S-Duality for Linearized Gravity

We develope the analogue of S-duality for linearized gravity in (3+1)-dimensions. Our basic idea is to consider the self-dual (anti-self-dual) curvature tensor for linearized gravity in the context of the Macdowell-Mansouri formalism. We find that the strong-weak coupling duality for linearized gravity is an exact symmetry and implies small-large duality for the cosmological constant.Comment: 18 pages, Latex, to be published in Phys. Lett.

Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

Background<p></p> Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.<p></p> Methods<p></p> We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.<p></p> Results<p></p> Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.<p></p> Conclusions<p></p> We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis

Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure

Prevention of type 2 diabetes in adults with impaired glucose tolerance: the European Diabetes Prevention RCT in Newcastle upon Tyne, UK

<p>Abstract</p> <p>Background</p> <p>Diabetes prevalence is increasing. The Finnish Diabetes Prevention Study (DPS) showed a 58% reduction in Type 2 Diabetes (T2D) incidence in adults with impaired glucose tolerance (IGT). The European Diabetes Prevention Study (EDIPS) extends the DPS to different European populations, using the same study design. In the Newcastle arm of this study (EDIPS-Newcastle), we tested the hypothesis that T2D can be prevented by lifestyle intervention and explored secondary outcomes in relation to diabetes incidence.</p> <p>Methods</p> <p>We recruited 102 participants (42 men and 60 women, mean age 57 years, mean BMI 34 kgm^-2) with IGT to EDIPS-Newcastle and randomised to Intervention and usual care Control groups. The intervention included individual motivational interviewing aimed at: weight reduction, increase in physical activity, fibre and carbohydrate intake and reduction of fat intake (secondary outcomes). The primary outcome was diagnosis of T2D.</p> <p>Results</p> <p>Mean duration of follow-up was 3.1 years. T2D was diagnosed in 16 participants (I = 5, C = 11). Absolute incidence of T2D was 32.7 per 1000 person-years in the Intervention-group and 67.1 per 1000 person-years in the Control-group. The overall incidence of diabetes was reduced by 55% in the Intervention-group, compared with the Control-group: RR 0.45 (95%CI 0.2 to 1.2).</p> <p>Explanatory survival analysis of secondary outcomes showed that those who sustained beneficial changes for two or more years reduced their risk of developing T2D.</p> <p>Conclusion</p> <p>Our results are consistent with other diabetes prevention trials. This study was designed as part of a larger study and although the sample size limits statistical significance, the results contribute to the evidence that T2D can be prevented by lifestyle changes in adults with IGT. In explanatory analysis small sustained beneficial changes in weight, physical activity or dietary factors were associated with reduction in T2D incidence.</p> <p>Trial Registration</p> <p>International Standard Randomised Controlled Trial Number registry (ISRCTN)</p> <p>Registry number: ISRCTN 15670600</p> <p><url>http://www.controlled-trials.com/isrctn/search.html?srch=15670600&sort=3&dir=desc&max=10</url></p

Including cognitive aspects in multiple criteria decision analysis

"First Online: 21 December 2016"Many Multiple Criteria Decision Analysis (MCDA) methods have been proposed over the last decades. Some of the most known methods share some similarities in the way they are used and configured. However, we live in a time of change and nowadays the decision-making process (especially when done in group) is even more demanding and dynamic. In this work, we propose a Multiple Criteria Decision Analysis method that includes cognitive aspects (Cognitive Analytic Process). By taking advantage of aspects such as expertise level, credibility and behaviour style of the decision-makers, we propose a method that relates these aspects with problem configurations (alternatives and criteria preferences) done by each decision-maker. In this work, we evaluated the Cognitive Analytic Process (CAP) in terms of configuration costs and the capability to enhance the quality of the decision. We have used the satisfaction level as a metric to compare our method with other known MCDA methods in literature (Utility function, AHP and TOPSIS). Our method proved to be capable to achieve higher satisfaction levels compared to other MCDA methods, especially when the decision suggested by CAP is different from the one proposed by those methods.This work was supported by COMPETE Programme (operational programme for competitiveness) within project POCI-01-0145-FEDER-007043, by National Funds through the FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within the Projects UID/CEC/00319/2013, UID/EEA/00760/2013, and the João Carneiro PhD grant with the reference SFRH/BD/89697/2012.info:eu-repo/semantics/publishedVersio

How to find and diagnose a CDG due to defective N-glycosylation

Item does not contain fulltex

A Familial Case of Wiskott-Aldrich Syndrome with a Hotspot Mutation in Exon 2 of the WAS Gene

The Wiskott-Aldrich syndrome (WAS) is a severe X-linked disorder characterized classically by thrombocytopenia, immunodeficiency, and eczema. The phenotype observed in this syndrome is caused by mutation in the WAS gene. Peripheral blood DNAs were isolated from an 18-month-old boy with WAS and his mother, maternal uncle, and maternal grandmother. Genetic analysis for the detection of a mutation of WAS gene was performed by polymerase chain reaction-single strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing of the PCR product. In PCR-SSCP, the patient and his maternal uncle had an abnormal shift band, which was not found in normal controls, and his mother and maternal grandmother showed heterozygous bands. In direct sequencing analysis, the patient with WAS had CGC→CAC point mutation in exon 2 that resulted in an amino acid change in codon 86 (Arg86His). The present study identified a gene mutation responsible for WAS at a mutation hotspot of the WAS gene in a Korean family