A Web-based multimedia collaboratory. Empirical work studies in film archives

This report represents the latest study in the activity on Ecological Information Systems conducted in the Center for Human Machine Interaction situated at Ris National Laboratory and the University of Aarhus. The purpose of this activity is to give a description of the characteristics of work domains that will serve to outline the general context of concern to design of collaboratories. In addition, a set of preliminary implications for the design of a collaboratory are derived from the cognitive work analysis. To anticipate, further research on this approach to the design of collaboratories will show how the preceding analysis is likely to lead to a novel theoretical framework, called Ecological Collaborative Information Systems (ECIS), required for the design of collaboratories. The intention is to illustrate how the general principles of ECIS can be instantiated to develop a concrete design product: A crossdisciplinary and cross-cultural collaboratory to support customer service and professional research in archives. A web based Collaboratory Numerous valuable historic and cultural films and their sources are scattered in various national archives. Knowledge and usage of the multinational film material are severely impeded by access problems. To fully exploit the cultural film heritage internationally, a high degree of cross-disciplinary and international collaboration among professionals working with the film media is required. The Collaboratory for Annotation, Indexing and Retrieval of Digitized Historical Archive Material (Collate) is intended to foster and support collaboration on research, cultural mediation and preservation of films through a distributed multimedia repository. The collaboratory will provide webbased tools and interfac..

The Free-movement pattern Y-maze:A cross-species measure of working memory and executive function

Numerous neurodegenerative and psychiatric disorders are associated with deficits in executive functions, such as working memory and cognitive flexibility. Progress in developing effective treatments for disorders may benefit from targeting these cognitive impairments, the success of which is predicated on the development of animal models with validated behavioural assays. Zebrafish offer a promising model for studying complex brain disorders, but tasks assessing executive function are lacking. The Free movement pattern (FMP) Ymaze combines aspects of the common Y-maze assay, which exploits the inherent motivation of an organism to explore an unknown environment, with analysis based on a series of sequential two-choice discriminations. We validate the task as a measure of working memory and executive function by comparing task performance parameters in adult zebrafish treated with a range of glutamatergic, cholinergic and dopaminergic drugs known to impair working memory and cognitive flexibility. We demonstrate the cross-species validity of the task by assessing performance parameters in adapted versions of the task for mice and Drosophila, and finally a virtual version in humans, and identify remarkable commonalities between vertebrate species’ navigation of the maze. Together, our results demonstrate that the FMP Y-maze is a sensitive assay for assessing working memory and cognitive flexibility across species from invertebrates to humans, providing a simple and widely applicable behavioural assay with exceptional translational relevance

A factor analysis approach to modelling the early diversification of terrestrial vegetation

peer reviewedData from a new comprehensive macrofossil-based compilation of early plant genera are analyzed via a Q-mode factor analysis. This compilation ranges from the Silurian to the earliest Carboniferous and illustrates the key vegetation changes that took place during the configuration of early terrestrial ecosystems. Results reveal that four factors can be used to explain more than 90% of the variance in the data. These factors are interpreted as the major phases of the early land plant evolution: a first Eotracheophytic flora (Silurian-Lochkovian) dominated by basal eutracheophytes and rhyniophytoids, an early Eophytic Flora (Early Devonian) dominated by zosterophylls, a transitional late Eophytic Flora (Middle Devonian-earliest Carboniferous) dominated by lycopsids and cladoxylopsids, and finally, the earliest phase of the Palaeophytic Flora (Late Devonian-earliest Carboniferous) dominated by the first seed plants. These floras present different but complementary diversity patterns, which help us to understand the overall trajectory of changes in plant diversity. Results further show how the maximum peaks of diversity appear linked to the rise of each new flora but, interestingly, these diversifications are not associated with any exponential declines of the previously dominant one. This new four-phase diversification model reflects the early steps of Earth's greening

Effort-reward imbalance at work and risk of type 2 diabetes in a national sample of 50,552 workers in Denmark : A prospective study linking survey and register data

Objective: To examine the prospective relation between effort-reward imbalance at work and risk of type 2 diabetes. Methods: We included 50,552 individuals from a national survey of the working population in Denmark, aged 30-64 years and diabetes-free at baseline. Effort-reward imbalance was defined, in accordance with the literature, as a mismatch between high efforts at work (e.g. high work pace, time pressure), and low rewards received in return (e.g. low recognition, job insecurity) and assessed as a continuous and a categorical variable. Incident type 2 diabetes was identified in national health registers. Using Cox regression we calculated hazard ratios (HR) and 95% confidence intervals (95% CI) for estimating the association between effort-reward imbalance at baseline and risk of onset of type 2 diabetes during follow-up, adjusted for sex, age, socioeconomic status, cohabitation, children at home, migration background, survey year and sample method. Results: During 136,239 person-years of follow-up (mean = 2.7 years) we identified 347 type 2 diabetes cases (25.5 cases per 10,000 person-years). For each one standard deviation increase of the effort-reward imbalance score at baseline, the fully adjusted risk of type 2 diabetes during follow-up increased by 9% (HR: 1.09, 95% CI: 0.98-1.21). When we used effort-reward imbalance as a dichotomous variable, exposure to effort-reward imbalance was associated with an increased risk of type 2 diabetes with a HR of 1.27 (95% CI: 1.02-1.58). Conclusion The results of this nationwide study of the Danish workforce suggest that effort-reward imbalance at work may be a risk factor for type 2 diabetes.Peer reviewe

Effort-reward imbalance at work and risk of type 2 diabetes in a national sample of 50,552 workers in Denmark: A prospective study linking survey and register data

Objective: To examine the prospective relation between effort-reward imbalance at work and risk of type 2 diabetes.Methods: We included 50,552 individuals from a national survey of the working population in Denmark, aged 30-64 years and diabetes-free at baseline. Effort-reward imbalance was defined, in accordance with the literature, as a mismatch between high efforts at work (e.g. high work pace, time pressure), and low rewards received in return (e.g. low recognition, job insecurity) and assessed as a continuous and a categorical variable. Incident type 2 diabetes was identified in national health registers. Using Cox regression we calculated hazard ratios (HR) and 95% confidence intervals (95% CI) for estimating the association between effort-reward imbalance at baseline and risk of onset of type 2 diabetes during follow-up, adjusted for sex, age, socioeconomic status, cohabitation, children at home, migration background, survey year and sample method.Results: During 136,239 person-years of follow-up (mean = 2.7 years) we identified 347 type 2 diabetes cases (25.5 cases per 10,000 person-years). For each one standard deviation increase of the effort-reward imbalance score at baseline, the fully adjusted risk of type 2 diabetes during follow-up increased by 9% (HR: 1.09, 95% CI: 0.98-1.21). When we used effort-reward imbalance as a dichotomous variable, exposure to effort-reward imbalance was associated with an increased risk of type 2 diabetes with a HR of 1.27 (95% CI: 1.02-1.58).Conclusion The results of this nationwide study of the Danish workforce suggest that effort-reward imbalance at work may be a risk factor for type 2 diabetes

DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency.

During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE, encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C. POLE1-deficient individuals also exhibited distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency. All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases

An introductory view on archaeoastronomy

Archaeoastronomy is still a marginalised topic in academia and is described by the Sophia Centre, the only UK institution offering a broader MA containing this field, as ‘the study of the incorporation of celestial orientation, alignments or symbolism in human monuments and architecture’. By many it is associated with investigating prehistoric monuments such as Stonehenge and combining astronomy and archaeology. The following will show that archaeoastronomy is far more than just an interdisciplinary field linking archaeology and astronomy. It merges aspects of anthropology, ethno-astronomy and even educational research, and is possibly better described as cultural astronomy. In the past decades it has stepped away from its quite speculative beginnings that have led to its complete rejection by the archaeology community. Overcoming these challenges it embraced full heartedly solid scientific and statistical methodology and achieved more credibility. However, in recent times the humanistic influences of a cultural context motivate a new generation of archaeoastronomers that are modernising this subject; and humanists might find it better described as post-modern archaeoastronomy embracing the pluralism of today’s academic approach to landscape and ancient people