Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma

Background: Earlier studies have suggested that the leukocyte redistribution can be considered as an immunological marker of the clinical response to corticosteroids (CS), representing an easy measurable potential biomarker in severe asthma. Objective: The aim of this study was to determinate the utility of the leukocyte redistribution as a biomarker of disease heterogeneity in patients with severe asthma and as a bioindicator of potential CS resistance. Methods: We developed an unbiased clustering approach based on the clinical data and the flow cytometry results of peripheral blood leukocyte phenotypes of 142 patients with severe asthma before and after systemic CS administration. Results: Based on the differences in the blood count eosinophils, neutrophils and lymphocytes, together with the flow cytometry measurements of basic T cell, B cell and NK cell subpopulations before and after systemic CS administration, we identified two severe asthma clusters, which differed in the cell frequencies, response to CS and atopy status. Patients in cluster 1 had higher frequency of blood eosinophils at baseline, were sensitized to less allergens and had better steroid responsiveness, measured as the pronounced leukocyte redistribution after the administration of systemic CS. Patients in cluster 2 were determined by the higher frequency of B-cells and stronger IgE sensitization status to the multiple allergens. They also displayed higher steroid resistance, as the clinical correlate for the lower leukocyte redistribution after administration of systemic CS. Conclusion: The flow cytometry-based profiling of the basic populations of immune cells in the blood and its analysis before and after systemic corticosteroid administration could improve personalized treatment approaches in patients with severe asthma. Keywords: asthma phenotypes; biological therapy; corticosteroids resistance; leukocyte redistribution; severe asthma; treatment asthm

Exploitation of the Timing Capabilities of Metallic Magnetic Calorimeters for a Coincidence Measurement Scheme

In this report, we compare two filter algorithms for extracting timing information using novel metallic magnetic calorimeter detectors, applied to the precision X-ray spectroscopy of highly charged ions in a storage ring. Accurate timing information is crucial when exploiting coincidence conditions for background suppression to obtain clean spectra. For X-rays emitted by charge-changing interactions between ions and a target, this is a well-established technique when relying on conventional semiconductor detectors that offer a good temporal resolution. However, until recently, such a coincidence scheme had never been realized with metallic magnetic calorimeters, which typically feature much longer signal rise times. In this report, we present optimized timing filter algorithms for this type of detector. Their application to experimental data recently obtained at the electron cooler of CRYRING@ESR at GSI, Darmstadt is discussed

Towards an Intrinsic Doppler Correction for X-ray Spectroscopy of Stored Ions at CRYRING@ESR

We report on a new experimental approach for the Doppler correction of X-rays emitted by heavy ions, using novel metallic magnetic calorimeter detectors which uniquely combine a high spectral resolution with a broad bandwidth acceptance. The measurement was carried out at the electron cooler of CRYRING@ESR at GSI, Darmstadt, Germany. The X-ray emission associated with the radiative recombination of cooler electrons and stored hydrogen-like uranium ions was investigated using two novel microcalorimeter detectors positioned under 0∘ and 180∘ with respect to the ion beam axis. This new experimental setup allowed the investigation of the region of the N, M → L transitions in helium-like uranium with a spectral resolution unmatched by previous studies using conventional semiconductor X-ray detectors. When assuming that the rest-frame energy of at least a few of the recorded transitions is well-known from theory or experiments, a precise measurement of the Doppler shifted line positions in the laboratory system can be used to determine the ion beam velocity using only spectral information. The spectral resolution achievable with microcalorimeter detectors should, for the first time, allow intrinsic Doppler correction to be performed for the precision X-ray spectroscopy of stored heavy ions. A comparison with data from a previous experiment at the ESR electron cooler, as well as the conventional method of conducting Doppler correction using electron cooler parameters, will be discussed

The Strategist's Change - How successful CSOs transform their Companies : Key Findings of the Chief Strategy Officer Survey 2014

In a world where business parameters are constantly changing, where uncertainty and geopolitical instability are on the rise, successful corporate transformation is one of the most critical – and most difficult – tasks for the Chief Strategy Officer (CSO). Adjusting to new conditions, which in an age of digitalization and hypercompetition often has to happen in real time, is akin to open-heart surgery. Strategies have to be developed, support organized, resistance overcome, patterns broken, exemplary behaviors demonstrated, routines rehearsed, successes (or failures) measured – while the operation is in full swing. How does the CSO position himself in this environment? What role does he adopt? What priorities does he set, how does he interact with other stakeholders? What makes him succeed – and what lets him fail? These questions stand in the limelight of our fourth CSO Survey, the leading international study of chief strategists and strategy departments. This year, Roland Berger Strategy Consultants and the University of St. Gallen asked nearly 600 companies from more than 15 countries for a self-assessment. About 160 participated in the survey, and this 27% response rate testifies to the high degree of acceptance that the CSO Survey has achieved in its target group

The Chief Strategy Officer in the European Firm : Professionalising Strategy in Times of Uncertainty

The chief strategy officer (CSO) position has recently been gaining prominence in European firms. However, little is known about this new executive role. In this article, the authors report some of their findings from a major research program that involved two surveys of CSOs and give a portrayal of the CSO's role in continental European firms. The article further highlights how CSOs deal with the current uncertainty and how they professionalise their firm's strategy activities

CSO's Role in Times of Uncertainty : Report of the CSO Survey 2012

A new study by the IfB-HSG and Roland Berger Strategy Consultants reveals how chief strategy officers deal with the current uncertainty. A leaner strategy process, long-term strategic planning, and cross-functional collaboration are particularly important

A scintillator‐based particle detector for CRYRING@ESR

With the unprecedented range of ion species and energies offered by the newly commissioned CRYRING facility, the availability of single ion detectors is of significant importance as part of standard instrumentation as well as for novel experiments. A detector system was constructed on the basis of the YAP:Ce crystal scintillator, which is at once radiation‐hard, fast, and affordable. Results of a characterization experiment confirmed the feasibility of the setup for incident ion rates on the order of MHz and found a critical fluence of some $10^{13} cm^{-2}$ upon which the crystal is rendered locally blind to further ion irradiation. The device was first used in CRYRING commissioning runs in August and November 2018. Future efforts will complete the integration of the detector into the GSI control and data acquisition system MBS

Die vier Gesichter des Chefstrategen

In immer mehr Unternehmen gibt es einen Chief Strategy Officer. Die erste systematische Studie für den deutschsprachigen Raum zeigt, auf welche Kompetenzen es in diesem Job ankommt und wie Unternehmen die Rolle definieren