The Heritability of Kidney Function Using an Older Australian Twin Population

Introduction: Twin studies are unique population models which estimate observed rather than inferred genetic components of complex traits. Nonmonogenic chronic kidney disease (CKD) is a complex disease process with strong genetic and environmental influences, amenable to twin studies. We aimed to assess the heritability of CKD using twin analysis and modeling within Older Australian Twin Study (OATS) data. Methods: OATS had 109 dizygotic (DZ) and 126 monozygotic (MZ) twin pairs with paired serum creatinine levels. Heritability of kidney function as estimated glomerular filtration rate (eGFR CKD Epidemiology Collaboration [CKD-EPI]) was modeled using the ACE model to estimate additive heritability (A), common (C), and unique (E) environmental factors. Intratwin pair analysis using mixed effects logistic regression allowed analysis of variation in eGFR from established CKD risk factors. Results: The median age was 69.71 (interquartile range 78.4–83.0) years, with 65% female, and a mean CKD-EPI of 82.8 ml/min (SD 6.7). The unadjusted ACE model determined kidney function to be 33% genetically determined (A), 18% shared genetic-environmental (C), and 49% because of unique environment (E). This remained unchanged when adjusted for age, hypertension, and sex. Hypertension was associated with eGFR; however, intertwin variance in hypertension did not explain variance in eGFR. Two or more hypertension medications were associated with decreased eGFR (P = 0.009). Conclusion: This study estimates observed heritability at 33%, notably higher than inferred heritability in genome-wide association study (GWAS) (7.1%–18%). Epigenetics and other genomic phenomena may explain this heritability gap. Difference in antihypertension medications explains part of unique environmental exposures, though discordance in hypertension and diabetes does not

Playing Kant at the Court of King Arthur

This article contrasts the sense in which those whom Bernard Williams called ‘political realists’ and John Rawls are committed to the idea that political philosophy has to be distinctively political. Distinguishing the realist critique of political moralism from debates over ideal and non-ideal theory, it is argued that Rawls is more realist than many realists realise, and that realists can learn more about how to make a distinctively political vision of how our life together should be organised from his theorising, although it also points to a worrying tendency among Rawlsians to reach for inappropriately moralised arguments. G. A. Cohen’s advocacy of socialism and the second season of HBO’s The Wire are used as examples to illustrate these points

Distribué fibre optique des infrastructures du CERN dans la région des molasse

The European Centre for Nuclear Research (CERN) is a large underground laboratory and it is home to two large particle accelerators, including the «Large Hadron Collider» (LHC). The particles travel at the speed of light through a series of tunnels which must comply with the high serviceability requirements. However, the underground facilities have expanded over a period of 40 years with new tunnels, shafts and caverns. Structural ageing and deterioration of the infrastructure can alter the drainage conditions around tunnels and this can cause, in turn, excess deformation of the tunnels and serviceability issue for the particle accelerators. A remote monitoring system based on distributed fibre-optic strain sensing technology has been implemented in some of the concrete-lined tunnels in order to gain insight in the long-term mechanical behaviour of the underground system. This paper presents the results of the monitoring programme and the results show a slow development of ovalisation of the tunnel over a period of three years.Le Centre Européen pour la Recherche Nucléaire (CERN) est un grand laboratoire souterrain qui héberge deux accélérateurs de particules dont le « Large Hadron Collider » (LHC). Les particules se déplacent à la vitesse de la lumière à travers un réseau de tunnels qui doivent répondre à des exigences élevées de service. L’infrastructure souterraine du CERN s’est étendue sur une période de 40 ans avec la construction de nouveaux tunnels, puits et cavernes. Le vieillissement des matériaux et la détérioration structurelles des ouvrages peuvent altérer les conditions de drainage autour des tunnels ce qui peut engendrer, à son tour, des déformations excessives et atteindre la limite de service des accélérateurs de particules. Un système de monitoring à distance avec des câbles en fibre optique a été mis en place dans certains tunnels afin d’étudier le comportement à long terme. Cet article présente les résultats de la compagne de monitoring et démontre une ovalisation des tunnels sur une période de trois ans

Identification of optimal epitopes for Plasmodium falciparum rapid diagnostic tests that target histidine-rich proteins 2 and 3

Rapid diagnostic tests (RDTs) represent important tools to diagnose malaria infection. To improve understanding of the variable performance of RDTs that detect the major target in Plasmodium falciparum, namely, histidine-rich protein 2 (HRP2), and to inform the design of better tests, we undertook detailed mapping of the epitopes recognized by eight HRP-specific monoclonal antibodies (MAbs). To investigate the geographic skewing of this polymorphic protein, we analyzed the distribution of these epitopes in parasites from geographically diverse areas. To identify an ideal amino acid motif for a MAb to target in HRP2 and in the related protein HRP3, we used a purpose-designed script to perform bioinformatic analysis of 448 distinct gene sequences from pfhrp2 and from 99 sequences from the closely related gene pfhrp3. The frequency and distribution of these motifs were also compared to the MAb epitopes. Heat stability testing of MAbs immobilized on nitrocellulose membranes was also performed. Results of these experiments enabled the identification of MAbs with the most desirable characteristics for inclusion in RDTs, including copy number and coverage of target epitopes, geographic skewing, heat stability, and match with the most abundant amino acid motifs identified. This study therefore informs the selection of MAbs to include in malaria RDTs as well as in the generation of improved MAbs that should improve the performance of HRP-detecting malaria RDTs. Copyright © 2012, American Society for Microbiology

An investigation of supervector regression for forensic voice comparison on small data

International audienceThe present paper deals with an observer design for a nonlinear lateral vehicle model. The nonlinear model is represented by an exact Takagi-Sugeno (TS) model via the sector nonlinearity transformation. A proportional multiple integral observer (PMIO) based on the TS model is designed to estimate simultaneously the state vector and the unknown input (road curvature). The convergence conditions of the estimation error are expressed under LMI formulation using the Lyapunov theory which guaranties bounded error. Simulations are carried out and experimental results are provided to illustrate the proposed observer

Dengue disease outbreak definitions are implicitly variable.

Infectious diseases rarely exhibit simple dynamics. Outbreaks (defined as excess cases beyond response capabilities) have the potential to cause a disproportionately high burden due to overwhelming health care systems. The recommendations of international policy guidelines and research agendas are based on a perceived standardised definition of an outbreak characterised by a prolonged, high-caseload, extra-seasonal surge. In this analysis we apply multiple candidate outbreak definitions to reported dengue case data from Brazil to test this assumption. The methods identify highly heterogeneous outbreak characteristics in terms of frequency, duration and case burden. All definitions identify outbreaks with characteristics that vary over time and space. Further, definitions differ in their timeliness of outbreak onset, and thus may be more or less suitable for early intervention. This raises concerns about the application of current outbreak guidelines for early warning/identification systems. It is clear that quantitatively defining the characteristics of an outbreak is an essential prerequisite for effective reactive response. More work is needed so that definitions of disease outbreaks can take into account the baseline capacities of treatment, surveillance and control. This is essential if outbreak guidelines are to be effective and generalisable across a range of epidemiologically different settings

Distributed sensing of a masonry vault during nearby piling

Piles were constructed inside historic brick barrel vaults during the London Bridge Station Redevelopment. In order to ensure safe operation of the tracks above, movements of the vaults were monitored regularly by total stations. Concurrently, two distributed sensing technologies, fibre optic cables and laser scanners, were used to investigate the vault response to settlements. This paper discusses the monitoring data retrieved from these ‘point’ and ‘distributed’ sensing technologies and evaluates their use in structural assessment. The total station data are examined first. It is characterized by high precision and limited spatial coverage due to the use of optical targets. As a result, the total station data are useful for threshold detection but do not provide a detailed understanding of structural response or damage. In contrast, by utilizing distributed fibre optic sensors based on Brillouin optical domain reflectometry, the strain development in the structure during piling is quantified. The location and width of resulting crack openings are also determined, providing useful indicators for damage evaluation. The comparison of point clouds from laser scanners obtained at different stages of pile construction further expands the spatial coverage by detecting global movement of the structure on all visible surfaces. Using these data, the two hinge‐response mechanism of the vault is revealed. The rich distributed data enable the calibration of the 2D mechanism and the finite element models, elucidating the contribution of arch stiffness, arch and backfill interaction, potential lateral movements and inter‐ring sliding to the response