The pathogenetic basis for a disease continuum in early- and late-onset ataxia-dystonia supports a unified genetic diagnostic approach

INTRODUCTION: Genetically inherited ataxic disorders are classified by their age of disease presentation into early- and late-onset ataxia (EOA and LOA, presenting before or after the 25th year-of-life). In both disease groups, comorbid dystonia co-occurs frequently. Despite overlapping genes and pathogenetic features, EOA, LOA and dystonia are considered as different genetic entities with a separate diagnostic approach. This often leads to diagnostic delay. So far, the possibility of a disease continuum between EOA, LOA and mixed ataxia-dystonia has not been explored in silico. In the present study, we analyzed the pathogenetic mechanisms underlying EOA, LOA and mixed ataxia-dystonia.METHODS: We analyzed the association of 267 ataxia genes with comorbid dystonia and anatomical MRI lesions in literature. We compared anatomical damage, biological pathways, and temporal cerebellar gene expression between EOA, LOA and mixed ataxia-dystonia.RESULTS: The majority (≈65%) of ataxia genes were associated with comorbid dystonia in literature. Both EOA and LOA gene groups with comorbid dystonia were significantly associated with lesions in the cortico-basal-ganglia-pontocerebellar network. EOA, LOA and mixed ataxia-dystonia gene groups were enriched for biological pathways related to nervous system development, neural signaling and cellular processes. All genes revealed similar cerebellar gene expression levels before and after 25 years of age and during cerebellar development.CONCLUSION: In EOA, LOA and mixed ataxia-dystonia gene groups, our findings show similar anatomical damage, underlying biological pathways and temporal cerebellar gene expression patterns. These findings may suggest the existence of a disease continuum, supporting the diagnostic use of a unified genetic approach.</p

Ambient Intelligence and Persuasive Technology: The Blurring Boundaries Between Human and Technology

The currently developing fields of Ambient Intelligence and Persuasive Technology bring about a convergence of information technology and cognitive science. Smart environments that are able to respond intelligently to what we do and that even aim to influence our behaviour challenge the basic frameworks we commonly use for understanding the relations and role divisions between human beings and technological artifacts. After discussing the promises and threats of these technologies, this article develops alternative conceptions of agency, freedom, and responsibility that make it possible to better understand and assess the social roles of Ambient Intelligence and Persuasive Technology. The central claim of the article is that these new technologies urge us to blur the boundaries between humans and technologies also at the level of our conceptual and moral frameworks

Participation patterns of interactive playful museum exhibits: evaluating the participant journey map through situated observations

The Participant Journey Map (PJM) provides structured insight into participation with interactive play in (semi-) public environments. It supports understanding of participants’ behavior and was developed based on experiences with previously developed playful interfaces, related research and expert interviews. We apply the PJM to interactive playful museum exhibits and evaluate and refine it based on its usage in a situated context. We observed 672 play sessions with 6 interactive playful museum exhibits. The observation data was visualized and analyzed using the PJM. This study shows that the PJM provides a realistic representation of participant behaviour, can be used to identify stagnations and progressions in participation flow, and support identification of influencing design and contextual factors. With this paper we contribute by presenting the PJM as a well-grounded, valuable and realistic framework for evaluating and understanding participation with situated interactive play, based on post-hoc evaluation of multiple interfaces with many users.NWOComputer Systems, Imagery and Medi

The importance of the peak-end rule for repeated visits to Augmented Play Spaces

We propose a research direction into the role of the peak-end rule to engage people into Augmented Play Spaces (APS). The peak(s) and ending of an experience are defining moments for how an experience is remembered afterwards. An important factor contributing to the likelihood of engagement in an APS is a positive previous experience (with the same or a similar system).NWO023.013.062Computer Systems, Imagery and Medi

A panel analysis of UK industrial company failure

We examine the failure determinants for large quoted UK industrials using a panel data set comprising 539 firms observed over the period 1988-93. The empirical design employs data from company accounts and is based on Chamberlain’s conditional binomial logit model, which allows for unobservable, firm-specific, time-invariant factors associated with failure risk. We find a noticeable degree of heterogeneity across the sample companies. Our panel results show that, after controlling for unobservables, lower liquidity measured by the quick assets ratio, slower turnover proxied by the ratio of debtors turnover, and profitability were linked to the higher risk of insolvency in the analysis period. The findings appear to support the proposition that the current cash-flow considerations, rather than the future prospects of the firm, determined company failures over the 1990s recession

Експортно­імпортні операції в Чернігівській губернії на початку ХХ ст.

У статті на основі маловідомих фактів досліджується організація зовнішньої торгівлі в Чернігівській губернії Російської імперії на початку ХХ ст. Показані основні екпортно-імпортні операції, особливості економічного розвитку регіону.В научной статье на основании использования неизвестных ранее фактов исследуется организация внешней торговли в Черниговской губернии Российской империи в начале ХХ века. Показаны основные экспортно-импортные операции и особенности экономического развития региона.In scientific article author research the special organization of foreign trade in Chernigov’s region of Russian empire in the beginning of 20 century. Export-import operations and economic development had illustration in this work

Neurophysiology

Contains reports on five research projects.Bell Telephone Laboratories, IncorporatedNational Institutes of HealthTeagle Foundation, Incorporate