171 research outputs found

    Photography, Memory and Ekphrasis

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    Recollected Places: Photography, Memory and Ekphrasis The practice component of my PhD, ‘Recollected Places’, consists of exhibitions combining my work as an artist in still photography, video and installation and books that combine text and the photographic image. My written thesis, ‘Photography, Memory and Ekphrasis’ looks at a number of artworks from the 1950s to the present day which employ the photography-ekphrasis relationship. ‘Ekphrasis’ is the verbal description of visual works of art, for example, Homer's imaginary evocation of Achilles' shield in The Iliad. It became the object of intense academic scrutiny during the 1980s, as part of cultural theory’s emergent ‘visual turn’ and its attendant concentration upon image-text relations. The Iliad’s extended description of the shield, and the world of peace that it describes, are noticeably different from the ‘real’ events of the Trojan wars described throughout the rest of the poem. However, the ekphrastic scenes, whilst being distinctly different in tone, are arguably as ‘lifelike’ as the rest of the action described. So, from this very earliest recorded instance of ekphrasis, we can see how the mode opens up fundamental ontological questions about art and its place in the world that would be highlighted by conceptual art almost three millennia later. What holds more presence? The physical work itself, or the idea of the work? In a similar fashion, the invention of photography raised questions that were not methodically articulated until the 1980s. Thus a body of research from the early 1990s onwards has addressed the relationship between ekphrasis and photography. However, the vast majority focuses on ekphrastic writing about photography: ‘poems for photographs’, in James Heffernan’s phrase. The small extant literature that focuses on photography’s relationship to ekphrasis tends to emphasise the technical aspects of the medium. My research is both the first book-length study that I am aware of to examine ekphrasis’s relationship to photography and the first such study that I know of to be written by a practising visual artist. I consider recent writing on ekphrasis through the prism of various psychoanalytic theories, particularly those from recent debates on photography and melancholia. I examine the absence of the ‘lost object’ that is both the very condition for ekphrasis and melancholia and a precondition of all photographs: simultaneously trace of the object and reminder of its absence

    Whole family-based physical activity promotion intervention: the Families Reporting Every Step to Health pilot randomised controlled trial protocol

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    Introduction : Family-based physical activity (PA) interventions present a promising avenue to promote children’s activity, however, high-quality experimental research is lacking. This paper describes the protocol for the FRESH (Families Reporting Every Step to Health) pilot trial, a child-led family-based PA intervention delivered online.  Methods and analysis : FRESH is a three-armed, parallel-group, randomised controlled pilot trial using a 1:1:1 allocation ratio with follow-up assessments at 8- and 52-weeks post-baseline. Families will be eligible if a minimum of one child in school Years 3-6 (aged 7-11 years) and at least one adult responsible for that child are willing to participate. Family members can take part in the intervention irrespective of their participation in the accompanying evaluation and vice versa. Following baseline assessment, families will be randomly allocated to one of three arms: (1) FRESH, (2) pedometer-only, or (3) no-intervention control. All family members in the pedometer-only and FRESH arms receive pedometers and generic PA promotion information. FRESH families additionally receive access to the intervention website; allowing participants to select step challenges to ‘travel’ to target cities around the world, log steps, and track progress as they virtually globetrot. Control families will receive no treatment. All family members will be eligible to participate in the evaluation with two follow-ups (8 and 52 weeks). Physical (e.g., fitness, blood pressure), psychosocial (e.g., social support), and behavioural (e.g., objectively-measured family PA) measures will be collected each time point. At 8-week follow-up, a mixed-methods process evaluation will be conducted (questionnaires and family focus groups) assessing acceptability of the intervention and evaluation. FRESH families’ website engagement will also be explored.  Ethics and dissemination : This study received ethical approval from the Ethics Committee for the School of the Humanities and Social Sciences at the University of Cambridge. Findings will be disseminated via peer-reviewed publications, conferences, and to participating families

    CK1δ modulates the transcriptional activity of ERα via AIB1 in an estrogen-dependent manner and regulates ERα–AIB1 interactions

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    Oncogenesis in breast cancer often requires the overexpression of the nuclear receptor coactivator AIB1/SRC-3 acting in conjunction with estrogen receptor-α (ERα). Phosphorylation of both ERα and AIB1 has been shown to have profound effects on their functions. In addition, proteasome-mediated degradation plays a major role by regulating their stability and activity. CK1δ, a member of the ubiquitous casein kinase-1 family, is implicated in the progression of breast cancer. In this study, we show that both ERα and AIB1 are substrates for CK1δ in vitro, and identify a novel AIB1 phosphorylation site (S601) targeted by CK1δ, significant for the co-activator function of AIB1. CK1δ is able to interact with ERα and AIB1 in vivo, while overexpression of CK1δ in breast cancer cells results in an increased association of ERα with AIB1 as confirmed by co-immunoprecipitation assays from cell lysates. Using an siRNA-based approach, luciferase reporter assays and qRT-PCR, we observe that silencing of CK1δ leads to reduced ERα transcriptional activity, despite increased ERα levels, similarly to proteasome inhibition. We provide evidence that AIB1 protein levels are reduced by CK1δ silencing, in an estradiol-dependent manner; such destabilization can be inhibited by pre-treatment with the proteasome inhibitor MG132. We propose that differing activities adopted by ERα and AIB1 as a consequence of their interactions with and phosphorylation by CK1δ, particularly AIB1 stabilization, influence the transcriptional activity of ERα, and therefore have a role in breast cancer development

    A whole family-based physical activity promotion intervention: findings from the families reporting every step to health (FRESH) pilot randomised controlled trial

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    Funder: National Institute for Health Research Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme; Grant(s): IS-BRC-1215-20014Abstract: Introduction: This study assessed the feasibility and acceptability of FRESH (Families Reporting Every Step to Health), a theory-based child-led family physical activity (PA) intervention delivered online. We also assessed the preliminary effectiveness of the intervention on outcomes of interest and whether pre-specified criteria were met to progress to a full-scale definitive trial. Methods: In a three-armed randomised pilot trial, 41 families (with a 7–11-year-old index child) were allocated to a: ‘family’ (FAM), ‘pedometer-only’ (PED), or a no-treatment control (CON) arm. The FAM arm received access to the FRESH website, allowing participants to select step challenges to ‘travel’ to target cities around the world, log their steps, and track progress as families virtually globetrot. FAM and PED arms also received family sets of pedometers. All family members could participate in the evaluation. Physical (e.g., fitness, blood pressure), psychosocial (e.g., social support), behavioural (e.g., objectively-measured PA), and economic (e.g., expenditure for PA) data were collected at baseline, 8- and 52-weeks. Results: At 8- and 52-weeks, 98 and 88% of families were retained, respectively. Most children liked participating in the study (> 90%) and thought it was fun (> 80%). Compared to the PED (45%) and CON (39%) arms, a higher percentage of children in the FAM (81%) arm reported doing more activities with their family. Adults agreed that FRESH encouraged their family do more PA and made their family more aware of the amount of PA they do. No notable between-group differences were found for childrens’ minutes in moderate-to-vigorous PA. Sizeable changes of 9.4 (95%CI: 0.4, 18.4) and 15.3 (95%CI: 6.0, 24.5) minutes in moderate-to-vigorous PA was found for adults in the FAM group compared to those in the PED or CON groups, respectively. No other notable differences were found. Conclusion: This study demonstrates feasibility and acceptability of the FRESH intervention. All progression criteria were at least partially satisfied. However, we failed to recruit the target sample size and did not find a signal of effectiveness on PA particularly long-term or in children. Further refinements are required to progress to a full-scale trial. Trial registration: This study was prospectively registered (ISRCTN12789422) on 16/03/2016

    The Use of Preoperative Prophylactic Systemic Antibiotics for the Prevention of Endopthalmitis in Open Globe Injuries:A Meta-Analysis

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    Topic:This study reports the effect of systemic prophylactic antibiotics (and their route) on the risk of endophthalmitis after open globe injury. Clinical relevance:Endophthalmitis is a major complication of open globe injury, it can lead to rapid sight loss in the affected eye. The administration of systemic antibiotic prophylaxis is common practice in some health care systems, although there is no consensus on their use. PubMed, CENTRAL, Web of Science, CINAHL and Embase were searched. This was completed 6th July 2021 and updated 10th Dec 2022. We included randomised and non-randomised prospective studies which reported the rate of post-open globe injury endophthalmitis, when systemic pre-operative antibiotic prophylaxis (via the oral or intravenous route) was given. The Cochrane Risk of Bias tool and ROBINS-I tool were used for assessing the risk of bias. Where meta-analysis was performed results were reported as odds ratio. PROSPERO registration: CRD42021271271. Three studies were included. One prospective observational study compared outcomes of patients who had received systemic or no systemic pre-operative antibiotics. The endophthalmitis rates reported were 3.75% and 4.91% in the systemic and no systemic pre-operative antibiotics groups, a non-significant difference (p = 0.68). Two randomised controlled trials were included (1,555 patients). The rates of endophthalmitis were 17 events in 751 patients (2.26%) and 17 events in 804 patients (2.11%) in the oral antibiotics and intravenous (+/- oral) antibiotics groups, respectively. Meta-analysis demonstrated no significant differences between groups (OR 1.07 [95% confidence interval 0.54 – 2.12]). The incidences of endophthalmitis after open globe injury were low with and without systemic antibiotic prophylaxis, although high risk cases were excluded in the included studies. When antibiotic prophylaxis is considered, there is moderate evidence that oral antibiotic administration is non-inferior to intravenous

    The Risk of Sympathetic Ophthalmia Associated with Open-Globe Injury Management Strategies:A Meta-analysis

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    Topic: Sympathetic ophthalmia (SO) is a sight-threatening granulomatous panuveitis caused by a sensitizing event. Primary enucleation or primary evisceration, versus primary repair, as a risk management strategy after open-globe injury (OGI) remains controversial.Clinical Relevance: This systematic review was conducted to report the incidence of SO after primary repair compared with that of after primary enucleation or primary evisceration. This enabled the reporting of an estimated number needed to treat.Methods: Five journal databases were searched. This review was registered with International Prospective Register of Systematic Reviews (identifier, CRD42021262616). Searches were carried out on June 29, 2021, and were updated on December 10, 2022. Prospective or retrospective studies that reported outcomes (including SO or lack of SO) in a patient population who underwent either primary repair and primary enucleation or primary evisceration were included. A systematic review and meta-analysis were carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Random effects modelling was used to estimate pooled SO rates and absolute risk reduction (ARR).Results: Eight studies reporting SO as an outcome were included in total. The included studies contained 7500 patients and 7635 OGIs. In total, 7620 OGIs met the criteria for inclusion in this analysis; SO developed in 21 patients with OGI. When all included studies were pooled, the estimated SO rate was 0.12% (95% confidence interval [CI], 0.00%–0.25%) after OGI. Of 779 patients who underwent primary enucleation or primary evisceration, no SO cases were reported, resulting in a pooled SO estimate of 0.05% (95% CI, 0.00%–0.21%). For primary repair, the pooled estimate of SO rate was 0.15% (95% CI, 0.00%–0.33%). The ARR using a random effects model was −0.0010 (in favour of eye removal; 95% CI, −0.0031 [in favor of eye removal] to 0.0011 [in favor of primary repair]). Grading of Recommendations, Assessment, Development, and Evaluations analysis highlighted a low certainty of evidence because the included studies were observational, and a risk of bias resulted from missing data.Discussion: Based on the available data, no evidence exists that primary enucleation or primary evisceration reduce the risk of secondary SO.Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

    miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts

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    Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to directly inhibit a number of genes implicated in cytoskeletal remodeling in BC cells. Through intracellular signal transduction, growth factors activate the transcription factor AP-1, and we show that this in turn reduces miR-23b levels by direct binding to its promoter, releasing the pro-invasive genes from translational inhibition. In aggregate, miR-23b expression invokes a sophisticated interaction network that co-ordinates a wide range of cellular responses required to alter the cytoskeleton during cancer cell motility

    Whole genome sequence analysis suggests intratumoral heterogeneity in dissemination of breast cancer to lymph nodes.

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    BACKGROUND: Intratumoral heterogeneity may help drive resistance to targeted therapies in cancer. In breast cancer, the presence of nodal metastases is a key indicator of poorer overall survival. The aim of this study was to identify somatic genetic alterations in early dissemination of breast cancer by whole genome next generation sequencing (NGS) of a primary breast tumor, a matched locally-involved axillary lymph node and healthy normal DNA from blood. METHODS: Whole genome NGS was performed on 12 µg (range 11.1-13.3 µg) of DNA isolated from fresh-frozen primary breast tumor, axillary lymph node and peripheral blood following the DNA nanoball sequencing protocol. Single nucleotide variants, insertions, deletions, and substitutions were identified through a bioinformatic pipeline and compared to CIN25, a key set of genes associated with tumor metastasis. RESULTS: Whole genome sequencing revealed overlapping variants between the tumor and node, but also variants that were unique to each. Novel mutations unique to the node included those found in two CIN25 targets, TGIF2 and CCNB2, which are related to transcription cyclin activity and chromosomal stability, respectively, and a unique frameshift in PDS5B, which is required for accurate sister chromatid segregation during cell division. We also identified dominant clonal variants that progressed from tumor to node, including SNVs in TP53 and ARAP3, which mediates rearrangements to the cytoskeleton and cell shape, and an insertion in TOP2A, the expression of which is significantly associated with tumor proliferation and can segregate breast cancers by outcome. CONCLUSION: This case study provides preliminary evidence that primary tumor and early nodal metastasis have largely overlapping somatic genetic alterations. There were very few mutations unique to the involved node. However, significant conclusions regarding early dissemination needs analysis of a larger number of patient samples
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