Antimicrobial effects of murine mesenchymal stromal cells directed against Toxoplasma gondii and Neospora caninum: role of immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs).

Mesenchymal stromal cells (MSCs) have a multilineage differentiation potential and provide immunosuppressive and antimicrobial functions. Murine as well as human MSCs restrict the proliferation of T cells. However, species-specific differences in the underlying molecular mechanisms have been described. Here, we analyzed the antiparasitic effector mechanisms active in murine MSCs. Murine MSCs, in contrast to human MSCs, could not restrict the growth of a highly virulent strain of Toxoplasma gondii (BK) after stimulation with IFN-γ. However, the growth of a type II strain of T. gondii (ME49) was strongly inhibited by IFN-γ-activated murine MSCs. Immunity-related GTPases (IRGs) as well as guanylate-binding proteins (GBPs) contributed to this antiparasitic effect. Further analysis showed that IFN-γ-activated mMSCs also inhibit the growth of Neospora caninum, a parasite belonging to the apicomplexan group as well. Detailed studies with murine IFN-γ-activated MSC indicated an involvement in IRGs like Irga6, Irgb6 and Irgd in the inhibition of N. caninum. Additional data showed that, furthermore, GBPs like mGBP1 and mGBP2 could have played a role in the anti-N. caninum effect of murine MSCs. These data underline that MSCs, in addition to their regenerative and immunosuppressive activity, function as antiparasitic effector cells as well. However, IRGs are not present in the human genome, indicating a species-specific difference in anti-T. gondii and anti-N. caninum effect between human and murine MSCs.

The need for transparency and good practices in the qPCR literature

Two surveys of over 1,700 publications whose authors use quantitative real-time PCR (qPCR) reveal a lack of transparent and comprehensive reporting of essential technical information. Reporting standards are significantly improved in publications that cite the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, although such publications are still vastly outnumbered by those that do not.

Strategies for reducing fumigant loss to the atmosphere

A model is developed to describe transport and loss of methyl bromide (MeBr) in soil following application as a soil fumigant. The model is used to investigate the effect of soil and management factors on MeBr volatilization. Factors studied include depth of injection, soil water content, presence or absence of tarp, depth to downward barrier, and irrigation after injection. Of these factors, the most important was irrigation after injection followed by covering with the tarp, which increased the diffusive resistance of the soil and prevented early loss of MeBr. The model offers an explanation for the apparently contradictory observations of earlier field studies of MeBr volatilization from soils under different conditions. The model was also used to calculate the concentration-time index for various management alternatives, showing that the irrigation application did not make the surface soil more difficult to fumigate, except at very early times. Therefore, irrigation shows promise for reducing fumigant loss while at the same time permitting control of target organisms during fumigation.

Temperature and Resource Availability May Interactively Affect Over-Wintering Success of Juvenile Fish in a Changing Climate

The predicted global warming may affect freshwater systems at several organizational levels, from organism to ecosystem. Specifically, in temperate regions, the projected increase of winter temperatures may have important effects on the over-winter biology of a range of organisms and especially for fish and other ectothermic animals. However, temperature effects on organisms may be directed strongly by resource availability. Here, we investigated whether over-winter loss of biomass and lipid content of juvenile roach (Rutilus rutilus) was affected by the physiologically relatively small (2-5°C) changes of winter temperatures predicted by the Intergovernmental Panel on Climate Change (IPCC), under both natural and experimental conditions. This was investigated in combination with the effects of food availability. Finally, we explored the potential for a correlation between lake temperature and resource levels for planktivorous fish, i.e., zooplankton biomass, during five consecutive winters in a south Swedish lake. We show that small increases in temperature (+2°C) affected fish biomass loss in both presence and absence of food, but negatively and positively respectively. Temperature alone explained only a minor part of the variation when food availability was not taken into account. In contrast to other studies, lipid analyses of experimental fish suggest that critical somatic condition rather than critical lipid content determined starvation induced mortality. Our results illustrate the importance of considering not only changes in temperature when predicting organism response to climate change but also food-web interactions, such as resource availability and predation. However, as exemplified by our finding that zooplankton over-winter biomass in the lake was not related to over-winter temperature, this may not be a straightforward task.

Review of lattice results concerning low-energy particle physics

We review lattice results related to pion, kaon, D- and B-meson physics with the aim of making them easily accessible to the particle-physics community. More specifically, we report on the determination of the lightquark masses, the form factor f+(0), arising in semileptonic K → π transition at zero momentum transfer, as well as the decay-constant ratio fK / fπ of decay constants and its consequences for the CKM matrix elements Vus and Vud. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of SU(2)L × SU(2)R and SU(3)L×SU(3)R Chiral Perturbation Theory and review the determination of the BK parameter of neutral kaon mixing. The inclusion of heavy-quark quantities significantly expands the FLAG scope with respect to the previous review. Therefore, we focus here on D- and B-meson decay constants, form factors, and mixing parameters, since these are most relevant for the determination of CKM matrix elements and the global CKM unitarity-triangle fit. In addition we review the status of lattice determinations of the strong coupling constant αs.

Endovascular treatment for acute ischemic stroke patients: implications and interpretation of IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials: A report from the Working Group of International Congress of Interventional Neurology

OBJECTIVE The results of Interventional Management of Stroke (IMS) III, Magnetic Resonance and REcanalization of Stroke Clots Using Embolectomy (MR RESCUE), and SYNTHESIS EXPANSION trials are expected to affect the practice of endovascular treatment for acute ischemic stroke. The purpose of this report is to review the components of the designs and methods of these trials and to describe the influence of those components on the interpretation of trial results. METHODS A critical review of trial design and conduct of IMS III, MR RESCUE, and SYNTHESIS EXPANSION is performed with emphasis on patient selection, shortcomings in procedural aspects, and methodology of data ascertainment and analysis. The influence of each component is estimated based on published literature including multicenter clinical trials reporting on endovascular treatment for acute ischemic stroke and myocardial infarction. RESULTS We critically examined the time interval between symptom onset and treatment and rates of angiographic recanalization to differentiate between "endovascular treatment" and "parameter optimized endovascular treatment" as it relates to the IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials. All the three trials failed to effectively test "parameter optimized endovascular treatment" due to the delay between symptom onset and treatment and less than optimal rates of recanalization. In all the three trials, the magnitude of benefit with endovascular treatment required to reject the null hypothesis was larger than could be expected based on previous studies. The IMS III and SYNTHESIS EXPANSION trials demonstrated that rates of symptomatic intracerebral hemorrhages subsequent to treatment are similar between IV thrombolytics and endovascular treatment in matched acute ischemic stroke patients. The trials also indirectly validated the superiority/equivalence of IV thrombolytics (compared with endovascular treatment) in patients with minor neurological deficits and those without large vessel occlusion on computed tomographic/magnetic resonance angiography. CONCLUSIONS The results do not support a large magnitude benefit of endovascular treatment in subjects randomized in all the three trials. The possibility that benefits of a smaller magnitude exist in certain patient populations cannot be excluded. Large magnitude benefits can be expected with implementation of "parameter optimized endovascular treatment" in patients with ischemic stroke who are candidates for IV thrombolytics.

Institutions for sustainable governance of forests: Equity, robustness and cross-level interactions in Mawlyngbna, Meghalaya, India

This study adopts Ostrom’s Social-Ecological Systems (SES) framework in empirical fieldwork to explain how local forestry institutions affect forest ecosystems and social equity in the community of Mawlyngbna in North-East India. Data was collected through 26 semi-structured interviews, participatory timeline development, policy documents, direct observation, periodicals, transect walks, and a concurrent forest-ecological study in the village. Results show that Mawlyngbna's forests provide important sources of livelihood benefits for the villagers. However, ecological disturbance and diversity varies among the different forest ownership types and forest-based livelihood benefits are inequitably distributed. Based on a bounded rationality approach, our analysis proposes a set of causal mechanisms that trace these observed social-ecological outcomes to the attributes of the resource system, resource units, actors and governance system. We analyse opportunities and constraints of interactions between the village, regional, and state levels. We discuss how Ostrom’s design principles for community-based resource governance inform the explanation of robustness but have a blind spot in explaining social equity. We report experiences made using the SES framework in empirical fieldwork. We conclude that mapping cross-level interactions in the SES framework needs conceptual refinement and that explaining social equity of forest governance needs theoretical advances.

BitWorker, a Decentralized Distributed Computing System based on BitTorrent

In this paper we present BitWorker, a platform for community distributed computing based on BitTorrent. Any splittable task can be easily specified by a user in a meta-information task file, such that it can be downloaded and performed by other volunteers. Peers find each other using Distributed Hash Tables, download existing results, and compute missing ones. Unlike existing distributed computing schemes relying on centralized coordination point(s), our scheme is totally distributed, therefore, highly robust. We evaluate the performance of BitWorker using mathematical models and real tests, showing processing and robustness gains. BitWorker is available for download and use by the community.

Monitoring the temporal development of natural hazard risks as a basis indicator for climate change adaptation.

The potential effects of climatic changes on natural risks are widely discussed. But the formulation of strategies for adapting risk management practice to climate changes requires knowledge of the related risks for people and economic values. The main goals of this work were (1) the development of a method for analysing and comparing risks induced by different natural hazard types, (2) highlighting the most relevant natural hazard processes and related damages, (3) the development of an information system for the monitoring of the temporal development of natural hazard risk and (4) the visualisation of the resulting information for the wider public. A comparative exposure analysis provides the basis for pointing out the hot spots of natural hazard risks in the province of Carinthia, Austria. An analysis of flood risks in all municipalities provides the basis for setting the priorities in the planning of flood protection measures. The methods form the basis for a monitoring system that periodically observes the temporal development of natural hazard risks. This makes it possible firstly to identify situations in which natural hazard risks are rising and secondly to differentiate between the most relevant factors responsible for the increasing risks. The factors that most influence the natural risks could be made evident.

Mechanical thrombectomy in acute ischemic stroke: Consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN

The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16-18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).

Expanded Clinical Spectrum of Multiple Evanescent White Dot Syndrome with Multimodal Imaging

PURPOSE: To evaluate and characterize multiple evanescent white dot syndrome abnormalities with modern multimodal imaging modalities. METHODS: This retrospective cohort study evaluated fundus photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, enhanced depth imaging optical coherence tomography, short-wavelength autofluorescence, and near-infrared autofluorescence. RESULTS: Thirty-four multiple evanescent white dot syndrome patients with mean age of 28.7 years were studied (range, 14-49 years). Twenty-six patients were women, and eight were men. Initial mean visual acuity was 0.41 logMAR. Final mean visual acuity was 0.03 logMAR. Fluorescein angiography shows a variable number of mid retinal early fluorescent dots distributed in a wreathlike pattern, which correlate to fundus photography, fundus autofluorescence, and indocyanine green angiography. Indocyanine green angiography imaging shows the dots and also hypofluorescent, deeper, and larger spots, which are occasionally confluent, demonstrating a large plaque of deep retinal hypofluorescence. Optical coherence tomography imaging shows multifocal debris centered at and around the ellipsoid layer, corresponding to the location of spots seen with photography, indocyanine green angiography, and fluorescein angiography. Protrusions of the hyperreflectant material from the ellipsoid layer toward the outer nuclear layer correspond to the location of dots seen with photography, indocyanine green angiography, and fluorescein angiography. CONCLUSION: Multimodal imaging analysis of the retina in patients with multiple evanescent white dot syndrome shows additional features that may help in the diagnosis of the disease and in further understanding its etiology. Multiple evanescent white dot syndrome is predominantly a disease of the outer retina, centered at the ellipsoid zone, but also involving the interdigitation zone and the outer nuclear layer.

Entwicklung und Implementierung von Modellen für ein Skills-Training-Parcours für internistische Assistenzärzte

„Entwicklung und Implementierung von Modellen für ein Skills-Training-Parcours für internistische Assistenzärzte “ V. Maier1 - K. Schnabel2 1 Universitätslinik für Allgemeine Innere Medizin, Inselspital, Bern 2 Berner interdisziplinäres Skills- und Schauspielpatientenzentrum (BiSS), Institut für Medizinische Lehre (IML), Abteilung für Unterricht und Medien (AUM) Einleitung: Im klinischen Alltag sind praktische Fertigkeiten gefordert, um Patienten sicher zu behandeln. Auch in der Schweizer Fachgesellschaft FMH kam es zu einer stärkeren Gewichtung der praktischen Fertigkeiten und müssen jetzt ein Logbuch über Art und Zeitpunkt der Intervention führen [1]. Am Inselspital Bern wurde dafür ein Skillsparcours etabliert, da in vielen Bereichen simulationsbasierte Ausbildungen traditionellen Methoden überlegen ist [2]. Der Skillsparcours besteht aus einem Nachmittag mit 4 nicht-invasiven Prozeduren und einem Nachmittag mit 5 invasiven Prozeduren. Eigens dafür wurden drei Modelle entwickelt und deren Tauglichkeit evaluiert. Fragestellung: Bilden die selbst gefertigten Modelle die Realität ausreichend ab? Material und Methoden: Innerhalb der 9 Posten (5 invasiv und 4 nichtinvasiv) wurden für die 5 invasiven Posten zwei Modelle aus dem Skillslab (BiSS) genutzt (Lumbalpunktion (LP) und Blasenkatheter (BK)) und drei Modelle neu entwickelt (Pleura-(PP), Aszites-(AP) und Knochenmarks-Punktion (KMP)). Die Modelle wurden mit Materialien aus dem Baumarkt entwickelt (Material ca. CHF 50/Stück). Der Aufbau der Modelle soll auf der Tagung demonstriert werden. Die Teilnehmer (N=12) und Dozenten (N=5) wurden zu der Qualität mittels Fragebogen befragt. Dabei wurde die individuelle Vorerfahrung und die Einschätzung der Teilnehmer erfragt. Die Frage zur Eignung des Modells war: „Das Modell war zum Üben geeignet“. Als Skala wurde eine Likert-Skala von 0 bis 5 (1=sehr ungeeignet, 5=sehr geeignet) benutzt. Ergebnisse: Die Assistenzärzte beurteilten die Modelleignung wie folgt (Median (Min;Max)): LP: 5 (4;5) KMP: 4.5 (3;5), PP: 4 (3;5), AP: 4.5 (2;5), BK-Einlage: 4.5 (4;6). Die Oberärzte, die jeweils nur das Modell bewerteten, an welchem sie den Kurs durchführten, beurteilten die Modelleignung wie folgt: LP 5.0, KMP: 5.0, PP 5.0, AP: 4.0, BK-Einlage: 3.0. Diskussion: Alle Modelle wurden sowohl von den Oberärzten als auch von den Assistenzärzten als zum Üben tauglich eingeschätzt. Zwischen den selbst hergestellten Low-Fidelity Modellen und den High-Fidelity Modellen gab es hierein keinen signifikanten Unterschied. Als am wenigsten tauglich wurde von den Oberärzten mit der Simulation der Blasenkatheter-Einlage ein High-Fidelity-Modell bewertet. Schlussfolgerungen: Alle Modelle für die Simulation der Punktionstechniken haben gut bis sehr gut funktioniert. Die selbst hergestellten Modelle bilden die Wirklich zum Üben der Techniken hinreichend gut und nicht schlechter als die High-Fidelity-Modelle ab. Selbst gebaute Modelle mit Materialien aus dem Baumarkt können das sonst sehr materialaufwändige Training mit Simulatoren genauso effektiv aber wesentlich effizienter durchführbar machen. Literatur bei den Autoren (1) Weiterbildungsordnung FMH 2014 (letzte Revision 4. September 2014). www.fmh.ch/files/pdf15/wbo_d.pdf (2) McGaghie WC, Issenberg SB, Cohen ER, Barsuk JH, Wayne DB (2011) Does simulation-based medical education with deliberate practice yield better results than traditional clinical education? A meta-analytic comparative review of the evidence. Acad Med. 2011 Jun;86(6):706-11

Évaluation: l’indépendance à l’épreuve de la relation entre mandants et mandataires

L’article suivant rend compte des résultats d’un atelier tenu à l’occasion du congrès 2015 de la SEVAL. L’atelier portait sur l’indépendance des évaluateurs et des évaluatrices du point de vue de leur relation avec les commanditaires de l’évaluation. Sur la base d’un exemple de mandat concret présenté par deux intervenants – l’évaluatrice ainsi que le conseiller d’État mandant de l’évaluation en question – les différents garde-fous contractuels, communicationnels et procéduraux aptes à garantir une pleine indépendance de l’évaluation ont été discutés. Il en est ressorti que quatre dimensions étaient cruciales pour le succès de la démarche : les conditions-cadres de l’évaluation, la récolte des données, les relations avec les évalués, ainsi que la phase de restitution des résultats.