A discrete methodology for controlling the sign of curvature and torsion for NURBS

This paper develops a discrete methodology for approximating the so-called convex domain of a NURBS curve, namely the domain in the ambient space, where a user-specified control point is free to move so that the curvature and torsion retains its sign along the NURBS parametric domain of definition. The methodology provides a monotonic sequence of convex polyhedra, converging from the interior to the convex domain. If the latter is non-empty, a simple algorithm is proposed, that yields a sequence of polytopes converging uniformly to the restriction of the convex domain to any user-specified bounding box. The algorithm is illustrated for a pair of planar and a spatial Bézier configuration

FGF-1 and FGF-2 modulate the E-cadherin/catenin system in pancreatic adenocarcinoma cell lines

Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) have been increasingly recognized to play an important role in the pathobiology of pancreatic malignancy. We have investigated the effects of FGF-1 and FGF-2 on the behaviour and adhesion properties of human pancreatic adenocarcinoma cell lines (BxPc3, T3M4 and HPAF) that were previously characterised for the expression of FGFRs. Here we show that exposure to FGF-1 and FGF-2 leads to significant and dose-dependent increase in E-cadherin-dependent cell-cell adhesion, tubular differentiation, and a reduced capacity to invade collagen gels. FGF stimulation produces phosphorylation of E-cadherin and β-catenin on tyrosine residues, as well as increased E-cadherin localisation to the cytoplasmic membrane and association with FGFR1 demonstrable by coimmunoprecipitation. These results demonstrate that FGF-1 and FGF-2 may be involved in the regulation of cell adhesion, differentiation and invasion of pancreatic cancer. © Cancer Research Campaign http://www.bjcancer.co

POLYMORPHISM OF OSTEOPROTEGERIN GENE IN INDONESIAN MEN WITH PERIODONTITIS

Objective: This work aimed to clarify the association of the severity of periodontitis and polymorphism in osteoprotegerin (OPG) (T950C) inIndonesian men.Methods: For DNA extraction, blood serum samples were used from 100 consenting Indonesian males for whom also the status of periodontitis hadbeen classified as mild, moderate, or severe. Polymerase chain reaction and restriction fragment length polymorphism techniques were applied toevaluate OPG (T950C) polymorphism, using Hind II restriction enzyme and electrophoresis on agarose gel to separate the indicative fragments.Results: The genotype distribution of the OPG (T950C) polymorphism had an appearance of an increasing percentage of TT genotype (allele T) withincreasing severitPeriodontitisy of periodontitis. The CC genotype was relatively rare (1%) in the tested Indonesian male population.Conclusions: The results show no significant association between the severity of periodontitis and polymorphism of OPG (T950C) in Indonesian men

The RECORD reporting guidelines: meeting the methodological and ethical demands of transparency in research using routinely-collected health data

Routinely-collected health data (RCD) are now used for a wide range of studies, including observational studies, comparative effectiveness research, diagnostics, studies of adverse effects, and predictive analytics. At the same time, limitations inherent in using data collected without specific a priori research questions are increasingly recognized. There is also a growing awareness of the suboptimal quality of reports presenting research based on RCD. This has created a perfect storm of increased interest and use of RCD for research, together with inadequate reporting of the strengths and weaknesses of these data resources. The REporting of studies Conducted using Observational Routinely-collected Data (RECORD) statement was developed to address these limitations and to help researchers using RCD to meet their ethical obligations of complete and accurate reporting, as well as improve the utility of research conducted using RCD. The RECORD statement has been endorsed by more than 15 journals, including Clinical Epidemiology. This journal now recommends that authors submit the RECORD checklist together with any manuscript reporting on research using RCD

Understanding the factors influencing yield strength on Mg alloys

Taking the Hall–Petch relationship as a starting point, the factors contributing towards Mg alloy strengthening are analysed, and their relative importance quantified. Solid-solution strengthening is modelled employing a power-law approach. The effects of various processing schedules are reviewed, showing that these play a relatively minor role. Grain refinement effects are described employing thermodynamic and kinetic formulations via the interdependence theory approach. The effects of rare earths are examined, showing that their major contribution is towards grain size control, an effect often in conflict with solid-solution strengthening. A computational approach is proposed, successfully modelling 104 grades reported in the literature. The approach may aid in tailoring and designing Mg alloys for yield strength.The authors wish to acknowledge nancial support from the Accelerated Metallurgy Project, which is co-funded by the European Commission in the 7th Framework Programme (Contract NMP4-LA-2011-263206), by the European Space Agency and by the individual partner organisations.This is the original submitted version of the manuscript. It does not include changes arising from peer-review or editing. The final published version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S1359645414003279#

EQRbot: A chatbot delivering EQR argument-based explanations

Data availability statement: The provided link: https://github.com/FCast07/EQRbot refers to the GitHub repository that stores the chatbot programming code.Recent years have witnessed the rise of several new argumentation-based support systems, especially in the healthcare industry. In the medical sector, it is imperative that the exchange of information occurs in a clear and accurate way, and this has to be reflected in any employed virtual systems. Argument Schemes and their critical questions represent well-suited formal tools for modeling such information and exchanges since they provide detailed templates for explanations to be delivered. This paper details the EQR argument scheme and deploys it to generate explanations for patients' treatment advice using a chatbot (EQRbot). The EQR scheme (devised as a pattern of Explanation-Question-Response interactions between agents) comprises multiple premises that can be interrogated to disclose additional data. The resulting explanations, obtained as instances of the employed argumentation reasoning engine and the EQR template, will then feed the conversational agent that will exhaustively convey the requested information and answers to follow-on users' queries as personalized Telegram messages. Comparisons with a previous baseline and existing argumentation-based chatbots illustrate the improvements yielded by EQRbot against similar conversational agents.This research was partially funded by the UK Engineering & Physical Sciences Research Council (EPSRC) under Grant #EP/P010105/1

Metformin Decreases the Incidence of Pancreatic Ductal Adenocarcinoma Promoted by Diet-induced Obesity in the Conditional KrasG12D Mouse Model.

Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the KrasG12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-KrasG12D/+;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months. After 3 months, metformin prevented HFCD-induced weight gain, hepatic steatosis, depletion of intact acini, formation of advanced PanIN lesions, and stimulation of ERK and mTORC1 in pancreas. In addition to reversing hepatic and pancreatic histopathology, metformin normalized HFCD-induced hyperinsulinemia and hyperleptinemia among the 9-month cohort. Importantly, the HFCD-increased PDAC incidence was completely abrogated by metformin (p < 0.01). The obesogenic diet also induced a marked increase in the expression of TAZ in pancreas, an effect abrogated by metformin. In conclusion, administration of metformin improved the metabolic profile and eliminated the promoting effects of diet-induced obesity on PDAC formation in KC mice. Given the established safety profile of metformin, our findings have a strong translational potential for novel chemo-preventive strategies for PDAC

Heritable functional architecture in human visual cortex

How much of the functional organization of our visual system is inherited? Here we tested the heritability of retinotopic maps in human visual cortex using functional magnetic resonance imaging. We demonstrate that retinotopic organization shows a closer correspondence in monozygotic (MZ) compared to dizygotic (DZ) twin pairs, suggesting a partial genetic determination. Using population receptive field (pRF) analysis to examine the preferred spatial location and selectivity of these neuronal populations, we estimate a heritability around 10–20% for polar angle preferences and spatial selectivity, as quantified by pRF size, in extrastriate areas V2 and V3. Our findings are consistent with heritability in both the macroscopic arrangement of visual regions and stimulus tuning properties of visual cortex. This could constitute a neural substrate for variations in a range of perceptual effects, which themselves have been found to be at least partially genetically determined. These findings also add convergent evidence for the hypothesis that functional map topology is linked with cortical morphology

How often should we monitor for reliable detection of atrial fibrillation recurrence? Efficiency considerations and implications for study design

OBJECTIVE: Although atrial fibrillation (AF) recurrence is unpredictable in terms of onset and duration, current intermittent rhythm monitoring (IRM) diagnostic modalities are short-termed and discontinuous. The aim of the present study was to investigate the necessary IRM frequency required to reliably detect recurrence of various AF recurrence patterns. METHODS: The rhythm histories of 647 patients (mean AF burden: 12±22% of monitored time; 687 patient-years) with implantable continuous monitoring devices were reconstructed and analyzed. With the use of computationally intensive simulation, we evaluated the necessary IRM frequency to reliably detect AF recurrence of various AF phenotypes using IRM of various durations. RESULTS: The IRM frequency required for reliable AF detection depends on the amount and temporal aggregation of the AF recurrence (p<0.0001) as well as the duration of the IRM (p<0.001). Reliable detection (>95% sensitivity) of AF recurrence required higher IRM frequencies (>12 24-hour; >6 7-day; >4 14-day; >3 30-day IRM per year; p<0.0001) than currently recommended. Lower IRM frequencies will under-detect AF recurrence and introduce significant bias in the evaluation of therapeutic interventions. More frequent but of shorter duration, IRMs (24-hour) are significantly more time effective (sensitivity per monitored time) than a fewer number of longer IRM durations (p<0.0001). CONCLUSIONS: Reliable AF recurrence detection requires higher IRM frequencies than currently recommended. Current IRM frequency recommendations will fail to diagnose a significant proportion of patients. Shorter duration but more frequent IRM strategies are significantly more efficient than longer IRM durations. CLINICAL TRIAL REGISTRATION URL: Unique identifier: NCT00806689