Neuroimaging of chronic MDMA ("ecstasy") effects: A meta-analysis

In this meta-analysis, we aimed to assess the evidence from neuroimaging studies for chronic alterations in the brains of MDMA users. The databases PubMed, Embase, and Web of Science were searched for studies published from inception to August 24, 2018, without any language restriction. Sixteen independent studies comprising 356 MDMA users and 311 controls were included. Of these, five studies investigated frontal and occipital N-acetylaspartate/creatine and myo-inositol/creatine ratios, three studies assessed basal ganglia blood flow and ten studies investigated serotonin transporter (SERT) density in various regions. We found significantly decreased SERT density in eight of 13 investigated regions. Meta-regression indicated a positive association with abstinence, but none with lifetime episodes of use. Therefore, other variables (such as doses taken per occasion) might be more important determinants. Positive associations between time of abstinence and SERT density might indicate that these alterations are reversible to some extent. Furthermore, there were no significant differences between user and control groups in terms of neurochemical ratios in the frontal and occipital lobes and blood flow in the basal ganglia. Overall, MDMA user groups showed heavy use patterns and study quality was poor

Flop Transitions in M-theory Cosmology

We study flop-transitions for M-theory on Calabi-Yau three-folds and their applications to cosmology in the context of the effective five-dimensional supergravity theory. In particular, the additional hypermultiplet which becomes massless at the transition is included in the effective action. We find the potential for this hypermultiplet which includes quadratic and quartic terms as well as additional dependence on the Kahler moduli. By constructing explicit cosmological solutions, it is demonstrated that a flop-transition can indeed by achieved dynamically, as long as the hypermultiplet is set to zero. Once excitations of the hypermultiplet are taken into account we find that the transition is generically not completed but the system is stabilised close to the transition region. Regions of moduli space close to flop-transitions can, therefore, be viewed as preferred by the cosmological evolution.Comment: 18 pages, Latex, 8 eps-figures, typos correcte

Five-Branes in Heterotic Brane-World Theories

The effective action for five-dimensional heterotic M-theory in the presence of five-branes is systematically derived from Horava-Witten theory coupled to an M5-brane world-volume theory. This leads to a five-dimensional N=1 gauged supergravity theory on S^1/Z_2 coupled to four-dimensional N=1 theories residing on the two orbifold fixed planes and an additional bulk three-brane. We analyse the properties of this action, particularly the four-dimensional effective theory associated with the domain-wall vacuum state. The moduli Kahler potential and the gauge-kinetic functions are determined along with the explicit relations between four-dimensional superfields and five-dimensional component fields.Comment: 19 pages, Latex, typos corrected, reference adde

Heterotic M-Theory Cosmology in Four and Five Dimensions

We study rolling radii solutions in the context of the four- and five-dimensional effective actions of heterotic M-theory. For the standard four-dimensional solutions with varying dilaton and T-modulus, we find approximate five-dimensional counterparts. These are new, generically non-separating solutions corresponding to a pair of five-dimensional domain walls evolving in time. Loop corrections in the four-dimensional theory are described by certain excitations of fields in the fifth dimension. We point out that the two exact separable solutions previously discovered are precisely the special cases for which the loop corrections are time-independent. Generically, loop corrections vary with time. Moreover, for a subset of solutions they increase in time, evolving into complicated, non-separating solutions. In this paper we compute these solutions to leading, non-trivial order. Using the equations for the induced brane metric, we present a general argument showing that the accelerating backgrounds of this type cannot evolve smoothly into decelerating backgrounds.Comment: 15 pages, Latex, 1 eps figur

Local Water Loop : Vorstudie für einen energie- und wasserautarken Waschmaschinenbetrieb

Während der Bedarf an Süsswasser weltweit stetig steigt, wird dessen Verfügbarkeit immer knapper. Um dem entgegenzuwirken, ist die lokale Behandlung und Wiederverwendung von Grauwasser ein vielversprechender Ansatz. Von besonderem Interesse sind der Einsatz von grünen Wänden, als platzsparende Alternative zu Pflanzenkläranlagen, und Filtersäulen zur biologischen Reinigung des Abwassers. Im vorliegenden Projekt wurden die Grundlagen für einen energie- und wasserautarken Waschmaschinenbetrieb, basierend auf der biologischen Reinigungstechnologie, erarbeitet. Es wurde eine Reihe von Experimenten durchgeführt, um Waschmaschinenabwasser zu charakterisieren, eine geeignete Vorreinigung auszuwählen, ein geeignetes Filtersubstrat für die grüne Wand zu identifizieren, die Keimbelastung zu analysieren und den Energieautarkiegrad zu bestimmen und zu optimieren. Die Analyse des Waschmaschinenabwassers zeigte, dass ein Grossteil der Verschmutzung im Abwasser vom Waschmittel selbst stammt. Daher ist die Verwendung eines ökologischen Waschmittels und dessen korrekte Dosierung essenziell für einen ressourceneffizienten Betrieb. Für die physikalisch-mechanische Vorreinigung wurden ein Sandfilter und ein Feinfilter getestet. Aufgrund der hohen Faserbelastung im Waschmaschinenabwasser zeigte sich der Sandfilter als ungeeignet, da er schnell verstopfte. Stattdessen konnte mit dem Feinfilter eine gute Vorreinigung erzielt werden. Die Faserbelastung im Waschmaschinenabwasser betrug durchschnittlich 25 mg/L vor der Vorreinigung und konnte durch den Feinfilter auf 2 mg/L reduziert werden. Die Analyse der Reinigungsleistung verschiedener Substrate für die grüne Wand, darunter Vulkaponic, Vulkaponic/Pflanzenkohle-Mischung und Perlit, zeigte, dass mit reinem Vulkaponic die besten Ergebnisse erzielt wurden. Die Reinigungseffizienz von Vulkaponic betrug im Durchschnitt 85%, während die Mischung aus Vulkaponic und Pflanzenkohle eine Reinigungsleistung von 78% aufwies. Perlit erreichte eine Reinigungsleistung von 62%. Die Keimbelastung im Kreislaufsystem der Waschmaschine nimmt nach der Reinigung und UV-Behandlung stetig ab, sodass die Wasserqualität den Anforderungen an Badegewässer entspricht. Die Konzentration der aeroben mesophilen Keime sank von 130’000 KBE/mL auf 1’400 KBE/mL nach der UV-Behandlung. Dies bestätigt die Effektivität der angewandten Reinigungs- und Desinfektionsverfahren. Um den Energieautarkiegrad über ein Jahr zu bestimmen, wurden die gemessenen Werte auf ein Jahr extrapoliert. In der jetzigen Ausführung kann somit ein Autarkiegrad von 30% erzielt werden. Durch den Einsatz zusätzlicher Optimierungsmassnahmen wie die Nutzung von zusätzlichen Solarpanels und einer optimierten Steuerung kann dieser Wert auf 66% erhöht werden. Am Zielstandort in Kapstadt, Südafrika könnte damit ein Autarkiegrad von 86% erreicht werden. Die gewonnenen Erkenntnisse aus den Experimenten dienen dazu, den energie- und wasserautarken Waschmaschinenbetrieb in Folgeprojekten weiterzuentwickeln und zu optimieren

OJS Software Workshop Report

This report summarizes the achievements of the OJS community members from Germany and Switzerland in the OJS Workshop in Heidelberg University Library, Germany from February 20 and 21, 2020. Main goal of the workshop was to share knowledge and challenges, conceptualize and document problem solving suggestions and collectively develop software in and around OJS. Participants worked on a variety of subjects including data import/export plugins, search functionality, containerization, long-time archiving and XML workflows in and around OJS and OMP. The workshop is a continuation of fruitful meetings within the German OJS user and developer community under auspices of OJS-de.net networ

Glucocorticoid withdrawal and glucocorticoid-induced adrenal insufficiency: Study protocol of the randomized controlled «TOASST" (Taper Or Abrupt Steroid STop) multicenter trial

BACKGROUND Despite the widespread use of glucocorticoids in inflammatory and autoimmune disorders, there is uncertainty about the safe cessation of long-term systemic treatment, as data from prospective trials are largely missing. Due to potential disease relapse or glucocorticoid-induced hypocortisolism, the drug is often tapered to sub-physiological doses rather than stopped when the underlying disease is clinically stable, increasing the cumulative drug exposure. Conversely, the duration of exposure to glucocorticoids should be minimized to lower the risk of side effects. METHODS We designed a multicenter, randomized, triple-blinded, placebo-controlled trial to test the clinical noninferiority of abrupt glucocorticoid stop compared to tapering after ≥28 treatment days with ≥420 mg cumulative and ≥7.5 mg mean daily prednisone-equivalent dose. 573 adult patients treated systemically for various disorders will be included after their underlying disease has been stabilized. Prednisone in tapering doses or matching placebo is administered over 4 weeks. A 250 mg ACTH-test, the result of which will be revealed a posteriori, is performed at study inclusion; all patients are instructed on glucocorticoid stress cover dosing. Follow-up is for 6 months. The composite primary outcome measure is time to hospitalization, death, initiation of unplanned systemic glucocorticoid therapy, or adrenal crisis. Secondary outcomes include the individual components of the primary outcome, cumulative glucocorticoid doses, signs and symptoms of hypocortisolism, and the performance of the ACTH test in predicting the clinical outcome. Cox proportional hazard, linear, and logistic regression models will be used for statistical analysis. CONCLUSION This trial aims to demonstrate the clinical noninferiority and safety of abrupt treatment cessation after ≥28 days of systemic glucocorticoid therapy in patients with stabilized underlying disease. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03153527; EUDRA-CT: 2020-005601-48 https://clinicaltrials.gov/ct2/show/NCT03153527?term=NCT03153527&draw=2&rank=1

How Many Thymocytes Audition for Selection?

T cell maturation requires the rearrangement of clonotypic T cell receptors (TCR) capable of interacting with major histocompatibility complex (MHC) ligands to initiate positive and negative selection. Only 3–5% of thymocytes mature to join the peripheral T cell pool. To investigate the basis for this low success rate, we have measured the frequency of preselection thymocytes capable of responding to MHC. As many as one in five MHC-naive thymocytes show upregulation of activation markers on exposure to MHC-expressing thymic stroma in short-term reaggregate culture. The majority of these cells display physiological changes consistent with entry into the selection process within 24 h. By exposing TCR transgenic thymocytes to a range of MHC–peptide complexes, we show that CD69 induction is indicative of thymocyte selection, positive or negative. Our data provide evidence that the fraction of thymocytes that qualify to enter the thymic selection process far exceeds the fraction that successfully complete it, and suggest that most MHC-reactive thymocytes are actively eliminated in the course of selection