252 research outputs found

    Surgical Management of the Aortic Root

    Get PDF

    A new Holocene relative sea-level curve for western Brittany (France): Insights on isostatic dynamics along the Atlantic coasts of north-western Europe

    Get PDF
    International audienceThis study presents new Relative Sea Level (RSL) data that were obtained in the Finistère region (Western tip of Brittany, France) and the implications those data have for the understanding of the isostatic dynamics across north-western Europe, and more specifically along the Atlantic and Channel coasts. New stratigraphic sequences were obtained and analyzed to derive 24 new Sea-level Index Points, in which 6 are basal. These new data considerably increase the knowledge we have of the RSL evolution along the coasts of Western Brittany since the last 8 kyr B.P. From this new dataset, RSL was estimated to rise continuously over the last 8 kyr with a major inflection at ca. 6 kyr cal. BP. Our results show large vertical discrepancies between the RSL records of Brittany and South-Western UK, with the latter plotting several meters below the new data. From this comparison we suggest that the two regions underwent a very different pattern and/or amplitude of subsidence during the last 8 kyr which has implications for the spatial and temporal pattern of the peripheral bulge of the European ice sheets. We compared our data against predictions from Glacio-Isostatic Adjustment models (GIA models). There are large misfits between RSL observations and the predictions of the global (ICE-5G (VM2a) – Peltier, 2004, GLAC1-b – Tarasov and Peltier, 2002; Tarasov et al., 2012, Briggs et al., 2014) and regional UK models (“BIIS” – Bradley et al., 2009; Bradley et al., 2011; “Kuchar”- Kuchar et al., 2012), which can't be resolved through significant changes to the deglaciation history and size of the British–Irish Ice sheet. Paleo-tidal modelling corrections indicate regional changes in the tidal ranges played a negligible role in the data-model misfits. Hence, we propose that the misfits are due to some combination of: (i) unaccounted mass-loss of far-field ice-sheets (Antarctic ice-Sheet or Laurentide Ice-Sheet), (ii) unresolved differences in the deglaciation history and size of the Fennoscandian Ice sheet or, more likely, (iii) significant lateral variations in the Earth's structure across the English Channel

    Kinase/phosphatase overexpression reveals pathways regulating hippocampal neuron morphology

    Get PDF
    Kinases and phosphatases that regulate neurite number versus branching versus extension are weakly correlated.The kinase family that most strongly enhances neurite growth is a family of non-protein kinases; sugar kinases related to NADK.Pathway analysis revealed that genes in several cancer pathways were highly active in enhancing neurite growth

    Systematic reviews of complementary therapies - an annotated bibliography. Part 1: Acupuncture

    Get PDF
    Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with acupuncture. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of acupuncture; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. Results From a total of 48 potentially relevant reviews preselected in a screeening process 39 met the inclusion criteria. 22 were on various pain syndromes or rheumatic diseases. Other topics addressed by more than one review were addiction, nausea, asthma and tinnitus. Almost unanimously the reviews state that acupuncture trials include too few patients. Often included trials are heterogeneous regarding patients, interventions and outcome measures, are considered to have insufficient quality and contradictory results. Convincing evidence is available only for postoperative nausea, for which acupuncture appears to be of benefit, and smoking cessation, where acupuncture is no more effective than sham acupuncture. Conclusions A large number of systematic reviews on acupuncture exists. What is most obvious from these reviews is the need for (the funding of) well-designed, larger clinical trials

    Comparing phoneme frequency, age of acquisition, and loss in aphasia:Implications for phonological universals

    Get PDF
    Phonological complexity may be central to the nature of human language. It may shape the distribution of phonemes and phoneme sequences within languages, but also determine age of acquisition and susceptibility to loss in aphasia. We evaluated this claim using frequency statistics derived from a corpus of phonologically transcribed Italian words (phonitalia, available at phonitalia,org), rankings of phoneme age of acquisition (AoA) and rate of phoneme errors in patients with apraxia of speech (AoS) as an indication of articulatory complexity. These measures were related to cross-linguistically derived markedness rankings. We found strong correspondences. AoA, however, was predicted by both apraxic errors and frequency, suggesting independent contributions of these variables. Our results support the reality of universal principles of complexity. In addition they suggest that these complexity principles have articulatory underpinnings since they modulate the production of patients with AoS, but not the production of patients with more central phonological difficulties

    Multimodal behavioral treatment of migraine: An Internet-administered, randomized, controlled trial

    Get PDF
    Introduction. Multimodal approaches in behavioral treatment have gained recent interest, with proven efficacy for migraine. The utility of the Internet has been demonstrated for behavioral treatment of headache disorders, but not specifically for migraine. The aim of the study was to develop and evaluate an Internet-based multimodal behavior treatment (MBT) program for migraine and to test hand massage treatment as an adjunct. Methods. Eighty-three adults, 58 women and 25 men, with at least two migraine attacks a month were recruited via advertisements. An MBT program aiming at improvements in life-style and stress coping was developed for this study and, together with a diary, adapted for use over the Internet. Participants were randomized to MBT with and without hand massage and to a control group, and were followed for 11 months. Questionnaires addressing issues of quality of life (PQ23) and depressive symptoms (MADRS-S) were used. Results. A 50%, or greater, reduction in migraine frequency was found in 40% and 42% of participants of the two groups receiving MBT (with and without hand massage, respectively), who statistically were significantly more improved than participants in the control group. No effect of hand massage was detected, and gender did not show any independent contribution to the effect in a multivariate analysis. Conclusions. MBT administered over the Internet appears feasible and effective in the treatment of migraine, but no effect of hand massage was found. For increased knowledge on long-term effects and the modes of action of the present MBT program, further studies are needed

    Assessment of Narrow-Body Transport Airplane Evacuation by Numerical Simulation

    Get PDF
    This paper presents the results obtained with a new agent-based computer model that can simulate the evacuation of narrow-body transport airplanes in the conditions prescribed by the airworthiness regulations for certification. The model, described in detail in a former paper, has been verified with real data of narrow-body certification demonstrations. Numerical simulations of around 20 narrow-body aircraft, representative of current designs in various market segments, show the capabilities of the model and provide relevant information on the relationship between cabin features and emergency evacuation. The longitudinal location of emergency exits seems to be even more important than their size or the overall margin with respect to the prescribed number and type of exits indicated by the airworthiness requirement

    LV-pIN-KDEL: a novel lentiviral vector demonstrates the morphology, dynamics and continuity of the endoplasmic reticulum in live neurones

    Get PDF
    BACKGROUND The neuronal endoplasmic reticulum (ER) is an extensive, complex endomembrane system, containing Ca2+ pumps, and Ca2+ channels that permit it to act as a dynamic calcium store. Currently, there is controversy over the continuity of the ER in neurones, how this intersects with calcium signalling and the possibility of physical compartmentalisation. Unfortunately, available probes of ER structure such as vital dyes are limited by their membrane specificity. The introduction of ER-targeted GFP plasmids has been a considerable step forward, but these are difficult to express in neurones through conventional transfection approaches. To circumvent such problems we have engineered a novel ER-targeted GFP construct, termed pIN-KDEL, into a 3rd generation replication-defective, self-inactivating lentiviral vector system capable of mediating gene transduction in diverse dividing and post-mitotic mammalian cells, including neurones. RESULTS Following its expression in HEK293 (or COS-7) cells, LV-pIN-KDEL yielded a pattern of fluorescence that co-localised exclusively with the ER marker sec61beta but with no other major organelle. We found no evidence for cytotoxicity and only rarely inclusion body formation. To explore the utility of the probe in resolving the ER in live cells, HEK293 or COS-7 cells were transduced with LV-pIN-KDEL and, after 48 h, imaged directly at intervals from 1 min to several hours. LV-pIN-KDEL fluorescence revealed the endoplasmic reticulum as a tubular lattice structure whose morphology can change markedly within seconds. Although GFP can be phototoxic, the integrity of the cells and ER was retained for several weeks and even after light exposure for periods up to 24 h. Using LV-pIN-KDEL we have imaged the ER in diverse fixed neuronal cultures and, using real-time imaging, found evidence for extensive, dynamic remodelling of the neuronal ER in live hippocampal cultures, brain slices, explants and glia. Finally, through a Fluorescence Loss in Photobleaching (FLIP) approach, continuous irradiation at a single region of interest removed all the fluorescence of LV-pIN-KDEL-transduced nerve cells in explant cultures, thus, providing compelling evidence that in neurons the endoplasmic reticulum is not only dynamic but also continuous. CONCLUSION The lentiviral-based ER-targeted reporter, LV-pIN-KDEL, offers considerable advantages over present systems for defining the architecture of the ER, especially in primary cells such as neurones that are notoriously difficult to transfect. Images and continuous photobleaching experiments of LV-pIN-KDEL-transduced neurones demonstrate that the endoplasmic reticulum is a dynamic structure with a single continuous lumen. The introduction of LV-pIN-KDEL is anticipated to greatly facilitate a real-time visualisation of the structural plasticity and continuous nature of the neuronal ER in healthy and diseased brain tissue

    Synaptic Vesicle Docking: Sphingosine Regulates Syntaxin1 Interaction with Munc18

    Get PDF
    Consensus exists that lipids must play key functions in synaptic activity but precise mechanistic information is limited. Acid sphingomyelinase knockout mice (ASMko) are a suitable model to address the role of sphingolipids in synaptic regulation as they recapitulate a mental retardation syndrome, Niemann Pick disease type A (NPA), and their neurons have altered levels of sphingomyelin (SM) and its derivatives. Electrophysiological recordings showed that ASMko hippocampi have increased paired-pulse facilitation and post-tetanic potentiation. Consistently, electron microscopy revealed reduced number of docked vesicles. Biochemical analysis of ASMko synaptic membranes unveiled higher amounts of SM and sphingosine (Se) and enhanced interaction of the docking molecules Munc18 and syntaxin1. In vitro reconstitution assays demonstrated that Se changes syntaxin1 conformation enhancing its interaction with Munc18. Moreover, Se reduces vesicle docking in primary neurons and increases paired-pulse facilitation when added to wt hippocampal slices. These data provide with a novel mechanism for synaptic vesicle control by sphingolipids and could explain cognitive deficits of NPA patients
    corecore