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

"If only had I known":a qualitative study investigating a treatment of patients with a hip fracture with short time stay in hospital

Hip fractures are amongst the leading causes of admission to an orthopaedic ward. Systematized pathways with reduced admission time have become increasingly common as an essential tool for quality development and to improve efficiency in the hospital setting.  The aim of this study was to clarify if the patients feel empowered and able to perform self-care after short time stay in hospital (STSH) due to a hip fracture. The study used descriptive phenomenology to describe experiences of the pathway. Field studies were conducted in hospitals and in the patients' homes.  Interviews were performed with 10 patients recruited from two wards at a Danish University hospital, 4 family members and 15 health professionals from three hospitals.  The open attitude of reflective lifeworld research guided the analysis. The findings revealed that patients felt unprepared and insecure about their future, but also had a strong desire to be in charge of their own lives.  Of all the patients interviewed, none had any recollection of the information given to them by health professionals during their hospital admission. This study demonstrates that empowerment of patients with hip fractures is not adequately achieved in the pathway with STSH

The long-term impact of folic acid in pregnancy on offspring DNA methylation : follow-up of the Aberdeen folic acid supplementation trial (AFAST)

Funding This work was supported by the NIHR Bristol Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. R.C.R., G.C.S., N.K., T.G., G.D.S. and C.L.R. work in a unit that receives funds from the University of Bristol and the UK Medical Research Council (MC_UU_12013/1, MC_UU_12013/2 and MC_UU_12013/8). This work was also supported by CRUK (grant number C18281/A19169) and the ESRC (grant number ES/N000498/1). C.M.T. is supported by a Wellcome Trust Career Re-entry Fellowship (grant number 104077/Z/14/Z).Peer reviewedPublisher PD

The Effect of Amnion-derived Cellular Cytokine Solution on the Epithelialization of Partial-thickness Donor Site Wounds in Normal and Streptozotocin-induced Diabetic Swine

Objective: The purpose of this study was to determine whether amnion-derived cellular cytokine solution (ACCS) could improve the quality of epithelialization and accelerate closure of dermatome-created partial-thickness wounds in normal and streptozotocin-induced diabetic pigs. Methods: Dermatome-created partial-thickness wounds were sealed with wound chambers in healthy and diabetic pigs and were injected with ACCS. Wound fluid was exchanged daily for total protein concentration, and biopsies were taken on days 6, 8, 10, and 12. Epithelialization, thickness of epidermis, number of epidermal cell layers, and rete ridges were evaluated. Results: The macroscopic appearance of the wounds and speed of healing was similar in all groups at each time point. All wounds were healed by day 6. The epidermis was thicker in the ACCS-treated diabetic wounds than in the controls (140.6 μm vs 82.7 μm on day 12 in diabetic pigs). There were more cell layers (13 vs 7.7) in ACCS-treated diabetic pigs on day 12. The number of rete ridges per 2.5 mm was greater on day 12 in the ACCS-treated diabetic wounds (13 vs 8). There was also a significant increase in the number of rete ridges in ACCS-treated nondiabetic pigs but no difference in epidermal thickness or number of cell layers. Conclusion: In diabetic pigs, we found a significantly thicker epidermis and more cell layers and rete ridges in the ACCS-treated wounds. Healthy pigs showed more rete ridges but no difference in thickness of epidermis or number of cell layers on day 12

Using open-source data to construct 20 metre resolution maps of children’s travel time to the nearest health facility

Physical access to health facilities is an important factor in determining treatment seeking behaviour and has implications for targets within the Sustainable Development Goals, including the right to health. The increased availability of high-resolution land cover and road data from satellite imagery offers opportunities for fine-grained estimations of physical access which can support delivery planning through the provision of more realistic estimates of travel times. The data presented here is of travel time to health facilities in Uganda, Zimbabwe, Tanzania, and Mozambique. Travel times have been calculated for different facility types in each country such as Dispensaries, Health Centres, Clinics and Hospitals. Cost allocation surfaces and travel times are provided for child walking speeds but can be altered easily to account for adult walking speeds and motorised transport. With a focus on Uganda, we describe the data and method and provide the travel maps, software and intermediate datasets for Uganda, Tanzania, Zimbabwe and Mozambique

Detecting and reducing heterogeneity of error in acoustic classification

Passive acoustic monitoring can be an effective method for monitoring species, allowing the assembly of large audio datasets, removing logistical constraints in data collection and reducing anthropogenic monitoring disturbances. However, the analysis of large acoustic datasets is challenging and fully automated machine learning processes are rarely developed or implemented in ecological field studies. One of the greatest uncertainties hindering the development of these methods is spatial generalisability—can an algorithm trained on data from one place be used elsewhere? We demonstrate that heterogeneity of error across space is a problem that could go undetected using common classification accuracy metrics. Second, we develop a method to assess the extent of heterogeneity of error in a random forest classification model for six Amazonian bird species. Finally, we propose two complementary ways to reduce heterogeneity of error, by (i) accounting for it in the thresholding process and (ii) using a secondary classifier that uses contextual data. We found that using a thresholding approach that accounted for heterogeneity of precision error reduced the coefficient of variation of the precision score from a mean of 0.61 ± 0.17 (SD) to 0.41 ± 0.25 in comparison to the initial classification with threshold selection based on F-score. The use of a secondary, contextual classification with thresholding selection accounting for heterogeneity of precision reduced it further still, to 0.16 ± 0.13, and was significantly lower than the initial classification in all but one species. Mean average precision scores increased, from 0.66 ± 0.4 for the initial classification, to 0.95 ± 0.19, a significant improvement for all species. We recommend assessing—and if necessary correcting for—heterogeneity of precision error when using automated classification on acoustic data to quantify species presence as a function of an environmental, spatial or temporal predictor variable

Impact of tank background on the welfare of the African clawed frog, Xenopus laevis (Daudin)

The captive environment of a laboratory animal can profoundly influence its welfare and the scientific validity of research produced. The African clawed frog (Xenopus laevis) is a common model organism, however current husbandry guidelines lack supporting quantitative evidence. The visual environment is a fundamental aspect of a captive animal’s housing and may affect a number of physiological and behavioural responses. This is particularly important for species such as X. laevis where cryptic camouflage is a fundamental defence mechanism. Here male (n = 16) and female (n = 20) X. laevis were housed in tanks with ecologically relevant (black) and non-relevant (white) background colours and physiological and behavioural responses observed. Higher levels of water-borne corticosterone were observed in tanks with a white background compared to a black background in females (p = 0.047). Increased atypical active behaviours (Swimming: p = 0.042; Walling: p = 0.042) and a greater degree of body mass loss (p < 0.001) were also observed in the white background condition. Together these responses are indicative of increased stress of X. laevis when housed in tanks with a non-ecologically relevant background compared to an ecologically relevant background and suggest refined tank background colour may improve welfare in this species

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