Bonbonnieres in the gallery: (re)presenting sugar in a family gallery space

This paper charts an on‐going process emerging from a collaborative project between Manchester Art Gallery, and early childhood researchers and practitioners, who are currently working together to develop a new learning space for families. It revolves around the potential of exhibiting a collection of bonbonnieres in this space. These little 18th Century pots, originally filled with sweets or breath mints, are colourful and depict fanciful animals that have an almost cartoon like quality that may resonate with younger children. Yet the contents that once lay inside would have been cut from plantations by the hands of enslaved people. Sugar, in all its sweetness, is intrinsically linked to Britain’s colonial history. Sections of a poem by Tina Otito Tamsho‐Thomas (http://revealinghistories.org.uk/smoking‐drinking‐and‐the‐british‐sweet‐tooth/objects/bonbonniere.html) are emplaced throughout to unambiguously contextualise the bonbonniere as a symbol of enslavement legacy, sugar trade history and British colonialism. Today, excess sugar consumption sits at the heart of the healthy eating agenda, a key priority area for local early years providers. In this paper, textual ‘fragments’ act as provocations in a series of interdisciplinary conversations that were initiated as a strategy to unsettle the positions of the institution and its curators, educators and practitioners, opening up discursive thinking about the potential of this particular object‐space ensemble. By considering these bonbonnieres as ‘vibrant matter’ (Bennett, 2010) that can affect and be affected within the gallery space (Tolia‐Kelly, 2016) we ask questions about how these objects might sit alongside the daily interactions that occur in the space in a way that opens up ‘discomfort zones’

Complete and incomplete spin transitions in 1D chain iron(II) compounds.

The synthesis and characterisation of two new octahedral iron(II) SCO coordination polymers [FeL1(bimm)] (1) and [FeL2(bppa)](MeOH)0.5 (2) (L1 = [3,30]-[1,2- phenylenebis-(iminomethylidyne)bis(4-phenyl-,4-butanedionato)(2-)-N,N0,O2,O20], L2 = [E,E]-[{diethyl 2,20-1,2- phenylenebis(iminomethylidyne)bis(3-oxo-3-phenylpropanato)}(2-)-N,N0,O3,O30], bimm = bis(1H-imidazol-1-yl)methane and bppa = 1,3-bis(pyridine-4-yl)propane) is presented. Results from X-ray structure analysis at different temperatures revealed in the case of 1 that the transition from a gradual to a cooperative SCO with a 5 K wide hysteresis is due to an increase of the short intermolecular contacts, which exceed a certain threshold for the cooperative effect. In the case of compound 2 an incomplete spin transition with a 4 K wide hysteresis was observed. The low temperature wMT product remains constant at a value typical for a mixed HS/LS state in stepwise spin transitions. A quantitative correlation between the cooperative effects of 12 monomer and polymer iron(II) SCO complexes and their structural properties derived from X-ray structure analysis, the so-called crystal contact index, CCI, is introduced

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Folding Froebel with Deleuze: rethinking the significance of imitation in early childhood

The paper brings Froebel’s philosophy into conversation with that of Deleuze. We focus on the fold and on self-activity as key concepts that hold a special place in the monist philosophies of both thinkers. One point at which their (very different) ontologies coincide is their conceptualization of a cosmos in which everything is ultimately in relation. The philosophical convergences of such different thinkers in different eras are mapped in relation to the influences of a shared lineage with some earlier hermetic and romantic strains of thought. Both Froebel and Deleuze conceive of subjectivity as a relation of dynamic folding and unfolding of inner life and external world. The fold, as the operation that brings outside and inside together in a unitary system, counters the dualisms that still tend to structure thought: for instance, ideal/material, intelligible/sensible, nature/culture, individual/social. Reading Deleuze with Froebel helps to draw out some theoretical underpinnings of Froebel’s holism, by bringing movement, matter and the senses back into focus and rethinking the relation between children and their environment in learning and development. We discuss some empirical examples of what this might look like from a current research project, focusing on imitation as one example of the fold between the inner life and the outer worlds of young children. In particular, we are interested in exploring how Froebel’s conception of imitation as a dynamic and metamorphic act of self-transformation might share some affinities with the concept of becoming developed by Deleuze and Guattari

Seeking space for entanglements with young children in immanent material relationality

This paper explores haptic, affective, sensory and relational interconnections between a child (Erik) and objects, materials and a researcher-practitioner (Christina) at a nursery school in Manchester, United Kingdom (UK). In doing so, it draws upon a Post-humanist theoretical framework. Observational material was collected over the period of a school year. The discussion involves a diffractive three-way ‘thinking together’ conversation between the authors about what emerges as we attempt to listen to Erik’s voices. Improvisation in moments of physical sensation and action with objects, materials and Christina becomes a vehicle for tentative openings and immanent possibilities for all enfolded in the encounter. These are entangled, however, with national and international neoliberal expectations regarding literacy, numeracy and school readiness. We conclude that ‘dissenting from within’ is a necessary ethical practice if we are to offer something more optimistic for children’s becomings than acquiescence in the development of human economic capital

A Pedagogy of Suspensions: Infrathin Variations between London and Manchester

This paper takes as its catalyst a series of live art events that took place between London and Manchester in 2019. Thinking in conversation with Erin Manning’s propositions for “minor movements” and the Duchampian “infrathin”, we explore the potential for live art to temporarily suspend the thresholds of perceptibility and permissibility in the public realm. We argue that artful techniques of improvisation carry the potential to suspend capitalistic orderings of time by temporarily confounding the perceived barriers between art and life. Drawing together anarchival traces of improvised movement, sound, image, and thought, the paper is composed of vignettes that sketch the infrathin variations of a “pedagogy of suspensions” as elaborated through live art events in a public park, a moving train, a university gymnasium, and an anechoic sound chamber