Estimating the weight of ethnically diverse children attending an Australian emergency department: a prospective, blinded, comparison of age-based and length-based tools including Mercy, PAWPER and Broselow

Objective To prospectively compare the actual weights of Australian children in an ethnically diverse metropolitan setting with the predicted weights using the Paediatric Advanced Weight Prediction in the Emergency Room (PAWPER) tape, Broselow tape, Mercy system and calculated weights using the updated Advanced Paediatric Life Support (APLS), Luscombe and Owens and Best Guess formulae. Methods A prospective, cross-sectional, observational, blinded, convenience study conducted at the Children’s Hospital at Westmead Paediatric Emergency Department in Sydney, Australia. Comparisons were made using Bland-Altman plots, mean difference, limits of agreement and estimated weight within 10% and 20% of actual weight. Results 199 patients were enrolled in the study with a mean actual weight of 27.2 kg (SD 17.2). Length-based tools, with or without body habitus adjustment, performed better than age-based formulae. When measuring estimated weight within 10% of actual weight, PAWPER performed best with 73%, followed by Mercy (69%), PAWPER with no adjustment (62%), Broselow (60%), Best Guess (47%), Luscombe and Owens (41%) and revised APLS (40%). Mean difference was similar across all methods ranging from 0.4 kg (0.0, 0.9) for Mercy to −2.2 kg (−3.5, −0.9) for revised APLS. Limits of agreement were narrower for the lengthbased tools (−5.9, 6.8 Mercy; −8.3, 5.6 Broselow; −9.0, 7.1 PAWPER adjusted; −12.1, 9.2 PAWPER unadjusted) than the age-based formulae (−18.6, 17.4 Best Guess; −19.4, 15.1 revised APLS, −21.8, 17.7 Luscombe and Owens). Conclusion In an ethnically diverse population, lengthbased methods with or without body habitus modification are superior to age-based methods for predicting actual body weight. Body habitus modifications increase the accuracy and precision slightly

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA.See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275.</p

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways

UNLABELLED: Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma. SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275

"Looking all lost towards a Cook's guide for beauty”: the art of literature and the lessons of the guidebook in modernist writing

This article explores the impact of the guidebook, especially the Baedeker series, on modernist literary culture. It argues that the guidebook is a literary phenomenon in its own right and that, as such, it attracts special attention from those engaged in defending and/or extending the category of literature as part of a modernist agenda. In particular, modernist writers are concerned as to whether the guidebook counts as a form of literature and, if so, what this means for the more familiar forms seen in their own essays, fiction and travelogues. What might the invention of the star system to rank scenes and monuments mean for the future of art criticism? How might the guidebook help or hinder the traveller in his/her pursuit of the beautiful or the picturesque? What does recourse to the guidebook reveal about the taste and education of the traveller? And, more pointedly still, what kind and quality of writing is the guidebook itself? This article surveys the extent of modernism's interest in the guidebook, both as a noteworthy new form and as a form modernist writers adapted for use in their own books, before turning in detail to commentary on the guidebook by E.M. Forster, Ernest Hemingway, H.D. and Virginia Woolf. In conclusion, it finds that the guidebook in modernism is very rarely just that. Instead, the guidebook finds unexpected affinities with modernism in its attempt to “modernise” literature – to make it more rational, more totalising and, in the eyes of its critics, less able to discriminate.This is an Accepted Manuscript of an article published by Taylor & Francis in Studies in Travel Writing on 4th March 2015, available online: http://wwww.tandfonline.com/10.1080/13645145.2014.994924

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Wandering Pilgrimage: Mobile Expatriatism in Ernest Hemingway’s \u3cem\u3eThe Sun Also Rises\u3c/em\u3e, F. Scott Fitzgerald’s \u3cem\u3eTender is the Night\u3c/em\u3e and Claude McKay’s \u3cem\u3eBanjo\u3c/em\u3e

Comparison study of the spiritual ethics of the wandering pilgrim found in all three novels. Contesting Hemingway’s definition of The Sun Also Rises as tragedy, Peat positively characterizes the expatriate journey as an opportunity for the spiritual seeker to escape his deadening confines and gain a fresh perspective on the world

'A Word to Start an Argument with' : Virginia Woolf' s Crafts manship

This paper explores Virginia Woolf's 1937 radio broadcast (and later essay) 'Craftsmanship' in the context of craft culture. As Woolf considers the word judiciously and playfully throughout 'Craftsmanship', it becomes a nexus point for an entanglement of ideas around making, creating, and producing. This paper places Woolf's understanding of craft practices in the context of contemporary debates regarding the legacy of the arts and crafts movement, Roger Fry's work in the Omega Workshops, and her own experience in the Hogarth Press. While it is tempting to see the Hogarth Press as a model of craft culture, Woolf was sceptical about any nostalgia for craft practices, often rather sloppy with the craft of book making, and deeply ambivalent about any valorization of craft. Without dismissing the significant place of the Hogarth Press in discussions about craft culture, this paper is most interested in Woolf's repeated use of 'craft' to talk about the work of the writer. It explores Woolf's own ambivalent engagement with writing as 'craft' and questions what it might mean to see Woolf as a craftswoman. It pays attention to her suspicion of privileging 'well made' writing over imagination and emotion, her attitudes towards the professionalism of craft (particularly in the context of gender), as well as the often permeable boundaries between her 'craft' and her 'art'. For Woolf, the troublesome word 'craft' leads to, associates with, and intersects with concepts central to her life and work, including art, imagination, inspiration, production, process, amateurism, professionalism, education, skill, and vocation