50 research outputs found

    Modelling the underlying principles of human aesthetic preference in evolutionary art

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    Our understanding of creativity is limited, yet there is substantial research trying to mimic human creativity in artificial systems and in particular to produce systems that automatically evolve art appreciated by humans. We propose here to study human visual preference through observation of nearly 500 user sessions with a simple evolutionary art system. The progress of a set of aesthetic measures throughout each interactive user session is monitored and subsequently mimicked by automatic evolution in an attempt to produce an image to the liking of the human user

    Phospholipase C-ε Regulates Epidermal Morphogenesis in Caenorhabditis elegans

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    Migration of cells within epithelial sheets is an important feature of embryogenesis and other biological processes. Previous work has demonstrated a role for inositol 1,4,5-trisphosphate (IP3)-mediated calcium signalling in the rearrangement of epidermal cells (also known as hypodermal cells) during embryonic morphogenesis in Caenorhabditis elegans. However the mechanism by which IP3 production is stimulated is unknown. IP3 is produced by the action of phospholipase C (PLC). We therefore surveyed the PLC family of C. elegans using RNAi and mutant strains, and found that depletion of PLC-1/PLC-ε produced substantial embryonic lethality. We used the epithelial cell marker ajm-1::gfp to follow the behaviour of epidermal cells and found that 96% of the arrested embryos have morphogenetic defects. These defects include defective ventral enclosure and aberrant dorsal intercalation. Using time-lapse confocal microscopy we show that the migration of the ventral epidermal cells, especially of the leading cells, is slower and often fails in plc-1(tm753) embryos. As a consequence plc-1 loss of function results in ruptured embryos with a Gex phenotype (gut on exterior) and lumpy larvae. Thus PLC-1 is involved in the regulation of morphogenesis. Genetic studies using gain- and loss-of-function alleles of itr-1, the gene encoding the IP3 receptor in C. elegans, demonstrate that PLC-1 acts through ITR-1. Using RNAi and double mutants to deplete the other PLCs in a plc-1 background, we show that PLC-3/PLC-γ and EGL-8/PLC-β can compensate for reduced PLC-1 activity. Our work places PLC-ε into a pathway controlling epidermal cell migration, thus establishing a novel role for PLC-ε

    Relationship of circulating hyaluronic Acid levels to disease control in asthma and asthmatic pregnancy.

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    Uncontrolled asthma is a risk factor for pregnancy-related complications. Hyaluronic acid (HA), a potential peripheral blood marker of tissue fibrosis in various diseases, promotes eosinophil survival and plays a role in asthmatic airway inflammation as well as in physiological processes necessary to maintain normal pregnancy; however the level of circulating HA in asthma and asthmatic pregnancy is unknown. We investigated HA levels in asthmatic patients (N = 52; asthmatic pregnant (AP) N = 16; asthmatic non-pregnant (ANP) N = 36) and tested their relationship to asthma control. Serum HA level was lower in AP than in ANP patients (27 [24.7-31.55] vs. 37.4 [30.1-66.55] ng/mL, p = 0.006); the difference attenuated to a trend after its adjustment for patients' age (p = 0.056). HA levels and airway resistance were positively (r = 0.467, p = 0.004), HA levels and Asthma Control Test (ACT) total score inversely (r = -0.437, p = 0.01) associated in ANP patients; these relationships remained significant even after their adjustments for age. The potential value of HA in the determination of asthma control was analyzed using ROC analysis which revealed that HA values discriminate patients with ACT total score >/=20 (controlled patients) and <20 (uncontrolled patients) with a 0.826 efficacy (AUC, 95% CI: 0.69-0.97, p = 0.001) when 37.4 ng/mL is used as cut-off value in ANP group, and with 0.78 efficacy (AUC, 95% CI: 0.65-0.92, p = 0.0009) in the whole asthmatic cohort. In conclusion circulating HA might be a marker of asthma control, as it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease of HA level in pregnancy may be the consequence of pregnancy induced immune tolerance

    Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development

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    CONTEXT: Genetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM). OBJECTIVE: We assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy. METHODS: 960 pregnant women (after dropouts 820: case/control: m99'WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m'99WHO criteria based on standard OGTT values. RESULTS: The most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m'99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT. CONCLUSIONS: We confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99'WHO and the IADPSG GDM diagnostic criteria

    The development and evaluation of a five-language multi-perspective standardised measure: clinical decision-making involvement and satisfaction (CDIS).

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    BACKGROUND: The aim of this study was to develop and evaluate a brief quantitative five-language measure of involvement and satisfaction in clinical decision-making (CDIS) - with versions for patients (CDIS-P) and staff (CDIS-S) - for use in mental health services. METHODS: An English CDIS was developed by reviewing existing measures, focus groups, semistructured interviews and piloting. Translations into Danish, German, Hungarian and Italian followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force principles of good practice for translation and cultural adaptation. Psychometricevaluation involved testing the measure in secondary mental health services in Aalborg, Debrecen, London, Naples, Ulm and Zurich. RESULTS: After appraising 14 measures, the Control Preference Scale and Satisfaction With Decision-making English-language scales were modified and evaluated in interviews (n = 9), focus groups (n = 22) and piloting (n = 16). Translations were validated through focus groups (n = 38) and piloting (n = 61). A total of 443 service users and 403 paired staff completed CDIS. The Satisfaction sub-scale had internal consistency of 0.89 (0.86-0.89 after item-level deletion) for staff and 0.90 (0.87-0.90) for service users, both continuous and categorical (utility) versions were associated with symptomatology and both staff-rated and service userrated therapeutic alliance (showing convergent validity), and not with social disability (showing divergent validity), and satisfaction predicted staff-rated (OR 2.43, 95%CI 1.54- 3.83 continuous, OR 5.77, 95%CI 1.90-17.53 utility) and service user-rated (OR 2.21, 95%CI 1.51-3.23 continuous, OR 3.13, 95%CI 1.10-8.94 utility) decision implementation two months later. The Involvement sub-scale had appropriate distribution and no floor or ceiling effects, was associated with stage of recovery, functioning and quality of life (staff only) (showing convergent validity), and not with symptomatology or social disability (showing divergent validity), and staff-rated passive involvement by the service user predicted implementation (OR 3.55, 95%CI 1.53-8.24). Relationships remained after adjusting for clustering by staff. CONCLUSIONS: CDIS demonstrates adequate internal consistency, no evidence of item redundancy, appropriate distribution, and face, content, convergent, divergent and predictive validity. It can be recommended for research and clinical use. CDIS-P and CDIS-S in all 3 five languages can be downloaded at http://www.cedar-net.eu/instruments. TRIAL REGISTRATION: ISRCTN75841675.CEDAR study is funded by a grant from the Seventh Framework Programme (Research Area HEALTH-2007-3.1-4 Improving clinical decision making) of the European Union (Grant no. 223290)

    Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system

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    Primary headaches such as migraine are among the most prevalent neurological disorders, affecting up to one-fifth of the adult population. The scientific work in the last decade has unraveled much of the pathophysiological background of migraine, which is now considered to be a neurovascular disorder. It has been discovered that the trigemino-cerebrovascular system plays a key role in migraine headache pathophysiology by releasing the potent vasodilator calcitonin gene-related peptide (CGRP). This neuropeptide is released in parallel with the pain and its concentration correlates well with the intensity of the headache. The development of drugs of the triptan class has provided relief for the acute attacks but at the cost of, mainly cardiovascular, side effects. Thus, the intention to improve treatment led to the development of small CGRP receptor antagonists such as olcegepant (BIBN4096BS) and MK-0974 that alleviate the acute migraine attack without acute side events. The purpose of this review is to give a short overview of the pathological background of migraine headache and to illustrate the mechanisms behind the actions of triptans and the promising CGRP receptor blockers

    The interplay of landscape composition and configuration: new pathways to manage functional biodiversity and agroecosystem services across Europe

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    Managing agricultural landscapes to support biodiversity and ecosystem services is a key aim of a sustainable agriculture. However, how the spatial arrangement of crop fields and other habitats in landscapes impacts arthropods and their functions is poorly known. Synthesising data from 49 studies (1515 landscapes) across Europe, we examined effects of landscape composition (% habitats) and configuration (edge density) on arthropods in fields and their margins, pest control, pollination and yields. Configuration effects interacted with the proportions of crop and non‐crop habitats, and species’ dietary, dispersal and overwintering traits led to contrasting responses to landscape variables. Overall, however, in landscapes with high edge density, 70% of pollinator and 44% of natural enemy species reached highest abundances and pollination and pest control improved 1.7‐ and 1.4‐fold respectively. Arable‐dominated landscapes with high edge densities achieved high yields. This suggests that enhancing edge density in European agroecosystems can promote functional biodiversity and yield‐enhancing ecosystem services
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