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Search Results: 1 - 10 of 462155 matches for " Shane A. Heiney "
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Cerebellar Cortex Granular Layer Interneurons in the Macaque Monkey Are Functionally Driven by Mossy Fiber Pathways through Net Excitation or Inhibition
Jean Laurens, Shane A. Heiney, Gyutae Kim, Pablo M. Blazquez
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082239
Abstract: The granular layer is the input layer of the cerebellar cortex. It receives information through mossy fibers, which contact local granular layer interneurons (GLIs) and granular layer output neurons (granule cells). GLIs provide one of the first signal processing stages in the cerebellar cortex by exciting or inhibiting granule cells. Despite the importance of this early processing stage for later cerebellar computations, the responses of GLIs and the functional connections of mossy fibers with GLIs in awake animals are poorly understood. Here, we recorded GLIs and mossy fibers in the macaque ventral-paraflocculus (VPFL) during oculomotor tasks, providing the first full inventory of GLI responses in the VPFL of awake primates. We found that while mossy fiber responses are characterized by a linear monotonic relationship between firing rate and eye position, GLIs show complex response profiles characterized by “eye position fields” and single or double directional tunings. For the majority of GLIs, prominent features of their responses can be explained by assuming that a single GLI receives inputs from mossy fibers with similar or opposite directional preferences, and that these mossy fiber inputs influence GLI discharge through net excitatory or inhibitory pathways. Importantly, GLIs receiving mossy fiber inputs through these putative excitatory and inhibitory pathways show different firing properties, suggesting that they indeed correspond to two distinct classes of interneurons. We propose a new interpretation of the information flow through the cerebellar cortex granular layer, in which mossy fiber input patterns drive the responses of GLIs not only through excitatory but also through net inhibitory pathways, and that excited and inhibited GLIs can be identified based on their responses and their intrinsic properties.
Probabilistic Identification of Cerebellar Cortical Neurones across Species
Gert Van Dijck, Marc M. Van Hulle, Shane A. Heiney, Pablo M. Blazquez, Hui Meng, Dora E. Angelaki, Alexander Arenz, Troy W. Margrie, Abteen Mostofi, Steve Edgley, Fredrik Bengtsson, Carl-Fredrik Ekerot, Henrik J?rntell, Jeffrey W. Dalley, Tahl Holtzman
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057669
Abstract: Despite our fine-grain anatomical knowledge of the cerebellar cortex, electrophysiological studies of circuit information processing over the last fifty years have been hampered by the difficulty of reliably assigning signals to identified cell types. We approached this problem by assessing the spontaneous activity signatures of identified cerebellar cortical neurones. A range of statistics describing firing frequency and irregularity were then used, individually and in combination, to build Gaussian Process Classifiers (GPC) leading to a probabilistic classification of each neurone type and the computation of equi-probable decision boundaries between cell classes. Firing frequency statistics were useful for separating Purkinje cells from granular layer units, whilst firing irregularity measures proved most useful for distinguishing cells within granular layer cell classes. Considered as single statistics, we achieved classification accuracies of 72.5% and 92.7% for granular layer and molecular layer units respectively. Combining statistics to form twin-variate GPC models substantially improved classification accuracies with the combination of mean spike frequency and log-interval entropy offering classification accuracies of 92.7% and 99.2% for our molecular and granular layer models, respectively. A cross-species comparison was performed, using data drawn from anaesthetised mice and decerebrate cats, where our models offered 80% and 100% classification accuracy. We then used our models to assess non-identified data from awake monkeys and rabbits in order to highlight subsets of neurones with the greatest degree of similarity to identified cell classes. In this way, our GPC-based approach for tentatively identifying neurones from their spontaneous activity signatures, in the absence of an established ground-truth, nonetheless affords the experimenter a statistically robust means of grouping cells with properties matching known cell classes. Our approach therefore may have broad application to a variety of future cerebellar cortical investigations, particularly in awake animals where opportunities for definitive cell identification are limited.
Fusing Digital Elevation Models to Improve Hydrological Interpretations  [PDF]
Shane Furze, Jae Ogilvie, Paul A. Arp
Journal of Geographic Information System (JGIS) , 2017, DOI: 10.4236/jgis.2017.95035
Abstract: Improving the accuracy of digital elevation is essential for reducing hydro-topographic derivation errors pertaining to, e.g., flow direction, basin borders, channel networks, depressions, flood forecasting, and soil drainage. This article demonstrates how a gain in this accuracy is improved through digital elevation model (DEM) fusion, and using LiDAR-derived elevation layers for conformance testing and validation. This demonstration is done for the Province of New Brunswick (NB, Canada), using five province-wide DEM sources (SRTM 90 m; SRTM 30 m; ASTER 30 m; CDED 22 m; NB-DEM 10 m) and a five-stage process that guides the re-projection of these DEMs while minimizing their elevational differences relative to LiDAR-captured bare-earth DEMs, through calibration and validation. This effort decreased the resulting non-LiDAR to LiDAR elevation differences by a factor of two, reduced the minimum distance conformance between the non-LiDAR and LiDAR-derived flow channels to ± 10 m at 8.5 times out of 10, and dropped the non-LiDAR wet-area percentages of false positives from 59% to 49%, and of false negatives from 14% to 7%. While these reductions are modest, they are nevertheless not only consistent with already existing hydrographic data layers informing about stream and wet-area locations, they also extend these data layers across the province by comprehensively locating previously unmapped flow channels and wet areas.
Fluids and barriers of the CNS: a historical viewpoint
Shane A Liddelow
Fluids and Barriers of the CNS , 2011, DOI: 10.1186/2045-8118-8-2
Abstract: A large amount of information available on the barriers of the brain, especially in development, remains a tangled and somewhat controversial matter, despite research in the field going back centuries. This is partly due to the misunderstanding of several of the early experiments conducted by German neuroanatomists (such as Ehrlich and Goldmann), but also because there is a common belief that the barriers of the developing brain are immature. Some of these arguments are teleological at best, with Barcroft [1] arguing that:'There is no reason why the brain of the embryo should require an environment of very great chemical constancy. It will of course require a certain minimum of the various materials necessary for growth, but otherwise on first principles we must suppose that the good things of life may exist in and may vary in the foetal blood to an extent much greater than in the neonatal.'This misconception is amplified by the term 'blood-brain barrier' incorrectly used to describe all anatomical barriers of the brain, with no clear specification as to which particular barrier a researcher is considering. There are four (major) independent barriers in the brain (Figure 1). These are:1. The blood-CSF barrier, at the level of the choroid plexus epithelial cells (Figure 1A).2. The blood-brain barrier at the level of the endothelium of cerebral blood vessels (Figure 1B).3. The CSF-brain barrier created by separation of the ventricular system from the extracellular fluid of the brain, which is only present in the embryo [2] Figure 1C.4. The arachnoid barrier between the CSF in the subarachnoid space and the dura mater and overlying tissues (Figure 1D).The most closely scrutinised is the blood-brain barrier, in which the vascular endothelial cells of the central nervous system are connected by tight junctions, forming a restrictive barrier to the movement of molecules and electrolytes between the brain and the blood. It was originally thought that astrocytes were requir
Reduced Vasodilator Function Following Acute Resistance Exercise in Obese Women
Shane A. Phillips
Frontiers in Physiology , 2014, DOI: 10.3389/fphys.2014.00253
Abstract: Obesity contributes to stress induced impairments in endothelium-dependent vasodilation (EDV), a precursor to atherosclerosis. Since obesity is associated with inflammation and oxidative stress, we sought to determine if a single bout of strenuous weight lifting (SWL) reduces EDV among sedentary obese adults. Participants included 9 obese (OB) (BMI 30.0-40.0 kg/m2) and 8 lean (LN) (BMI 18.5-24.9 kg/m2) sedentary young women. All participants underwent a single bout of SWL using a progressive leg-press protocol. Brachial artery flow-mediated dilation (FMD) (an index of EDV) was determined using ultrasonography before and after SWL. Sublingual nitroglycerin (NTG) was used to determine brachial artery endothelium-independent vasodilation following SWL. Brachial artery FMD was significantly reduced in OB and LN women (LN: 6.4 ± 1.6%, p = 0.22) after SWL. There was no difference in the magnitude of change pre- and post-SWL between groups (OB: -2.4 ± 0.6% and LN: -2.2 ± 1.6%, p = 0.84). Dilation to NTG was lower in OB (21.6 ± 1.3%) compared to LN women (27.6 ± 2.1%, p = 0.02) and associated with body weight (r = -0.70, p = 0.01). These data suggest that endothelium-dependent vasodilation is reduced in woman after acute resistance exercise. Dilations to NTG were lower in obese compared to lean woman and associated with body weight suggesting that changes in sensitivity of blood vessels to NO occurs during obesity. These findings may be important for understanding vascular risk following acute exercise in obesity.
Communication skills: a new strategy for training
Shane A. Gordon,Paul Garrud
Research in Learning Technology , 1996, DOI: 10.3402/rlt.v4i1.9947
Abstract: In 1993 the General Medical Council (GMC) published Tomorrow's Doctors, a set of recommendations for medical education. Much of this document was concerned with the training of communication skills and how this could be improved. This recommendation follows decades of evidence about the importance of communication from many widely respected medical teachers from every discipline: Doctors can discharge (their) important tasks effectively only if they possess the relevant skills. Unfortunately, many do not appear to acquire them during their professional training. (Maguire, 1981) There appears to be a failure sometimes to notice what is really being said… the doctor avoids the acute discomfort of being aware of a problem in which he would rather not get involved. (Norell, 1972).
The Future of Clinical Pharmacy: Developing a Holistic Model
Patricia A. Shane,Eleanor Vogt
Pharmacy , 2013, DOI: 10.3390/pharmacy1020228
Abstract: This concept paper discusses the untapped promise of often overlooked humanistic skills to advance the practice of pharmacy. It highlights the seminal work that is, increasingly, integrated into medical and nursing education. The work of these educators and the growing empirical evidence that validates the importance of humanistic skills is raising questions for the future of pharmacy education and practice. To potentiate humanistic professional competencies, e.g., compassion, empathy, and emotional intelligence, how do we develop a more holistic model that integrates reflective and affective skills? There are many historical and current transitions in the profession and practice of pharmacy. If our education model is refocused with an emphasis on pharmacy’s therapeutic roots, the field has the opportunity to play a vital role in improving health outcomes and patient-centered care. Beyond the metrics of treatment effects, achieving greater patient-centeredness will require transformations that improve care processes and invest in patients’ experiences of the treatment and care they receive. Is layering on additional science sufficient to yield better health outcomes if we neglect the power of empathic interactions in the healing process?
Plasma Physics of Extreme Astrophysical Environments
Dmitri A. Uzdensky,Shane Rightley
Physics , 2014, DOI: 10.1088/0034-4885/77/3/036902
Abstract: Certain classes of astrophysical objects, namely magnetars and central engines of supernovae and gamma-ray bursts (GRBs), are characterized by extreme physical conditions not encountered elsewhere in the Universe. In particular, they possess magnetic fields that exceed the critical quantum field of 44 teragauss. Figuring out how these complex ultra-magnetized systems work requires understanding various plasma processes, both small-scale kinetic and large-scale magnetohydrodynamic (MHD). However, an ultra-strong magnetic field modifies the underlying physics to such an extent that many relevant plasma-physical problems call for building QED-based relativistic quantum plasma physics. In this review, after describing the extreme astrophysical systems of interest and identifying the key relevant plasma-physical problems, we survey the recent progress in the development of such a theory. We discuss how a super-critical field modifies the properties of vacuum and matter and outline the basic theoretical framework for describing both non-relativistic and relativistic quantum plasmas. We then turn to astrophysical applications of relativistic QED plasma physics relevant to magnetar magnetospheres and central engines of supernovae and long GRBs. Specifically, we discuss propagation of light through a magnetar magnetosphere; large-scale MHD processes driving magnetar activity and GRB jet launching and propagation; energy-transport processes governing the thermodynamics of extreme plasma environments; micro-scale kinetic plasma processes important in the interaction of intense magnetospheric electric currents with a magnetar's surface; and magnetic reconnection of ultra-strong magnetic fields. Finally, we point out that future progress will require the development of numerical modeling capabilities.
The Current Waist Circumference Cut Point Used for the Diagnosis of Metabolic Syndrome in Sub-Saharan African Women Is Not Appropriate
Nigel J. Crowther,Shane A. Norris
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048883
Abstract: The waist circumference cut point for diagnosing the metabolic syndrome in sub-Saharan African subjects is based on that obtained from studies in European populations. The aim of this study was to measure the prevalence of obesity and related metabolic disorders in an urban population of African females, a group at high risk for such diseases, and to determine the appropriate waist cut point for diagnosing the metabolic syndrome. Anthropometry and fasting lipid, glucose and insulin levels were measured in a cohort of 1251 African females participating in the Birth to Twenty cohort study in Soweto, Johannesburg. The waist circumference cut points for diagnosing metabolic syndrome (as defined using the new harmonised guidelines), insulin resistance, dysglycaemia, hypertension and dyslipidaemia were obtained using receiver operator characteristic curve analysis. The prevalence of obesity, type 2 diabetes and metabolic syndrome were 50.1%, 14.3% and 42.1%, respectively. The appropriate waist cut point for diagnosing metabolic syndrome was found to be 91.5 cm and was similar to the cuts points obtained for detecting increased risk of insulin resistance (89.0 cm), dysglycaemia (88.4 cm), hypertension (90.1 cm), hypo-high density lipoproteinaemia (87.6 cm) and hyper-low density lipoproteinaemia (90.5 cm). The present data demonstrates that urban, African females have a high prevalence of obesity and related disorders and the waist cut point currently recommended for the diagnosis of the metabolic syndrome (80.0 cm) in this population should be increased to 91.5 cm. This latter finding demonstrates a clear ethnic difference in the relationship between abdominal adiposity and metabolic disease risk. The similar waist cut points identified for the detection of the individual components of the metabolic syndrome and related cardiovascular risk factors demonstrates that the risk for different metabolic diseases increases at the same level of abdominal adiposity suggesting a common aetiological pathway.
Thrombin increases inflammatory cytokine and angiogenic growth factor secretion in human adipose cells in vitro
Jennifer L Strande, Shane A Phillips
Journal of Inflammation , 2009, DOI: 10.1186/1476-9255-6-4
Abstract: Human adipose tissue, isolated preadipocytes and differentiated adipocytes were used in this study. PAR1 and PAR4 mRNA and protein were detected by RT-PCR and immunoblot analysis in both adipose tissue and adipose microvessels. In separate studies, IL-1β, IL-6, MCP-1, TNF-α, IL-10, FGF-2, VEGF, and PDGF production were measured from adipose tissue (n = 5), adipocytes (n = 5), and preadipocytes (n = 3) supernatants with and without thrombin (1 or 10 U/ml; 24 hrs) treatment.Thrombin increased cytokine secretion of IL-1β, IL-6, MCP-1 and TNF-α and growth factor secretion of VEGF from adipocytes along with MCP-1 and VEGF from preadipocytes. The direct thrombin inhibitor lepirudin given in conjunction with thrombin prevented the thrombin-mediated increase in cytokine and growth factor secretion.Here we show that thrombin PAR1 and PAR4 receptors are present and that thrombin stimulates inflammatory cytokine generation and growth factor release in human adipose tissue and cells in vitro. These data suggest that thrombin may represent a molecular link between obesity and associated inflammation.Protease-Activated Receptors (PAR) belongs to a small family of seven transmembrane G protein-coupled receptors (GCPR) whose unique mechanism of action requires proteolytic cleavage of the N-terminus. This cleavage exposes a tethered ligand which then transactivates the receptor [1,2]. Serine proteases including thrombin and other coagulation factors such as Factor (F) Xa and the Tissue Factor (TF):FVIIa complex activate PAR1 and/or PAR4 [3,4]. PARs have been found to be expressed in a variety of tissues and cells including platelets, endothelial cells, leukocytes, and fibroblasts and modulate a variety of responses to thrombin including fibrosis, thrombosis, and inflammation [3].PAR activation in non-adipose tissue induces the hallmarks of inflammation, including up-regulation of proinflammatory mediators and adhesion molecules, enhanced vascular permeability and leukocyte extravasa
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