Tribological and Corrosion Behavior of Vacuum Plasma Sprayed Ti-Zr-Ni Quasicrystalline Coatings

This investigation deals with a study of the friction, wear, and corrosion behavior of vacuum plasma sprayed quasicrystalline (QC) Ti41.5Zr41.5Ni17 coatings. During pin on disc experiments, a change in the mode of wear has been found to occur with corresponding changes in normal load and sliding velocity. The low thermal conductivity of quasicrystals and its brittleness play a vital role in determining the friction and wear behavior of such materials. When these coatings are subjected to rubbing for a longer period of time, wear occurs by subsurface crack propagation, and subsequent delamination within the coated layer. By comparing the QC to its polycrystalline counterpart during potentiodynamic measurements according to ASTM G 31, higher currents were found over the whole range of potentials for QC when immersed in 1M HCl solutio

Swiss national guideline for reimbursement of enzyme replacement therapy in late-onset Pompe disease.

Glycogen storage disease type II is a rare multi-systemic disorder characterised by an intracellular accumulation of glycogen due a mutation in the acid alpha glucosidase (GAA) gene. The level of residual enzyme activity, the genotype and other yet unknown factors account for the broad variation of the clinical phenotype. The classical infantile form is characterised by severe muscle hypotonia and cardiomyopathy leading to early death. The late-onset form presents as a limb girdle myopathy with or without pulmonary dysfunction. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) in infants is life saving. In contrast, therapeutic efficacy of rhGAA in the late-onset form is modest. High expenses of rhGAA, on-going infusions and poor pharmacokinetic efficacy raised a discussion of the cost effectiveness of ERT in late-onset Pompe disease in Switzerland. This discussion was triggered by a Swiss federal court ruling which confirmed the reluctance of a health care insurer not to reimburse treatment costs in a 67-year-old female suffering from Pompe disease. As a consequence of this judgement ERT was stopped by all insurance companies in late-onset Pompe patients in Switzerland regardless of their clinical condition. Subsequent negotiations lead to the release of a national guideline of the management of late-onset Pompe disease. Initiation and limitation of ERT is outlined in a national Pompe registry. Reimbursement criteria are defined and individual efficacy of ERT with rhGAA is continuously monitored

Molecular quantum spin network controlled by a single qubit

Scalable quantum technologies will require an unprecedented combination of precision and complexity for designing stable structures of well-controllable quantum systems. It is a challenging task to find a suitable elementary building block, of which a quantum network can be comprised in a scalable way. Here we present the working principle of such a basic unit, engineered using molecular chemistry, whose control and readout are executed using a nitrogen vacancy (NV) center in diamond. The basic unit we investigate is a synthetic polyproline with electron spins localized on attached molecular sidegroups separated by a few nanometers. We demonstrate the readout and coherent manipulation of very few ($\leq 6$) of these $S=1/2$ electronic spin systems and access their direct dipolar coupling tensor. Our results show, that it is feasible to use spin-labeled peptides as a resource for a molecular-qubit based network, while at the same time providing simple optical readout of single quantum states through NV-magnetometry. This work lays the foundation for building arbitrary quantum networks using well-established chemistry methods, which has many applications ranging from mapping distances in single molecules to quantum information processing.Comment: Author name typ

Integration des Community-Gedankens in das Collaborative Engineering am Beispiel des Schiffbaus

E-Collaboration als aktuell vieldiskutierte Form der zwischenbetrieblichen Zusammenarbeit bietet Unternehmen auch im Bereich der Produktentwicklung neue Möglichkeiten, dem steigenden Wettbewerbsdruck zu begegnen. Zielsetzung dieses Beitrages ist es, das Konzept des Collaborative Engineering darzustellen und durch die Idee der Communities, die sich als neue Organisationsform von Benutzern elektronischer Kommunikationsmedien entwickelt haben, zu erweitern. Dazu werden am Beispiel des Schiffbaus aktuelle Fragestellungen diskutiert sowie ein Lösungsansatz für eine Collaborative Engineering Plattform vorgestellt. Darauf aufbauend wird der Community- Gedanke auf die Produktentwicklung übertragen; Anforderungen an Communities im Engineering-Bereich werden abgeleitet. Abschließend erfolgt die Beschreibung einer Rahmenarchitektur sowie die Formulierung von Forschungsfragen zur Realisierung von Collaborative Engineering Communities

Analysis of the “Sonar Hopf” Cochlea

The “Sonar Hopf” cochlea is a recently much advertised engineering design of an auditory sensor. We analyze this approach based on a recent description by its inventors Hamilton, Tapson, Rapson, Jin, and van Schaik, in which they exhibit the “Sonar Hopf” model, its analysis and the corresponding hardware in detail. We identify problems in the theoretical formulation of the model and critically examine the claimed coherence between the described model, the measurements from the implemented hardware, and biological data

Characteristics of Severe Asthma Patients and Predictors of Asthma Control in the Swiss Severe Asthma Registry

Background: Asthma is a chronic airway disease, affecting over 300 million people worldwide. 5–10% of patients suffer from severe asthma and account for 50% of asthma-related financial burden. Availability of real-life data about the clinical course of severe asthma is insufficient. Objectives: The aims of this study were to characterize patients with severe asthma in Switzerland, enrolled in the Swiss Severe Asthma Registry (SSAR), and evaluate predictors for asthma control. Method: A descriptive characterisation of 278 patients was performed, who were prospectively enrolled in the registry until January 2022. Socio-demographic variables, comorbidities, diagnostic values, asthma treatment, and healthcare utilisation were evaluated. Groups of controlled and uncontrolled asthma according to the asthma control test were compared. Results: Forty-eight percent of patients were female and the mean age was 55.8 years (range 13–87). The mean body mass index (BMI) was 27.4 kg/m2 (±6). 10.8% of patients were current smokers. Allergic comorbidities occurred in 54.3% of patients, followed by chronic rhinosinusitis (46.4%) and nasal polyps (34.1%). According to the ACT score, 54.7% had well controlled, 16.2% partly controlled and 25.9% uncontrolled asthma. The most common inhalation therapy was combined inhaled corticosteroids/long-acting β2-agonists (78.8%). Biologics were administered to 81.7% of patients and 19.1% received oral steroids. The multivariable analysis indicated that treatment with biologics was positively associated with asthma control whereas higher BMI, oral steroids, exacerbations, and COPD were negative predictors for asthma control. Conclusion: Biologics are associated with improved control in severe asthma. Further studies are required to complete the picture of severe asthma in order to provide improved care for those patients

The clinical features of asthma exacerbations in early-onset and eosinophilic late-onset asthma may differ significantly

Over 20 years ago, the concept of asthma control was created and appropriate measurement tools were developed and validated. Loss of asthma control can lead to an exacerbation. Years ago, the term "clinically significant asthma exacerbation" was introduced to define when a loss of control is severe enough to declare it an asthma exacerbation. This term is also used by health insurances to determine when an exacerbation is eligible for reimbursement of biologics in clinical practice, however, it sometimes becomes apparent that a clear separation between loss of "asthma control" and an exacerbation is not always possible. In this review, we attempt to justify why exacerbations in early allergic asthma and adult eosinophilic asthma can differ significantly and why this is important in clinical practice as well as when dealing with health insurers

Signature of altered retinal microstructures and electrophysiology in schizophrenia spectrum disorders is associated with disease severity and polygenic risk

BACKGROUND Optical coherence tomography (OCT) and electroretinography (ERG) studies have revealed structural and functional retinal alterations in individuals with schizophrenia spectrum disorders (SSD). However, it remains unclear which specific retinal layers are affected, how the retina, brain, and clinical symptomatology are connected, and how alterations of the visual system are related to genetic disease risk. METHODS OCT, ERG, and brain magnetic resonance imaging (MRI) were applied to comprehensively investigate the visual system in a cohort of 103 patients with SSD and 130 healthy control individuals. The sparse partial least squares (SPLS) algorithm was used to identify multivariate associations between clinical disease phenotype and biological alterations of the visual system. The association of the revealed patterns with the individual polygenetic disease risk for schizophrenia was explored in a post hoc analysis. In addition, covariate-adjusted case-control comparisons were performed for each individual OCT and ERG parameter. RESULTS The SPLS analysis yielded a phenotype-eye-brain signature of SSD in which greater disease severity, longer duration of illness, and impaired cognition were associated with electrophysiological alterations and microstructural thinning of most retinal layers. Higher individual loading onto this disease-relevant signature of the visual system was significantly associated with elevated polygenic risk for schizophrenia. In case-control comparisons, patients with SSD had lower macular thickness, thinner retinal nerve fiber and inner plexiform layers, less negative a-wave amplitude, and lower b-wave amplitude. CONCLUSIONS This study demonstrates multimodal microstructural and electrophysiological retinal alterations in individuals with SSD that are associated with disease severity and individual polygenetic burden

Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways

Purpose: Immune-related cutaneous adverse events (ircAEs) occur in ≥50% of patients treated with checkpoint inhibitors (CPI), but mechanisms are poorly understood. Experimental Design: Phenotyping/biomarker analyses were conducted in 200 patients on CPIs (139 with ircAEs, 61 without, control) to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip (STS) extracts and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays. Results: Eight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFN-gamma mRNA in patients with lichenoid (p<0.0001) and psoriasiform dermatitis (p<0.01) as compared to patients without ircAEs, while the highest IL-13 mRNA levels were detected in the eczema (p<0.0001, compared to control). IL-17A mRNA was selectively increased in psoriasiform (p<0.001), lichenoid (p<0.0001), bullous dermatitis (p<0.05) and MPR (p<0.001), compared to control. Distinct cytokine profiles were confirmed in STS and plasma. Analysis determined increased skin/plasma IL-4 cytokine in pruritus, skin IL-13 in eczema, plasma IL-5 and IL-31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2-cytokine targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo. Conclusions: Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions