Summary and Evaluation of the EDEN ISS Public Outreach Activities

EDEN ISS is a European project focused on advancing bio-regenerative life support systems, in particular plant cultivation in space. A mobile test facility was designed and built between March 2015 and October 2017. The facility incorporates a Service Section which houses several subsystems necessary for plant cultivation and the Future Exploration Greenhouse. The latter is built similar to a future space greenhouse and provides a fully controlled environment for plant cultivation. The facility was setup in Antarctica in January 2018 and successfully operated between February and November of the same year. During that nine month period around 270 kg of food was produced by the crops cultivation in the greenhouse. It is the wish and more often the need for scientific projects to communicate their outcomes not only to the scientific community, but also to the general public. The EDEN ISS project and in particular the experimental phase in Antarctica was accompanied by extensive public outreach activities. Presence in social media, a project website, informative flyers, an experimental toolkit for young students were created in order to engage with the general public. This paper describes the different public outreach activities of the project and also evaluates their effectiveness. For the evaluation, statistics from the website and social media accounts as well as responses to press releases and educational activities are being displayed. Based on the experience from the outreach campaign of EDEN ISS, the paper provides recommendations on how to organize and conduct public outreach activities for scientific projects in space exploratio

Quality assessment of a randomly selected sample of Swiss medical expertises : a pilot study

Background: Considerable criticism has lately been raised by the media regarding the quality of Swiss medical expertises. The present investigation was therefore undertaken to assess the professional quality of Swiss medical expertises. The study was part of a market analysis of medical expertises (MGS study). Methods: A sample of 97 anonymised expertises randomly chosen from a total of 3165, collected in the MGS study over a period of 3 months, were evaluated by an international board of medical experts and reviewers, using a stepwise developed questionnaire. Each expertise was independently evaluated by two experts. Data were then tested for plausibility (obvious errors and misunderstandings). The main outcome was the overall quality rating of the expertise that was graded from 1 (very poor) to 6 (excellent) in analogy to the Swiss school grading system. For analysis and interpretation the grades were divided into sufficient (grades >= 4) and insufficient (grades <4). Results: Overall 19.6% (95% confidence interval: 13.1%; 28.3%) of the expertises were rated to be of insufficient quality. The quality was inversely related to the number of involved medical disciplines, the time relapsed since injury and positively related to the difficulty of the expertise. In addition, expertises in the French and Italian languages were rated superior to those in German. Conclusions: Our results confirm recent criticisms that the professional quality of expertises does not suffice. This is hardly acceptable in face of the financial and personal consequences. There is an obvious need for further research using larger samples and for educational programmes on all levels

The provision of out-of-hours care and associated costs in an urban area of Switzerland: a cost description study

BACKGROUND: In Switzerland, General Practitioners (GPs) play an important role for out-of-hours emergency care as one service option beside freely accessible and costly emergency departments of hospitals. The aim of this study was to evaluate the services provided and the economic consequences of a Swiss GP out-of-hours service. METHODS: GPs participating in the out-of-hours service in the city of Zurich collected data on medical problems (ICPC coding), mode of contact, mode of resource use and services provided (time units; diagnostics; treatments). From a health care insurance perspective, we assessed the association between total costs and its two components (basic costs: charges for time units and emergency surcharge; individual costs: charges for clinical examination, diagnostics and treatment in the discretion of the GP). RESULTS: 125 GPs collected data on 685 patient contacts. The most prevalent health problems were of respiratory (24%), musculoskeletal (13%) and digestive origin (12%). Home visits (61%) were the most common contact mode, followed by practice (25%) and telephone contacts (14%). 82% of patients could be treated by ambulatory care. In 20% of patients additional technical diagnostics, most often laboratory tests, were used. The mean total costs for one emergency patient contact were €144 (95%-CI: 137-151). The mode of contact was an important determinant of total costs (mean total costs for home visits: €176 [95%-CI: 168-184]; practice contact: €90 [95%-CI: 84-98]; telephone contact: €48 [95%-CI: 40-55]). Basic costs contributed 83% of total costs for home visits and 70% of total costs for practice contacts. Individual mean costs were similarly low for home visits (€30) and practice contacts (€27). Medical problems had no relevant influence on this cost pattern. CONCLUSIONS: GPs managed most emergency demand in their out-of-hours service by ambulatory care. They applied little diagnostic testing and basic care. Our findings are of relevance for policy makers even from other countries with different pricing policies. Policy makers should be interested in a reimbursement system promoting out-of-hours care run by GPs as one valuable service option

Targeting the innate repair receptor axis via erythropoietin or pyroglutamate helix B surface peptide attenuates hemolytic-uremic syndrome in mice

Hemolytic-uremic syndrome (HUS) can occur as a systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli and is characterized by microangiopathic hemolytic anemia and acute kidney injury. Hitherto, therapy has been limited to organ-supportive strategies. Erythropoietin (EPO) stimulates erythropoiesis and is approved for the treatment of certain forms of anemia, but not for HUS-associated hemolytic anemia. EPO and its non-hematopoietic analog pyroglutamate helix B surface peptide (pHBSP) have been shown to mediate tissue protection via an innate repair receptor (IRR) that is pharmacologically distinct from the erythropoiesis-mediating receptor (EPO-R). Here, we investigated the changes in endogenous EPO levels in patients with HUS and in piglets and mice subjected to preclinical HUS models. We found that endogenous EPO was elevated in plasma of humans, piglets, and mice with HUS, regardless of species and degree of anemia, suggesting that EPO signaling plays a role in HUS pathology. Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS. Administration of EPO or pHBSP improved 7-day survival and attenuated renal oxidative stress but did not significantly reduce renal dysfunction and injury in the employed model. pHBSP, but not EPO, attenuated renal nitrosative stress and reduced tubular dedifferentiation. In conclusion, targeting the EPO-R/IRR axis reduced mortality and renal oxidative stress in murine HUS without occurrence of thromboembolic complications or other adverse side effects. We therefore suggest that repurposing EPO for the treatment of patients with hemolytic anemia in HUS should be systematically investigated in future clinical trials

SimpleHome [home automation system]

The current method of configuring a home automation system is by setting rules which the system will follow or by using a smart phone to set the state of a light or plug. In most cases, it becomes a task to set up such a complicated system or to fish out a phone to open an app, only to flip a light switch on! Lights and electronics which are currently in use don’t adjust with a change in schedule or based on the weather unless a specific rule is set. SimpleHome is a device that will automatically find, connect and collect data from sensors in the home and then use that data to make power saving decisions. Unlike a smart thermostat which reduces electricity consumption by only controlling a furnace, the SimpleHome can monitor and modify controls for almost all electrical objects in a household. Our product will control the blinds and let the user know whether it is better to open a window or turn on the AC. SimpleHome aims to help make the most of every dollar spent on electricity, as well as, provide a solution which can be used immediately after plugging it in. &nbsp

Satisfaction of staff of Swiss insurance companies with medical appraisals: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>A high quality of timely delivered medical appraisals is crucial for social and other insurances to judge possible occupational reintegration measures for patients with medical conditions who are in danger to lose their job. However, little is known about the satisfaction of staff of insurance companies with medical appraisals that they have commissioned.</p> <p>Our questionnaire survey prospectively included all medical appraisals arriving at Swiss insurances from FEB to APR 2008. We assessed the satisfaction of the commissioner with medical appraisals performed by medical assessors. In addition, we evaluated the contribution of several factors to overall satisfaction. The unit of sample was the medical appraisal.</p> <p>Findings</p> <p>We analysed 3165 medical appraisals, 2444 (77%) of them from the public disability insurance, 678 (22%) from private accident, liability and loss of income insurances and 43 (1%) from other insurances. Overall satisfaction of staff of insurance companies in Switzerland was high, but satisfaction of the disability insurance with appraisals was generally lower compared to satisfaction of private insurances. The staff of the disability insurance judged time for preparation as too long in 30%. For staff of private insurance companies 20% of appraisals were not "worth its price". Well-grounded and comprehensible conclusions were the single most important factor for high overall satisfaction (OR 10.1; 95%-CI: 1.1-89.3).</p> <p>Conclusions</p> <p>From the viewpoint of staff of insurance companies, a relevant part of medical appraisals arrives too late. Medical assessors have to take the specific needs of insurances into account, to perform more appraisals with sound conclusions in due time.</p

Development of a highly effective combination monoclonal antibody therapy against Herpes simplex virus.

BACKGROUND Infections with Herpes simplex virus (HSV)-1 or -2 usually present as mild chronic recurrent disease, however in rare cases can result in life-threatening conditions with a large spectrum of pathology. Monoclonal antibody therapy has great potential especially to treat infections with virus resistant to standard therapies. HDIT101, a humanized IgG targeting HSV-1/2 gB was previously investigated in phase 2 clinical trials. The aim of this study was to develop a next-generation therapy by combining different antiviral monoclonal antibodies. METHODS A lymph-node derived phage display library (LYNDAL) was screened against recombinant gB from Herpes simplex virus (HSV) -1 and HDIT102 scFv was selected for its binding characteristics using bio-layer interferometry. HDIT102 was further developed as fully human IgG and tested alone or in combination with HDIT101, a clinically tested humanized anti-HSV IgG, in vitro and in vivo. T-cell stimulating activities by antigen-presenting cells treated with IgG-HSV immune complexes were analyzed using primary human cells. To determine the epitopes, the cryo-EM structures of HDIT101 or HDIT102 Fab bound to HSV-1F as well as HSV-2G gB protein were solved at resolutions < 3.5 Å. RESULTS HDIT102 Fab showed strong binding to HSV-1F gB with Kd of 8.95 × 10-11 M and to HSV-2G gB with Kd of 3.29 × 10-11 M. Neutralization of cell-free virus and inhibition of cell-to-cell spread were comparable between HDIT101 and HDIT102. Both antibodies induced internalization of gB from the cell surface into acidic endosomes by binding distinct epitopes in domain I of gB and compete for binding. CryoEM analyses revealed the ability to form heterogenic immune complexes consisting of two HDIT102 and one HDIT101 Fab bound to one gB trimeric molecule. Both antibodies mediated antibody-dependent phagocytosis by antigen presenting cells which stimulated autologous T-cell activation. In vivo, the combination of HDIT101 and HDIT102 demonstrated synergistic effects on survival and clinical outcome in immunocompetent BALB/cOlaHsd mice. CONCLUSION This biochemical and immunological study showcases the potential of an effective combination therapy with two monoclonal anti-gB IgGs for the treatment of HSV-1/2 induced disease conditions

Effect of Conformational Diversity on the Bioactivity of µ-Conotoxin PIIIA Disulfide Isomers

Cyclic µ-conotoxin PIIIA, a potent blocker of skeletal muscle voltage-gated sodium channel NaV1.4, is a 22mer peptide stabilized by three disulfide bonds. Combining electrophysiological measurements with molecular docking and dynamic simulations based on NMR solution structures, we investigated the 15 possible 3-disulfide-bonded isomers of µ-PIIIA to relate their blocking activity at NaV1.4 to their disulfide connectivity. In addition, three µ-PIIIA mutants derived from the native disulfide isomer, in which one of the disulfide bonds was omitted (C4-16, C5-C21, C11-C22), were generated using a targeted protecting group strategy and tested using the aforementioned methods. The 3-disulfide-bonded isomers had a range of different conformational stabilities, with highly unstructured, flexible conformations with low or no channel-blocking activity, while more constrained molecules preserved 30% to 50% of the native isomer’s activity. This emphasizes the importance and direct link between correct fold and function. The elimination of one disulfide bond resulted in a significant loss of blocking activity at NaV1.4, highlighting the importance of the 3-disulfide-bonded architecture for µ-PIIIA. µ-PIIIA bioactivity is governed by a subtle interplay between an optimally folded structure resulting from a specific disulfide connectivity and the electrostatic potential of the conformational ensemble

Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells

LFA-1 is a leukocyte specific β2 integrin that plays a major role in regulating adhesion and migration of different immune cells. Recent data suggest that LFA-1 on mature dendritic cells (mDCs) may function as a chemokine-inducible anchor during homing of DCs through the afferent lymphatics into the lymph nodes, by transiently switching its molecular conformational state. However, the role of LFA-1 mobility in this process is not yet known, despite that the importance of lateral organization and dynamics for LFA-1-mediated adhesion regulation is broadly recognized. Using single particle tracking approaches we here show that LFA-1 exhibits higher mobility on resting mDCs compared to monocytes. Lymphoid chemokine CCL21 stimulation of the LFA-1 high affinity state on mDCs, led to a significant reduction of mobility and an increase on the fraction of stationary receptors, consistent with re-activation of the receptor. Addition of soluble monomeric ICAM-1 in the presence of CCL21 did not alter the diffusion profile of LFA-1 while soluble ICAM-1 nano-aggregates in the presence of CCL21 further reduced LFA-1 mobility and readily bound to the receptor. Overall, our results emphasize the importance of LFA-1 lateral mobility across the membrane on the regulation of integrin activation and its function as adhesion receptor. Importantly, our data show that chemokines alone are not sufficient to trigger the high affinity state of the integrin based on the strict definition that affinity refers to the adhesion capacity of a single receptor to its ligand in solution. Instead our data indicate that nanoclustering of the receptor, induced by multi-ligand binding, is required to maintain stable cell adhesion once LFA-1 high affinity state is transiently triggered by inside-out signals.Peer ReviewedPostprint (published version

Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity.

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naïve OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1 -/- and Rgs1 +/+ T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1 +/+ T cells outnumbered the co-transferred OT-I Rgs1- /- T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1 -/- T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1 +/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1 -/- TRM cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8+ T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens