Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

Education Can Compensate for Society - a Bit

In this paper I reflect on the findings of a number of loosely related research projects undertaken with colleagues over the last ten years. Their common theme is equity, in formal education and beyond, in wider family and social settings, and with inequity expressed as the stratification of a variety of educational outcomes. The projects are based on a standard mixture of pre-existing records, official documents, large-scale surveys, observations, interviews and focus groups. The numeric data were largely used to create biographical models of educational experiences, and the in-depth data were used to try to explain individual decisions and disparities at each stage of the model. Data have been collected for England and Wales, in five other countries of the European Union and for Japan. A meta-view of these various findings suggests that national school intakes tend to be at least moderately segregated by prior attainment and socio-economic factors, and that learning outcomes as assessed by formal means, such as examinations, are heavily stratified by these same factors. There is no convincing evidence that compulsory schooling does very much to overcome the initial disparity in the resources and attainment of school intakes. On the other hand, there are indications that the nature of a national school system and the social experiences of young people in schools can begin to equalise educational outcomes as more widely envisaged, including learning to trust and willingness to help others, aspirations, and attitudes to continuing in education and training. The cost-free implications of the argument in this paper, if accepted, are that everything possible should be done to make school intakes comprehensive, and that explicit consideration, by teachers and leaders, of the applied principles of equity could reduce potentially harmful misunderstandings in educational contexts

Improving Teacher Recruitment and Retention: The Importance of workload and Pupil Behaviour

The shortage of teachers in England and Wales continues to be a high profile area of scrutiny. Particular subjects (including mathematics; science and English) are categorized by the Training and Development Agency (TDA)for schools as priority or shortage subjects, and London especially has experienced particular shortages in teacher numbers over recent years

Learning to Teach About Ideas and Evidence in Science : The Student Teacher as Change Agent

A collaborative curriculum development project was set up to address the lack of good examples of teaching about ideas and evidence and the nature of science encountered by student teachers training to teach in the age range 11-16 in schools in England. Student and teacher-mentor pairs devised, taught and evaluated novel lessons and approaches. The project design required increasing levels of critique through cycles of teaching, evaluation and revision of lessons. Data were gathered from interviews and students' reports to assess the impact of the project on student teachers and to what extent any influences survived when they gained their first teaching posts. A significant outcome was the perception of teaching shifting from the delivery of standard lessons in prescribed ways to endeavours demanding creativity and decision-making. Although school-based factors limited newly qualified teachers' chances to use new lessons and approaches and therefore act as change-agents in schools, the ability to critique curriculum materials and the recognition of the need to create space for professional dialogue were durable gains

Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma

Extent: 15p.Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.Derek J. Nancarrow, Andrew D. Clouston, B. Mark Smithers, David C. Gotley, Paul A. Drew, David I. Watson, Sonika Tyagi, Nicholas K. Hayward, David C. Whiteman, for the Australian Cancer Study and the Study of Digestive Healt

Academic self-concept, gender and single-sex schooling

This paper assesses gender differences in academic self-concept for a cohort of children born in 1958 (the National Child Development Study). We address the question of whether attending single-sex or co-educational schools affected students’ perceptions of their own academic abilities (academic self-concept). Academic selfconcept was found to be highly gendered, even controlling for prior test scores. Boys had higher self-concepts in maths and science, and girls in English. Single-sex schooling reduced the gender gap in self-concept, while selective schooling was linked to lower academic self-concept overall

Do dietary trajectories between infancy and toddlerhood influence IQ in childhood and adolescence? Results from a prospective birth cohort study

Extent: 9 p.OBJECTIVE: We examined whether trajectories of dietary patterns from 6 to 24 months of age are associated with intelligence quotient (IQ) in childhood and adolescence. METHODS: Participants were children enrolled in a prospective UK birth cohort (n = 7652) who had IQ measured at age 8 and/or 15 years. Dietary patterns were previously extracted from questionnaires when children were aged 6, 15 and 24 months using principal component analysis. Dietary trajectories were generated by combining scores on similar dietary patterns across each age, using multilevel mixed models. Associations between dietary trajectories and IQ were examined in generalized linear models with adjustment for potential confounders. RESULTS: Four dietary pattern trajectories were constructed from 6 to 24 months of age and were named according to foods that made the strongest contribution to trajectory scores; Healthy (characterised by breastfeeding at 6 months, raw fruit and vegetables, cheese and herbs at 15 and 24 months); Discretionary (biscuits, chocolate, crisps at all ages), Traditional (meat, cooked vegetables and puddings at all ages) and, Ready-to-eat (use of ready-prepared baby foods at 6 and 15 months, biscuits, bread and breakfast cereals at 24 months). In fully-adjusted models, a 1 SD change in the Healthy trajectory was weakly associated with higher IQ at age 8 (1.07 (95%CI 0.17, 1.97)) but not 15 years (0.49 (20.28, 1.26)). Associations between the Discretionary and Traditional trajectories with IQ at 8 and 15 years were as follows; Discretionary; 8 years 20.35(21.03, 0.33), 15 years 20.73(21.33, 20.14) Traditional; 8 years 20.19(20.71, 0.33)15 years 20.41(20.77, 20.04)). The Ready-to-eat trajectory had no association with IQ at either age (8 years 0.32(24.31, 4.95), 15 years 1.11(23.10, 5.33). CONCLUSIONS: The Discretionary and Traditional dietary pattern trajectories from 6 to 24 months of age, over the period when food patterns begin to emerge, are weakly associated with IQ in adolescence.Lisa G. Smithers, Rebecca K. Golley, Murthy N. Mittinty, Laima Brazionis, Kate Northstone, Pauline Emmett and John W. Lync

Successful management of an aortoesophageal fistula caused by a fish bone – case report and review of literature

We report a case of aortoesophageal fistula (AEF) caused by a fish bone that had a successful outcome. Aortoesophageal fistula is a rare complication of foreign body ingestion from which few patients survive. Over one hundred cases of AEF secondary to foreign body ingestion have been documented but only seven, including our case, have survived over 12 months. Treatment involved stabilising the patient with a Sengstaken-Blakemore tube and insertion of a thoracic aortic endovascular stent-graft. Unfortunately the stent became infected and definitive open surgical repair involved removing the stent, replacing the aorta with a homograft and coverage with a left trapezius flap while under deep hypothermic arrest

Going, Going, Gone: A Feminist Bourdieusian Analysis of Young Women's Trajectories in, Through and Out of Physics, Age 10–19

This chapter draws on longitudinal interview data collected from seven young woman in England who were tracked from age 10–19 and who had all expressed an aspiration at age 16 to study Advanced level (A level) physics. Applying a feminist Bourdieusian conceptual lens, we explore their trajectories in, through and out of physics: from Danielle, who is denied entry to A level physics; to Victoria and Thalia, who are debarred from the course before completion; to Davina, Kate and Mienie, who complete the A level but who choose not to pursue the subject further; and finally Hannah, who goes on to study physics at university. Attention is drawn to the pedagogic work conducted by the field of physics, notably the cultivation of habitus and hexis through the bodies, minds and identities of the young women, and its stringent gate-keeping practices, which ensure the reproduction of the elite status of the field and the simultaneous disadvantaging of women