Hands-On Parameter Search for Neural Simulations by a MIDI-Controller

Computational neuroscientists frequently encounter the challenge of parameter fitting – exploring a usually high dimensional variable space to find a parameter set that reproduces an experimental data set. One common approach is using automated search algorithms such as gradient descent or genetic algorithms. However, these approaches suffer several shortcomings related to their lack of understanding the underlying question, such as defining a suitable error function or getting stuck in local minima. Another widespread approach is manual parameter fitting using a keyboard or a mouse, evaluating different parameter sets following the users intuition. However, this process is often cumbersome and time-intensive. Here, we present a new method for manual parameter fitting. A MIDI controller provides input to the simulation software, where model parameters are then tuned according to the knob and slider positions on the device. The model is immediately updated on every parameter change, continuously plotting the latest results. Given reasonably short simulation times of less than one second, we find this method to be highly efficient in quickly determining good parameter sets. Our approach bears a close resemblance to tuning the sound of an analog synthesizer, giving the user a very good intuition of the problem at hand, such as immediate feedback if and how results are affected by specific parameter changes. In addition to be used in research, our approach should be an ideal teaching tool, allowing students to interactively explore complex models such as Hodgkin-Huxley or dynamical systems

Coding Efficiency of Fly Motion Processing Is Set by Firing Rate, Not Firing Precision

To comprehend the principles underlying sensory information processing, it is important to understand how the nervous system deals with various sources of perturbation. Here, we analyze how the representation of motion information in the fly's nervous system changes with temperature and luminance. Although these two environmental variables have a considerable impact on the fly's nervous system, they do not impede the fly to behave suitably over a wide range of conditions. We recorded responses from a motion-sensitive neuron, the H1-cell, to a time-varying stimulus at many different combinations of temperature and luminance. We found that the mean firing rate, but not firing precision, changes with temperature, while both were affected by mean luminance. Because we also found that information rate and coding efficiency are mainly set by the mean firing rate, our results suggest that, in the face of environmental perturbations, the coding efficiency is improved by an increase in the mean firing rate, rather than by an increased firing precision

Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Contribuciones a los Derechos Humanos y la Política de Drogas en Alemania

Die vorliegende Publikation befasst sich mit der aktuellen Debatte um die Drogenpolitik und Menschenrechte in Deutschland und der mangelnden Bereitschaft von Entscheidungsträgern, jenseits von Parteivereinbarungen Verantwortung für die Entkriminalisierung von Cannabis und verantwortungsvolle Regulierung für Erwachsene zu übernehmen. Eine Gruppe von Experten, teilweise LEAP(Law Enforcement Against Prohibition)-Deutschland Mitglieder und ein Team des Knowmad Instituts, hat eine Umfrage durchgeführt und Beiträge gesammelt, um einen Überblick über die internationale und nationale Situation zu geben und die Diskussion zu ergänzen. Die Ergebnisse zeigen, dass der Anteil der Cannabiskonsumenten in allen Bildungsschichten und Berufsgruppen höher ist als oft angenommen. Teilnehmende der Umfrage sprechen sich für eine Legalisierung oder staatliche Regulierung von Cannabis aus und sehen polizeiliche Maßnahmen und Strafverfolgung als ineffizient an. Eine Regulierung und Entkriminalisierung von Drogen könnte das Vertrauen in den Staat stärken und zu einem offeneren Umgang mit Substanzen führen, was letztendlich der Gesundheit und Sicherheit aller zugutekommen würde. Die Verfasser empfehlen die pragmatische Anwendung des Rome Consensus 2.0 als Instrument für Reformen hin zu einer humanen Drogenpolitik.&nbsp; Keywords: Menschenrechte, Drogenpolitik, Cannabis, Deutschland, Nekropolitik, Gesundheit, Polizei &nbsp;This publication addresses the current debate on drug policy and human rights in Germany and the unwillingness of decision-makers to take responsibility for cannabis decriminalization and responsible adult regulation beyond party agreements. A group of experts, partly LEAP(Law Enforcement Against Prohibition)-Germany members and a team from Knowmad Institute, conducted a survey and collected input to provide an overview of the international and national situation and add to the discussion. The results show that the proportion of cannabis users in all educational and professional groups is higher than often assumed. Participants in the survey are in favor of legalization or state regulation of cannabis and see police measures and prosecution as inefficient. Regulation and decriminalization of drugs could increase trust in the state and lead to a more open approach to substances, which would ultimately benefit everyone's health and safety. The contributors recommend the pragmatic application of the Rome Consensus 2.0 as a tool for reforms toward humane drug policies.&nbsp; Keywords: human rights, drug policy, cannabis, Germany, necropolitics, public health, police &nbsp;Esta publicación aborda el debate actual sobre la política de drogas y los derechos humanos en Alemania y la falta de voluntad de los responsables políticos para asumir la responsabilidad de la despenalización del cannabis y la regulación responsable de los adultos, más allá de los acuerdos entre partidos. Un grupo de expertos, en parte miembros de LEAP(Law Enforcement Against Prohibition)-Alemania y un equipo del Knowmad Institute, llevaron a cabo una encuesta y recogieron aportaciones para ofrecer una visión general de la situación internacional y nacional y contribuir al debate. Los resultados muestran que la proporción de consumidores de cannabis en todos los grupos educativos y profesionales es mayor de lo que se suele suponer. Los participantes en la encuesta están a favor de la legalización o la regulación estatal del cannabis y consideran ineficaces las medidas policiales y la persecución. La regulación y despenalización de las drogas podría aumentar la confianza en el Estado y conducir a un enfoque más abierto de las sustancias, lo que en última instancia redundaría en beneficio de la salud y la seguridad de todos. Los autores recomiendan la aplicación pragmática del Rome Consensus 2.0 como herramienta de reforma hacia políticas de drogas más humanas.&nbsp; Palabras Clave: derechos humanos, política de drogas, cannabis, Alemania, necropolítica, salud pública, policía &nbsp

CONTRIBUTIONS TO HUMAN RIGHTS AND DRUG POLICY IN GERMANY

Abstract This publication addresses the current debate on drug policy and human rights in Germany and the unwillingness of decision-makers to take responsibility for cannabis decriminalization and responsible adult regulation beyond party agreements. A group of experts, partly LEAP(Law Enforcement Against Prohibition)-Germany members and a team from Knowmad Institute, conducted a survey and collected input to provide an overview of the international and national situation and add to the discussion. The results show that the proportion of cannabis users in all educational and professional groups is higher than often assumed. Participants in the survey are in favor of legalization or state regulation of cannabis and see police measures and prosecution as inefficient. Regulation and decriminalization of drugs could increase trust in the state and lead to a more open approach to substances, which would ultimately benefit everyone's health and safety. The contributors recommend the pragmatic application of the Rome Consensus 2.0 as a tool for reforms toward humane drug policies. DE | Abstract:DievorliegendePublikationbefasstsichmitderaktuellenDebatteumdieDrogenpolitikundMenschenrechteinDeutschlandunddermangelndenBereitschaftvonEntscheidungsträgern,jenseitsvonParteivereinbarungenVerantwortungfürdieEntkriminalisierungvonCannabisundverantwortungsvolleRegulierungfürErwachsenezuübernehmen.EineGruppevonExperten,teilweiseLEAP(LawEnforcementAgainstProhibition)-DeutschlandMitgliederundeinTeamdesKnowmadInstituts,hateineUmfragedurchgeführtundBeiträgegesammelt,umeinenÜberblicküberdieinternationaleundnationaleSituationzugebenunddieDiskussionzuergänzen.DieErgebnissezeigen,dassderAnteilderCannabiskonsumenteninallenBildungsschichtenundBerufsgruppenhöheristalsoftangenommen.TeilnehmendederUmfragesprechensichfüreineLegalisierungoderstaatlicheRegulierungvonCannabisausundsehenpolizeilicheMaßnahmenundStrafverfolgungalsineffizientan.EineRegulierungundEntkriminalisierungvonDrogenkönntedasVertrauenindenStaatstärkenundzueinemoffenerenUmgangmitSubstanzenführen,wasletztendlichderGesundheitundSicherheitallerzugutekommenwürde.DieVerfasserempfehlendiepragmatischeAnwendungdesRomeConsensus2.0 als Instrument für Reformen hin zu einer humanen Drogenpolitik. ES | Abstract:EstapublicaciónabordaeldebateactualsobrelapolíticadedrogasylosderechoshumanosenAlemaniaylafaltadevoluntaddelosresponsablespolíticosparaasumirlaresponsabilidaddeladespenalizacióndelcannabisylaregulaciónresponsabledelosadultos,másalládelosacuerdosentrepartidos.Ungrupodeexpertos,enpartemiembrosdeLEAP(LawEnforcementAgainstProhibition)-AlemaniayunequipodelKnowmadInstitute,llevaronacabounaencuestayrecogieronaportacionesparaofrecerunavisióngeneraldelasituacióninternacionalynacionalycontribuiraldebate.Losresultadosmuestranquelaproporcióndeconsumidoresdecannabisentodoslosgruposeducativosyprofesionalesesmayordeloquesesuelesuponer.Losparticipantesenlaencuestaestánafavordelalegalizaciónolaregulaciónestataldelcannabisyconsideranineficaceslasmedidaspolicialesylapersecución.LaregulaciónydespenalizacióndelasdrogaspodríaaumentarlaconfianzaenelEstadoyconduciraunenfoquemásabiertodelassustancias,loqueenúltimainstanciaredundaríaenbeneficiodelasaludylaseguridaddetodos.LosautoresrecomiendanlaaplicaciónpragmáticadelRomeConsensus2.0comoherramientadereformahaciapolíticasdedrogasmáshumanas