Statistical issues and approaches in endophenotype research

This special topic comprises 9 papers which were presented at the Symposium. (Chinese Science Bulletin, 2011, v. 56 n. 32 Editorial. doi: 10.1007/s11434-011-4716-4)This journal issue entitled: SPECIAL TOPIC Endophenotype Strategies for the Study of Neuropsychiatric DisordersThe endophenotype concept was initially proposed to enhance the power of genetic studies of complex disorders. It is closely related to the genetic component in a liability-threshold model; a perfect endophenotype should have a correlation of 1 with the genetic component of the liability to disease. In reality, a putative endophenotype is unlikely to be a perfect representation of the genetic component of disease liability. The magnitude of the correlation between a putative endophenotype and the genetic component of disease liability can be estimated by fitting multivariate genetic models to twin data. A number of statistical methods have been developed for incorporating endophenotypes in genetic linkage and association analyses with the aim of improving statistical power. The most recent of such methods can handle multiple endophenotypes simultaneously for the greatest increase in power. In addition to increasing statistical power, endophenotype research plays an important role in helping to understand the mechanisms which connect the associated genetic variants with disease occurrence. Novel statistical approaches may be required for the analysis of the complex relationships between endophenotypes at different levels and how they converge to cause the occurrence of disease. © 2011 Science China Press and Springer-Verlag Berlin Heidelberg.published_or_final_versio

A new framework for characterization of poroelastic materials using indentation

To characterize a poroelastic material, typically an indenter is pressed onto the surface of the material with a ramp of a finite approach velocity followed by a hold where the indenter displacement is kept constant This leads to deformation of the porous matrix, pressurization of the interstitial fluid and relaxation due to redistribution of fluid through the pores. In most studies the poroelastic properties, including elastic modulus, Poisson ratio and poroelastic diffusion coefficient, are extracted by assuming an instantaneous step indentation. However, exerting step like indentation is not experimentally possible and usually a ramp indentation with a finite approach velocity is applied. Moreover, the poroelastic relaxation time highly depends on the approach velocity in addition to the poroelastic diffusion coefficient and the contact area. Here, we extensively studied the effect of indentation velocity using finite element simulations which has enabled the formulation of a new framework based on a master curve that incorporates the finite rise time. To verify our novel framework, the poroelastic properties of two types of hydrogels were extracted experimentally using indentation tests at both macro and micro scales. Our new framework that is based on consideration of finite approach velocity is experimentally easy to implement and provides more accurate estimation of poroelastic properties

Pigs vs people: the use of pigs as analogues for humans in forensic entomology and taphonomy research

Most studies of decomposition in forensic entomology and taphonomy have used non-human cadavers. Following the recommendation of using domestic pig cadavers as analogues for humans in forensic entomology in the 1980s, pigs became the most frequently used model cadavers in forensic sciences. They have shaped our understanding of how large vertebrate cadavers decompose in, for example, various environments, seasons and after various ante- or postmortem cadaver modifications. They have also been used to demonstrate the feasibility of several new or well-established forensic techniques. The advent of outdoor human taphonomy facilities enabled experimental comparisons of decomposition between pig and human cadavers. Recent comparisons challenged the pig-as-analogue claim in entomology and taphonomy research. In this review, we discuss in a broad methodological context the advantages and disadvantages of pig and human cadavers for forensic research and rebut the critique of pigs as analogues for humans. We conclude that experiments using human cadaver analogues (i.e. pig carcasses) are easier to replicate and more practical for controlling confounding factors than studies based solely on humans and, therefore, are likely to remain our primary epistemic source of forensic knowledge for the immediate future. We supplement these considerations with new guidelines for model cadaver choice in forensic science research.Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made

A comparison of two-coloured filter systems for treating visual reading difficulties

Copyright @ 2013 Informa UK Ltd.Purpose: Visual disturbances that make it difficult to read text are often termed “visual stress”. Coloured filters in spectacles may help some children overcome reading problems that are often caused by visual stress. It has been suggested that for optimal effect each child requires an individually prescribed colour for each eye, as determined in systems such as the “Harris Foundation” coloured filters. Alternatively, it has been argued that only blue or yellow filters, as used in the “Dyslexia Research Trust” (DRT) filter system, are necessary to affect the underlying physiology. Method: A randomised, double blind trial with 73 delayed readers, was undertaken to compare changes in reading and spelling as well as irregular and non-word reading skills after 3 months of wearing either the Harris or the DRT filters. Results: Reading improved significantly after wearing either type of filter (t = −8.4, p < 0.01), with 40% of the children improving their reading age by 6 months or more during the 3 month trial. However, spelling ability (t = 2.1, p = 0.05) and non-word reading (f = 4.7, p < 0.05) improved significantly more with the DRT than with the Harris filters. Conclusion: Education and rehabilitation professionals should therefore, consider coloured filters as an effective intervention for delayed readers experiencing visual stress

Genetic overlap between bipolar illness and event-related potentials

Background. Electrophysiological endophenotypes are far less explored in bipolar disorder as compared to schizophrenia. No previous twin study of event-related potentials (ERPs) in bipolar illness has been reported. This study uses a twin design and advanced genetic model fitting analyses aiming to (1) assess and quantify the relationship of a range of ERP components with bipolar disorder with psychotic features, and (2) examine the source of the relationship (due to genetic or environmental factors). Method. P300, P50 suppression and mismatch negativity (MMN) were recorded in 10 discordant monozygotic (MZ) bipolar twin pairs, six concordant MZ bipolar twin pairs and 78 control twin pairs. Statistical analyses were based on structural equation modelling. Results. Bipolar disorder was significantly associated with smaller P300 amplitude and decreased P50 suppression. Genetic correlations were the main source of the associations, estimated to be -0.33 for P300 amplitude and 0·46 for P50 ratio. Individual-specific environmental influences were not significant. MMN and P300 latency were not associated with the illness. Conclusions. The results provide supporting evidence that P300 amplitude and P50 suppression ratio are ERP endophenotypes for bipolar disorder. © 2007 Cambridge University Press.published_or_final_versio

Anchoring Knowledge in Interaction: Towards a Harmonic Subsymbolic/Symbolic Framework and Architecture of Computational Cognition

We outline a proposal for a research program leading to a new paradigm, architectural framework, and prototypical implementation, for the cognitively inspired anchoring of an agent’s learning, knowledge formation, and higher reasoning abilities in real-world interactions: Learning through interaction in real-time in a real environment triggers the incremental accumulation and repair of knowledge that leads to the formation of theories at a higher level of abstraction. The transformations at this higher level filter down and inform the learning process as part of a permanent cycle of learning through experience, higher-order deliberation, theory formation and revision. The envisioned framework will provide a precise computational theory, algorithmic descriptions, and an implementation in cyber-physical systems, addressing the lifting of action patterns from the subsymbolic to the symbolic knowledge level, effective methods for theory formation, adaptation, and evolution, the anchoring of knowledge-level objects, real-world interactions and manipulations, and the realization and evaluation of such a system in different scenarios. The expected results can provide new foundations for future agent architectures, multi-agent systems, robotics, and cognitive systems, and can facilitate a deeper understanding of the development and interaction in human-technological settings

Sensing electric fields using single diamond spins

The ability to sensitively detect charges under ambient conditions would be a fascinating new tool benefitting a wide range of researchers across disciplines. However, most current techniques are limited to low-temperature methods like single-electron transistors (SET), single-electron electrostatic force microscopy and scanning tunnelling microscopy. Here we open up a new quantum metrology technique demonstrating precision electric field measurement using a single nitrogen-vacancy defect centre(NV) spin in diamond. An AC electric field sensitivity reaching ~ 140V/cm/\surd Hz has been achieved. This corresponds to the electric field produced by a single elementary charge located at a distance of ~ 150 nm from our spin sensor with averaging for one second. By careful analysis of the electronic structure of the defect centre, we show how an applied magnetic field influences the electric field sensing properties. By this we demonstrate that diamond defect centre spins can be switched between electric and magnetic field sensing modes and identify suitable parameter ranges for both detector schemes. By combining magnetic and electric field sensitivity, nanoscale detection and ambient operation our study opens up new frontiers in imaging and sensing applications ranging from material science to bioimaging

Many-particle entanglement with Bose--Einstein condensates

We propose a method to produce entangled states of several particles starting from a Bose-Einstein condensate. In the proposal, a single fast $\pi/2$ pulse is applied to the atoms and due to the collisional interaction, the subsequent free time evolution creates an entangled state involving all atoms in the condensate. The created entangled state is a spin-squeezed state which could be used to improve the sensitivity of atomic clocks.Comment: 4 pages. Minor modification

Loss of PINK1 Increases the Heart's Vulnerability to Ischemia-Reperfusion Injury.

Mutations in PTEN inducible kinase-1 (PINK1) induce mitochondrial dysfunction in dopaminergic neurons resulting in an inherited form of Parkinson's disease. Although PINK1 is present in the heart its exact role there is unclear. We hypothesized that PINK1 protects the heart against acute ischemia reperfusion injury (IRI) by preventing mitochondrial dysfunction