25 research outputs found

    Group antenatal care (Pregnancy Circles) for diverse and disadvantaged women: study protocol for a randomised controlled trial with integral process and economic evaluations

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    Background Group antenatal care has been successfully implemented around the world with suggestions of improved outcomes, including for disadvantaged groups, but it has not been formally tested in the UK in the context of the NHS. To address this the REACH Pregnancy Circles intervention was developed and a randomised controlled trial (RCT), based on a pilot study, is in progress. Methods The RCT is a pragmatic, two-arm, individually randomised, parallel group RCT designed to test clinical and cost-effectiveness of REACH Pregnancy Circles compared with standard care. Recruitment will be through NHS services. The sample size is 1732 (866 randomised to the intervention and 866 to standard care). The primary outcome measure is a β€˜healthy baby’ composite measured at 1 month postnatal using routine maternity data. Secondary outcome measures will be assessed using participant questionnaires completed at recruitment (baseline), 35 weeks gestation (follow-up 1) and 3 months postnatal (follow-up 2). An integrated process evaluation, to include exploration of fidelity, will be conducted using mixed methods. Analyses will be on an intention to treat as allocated basis. The primary analysis will compare the number of babies born β€œhealthy” in the control and intervention arms and provide an odds ratio. A cost-effectiveness analysis will compare the incremental cost per Quality Adjusted Life Years and per additional β€˜healthy and positive birth’ of the intervention with standard care. Qualitative data will be analysed thematically. Discussion This multi-site randomised trial in England is planned to be the largest trial of group antenatal care in the world to date; as well as the first rigorous test within the NHS of this maternity service change. It has a recruitment focus on ethnically, culturally and linguistically diverse and disadvantaged participants, including non-English speakers. Trial registration Trial registration; ISRCTN, ISRCTN91977441. Registered 11 February 2019 - retrospectively registered. The current protocol is Version 4; 28/01/2020

    Grain refinement of Al-Mg-Sc alloy by ultrasonic treatment

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    In foundry practice, ultrasonic treatment has been used as an efficient technique to achieve grain refinement in aluminium and magnesium alloys. This article shows the strong effect of pouring temperature and ultrasonic treatment at various temperatures on the grain refinement of Al-1 wt% Mg-0.3 wt% Sc alloy. Without ultrasonic treatment, a fine grain structure was obtained at the pouring temperature of 700 Β°C. The average grain size sharply decreases from 487 Β± 20 to 103 Β± 2 ΞΌm when the pouring temperature decreases from 800 to 700 Β°C. Ultrasonic vibration proved to be a potential grain refinement technique with a wide range of pouring tem- perature. A microstructure with very fine and homogeneous grains was obtained by applying ultrasonic treatment to the melt at the temperature range between 700 and 740 Β°C, before pouring. Cavitation-enhanced hetero- geneous nucleation is the mechanism proposed to explain grain refinement by ultrasound in this alloy. Moreover, ultrasonic treatment of the melt was found to lead to cast samples with hardness values similar to those obtained in samples submitted to precipitation hardening, suggesting that ultrasonic treatment can avoid carrying out heat treatment of cast parts.This research was supported by The Project Bridging The Gap, funded by the Erasmus Mundus External Cooperation Window Programme. Acknowledgements also to the University of Minho, for the provision of research facilities

    New Alzheimer Amyloid Ξ² Responsive Genes Identified in Human Neuroblastoma Cells by Hierarchical Clustering

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    Alzheimer's disease (AD) is characterized by neuronal degeneration and cell loss. AΞ²42, in contrast to AΞ²40, is thought to be the pathogenic form triggering the pathological cascade in AD. In order to unravel overall gene regulation we monitored the transcriptomic responses to increased or decreased AΞ²40 and AΞ²42 levels, generated and derived from its precursor C99 (C-terminal fragment of APP comprising 99 amino acids) in human neuroblastoma cells. We identified fourteen differentially expressed transcripts by hierarchical clustering and discussed their involvement in AD. These fourteen transcripts were grouped into two main clusters each showing distinct differential expression patterns depending on AΞ²40 and AΞ²42 levels. Among these transcripts we discovered an unexpected inverse and strong differential expression of neurogenin 2 (NEUROG2) and KIAA0125 in all examined cell clones. C99-overexpression had a similar effect on NEUROG2 and KIAA0125 expression as a decreased AΞ²42/AΞ²40 ratio. Importantly however, an increased AΞ²42/AΞ²40 ratio, which is typical of AD, had an inverse expression pattern of NEUROG2 and KIAA0125: An increased AΞ²42/AΞ²40 ratio up-regulated NEUROG2, but down-regulated KIAA0125, whereas the opposite regulation pattern was observed for a decreased AΞ²42/AΞ²40 ratio. We discuss the possibilities that the so far uncharacterized KIAA0125 might be a counter player of NEUROG2 and that KIAA0125 could be involved in neurogenesis, due to the involvement of NEUROG2 in developmental neural processes

    Loss of Arc renders the visual cortex impervious to the effects of sensory experience or deprivation

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    A myriad of mechanisms have been suggested to account for the full richness of visual cortical plasticity. We found that visual cortex lacking Arc is impervious to the effects of deprivation or experience. Using intrinsic signal imaging and chronic visually evoked potential recordings, we found that Arcβˆ’/βˆ’ mice did not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation. Extended deprivation also failed to elicit a shift in ocular dominance or open-eye potentiation. Moreover, Arcβˆ’/βˆ’ mice lacked stimulus-selective response potentiation. Although Arcβˆ’/βˆ’ mice exhibited normal visual acuity, baseline ocular dominance was abnormal and resembled that observed after dark-rearing. These data suggest that Arc is required for the experience-dependent processes that normally establish and modify synaptic connections in visual cortex.Howard Hughes Medical InstituteNational Science Foundation (U.S.

    Fragile x syndrome and autism: from disease model to therapeutic targets

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    Autism is an umbrella diagnosis with several different etiologies. Fragile X syndrome (FXS), one of the first identified and leading causes of autism, has been modeled in mice using molecular genetic manipulation. These Fmr1 knockout mice have recently been used to identify a new putative therapeutic target, the metabotropic glutamate receptor 5 (mGluR5), for the treatment of FXS. Moreover, mGluR5 signaling cascades interact with a number of synaptic proteins, many of which have been implicated in autism, raising the possibility that therapeutic targets identified for FXS may have efficacy in treating multiple other causes of autism
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