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Human prion diseases, including Creutzfeldt-Jakob disease (CJD), are rapidly progressive, invariably fatal neurodegenerative conditions with no effective therapies. Their pathogenesis involves the obligate recruitment of cellular prion protein (PrPWe generated a fully humanised anti-PrPWe treated six patients (two men; four women) with CJD for 7-260 days at UCLH between Oct 9, 2018, and July 31, 2019. Repeated intravenous dosing of PRN100 was well tolerated and reached the target CSF drug concentration (50 nM) in four patients after 22-70 days; no clinically significant adverse reactions were seen. All patients showed progressive neurological decline on serial assessments with the MRC Scales. Neuropathological examination was done in two patients (patients 2 and 3) and showed no evidence of cytotoxicity. Patient 2, who was treated for 140 days, had the longest clinical duration we have yet documented for iatrogenic CJD and showed patterns of disease-associated PrP that differed from untreated patients with CJD, consistent with drug effects. Patient 3, who had sporadic CJD and only received one therapeutic dose of 80 mg/kg, had weak PrP synaptic labelling in the periventricular regions, which was not a feature of untreated patients with sporadic CJD. Brain tissue-bound drug concentrations across multiple regions in patient 2 ranged from 9·9 μg per g of tissue (SD 0·3) in the thalamus to 27·4 μg per g of tissue (1·5) in the basal ganglia (equivalent to 66-182 nM).Our academic-led programme delivered what is, to our knowledge, the first rationally designed experimental treatment for human prion disease to a small number of patients with CJD. The treatment appeared to be safe and reached encouraging CSF and brain tissue concentrations. These findings justify the need for formal efficacy trials in patients with CJD at the earliest possible clinical stages and as prophylaxis in those at risk of prion disease due to PRNP mutations or prion exposure.The Cure CJD Campaign, the National Institute for Health Research UCLH Biomedical Research Centre, the Jon Moulton Charitable Trust, and the UK MRC.

Social prescribing is a non-clinical approach to addressing social, environmental, and economic factors affecting how people feel physical and/or emotionally. It involves connecting people to “community assets” (e.g., local groups, organizations, and charities) that can contribute to positive well-being. We sought to explain in what ways, for whom, and why the cultural sector can support social prescribing with older people. We conducted semi-structured interviews with 28 older people (aged 60+) and 25 cultural sector staff. The following nine concepts, developed from interview data, progressed the understanding of tailoring cultural offers, which came from our previous realist review— immersion, buddying, café culture, capacity, emotional involvement, perseverance, autonomy, elitism, and virtual cultural offers. Through tailoring, we propose that older people might experience one or more of the following benefits from engaging with a cultural offer as part of social prescribing—being immersed, psychological holding, connecting, and transforming through self-growth.

Background Chlamydia trachomatis (chlamydia) is highly prevalent and is an important sexually transmitted infection as it can lead to increased risk of HIV seroconversion; and if left untreated, can cause infertility in women. Clinical guidelines recommend treating chlamydia presumptively when presenting symptomatically; however, clinicians are now questioning this due to increasing prevalence of antimicrobial resistance. Methods To determine the accuracy of presumptive chlamydia treatment practices at a walk-in sexual health service in regional Australia, we audited all same-day screen and treat presentations prescribed azithromycin over a 6-month period in 2018. Results A total of 325 cases were included in the analysis. Over half (54%) the presentations returned negative pathology for all pathogens investigated. One quarter (25%) of presentations were positive for chlamydia, and (4%) reported a dual infection. A further one fifth (20%) were negative for chlamydia but positive for another pathogen. More symptomatic males than females returned positive pathology for chlamydia (8% vs 4%). Conclusions While presumptive treatment is recommended in the current guidelines, our findings indicate this resulted in over-treatment. Considering the increasing resistance patterns for Mycoplasma genitalium, which include azithromycin, presumptive treatments need to balance immediate client care needs against long-term community antimicrobial resistance outcomes. This internal audit provided a feedback mechanism to the walk-in sexual service, enabling modification of practices to provide more precise, individual clinical care within the bounds of current STI guidelines, while balancing wider the objectives of antimicrobial stewardship.

Older people’s well-being can be bolstered by engaging with cultural activities and venues. They may be encouraged to try cultural offers by a link worker as part of social prescribing. However, the cultural sector, like all parts of life, was affected by the COVID-19 pandemic; this has had implications for cultural offers available to link workers. A study was conducted to explore the views and experiences of link workers in using the cultural sector within social prescribing, particularly for older people (aged 60+) during the pandemic. An online questionnaire was distributed to and completed by link workers in the UK. Data were analysed mainly using descriptive statistics. Open text responses were clustered into similar ideas to create key concepts. Useable responses were received from 148 link workers. They highlighted a general lack of interaction between link workers and the cultural sector about how the latter could support social prescribing. Results suggested that personal familiarity with cultural offers might prompt link workers to refer to them. Some respondents proposed that cultural offers were regarded as elitist, which deterred them from referring there. However, there was a general acknowledgement that the cultural sector could contribute to social prescribing. Link workers need to regard the cultural sector as accessible, appropriate, adequate, affordable and available before referring older people to cultural offers as part of social prescribing. Link workers may benefit from becoming more familiar with cultural sector staff and offers, including online resources, so they can then propose them to patients with confidence.

The Louth Contemporary Music Society festival, based in Dundalk, only six miles from the border with Northern Ireland, is now an established presence on the contemporary music scene. Thanks to its founder, Eamonn Quinn, it attracts both local musicians and major international figures and also issues CDs. This year, the programme featured a strong Irish connection and a lot of music that is quiet, meditative and minimal. Music for guitar formed another theme, with new work by the Norwegian guitarist/composer Fredrik Rasten and the Cuban Leo Brouwer.

Background Chlamydia trachomatis (chlamydia) is highly prevalent and is an important sexually transmitted infection as it can lead to increased risk of HIV seroconversion; and if left untreated, can cause infertility in women. Clinical guidelines recommend treating chlamydia presumptively when presenting symptomatically; however, clinicians are now questioning this due to increasing prevalence of antimicrobial resistance. Methods To determine the accuracy of presumptive chlamydia treatment practices at a walk-in sexual health service in regional Australia, we audited all same-day screen and treat presentations prescribed azithromycin over a 6-month period in 2018. Results A total of 325 cases were included in the analysis. Over half (54%) the presentations returned negative pathology for all pathogens investigated. One quarter (25%) of presentations were positive for chlamydia, and (4%) reported a dual infection. A further one fifth (20%) were negative for chlamydia but positive for another pathogen. More symptomatic males than females returned positive pathology for chlamydia (8% vs 4%). Conclusions While presumptive treatment is recommended in the current guidelines, our findings indicate this resulted in over-treatment. Considering the increasing resistance patterns for Mycoplasma genitalium, which include azithromycin, presumptive treatments need to balance immediate client care needs against long-term community antimicrobial resistance outcomes. This internal audit provided a feedback mechanism to the walk-in sexual service, enabling modification of practices to provide more precise, individual clinical care within the bounds of current STI guidelines, while balancing wider the objectives of antimicrobial stewardship.

Teaching Stravinsky: Nadia Boulanger and the Consecration of a Modernist Icon , by Kimberly A. Francis. New York: Oxford University Press, 2015. xxiii, 266 pp. The teasingly ambiguous title of Kimberly Francis's book gives us some clues as to the part played by Nadia Boulanger in Stravinsky's career. Boulanger was a champion of Stravinsky's music, both as the teacher of her own students and in what would now be termed public engagement, and she taught his younger son Soulima from 1929. But Francis also makes the bolder claim that “For all intents and purposes, [Boulanger] taught [Igor Stravinsky] how to view his own music; her analysis opened his eyes to his work. She helped him articulate his voice and the mechanisms underlying his ‘technique.’ She also taught him about presentation, the direct relationship between the score's appearance and its legacy” (p. 248). While Robert Craft considered Boulanger simply to be “a prodigious proof-reader” (quoted p. 9), Francis instead provides “a feminist account of Boulanger's professional interactions with Stravinsky, his family, and his music” (p. 9). She follows Suzanne Cusick and others in her wish to shed light on “woman's work and the culturally feminine so that they cease to be marginalized and devalued, but might be re-interpreted as important elements of musical culture” (quoted p. 9). Francis chooses to view the Boulanger-Stravinsky relationship through the lens of Pierre Bourdieu's theory, referencing particularly the concepts of cultural capital, consecration, and agency. Yet the theoretical framework is handled with a light touch after the introduction: Boulanger's …

The spiritual dimension of music was a prime concern of composers in the post-Second World War period. The group Jeune France had already emphasized the importance of the aspect of music in the mid-1930s, primarily in reaction against the frivolity of much French music of the 1920s. It is true that Bizet's musical orientalism – essentially the use of gapped scales and ostinato figures – can have no counterpart in the post-war musical universe, not least because these musical devices were absorbed into the musical language of French composers in the late nineteenth and early twentieth centuries. Many composers opted for continuity, while some of the younger generation briefly adopted a musical language which both radically broke with traditional rhetoric and eliminated all traces of personal style and expression. Frequently, composers use a pivot note as the focus of an ornamental melodic line which could be compared to a Debussian arabesque in its shape and its rhythmic plasticity.

Erik Satie's (1866-1925) music appeals to wide audiences and has influenced both experimental artists and pop musicians. Little about Satie was conventional, and he resists classification under easy headings such as 'classical music'. Instead of pursuing the path of a professional composer, Satie initially earned a living as a caf� pianist and moved in bohemian circles which prized satire, popularculture and experiment. Small wonder that his music is fundamentally new in conception. It is music which is not always designed to be listened to attentively: music which can be machine-like but isto be played by humans. For Satie, music was part of a wider concept of artistic creation, as evidenced by his collaborations with leading avant-garde artists and in works which cross traditional genre boundaries such as his texted piano pieces. His music was created in some of the most exciting and creatively stimulating environments of the late nineteenth and early twentieth century: Montmartreand Montparnasse. Paris was the artistic centre of Europe, and Satie was a notorious figure whose music and ideas are inextricably linked with the City of Light. This book situates Satie's work withinthe context and sonic environment of contemporary Paris. It shows that the influence of street music, musicians and poets interested in new technology, contemporary innovations and radical politics are all crucial to an understanding of Satie. Music from the ever-popular Gymnopédies to newly discovered works are discussed, and an online supplement features rare pieces recorded especially for the book. CAROLINE POTTER is Reader in Music at Kingston University London. A graduate in both French and Music, she has published widely on French music since Debussy and was Series Advisor to the Philharmonia Orchestra's Paris 2014-15 season.

In her all too brief career, Lili Boulanger (1893–1918) composed a number of works for which there is proof they existed but which have now disappeared. One of these missing pieces, Marche gaie , resurfaced in 2011 in a private collection in North Carolina; the owners of the manuscript are the grandchildren of the work’s dedicatee. As Marche gaie was registered with SACEM as a work for chamber orchestra in 1916, we can assume the work was composed in that year. While the manuscript is in an unknown hand, there is musical and circumstantial evidence which, combined with testimony from the family, provides compelling evidence that this is a missing work by Lili Boulanger. The piece is just under four minutes in duration and has been arranged for piano from the short-score manuscript by the author of this article. The article explores the background of the work’s dedicatee, Jeanne Leygues, focusing on her family’s artistic and political connections. Her marriage to an American who fought in the French Foreign Legion in World War I explains why the score of Marche gaie was discovered in North Carolina. The work’s position in Lili Boulanger’s output is considered; it shows the influences of Faure and Chabrier, and is stylistically linked to other short occasional pieces composed by her. A musical quotation (Boulanger was fond of quotation and allusion in her works) shows that the piece must have been composed as a wedding present.

Henri Dutilleux's manuscripts, most of which are now owned by the Paul Sacher Stiftung, are wonderful examples of calligraphy. The care Dutilleux takes with his manuscripts means that little information about his working methods can be gleaned from his final drafts. However, there is one notable exception to this general statement: Dutilleux often rewrites the final bars of his works, and even his most recent manuscripts show that he still finds endings tricky. This paper, based on my study in 2009–2010 of the Dutilleux collection at the Paul Sacher Stiftung, focuses on three questions. Why does Dutilleux find endings difficult? Why did he choose to revise the final bars of several works, and what difference do these revisions make? What are the successful strategies Dutilleux has employed for ending a work? I focus on the conclusions to the Second Symphony and two recent works, Sur le meme accord—Nocturne and Correspondances.

Summary Aims This paper reports a critical review of the literature examining burnout among nurses and physicians working in emergency departments. The objective was to draw together a diverse collection of literature to undertake an in-depth analyse of the issues raised by the review question. Background Burnout among nurses and physicians working in emergency departments has only been brought to the attention of researchers recently. It is thought that the highly stressful environment and unpredictable nature of the work puts nurses and physicians at risk of burnout. Method A literature review was undertaken using the electronic databases CINAHL and MEDLINE, Royal College of Nursing and British Medical Journal websites. The papers retrieved used quantitative and qualitative approaches and were scrutinised for relevance. Twelve articles met the inclusion criteria and corresponded to the aim of this review. Conclusion The findings of the review reinforce concerns about the adverse effects of burnout among nurses and physicians working in emergency departments. Future research in this field is recommended, particularly around the naturalistic paradigm, to gain a deeper insight into the lived experiences of emergency department nurses and physicians.