59 research outputs found

    Brain charts for the human lifespan

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    Fetal cortical plate segmentation using fully convolutional networks with multiple plane aggregation

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    Fetal magnetic resonance imaging (MRI) has the potential to advance our understanding of human brain development by providing quantitative information of cortical plate (CP) developmen

    The Cyclic AMP Cascade Is Altered in the Fragile X Nervous System

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    Fragile X syndrome (FX), the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP). Although research efforts have focused on FMRP's impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 3′, 5′-monophosphate (cAMP) cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in platelets and in brains of fmr1 knockout mice are substantially reduced. Cyclic AMP induction is also significantly reduced in human FX neural cells. Furthermore, cAMP production is decreased in the heads of FX Drosophila and this defect can be rescued by reintroduction of the dfmr gene. Our results indicate that a robust defect in cAMP production in FX is conserved across species and suggest that cAMP metabolism may serve as a useful biomarker in the human disease population. Reduced cAMP induction has implications for the underlying causes of FX and autism spectrum disorders. Pharmacological agents known to modulate the cAMP cascade may be therapeutic in FX patients and can be tested in these models, thus supplementing current efforts centered on mGluR signaling

    Partnering With Stakeholders to Inform the Co-Design of a Psychosocial Intervention for Prenatally Diagnosed Congenital Heart Disease

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    Input from diverse stakeholders is critical to the process of designing healthcare interventions. This study applied a novel mixed-methods, stakeholder-engaged approach to co-design a psychosocial intervention for mothers expecting a baby with congenital heart disease (CHD) and their partners to promote family wellbeing. The research team included parents and clinicians from 8 health systems. Participants were 41 diverse parents of children with prenatally diagnosed CHD across the 8 health systems. Qualitative data were collected through online crowdsourcing and quantitative data were collected through electronic surveys to inform intervention co-design. Phases of intervention co-design were: (I) Engage stakeholders in selection of intervention goals/outcomes; (II) Engage stakeholders in selection of intervention elements; (III) Obtain stakeholder input to increase intervention uptake/utility; (IV) Obtain stakeholder input on aspects of intervention design; and (V) Obtain stakeholder input on selection of outcome measures. Parent participants anticipated the resulting intervention, HEARTPrep, would be acceptable, useful, and feasible for parents expecting a baby with CHD. This model of intervention co-design could be used for the development of healthcare interventions across chronic diseases

    Nutritional considerations during prolonged exposure to a confined, hyperbaric, hyperoxic environment: Recommendations for saturation divers

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    Saturation diving is an occupation that involves prolonged exposure to a confined, hyperoxic, hyperbaric environment. The unique and extreme environment is thought to result in disruption to physiological and metabolic homeostasis, which may impact human health and performance. Appropriate nutritional intake has the potential to alleviate and/or support many of these physiological and metabolic concerns, whilst enhancing health and performance in saturation divers. Therefore, the purpose of this review is to identify the physiological and practical challenges of saturation diving and consequently provide evidence-based nutritional recommendations for saturation divers to promote health and performance within this challenging environment. Saturation diving has a high-energy demand, with an energy intake of between 44 and 52 kcal/kg body mass per day recommended, dependent on intensity and duration of underwater activity. The macronutrient composition of dietary intake is in accordance with the current Institute of Medicine guidelines at 45-65 % and 20-35 % of total energy intake for carbohydrate and fat intake, respectively. A minimum daily protein intake of 1.3 g/kg body mass is recommended to facilitate body composition maintenance. Macronutrient intake between individuals should, however, be dictated by personal preference to support the attainment of an energy balance. A varied diet high in fruit and vegetables is highly recommended for the provision of sufficient micronutrients to support physiological processes, such as vitamin B12 and folate intake to facilitate red blood cell production. Antioxidants, such as vitamin C and E, are also recommended to reduce oxidised molecules, e.g. free radicals, whilst selenium and zinc intake may be beneficial to reinforce endogenous antioxidant reserves. In addition, tailored hydration and carbohydrate fueling strategies for underwater work are also advised

    Combining self-assembling peptide gels with three-dimensional elastomer scaffolds

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    [EN] Some of the problems raised by the combination of porous scaffolds and self-assembling peptide (SAP) gels as constructs for tissue engineering applications are addressed for the first time. Scaffolds of poly(- ethyl acrylate) and the SAP gel RAD16-I were employed. The in situ gelation of the SAP gel inside the pores of the scaffolds was studied. The scaffold-cum-gel constructs were characterized morphologically, physicochemically and mechanically. The possibility of incorporating an active molecule (bovine serum albumin, taken here as a model molecule for others) in the gel within the scaffold’s pores was assessed, and the kinetics of its release in phosphate-buffered saline was followed. Cell seeding and colonization of these constructs were preliminarily studied with L929 fibroblasts and subsequently checked with sheep adipose-tissue-derived stem cells intended for further preclinical studies. Static (conventional) and dynamically assisted seedings were compared for bare scaffolds and the scaffold-cum-gel constructs. The SAP gel inside the pores of the scaffold significantly improved the uniformity and density of cell colonization of the three-dimensional (3-D) structure. These constructs could be of use in different advanced tissue engineering applications, where, apart from a cell-friendly extracellular matrix -like aqueous environment, a larger-scale 3-D structure able to keep the cells in a specific place, give mechanical support and/or conduct spatially the tissue growth could be required.The authors acknowledge funding through the European Commission FP7 project RECATABI (NMP3-SL-2009-229239), and from the Spanish Ministerio de Ciencia e Innovacion through projects MAT2011-28791-C03-02 and -03. Dr. J.C. Chachques (Hopital Europeen Georges Pompidou, Paris) is thanked for providing the ASCs employed in this study. MMP acknowledges support of CIBER-BBN initiative, financed by Institut de Salud Carlos III (Spain) with the assistance of the European Regional Development Fund.Vallés Lluch, A.; Arnal Pastor, MP.; Martínez Ramos, C.; Vilariño Feltrer, G.; Vikingsson, L.; Castells Sala, C.; Semino, CE.... (2013). Combining self-assembling peptide gels with three-dimensional elastomer scaffolds. Acta Biomaterialia. 9(12):9451-9460. https://doi.org/10.1016/j.actbio.2013.07.038S9451946091

    A Measure of Perceived Performance to Assess Resource Allocation

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    The final publication is available at Springer via http://dx.doi.org/10.1007/s00500-015-1696-3Performance measurement is a key issue when a company is designing new strategies to improve resource allocation. This paper offers a new methodology inspired by classic importance-performance analysis (IPA) that provides a global index of importance versus performance for firms. This index compares two rankings of the same set of features regarding importance and performance, taking into account underperforming features. The marginal contribution of each feature to the proposed global index defines a set of iso-curves that represents an improvement in the IPA diagram. The defined index, together with the new version of the diagram, will enable the assessment of a firm's overall performance and, therefore, enhance decision making in the allocation of resources. The proposed methodology has been applied to a Taiwanese multi-format retailer and managerial perceptions of performance and importance are compared to assess the firm's overall performance.Peer ReviewedPostprint (author's final draft
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