The ETH-Library’s Image Archive has been using the knowledge of volunteers for over 15 years to identify photographs (aerial images, documentary and scientific photographs, press photography, etc.) ...correct and improve image metadata or georeference images. The first big challenge in starting so-called crowdsourcing projects is how to find people who might be enthusiastic about such a project. The second big challenge is how to maintain a community and keep it going over a longer period. A variety of experiences, tips as well as do’s and don’ts are discussed in the article.
Soft tissue undifferentiated round cell sarcoma (URCS) occurring in infants is a heterogenous group of tumors, often lacking known genetic abnormalities. On the basis of a t(10;17;14) karyotype in a ...pelvic URCS of a 4-month-old boy showing similar breakpoints with clear cell sarcoma of kidney (CCSK), we have investigated the possibility of shared genetic abnormalities in CCSK and soft tissue URCS. Most CCSKs are characterized by BCOR exon 16 internal tandem duplications (ITDs), whereas a smaller subset shows YWHAE-NUTM2B/E fusions. Because of overlapping clinicopathologic features, we have also investigated these genetic alterations in the so-called primitive myxoid mesenchymal tumor of infancy (PMMTI). Among the 22 infantile URCSs and 7 PMMTIs selected, RNA sequencing was performed in 5 and 2 cases, with frozen tissue, respectively. The remaining cases with archival material were tested for YWHAE-NUTM2B/E by fluorescence in situ hybridization (FISH) or reverse transcription-polymerase chain reaction (RT-PCR), and BCOR ITD by PCR. A control group of 4 CCSKs and 14 URCSs in older children or adults without known gene fusion and 20 other sarcomas with similar histomorphology or age at presentation were also tested. A YWHAE-NUTM2B fusion was confirmed in the index case by FISH and RT-PCR, whereas BCOR ITD was lacking. An identical YWHAE-NUTM2B fusion was found in another URCS case of a 5-month-old girl with a back lesion. The remaining cases and control group lacked YWHAE gene rearrangements; instead, consistent BCOR ITDs, similar to CCSK, were found in 15/29 (52%) infantile sarcoma cases (9/22 infantile URCS and 6/7 PMMTI). In the control cohort, BCOR ITD was found only in 3 CCSK cases but not in the other sarcomas. Histologically, URCS with both genotypes and PMMTI shared significant histologic overlap, with uniform small blue round cells with fine chromatin and indistinct nucleoli. A prominent capillary network similar to CCSK, rosette structures, and varying degree of myxoid change were occasionally seen. BCOR ITD-positive tumors occurred preferentially in the somatic soft tissue of the trunk, abdomen, and head and neck, sparing the extremities. RNAseq showed high BCOR mRNA levels in BCOR ITD-positive cases, compared with other URCSs. In summary, we report recurrent BCOR exon 16 ITD and YWHAE-NUTM2B fusions in half of infantile soft tissue URCS and most PMMTI cases, but not in other pediatric sarcomas. These findings suggest a significant overlap between infantile URCS and CCSK, such as age at presentation, histologic features, and genetic signature, thus raising the possibility of a soft tissue counterpart to CCSK.
Background Subcutaneous allergen-specific immunotherapy frequently causes allergic side effects and requires 30 to 80 injections over 3 to 5 years. Objective We sought to improve immunotherapy by ...using intralymphatic allergen administration (intralymphatic immunotherapy ILIT) and by targeting allergen to the MHC class II pathway. Methods Recombinant major cat dander allergen Fel d 1 was fused to a translocation sequence (TAT) and to part of the human invariant chain, generating a modular antigen transporter (MAT) vaccine (MAT–Fel d 1). In a randomized double-blind trial ILIT with MAT–Fel d 1 in alum was compared with ILIT with placebo (saline in alum) in allergic patients ( ClinicalTrials.gov NCT00718679 ). Results ILIT with MAT–Fel d 1 elicited no adverse events. After 3 placebo injections within 2 months, nasal tolerance increased less than 3-fold, whereas 3 intralymphatic injections with MAT–Fel d 1 increased nasal tolerance 74-fold ( P < .001 vs placebo). ILIT with MAT–Fel d 1 stimulated regulatory T-cell responses ( P = .026 vs placebo) and increased cat dander–specific IgG4 levels by 5.66-fold ( P = .003). The IgG4 response positively correlated with IL-10 production ( P < .001). Conclusion In a first-in-human clinical study ILIT with MAT–Fel d 1 was safe and induced allergen tolerance after 3 injections.
Articulated legs enable the selection of robot gaits, including walking in different directions such as forward or sideways. For longer distances, the best gaits might maximize velocity or minimize ...the cost of transport (COT). While animals often have morphology suited to walking either forward (like insects) or sideways (like crabs), hexapod robots often default to forward walking. In this paper, we compare forward walking with crab-like sideways walking. To do this, a simple gait design method is introduced for determining forward and sideways gaits with equivalent body heights and step heights. Specifically, the frequency and stride lengths are tuned within reasonable constraints to find gaits that represent a robot's performance potential in terms of speed and energy cost. Experiments are performed in both dynamic simulation in Webots and a laboratory environment with our 18 degree-of-freedom hexapod robot, Sebastian. With the common three joint leg design, the results show that sideways walking is overall better (75% greater walking speed and 40% lower COT). The performance of sideways walking was better on both hard floors and granular media (dry play sand). This supports development of future crab-like walking robots for future applications. In future work, this approach may be used to develop nominal gaits without extensive optimization, and to explore whether the advantages of sideways walking persist for other hexapod designs.
Sandy beaches are areas that challenge robots of all sizes, especially smaller scale robots. Sand can hinder locomotion and waves apply hydrodynamic forces which can displace, reorient, or even ...invert the robot. Crab-like legs and gaits are well suited for this environment and could be used as inspiration for an improved design of robots operating in this terrain. Tapered, curved feet (similar to crab dactyl shape) paired with a distributed inward gripping method are hypothesized to enable better anchoring in sand to resist hydrodynamic forces. This work demonstrates that crab-like legs can withstand vertical forces that are larger than the body weight (e.g. in submerged sand, the force required to lift the robot can be up to 138% of the robot weight). Such legs help the robot hold its place against hydrodynamic forces imparted by waves (e.g. compared to displacement of 42.7 mm with the original feet, crab-like feet reduced displacement to 1.6 mm in lab wave tests). These feet are compatible with walking on sandy and rocky terrain (tested at three speeds: slow, medium, and fast), albeit at reduced speeds from traditional feet. This work shows potential for future robots to utilize tapered and curved feet to traverse challenging surf zone terrain where biological crabs thrive.
Background Subcutaneous allergen-specific immunotherapy is an effective treatment of IgE-mediated allergies, but it requires repeated allergen injections with a risk of systemic allergic reactions. ...Transcutaneous immunotherapy may improve patient compliance and safety. Objective To assess the safety and efficacy of epicutaneous allergen immunotherapy. Methods This monocentric, placebo-controlled, double-blind trial was conducted from March 2006 to December 2007 at the University Hospital Zurich. Thirty-seven adult patients with positive skin prick and nasal provocation tests to grass pollen were randomized to receive patches containing either allergen (n = 21) or placebo (n = 16). Treatment took place before and during the pollen season 2006, and follow-up visits took place before (n = 26) and after the pollen season 2007 (n = 30). The primary outcome measures were nasal provocation tests. Results Allergen-treated patients showed significantly decreased scores in nasal provocation tests in the first ( P < .001) and second year ( P = .003) after treatment. In contrast, placebo-treated patients had decreased scores in the first treatment year, 2006 ( P = .03), but the effect diminished in the second year ( P = .53). Although improvement of nasal provocation test scores was not significantly better in the verum versus placebo group, the overall treatment success was rated significantly higher by the allergen-treated group than by the placebo group (2006, P = .02; 2007, P = .005). No severe adverse events were observed. Occurrence of eczema after allergen patch applications proved stimulation of specific T-cell responses, but was noted as an adverse effect of the treatment. Conclusion Epicutaneous allergen immunotherapy is a promising strategy to treat allergies and merits further investigation.
Background Epicutaneous allergen administration using a patch may be an alternative to subcutaneous or sublingual immunotherapy. Objective To optimize treatment dose and to demonstrate the efficacy ...and safety of epicutaneous immunotherapy. Methods This monocentric, placebo-controlled, double-blind trial included 132 patients with grass pollen–induced rhinoconjunctivitis. In February 2008, patients were randomly allocated to receive placebo or 3 different doses of allergen. Before and during the pollen season 2008, patients received 6 weekly patches. Efficacy was assessed 4 to 5 months later (n = 110) and during the pollen season of the treatment-free follow-up year in 2009 (n = 93). The primary outcome was patient-reported changes in hay fever symptoms assessed by a visual analog scale. Secondary outcome measures were weekly visual analog scale symptom scores during pollen season, use of rescue medication, changes in conjunctival and skin reactivity, as well as safety. Results Hay fever symptoms during the pollen season were reduced by more than 30% in 2008 and by 24% in 2009 in the high-dose group as compared with that in the placebo group, and the alleviation of symptoms in the follow-up year was dependent on the treatment dose. Higher allergen doses were associated with drug-related adverse events (AEs), predominantly manifested by pruritus, erythema, wheal, or eczema. Eleven systemic AEs of grades 1 to 2 required treatment and led to study exclusion. The dropout rate due to AEs was 8.3%. No drug-related serious AE was recorded. Conclusion Epicutaneous immunotherapy is safe and efficacious in a dose-dependent manner after 6 patches only.
The aim of this study was to test whether an investigational two layer stocking exerting 27–29 mmHg pressure at the medial supramalleolar level, but without compression in the foot and heel, is ...easier to put on and take off than a standard stocking of the same compression class (23–32 mmHg), and also to assess the prevention of diurnal oedema with both types of stocking.
This was an open label randomised controlled trial, which included 47 patients. All participants were at least 65 years of age and suffered from chronic venous disease class C3 – C6 in one leg. The primary end point was donning success; secondary endpoints were doffing success, prevention of diurnal oedema over one day, and the comfort of wearing the stocking. Patients were randomly allocated to one of two groups. Both types of compression stocking were compared in each group for ease of donning and doffing in the manner of a crossover study. Subsequently, patients wore the stocking type assigned to their group for a whole day to evaluate comfort and the effect on diurnal leg volume.
All participants were able to don the investigational stocking unaided, compared with 75% for the standard stocking (p < .001). Unaided removal success was 100% with the investigational stocking vs. 66% for the standard stocking (p < .001). There was no significant difference in leg volume reduction between the study groups after a day of wear. The investigational stocking was also rated as being more comfortable than the standard stocking (p < .001).
The investigational stocking, which has no compression in the foot or heel area, is significantly easier to don and doff, with no inferiority in oedema prevention, compared with a standard stocking of the same compression class.
Improvement of skin fibrosis is part of the natural course of diffuse cutaneous systemic sclerosis (dcSSc). Recognising those patients most likely to improve could help tailoring clinical management ...and cohort enrichment for clinical trials. In this study, we aimed to identify predictors for improvement of skin fibrosis in patients with dcSSc.
We performed a longitudinal analysis of the European Scleroderma Trials And Research (EUSTAR) registry including patients with dcSSc, fulfilling American College of Rheumatology criteria, baseline modified Rodnan skin score (mRSS) ≥7 and follow-up mRSS at 12±2 months. The primary outcome was skin improvement (decrease in mRSS of >5 points and ≥25%) at 1 year follow-up. A respective increase in mRSS was considered progression. Candidate predictors for skin improvement were selected by expert opinion and logistic regression with bootstrap validation was applied.
From the 919 patients included, 218 (24%) improved and 95 (10%) progressed. Eleven candidate predictors for skin improvement were analysed. The final model identified high baseline mRSS and absence of tendon friction rubs as independent predictors of skin improvement. The baseline mRSS was the strongest predictor of skin improvement, independent of disease duration. An upper threshold between 18 and 25 performed best in enriching for progressors over regressors.
Patients with advanced skin fibrosis at baseline and absence of tendon friction rubs are more likely to regress in the next year than patients with milder skin fibrosis. These evidence-based data can be implemented in clinical trial design to minimise the inclusion of patients who would regress under standard of care.
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