A rare duplication on chromosome 16p11.2 is identified in patients with psychosis in Alzheimer's disease

Epidemiological and genetic studies suggest that schizophrenia and autism may share genetic links. Besides common single nucleotide polymorphisms, recent data suggest that some rare copy number variants (CNVs) are risk factors for both disorders. Because we have previously found that schizophrenia and psychosis in Alzheimer's disease (AD+P) share some genetic risk, we investigated whether CNVs reported in schizophrenia and autism are also linked to AD+P. We searched for CNVs associated with AD+P in 7 recurrent CNV regions that have been previously identified across autism and schizophrenia, using the Illumina HumanOmni1-Quad BeadChip. A chromosome 16p11.2 duplication CNV (chr16: 29,554,843-30,105,652) was identified in 2 of 440 AD+P subjects, but not in 136 AD subjects without psychosis, or in 593 AD subjects with intermediate psychosis status, or in 855 non-AD individuals. The frequency of this duplication CNV in AD+P (0.46%) was similar to that reported previously in schizophrenia (0.46%). This duplication CNV was further validated using the NanoString nCounter CNV Custom CodeSets. The 16p11.2 duplication has been associated with developmental delay, intellectual disability, behavioral problems, autism, schizophrenia (SCZ), and bipolar disorder. These two AD+P patients had no personal of, nor any identified family history of, SCZ, bipolar disorder and autism. To the best of our knowledge, our case report is the first suggestion that 16p11.2 duplication is also linked to AD+P. Although rare, this CNV may have an important role in the development of psychosis

Robust whole-brain segmentation: Application to traumatic brain injury

We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called "Multi-Atlas Label Propagation with Expectation-Maximisation based refinement" (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to differentiate subjects with the presence of a mass lesion or midline shift from those with diffuse brain injury with 76.0% accuracy. The thalamus, putamen, pallidum and hippocampus are particularly affected. Their involvement predicts TBI disease progression.This work was partially funded under the 7th Framework Programme by the European Commission (http://cordis.europa.eu/ist/, TBIcare: http://www.tbicare.eu/, last accessed: 8 December 2014). The research was further supported by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. AH is supported by the Department of Health via the NIHR comprehensive BRC award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and Kings College Hospital NHS Foundation Trust. This work was further supported by a Medical Research Council (UK) Program Grant (Acute brain injury: heterogeneity of mechanisms, therapeutic targets and outcome effects [G9439390 ID 65883]), the UK National Institute of Health Research Biomedical Research Centre at Cambridge, the Technology Platform funding provided by the UK Department of Health and an EPSRC Pathways to Impact award. VFJN is supported by a Health Foundation/Academy of Medical Sciences Clinician Scientist Fellowship. DKM is supported by an NIHR Senior Investigator Award. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in study design, data collection and analyses, decision to publish, or preparation of the manuscript

Evaluation of the Detectability of Electromechanical Faults in Induction Motors Via Transient Analysis of the Stray Flux

© 1972-2012 IEEE. The stray flux that is present in the vicinity of an induction motor is a very interesting information source to detect several types of failures in these machines. The analysis of this quantity can be employed, in some cases, as a supportive tool to complement the diagnosis provided by other quantities. In other cases, when no other motor quantities are available, stray flux analysis can become one of the few alternatives to evaluate the motor condition. Its noninvasive nature, low cost, and easy implementation makes it a very interesting option that requires further investigation. The aim of this work is to evaluate the suitability of the stray flux analysis under the starting transient as a way to detect certain faults in induction motors (broken rotor bars and misalignments), even when these types of faults coexist in the motor. To this end, advanced signal processing tools will be applied. Several positions of the flux sensors are considered in this study. Also, for the first time, a fault indicator based on the stray flux analysis under the starting is introduced and its sensitivity is compared versus other indicators relying on other quantities. It must be emphasized that, since the capture of the transient and steady-state flux signals can be carried out in the same measurement, the application of the approach presented in this work is straightforward and its derived information may become crucial for the diagnosis of some faults.Ministerio de Economía y Competitividad’ (MINECO) and FEDER program in the framework of the ‘Proyectos I+D del Subprograma de Generación de Conocimiento, Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia’ (ref: DPI2014-52842-P)

Evaluating a transfer gradient assumption in a fomite-mediated microbial transmission model using an experimental and Bayesian approach

Current microbial exposure models assume that microbial exchange follows a concentration gradient during hand-to-surface contacts. Our objectives were to evaluate this assumption using transfer efficiency experiments and to evaluate a model's ability to explain concentration changes using approximate Bayesian computation (ABC) on these experimental data. Experiments were conducted with two phages (MS2, ΦX174) simultaneously to study bidirectional transfer. Concentrations on the fingertip and surface were quantified before and after fingertip-to-surface contacts. Prior distributions for surface and fingertip swabbing efficiencies and transfer efficiency were used to estimate concentrations on the fingertip and surface post contact. To inform posterior distributions, Euclidean distances were calculated for predicted detectable concentrations (log10 PFU cm−2) on the fingertip and surface post contact in comparison with experimental values. To demonstrate the usefulness of posterior distributions in calibrated model applications, posterior transfer efficiencies were used to estimate rotavirus infection risks for a fingertip-to-surface and subsequent fingertip-to-mouth contact. Experimental findings supported the transfer gradient assumption. Through ABC, the model explained concentration changes more consistently when concentrations on the fingertip and surface were similar. Future studies evaluating microbial transfer should consider accounting for differing fingertip-to-surface and surface-to-fingertip transfer efficiencies and extend this work for other microbial types

Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging

In-play sports betting: a scoping study

Technology has changed the nature of gambling practices over the last decade and is continuing to do so. The online sports betting industry has become a rapidly growing sector of the global economy, with online sports betting contributing 37% of the annual online gambling market in Europe. There has been an integration of social and technological processes that has enabled the cultural saliency of contemporary online betting. One of the more newly introduced forms of online sports betting is in-play sports betting behaviour (the betting on events within a sporting event such as football and cricket). In-play sports betting features (such as 'cash out') are increasing in popularity amongst online gambling operators. A scoping study was carried out examining the evolution of this new form of gambling practice which included both a systematic literature review and the examination of 338 online gambling websites that offered sports betting. The present study identified a comprehensive list of what in-play betting features are currently being offered on online gambling websites as well as other information concerning in-play sports betting. A total of 16 academic papers and two 'grey literature' reports and were identified in the systematic review. Out of 338 online gambling websites that were visited, 26% of these offered at least on in-play betting feature. Results from the systematic review suggest that in-play sports betting has the potential to be more harmful than other ways of gambling because of the inherent structural characteristics