Folic acid in pregnancy and mortality from cancer and cardiovascular disease : further follow-up of the Aberdeen folic acid supplementation trial

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. Acknowledgements The authors wish to acknowledge Professor Marion Hall, who set up the original randomised trial of folic acid supplementation. The authors also thank Ms Katie Wilde and the Data Management Team, University of Aberdeen, for their help with the extraction and linking of data and the data analysts from ISD Scotland.Peer reviewedPublisher PD

Developmental Genes Targeted for Epigenetic Variation between Twin-Twin Transfusion Syndrome Children

Background: Epigenetic mechanisms are thought to be critical in mediating the role of the intrauterine environment on lifelong health and disease. Twin-twin transfusion syndrome (TTTS) is a rare condition wherein fetuses share the placenta and develop vascular anastomoses, which allow blood to flow between the fetuses. The unequal flow results in reciprocal hypo- and hypervolemia in the affected twins, striking growth differences and physiologic adaptations in response to this significant stressor. The donor twin in the TTTS syndrome can be profoundly growth restricted and there is likely a nutritional imbalance between the twins. The consequences of TTTS on fetal programming are unknown. This condition can now be effectively treated through the use of fetal laparoscopic procedures, but the potential for lifelong morbidity related to this condition during development is apparent. As this condition and the resulting uteroplacental discordance can play a role in the epigenetic process, we sought to investigate the DNA methylation profiles of childhood survivors of TTTS (n = 14). We focused on differences in both global measures and genome-wide CpG specific DNA methylation between donor and recipient children in this pilot study in order to generate hypotheses for further research. Results: We identified significant hypomethylation of the LINE1 repetitive element in the peripheral blood of donor children and subtle variation in the genome-wide profiles of CpG specific methylation most prominent at CpG sites which are targets for polycomb group repressive complexes. Conclusions: These preliminary results suggest that coordinated epigenetic alterations result from the intrauterine environment experienced by infants with TTTS and may, at least in part, be responsible for downstream health conditions experienced by individuals surviving this condition

Gene therapy with Angiotensin-(1-9) preserves left ventricular systolic function after myocardial infarction

BACKGROUND: Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin angiotensin system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic minipump in mice. Here, we investigate whether gene transfer of Ang-(1-9) is cardioprotective in a murine model of myocardial infarction (MI). OBJECTIVES: To evaluate effects of Ang-(1-9) gene therapy on myocardial structural and functional remodeling post infarction. METHODS: C57BL/6 mice underwent permanent left anterior descending coronary artery ligation and cardiac function was assessed using echocardiography for 8 weeks followed by a terminal measurement of left ventricular (LV) pressure-volume loops. Ang-(1-9) was delivered by adeno-associated viral vector via single tail vein injection immediately following induction of MI. Direct effects of Ang-(1-9) on cardiomyocyte excitation–contraction coupling and cardiac contraction were evaluated in isolated mouse and human cardiomyocytes and in an ex vivo Langendorff perfused whole heart model. RESULTS: Gene delivery of Ang-(1-9) significantly reduced sudden cardiac death post-MI. Pressure–volume measurements revealed complete restoration of end systolic pressure, ejection fraction, end systolic volume and the end diastolic pressure–volume relationship by Ang-(1-9) treatment. Stroke volume and cardiac output were significantly increased versus sham. Histological analysis revealed only mild effects on cardiac hypertrophy and fibrosis, but a significant increase in scar thickness. Direct assessment of Ang-(1-9) on isolated cardiomyocytes demonstrated a positive inotropic effect via increasing calcium transient amplitude and increasing contractility. Ang-(1-9) increased contraction in the Langendorff model through a protein kinase A-dependent mechanism. CONCLUSIONS: Our novel findings show that Ang-(1-9) gene therapy preserves LV systolic function post-MI, restoring cardiac function. Furthermore, Ang-(1-9) has a direct effect on cardiomyocyte 3 calcium handling through a protein kinase A-dependent mechanism. These data highlight Ang-(1-9) gene therapy as a potential new strategy in the context of MI

Collaboration and contestation in further and higher education partnerships in England: a Bourdieusian field analysis

Internationally, ‘College for All’ policies are creating new forms of vocational higher education (HE), and shifting relationships between HE and further education (FE) institutions. In this paper, we consider the way in which this is being implemented in England, drawing on a detailed qualitative case study of a regional HE–FE partnership to widen participation. We focus on the complex mix of collaboration and contestation that arose within it, and how these affected socially differentiated groups of students following high- and low-status routes through its provision. We outline Bourdieu’s concept of ‘field’ as a framework for our analysis and interpretation, including its theoretical ambiguities regarding the definition and scale of fields. Through hermeneutic dialogue between data and theory, we tentatively suggest that such partnerships represent bridges between HE and FE. These bridges are strong between higher-status institutions, but highly contested between lower-status institutions competing closely for distinction. We conclude that the trajectories and outcomes for socially disadvantaged students require attention and collective action to address the inequalities they face, and that our theoretical approach may have wider international relevance beyond the English case

Equity of access to treatment on the Cancer Drugs Fund:A missed opportunity for cancer research?

AbstractUsing mixed-methods, we investigated the CDF in the South West of England (3193 cancer patients treated through the CDF, April 1st 2011–March 31st 2013) for evidence of: (1) equitable access across socioeconomic groups, age groups, sex, and Cancer Network; (2) time-to-treatment by socioeconomic group; and (3) the perception of the CDF as fair, using semi-structured interviews with oncology consultants.There was no evidence of inequitable access to anti-cancer therapy for those in more deprived areas. For all cancer types, there was a lower proportion of women in the CDF cohort than in the Cancer Registry reference population (e.g., melanoma, CDF 36.8% female, reference population 48.7%; difference 11.9%, 95% CI 3.1–20.7%). There was a lower proportion of older patients in the CDF compared with the reference population (e.g., colorectal cancer, CDF 6.9% ≥80 years, reference population 30.1%; difference 23.2%, 95% CI 20.2–26.2%). Interviewed oncologists felt differences in performance status, not age, influenced referral to the CDF, with neither deprivation, nor gender contributing.Our study suggests that the CDF has differential access by age and sex, but not by deprivation. The absence of high quality CDF data represents a missed opportunity to fully evaluate equity of access and the real-world costs and outcomes of novel anti-cancer drugs