Placental determinants of fetal growth: identification of key factors in the insulin-like growth factor and cytokine systems using artificial neural networks

<p>Abstract</p> <p>Background</p> <p>Changes and relationships of components of the cytokine and IGF systems have been shown in placenta and cord serum of fetal growth restricted (FGR) compared with normal newborns (AGA). This study aimed to analyse a data set of clinical and biochemical data in FGR and AGA newborns to assess if a mathematical model existed and was capable of identifying these two different conditions in order to identify the variables which had a mathematically consistent biological relevance to fetal growth.</p> <p>Methods</p> <p>Whole villous tissue was collected at birth from FGR (N = 20) and AGA neonates (N = 28). Total RNA was extracted, reverse transcribed and then real-time quantitative (TaqMan) RT-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6. The corresponding proteins with TNF-α in addition were assayed in placental lysates using specific kits. The data were analysed using Artificial Neural Networks (supervised networks), and principal component analysis and connectivity map.</p> <p>Results</p> <p>The IGF system and IL-6 allowed to predict FGR in approximately 92% of the cases and AGA in 85% of the cases with a low number of errors. IGF-II, IGFBP-2, and IL-6 content in the placental lysates were the most important factors connected with FGR. The condition of being FGR was connected mainly with the IGF-II placental content, and the latter with IL-6 and IGFBP-2 concentrations in placental lysates.</p> <p>Conclusion</p> <p>These results suggest that further research in humans should focus on these biochemical data. Furthermore, this study offered a critical revision of previous studies. The understanding of this system biology is relevant to the development of future therapeutical interventions possibly aiming at reducing IL-6 and IGFBP-2 concentrations preserving IGF bioactivity in both placenta and fetus.</p

Women’s experiences of wearing therapeutic footwear in three European countries

Background: Therapeutic footwear is recommended for those people with severe foot problems associated with rheumatoid arthritis (RA). However, it is known that many do not wear them. Although previous European studies have recommended service and footwear design improvements, it is not known if services have improved or if this footwear meets the personal needs of people with RA. As an earlier study found that this footwear has more impact on women than males, this study explores women’s experiences of the process of being provided with it and wearing it. No previous work has compared women’s experiences of this footwear in different countries, therefore this study aimed to explore the potential differences between the UK, the Netherlands and Spain. Method: Women with RA and experience of wearing therapeutic footwear were purposively recruited. Ten women with RA were interviewed in each of the three countries. An interpretive phenomenological approach (IPA) was adopted during data collection and analysis. Conversational style interviews were used to collect the data. Results: Six themes were identified: feet being visibly different because of RA; the referring practitioners’ approach to the patient; the dispensing practitioners’ approach to the patient; the footwear being visible as different to others; footwear influencing social participation; and the women’s wishes for improved footwear services. Despite their nationality, these women revealed that therapeutic footwear invokes emotions of sadness, shame and anger and that it is often the final and symbolic marker of the effects of RA on self perception and their changed lives. This results in severe restriction of important activities, particularly those involving social participation. However, where a patient focussed approach was used, particularly by the practitioners in Spain and the Netherlands, the acceptance of this footwear was much more evident and there was less wastage as a result of the footwear being prescribed and then not worn. In the UK, the women were more likely to passively accept the footwear with the only choice being to reject it once it had been provided. All the women were vocal about what would improve their experiences and this centred on the consultation with both the referring practitioner and the practitioner that provides the footwear. Conclusion: This unique study, carried out in three countries has revealed emotive and personal accounts of what it is like to have an item of clothing replaced with an ‘intervention’. The participant’s experience of their consultations with practitioners has revealed the tension between the practitioners’ requirements and the women’s ‘social’ needs. Practitioners need greater understanding of the social and emotional consequences of using therapeutic footwear as an intervention

What is Donald Trump?:Forms of 'Celebrity' in Celebrity Politics

It is widely assumed that Donald Trump is a ‘celebrity politician’, and that he has cashed in his success on the reality show The Apprentice to secure political credibility and attention. In this respect he fits what Matthew Wood et al (2016) have labelled the ‘superstar celebrity politician’. This characterisation is the latest in a number of refinements to the definition and understanding of the celebrity politician. While this is a helpful move, I want to suggest that it might overlook one key dimension of the phenomenon. Definitions of the celebrity politician tend to focus on the source of their ‘celebrity’ – how they became famous, rather than on how they act out their celebrity role. This latter dimension features in media coverage, where journalists and commentators borrow from showbusiness to describe politics, but is less often analysed in the political science literature. It matters because, I want to suggest, celebrity politicians like Trump act as stars, whether of reality television, rock music or film. They do not just resemble stars; they are them. This is evident in how they are represented, how they perform and how their ‘fans’ respond to them. It is also symptomatic of wider changes in the conduct and form of the contemporary, mediatised political realm

Polymorphisms in folate-metabolizing genes, chromosome damage, and risk of Down syndrome in Italian women: identification of key factors using artificial neural networks

<p>Abstract</p> <p>Background</p> <p>Studies in mothers of Down syndrome individuals (MDS) point to a role for polymorphisms in folate metabolic genes in increasing chromosome damage and maternal risk for a Down syndrome (DS) pregnancy, suggesting complex gene-gene interactions. This study aimed to analyze a dataset of genetic and cytogenetic data in an Italian group of MDS and mothers of healthy children (control mothers) to assess the predictive capacity of artificial neural networks assembled in TWIST system in distinguish consistently these two different conditions and to identify the variables expressing the maximal amount of relevant information to the condition of being mother of a DS child.</p> <p>The dataset consisted of the following variables: the frequency of chromosome damage in peripheral lymphocytes (BNMN frequency) and the genotype for 7 common polymorphisms in folate metabolic genes (<it>MTHFR </it>677C>T and 1298A>C, <it>MTRR </it>66A>G, <it>MTR </it>2756A>G, <it>RFC1 </it>80G>A and <it>TYMS </it>28bp repeats and 1494 6bp deletion). Data were analysed using TWIST system in combination with supervised artificial neural networks, and a semantic connectivity map.</p> <p>Results</p> <p>TWIST system selected 6 variables (BNMN frequency, <it>MTHFR </it>677TT, <it>RFC1 </it>80AA, <it>TYMS </it>1494 6bp +/+, <it>TYMS </it>28bp 3R/3R and <it>MTR </it>2756AA genotypes) that were subsequently used to discriminate between MDS and control mothers with 90% accuracy. The semantic connectivity map provided important information on the complex biological connections between the studied variables and the two conditions (being MDS or control mother).</p> <p>Conclusions</p> <p>Overall, the study suggests a link between polymorphisms in folate metabolic genes and DS risk in Italian women.</p

Probabilistic downscaling of remote sensing data with applications for multi-scale biogeochemical flux modeling

Upscaling ecological information to larger scales in space and downscaling remote sensing observations or model simulations to finer scales remain grand challenges in Earth system science. Downscaling often involves inferring subgrid information from coarse-scale data, and such ill-posed problems are classically addressed using regularization. Here, we apply two-dimensional Tikhonov Regularization (2DTR) to simulate subgrid surface patterns for ecological applications. Specifically, we test the ability of 2DTR to simulate the spatial statistics of high-resolution (4 m) remote sensing observations of the normalized difference vegetation index (NDVI) in a tundra landscape. We find that the 2DTR approach as applied here can capture the major mode of spatial variability of the high-resolution information, but not multiple modes of spatial variability, and that the Lagrange multiplier (γ) used to impose the condition of smoothness across space is related to the range of the experimental semivariogram. We used observed and 2DTR-simulated maps of NDVI to estimate landscape-level leaf area index (LAI) and gross primary productivity (GPP). NDVI maps simulated using a γ value that approximates the range of observed NDVI result in a landscape-level GPP estimate that differs by ca 2% from those created using observed NDVI. Following findings that GPP per unit LAI is lower near vegetation patch edges, we simulated vegetation patch edges using multiple approaches and found that simulated GPP declined by up to 12% as a result. 2DTR can generate random landscapes rapidly and can be applied to disaggregate ecological information and compare of spatial observations against simulated landscapes

Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials

The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based endpoint selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy, corticobasal syndrome, multiple system atrophy and related disorders, to compare candidate clinical trial endpoints. In this multicentre United Kingdom study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and magnetic resonance imaging assessments at baseline, six and twelve-months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, progressive supranuclear palsy-subcortical (progressive supranuclear palsy-parkinsonism and progressive gait freezing subtypes), progressive supranuclear palsy-cortical (progressive supranuclear palsy-frontal, progressive supranuclear palsy-speech-and-language, and progressive supranuclear palsy-corticobasal syndrome subtypes), multiple system atrophy-parkinsonism, multiple system atrophy-cerebellar, corticobasal syndrome with and without evidence of Alzheimer’s disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling, and sample sizes for clinical trials of disease modifying agents, according to group and assessment type. Two hundred forty-three people were recruited (117 progressive supranuclear palsy, 68 corticobasal syndrome, 42 multiple system atrophy and 16 indeterminate; 138 [56.8%] male; age at recruitment 68.7 ± 8.61 years). One hundred fifty-nine completed six-month assessment (82 progressive supranuclear palsy, 27 corticobasal syndrome, 40 multiple system atrophy and 10 indeterminate) and 153 completed twelve-month assessment (80 progressive supranuclear palsy, 29 corticobasal syndrome, 35 multiple system atrophy and 9 indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N &amp;lt; 100 required for one-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease specific. In conclusion, phenotypic variance within progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial endpoints, from potential functional, cognitive, clinical or neuroimaging measures of disease progression