'Something that helped the whole picture': Experiences of parents offered rapid prenatal exome sequencing in routine clinical care in the English National Health Service.

OBJECTIVES: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England. This study aimed to explore parent experiences and their information and support needs from the perspective of parents offered pES and of health professionals involved in its delivery. METHODS: In this qualitative study, semi-structured interviews were conducted with 42 women and 6 male partners and 63 fetal medicine and genetic health professionals. Interviews were transcribed verbatim and analysed using thematic analysis. RESULTS: Overall views about pES were positive and parents were grateful to be offered the test. Highlighted benefits of pES included the value of the additional information for pregnancy management and planning for future pregnancies. An anxious wait for results was common, often associated with the need to make decisions near to 24 weeks in pregnancy when there are legal restrictions for late termination. Descriptions of dealing with uncertainty were also common, even when results had been returned. Many parents described pES results as informing decision-making around whether or not to terminate pregnancy. Some professionals were concerned that a non-informative result could be overly reassuring and highlighted that careful counselling was needed to ensure parents have a good understanding of what the result means for their pregnancy. Emotional support from professionals was valued; however, some parents felt that post-test support was lacking. CONCLUSION: Parents and professionals welcomed the introduction of pES. Results inform parents' decision-making around the termination of pregnancy. When there are no diagnostic findings or uncertain findings from pES, personalised counselling that considers scans and other tests are crucial. Directing parents to reliable online sources of information and providing emotional support throughout could improve their experiences of care.

Active juvenile systemic lupus erythematosus is associated with distinct NK cell transcriptional and phenotypic alterations.

While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the contribution of natural killer (NK) cells to disease pathogenesis. There is even less evidence about the role of NK cells in the more severe phenotype with juvenile-onset (J)SLE. In this study, analysis of the phenotype and function of NK cells in a large cohort of JSLE patients demonstrated that total NK cells, as well as perforin and granzyme A expressing NK cell populations, were significantly diminished in JSLE patients compared to age- and sex-matched healthy controls. The reduction in NK cell frequency was associated with increased disease activity, and transcriptomic analysis of NK populations from active and low disease activity JSLE patients versus healthy controls confirmed that disease activity was the main driver of differential NK cell gene expression. Pathway analysis of differentially expressed genes revealed an upregulation of interferon-α responses and a downregulation of exocytosis in active disease compared to healthy controls. Further gene set enrichment analysis also demonstrated an overrepresentation of the apoptosis pathway in active disease. This points to increased propensity for apoptosis as a potential factor contributing to NK cell deficiency in JSLE.

Delivery of a national prenatal exome sequencing service in England: a mixed methods study exploring healthcare professionals' views and experiences.

Introduction: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during the first 2 years of its delivery in the NHS. Methods: A survey (n = 159) and semi-structured interviews (n = 63) with healthcare professionals, including clinical geneticists, FM specialists, and clinical scientists (interviews only) were used to address: 1) Views on the pES service; 2) Capacity and resources involved in offering pES; 3) Awareness, knowledge, and educational needs; and 4) Ambitions and goals for the future. Results: Overall, professionals were positive about the pES service with 77% rating it as Good or Excellent. A number of benefits were reported, including the increased opportunity for receiving actionable results for parental decision-making, improving equity of access to genomic tests and fostering close relationships between FM and genetics departments. Nonetheless, there was evidence that the shift to offering pES in a clinical setting had brought some challenges, such as additional clinic time, administrative processes, perceived lack of autonomy in decision-making regarding pES eligibility and difficulty engaging with peripheral maternity units. Concerns were also raised about the lack of confidence and gaps in genomics knowledge amongst non-genetics professionals - especially midwives. However, the findings also highlighted value in both FM, obstetric and genetics professionals benefiting from further training with a focus on recognising and managing prenatally diagnosed genetic conditions. Conclusion: Healthcare professionals are enthusiastic about the benefits of pES, and through multi-collaborative working, have developed relationships that have contributed to effective communication across specialisms. Although limitations on resources and variation in knowledge about pES have impacted service delivery, professionals were hopeful that improvements to infrastructure and the upskilling of all professionals involved in the pathway would optimise the benefits of pES for both parents and professionals.

Self-perceived disease activity was the strongest predictor of COVID-19 pandemic-related concerns in young people with autoimmune rheumatic diseases, irrespective of their gender, with females reporting higher concerns.

Objectives: We report the results of a pilot young patient survey that targeted patients with JSLE and JDM, exploring well-being, resilience and general concern about the coronavirus disease 2019 (COVID-19) pandemic as well as self-assessment of disease activity. Methods: The survey was completed anonymously by patients who had been approached via the automatically generated hospital database between June and December 2020. In addition to disease characteristics, geographic location, education and employment level, we explored young patients' resilience, mood and feelings, mental well-being, self-assessed disease activity and general COVID-19 concerns using validated tools and visual analogue scales. Results: This pilot study found that self-perceived disease activity was the strongest predictor of COVID-19 concern, irrespective of gender, employment and education status or well-being and resilience. Generalized concerns regarding the COVID-19 pandemic were significantly higher in females, although their self-reported DASs were comparable to male respondents. Conclusion: Our findings highlight a gender bias in the generalized concern related to the COVID-19 pandemic, irrespective of the examined potential confounders. This suggests the need for further research around young patient self-reported outcomes outside hospital visits, especially in the context of gender differences and potential challenges of future pandemics.

Marital Status and Gender Differences as Key Determinants of COVID-19 Impact on Wellbeing, Job Satisfaction and Resilience in Health Care Workers and Staff Working in Academia in the UK During the First Wave of the Pandemic.

Background: The COVID-19 pandemic is an unprecedented global public health crisis that continues to exert immense pressure on healthcare and related professional staff and services. The impact on staff wellbeing is likely to be influenced by a combination of modifiable and non-modifiable factors. Objectives: The aim of this study is to evaluate the effect of the COVID-19 pandemic on the self-reported wellbeing, resilience, and job satisfaction of National Health Service (NHS) and university staff working in the field of healthcare and medical research. Methods: We conducted a cross sectional survey of NHS and UK university staff throughout the COVID-19 pandemic between May-November 2020. The anonymous and voluntary survey was disseminated through social media platforms, and via e-mail to members of professional and medical bodies. The data was analyzed using descriptive and regression (R) statistics. Results: The enjoyment of work and satisfaction outside of work was significantly negatively impacted by the COVID-19 pandemic for all of staff groups independent of other variables. Furthermore, married women reporting significantly lower wellbeing than married men (P = 0.028). Additionally, the wellbeing of single females was significantly lower than both married women and men (P = 0.017 and P < 0.0001, respectively). Gender differences were also found in satisfaction outside of work, with women reporting higher satisfaction than men before the COVID-19 pandemic (P = 0.0002). Conclusion: Our study confirms that the enjoyment of work and general satisfaction of staff members has been significantly affected by the first wave of the COVID-19 pandemic. Interestingly, being married appears to be a protective factor for wellbeing and resilience but the effect may be reversed for life satisfaction outside work. Our survey highlights the critical need for further research to examine gender differences using a wider range of methods.

Corrigendum: Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.

This corrects the article DOI: 10.1038/ncomms11208.

Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.

The production of megakaryocytes (MKs)--the precursors of blood platelets--from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.

A vascular physician's view of venous thromboembolism and apixaban.

Alexander Cohen speaks to Wing Han Wu, Commissioning Editor: Dr Cohen is a vascular physician and epidemiologist involved in clinical work, designing, managing and analyzing clinical trials from Phase I to IV. He is the Chairman and member of many international steering committees for multicenter trials, and epidemiological and pharmaco-economic studies. Dr Cohen graduated with honors in Medicine and Surgery from the University of Melbourne, Australia (MBBS). He achieved his fellow of the Royal Australasian College of Physicians (FRACP) in 1990, and received an MSc in Epidemiology in 1991 from the University of London. His MSc thesis in 1991 was on the Metabolic Syndrome in South Asia. In 1998, he achieved MD with a thesis on Epidemiology of VTE and Thromboprophylaxis. He has written or co-authored over 300 publications since 1990, including 40 publications in The Lancet and New England Journal of Medicine.