890 research outputs found

    Mothers' perceptions of child weight status and the subsequent weight gain of their children : a population based longitudinal study

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    BACKGROUND: There is a plethora of cross sectional work on maternal perceptions of child weight status showing that mothers typically do not classify their overweight child as being overweight according to commonly used clinical criteria. Awareness of overweight in their child is regarded as an important prerequisite for mothers to initiate appropriate action. The gap in the literature is determining whether, if mothers do classify their overweight child's weight status correctly, this is associated with a positive outcome for the child's body mass index (BMI) at a later stage. OBJECTIVE: To explore longitudinal perceptions of child weight status from mothers of a contemporary population-based birth cohort (Gateshead Millennium Study) and relationships of these perceptions with future child weight gain. METHODS: Data collected in the same cohort at 7, 12 and 15 years of age: mothers' responses to two items concerning their child's body size; child's and mother's BMI; pubertal maturation; demographic information. RESULTS: Mothers' perceptions of whether their child was overweight did not change markedly over time. Child BMI was the only significant predictor of mothers' classification of overweight status, and it was only at the extreme end of the overweight range and in the obese range that mothers reliably described their child as overweight. Even when mothers did appropriately classify their child as overweight at an earlier stage, this was not related to relatively lower child BMI a few years later. CONCLUSIONS: Mothers tend to classify their child as overweight in only more extreme cases. It is an important finding that no beneficial impact was shown on later child BMI in overweight children whose mothers classified their child's weight status as overweight at an earlier stage.International Journal of Obesity accepted article preview online, 25 January 2017. doi:10.1038/ijo.2017.20

    Spatio-temporal Models of Lymphangiogenesis in Wound Healing

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    Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

    Quantifying Inactive Lithium in Lithium Metal Batteries

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    Inactive lithium (Li) formation is the immediate cause of capacity loss and catastrophic failure of Li metal batteries. However, the chemical component and the atomic level structure of inactive Li have rarely been studied due to the lack of effective diagnosis tools to accurately differentiate and quantify Li+ in solid electrolyte interphase (SEI) components and the electrically isolated unreacted metallic Li0, which together comprise the inactive Li. Here, by introducing a new analytical method, Titration Gas Chromatography (TGC), we can accurately quantify the contribution from metallic Li0 to the total amount of inactive Li. We uncover that the Li0, rather than the electrochemically formed SEI, dominates the inactive Li and capacity loss. Using cryogenic electron microscopies to further study the microstructure and nanostructure of inactive Li, we find that the Li0 is surrounded by insulating SEI, losing the electronic conductive pathway to the bulk electrode. Coupling the measurements of the Li0 global content to observations of its local atomic structure, we reveal the formation mechanism of inactive Li in different types of electrolytes, and identify the true underlying cause of low Coulombic efficiency in Li metal deposition and stripping. We ultimately propose strategies to enable the highly efficient Li deposition and stripping to enable Li metal anode for next generation high energy batteries

    MicroRNAs in pulmonary arterial remodeling

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    Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

    Protocol for a prospective collaborative systematic review and meta-analysis of individual patient data from randomised controlled trials of vasoactive drugs in acute stroke: the Blood pressure in Acute Stroke Collaboration, stage-3 (BASC-3)

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    Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains, particularly for ischaemic stroke. The ‘Blood pressure in Acute Stroke Collaboration’ (BASC) commenced in the mid 1990s focusing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, BASC planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, encompassing both intracerebral haemorrhage and ischaemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on haemodynamic variables. Methods and design Individual patient data from randomised controlled trials of blood pressure management in participants with ischaemic stroke and/or intracerebral haemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 hours), acute (<48 hours) and sub-acute (<168 hours) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in prespecified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, haemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration

    Genotype at the P554L Variant of the Hexose-6 Phosphate Dehydrogenase Gene Is Associated with Carotid Intima-Medial Thickness

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    Objective: The combined thickness of the intima and media of the carotid artery (carotid intima-medial thickness, CIMT) is associated with cardiovascular disease and stroke. Previous studies indicate that carotid intima-medial thickness is a significantly heritable phenotype, but the responsible genes are largely unknown. Hexose-6 phosphate dehydrogenase (H6PDH) is a microsomal enzyme whose activity regulates corticosteroid metabolism in the liver and adipose tissue; variability in measures of corticosteroid metabolism within the normal range have been associated with risk factors for cardiovascular disease. We performed a genetic association study in 854 members of 224 families to assess the relationship between polymorphisms in the gene coding for hexose-6 phosphate dehydrogenase (H6PD) and carotid intima-medial thickness. Methods: Families were ascertained via a hypertensive proband. CIMT was measured using B-mode ultrasound. Single nucleotide polymorphisms (SNPs) tagging common variation in the H6PD gene were genotyped. Association was assessed following adjustment for significant covariates including "classical" cardiovascular risk factors. Functional studies to determine the effect of particular SNPs on H6PDH were performed. Results: There was evidence of association between the single nucleotide polymorphism rs17368528 in exon five of the H6PD gene, which encodes an amino-acid change from proline to leucine in the H6PDH protein, and mean carotid intima-medial thickness (p = 0.00065). Genotype was associated with a 5% (or 0.04 mm) higher mean carotid intima-medial thickness measurement per allele, and determined 2% of the population variability in the phenotype. Conclusions: Our results suggest a novel role for the H6PD gene in atherosclerosis susceptibility

    Root morphology and seed and leaf ionomic traits in a Brassica napus L. diversity panel show wide phenotypic variation and are characteristic of crop habit

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    Background: Mineral nutrient uptake and utilisation by plants are controlled by many traits relating to root morphology, ion transport, sequestration and translocation. The aims of this study were to determine the phenotypic diversity in root morphology and leaf and seed mineral composition of a polyploid crop species, Brassica napus L., and how these traits relate to crop habit. Traits were quantified in a diversity panel of up to 387 genotypes: 163 winter, 127 spring, and seven semiwinter oilseed rape (OSR) habits, 35 swede, 15 winter fodder, and 40 exotic/unspecified habits. Root traits of 14 d old seedlings were measured in a ‘pouch and wick’ system (n = ~24 replicates per genotype). The mineral composition of 3–6 rosette-stage leaves, and mature seeds, was determined on compost-grown plants from a designed experiment (n = 5) by inductively coupled plasma-mass spectrometry (ICP-MS). Results: Seed size explained a large proportion of the variation in root length. Winter OSR and fodder habits had longer primary and lateral roots than spring OSR habits, with generally lower mineral concentrations. A comparison of the ratios of elements in leaf and seed parts revealed differences in translocation processes between crop habits, including those likely to be associated with crop-selection for OSR seeds with lower sulphur-containing glucosinolates. Combining root, leaf and seed traits in a discriminant analysis provided the most accurate characterisation of crop habit, illustrating the interdependence of plant tissues. Conclusions: High-throughput morphological and composition phenotyping reveals complex interrelationships between mineral acquisition and accumulation linked to genetic control within and between crop types (habits) in B. napus. Despite its recent genetic ancestry (<10 ky), root morphology, and leaf and seed composition traits could potentially be used in crop improvement, if suitable markers can be identified and if these correspond with suitable agronomy and quality traits

    The right to know and the right not to know revisited:Part One

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    Prompted by developments in human genetics, a recurrent bioethical question concerns a person’s ‘right to know’ and ‘right not to know’ about genetic information held that is intrinsically related to or linked to them. In this paper, we will revisit the claimed rights in relation to two particular test cases. One concerns the rights of the 500,000 participants in UK Biobank (UKB) whose biosamples, already having been genotyped, will now be exome sequenced, and the other concerns the rights of pregnant women (and their children) who undergo non-invasive prenatal testing (NIPT)—a simple blood test that can reveal genetic information about both a foetus and its mother. This two-part paper is in four principal sections. First, we sketch the relevant features of our two test cases. Secondly, we consider the significance of recent legal jurisprudence in the UK and Singapore. Thirdly, we consider how, the jurisprudence apart, the claimed rights might be grounded. Fourthly, we consider the limits on the rights. We conclude with some short remarks about the kind of genetically aware society that we might want to be and how far there is still an opportunity meaningfully to debate the claimed rights.</p

    Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

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    New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

    Impact of meta-roles on the evolution of organisational institutions

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    This paper investigates the impact of changes in agents' beliefs coupled with dynamics in agents' meta-roles on the evolution of institutions. The study embeds agents' meta-roles in the BDI architecture. In this context, the study scrutinises the impact of cognitive dissonance in agents due to unfairness of institutions. To showcase our model, two historical long-distance trading societies, namely Armenian merchants of New-Julfa and the English East India Company are simulated. Results show how change in roles of agents coupled with specific institutional characteristics leads to changes of the rules in the system.Comment: arXiv admin note: text overlap with arXiv:2004.1185
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