Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia

Rationale: Nighttime agitation occurs frequently in patients with dementia and represents the number one burden on caregivers today. Current treatment options are few and limited due to substantial side effects. Objectives: The aim of the study was to measure the effect of the cannabinoid dronabinol on nocturnal motor activity. Methods: In an open-label pilot study, six consecutive patients in the late stages of dementia and suffering from circadian and behavioral disturbances—five patients with Alzheimer's disease and one patient with vascular dementia—were treated with 2.5mg dronabinol daily for 2weeks. Motor activity was measured objectively using actigraphy. Results: Compared to baseline, dronabinol led to a reduction in nocturnal motor activity (P=0.028). These findings were corroborated by improvements in Neuropsychiatric Inventory total score (P=0.027) as well as in subscores for agitation, aberrant motor, and nighttime behaviors (P<0.05). No side effects were observed. Conclusions: The study suggests that dronabinol was able to reduce nocturnal motor activity and agitation in severely demented patients. Thus, it appears that dronabinol may be a safe new treatment option for behavioral and circadian disturbances in dementi

Three-dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication

All positive strand RNA viruses are known to replicate their genomes in close association with intracellular membranes. In case of the hepatitis C virus (HCV), a member of the family Flaviviridae, infected cells contain accumulations of vesicles forming a membranous web (MW) that is thought to be the site of viral RNA replication. However, little is known about the biogenesis and three-dimensional structure of the MW. In this study we used a combination of immunofluorescence- and electron microscopy (EM)-based methods to analyze the membranous structures induced by HCV in infected cells. We found that the MW is derived primarily from the endoplasmic reticulum (ER) and contains markers of rough ER as well as markers of early and late endosomes, COP vesicles, mitochondria and lipid droplets (LDs). The main constituents of the MW are single and double membrane vesicles (DMVs). The latter predominate and the kinetic of their appearance correlates with kinetics of viral RNA replication. DMVs are induced primarily by NS5A whereas NS4B induces single membrane vesicles arguing that MW formation requires the concerted action of several HCV replicase proteins. Three-dimensional reconstructions identify DMVs as protrusions from the ER membrane into the cytosol, frequently connected to the ER membrane via a neck-like structure. In addition, late in infection multi-membrane vesicles become evident, presumably as a result of a stress-induced reaction. Thus, the morphology of the membranous rearrangements induced in HCV-infected cells resemble those of the unrelated picorna-, corona- and arteriviruses, but are clearly distinct from those of the closely related flaviviruses. These results reveal unexpected similarities between HCV and distantly related positive-strand RNA viruses presumably reflecting similarities in cellular pathways exploited by these viruses to establish their membranous replication factories

Wissenschaftliche Zeitschrift und Digitale Bibliothek: Wissenschaftsforschung Jahrbuch 2002

Elektronische Produktion, Verbreitung und Rezeption von wissenschaftlichen Zeitschriften - deren integrative Wechselbeziehungen eingeschlossen - verändern unausweichlich die Forschungssituation unserer Zeit. Inzwischen sind elektronische Zeitschriften ein fester Bestandteil des wissenschaftlichen Publikationswesens geworden, auf den die meisten Forscher nicht mehr verzichten möchten. In diesem Wandel braucht es Orientierungen und Kompetenzen. Seit ihrem Aufkommen in der zweiten Hälfte des 17. Jahrhunderts haben wissenschaftliche Zeitschriften sich selbst als Forschungsbibliotheken der Wissenschaftsdisziplinen verstanden und dies mit der weiteren Differenzierung der Wissenschaft in einem Maße realisiert, dass ihre zunehmend elektronische Produktion die Entwicklung der Digitalen Bibliothek in der Wissenschaft nachhaltig forciert. Untersuchungen über diesen grundlegenden Vorgang neuerer Wissenschaftsentwicklung sind ein wichtiges Anliegen der Wissenschaftsforschung. Die Gesellschaft für Wissenschaftsforschung hat sich dieser Fragestellung angenommen und sie im Rahmen ihrer Jahrestagung 2002 unter dem Thema „Wissenschaftliche Zeitschrift und Digitale Bibliothek“ analysiert. Vorausgegangen waren Diskussionen über „Wissenschaft - Informationszeitalter - Digitale Bibliothek“ auf der Jahrestagung 1998 und über „Organisationsinformatik und Digitale Bibliothek in der Wissenschaft“ auf der Jahrestagung 2000, die in den jeweiligen Jahrbüchern Wissenschaftsforschung 1998 und 2000 publiziert wurden. Die Ergebnisse der Tagung vom März 2002, die im Institut für Bibliothekswissenschaft der Humboldt-Universität zu Berlin stattgefunden hat, werden hiermit - in Fortführung der Publikationsreihe - als Wissenschaftsforschung Jahrbuch 2002 dem interessierten Leser vorgestellt.Peer Reviewe

Integrität wissenschaftlicher Publikationen in der Digitalen Bibliothek: Wissenschaftsforschung Jahrbuch 2007

Im digitalen Zeitalter kommt es zu einem Wandel wissenschaftlichen Arbeitens, zur Zeit vor allem in dem Maße, wie die Potenziale der elektronischen Laborjournale und des elektronischen Publizierens im Internet als unverzichtbares Medium der Bereitstellung und Verbreitung von wissenschaftlichen Dokumenten genutzt werden. Den Vorzügen der elektronischen Publikationsform stehen zwei miteinander verbundene Probleme gegenüber, die noch nicht zufriedenstellend gelöst sind: das Problem der Authentizität und das der Langzeitarchivierung. Um die Vorzüge des elektronischen Publizierens für wissenschaftliche Dokumente voll wirksam werden zu lassen, müssen Lösungen gefunden und eingeführt werden, die die Integrität der wissenschaftlichen Veröffentlichungen langfristig sichern. Erste Lösungen liegen vor und werden in der Anwendung überprüft, weitere Lösungen werden zu finden und in ihrer Anwendung zu überprüfen sein. Die Vorteile elektronischer wissenschaftlicher Publikationen liegen auf der Hand − Schnelligkeit und weltweiter Zugriff auf alle relevanten Informationen. Einiges spricht dafür, dass wir erst am Anfang einer zweiten Medienrevolution stehen. Es ist aber heute schon gewiss, dass die elektronischen Medien nicht nur technisch neue Möglichkeiten der Wissensvermittlung erschließen, sondern die Wissensproduktion selbst verändern werden. Untersuchungen zur Qualitätssicherung und Integrität wissenschaftlicher Publikationen in der Digitalen Bibliothek sind ein wichtiges Anliegen der Wissenschaftsforschung, dem sich die Gesellschaft für Wissenschaftsforschung im Rahmen ihrer Jahrestagung am 23. und 24. März 2007 gemeinsam mit dem Institut für Bibliotheks- und Informationswissenschaft der Humboldt-Universität zu Berlin zugewandt hat. Die Beiträge dieses Jahrbuchs sollen dazu beitragen, einen Einblick in theoretische und praktische Probleme der neuen Kultur des elektronischen Publizierens in der Wissenschaft zu geben.Peer Reviewe

Online calculator for individual affiliation to a major population group

Because of their sensitivity and high level of discrimination, short tandem repeat (STR) maker systems are currently the method of choice in routine forensic casework and data banking, usually in multiplexes up to 15–17 loci. Constraints related to sample amount and quality, frequently encountered in forensic casework, will not allow to change this picture in the near future, notwithstanding the technological developments. In this study, we present a free online calculator named PopAffiliator (http://cracs.fc.up.pt/popaffiliator) for individual population affiliation in the three main population groups, Eurasian, East Asian and sub-Saharan African, based on genotype profiles for the common set of STRs used in forensics. This calculator performs affiliation based on a model constructed using machine learning techniques. The model was constructed using a data set of approximately fifteen thousand individuals collected for this work. The accuracy of individual population affiliation is approximately 86%, showing that the common set of STRs routinely used in forensics provide a considerable amount of information for population assignment, in addition to being excellent for individual identification

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala

In rodents, the medial nucleus of the amygdala receives direct inputs from the accessory olfactory bulbs and is mainly implicated in pheromone-mediated reproductive and defensive behaviors. The principal neurons of the medial amygdala are GABAergic neurons generated principally in the caudo-ventral medial ganglionic eminence and preoptic area. Beside GABAergic neurons, the medial amygdala also contains glutamatergic Otp-expressing neurons cells generated in the lateral hypothalamic neuroepithelium and a non-well characterized Pax6-positive population. In the present work, we describe a novel glutamatergic Ebf3-expressing neuronal subpopulation distributed within the periphery of the postero-ventral medial amygdala. These neurons are generated in a pallial domain characterized by high expression of Gdf10. This territory is topologically the most caudal tier of the ventral pallium and accordingly, we named it Caudo-Ventral Pallium (CVP). In the absence of Pax6, the CVP is disrupted and Ebf3-expressing neurons fail to be generated. Overall, this work proposes a novel model of the neuronal composition of the medial amygdala and unravels for the first time a new novel pallial subpopulation originating from the CVP and expressing the transcription factor Ebf3.This work was supported by Grants of the French National Research Agency (Agence Nationale de la Recherche; ANR) [ANR-13-BSV4-0011] and by the French Government through the ‘Investments for the Future’ LABEX SIGNALIFE [ANR-11-LABX-0028-01] to M.S., by the Spanish Government (BFU2007-60263 and BFU2010-17305) to A.F, and by the Medical Research Council (MR/K013750/1) to T.T. N.R.-R. is funded by a postdoctoral fellowship from the Ville de Nice, France (“Aide Individuelle aux Jeunes Chercheurs 2016”).Peer reviewe

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe