Survey of the needs of patients with spinal cord injury: impact and priority for improvement in hand function in tetraplegics\ud

Objective: To investigate the impact of upper extremity deficit in subjects with tetraplegia.\ud \ud Setting: The United Kingdom and The Netherlands.\ud \ud Study design: Survey among the members of the Dutch and UK Spinal Cord Injury (SCI) Associations.\ud \ud Main outcome parameter: Indication of expected improvement in quality of life (QOL) on a 5-point scale in relation to improvement in hand function and seven other SCI-related impairments.\ud \ud Results: In all, 565 subjects with tetraplegia returned the questionnaire (overall response of 42%). Results in the Dutch and the UK group were comparable. A total of 77% of the tetraplegics expected an important or very important improvement in QOL if their hand function improved. This is comparable to their expectations with regard to improvement in bladder and bowel function. All other items were scored lower.\ud \ud Conclusion: This is the first study in which the impact of upper extremity impairment has been assessed in a large sample of tetraplegic subjects and compared to other SCI-related impairments that have a major impact on the life of subjects with SCI. The present study indicates a high impact as well as a high priority for improvement in hand function in tetraplegics.\ud \u

Characterization of intrinsic properties of cingulate pyramidal neurons in adult mice after nerve injury

The anterior cingulate cortex (ACC) is important for cognitive and sensory functions including memory and chronic pain. Glutamatergic excitatory synaptic transmission undergo long-term potentiation in ACC pyramidal cells after peripheral injury. Less information is available for the possible long-term changes in neuronal action potentials or intrinsic properties. In the present study, we characterized cingulate pyramidal cells in the layer II/III of the ACC in adult mice. We then examined possible long-term changes in intrinsic properties of the ACC pyramidal cells after peripheral nerve injury. In the control mice, we found that there are three major types of pyramidal cells according to their action potential firing pattern: (i) regular spiking (RS) cells (24.7%), intrinsic bursting (IB) cells (30.9%), and intermediate (IM) cells (44.4%). In a state of neuropathic pain, the population distribution (RS: 21.3%; IB: 31.2%; IM: 47.5%) and the single action potential properties of these three groups were indistinguishable from those in control mice. However, for repetitive action potentials, IM cells from neuropathic pain animals showed higher initial firing frequency with no change for the properties of RS and IB neurons from neuropathic pain mice. The present results provide the first evidence that, in addition to synaptic potentiation reported previously, peripheral nerve injury produces long-term plastic changes in the action potentials of cingulate pyramidal neurons in a cell type-specific manner

Efficient Bayesian inference for COM-Poisson regression models

COM-Poisson regression is an increasingly popular model for count data. Its main advantage is that it permits to model separately the mean and the variance of the counts, thus allowing the same covariate to affect in different ways the average level and the variability of the response variable. A key limiting factor to the use of the COM-Poisson distribution is the calculation of the normalisation constant: its accurate evaluation can be time-consuming and is not always feasible. We circumvent this problem, in the context of estimating a Bayesian COM-Poisson regression, by resorting to the exchange algorithm, an MCMC method applicable to situations where the sampling model (likelihood) can only be computed up to a normalisation constant. The algorithm requires to draw from the sampling model, which in the case of the COM-Poisson distribution can be done efficiently using rejection sampling. We illustrate the method and the benefits of using a Bayesian COM-Poisson regression model, through a simulation and two real-world data sets with different levels of dispersion

E2F1 drives chemotherapeutic drug resistance via ABCG2

Multidrug resistance is a major barrier against successful chemotherapy, and this has been shown in vitro to be often caused by ATP-binding cassette (ABC) transporters. These transporters are frequently overexpressed in human cancers and confer an adverse prognosis in many common malignancies. The genetic factors, however, that initiate their expression in cancer are largely unknown. Here we report that the major multidrug transporter ABCG2 (BCRP/MXR) is directly and specifically activated by the transcription factor E2F1—a factor perturbed in the majority of human cancers. E2F1 regulates ABCG2 expression in multiple cell systems, and, importantly, we have identified a significant correlation between elevated E2F1 and ABCG2 expression in human lung cancers. We show that E2F1 causes chemotherapeutic drug efflux both in vitro and in vivo via ABCG2. Furthermore, the E2F1–ABCG2 axis suppresses chemotherapy-induced cell death that can be restored by the inhibition of ABCG2. These findings therefore identify a new axis in multidrug resistance and highlight a radical new function of E2F1 that is relevant to tumor therapy

Virtual finger boosts three-dimensional imaging and microsurgery as well as terabyte volume image visualization and analysis

Three-dimensional (3D) bioimaging, visualization and data analysis are in strong need of powerful 3D exploration techniques. We develop virtual finger (VF) to generate 3D curves, points and regions-of-interest in the 3D space of a volumetric image with a single finger operation, such as a computer mouse stroke, or click or zoom from the 2D-projection plane of an image as visualized with a computer. VF provides efficient methods for acquisition, visualization and analysis of 3D images for roundworm, fruitfly, dragonfly, mouse, rat and human. Specifically, VF enables instant 3D optical zoom-in imaging, 3D free-form optical microsurgery, and 3D visualization and annotation of terabytes of whole-brain image volumes. VF also leads to orders of magnitude better efficiency of automated 3D reconstruction of neurons and similar biostructures over our previous systems. We use VF to generate from images of 1,107 Drosophila GAL4 lines a projectome of a Drosophila brain. © 2014 Macmillan Publishers Limited. All rights reserved

Strategies to overcome physician shortages in northern Ontario: A study of policy implementation over 35 years

<p>Abstract</p> <p>Background</p> <p>Shortages and maldistibution of physicians in northern Ontario, Canada, have been a long-standing issue. This study seeks to document, in a chronological manner, the introduction of programmes intended to help solve the problem by the provincial government over a 35-year period and to examine several aspects of policy implementation, using these programmes as a case study.</p> <p>Methods</p> <p>A programme analysis approach was adopted to examine each of a broad range of programmes to determine its year of introduction, strategic category, complexity, time frame, and expected outcome. A chronology of programme initiation was constructed, on the basis of which an analysis was done to examine changes in strategies used by the provincial government from 1969 to 2004.</p> <p>Results</p> <p>Many programmes were introduced during the study period, which could be grouped into nine strategic categories. The range of policy instruments used became broader in later years. But conspicuous by their absence were programmes of a directive nature. Programmes introduced in more recent years tended to be more complex and were more likely to have a longer time perspective and pay more attention to physician retention. The study also discusses the choice of policy instruments and use of multiple strategies.</p> <p>Conclusion</p> <p>The findings suggest that an examination of a policy is incomplete if implementation has not been taken into consideration. The study has revealed a process of trial-and-error experimentation and an accumulation of past experience. The study sheds light on the intricate relationships between policy, policy implementation and use of policy instruments and programmes.</p

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro. In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research