Memantine Improves Attentional Processes in Fragile X-Associated Tremor/Ataxia Syndrome: Electrophysiological Evidence from a Randomized Controlled Trial.

Progressive cognitive deficits are common in patients with fragile X-associated tremor/ataxia syndrome (FXTAS), with no targeted treatment yet established. In this substudy of the first randomized controlled trial for FXTAS, we examined the effects of NMDA antagonist memantine on attention and working memory. Data were analyzed for patients (24 in each arm) who completed both the primary memantine trial and two EEG recordings (at baseline and follow-up) using an auditory "oddball" task. Results demonstrated significantly improved attention/working memory performance after one year only for the memantine group. The event-related potential P2 amplitude elicited by non-targets was significantly enhanced in the treated group, indicating memantine-associated improvement in attentional processes at the stimulus identification/discrimination level. P2 amplitude increase was positively correlated with improvement on the behavioral measure of attention/working memory during target detection. Analysis also revealed that memantine treatment normalized the P2 habituation effect at the follow-up visit. These findings indicate that memantine may benefit attentional processes that represent fundamental components of executive function/dysfunction, thought to comprise the core cognitive deficit in FXTAS. The results provide evidence of target engagement of memantine, as well as therapeutically relevant information that could further the development of specific cognitive or disease-modifying therapies for FXTAS

The use of electron probe microanalysis and laser ablation-inductively coupled plasma-mass spectrometry for the investigation of 8th–14th century plant ash glasses from the Middle East

This is the first broad survey using major, minor and trace element analysis of 8th-15th AD plant ash glass from the Middle East across a 2000 mile area stretching from Egypt to northern Iran. This was part of the ancient Silk Road that extended from the Middle East, through central Asia to China. Up to now, some compositional distinctions have been identified for such glasses mainly using major and minor element oxides and radiogenic isotopes. Our new trace element characterisation is for glass found in selected cosmopolitan hubs, including one where there is archaeological evidence for primary glass making. It provides not only far clearer provenance definitions for regional centres of production, in the Levant, northern Syria and in Iraq and Iran, but also for sub-regional zones of production. This fingerprinting is provided by trace elements associated with the primary glass making raw materials used: ashed halophytic plants and sands. Even more surprising is a correlation between some of the sub-regional production hubs and the types of glass vessels with diagnostic decoration apparently manufactured in or near the cosmopolitan hubs where the glass was found such as colourless cut and engraved vessels (in Iraq and Iran) and trail-decorated vessels (in the Levant). This therefore provides evidence for centres of specialisation. Our trace element characterisation provides a new way of defining the Silk Road by characterising the glass that was traded or exchanged along it. Taken together this data provides a new decentralised model for ancient glass production

Testing the accuracy of feldspar single grains to date late Holocene cyclone and tsunami deposits

Quartz is the preferred dosimeter for luminescence dating of Holocene sediments as optically stimulated luminescence (OSL) signals reset rapidly upon light exposure, and are stable over time. However, feldspar is required where quartz luminescence properties are inappropriate for dating, as is often the case in geologically young mountain ranges and areas with young volcanism. Here we aim to evaluate the potential of single grain feldspar luminescence dating applied to late Holocene cyclone and tsunami deposits, for which complete signal resetting can a priori not be guaranteed. To address potential problems of feldspar dating of such deposits associated with heterogeneous bleaching, remnant doses and anomalous fading, we use a low-temperature post infrared infrared stimulated luminescence protocol (pIRIR150) on single grains. For most samples, good agreement between fading corrected IR50 and non-fading corrected pIRIR150 ages is observed. Both feldspar ages generally also show good agreement with age control provided by historical data and quartz luminescence ages. pIRIR150 remnant ages in modern analogue samples are shown to be 150, IR50 and quartz ages, indicates that a significant number of grains must have experienced relatively complete signal resetting during or immediately prior to transport, as the three signals are known to bleach at different rates. Since light exposure during the event is expected to be limited, we deduce that a significant portion of the grains in the cyclone and tsunami deposits was already bleached prior to the event of interest. These well-bleached grains were likely eroded at the beach, while other grains with larger remnant ages probably originate from the shallow subtidal, coastal barriers or even further inland sources. Additional signal resetting during storm and tsunami transport is indicated by slightly younger quartz than feldspar ages for grains with incomplete pre-transport resetting that were eroded at the Holocene coastal barrier.</p

The Isaacson expansion in quantum cosmology

This paper is an application of the ideas of the Born-Oppenheimer (or slow/fast) approximation in molecular physics and of the Isaacson (or short-wave) approximation in classical gravity to the canonical quantization of a perturbed minisuperspace model of the kind examined by Halliwell and Hawking. Its aim is the clarification of the role of the semiclassical approximation and the backreaction in such a model. Approximate solutions of the quantum model are constructed which are not semiclassical, and semiclassical solutions in which the quantum perturbations are highly excited.Comment: Revtex, 11 journal or 24 preprint pages. REPLACEMENT: A comment on previous work by Dowker and Laflamme is corrected. Utah preprint UU-REL-93/3/1

Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1, and GAT-3 by astrocytes of inferior colliculus and hippocampus.

Neuronal inhibition is mediated by glycine and/or GABA. Inferior colliculus (IC) neurons receive glycinergic and GABAergic inputs, whereas inhibition in hippocampus (HC) predominantly relies on GABA. Astrocytes heterogeneously express neurotransmitter transporters and are expected to adapt to the local requirements regarding neurotransmitter homeostasis. Here we analyzed the expression of inhibitory neurotransmitter transporters in IC and HC astrocytes using whole-cell patch-clamp and single-cell reverse transcription-PCR. We show that most astrocytes in both regions expressed functional glycine transporters (GlyTs). Activation of these transporters resulted in an inward current (IGly) that was sensitive to the competitive GlyT1 agonist sarcosine. Astrocytes exhibited transcripts for GlyT1 but not for GlyT2. Glycine did not alter the membrane resistance (RM) arguing for the absence of functional glycine receptors (GlyRs). Thus, IGly was mainly mediated by GlyT1. Similarly, we found expression of functional GABA transporters (GATs) in all IC astrocytes and about half of the HC astrocytes. These transporters mediated an inward current (IGABA) that was sensitive to the competitive GAT-1 and GAT-3 antagonists NO711 and SNAP5114, respectively. Accordingly, transcripts for GAT-1 and GAT-3 were found but not for GAT-2 and BGT-1. Only in hippocampal astrocytes, GABA transiently reduced RM demonstrating the presence of GABAA receptors (GABAARs). However, IGABA was mainly not contaminated by GABAAR-mediated currents as RM changes vanished shortly after GABA application. In both regions, IGABA was stronger than IGly. Furthermore, in HC the IGABA/IGly ratio was larger compared to IC. Taken together, our results demonstrate that astrocytes are heterogeneous across and within distinct brain areas. Furthermore, we could show that the capacity for glycine and GABA uptake varies between both brain regions

Cannabis oil extracts for chronic pain: What else can be learned from another structured prospective cohort?

INTRODUCTION: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials. OBJECTIVES: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain. METHODS: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 months thereafter. Generalized linear mixed model was used to analyze changes over time. In addition, responders (≥30% reduction in weekly pain at any time point) were identified. RESULTS: The study included 218 patients at baseline, and 188, 154, and 131 at 1, 3, and 6 months, respectively. At 6 months, the mean daily doses of cannabidiol and Δ9-tetrahydrocannabinol were 22.4 ± 24.0 mg and 20.8 ± 30.1 mg, respectively. Pain decreased from 7.9 ± 1.7 at baseline to 6.6 ± 2.2 at 6 months ( CONCLUSION: This prospective cohort demonstrated a modest overall long-term improvement in chronic pain and related symptoms and a reasonable safety profile with the use of relatively low doses of individually titrated Δ9-tetrahydrocannabinol and cannabidiol

Food lokal/global in Bewegung

Nahrungsmittel und Ernährung sind eng verwoben mit Lebensstilen, kulturellen Praktiken, Konsumgewohnheiten sowie mit Vorstellungen von gesundem und ungesundem Leben. Gleichzeitig bergen der Umgang mit Nahrungsmitteln, ihre Produktion, Verarbeitung, Vermarktung, aber auch ihr Konsum in einer globalisierten Welt politisches Konfliktpotenzial. Die hier präsentierte sozial- und kulturwissenschaftliche Auseinandersetzung mit Nahrungsmitteln sowie Ernährung und Essen basiert auf einem transdisziplinären Zugang und richtet den Blick auf Food-Politiken und -Praktiken. Das Feld der Food-Politiken nimmt Bezug auf die (lokalen) Antworten auf die skizzierten globalen agrar- und finanzwirtschaftlichen Problematiken in Verbindung mit Ernährungsweisen und Essen sowie Nahrungsmittelproduktion und -handel. Der Themenblock Food-Praktiken analysiert und diskutiert lokale Ernährungs- und Nahrungsmittelpraktiken, in denen sich globale Praktiken, Politiken und Herausforderungen, ausgelöst nicht zuletzt durch die Covid-19 Pandemie, abbilden. Insgesamt zeigen die Beiträge die Bandbreite des Themas Food und die Produktivität einer transdisziplinären Forschung, durch die Spannungsverhältnisse von In-Wert-Setzung von Nahrungsmitteln und Ernährung im Geflecht globaler und lokaler Praktiken und Politiken sichtbar gemacht und bearbeitet werden können.Peer Reviewe

Towards the classification of static vacuum spacetimes with negative cosmological constant

We present a systematic study of static solutions of the vacuum Einstein equations with negative cosmological constant which asymptotically approach the generalized Kottler (``Schwarzschild--anti-de Sitter'') solution, within (mainly) a conformal framework. We show connectedness of conformal infinity for appropriately regular such space-times. We give an explicit expression for the Hamiltonian mass of the (not necessarily static) metrics within the class considered; in the static case we show that they have a finite and well defined Hawking mass. We prove inequalities relating the mass and the horizon area of the (static) metrics considered to those of appropriate reference generalized Kottler metrics. Those inequalities yield an inequality which is opposite to the conjectured generalized Penrose inequality. They can thus be used to prove a uniqueness theorem for the generalized Kottler black holes if the generalized Penrose inequality can be established.Comment: the discussion of our results includes now some solutions of Horowitz and Myers; typos corrected here and there; a shortened version of this version will appear in Journal of Mathematical Physic

A Mechanism for Detecting Coincidence of Auditory and Visual Spatial Signals

Abstract Information about the world is captured by our separate senses, and must be integrated to yield a unified representation. This raises the issue of which signals should be integrated and which should remain separate, as inappropriate integration will lead to misrepresentation and distortions. One strong cue suggesting that separate signals arise from a single source is coincidence, in space and in time. We measured increment thresholds for discriminating spatial intervals defined by pairs of simultaneously presented targets, one flash and one auditory sound, for various separations. We report a &apos;dipper function&apos;, in which thresholds follow a &apos;U-shaped&apos; curve, with thresholds initially decreasing with spatial interval, and then increasing for larger separations. The presence of a dip in the audiovisual increment-discrimination function is evidence that the auditory and visual signals both input to a common mechanism encoding spatial separation, and a simple filter model with a sigmoidal transduction function simulated the results well. The function of an audiovisual spatial filter may be to detect coincidence, a fundamental cue guiding whether to integrate or segregate

Is the tetraneutron a bound dineutron-dineutron molecule?

In light of a new experiment which claims a positive identification, we discuss the possible existence of the tetraneutron. We explore a novel model based on a dineutron-dineutron molecule. We show that this model is not able to explain the tetraneutron as a bound state, in agreement with other theoretical models already discussed in the literature.Comment: 9 pages, 3 figures, J. Phys. G, in pres