Outcomes in Trials for Management of Caries Lesions (OuTMaC):protocol

Background Clinical trials on caries lesion management use an abundance of outcomes, hampering comparison or combination of different study results and their efficient translation into clinical practice. Core outcome sets are an agreed standardized collection of outcomes which should be measured and reported in all trials for a specific clinical area. We aim to develop a core outcome set for trials investigating management of caries lesions in primary or permanent teeth conducted in primary or secondary care encompassing all stages of disease. Methods To identify existing outcomes, trials on prevention and trials on management of caries lesions will be screened systematically in four databases. Screening, extraction and deduplication will be performed by two researchers until consensus is reached. The definition of the core outcome set will by based on an e-Delhi consensus process involving key stakeholders namely patients, dentists, clinical researchers, health economists, statisticians, policy-makers and industry representatives. For the first stage of the Delphi process, a patient panel and a separate panel consisting of researchers, clinicians, teachers, industry affiliated researchers, policy-makers, and other interested parties will be held. An inclusive approach will be taken to involve panelists from a wide variety of socio-economic and geographic backgrounds. Results from the first round will be summarized and fed back to individuals for the second round, where panels will be combined and allowed to modify their scoring in light of the full panel’s opinion. Necessity for a third round will be dependent on the outcome of the first two. Agreement will be measured via defined consensus rules; up to a maximum of seven outcomes. If resources allow, we will investigate features that influence decision making for different groups. Discussion By using an explicit, transparent and inclusive multi-step consensus process, the planned core outcome set should be justifiable, relevant and comprehensive. The dissemination and application of this core outcome set should improve clinical trials on managing caries lesions and allow comparison, synthesis and implementation of scientific data. Trial registration Registered 12 April 2015 at COMET (http://www.comet-initiative.org

Evolution of Li, Be and B in the Galaxy

In this paper we study the production of Li, Be and B nuclei by Galactic cosmic ray spallation processes. We include three kinds of processes: (i) spallation by light cosmic rays impinging on interstellar CNO nuclei (direct processes); (ii) spallation by CNO cosmic ray nuclei impinging on interstellar p and 4He (inverse processes); and (iii) alpha-alpha fusion reactions. The latter dominate the production of 6Li and 7Li. We calculate production rates for a closed-box Galactic model, verifying the quadratic dependence of the Be and B abundances for low values of Z. These are quite general results and are known to disagree with observations. We then show that the multi-zone multi-population model we used previously for other aspects of Galactic evolution produces quite good agreement with the linear trend observed at low metallicities without fine tuning. We argue that reported discrepancies between theory and observations do not represent a nucleosynthetic problem, but instead are the consequences of inaccurate treatments of Galactic evolution.Comment: 26 pages, 5 figures, LaTeX. The Astrophysical Journal, in pres

Weight-for-Height, Body Fat, and Development in Children in the East Asia and Pacific Region

Importance: Weight-for-height z score (WHZ) is a standard indicator of children’s nutritional status even though it does not fully reflect body fat. Objective: To examine the combined association of WHZ and body fat with early development in the East Asia and Pacific region. Design, Setting, and Participants: Children from the East Asia–Pacific Early Child Development Scales validation study, with full data available regarding their nutritional status and outcomes, were included in this cross-sectional analysis. In brief, a multilevel stratified random sampling was used to select representative samples from each participating country in the study. WHZ and body fat were independently trichotomized using established references and were combined to form a 9-category exposure variable. Data collection was performed between 2012 and 2014, and the analyses were conducted in June 2021. Main Outcomes and Measures: The binary outcome variable of not being developmentally on track (hereafter referred to as poor development) was defined as a score less than the 25th percentile in the following domains: cognitive, language, socioemotional, motor development, and total development score. Poisson regression models were used to analyze the associations between the combined categories and poor development, adjusted for sociodemographic factors. Results: A total of 6815 children (mean [SD] age, 4.02 [0.8] years; 3434 girls [50.4%]) had full data available and were included in this study. Compared with children with normal weight and normal fat, those with wasting and low body fat had the highest likelihood of total poor development (prevalence ratio, 1.47; 95% CI, 1.28-1.70), followed by those with normal weight but low fat (prevalence ratio, 1.23; 95% CI, 1.11-1.36). Similar associations were found in language, cognitive, and socioemotional development, but not in motor development. Conclusions and Relevance: Poor development was more commonly found in children with low body fat independent of WHZ (wasted or normal weight). Early public health strategies may consider using a combination of WHZ and body fat as an indicator of poor development

Efficient Symmetry Reduction and the Use of State Symmetries for Symbolic Model Checking

One technique to reduce the state-space explosion problem in temporal logic model checking is symmetry reduction. The combination of symmetry reduction and symbolic model checking by using BDDs suffered a long time from the prohibitively large BDD for the orbit relation. Dynamic symmetry reduction calculates representatives of equivalence classes of states dynamically and thus avoids the construction of the orbit relation. In this paper, we present a new efficient model checking algorithm based on dynamic symmetry reduction. Our experiments show that the algorithm is very fast and allows the verification of larger systems. We additionally implemented the use of state symmetries for symbolic symmetry reduction. To our knowledge we are the first who investigated state symmetries in combination with BDD based symbolic model checking

Data Fusion of Objects Using Techniques Such as Laser Scanning, Structured Light and Photogrammetry for Cultural Heritage Applications

In this paper we present a semi-automatic 2D-3D local registration pipeline capable of coloring 3D models obtained from 3D scanners by using uncalibrated images. The proposed pipeline exploits the Structure from Motion (SfM) technique in order to reconstruct a sparse representation of the 3D object and obtain the camera parameters from image feature matches. We then coarsely register the reconstructed 3D model to the scanned one through the Scale Iterative Closest Point (SICP) algorithm. SICP provides the global scale, rotation and translation parameters, using minimal manual user intervention. In the final processing stage, a local registration refinement algorithm optimizes the color projection of the aligned photos on the 3D object removing the blurring/ghosting artefacts introduced due to small inaccuracies during the registration. The proposed pipeline is capable of handling real world cases with a range of characteristics from objects with low level geometric features to complex ones

Activation of Smoothened in the Hedgehog pathway unexpectedly increases Gα(s)-dependent cAMP levels in Drosophila

Hedgehog (Hh) signaling plays a key role in the development and maintenance of animal tissues. This signaling is mediated by the atypical G protein-coupled receptor (GPCR) Smoothened (Smo). Smo activation leads to signaling through several well-characterized effectors to activate Hh target gene expression. Recent studies have implicated activation of the heterotrimeric G protein subunit Gα(i) and the subsequent decrease in cellular cAMP levels in promoting the Hh response in flies and mammals. Although Hh stimulation decreases cAMP levels in some insect cell lines, here using a bioluminescence resonance energy transfer (BRET)-based assay we found that this stimulation had no detectable effect in Drosophila S2-R+ cells. However, we observed an unexpected and significant Gα(s)-dependent increase in cAMP levels in response to strong Smo activation in Smo-transfected cells. This effect was mediated by Smo's broadly conserved core, and was specifically activated in response to phosphorylation of the Smo C-terminus by GPCR kinase 2 (Gprk2). Genetic analysis of heterotrimeric G protein function in the developing Drosophila wing revealed a positive role for cAMP in the endogenous Hh response. Specifically, we found that mutation or depletion of Gα(s) diminished low-threshold Hh responses in Drosophila, whereas depletion of Gα(i) potentiated them (in contrast to previous findings). Our analysis suggested that regulated cAMP production is important for controlling the sensitivity of cellular responses to Hh in Drosophila

A DFT study of addition reaction between fragment ion (CH2) units and fullerene (C60) molecule

The theoretical study of the interaction between CH2 and fullerene (C60) suggests the existence of an addition reaction mechanism; this feature is studied by applying an analysis of electronic properties. Several different effects are evident in this interaction as a consequence of the particular electronic transfer which occurs during the procedure. The addition or insertion of the methylene group results in a process, where the inclusion of CH2 into a fullerene bond produces the formation of several geometric deformations. A simulation of these procedures was carried out, taking advantage of the dynamic semi-classical Born-Oppenheimer approximation. Dynamic aspects were analyzed at different speeds, for the interaction between the CH2 group and the two bonds: CC (6, 6) and CC (6, 5) respectively on the fullerene (C60) rings. All calculations which involved electrons employed DFT as well as exchange and functional correlation. The results indicate a tendency for the CH2 fragment to attack the CC (6, 5) bond

Potential economic impacts from improving breastfeeding rates in the UK

This article has been made available through the Brunel Open Access Publishing Fund.RATIONALE: Studies suggest that increased breastfeeding rates can provide substantial financial savings, but the scale of such savings in the UK is not known. OBJECTIVE: To calculate potential cost savings attributable to increases in breastfeeding rates from the National Health Service perspective. DESIGN AND SETTINGS: Cost savings focussed on where evidence of health benefit is strongest: reductions in gastrointestinal and lower respiratory tract infections, acute otitis media in infants, necrotising enterocolitis in preterm babies and breast cancer (BC) in women. Savings were estimated using a seven-step framework in which an incidence-based disease model determined the number of cases that could have been avoided if breastfeeding rates were increased. Point estimates of cost savings were subject to a deterministic sensitivity analysis. RESULTS: Treating the four acute diseases in children costs the UK at least £89 million annually. The 2009-2010 value of lifetime costs of treating maternal BC is estimated at £959 million. Supporting mothers who are exclusively breast feeding at 1 week to continue breast feeding until 4 months can be expected to reduce the incidence of three childhood infectious diseases and save at least £11 million annually. Doubling the proportion of mothers currently breast feeding for 7-18 months in their lifetime is likely to reduce the incidence of maternal BC and save at least £31 million at 2009-2010 value. CONCLUSIONS: The economic impact of low breastfeeding rates is substantial. Investing in services that support women who want to breast feed for longer is potentially cost saving