Molecular mechanism of activation-triggered subunit exchange in Ca(2+)/calmodulin-dependent protein kinase II.

Activation triggers the exchange of subunits in Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), an oligomeric enzyme that is critical for learning, memory, and cardiac function. The mechanism by which subunit exchange occurs remains elusive. We show that the human CaMKII holoenzyme exists in dodecameric and tetradecameric forms, and that the calmodulin (CaM)-binding element of CaMKII can bind to the hub of the holoenzyme and destabilize it to release dimers. The structures of CaMKII from two distantly diverged organisms suggest that the CaM-binding element of activated CaMKII acts as a wedge by docking at intersubunit interfaces in the hub. This converts the hub into a spiral form that can release or gain CaMKII dimers. Our data reveal a three-way competition for the CaM-binding element, whereby phosphorylation biases it towards the hub interface, away from the kinase domain and calmodulin, thus unlocking the ability of activated CaMKII holoenzymes to exchange dimers with unactivated ones.

Molecular mechanism of activation-triggered subunit exchange in Ca(2+)/calmodulin-dependent protein kinase II.

Activation triggers the exchange of subunits in Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), an oligomeric enzyme that is critical for learning, memory, and cardiac function. The mechanism by which subunit exchange occurs remains elusive. We show that the human CaMKII holoenzyme exists in dodecameric and tetradecameric forms, and that the calmodulin (CaM)-binding element of CaMKII can bind to the hub of the holoenzyme and destabilize it to release dimers. The structures of CaMKII from two distantly diverged organisms suggest that the CaM-binding element of activated CaMKII acts as a wedge by docking at intersubunit interfaces in the hub. This converts the hub into a spiral form that can release or gain CaMKII dimers. Our data reveal a three-way competition for the CaM-binding element, whereby phosphorylation biases it towards the hub interface, away from the kinase domain and calmodulin, thus unlocking the ability of activated CaMKII holoenzymes to exchange dimers with unactivated ones.

Evaluation of creative problem solving abilities in undergraduate structural engineers through interdisciplinary problem based learning

For a structural engineer, effective communication and interaction with architects cannot be underestimated as a key skill to success throughout their professional career. Structural engineers and architects have to share a common language and understanding of each other in order to achieve the most desirable architectural and structural designs. This interaction and engagement develops during their professional career but needs to be nurtured during their undergraduate studies. The objective of this paper is to present the strategies employed to engage higher order thinking in structural engineering students in order to help them solve complex problem-based learning (PBL) design scenarios presented by architecture students. The strategies employed were applied in the experimental setting of an undergraduate module in structural engineering at Queen’s University Belfast in the UK. The strategies employed were active learning to engage with content knowledge, the use of physical conceptual structural models to reinforce key concepts and finally, reinforcing the need for hand sketching of ideas to promote higher order problem-solving. The strategies employed were evaluated through student survey, student feedback and module facilitator (this author) reflection. The strategies were qualitatively perceived by the tutor and quantitatively evaluated by students in a cross-sectional study to help interaction with the architecture students, aid interdisciplinary learning and help students creatively solve problems (through higher order thinking). The students clearly enjoyed this module and in particular interacting with structural engineering tutors and students from another discipline

Bespoke Radiology e-Learning

Introduction: Foundation doctors are expected to assess and interpret plain x-ray studies of the chest/abdomen before a definitive report is issued by senior staff. The Royal College of Radiologists have published guidelines (RCR curriculum) on the scope of plain film findings medical students should be familiar with.1 Studies have shown that the x-ray interpretation without feedback does not significantly improve diagnostic ability. 2 Queen’s University, Belfast Trust Radiology and Experior Medical developed an online system to assess individual student ability to interpret X-ray findings. Over a series of assessments each student’s profile is built up, identifying strengths and weakness. The system can then create bespoke individual assessments re-evaluating previously identified weak areas and quantifying interpretative skill improvement. Aim: To determine how readily an online system is adopted by senior medical students, investigating if increasing exposure to x-ray interpretation combined with cyclical formative feedback enhances performance. Methods: The system was offered to all 270 final year medical students as an online resource. The system comprised a series of 20 weekly 30 minute assessments, containing normal and abnormal x-rays within the RCR curriculum. After each assessment students were given formative feedback, including their own result, annotated answers, peer group comparison and a breakdown of areas of strength and weakness. Focus groups of 4-5 students addressed student perspectives of the system, including ease of use, image resolution, system performance across different operating platforms, perceived value of formative feedback loops, breakdown of performance and the value of bespoke personalised assessments. Research Ethics Approval was granted for the study. Data analysis was via two-sided one-sample t-test; initial minimal recruitment was estimated as 60 students, to detect a mean 10% change in performance, with a standard deviation of 20%. Results and Discussion: Over 80% (n = XXX/270) of the student cohort engaged with the study. Student baseline average was 39%, increasing to 62% by the exit test. The steadily sustained improvement (57% relative performance in interpretative diagnostic accuracy) was despite increasing test difficulty. Student feedback via focus groups was universally positive throughout the examined domains. Conclusion: The online resource proved to be valuable, with high levels of student engagement, improving performance despite increasingly difficulty testing and positive learner experience with the system. References: 1. Undergraduate Radiology Curriculum, The Royal College of Ra, April 2012. Ref No. BFCR(12)4 The Royal College of Radiologists, April 2012 2. I Satia, S Bashagha, A Bibi, R Ahmed, S Mellor, F Zaman. Assessing the accuracy and certainty in interpretating chest x-rays in the medical division. Clin Med August 2013 Vol.13 no. 4 349-352

Seeing How it Sounds: Observation, Imitation and Improved Learning in Piano Playing

Research in various fields has shown that students benefit from teacher action demonstrations during instruction, establishing the need to better understand the effectiveness of different demonstration types across student proficiency levels. This study centres upon a piano learning and teaching environment in which beginners and intermediate piano students (N=48) learning to perform a specific type of staccato were submitted to three different (group exclusive) teaching conditions: audio-only demonstration of the musical task; observation of the teacher's action demonstration followed by student imitation (blockedobservation); and observation of the teacher's action demonstration whilst alternating imitation of the task with the teacher's performance (interleaved-observation). Learning was measured in relation to students' range of wrist amplitude (RWA) and ratio of sound and inter-sound duration (SIDR) before, during and after training. Observation and imitation of the teacher’s action demonstrations had a beneficial effect on students' staccato knowledge retention at different times after training: students submitted to interleaved-observation presented significantly shorter note duration and larger wrist rotation, and as such, were more proficient at the learned technique in each of the lesson and retention tests than students in the other learning conditions. There were no significant differences in performance or retention for students of different proficiency levels. These findings have relevant implications for instrumental music pedagogy and other contexts where embodied action is an essential aspect of the learning process.

Le sommeil comme marqueur du déclin cognitif dans la maladie de Parkinson

La maladie de Parkinson (MP) est une maladie neurodégénérative qui se caractérise principalement par la présence de symptômes moteurs. Cependant, d’autres symptômes, dits non moteurs, sont fréquents dans la MP et assombrissent le pronostic; ceux ci incluent notamment les désordres du sommeil et les troubles cognitifs. De fait, sur une période de plus de 10 ans, jusqu’à 90 % des patients avec la MP développeraient une démence. L’identification de marqueurs de la démence dans la MP est donc primordiale pour permettre le diagnostic précoce et favoriser le développement d’approches thérapeutiques préventives. Plusieurs études ont mis en évidence la contribution du sommeil dans les processus de plasticité cérébrale, d’apprentissage et de consolidation mnésique, notamment l’importance des ondes lentes (OL) et des fuseaux de sommeil (FS). Très peu de travaux se sont intéressés aux liens entre les modifications de la microarchitecture du sommeil et le déclin cognitif dans la MP. L’objectif de cette thèse est de déterminer, sur le plan longitudinal, si certains marqueurs électroencéphalographiques (EEG) en sommeil peuvent prédire la progression vers la démence chez des patients atteints de la MP. La première étude a évalué les caractéristiques des OL et des FS durant le sommeil lent chez les patients avec la MP selon qu’ils ont développé ou non une démence (MP démence vs MP sans démence) lors du suivi longitudinal, ainsi que chez des sujets contrôles en santé. Comparativement aux patients MP sans démence et aux sujets contrôles, les patients MP démence présentaient au temps de base une diminution de la densité, de l’amplitude et de la fréquence des FS. La diminution de l’amplitude des FS dans les régions postérieures était associée à de moins bonnes performances aux tâches visuospatiales chez les patients MP démence. Bien que l’amplitude des OL soit diminuée chez les deux groupes de patients avec la MP, celle ci n’était pas associée au statut cognitif lors du suivi. La deuxième étude a évalué les marqueurs spectraux du développement de la démence dans la MP à l’aide de l’analyse quantifiée de l’EEG en sommeil lent, en sommeil paradoxal et à l’éveil. Les patients MP démence présentaient une diminution de la puissance spectrale sigma durant le sommeil lent dans les régions pariétales comparativement aux patients MP sans démence et aux contrôles. Durant le sommeil paradoxal, l’augmentation de la puissance spectrale en delta et en thêta, de même qu’un plus grand ratio de ralentissement de l’EEG, caractérisé par un rapport plus élevé des basses fréquences sur les hautes fréquences, était associée au développement de la démence chez les patients avec la MP. D’ailleurs, dans la cohorte de patients, un plus grand ralentissement de l’EEG en sommeil paradoxal dans les régions temporo occipitales était associé à des performances cognitives moindres aux épreuves visuospatiales. Enfin, durant l’éveil, les patients MP démence présentaient au temps de base une augmentation de la puissance spectrale delta, un plus grand ratio de ralentissement de l’EEG ainsi qu’une diminution de la fréquence dominante occipitale alpha comparativement aux patients MP sans démence et aux contrôles. Cette thèse suggère que des anomalies EEG spécifiques durant le sommeil et l’éveil peuvent identifier les patients avec la MP qui vont développer une démence quelques années plus tard. L’activité des FS, ainsi que le ralentissement de l’EEG en sommeil paradoxal et à l’éveil, pourraient donc servir de marqueurs potentiels du développement de la démence dans la MP.

Sleep and school education

Sleep has emerged in the past decades as a key process for memory consolidation and restructuring. Given the universality of sleep across cultures, the need to reduce educational inequality, the low implementation cost of a sleep-based pedagogy, and its global scalability, it is surprising that the potential of improved sleep as a means of enhancing school education has remained largely unexploited. Students of various socio-economic status often suffer from sleep deficits. In principle, the optimization of sleep schedules both before and after classes should produce large positive benefits for learning. Here we review the biological and psychological phenomena underlying the cognitive role of sleep, present the few published studies on sleep and learning that have been performed in schools, and discuss potential applications of sleep to the school setting. Translational research on sleep and learning has never seemed more appropriate.

Upper Secondary Students’ Beliefs About Learning English as a Foreign Language : A contrast between the students’ beliefs and the Swedish curriculum

Learning English as a foreign language (EFL) entails different factors. Language learners use different strategies in order to make their language acquisition successful. Motivation and self-regulated learning are other factors that influence how successful the EFL learner is. This paper aims to analyze the beliefs of upper secondary students in a Swedish school about learning EFL, as well as how their beliefs relate to what is specified in the Swedish curriculum. An analysis of the differences between students’ beliefs and what is stated in the curriculum was done. A survey was conducted on a total of 54 students who were enrolled in the social sciences program. The results showed that students believed that motivation and self-regulated learning were important factors for a successful learning. For them, the language skill of reception is more important than production, which does not correspond with what it is stated in the national curriculum. First and second year students’ beliefs were similar in most of the cases, but not all of them.

A review of Parkinson’s disease cardinal and dyskinetic motor symptoms assessment methods using sensor systems

This paper is reviewing objective assessments of Parkinson’s disease(PD) motor symptoms, cardinal, and dyskinesia, using sensor systems. It surveys the manifestation of PD symptoms, sensors that were used for their detection, types of signals (measures) as well as their signal processing (data analysis) methods. A summary of this review’s finding is represented in a table including devices (sensors), measures and methods that were used in each reviewed motor symptom assessment study. In the gathered studies among sensors, accelerometers and touch screen devices are the most widely used to detect PD symptoms and among symptoms, bradykinesia and tremor were found to be mostly evaluated. In general, machine learning methods are potentially promising for this. PD is a complex disease that requires continuous monitoring and multidimensional symptom analysis. Combining existing technologies to develop new sensor platforms may assist in assessing the overall symptom profile more accurately to develop useful tools towards supporting better treatment process.

Child Safety Signal Learning in the Context of Parental Worry, Overprotection, PTSD, and Depression

Thesis (Ph.D.)--University of Washington, 2016-08

New tools for cognitive and motor rehabilitation: development and clinical validation

Nervous system disorders are associated with cognitive and motor deficits, and are responsible for the highest disability rates and global burden of disease. Their recovery paths are vulnerable and dependent on the effective combination of plastic brain tissue properties, with complex, lengthy and expensive neurorehabilitation programs. This work explores two lines of research, envisioning sustainable solutions to improve treatment of cognitive and motor deficits. Both projects were developed in parallel and shared a new sensible approach, where low-cost technologies were integrated with common clinical operative procedures. The aim was to achieve more intensive treatments under specialized monitoring, improve clinical decision-making and increase access to healthcare. The first project (articles I – III) concerned the development and evaluation of a web-based cognitive training platform (COGWEB), suitable for intensive use, either at home or at institutions, and across a wide spectrum of ages and diseases that impair cognitive functioning. It was tested for usability in a memory clinic setting and implemented in a collaborative network, comprising 41 centers and 60 professionals. An adherence and intensity study revealed a compliance of 82.8% at six months and an average of six hours/week of continued online cognitive training activities. The second project (articles IV – VI) was designed to create and validate an intelligent rehabilitation device to administer proprioceptive stimuli on the hemiparetic side of stroke patients while performing ambulatory movement characterization (SWORD). Targeted vibratory stimulation was found to be well tolerated and an automatic motor characterization system retrieved results comparable to the first items of the Wolf Motor Function Test. The global system was tested in a randomized placebo controlled trial to assess its impact on a common motor rehabilitation task in a relevant clinical environment (early post-stroke). The number of correct movements on a hand-to-mouth task was increased by an average of 7.2/minute while the probability to perform an error decreased from 1:3 to 1:9. Neurorehabilitation and neuroplasticity are shifting to more neuroscience driven approaches. Simultaneously, their final utility for patients and society is largely dependent on the development of more effective technologies that facilitate the dissemination of knowledge produced during the process. The results attained through this work represent a step forward in that direction. Their impact on the quality of rehabilitation services and public health is discussed according to clinical, technological and organizational perspectives. Such a process of thinking and oriented speculation has led to the debate of subsequent hypotheses, already being explored in novel research paths.

Promoting oral health in adults with learning disability

Introduction: It is complex to define learning disabilities, there is no single universal definition used; there are different interpretations and definitions used for learning disabilities in different countries and communities. Primarily, the term “learning disability” sometimes used as “learning difficulties” is a term widely used in UK. There are various types and degree of severity of learning disabilities depending upon the extent of disorder. Though different definitions used all over the world, its types and classification coupled with their health and oral health needs are discussed in this review. Objectives:  To review the background literature on definitions of learning disabilities and health needs of this population.  To review literature on individual clinical preventive intervention to determine the effectiveness in promoting oral health amongst adults in learning disabilities.  To review literature in relation to community based preventive dental measures.  To determine the interventions in this areas are appropriate to support policy and practice and if these interventions establish good evidence to suggest that the oral health needs of adults with learning disabilities are met or not.  To make recommendations in implementing future preventive oral health interventions for adults with learning disabilities. Methodology: It was develop a comprehensive narrative synthesis of previously published literature from different sources and summarizes the whole research in a particular area identifying gap of knowledge. It provides a broad perspective of a subject and supports continuing education. It also is directed to inform policy and further research. It is a qualitative type of research with a broad question and critical analysis of literature published in books, article and journals. The research question evaluated on PICOS criteria is: Effectiveness of preventive dental interventions in adults with learning disabilities. The research question clearly defines the PICOS i.e. participants, interventions, comparison, outcome and study design. The Cochrane database of systematic reviews (CDSR), Database of Abstracts of Reviews of effects (DARE) through York University and National institute of Health and Clinical Excellence (NICE) was searched to identify need of this review. There was no literature review found on the preventive dental interventions found hence, justifying this review. The guidance used in this review is from York University and methods opted for search of literature is based on the following: Type of participants, interventions, outcome measure, studies and search. The review of literature; author search; systematic and narrative reviews, through the following electronic databases via UFP library services: Pub-Med, Medline, EMBASE, CINHAL, Google scholar; Science Direct; Social and Medicine. A comprehensive search of all available literature from 1990-2015, including systematic reviews, policy documents and some guideline documents was done. Internet resource used to access; Department of Health, World Health Organization, Disability World, Disability Rights Commission, the Stationery office, MENCAP, Australian Learning Disability Association. The literature search was carried out with single word, combined words and phrases, authors' names and the title of literature search. Results: It is primarily looking at the oral health interventions available for adults with learning disabilities in clinical settings and the community measures observed over a period of 25 years 1990-2015. There were 7of the clinical intervention studies and one community based intervention study was added in this review. Conclusion: There is a gap of knowledge identified in not having ample research in the area of preventive dental interventions in adults with learning or intellectual disabilities and there is a need of more research, studies need to be of a better quality and a special consideration is required in the community settings where maintenance of oral hygiene for this vulnerable group of society is hugely dependent on their caregivers. Though, the policy and guideline directs on the preventive dental interventions of adults with LD there still a gap evident in understanding and implication of the guidance in practice by the dental and care support team. Understanding learning disabilities and to identify their behavior, compliance and oral health needs is paramount for all professionals working with or for them at each level.

Organisatorische Umsetzung eines E-Learning-Konzepts einer Hochschule am Beispiel des Zentrums virtUOS der Universität Osnabrück

Die ELAN-Initiative des Landes Niedersachsen treibt zurzeit den vermehrten Einsatz moderner E-Learning-Konzepte in Form dreier Pilotprojekte mit dem Ziel voran, landesweit ein akademisches Kompetenznetzwerk aufzubauen. Sämtliche Hochschulen des Landes sollen von den Kompetenzen der jeweils anderen Universitäten und Fachhochschulen profitieren und die Lehre damit effizienter gestalten. Die an einem dieser Piloten beteiligte Universität Osnabrück nahm die Initiative zum Anlass, ein neues Dienstleistungszentrum zu gründen, dessen Aufgabe sich durch die Unterstützung der multi- und telemedialen Lehre definiert. Dieser Beitrag gibt einen Einblick in die Organisation dieses Zentrums, dessen Forschungs- und Dienstleistungen und zeigt die daraus resultierenden Vorteile auf. (DIPF/Orig.)

The introduction of e-learning in European universities: models and strategies

The aim of this paper is to present the models and the strategies of adoption of e-learning in a group of European universities, most of them located in the regions called “the four motors of Europe” (Baden-Württenberg, Catalunya, Lombardy and Rhône-Alpes) and in Switzerland. Our analysis focuses on four dimensions: the rationale behind the introduction of e-learning, the organisation of the activities and, in particular, the existence of a university centre for e-learning, the type of activities, and, finally, the type of public reached by e-learning. The majority of campus universities in our sample introduced e-learning to improve the quality of education of their students and, for the most part, as a support for existing courses. Some of the campus universities went even further insofar as they have introduced some online courses into their curricula. This has led to forms of cooperation where different universities share some of their courses. Finally, a small number of campus universities have included as part of their educational offer full distance degree programs which can be attended also by non residential students. The above cases show that there is no general move from campus universities towards distance education, but rather a more selective behaviour. Thus we conclude that e-learning, although it is undoubtedly spreading in both distance and presence universities, is not yet bringing fundamental changes in the institutions themselves. E-learning is at the moment integrated into the existing organization and educational offer. (DIPF/Orig.)

If not the Virtual university then what? Co-producing e-learning and configuring its users

This paper reflects the changing notion of the Virtual University and its realization. We introduce an approach from the Sociology of Science and Technology (STS) which analyses the construction of the “student as a user” as seen through the “eyes of designers”. We ask how social relations are built into technological artefacts. In showing how socio-technical developments transcend sometimes contradict and various notions of “the student” we discuss difficulties and chances of bridging the gap between designers of e-learning-artefacts and its assumed addresses. (DIPF/Orig.)