Page and stage: translation and transformation for Gil Vicente's new audience.

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Inside mentoring relationships : influences and impacts on mentorship learning for acute care nurses in the NHS

Supervised practice as a mentor is an integral component of professionally-accredited\ud nurse mentor education. However, the literature tends to focus on the mentor-student\ud relationship rather than the relationships facilitating mentors' workplace learning. This\ud thesis begins to redress this gap in the literature by asking the research question:\ud Which relationships are important in developing nurses as mentors in practice, and\ud how is their mentorship impacted by professional, organisational and political\ud agendas in NHS settings?\ud A qualitative case study of two NHS Trusts was undertaken with three modes of data\ud collection utilised. Firstly, semi-structured interviews were undertaken with three recently\ud qualified mentors, and those they identified as significant in their own learning to become\ud a mentor. In total six mentors were interviewed. Interviews with nurses in senior NHS\ud Trust-based educational roles, and senior policy-making and education figures augmented\ud these initial interviews. Secondly professional mentorship standards were mapped across\ud each of the mentors' interviews to gain an idea of their penetration into practice. Finally,\ud each interview participant developed a developmental mentorship constellation which\ud identified colleagues significant to their own development as a mentor or educator, and\ud the attributes which enabled this.\ud The findings reveal complex learning relationships and situational factors affecting mentor\ud development and ongoing practice. They suggest that dyadic forms of supervisory\ud mentorship may not offer the range of skills and attributes that developing mentors\ud require. Mentor network type, orientation to learning, learning strategies and\ud organisational focus emerge as the foci of tensions in learning to be a mentor. The study\ud recommends that nursing teams in acute areas further develop a shared culture of learning\ud and development in providing multiple opportunities for supporting developing mentors

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Writing groups in the digital age: a case study analysis of Shut Up & Write Tuesdays

Social media writing groups are an emerging phenomenon in the academic world. Combining the discipline, mentorship, and peer support of face-to-face writing groups, with the convenience, global reach, and interdisciplinary networks of social media, they offer a way for scholars to apply new digital technologies to the old problem of developing, maintaining, and protecting an academic writing practice. Despite their growing popularity, however, there has been little critical or empirical analysis of these groups. Using Shut Up & Write Tuesdays (SUWT) as a case study, this chapter examines the purpose, use, outcomes, and challenges of a social media writing group for academics. Usage data from the three SUWT Twitter accounts, a survey of SUWT participants, and the narrative reflections of the SUWT hosts, are drawn together to highlight the value, strengths, and limitations of social media writing groups as a scholarly activity in the digital age

Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier.

BackgroundThe proteasome plays a vital role in the physiology of glioblastoma (GBM), and proteasome inhibition can be used as a strategy for treating GBM. Marizomib is a second-generation, irreversible proteasome inhibitor with a more lipophilic structure that suggests the potential for penetrating the blood-brain barrier. While bortezomib and carfilzomib, the 2 proteasome inhibitors approved for treatment of multiple myeloma, have little activity against malignant gliomas in vivo, marizomib could be a novel therapeutic strategy for primary brain tumors.MethodsThe in-vitro antitumor activity of marizomib was studied in glioma cell lines U-251 and D-54. The ability of marizomib to cross the blood-brain barrier and regulate proteasome activities was evaluated in cynomolgus monkeys and rats. The antitumor effect of marizomib in vivo was tested in an orthotopic xenograft model of human GBM.ResultsMarizomib inhibited the proteasome activity, proliferation, and invasion of glioma cells. Meanwhile, free radical production and apoptosis induced by marizomib could be blocked by antioxidant N-acetyl cysteine. In animal studies, marizomib distributed into the brain at 30% of blood levels in rats and significantly inhibited (>30%) baseline chymotrypsin-like proteasome activity in brain tissue of monkeys. Encouragingly, the immunocompromised mice, intracranially implanted with glioma xenografts, survived significantly longer than the control animals (P < .05) when treated with marizomib.ConclusionsThese preclinical studies demonstrated that marizomib can cross the blood-brain barrier and inhibit proteasome activity in rodent and nonhuman primate brain and elicit a significant antitumor effect in a rodent intracranial model of malignant glioma

Extracorporeal Membrane Oxygenation in Pregnant and Postpartum Women:A Systematic Review and Meta-Regression Analysis

Background: Although extracorporeal membrane oxygenation (ECMO) is frequently utilized as a salvage therapy for patients with cardiopulmonary failure, outcomes of its use in peripartum patients have not been clearly established. We aimed to review peer-reviewed publications on the use of ECMO in pregnant and postpartum patients, with analyses of maternal and fetal outcomes. Methods: Data were retrieved from MEDLINE, EMBASE, and Scopus databases from 1972 up to November 2017 for publications on ECMO in peripartum patients. Search terms included "ECMO," "ECLS,", "pregnancy," "postpartum," and "peripartum." Publications with 3 or more patients were reviewed for quality using the Joanna Briggs Institute checklist for prevalence studies and case series. Results: After reviewing 143 publications, 9 observational studies met our inclusion criteria. Pooled prevalence of maternal survival was 77.2% (95% confidence interval [CI]: 64.1%-88.4%). Pooled prevalence of fetal survival was 69.1% (95% CI: 44.7%-89.8%). The level of heterogeneity across studies was low for both outcomes. Meta-regression did not reveal any correlation between pregnant women with pulmonary or cardiac indications and maternal survival. Individual patient data meta-regression demonstrated higher odds of survival for patients on venovenous ECMO compared to those on venoarterial ECMO that was close to statistical significance (odds ratio = 3.016, 95% CI: 0.901-11.144; P = .081) after adjusting for pregnancy status. Conclusions: Extracorporeal membrane oxygenation can be considered as an acceptable salvage therapy for pregnant and postpartum patients with critical cardiac or pulmonary illness