22,385 research outputs found

    What is the pathogenic CAG expansion length in Huntington’s disease?

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    Huntington’s disease (HD) (OMIM 143100) is caused by an expanded CAG repeat tract in the HTT gene. The inherited CAG length is known to expand further in somatic and germline cells in HD subjects. Age at onset of the disease is inversely correlated with the inherited CAG length, but is further modulated by a series of genetic modifiers which are most likely to act on the CAG repeat in HTT that permit it to further expand. Longer repeats are more prone to expansions, and this expansion is age dependent and tissue-specific. Given that the inherited tract expands through life and most subjects develop disease in mid-life, this implies that in cells that degenerate, the CAG length is likely to be longer than the inherited length. These findings suggest two thresholds – the inherited CAG length which permits further expansion, and the intracellular pathogenic threshold, above which cells become dysfunctional and die. This two-step mechanism has been previously proposed and modelled mathematically to give an intracellular pathogenic threshold at a tract length of 115 CAG (95% confidence intervals 70-165 CAG). Empirically, the intracellular pathogenic threshold is difficult to determine. Clues from studies of people and models of HD, and from other diseases caused by expanded repeat tracts, place this threshold between 60-100 CAG, most likely towards the upper part of that range. We assess this evidence and discuss how the intracellular pathogenic threshold in manifest disease might be better determined. Knowing the cellular pathogenic threshold would be informative for both understanding the mechanism in HD and deploying treatments

    What is a good job? Modelling, measuring and improving job quality

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    Job quality is important: there is a substantial evidence base which illustrates the potential risks of poor quality work. These arise from the occurrence of accidents and disease due to unmanaged hazards, as well as from psychosocial factors such as poor pay and security, shift working or the combination of low control and high demands. There is also a body of evidence which demonstrates a positive impact from good quality work, with contributions to longevity, improved health and happiness, and business success. Despite this recognition of the importance of job quality, there is a lack of agreement around exactly what it is: particularly when trying to define it as a single construct. This research aimed to address this insufficiency by exploring the concept of the good job, and seeking to define job quality from an ergonomics perspective. This approach encourages a broad outlook, taking account of the physical and psychosocial aspects of work, the interactions between them, and the impact of individual variation. A theoretical model is presented to summarise the concept of job quality based on these considerations: this was applied to a study of three bus companies using both a quantitative survey tool and qualitative methods. In developing the model, an initial study was undertaken using repertory grid interviews to explore notions of work and job quality, and to identify the most important areas for further investigation. Interviews were conducted with individuals (n=18) who were employed in a wide range of jobs, and varied substantially in their priorities and preferences. Job content and relationships were often identified as more important than pay levels; but there was also evidence of compromise, where interviewees had prioritised jobs which met their practical needs. Also, individuals perceived a good job differently from one which was good for their health, and overall did not consider good health to be an essential outcome of a good job. Two subsequent studies were undertaken with a focus on jobs commonly done by those with low formal education, who may have more to gain from improved job quality. Semi-structured interviews were carried out firstly with cleaners and manufacturing employees (n=30) and then with bus drivers (n=80). A number of job features such as safety and job/employment security were found to be important for almost all interviewees, and thus were identified as core features of a good job. Other factors such as autonomy and preferences for particular working patterns were more variable, highlighting the importance of job-employee fit. The theoretical model of job quality constructed was based on these findings and the literature. The model was applied in a qualitative study of bus and coach drivers in three companies to assess whether this was a good job, whether it could be a good job, and what the barriers to this might be. In two of the companies bus driving was found to be a poor job, with low pay and inadequate health and safety management. In the third company it was better but there were still challenges: particularly time pressures, low physical activity, and varied and unsociable working patterns. It was identified that some of the barriers to good job quality for bus drivers and potentially in jobs more generally are difficult to address as they are intrinsic to the job. The best solution to these difficulties is to ensure a good fit between job and employee. Other barriers were identified which appeared to be financial, such as low pay in the two smaller companies, but they could also reflect cultural factors within the organisation or within wider society. A final study considered the measurement of job quality, in the light of the importance and extent of individual variation highlighted throughout the research. The DGB-Index (Deutscher Gewerkschaftsbund Index), a questionnaire tool designed and used in Germany which specifically accounts for this, was used in the same three bus companies (n=423). The results were compared with those from the qualitative study and reached similar conclusions, thus confirming the utility of the DGB-Index for job measurement and comparison when translated into English. The research demonstrated that it is possible to define and measure job quality and to compare it between organisations. The model of a good job constructed to facilitate this differs from those found in the literature: it takes into account the variation between individuals and the fact that they construe good jobs in different ways. Thus it highlights the importance to job quality of a good fit between job and individual in addition to the need for work to be good in terms of the more universal features such as job security, safety and adequate pay

    Novel modeling of task versus rest brain state predictability using a dynamic time warping spectrum: comparisons and contrasts with other standard measures of brain dynamics

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    Dynamic time warping, or DTW, is a powerful and domain-general sequence alignment method for computing a similarity measure. Such dynamic programming-based techniques like DTW are now the backbone and driver of most bioinformatics methods and discoveries. In neuroscience it has had far less use, though this has begun to change. We wanted to explore new ways of applying DTW, not simply as a measure with which to cluster or compare similarity between features but in a conceptually different way. We have used DTW to provide a more interpretable spectral description of the data, compared to standard approaches such as the Fourier and related transforms. The DTW approach and standard discrete Fourier transform (DFT) are assessed against benchmark measures of neural dynamics. These include EEG microstates, EEG avalanches, and the sum squared error (SSE) from a multilayer perceptron (MLP) prediction of the EEG time series, and simultaneously acquired FMRI BOLD signal. We explored the relationships between these variables of interest in an EEG-FMRI dataset acquired during a standard cognitive task, which allowed us to explore how DTW differentially performs in different task settings. We found that despite strong correlations between DTW and DFT-spectra, DTW was a better predictor for almost every measure of brain dynamics. Using these DTW measures, we show that predictability is almost always higher in task than in rest states, which is consistent to other theoretical and empirical findings, providing additional evidence for the utility of the DTW approach

    A review of Multi-Agent Simulation Models in Agriculture

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    Multi-Agent Simulation (MAS) models are intended to capture emergent properties of complex systems that are not amenable to equilibrium analysis. They are beginning to see some use for analysing agricultural systems. The paper reports on work in progress to create a MAS for specific sectors in New Zealand agriculture. One part of the paper focuses on options for modelling land and other resources such as water, labour and capital in this model, as well as markets for exchanging resources and commodities. A second part considers options for modelling agent heterogeneity, especially risk preferences of farmers, and the impacts on decision-making. The final section outlines the MAS that the authors will be constructing over the next few years and the types of research questions that the model will help investigate.multi-agent simulation models, modelling, agent-based model, cellular automata, decision-making, Crop Production/Industries, Environmental Economics and Policy, Farm Management, Land Economics/Use, Livestock Production/Industries,

    What you see is not what you get:The impact of vision impairment on judo performance

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    Paralympic sports provide opportunities for athletes with impairment to participate and excel in sport competitions. To compete in Paralympic sports, all athletes must undergo classification to determine whether they are eligible to compete and to allocate eligible athletes to different sport classes. Classification criteria need to be based on scientific evidence showing the relationship between impairment and performance. Judo is a Paralympic sport for athletes with vision impairment (VI), which does not yet have an evidence-based classification system in place. The aim of this thesis was therefore to examine the impact of vision impairment on performance in judo. The results of this thesis suggested that vision impairment impacts performance in judo, both when starting without and with a grip in place. On the basis of the results of this thesis, new classification criteria for VI judo are currently proposed and being discussed by the International Blind Sports Federation in consultation with the wider VI judo community. The proposed changes include new minimum impairment criteria as well as split of VI judo competition into separate sport classes for partially sighted and functionally blind judokas. Besides providing practical recommendations for the organisation of judo for individuals with vision impairment, the current thesis exemplifies the remarkable capabilities of skilled performers to functionally adapt under suboptimal visual conditions

    Are you Experienced? – A Model of Learning Systems Dynamics

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    37 p.Este artículo propone una contribución al campo de las habilidades de pensamiento sistémico en el ámbito de la dinámica de sistemas. Estudios empíricos mostraron que sujetos sin formación previa tienen graves problemas para comprender el comportamiento de un sistema simple de una variable flujo y una de estado. Aquí se propone que la integración implícita de Polanyi puede ser aplicada. Dentro de esta línea, Dreyfus y Dreyfus desarrollaron un modelo de aprendizaje de habilidades en cinco fases; de este modelo se derivan tres hipótesis acerca del aprendizaje de las habilidades de pensamiento sistémico y su importancia para elaborar e interactuar con modelos. Las pruebas de Ossimitz son adaptadas para una evaluación empírica. Esta corroboración esta en progreso, por lo cual es presente artículo se limita a la construcción conceptual

    Current advances in systems and integrative biology

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    Systems biology has gained a tremendous amount of interest in the last few years. This is partly due to the realization that traditional approaches focusing only on a few molecules at a time cannot describe the impact of aberrant or modulated molecular environments across a whole system. Furthermore, a hypothesis-driven study aims to prove or disprove its postulations, whereas a hypothesis-free systems approach can yield an unbiased and novel testable hypothesis as an end-result. This latter approach foregoes assumptions which predict how a biological system should react to an altered microenvironment within a cellular context, across a tissue or impacting on distant organs. Additionally, re-use of existing data by systematic data mining and re-stratification, one of the cornerstones of integrative systems biology, is also gaining attention. While tremendous efforts using a systems methodology have already yielded excellent results, it is apparent that a lack of suitable analytic tools and purpose-built databases poses a major bottleneck in applying a systematic workflow. This review addresses the current approaches used in systems analysis and obstacles often encountered in large-scale data analysis and integration which tend to go unnoticed, but have a direct impact on the final outcome of a systems approach. Its wide applicability, ranging from basic research, disease descriptors, pharmacological studies, to personalized medicine, makes this emerging approach well suited to address biological and medical questions where conventional methods are not ideal
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