wide population structure observed in modern dingo populations had already emerged several thousand years ago. We also detected excess allele sharing between New Guinea singing dogs and ancient dingoes from coastal New South Wales (NSW) compared to ancient dingoes from southern Australia, irrespective of any post-Colonial hybrid ancestry in the genomes of modern individuals. Our results are consistent with several demographic scenarios, including a scenario where the ancestry of dingoes from the east coast of Australia results from at least two waves of migration from source populations with varying affinities to New Guinea singing dogs. We also contribute to the growing body of evidence that modern dingoes derive little genomic ancestry from post-Colonial hybridization with other domestic dog lineages, instead descending primarily from ancient canids introduced to Sahul thousands of years ago.

Patient and clinician preferences for biologic treatments for severe uncontrolled asthma: a discrete choice experiment (DCE).

OBJECTIVES: To estimate the preferences of patients with asthma and asthma-treating clinicians for attributes of biologic treatments, to compare patients' and clinicians' preferences, and to better understand the reasons for their preferences. METHODS: Adults with moderate-to-severe asthma and clinicians who treat asthma in the US completed a cross-sectional, online survey including a discrete choice experiment (DCE) that consisted of seven attributes spanning treatment efficacy, risk and convenience. Marginal utilities were estimated using a mixed logit model, and relative attribute importance scores calculated. Clinicians were also asked about the value of biomarker agnostic biologic treatments. The survey was followed by qualitative interviews targeting a sub-sample of survey participants, in which the rationale behind their survey responses was discussed. RESULTS: In the DCE, both patients and clinicians placed the most importance on exacerbation and hospitalization rate reduction, and risk of injection site reaction. Patients valued location of administration more than clinicians. Rationale for individual-level preferences varied, with patients and clinicians reporting their preference depended on event frequency and anticipated quality of life impacts. Clinicians mentioned compliance and financial impacts, while patients mentioned personal experience, particularly around site reactions. Most patients and clinicians would value a biomarker agnostic asthma treatment. CONCLUSIONS: Asthma treatment preferences are largely driven by treatment efficacy and minimizing the risk of site reactions, although preferences differ between patients and clinicians across other attributes, highlighting the need for shared decision-making and individualized care.

Depression at the intersection of race/ethnicity, sex/gender, and sexual orientation in a nationally representative sample of US adults: A design-weighted intersectional MAIHDA.

This study examined how race/ethnicity, sex/gender, and sexual orientation intersect under interlocking systems of oppression to socially pattern depression among US adults. With cross-sectional data from the 2015-2020 National Survey on Drug Use and Health (NSDUH; n=234,722), we conducted design-weighted multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) under an intersectional framework to predict past-year and lifetime major depressive episode (MDE). With 42 intersectional groups constructed from seven race/ethnicity, two sex/gender, and three sexual orientation categories, we estimated age-standardized prevalence and excess/reduced prevalence attributable to two-way or higher interaction effects. Models revealed heterogeneity across groups, with prevalence ranging from 1.9-19.7% (past-year) and 4.5-36.5% (lifetime). Approximately 12.7% (past-year) and 12.5% (lifetime) of total individual variance were attributable to between-group differences, indicating key relevance of intersectional groups in describing the population distribution of depression. Main effects indicated, on average, people who were White, women, gay/lesbian, or bisexual had greater odds of MDE. Main effects explained most between-group variance. Interaction effects (past-year: 10.1%; lifetime: 16.5%) indicated a further source of heterogeneity around averages with groups experiencing excess/reduced prevalence compared to main effects expectations. We extend the MAIHDA framework to calculate nationally representative estimates from complex sample survey data using design-weighted, Bayesian methods.

Association of neighborhood socioeconomic status with echocardiographic parameters and re-admission following transcatheter aortic valve replacement.

BACKGROUND: Data on predictors of poor hemodynamic presentation and rehospitalizations following transcatheter aortic valve replacement (TAVR) are limited. We evaluate the association between neighborhood socioeconomic status (NSES) on echocardiographic presentation and post-TAVR readmission at a high-volume institution. METHODS: All patients undergoing TAVR at a single institution between 2012 and 2022 were included. Patient addresses, baseline variables including Society of Thoracic Surgeons (STS) preoperative risk of mortality and frailty, and post-procedural outcomes were extracted from electronic health records. Using a validated US Census Bureau Index, the NSES of each patient (1-100) was tabulated, with lower values correlating to increased social deprivation. Patients were separated into four ranked groups based on NSES (rank 1: 1-25, rank 4: 76-100). Multivariable regression was performed to determine variables associated with number of days hospitalized in one-year following index TAVR procedure. RESULTS: A total of 2031 patients were included. The median NSES was 68 (IQR: 53-80). There was a total of 232 (11.4%) readmissions. The median number of days hospitalized in one year following TAVR was 4 (interquartile range [IQR]: 2-7) After adjusting for baseline variables including STS risk score and patient frailty, compared to patients in the lowest ranked socioeconomic group, patients of higher NSES were associated with lower aortic valve gradients at baselines (Exp[ß]=0.997, 95% CI: 0.993-0.999, P=0.049). Additionally, compared to patients in the lowest ranked socioeconomic group, patients of NSES were associated with shorter duration of readmission after risk-factor adjustments (Exp[ß]=0.996, 95% CI: 0.992-0.999, P=0.032). CONCLUSIONS: Patients of lower socioeconomic status are associated with higher aortic valve gradient at baseline and more days hospitalized in the first year after their index TAVR procedure after adjusting for other risk factors. As TAVR volume continues to expand, physicians and health systems must consider this independent factor when determining patient prognosis and readmission policies.

Ultraviolet light and riboflavin accelerates red blood cell dysfunction in vitro and in a guinea pig transfusion model.

BACKGROUND: Quality assessment of modified or processed red blood cell (RBC) components, such as pathogen-reduced RBCs, using only in vitro testing may not always be predictive of in vivo performance. Mouse or rat in vivo models are limited by a lack of applicability to certain aspects of human RBC biology. Here, we used a guinea pig model to study the effects of riboflavin combined with UV light on the integrity of RBCs in vitro and following transfusion in vivo. MATERIALS AND METHODS: Guinea pig RBCs were collected from whole blood (WB) treated with varying UV doses (10, 20, 40 or 80 J/mL) in the presence of riboflavin (UVR-RBCs). In vitro tests for UVR-RBCs included hemolysis, osmotic fragility, and cellular morphology by scanning electron microscopy. Guinea pigs transfused with one-day post-treatment UVR-RBCs were evaluated for plasma hemoglobin (Hb), non-transferrin bound iron (NTBI), total iron and Perls-detectable hemosiderin deposition in the spleen and kidney, and renal uptake of Hb. RESULTS: Acute RBC injury was dose dependently accelerated after treatment with UV light in the presence of riboflavin. Aberrant RBC morphology was evident at 20, 40, and 80 J/mL, and membrane lysis with Hb release was prominent at 80 J/mL. Guinea pigs transfused with 40 and 80 J/mL UVR-RBCs showed increased plasma Hb levels, and plasma NTBI was elevated in all UVR-RBC groups (10-80 J/mL). Total iron levels and Perls-hemosiderin staining in spleen and kidney as well as Hb uptake in renal proximal tubules were increased 8 hours post-transfusion with 40 and 80 J/mL UVR-RBCs. DISCUSSION: UVR-RBCs administered to guinea pigs increased markers of intravascular and extravascular hemolysis in a UV dose-dependent manner. This model may allow for the discrimination of RBC injury during testing of extensively processed RBCs intended for transfusion.

Correction: Quantifying spatial variability in shell midden formation in the Farasan Islands, Saudi Arabia.

[This corrects the article DOI: 10.1371/journal.pone.0217596.].

Novel dosimetric validation of a commercial CT scanner based deep learning automated contour solution for prostate radiotherapy.

PURPOSE: OAR delineation accuracy influences: (i) a patient's optimised dose distribution (PD), (ii) the reported doses (RD) presented at approval, which represent plan quality. This study utilised a novel dosimetric validation methodology, comprehensively evaluating a new CT-scanner-based AI contouring solution in terms of PD and RD within an automated planning workflow. METHODS: 20 prostate patients were selected to evaluate AI contouring for rectum, bladder, and proximal femurs. Five planning 'pipelines' were considered; three using AI contours with differing levels of manual editing (nominally none (AIStd), minor editing in specific regions (AIMinEd), and fully corrected (AIFullEd)). Remaining pipelines were manual delineations from two observers (MDOb1, MDOb2). Automated radiotherapy plans were generated for each pipeline. Geometric and dosimetric agreement of contour sets AIStd, AIMinEd, AIFullEd and MDOb2 were evaluated against the reference set MDOb1. Non-inferiority of AI pipelines was assessed, hypothesising that compared to MDOb1, absolute deviations in metrics for AI contouring were no greater than that from MDOb2. RESULTS: Compared to MDOb1, organ delineation time was reduced by 24.9 min (96 %), 21.4 min (79 %) and 12.2 min (45 %) for AIStd, AIMinEd and AIFullEd respectively. All pipelines exhibited generally good dosimetric agreement with MDOb1. For RD, median deviations were within ± 1.8 cm3, ± 1.7 % and ± 0.6 Gy for absolute volume, relative volume and mean dose metrics respectively. For PD, respective values were within ± 0.4 cm3, ± 0.5 % and ± 0.2 Gy. Statistically (p < 0.05), AIMinEd and AIFullEd were dosimetrically non-inferior to MDOb2. CONCLUSIONS: This novel dosimetric validation demonstrated that following targeted minor editing (AIMinEd), AI contours were dosimetrically non-inferior to manual delineations, reducing delineation time by 79 %.

Adaptation to ex vivo culture reduces human hematopoietic stem cell activity independently of the cell cycle.

ABSTRACT: Loss of long-term hematopoietic stem cell (LT-HSC) function ex vivo hampers the success of clinical protocols that rely on culture. However, the kinetics and mechanisms through which this occurs remain incompletely characterized. In this study, through time-resolved single-cell RNA sequencing, matched in vivo functional analysis, and the use of a reversible in vitro system of early G1 arrest, we defined the sequence of transcriptional and functional events that occur during the first ex vivo division of human LT-HSCs. We demonstrated that the sharpest loss in LT-HSC repopulation capacity happens early on, between 6 and 24 hours of culture, before LT-HSCs commit to cell cycle progression. During this time window, LT-HSCs adapt to the culture environment, limit the global variability in gene expression, and transiently upregulate gene networks involved in signaling and stress responses. From 24 hours, LT-HSC progression past early G1 contributes to the establishment of differentiation programs in culture. However, contrary to the current assumptions, we demonstrated that the loss of HSC function ex vivo is independent of cell cycle progression. Finally, we showed that targeting LT-HSC adaptation to culture by inhibiting the early activation of JAK/STAT signaling improves HSC long-term repopulating function ex vivo. Collectively, our study demonstrated that controlling early LT-HSC adaptation to ex vivo culture, for example, via JAK inhibition, is critically important to improve HSC gene therapy and expansion protocols.

An Undergraduate Health Care Experience Course Increases Confidence and Improves Student Understanding of Health Care Careers.

Increasing the health care work force is critical to underserved communities. Unfortunately, students in these areas lack accessibility to the clinical experiences needed to get an introductory understanding of careers in health care. Therefore, a health care experience (HCE) course was created for undergraduate students that included didactic training, active learning exercises, and coordinated shadowing experiences. To evaluate the effect of the HCE on student interest in science, health care, and rural health a study was performed on HCE participants. This study assessed student background, interest in health care, and plans for future careers in underserved settings. Students who enrolled in the HCE demonstrated high interest in science, health care, and rural health. Evaluation of student reflections indicated students attained novel learning, gained insights, and recognized the importance of communication. The HCE course students exhibited amplified confidence in HCEs and had a significant increase in understanding of health care compared with a control group of students who had not completed the HCE. Undergraduate institutions can include courses like the HCE into curricula to increase accessibility to career experiences for students interested in health care careers.

Synthesis, Characterization, and the Effect of Lewis Bases on the Nuclearity of Iron Alkoxide Complexes.

Inspired by the potential of alkoxides as weak-field ligands and their ability to bridge, we report herein a series of high-spin iron complexes supported by a bis-alkoxide framework PhDbf. A diiron complex [Fe2(PhDbf)2] (1a) is obtained upon metalation of the ligand, whereas addition of substituted pyridines affords five-coordinate mononuclear iron complexes [(R-Py)2Fe(PhDbf)] (2a-4a, R = H, p-tBu, p-CF3). The potential for nuclearity control of the metal complexes via auxiliary ligands is highlighted by the formation of asymmetric diiron species [(p-CF3-Py)Fe2(PhDbf)2] (5a) and [(m-CF3-Py)Fe2(PhDbf)2] (6a) with trifluoromethyl substituted pyridines, while electron-rich pyridines only produced monomeric species. Electronic properties analysis via UV-vis, electron paramagnetic resonance, 57Fe Mössbauer spectroscopy, and time-dependent density functional theory, along with redox capabilities of these complexes are reported to illustrate the effect of nuclearity on reactivity and the potential of these complexes to access higher oxidation states relevant in oxidative chemistry. Species 1a-5a, [(THF)2Fe(PhDbf)][PF6] (7), [PyFe(PhDbf)Cl] (2b), and [Py2Fe(PhDbf)][PF6] (2c) were characterized via SCXRD. Indirect evidence for the formation of dimeric Fe(III) species (1b, 5b, and 6b) is discussed.

In chronic kidney disease altered cardiac metabolism precedes cardiac hypertrophy.

Conduit arterial disease in chronic kidney disease (CKD) is an important cause of cardiac complications. Cardiac function in CKD has not been studied in the absence of arterial disease. In an Alport syndrome model bred not to have conduit arterial disease, mice at 225 days of life (dol) had CKD equivalent to humans with CKD stage 4-5. Parathyroid hormone (PTH) and FGF23 levels were one log order elevated, circulating sclerostin was elevated, and renal activin A was strongly induced. Aortic Ca levels were not increased, and vascular smooth muscle cell (VSMC) transdifferentiation was absent. The CKD mice were not hypertensive, and cardiac hypertrophy was absent. Freshly excised cardiac tissue respirometry (Oroboros) showed that ADP-stimulated O2 flux was diminished from 52 to 22 pmol/mg (P = 0.022). RNA-Seq of cardiac tissue from CKD mice revealed significantly decreased levels of cardiac mitochondrial oxidative phosphorylation genes. To examine the effect of activin A signaling, some Alport mice were treated with a monoclonal Ab to activin A or an isotype-matched IgG beginning at 75 days of life until euthanasia. Treatment with the activin A antibody (Ab) did not affect cardiac oxidative phosphorylation. However, the activin A antibody was active in the skeleton, disrupting the effect of CKD to stimulate osteoclast number, eroded surfaces, and the stimulation of osteoclast-driven remodeling. The data reported here show that cardiac mitochondrial respiration is impaired in CKD in the absence of conduit arterial disease. This is the first report of the direct effect of CKD on cardiac respiration.NEW & NOTEWORTHY Heart disease is an important morbidity of chronic kidney disease (CKD). Hypertension, vascular stiffness, and vascular calcification all contribute to cardiac pathophysiology. However, cardiac function in CKD devoid of vascular disease has not been studied. Here, in an animal model of human CKD without conduit arterial disease, we analyze cardiac respiration and discover that CKD directly impairs cardiac mitochondrial function by decreasing oxidative phosphorylation. Protection of cardiac oxidative phosphorylation may be a therapeutic target in CKD.

OCA-B/Pou2af1 is sufficient to promote CD4+ T cell memory and prospectively identifies memory precursors.

The molecular mechanisms leading to the establishment of immunological memory are inadequately understood, limiting the development of effective vaccines and durable antitumor immune therapies. Here, we show that ectopic OCA-B expression is sufficient to improve antiviral memory recall responses, while having minimal effects on primary effector responses. At peak viral response, short-lived effector T cell populations are expanded but show increased Gadd45b and Socs2 expression, while memory precursor effector cells show increased expression of Bcl2, Il7r, and Tcf7 on a per-cell basis. Using an OCA-B mCherry reporter mouse line, we observe high OCA-B expression in CD4+ central memory T cells. We show that early in viral infection, endogenously elevated OCA-B expression prospectively identifies memory precursor cells with increased survival capability and memory recall potential. Cumulatively, the results demonstrate that OCA-B is both necessary and sufficient to promote CD4 T cell memory in vivo and can be used to prospectively identify memory precursor cells.

What might make nurses stay? A protocol for discrete choice experiments to understand NHS nurses' preferences at early-career and late-career stages.

INTRODUCTION: Like many countries, England has a national shortage of registered nurses. Employers strive to retain existing staff, to ease supply pressures. Disproportionate numbers of nurses leave the National Health Services (NHS) both early in their careers, and later, as they near retirement age. Research is needed to understand the job preferences of early-career and late-career nurses working in the NHS, so tailored policies can be developed to better retain these two groups. METHODS AND ANALYSIS: We will collect job preference data for early-career and late-career NHS nurses, respectively using two separate discrete choice experiments (DCEs). Findings from the literature, focus groups, academic experts and stakeholder discussions will be used to identify and select the DCE attributes (ie, job features) and levels. We will generate an orthogonal, fractional factorial design using the experimental software Ngene. The DCEs will be administered through online surveys distributed by the regulator Nursing and Midwifery Council. For each group, we expect to achieve a final sample of 2500 registered NHS nurses working in England. For early-career nurses, eligible participants will be registered nurses who graduated in the preceding 5 years (ie, 2019-2023). Eligible participants for the late-career survey will be registered nurses aged 55 years and above. We will use conditional and mixed logit models to analyse the data. Specifically, study 1 will estimate the job preferences of early-career nurses and the possible trade-offs. Study 2 will estimate the retirement preferences of late-career NHS nurses and the potential trade-offs. ETHICS AND DISSEMINATION: The research protocol was reviewed and approved by the host research organisation Ethics Committees Research Governance (University of Southampton, number 80610) (https://www.southampton.ac.uk/about/governance/regulations-policies/policies/ethics). The results will be disseminated via conference presentations, publications in peer-reviewed journals and annual reports to key stakeholders, the Department of Health and Social Care, and NHS England/Improvement retention leaders. REGISTRATION DETAILS: Registration on OSF http://doi.org/10.17605/OSF.IO/RDN9G.

Living in disadvantaged neighborhoods linked to less intervention for severe aortic stenosis.

To investigate the association between area deprivation index (ADI) and aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Patients aged 40-95 years with severe AS confirmed by echocardiography were included. The 9-digit zip code of patient residence address was used to identify the ADI ranking, based on which patients were divided into 5 groups (with Group E being most deprived). The rates of AV intervention were compared among 5 groups using competing risks analysis, with death as a competing event. We included 1751 patients with severe AS from 2013 to 2018 followed for a median 2.8 (interquartile range, 1.5-4.8) years. The more distressed ADI groups tended to be younger (P = 0.002), female (P < 0.001), and of African American race (P < 0.001), have higher presentation of sepsis (P = 0.031), arrhythmia (P = 0.022), less likely to have previous diagnosis of AS (P < 0.001); and were less likely to undergo AVR (52.5% vs 46.9% vs 46.1% vs 48.9% vs 39.7%, P = 0.023). Using competing risk analysis, the highest ADI group (E) were the least and the lowest ADI group (A) the most likely to undergo AVR (Gray's test, P = 0.025). The association between ADI ranking and AVR rates was influenced by sex and race. Within group analysis, there was significant association between race and AVR (Gray's test, P < 0.001), and between sex and AVR (Gray's test, P < 0.001). Patients with severe AS living in more deprived neighborhoods were less likely to undergo aortic valve interventions, which was influenced by female gender, and African American race.