Assessment of motor symptoms and functional impact in prodromal and early Huntington disease.

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess functional impact of motor manifestations in prHD and early HD individuals.

Are property prices non-linear? An investigation of the behaviour of US REITs and UK property company shares

Linear models of market performance may be misspecified if the market is subdivided into distinct regimes exhibiting different behaviour. Price movements in the US Real Estate Investment Trusts and UK Property Companies Markets are explored using a Threshold Autoregressive (TAR) model with regimes defined by the real rate of interest. In both US and UK markets, distinctive behaviour emerges, with the TAR model offering better predictive power than a more conventional linear autoregressive model. The research points to the possibility of developing trading rules to exploit the systematically different behaviour across regimes.

Property company performance and real interest rates: a regime-switching approach

Linear models of property market performance may be misspecified if there exist distinct states where the market drivers behave in different ways. This paper examines the applicability of non-linear regime-based models. A Self Exciting Threshold Autoregressive (SETAR) model is applied to property company share data, using the real rate of interest to define regimes. Distinct regimes appear exhibiting markedly different market behaviour. The model both casts doubt on the specification of conventional linear models and offers the possibility of developing effective trading rules for real estate equities.

Analysis of EEG signal to detect motor command generation towards stroke rehabilitation

Our aim is to reconstruct the brain-body loop of stroke patients via an EEG-driven robotic system. After the detection of motor command generation, the robotic arm should assist patient’s movement at the correct moment and in a natural way. In this study we performed EEG measurements from healthy subjects performing discrete spontaneous motion. An EEG analysis based on the temporal correlation of the brain activity was employed to determine the onset of single motion motor command generation.

Perceived helplessness is associated with individual differences in the central motor output system

Learned helplessness is a maladaptive response to uncontrollable stress characterized by impaired motor escape responses, reduced motivation and learning deficits. There are important individual differences in the likelihood of becoming helpless following exposure to uncontrollable stress but little is known about the neural mechanisms underlying these individual differences. Here we used structural MRI to measure gray and white matter in individuals with chronic pain, a population at high risk for helplessness due to prolonged exposure to a poorly controlled stressor (pain). Given that self-reported helplessness is predictive of treatment outcomes in chronic pain, understanding such differences might provide valuable clinical insight. We found that the magnitude of self-reported helplessness correlated with cortical thickness in the supplementary motor area (SMA) and midcingulate cortex, regions implicated in cognitive aspects of motor behavior. We then examined the white matter connectivity of these regions and found that fractional anisotropy of connected white matter tracts along the corticospinal tract was associated with helplessness and mediated the relationship between SMA cortical thickness and helplessness. These data provide novel evidence that links individual differences in the motor output pathway with perceived helplessness over a chronic and poorly controlled stressor.

Managing non-standard international experience: evidence from a Finnish company

Purpose – This paper extends the increasing debates about the role of international experience through mechanisms other than standard expatriation packages, in particular through the use of short-term assignments. It explores the different forms of short-term assignments (project work, commuter assignments, virtual international working and development assignments) and the different sets of positive and negative implications these can have for the company and the individuals concerned. The integration-differentiation debate is reflected here as elsewhere in IHRM, with the company moving towards greater centralization and control of its use of these assignments. Design/methodology/approach – Since the research is exploratory, we adopted a qualitative approach to get a more in-depth understanding on the realities the corporations and the assignees are facing. The study was implemented through a single case study setting in which the data were collected by interviewing (n=20) line managers, human resource management (HRM) staff and assignees themselves. In addition corporate documentation and other materials were reviewed. Findings – The present case study provides evidence about the characteristics of short-term assignments as well as the on the management of such assignments. The paper identifies various benefits and challenges involved in the use of short-term assignments both from the perspectives of the company and assignees. Furthermore, the findings support the view that a recent increase in the popularity of short-term assignments has not been matched by the development of HRM policies for such assignments. Research limitations/implications – As a single case study, limitations in the generalizability of the findings should be kept in mind. More large-scale research evidence is needed around different forms of international assignments beyond standard expatriation in order to fully capture the realities faced by international HRM specialists Practical implications – The paper identifies many challenges but also benefits of using short-term assignments. The paper reports in-depth findings on HR development needs that organizations face when expanding the use of such assignments. Social implications – The paper identifies many challenges but also benefits of using short-term assignments. The paper reports in-depth findings on HR development needs that organizations face when expanding the use of such assignments. Originality/value – Empirical research on short-term assignments is still very limited. In that way the paper provides much needed in-depth evidence on why such assignments are used, what challenges are involved in the use of such assignments and what kinds of HR-development needs are involved.

Transcription factor NF-kappaB is transported to the nucleus via cytoplasmic dynein/dynactin motor complex in hippocampal neurons

Background Long-term changes in synaptic plasticity require gene transcription, indicating that signals generated at the synapse must be transported to the nucleus. Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-κB. Transcription factors of the NF-κB family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory. Principal Findings In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-κB to the nucleus in response to synaptic stimulation. We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-κB p65 and reduces NF-κB-dependent transcription activity. In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS) within NF-κB p65 is essential for this binding. Conclusion This study shows the molecular mechanism for the retrograde transport of activated NF-κB from distant synaptic sites towards the nucleus.

The Mystery of Privity: Grand Trunk Railway Company of Canada v Robinson (1915)

This article examines a little known decision of the Judicial Committee of the Privy Council: Grand Trunk Railway Company of Canada v Robinson (1915). The examination is historical and it provides a different insight into the understanding of privity of contract, a doctrine central to contract law. The examination reveals a process of trans-Atlantic legal migration in which English law was applied to resolve an Ontario case. The nature of the resolution is surprising because it appears to conflict with the better known decision of the House of Lords, Dunlop Pneumatic Tyre Company, Limited v Selfridge and Company, Limited, which a similarly constituted panel delivered in the same week. This article argues that there was a greater malleability in the resolution of cases concerned with privity than was thought to have existed. It is also argued that the power of Canadian railway capitalism is a significant factor in understanding the legal resolution of the case. Finally, it the article considers the use of English and American precedents relevant to the case. The application of English precedents to the case led to a resolution not entirely befitting Canadian conditions.

MiR-375 is essential for human spinal motor neuron development and may be involved in motor neuron degeneration

The transcription factor REST is a key suppressor of neuronal genes in non-neuronal tissues. REST has been shown to suppress pro-neuronal microRNAs in neural progenitors indicating that REST-mediated neurogenic suppression may act in part via microRNAs. We used neural differentiation of Rest-null mouse ESC to identify dozens of microRNAs regulated by REST during neural development. One of the identified microRNAs, miR-375, was upregulated during human spinal motor neuron development. We found that miR-375 facilitates spinal motor neurogenesis by targeting the cyclin kinase CCND2 and the transcription factor PAX6. Additionally, miR-375 inhibits the tumor suppressor p53 and protects neurons from apoptosis in response to DNA damage. Interestingly, motor neurons derived from a spinal muscular atrophy patient displayed depressed miR-375 expression and elevated p53 protein levels. Importantly, SMA motor neurons were significantly more susceptible to DNA damage induced apoptosis suggesting that miR-375 may play a protective role in motor neurons.