Amplification of simian retroviral sequences from human recipients of baboon liver transplants

Investigations into the use of baboons as organ donors for human transplant recipients, a procedure called xenotransplantation, have raised the specter of transmitting baboon viruses to humans and possibly establishing new human infectious diseases. Retrospective analysis of tissues from two human transplant recipients with end-stage hepatic disease who died 70 and 27 days after the transplantation of baboon livers revealed the presence of two simian retroviruses of baboon origin, simian foamy virus (SFV) and baboon endogenous virus (BaEV), in multiple tissue compartments. The presence of baboon mitochondrial DNA was also detected in these same tissues, suggesting that xenogeneic 'passenger leukocytes' harboring latent or active viral infections had migrated from the xenografts to distant sites within the human recipients. The persistence of SFV and BaEV in human recipients throughout the posttransplant period underscores the potential infectious risks associated with xenotransplantation

A qualitative evaluation of the impact of a palliative care course on preregistration nursing students' practice in Cameroon

Background Current evidence suggests that palliative care education can improve preregistration nursing students’ competencies in palliative care. However, it is not known whether these competencies are translated into students’ practice in the care of patients who are approaching the end of life. This paper seeks to contribute to the palliative care evidence base by examining how nursing students in receipt of education report transfer of learning to practice, and what the barriers and facilitators may be, in a resource-poor country. Methods We utilised focus groups and individual critical incident interviews to explore nursing students’ palliative care learning transfer. Three focus groups, consisting of 23 participants and 10 individual critical incident interviews were conducted with preregistration nursing student who had attended a palliative care course in Cameroon and had experience caring for a patient approaching the end of life. Data was analysed thematically, using the framework approach. Results The results suggest that nursing students in receipt of palliative care education can transfer their learning to practice. Students reported recognizing patients with palliative care needs, providing patients with physical, psychosocial and spiritual support and communicating patient information to the wider care team. They did however perceive some barriers to this transfer which were either related to themselves, qualified nurses, the practice setting or family caregivers and patients. Conclusion The findings from this study suggest that nursing student in receipt of palliative care education can use their learning in practice to provide care to patients and their families approaching the end of life. Nevertheless, these findings need to be treated with some caution given the self-reported nature of the data. Demonstrating the link between preregistration palliative care education and patient care is vital to ensuring that newly acquired knowledge and skills are translated and embedded into clinical practice. This study also has implications for advocating for palliative care policies and adequately preparing clinical placement sites for students’ learning and transfer of learning

Multifactorial falls prevention programme compared with usual care in UK care homes for older people: Multicentre cluster randomised controlled trial with economic evaluation

Objectives: To determine the clinical and cost effectiveness of a multifactorial fall prevention programme compared with usual care in long term care homes. Design: Multicentre, parallel, cluster randomised controlled trial. Setting: Long term care homes in the UK, registered to care for older people or those with dementia. Participants: 1657 consenting residents and 84 care homes. 39 were randomised to the intervention group and 45 were randomised to usual care. Interventions: Guide to Action for Care Homes (GtACH): a multifactorial fall prevention programme or usual care. Main outcome measures: Primary outcome measure was fall rate at 91-180 days after randomisation. The economic evaluation measured health related quality of life using quality adjusted life years (QALYs) derived from the five domain five level version of the EuroQoL index (EQ-5D-5L) or proxy version (EQ-5D-5L-P) and the Dementia Quality of Life utility measure (DEMQOL-U), which were self-completed by competent residents and by a care home staff member proxy (DEMQOL-P-U) for all residents (in case the ability to complete changed during the study) until 12 months after randomisation. Secondary outcome measures were falls at 1-90, 181-270, and 271-360 days after randomisation, Barthel index score, and the Physical Activity Measure-Residential Care Homes (PAM-RC) score at 91, 180, 270, and 360 days after randomisation. Results: Mean age of residents was 85 years. 32% were men. GtACH training was delivered to 1051/1480 staff (71%). Primary outcome data were available for 630 participants in the GtACH group and 712 in the usual care group. The unadjusted incidence rate ratio for falls between 91 and 180 days was 0.57 (95% confidence interval 0.45 to 0.71, P<0.001) in favour of the GtACH programme (GtACH: six falls/1000 residents v usual care: 10 falls/1000). Barthel activities of daily living indices and PAM-RC scores were similar between groups at all time points. The incremental cost was £108 (95% confidence interval −£271.06 to 487.58), incremental QALYs gained for EQ-5D-5L-P was 0.024 (95% confidence interval 0.004 to 0.044) and for DEMQOL-P-U was 0.005 (−0.019 to 0.03). The incremental costs per EQ-5D-5L-P and DEMQOL-P-U based QALY were £4544 and £20 889, respectively. Conclusions: The GtACH programme was associated with a reduction in fall rate and cost effectiveness, without a decrease in activity or increase in dependency. Trial registration: ISRCTN34353836

A multidomain decision support tool to prevent falls in older people: the FinCH cluster RCT

BackgroundFalls in care home residents are common, unpleasant, costly and difficult to prevent.ObjectivesThe objectives were to evaluate the clinical effectiveness and cost-effectiveness of the Guide to Action for falls prevention in Care Homes (GtACH) programme.DesignA multicentre, cluster, parallel, 1 : 1 randomised controlled trial with embedded process evaluation and economic evaluation. Care homes were randomised on a 1 : 1 basis to the GtACH programme or usual care using a secure web-based randomisation service. Research assistants, participating residents and staff informants were blind to allocation at recruitment; research assistants were blind to allocation at follow-up. NHS Digital data were extracted blindly.SettingOlder people’s care homes from 10 UK sites.ParticipantsOlder care home residents.InterventionThe GtACH programme, which includes care home staff training, systematic use of a multidomain decision support tool and implementation of falls prevention actions, compared to usual falls prevention care.OutcomesThe primary trial outcome was the rate of falls per participating resident occurring during the 90-day period between 91 and 180 days post randomisation. The primary outcome for the cost-effectiveness analysis was the cost per fall averted, and the primary outcome for the cost–utility analysis was the incremental cost per quality adjusted life-year. Secondary outcomes included the rate of falls over days 0–90 and 181–360 post randomisation, activity levels, dependency and fractures. The number of falls per resident was compared between arms using a negative binomial regression model (generalised estimating equation).ResultsA total of 84 care homes were randomised: 39 to the GtACH arm and 45 to the control arm. A total of 1657 residents consented and provided baseline measures (mean age 85 years, 32% men). GtACH programme training was delivered to 1051 staff (71% of eligible staff) over 146 group sessions. Primary outcome data were available for 630 GtACH participants and 712 control participants. The primary outcome result showed an unadjusted incidence rate ratio of 0.57 (95% CI 0.45 to 0.71; p < 0.01) in favour of the GtACH programme. Falls rates were lower in the GtACH arm in the period 0–90 days. There were no other differences between arms in the secondary outcomes. Care home staff valued the training, systematic strategies and specialist peer support, but the incorporation of the GtACH programme documentation into routine care home practice was limited. No adverse events were recorded. The incremental cost was £20,889.42 per Dementia Specific Quality of Life-based quality-adjusted life-year and £4543.69 per quality-adjusted life-year based on the EuroQol-5 dimensions, five-level version. The mean number of falls was 1.889 (standard deviation 3.662) in the GtACH arm and 2.747 (standard deviation 7.414) in the control arm. Therefore, 0.858 falls were averted. The base-case incremental cost per fall averted was £190.62.ConclusionThe GtACH programme significantly reduced the falls rate in the study care homes without restricting residents’ activity levels or increasing their dependency, and was cost-effective at current thresholds in the NHS.Future workFuture work should include a broad implementation programme, focusing on scale and sustainability of the GtACH programme.LimitationsA key limitation was the fact that care home staff were not blinded, although risk was small because of the UK statutory requirement to record falls in care homes.Trial registrationThis trial is registered as ISRCTN34353836.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 9. See the NIHR Journals Library website for further project information

Infectious Fear: The Rhetoric of Pestilence in Middle English Didactic Texts on Death

This article examines literary references to bubonic plague in a sample of late fourteenth- and fifteenth-century English texts that are didactic in tone and address the theme of death, including Geoffrey Chaucer’s “The Pardoner’s Tale”, John Lydgate’s “Danse Macabre” and the anonymous The Castle of Perseverance and “A Disputation between the Body and Worms”. Although there have been broad surveys of bubonic plague in Middle English literature, as well as studies of isolated texts, this article is the first to examine the role of pestilence in a group of texts linked by theme and authorial intention. It contributes to current understanding of the disease in late medieval literature and culture, showing how authors utilised the idea of pestilence as a frightening cause of sudden death and as a form of rhetoric serving to encourage readers to reflect on mortality, the spiritual health of the soul and the prospect of salvation. Whereas previous research has shown that doctors, priests and writers interpreted the pestilence as a divine punishment for sin, this study demonstrates how that belief could be exploited for rhetorical purposes. The rhetoric of pestilence emerges as a powerful contemplative tool urging readers to practise self-examination, penitence and a more active, strategic approach to death

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Demographic, clinical, and service-use characteristics related to the clinician’s recommendation to transition from child to adult mental health services

Purpose: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians’ advice to continue treatment at AMHS. Methods: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians’ transition recommendations. Results: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. Conclusion: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services

Electrochemical detection of faraday waves on the surface of a gas bubble

The oscillation of a gas bubble driven by an acoustic field has been investigated using an electrochemical sensing technique. A low-resolution scanning electrochemical microscopy technique, employing an L-shaped microelectrode, has been employed to address the equator of a tethered bubble. Real-time mass transfer enhancements as the result of bubble wall motion have been detected using the electrochemical reduction of Fe(CN)(6)(3-). A comparison of the pressure threshold measurements of the onset of surface oscillations with a theoretical model is presented. Photographic evidence of the presence and shape distortions of the bubble surface is also demonstrated