Uptake of breast cancer preventive therapy in the UK: results from a multicentre prospective survey and qualitative interviews

Purpose: Uptake of preventive therapy for women at increased breast cancer risk in England is unknown following the introduction of UK clinical guidelines in 2013. Preventive therapy could create socioeconomic inequalities in cancer incidence if it is more readily accepted by particular socio-demographic groups. In this multicentre study, we investigated uptake of tamoxifen and evaluated socio-demographic and clinical factors associated with initiation. We explored women’s experiences of treatment decision-making using qualitative interview data. Methods: Between September 2015 and December 2016, women (n=732) attending an appointment at one of 20 centres in England to discuss breast cancer risk were approached to complete a survey containing socio-demographic details and nulliparity. Of the baseline survey respondents (n=408/732, 55.7% response rate), self-reported uptake of tamoxifen at 3-month follow-up was reported in 258 (63.2%). Sixteen women participated in semi-structured interviews. Results: One in seven (38/258=14.7%) women initiated tamoxifen. Women who had children were more likely to report use of tamoxifen than those without children (OR=5.26; 95%CI: 1.13–24.49, p=0.035). Interview data suggested that women weigh up risks and benefits of tamoxifen within the context of familial commitments, with exposure to significant other’s beliefs and experiences of cancer and medication a basis for their decision. Conclusions: Uptake of tamoxifen is low in clinical practice. There were no socio-demographic differences in uptake, suggesting that the introduction of breast cancer preventive therapy is unlikely to create socioeconomic inequalities in cancer incidence. Women’s decision-making was influenced by familial priorities, particularly having children

SlTPR1, a tomato tetratricopeptide repeat protein, interacts with the ethylene receptors NR and LeETR1, modulating ethylene and auxin responses and development

The gaseous hormone ethylene is perceived by a family of ethylene receptors which interact with the Raf-like kinase CTR1. SlTPR1 encodes a novel TPR (tetratricopeptide repeat) protein from tomato that interacts with the ethylene receptors NR and LeETR1 in yeast two-hybrid and in vitro protein interaction assays. SlTPR1 protein with a GFP fluorescent tag was localized in the plasmalemma and nuclear membrane in Arabidopsis, and SlTPR1-CFP and NR-YFP fusion proteins were co-localized in the plasmalemma and nuclear membrane following co-bombardment of onion cells. Overexpression of SlTPR1 in tomato resulted in ethylene-related pleiotropic effects including reduced stature, delayed and reduced production of inflorescences, abnormal and infertile flowers with degenerate styles and pollen, epinasty, reduced apical dominance, inhibition of abscission, altered leaf morphology, and parthenocarpic fruit. Similar phenotypes were seen in Arabidopsis overexpressing SlTPR1. SlTPR1 overexpression did not increase ethylene production but caused enhanced accumulation of mRNA from the ethylene responsive gene ChitB and the auxin-responsive gene SlSAUR1-like, and reduced expression of the auxin early responsive gene LeIAA9, which is known to be inhibited by ethylene and to be associated with parthenocarpy. Cuttings from the SlTPR1-overexpressors produced fewer adventitious roots and were less responsive to indole butyric acid. It is suggested that SlTPR1 overexpression enhances a subset of ethylene and auxin responses by interacting with specific ethylene receptors. SlTPR1 shares features with human TTC1, which interacts with heterotrimeric G-proteins and Ras, and competes with Raf-1 for Ras binding. Models for SlTPR1 action are proposed involving modulation of ethylene signalling or receptor levels

Cloning and characterization of tomato leaf senescence-related cDNAs

Senescence-related cDNA clones designated SENU1, 4, 5 (senescence up-regulated) and SEND32, 33, 34, 35 and 36 (senescence down-regulated) isolated from a tomato leaf cDNA library [9] were characterized. Southern analysis showed that SEND32 is encoded by a single-copy gene while SEND33, 34, 35, 36 and SENU1 and SENU5 are members of small gene families. DNA and protein database searches revealed that SEND32, SEND35, SENU1 and SENU5 are novel cDNAs of unknown function. SEND33 encodes ferredoxin, SEND34 encodes a photosystem II 10 kDa polypeptide and SEND36 encodes catalase. The SENU4 sequence is identical to the P6 tomato protein previously reported to be pathogenesis-related [46]. The mRNA levels of SENU1, 4 and 5 increased during leaf senescence and SENU1 and SENU5 were also expressed at high levels during leaf development and in other plant organs. The SENU4 mRNA was associated more specifically with leaf senescence, although low expression was also detected in green fruit. The mRNAs for all SEND clones decreased during tomato leaf development and senescence and all except SEND32 were expressed at low levels in other plant organs. The accumulation of mRNA homologous to SENU4 and the decrease in abundance of SEND32 provide good molecular markers for leaf senescence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43443/1/11103_2004_Article_125247.pd

Young children’s museum geographies; spatial, material and bodily ways of knowing

In this guest editorial we outline a new field of children’s museum geographies. We do this by opening up a space for the reader to engage with a collection of papers that trace embodiment, tacit and emplaced knowing, material entanglements and non-representational aspects of experience in accounts of children’s presence in museums. We hope that this special issue will act as an impetus for further working, thinking and collaborating, firstly by disrupting the conflation of children in museums with narrowing notions such as learning and talk, and secondly by highlighting the rich potential of museums as a space of interest for the field of children’s geographies

The Clinical Sustainability Assessment Tool: Measuring organizational capacity to promote sustainability in healthcare

BACKGROUND: Few validated assessment tools are available to increase understanding and measure factors associated with sustainment of clinical practices, an increasingly recognized need among clinicians. We describe the development of the Clinical Sustainability Assessment Tool (CSAT), designed to assess factors that contribute to sustainable practices in clinical settings. METHODS: Sixty-four participants from clinical and research fields participated in concept mapping and were recruited to brainstorm factors that lead to sustained clinical practices. Once repeated factors were removed, participants sorted items based on similarity and rated them by importance and feasibility. Using concept mapping analyses, items were grouped into meaningful domains to develop an initial tool. We then recruited pilot sites and early adopters, for a total of 286 practicing clinicians, to pilot and evaluate the tool. Individuals were recruited from clinical settings across pediatric and adult medical and surgical subspecialties. The data were analyzed using confirmatory factor analysis (CFA) to test hypothesized subscale structure in the instrument. We used root mean square error of approximation (RMSEA) and the standardized root mean square residual (SRMR) to assess fit and thus the ability of CSAT to measure the identified domains. RESULTS: The concept mapping produced sorted statements that were edited into items that could be responded to, resulting in the creation of a tool with seven determinant domains and 47 items. The pilot and CFA testing resulted in a final CSAT instrument made up 35 items, five per domain. CFA results demonstrated very good fit of the seven domain structure of the CSAT (RMSEA = 0.049; SRMR = 0.049). Usability testing indicated the CSAT is brief, easy to use, easy to learn, and does not require extensive training. Additionally, the measure scored highly (18/20) on the Psychometric and Pragmatic Evidence Rating Scale (PAPERS). The seven final CSAT domains were engaged staff and leadership, engaged stakeholders, organizational readiness, workflow integration, implementation and training, monitoring and evaluation, and outcomes and effectiveness. CONCLUSIONS: The CSAT is a new reliable assessment tool which allows for greater practical and scientific understanding of contextual factors that enable sustainable clinical practices over time

The Human Airway Epithelial Basal Cell Transcriptome

The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population.. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium

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’

Investigating genome wide dna methylation in airway and parenchymal fibroblasts from healthy individuals and individuals with copd

Rationale: Lung fibroblasts are implicated in respiratory disease pathology including chronic obstructive pulmonary disease (COPD). Phenotypic differences between fibroblasts isolated from the airway versus the parenchyma have been described but no studies have compared the cell types on a genome wide scale. DNA methylation is a reversible modification of the DNA structure with the ability to affect cell function via the alteration of gene expression. Here we compared genome wide DNA methylation profiles from airway and parenchymal fibroblasts and assessed modification to these profiles in cells isolated from individuals with COPD. Methods: DNA was isolated from parenchymal and airway fibroblasts at passage 4, and bisulphite treated. Site specific, quantitative genome wide methylation was determined using the Illumina 450K Infinium Methylation BeadChip array. Linear modelling and DMRcate functions identified differentially methylated sites and regions respectively between airway and parenchymal fibroblasts isolated from individuals with normal lung function versus those with COPD. Results: 3980 CpG (methylation) sites significantly differed after Bonferroni correction between airway and parenchymal fibroblasts isolated from healthy individuals. These sites had a broad distribution of effect size, with 240 CpG sites displaying a difference in methylation of >50%. 78 of these sites validated in a second cohort of 7 sets of paired airway and parenchymal fibroblasts isolated from the same individual. There was genomic proximity to these sites and DMRcate was used to refine the individual CpG sites to 5 regions of interest associated with 5 genes; HLX, TWIST1, CREB5, SKAP2 and PRDM16. Differences in methylation were less pronounced when comparing cells isolated from healthy individuals to those with COPD. In airway fibroblasts 47 DMRcate regions were identified with a maximum difference in methylation of at least 20%. In parenchymal fibroblasts 3 DMRcate regions were identified with a maximum difference in methylation of at least 20%. Conclusions: DNA methylation profiles are significantly different between airway and parenchymal fibroblasts but only small modifications are associated with COPD. Future work will focus on validating a methylation based markers of parenchymal versus airway fibroblasts and associating our differential observations with gene/protein expression