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

Outbreak detection algorithms for seasonal disease data: a case study using ross river virus disease

<p>Abstract</p> <p>Background</p> <p>Detection of outbreaks is an important part of disease surveillance. Although many algorithms have been designed for detecting outbreaks, few have been specifically assessed against diseases that have distinct seasonal incidence patterns, such as those caused by vector-borne pathogens.</p> <p>Methods</p> <p>We applied five previously reported outbreak detection algorithms to Ross River virus (RRV) disease data (1991-2007) for the four local government areas (LGAs) of Brisbane, Emerald, Redland and Townsville in Queensland, Australia. The methods used were the Early Aberration Reporting System (EARS) C1, C2 and C3 methods, negative binomial cusum (NBC), historical limits method (HLM), Poisson outbreak detection (POD) method and the purely temporal SaTScan analysis. Seasonally-adjusted variants of the NBC and SaTScan methods were developed. Some of the algorithms were applied using a range of parameter values, resulting in 17 variants of the five algorithms.</p> <p>Results</p> <p>The 9,188 RRV disease notifications that occurred in the four selected regions over the study period showed marked seasonality, which adversely affected the performance of some of the outbreak detection algorithms. Most of the methods examined were able to detect the same major events. The exception was the seasonally-adjusted NBC methods that detected an excess of short signals. The NBC, POD and temporal SaTScan algorithms were the only methods that consistently had high true positive rates and low false positive and false negative rates across the four study areas. The timeliness of outbreak signals generated by each method was also compared but there was no consistency across outbreaks and LGAs.</p> <p>Conclusions</p> <p>This study has highlighted several issues associated with applying outbreak detection algorithms to seasonal disease data. In lieu of a true gold standard, a quantitative comparison is difficult and caution should be taken when interpreting the true positives, false positives, sensitivity and specificity.</p

Monitoring bridge degradation using dynamic strain, acoustic emission and environmental data

This paper studies the long term structural behaviour of a Victorian railway viaduct under train loading and temperature variation. A multi-sensing, self-sustaining and remotely controlled data acquisition system combines fibre Bragg grating strain sensors with acoustic emission sensors for the study of both global dynamic deformation and local masonry deterioration. A statistical analysis of fibre Bragg grating signals reveals regions with permanent change in the dynamic deformation of the bridge over the last two years, whereas in other locations the deformation follows a seasonal cyclic pattern. In order to decouple changes in structural behaviour due to real mechanical damage from normal seasonal effect, the paper studies the ambient temperature effect on the dynamic deformation of the bridge, showing a clear linear dependence. In particular, when temperature increases, the dynamic strain due to train loading decreases uniformly in the longitudinal direction. In the transverse direction, where the thermal expansion is not constrained, the decrease is smaller. Decoupling damage from normal seasonal effect is of critical importance for the development of reliable early warning structural alert systems for infrastructure networks. The paper further studies local masonry deterioration at four critical location by combining data from the two sensing technologies: fibre optic and acoustic emission sensors.This work is being funded by the Lloyd’s Register Foundation, EPSRC and Innovate UK through the Data-Centric Engineering programme of the Alan Turing Institute and through the Cambridge Centre for Smart Infrastructure and Construction. Funding for the monitoring installation was provided by EPSRC under the Ref. EP/N021614/1 grant and by Innovate UK under the Ref. 920035 grant

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

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

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

Seismic response of partially saturated soils beneath shallow foundations under sequential ground motions

Induced partial saturation is an innovative soil improvement technique intended to mitigate earthquake-induced liquefaction. Historical records indicate that successive earthquakes may occur in high seismic areas. Therefore, a comprehensive understanding of the response of partially saturated soils to sequential ground motions is of great significance for the rational design and execution of this method in engineering practice. In this study, a series of dynamic centrifuge experiments were conducted to investigate the impacts of sequential ground motions on the behavior of partially saturated soils beneath shallow foundations. Two different shallow foundation models with a bearing pressure of 135 kPa and 50 kPa were examined. Three seismic simulations, in order of increasing amplitudes, were sequentially applied to loosely-packed partially saturated sand models prepared with air injection technique. The assessment of the test results indicated that shallow foundations resting on saturated models of loose sand did suffer excessive settlements with each event, producing a large embedment of the foundation. However, much smaller settlements were recorded for partially saturated ground, and the level of the foundation embedment remained limited in this case. The deformation vector fields also indicated that different displacement mechanisms were observed for each successive event