The Novel CarbaLux Test for Carbapenemases and Carbapenem Deactivating AmpC Beta-Lactamases

Objectives: To evaluate the rapid phenotypic CarbaLux test for routine diagnostics in the medical laboratory in a proof of concept study. Methods: isolates of Gram-negative bacteria suspicious for carbapenem resistance including Enterobacterales (67), Pseudomonas (10), Acinetobacter (5), and Stenotrophomonas (1) species, collected between 2016 and 2018 from in-patients, were tested for carbapenemase activity using a novel fluorescent carbapenem. When subjected to extracted bacterial carbapenemases its fluorescence disappears. All bacteria to be tested were cultured on Columbia blood agar and few on other commercial media. MALDI TOF MS, molecular assays, automated MIC testing, and in part, agar diffusion tests served to characterize the isolates. For comparison, few selected bacteria were also investigated by prior phenotypic tests for carbapenemase detection. Results: Under UV light, the CarbaLux test allowed a rapid detection of 39/39 carbapenemase-producing bacteria, including 15 isolates with OXA carbapenemases (e.g., OXA-23, OXA-24/40-like OXA-48-like or OXA-181). Several isolates had low MICs but still expressed carbapenemases. Among Enterobacter spp., it detected six strains with hyper-produced AmpC beta-lactamases, which deactivated carbapenems but were not detectable by prior rapid phenotypic assays. An unexpected high carbapenemase activity appeared with these enzymes. They were identified as AmpC variants by inhibition with cloxacillin. Conclusion: Other than prior rapid phenotypic assessments for carbapenemases, which use secondary effects such as a change of pH, the inactivation of the fluorescent carbapenem substrate can be visualized directly under UV light. The new test works at 100 to 200-fold lower, therapy-like substrate concentrations. It takes advantage of the high substrate affinity to carbapenemases allowing also the detection of less reactive resistance enzymes via a trapping mechanism, even from bacteria, which might appear unsuspicious from initial antibiograms. The novel fluorescence method allows simple and safe handling, reliable readings, and documentation and is suitable for primary testing in the clinical laboratory

Mechanical frequency control in inductively coupled electromechanical systems

Nano-electromechanical systems implement the opto-mechanical interaction combining electromagnetic circuits and mechanical elements. We investigate an inductively coupled nano-electromechanical system, where a superconducting quantum interference device (SQUID) realizes the coupling. We show that the resonance frequency of the mechanically compliant string embedded into the SQUID loop can be controlled in two different ways: (i) the bias magnetic flux applied perpendicular to the SQUID loop, (ii) the magnitude of the in-plane bias magnetic field contributing to the nano-electromechanical coupling. These findings are quantitatively explained by the inductive interaction contributing to the effective spring constant of the mechanical resonator. In addition, we observe a residual field dependent shift of the mechanical resonance frequency, which we attribute to the finite flux pinning of vortices trapped in the magnetic field biased nanostring.Comment: 5 pages, 3 figure

Current state of musculoskeletal ultrasound training and implementation in Europe: results of a survey of experts and scientific societies

Objective. To document the current state of musculoskeletal US (MSUS) training and extent of implementation among rheumatologists in the member countries of EULAR. Methods. An English-language questionnaire, divided into five sections (demographics, clinical use of MSUS, overall MSUS training for rheumatologists, MSUS education in the rheumatology training curriculum and education in MSUS offered by the national rheumatology society) was sent by e-mail to three different groups: (i) all national rheumatology societies of EULAR; (ii) all national societies of the European Federation of Societies for Ultrasound in Medicine and Biology; and (iii) 19 senior rheumatologists involved in MSUS training from 14 European countries. Results. Thirty-one (70.5%) out of 44 countries responded to the questionnaire (59.1% of national rheumatology societies, 34.5% of the national US societies and 100% of expert ultrasonographers). Rheumatology was listed among medical specialities that mainly perform MSUS in 20 (64.5%) countries; however, in most [19 (63.3%)] countries <10% of rheumatologists routinely perform MSUS in clinical practice. Training varies widely from country to country, with low rates of competency assessment. MSUS education is part of the rheumatology training curriculum in over half the surveyed countries, being compulsory in 7 (22.6%) countries and optional in 11 (35.5%). Conclusions. This study confirms the high uptake of MSUS across Europe. The reported variation in training and practice between countries suggests a need for standardization in areas including training guideline

Late 1920s film theory and criticism as a test-case for Benjamin’s generalizations on the experiential effects of editing

This article investigates Walter Benjamin’s influential generalization that the effects of cinema are akin to the hyper-stimulating experience of modernity. More specifically, I focus on his oft-cited 1935/36 claim that all editing elicits shock-like disruption. First, I propose a more detailed articulation of the experience of modernity understood as hyper-stimulation and call for distinguishing between at least two of its subsets: the experience of speed and dynamism, on the one hand, and the experience of shock/disruption, on the other. Then I turn to classical film theory of the late 1920s to demonstrate the existence of contemporary views on editing alternative to Benjamin’s. For instance, whereas classical Soviet and Weimar theorists relate the experience of speed and dynamism to both Soviet and classical Hollywood style editing, they reserve the experience of shock/disruption for Soviet montage. In order to resolve the conceptual disagreement between these theorists, on the one hand, and Benjamin, on the other, I turn to late 1920s Weimar film criticism. I demonstrate that, contrary to Benjamin’s generalizations about the disruptive and shock-like nature of all editing, and in line with other theorists’ accounts, different editing practices were regularly distinguished by comparison to at least two distinct hyper-stimulation subsets: speed and dynamism, and shock-like disruption. In other words, contemporaries regularly distinguished between Soviet montage and classical Hollywood editing patterns on the basis of experiential effects alone. On the basis of contemporary reviews of city symphonies, I conclude with a proposal for distinguishing a third subset – confusion. This is an original manuscript / preprint of an article published by Taylor & Francis in Early Popular Visual Culture on 02 Aug 2016 available online: https://doi.org/10.1080/17460654.2016.1199322

Practice of ultrasound-guided arthrocentesis and joint injection, including training and implementation, in Europe: results of a survey of experts and scientific societies

Objectives. To document the practice and training opportunities of US-guided arthrocentesis and joint injection (UGAJ) among rheumatologists in the member countries of the European League Against Rheumatism (EULAR). Methods. An English-language questionnaire, containing questions on demographics, clinical and practical aspects of UGAJ, training options in UGAJ for rheumatologists, UGAJ education in the rheumatology training curriculum and other structured education programmes in UGAJ was sent to three different groups: (i) all national rheumatology societies of EULAR; (ii) all national societies of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB); and (iii) 22 senior rheumatologists involved in EULAR musculoskeletal US training from 14 European countries, who were also asked to circulate the questionnaire among relevant colleagues. Results. Thirty-three (75%) of 44 countries responded to the questionnaire (61.3% of national rheumatology societies, 25% of the national US societies and 100% of expert ultrasonographers). In the majority of countries (85%) 80%) rate of rheumatologists performing conventional joint injection in most of the surveyed countries. The reported variations in practice and the lack of available structured training programmes for trainees in most countries indicates the need for standardization in areas including training guideline

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies

Neuregulin/ErbB regulate neuromuscular junction development by phosphorylation of α-dystrobrevin

Neuregulin/ErbB signaling maintains high efficacy of synaptic transmission by stabilizing the postsynaptic apparatus via phosphorylation of α-dystrobrevin1