The edge of the sea: complexity, layering and gesture as analogy and meaning

The output is a creative project, ‘The edge of the sea: complexity, layering and gesture as analogy and meaning’, comprising a body of work responding to rockpool formations and the translation of field drawings into print and sequential imagery. Research process: The project began with the Rachel Carson book The Edge of the Sea (1955), dealing with the complexities and balance of a transient ecosystem. The research processes focussed on Johann Wolfgang von Goethe’s singular, romantic idea of “All is Leaf”; that within the details of a phenomena we can bear witness to the whole. Mills uses drawing to explore whether an isolated shape, line, texture, open up the reading of an image to broader interpretation that the initial observation and how we can communicate something other, or something more, than what we are representing on the page. Research insights: The project found ways and means that image-making can be used to communicate the complex, transient, self-organising system of a rockpool and how the isolation of visual devices can help communicate those findings on a more analogous level. The research revealed that our perception of an element, a fraction of the whole, can help us understand wider context. The work led to insights into the communicative nature of mark-making, the process of translation of experience and the meaning of this particular ornamentation. Dissemination: The research was disseminated at Decriminalising Ornament: The Pleasures of Pattern, The Illustration Research Symposium, 17 – 18 November 2018 at Anglia Ruskin University

Print stuff – independent print & publishing fair

Print Stuff is an independent print & publishing fair held, for the past three years at the De Grey Rooms, York. Crossing between illustration, textiles, graphic design, photography, poetry and comics, the curated event champions the interdisciplinary space that printmaking and self-publishing provides. The fair functions as an affordable space for artists and publishers to exhibit and sell their work, start conversations and promote an authorial approach to contemporary print. The event was started in 2017, with over 50 exhibitors showing work and free monoprint workshops on-site run by Leeds Print Workshop with approximately 900 visitors throughout the day. The 2018 event also included a series of exhibitions held across York in the lead-up to the fair itself (at Fossgate Social, Kiosk Project Space and Random Encounter) and welcomed around 1200 visitors on the day. The 2019 event was held over 2 days, with talks and workshops across the weekend from exhibitors and academics in the field of print and self-publishing, as well as featuring over 50 exhibitors and an exhibition of artists' work held at York College. The Print Stuff project has sought to provide a platform for contemporary, self-authored work in order to seek connections between disciplines and explore the potential of printed matter as a unifying factor of creative practice. Over the past three years, we have been able to situate photobooks alongside comic artists and more traditional printmakers in order to establish a dialogue about the value, role and future of the printed form. http://www.print-stuff.co.u

The 8p11-P12 Amplicon Oncogenes ASH2L and NSD3 Regulate Cell Cycle Progression via Epigenetic Alterations and Result in Overexpression and Estrogen-Independent Activation of ERα in Breast Cancer

Breast cancer is a highly heterogeneous disease classified clinically by expression of estrogen receptor alpha ERα, progesterone receptor, and human epidermal growth factor receptor. Molecular expression profiling identified a luminal breast cancer sub-type that can be sub-divided into luminal A and B. Compared to luminal A, luminal B tumors have increased proliferation, poor prognosis, endocrine therapy resistance, and complex genomes, including amplification of the 8p11-p12 genomic region. This amplicon occurs in 15% of primary breast tumors, correlates with poor prognosis and tamoxifen resistance, and harbors several oncogenes. Two of these oncogenes, ASH2L and NSD3 (WHSC1L1), promote transcription via epigenetic modification of histone proteins. NSD3 has a long isoform that is associated with di-methylation of lysine 36 on histone 3 (H3K36me2) and a short isoform that lacks a catalytic SET domain but retains the ability to interact with chromatin. ASH2L also lacks a catalytic SET domain yet is tightly and specifically linked to tri-methylation of lysine 4 on histone 3 (H3K4me3) in gene promoters. In this study, we tested the hypothesis that ASH2L and NSD3 cooperate to regulate expression of a suite of genes important in breast cancer, including ESR1, which encodes ERα. We discovered that NSD3-short is the major oncogenic isoform of NSD3 and its amplification and overexpression leads to overexpression and estrogen-independent activation of ERα. We also demonstrated that knockdown of ASH2L reduces H3K4me3 specifically in promoters of genes important to cell cycle progression. ASH2L also regulates promoter H3K4me3 at NSD3 and expression of both NSD3 and ERα. Knockdown of ASH2L reduced sensitivity to the cell cycle inhibitor palbociclib in the 8p11-p12 amplicon-bearing SUM-44 cell line. Together, the data presented here identify a role for ASH2L and NSD3 in cooperative regulation of genes important to cell cycle regulation, including ESR1, and demonstrate that ERα is active in an estrogen-independent manner in the context of overexpression of these oncogenes. We have discovered a novel mechanism of endocrine resistance in luminal B breast cancers and provided evidence for the 8p11-p12 amplicon as a biomarker of patients who will respond to cell cycle inhibitors and epigenetic therapies against histone methyltransferase enzymes

Enhancing Teachers’ Knowledge of Core Academic Standards through a Digital Content Development Workshop

There is an immediate need to help classroom teachers understand the common core standards so they can more effectively teach the content to students of the digital generation. This study summarized the activities in a digital content development workshop for empowering teachers to develop standards-based digital content for K-8 students in need of accelerated learning. Using a pretest-posttest design, the study also examined the impact of the digital content development workshop on participating teachers’ knowledge of core academic standards. A self-developed Knowledge of Core Academic Standards (KCAS) survey was used to measure teachers’ recall of core academic standards, teachers’ awareness of possible changes expected from the implementation of core academic standards, and teachers’ understanding of the differences between the previous standards and the new core academic standards. Paired-samples t-tests were used to evaluate the mean differences before and after the KCAS survey in teachers’ recall scores, teachers’ awareness ratings, and the ratings of teachers’ understanding of the differences. Findings indicated that participating teachers in the digital content development workshop gained significantly in the recall of core academic standards scores on the KCAS survey. Moreover, participating teachers also gained significantly in ratings of the awareness of possible changes and understanding of differences. The digital content development workshop offered a content-embedded pathway for enhancing teachers’ knowledge of core academic standards. Limitations to the study are also discussed

Screening of the COL8A2 gene in an Australian family with early-onset Fuchs’ endothelial corneal dystrophy

This item is under embargo for a period of 12 months from the date of publication, in accordance with the publisher's policy

Review of the prevalence of diabetic retinopathy in Indigenous Australians

Author version made available in accordance with Publisher copyright policy.The purpose of this review is to compare the prevalence of diabetic retinopathy (DR) between Indigenous and non-Indigenous Australians with Diabetes Mellitus (DM). Australian DR prevalence data from 6 Indigenous studies (n = 2865) and 5 non-Indigenous studies (n = 9801) conducted between 1985 and 2013 were included for analysis. Estimated prevalence of any DR among Indigenous Australians with DM was 23.4% compared with 28.9% for non-Indigenous Australians (χ2 = 26.9, P < 0.001). In studies performed after 1990, a significantly higher rate of diabetic macular edema was found in Indigenous compared with non-Indigenous Australians with DM (7.6% versus 4.9%, χ2 = 6.67, P = 0.01). Although there are limitations in comparing these studies, one explanation for the observed data could be a model in which Indigenous Australians are relatively resistant to early stage DR, but with a subset progressing to sight threatening DR due to individual genetic and environmental susceptibility factors coupled with poor glycemic control

Differentiation of a contractile, ureter-like tissue, from Embryonic Stem cell-derived ureteric bud and <i>Ex-Fetu</i> mesenchyme

BACKGROUND: There is intense interest in replacing kidneys from stem cells. It is now possible to produce, from embryonic or induced pluripotent stem cells, kidney organoids that represent immature kidneys and display some physiologic functions. However, current techniques have not yet resulted in renal tissue with a ureter, which would be needed for engineered kidneys to be clinically useful. METHODS: We used a published sequence of growth factors and drugs to induce mouse embryonic stem cells to differentiate into ureteric bud tissue. We characterized isolated engineered ureteric buds differentiated from embryonic stem cells in three-dimensional culture and grafted them into ex fetu mouse kidney rudiments. RESULTS: Engineered ureteric buds branched in three-dimensional culture and expressed Hoxb7, a transcription factor that is part of a developmental regulatory system and a ureteric bud marker. When grafted into the cortex of ex fetu kidney rudiments, engineered ureteric buds branched and induced nephron formation; when grafted into peri-Wolffian mesenchyme, still attached to a kidney rudiment or in isolation, they did not branch but instead differentiated into multilayer ureter-like epithelia displaying robust expression of the urothelial marker uroplakin. This engineered ureteric bud tissue also organized the mesenchyme into smooth muscle that spontaneously contracted, with a period a little slower than that of natural ureteric peristalsis. CONCLUSIONS: Mouse embryonic stem cells can be differentiated into ureteric bud cells. Grafting those UB-like structures into peri-Wolffian mesenchyme of cultured kidney rudiments can induce production of urothelium and organize the mesenchyme to produce rhythmically contracting smooth muscle layers. This development may represent a significant step toward the goal of renal regeneration

Trends and level of control of hypertension among adults attending an ambulatory HIV clinic in Kampala, Uganda: a retrospective study.

BACKGROUND: With an ageing HIV-positive population, sub-Saharan Africa is now facing a dual epidemic of communicable and non-communicable diseases (NCDs). This study aimed to assess trends in the prevalence of hypertension and factors associated with hypertension, among adults attending an ambulatory HIV clinic in Kampala, Uganda. METHODS: We conducted a retrospective chart review to identify patients with hypertension. We used a random number generator to select 400 patient charts from each year from 2009 to 2014. Blood pressure, age, body mass index (BMI), WHO disease stage and Karnofsky scores were extracted. Logistic regression was used to estimate the strength of the association between each of these factors and the presence of hypertension. RESULTS: In total, 1996 charts were included in this analysis. The mean age of participants was 31 years and 1311/1996 (65.7%) were female. The overall prevalence of hypertension was 418/1996 (20.9%). This rose from 16.9% in 2009 to 32.3% in 2013. Of the patients with hypertension, 96/418 (23.0%) were receiving adequate treatment. Patients >50 years of age had 3.12 times the odds of hypertension compared with patients aged 20-29 years (95% CI 2.00 to 4.85). Men had 1.65 times the odds of hypertension compared with women (95% CI 1.34 to 2.03) and patients with a BMI of 35-39 kg/m2 had 3.93 times the odds of hypertension compared with patients with a BMI <25 kg/m2. CONCLUSIONS: The prevalence of hypertension is rising in the Ugandan HIV-positive population. There remains inadequate management and control of hypertension in this group highlighting the need to better integrate NCD care within the HIV clinical settings

Life expectancy among HIV-positive patients in Rwanda: a retrospective observational cohort study

Background Rwanda has achieved substantial progress in scaling up of antiretroviral therapy. We aimed to assess the eff ect of increased access to antiretroviral therapy on life expectancy among HIV-positive patients in two distinct periods of lower and higher antiretroviral therapy coverage (1997–2007 and 2008–11). Methods In a retrospective observational cohort study, we collected clinical and demographic data for all HIV-positive patients enrolled in care at 110 health facilities across all fi ve provinces of Rwanda. We included patients aged 15 years or older with a known enrolment date between 1997 and 2014. We constructed abridged life tables from age-specifi c mortality rates and life expectancy stratifi ed by sex, CD4 cell count, and WHO disease stage at enrolment in care and initiation of antiretroviral therapy. Findings We included 72 061 patients in this study, contributing 213 983 person-years of follow-up. The crude mortality rate was 33·4 deaths per 1000 person-years (95% CI 32·7–34·2). Life expectancy for the overall cohort was 25·6 additional years (95% CI 25·1–26·1) at 20 years of age and 23·3 additional years (95% CI 22·9–23·7) at 35 years of age. Life expectancy at 20 years of age in the period of 1997–2007 was 20·4 additional years (95% CI 19·5–21·3); for the period of 2008–11, life expectancy had increased to 25·6 additional years (95% CI 24·8–26·4). Individuals enrolling in care with CD4 cell counts of 500 cells per μL or more, and with WHO disease stage I, had the highest life expectancies. Interpretation This study adds to the growing body of evidence showing the benefi t to HIV-positive patients of early enrolment in care and initiation of antiretroviral therapy