Transkranieller Doppler-Ultraschall (TCD):die Entwicklung von "Fingerabdruckspektren" in der transkraniellen Dopplersonographie zur Diagnose der Zerebralen Mikroangiopathie

Hintergrund: Es gibt einen großen an Screeningmethoden hinsichtlich des Vorliegens einer zerebralen Mikroangiopathie. Mittels TCD gewonnene Flussspektren können einen indirekten Hinweis auf die Mikrozirkulation innerhalb des Gehirns geben. Methoden: Aus der ACM wurden Flussspektren erzeugt, standardisiert und per AVERAGE Mittelwerte berechnet. Dann wurden Beschleunigungskurven erstellt und aus diesen die positiven wie negativen Extremwerte extrahiert. Validierung bei 5 Gesunden mit reproduzierbaren Ergebnissen. Ferner wurden in ebenso die Trennschärfe zwischen gesunden und erkrankten Probanden untersucht. Ergebnisse: Es konnte die Reproduzierbarkeit der Daten und die Trennschärfe bewiesen werden. Es bestand keine Abhängigkeit der gewonnenen Daten von Herzfrequenz, Blutdruck oder CO2-Gehalt der Ausatemluft. Schlussfolgerung: Die dopplersonographische Erfassung der Flussspektren der ACM und die anschließende Aufarbeitung mittels AVERAGE stellen eine verlässliche Untersuchungsmethode dar

Comparative Safety of the BNT162b2 Messenger RNA COVID-19 Vaccine vs Other Approved Vaccines in Children Younger Than 5 Years.

Importance SARS-CoV-2 vaccines are authorized for use in most age groups. The safety of SARS-CoV-2 vaccines is unknown in children younger than 5 years. Objective To retrospectively evaluate the safety of the BNT162b2 vaccine used off-label in children younger than 5 years compared with the safety of non-SARS-CoV-2 vaccines in the same sample. Design, Setting, and Participants This investigator-initiated retrospective cohort study included parents or caregivers who registered children for SARS-CoV-2 vaccination in outpatient care facilities in Germany. The study was performed as an authenticated online survey. A total of 19 000 email addresses were contacted from vaccination registration databases between April 14 and May 9, 2022. Inclusion criteria were child age younger than 5 years at the first BNT162b2 vaccination and use of a correct authentication code to prove invitation. Exposures Off-label BNT162b2 vaccination and on-label non-SARS-CoV-2 vaccinations. Main Outcomes and Measures Reported short-term safety data of 1 to 3 doses of 3 to 10 μg BNT162b2 in children from birth to younger than 60 months are presented. Coprimary outcomes were the frequencies of 11 categories of symptoms after vaccination with bivariate analyses and regression models adjusting for age, sex, weight, and height. Results The study included 7806 children (median age, 3 years [IQR, 2-4 years]; 3824 [49.0%] female) who were followed up of for a mean (SD) of 91.4 (38.8) days since first BNT162b2 vaccination (survey response rate, 41.1%). A 10-μg dosage was more frequently associated with local injection-site symptoms compared with lower dosages. In the active-comparator analysis, the probability of any symptoms (odds ratio [OR], 1.62; 95% CI, 1.43-1.84), local symptoms (OR, 1.68; 95% CI, 1.38-2.05), musculoskeletal symptoms (OR, 2.55; 95% CI, 1.32-4.94), dermatologic symptoms (OR, 2.18; 95% CI, 10.7-4.45), or otolaryngologic symptoms (OR, 6.37; 95% CI, 1.50-27.09) were modestly elevated after BNT162b2 compared with non-SARS-CoV-2 vaccines, whereas the probabilities of general symptoms (OR, 0.77; 95% CI, 0.63-0.95) and fever (OR, 0.42; 95% CI, 0.32-0.55) were lower after BNT162b2. Symptoms requiring hospitalization (n = 10) were reported only at BNT162b2 dosages above 3 μg. Conclusions and Relevance In this cohort study, the symptoms reported after BNT162b2 administration were comparable overall to those for on-label non-SARS-CoV-2 vaccines in this cohort of children younger than 5 years. The present data may be used together with prospective licensure studies of BNT162b2 efficacy and safety and could help guide expert recommendations about BNT162b2 vaccinations in this age group

Characterization of Accumulated B-Integral of Regenerative Amplifier Based CPA Systems

We report on a new approach to measure the accumulated B-integral in the regenerative and multipass amplifier stages of ultrashort-pulse high-power laser systems by B-integral-induced coupling between delayed test post-pulses and the main pulse. A numerical model for such non-linear pulse coupling is presented and compared to data taken at the high-power laser Draco with self-referenced spectral interferometry (SRSI). The dependence of the B-integral accumulated in the regenerative amplifier on its operation mode enables optimization strategies for extracted energy vs. collected B-integral. The technique presented here can, in principle, be applied to characterize any type of ultrashort pulse laser system and is essential for pre-pulse reduction

Characterization of Accumulated B-Integral of Regenerative Amplifier Based CPA Systems

We report on a new approach to measure the accumulated B-integral in the regenerative and multipass amplifier stages of ultrashort-pulse high-power laser systems by B-integral-induced coupling between delayed test post-pulses and the main pulse. A numerical model for such non-linear pulse coupling is presented and compared to data taken at the high-power laser Draco with self-reference spectral interferometry (SRSI). The dependence of the B-integral accumulated in the regenerative amplifier on its operation mode enables optimization strategies for extracted energy vs. collected-integral. The technique presented here can, in principle, be applied to characterize any type of ultrashort pulse laser system and is essential for pre-pulse reduction

When Cortical Bone Matrix Properties Are Indiscernible between Elderly Men with and without Type 2 Diabetes, Fracture Resistance Follows Suit

ABSTRACT Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting bone tissue and leading to increased fracture risk in men and women, independent of bone mineral density (BMD). Thus, bone material quality (i.e., properties that contribute to bone toughness but are not attributed to bone mass or quantity) is suggested to contribute to higher fracture risk in diabetic patients and has been shown to be altered. Fracture toughness properties are assumed to decline with aging and age‐related disease, while toughness of human T2DM bone is mostly determined from compression testing of trabecular bone. In this case‐control study, we determined fracture resistance in T2DM cortical bone tissue from male individuals in combination with a multiscale approach to assess bone material quality indices. All cortical bone samples stem from male nonosteoporotic individuals and show no significant differences in microstructure in both groups, control and T2DM. Bone material quality analyses reveal that both control and T2DM groups exhibit no significant differences in bone matrix composition assessed with Raman spectroscopy, in BMD distribution determined with quantitative back‐scattered electron imaging, and in nanoscale local biomechanical properties assessed via nanoindentation. Finally, notched three‐point bending tests revealed that the fracture resistance (measured from the total, elastic, and plastic J‐integral) does not significantly differ in T2DM and control group, when both groups exhibit no significant differences in bone microstructure and material quality. This supports recent studies suggesting that not all T2DM patients are affected by a higher fracture risk but that individual risk profiles contribute to fracture susceptibility, which should spur further research on improving bone material quality assessment in vivo and identifying risk factors that increase bone fragility in T2DM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research

Neue Horizonte für die in vivo Bestimmung wesentlicher Aspekte der Knochenqualität: Mikrostruktur und Materialeigenschaften, bestimmt mit Quantitativer Computertomographie und Quantitativen Ultrasound Methoden, entwickelt durch das BioAsset Konsortium

The Biomechanically founded individualised osteoporosis Assessment and treatment (BioAsset) consortium pursues experimental and clinical studies in the context of skeletal effects of bisphosphonate treatment. Here, first results using newly developed diagnostic methods in a set of vertebral bone specimen obtained from donors with documented bisphosphonate history ranging from 0 to more than 5 years of treatment are presented. A new thoracolumbar quantitative computed tomography (QCT) protocol covering T6 to L4 plus high-resolution QCT (HRQCT) assessment of T12 were compared with high-resolution peripheral QCT (HRpQCT) and micro-CT scans of excised specimens serving as gold standard techniques. Finite element (FE) modelling was performed. Material, ultrastructural, and micromechanical properties were tested on a set of single trabeculae obtained from the donor specimens. A newly developed quantitative ultrasound (QUS) device for measuring the anisotropy of cortical material properties was designed and built. The thoracolumbar QCT protocol permitted in situ imaging with good image quality and automated segmentation of vertebral bodies in the whole range from T6 to L4. The duration of bisphosphonate treatment was significantly associated with increased levels of mineralization and this effect could be measured with HRQCT performed on excised specimens. Microstructural parameters contributed to vertebral bone strength modelled by FE analysis independently of bone mineral density. The new QUS scanner permitted measuring the acoustical anisotropy of reference materials. Taken together, these results document that new methods developed in BioAsset permit a more comprehensive assessment of bone fragility. The set of donor specimens with a documented history of bisphosphonate treatment allows for the assessment of the effects of long-term treatment from the organ down to the tissue and material level. These results will ultimately be linked to the parallel clinical study to provide guidance for determining the optimum duration of bisphosphonate treatment to reduce the incidence of osteoporotic fractures.Das Biomechanically founded individualised osteoporosis Assessment and treatment (BioAsset) Konsortium führt experimentelle und klinische Studien zu skelettalen Effekten von Bisphosphonaten durch. Neue diagnostische Verfahren zur Analyse von Wirbelkörperproben von Spendern mit dokumentierter Bisphosphonateinnahme über 0 bis >5 Jahre wurden entwickelt. Mittels thorakolumbaler Quantitativer Computertomographie (QCT) und hochauflösender QCT (HRQCT) wurden Knochenmineraldichte (BMD), Mikrostrukturvariablen und Materialeigenschaften, insbesondere Mineralisierung, untersucht. Finite Element (FE) Modellierung dient der Bestimmung der Wirbelkörperbruchlast. Ein neues Quantitatives Ultraschall (QUS) Gerät zur Messung anisotroper kortikaler Materialeigenschaften wurde konstruiert. Ein signifikanter Zusammenhang von Mineralisierung und (Dauer der) Bisphosphonattherapie konnte mit Mikro-CT und HRQCT nachgewiesen werden. Das thorakolumbale QCT Protokoll ermöglichte eine Dosisreduktion von 60% gegenüber Standardprotokollen. Eine Finite Elemente Analyse zeigte BMD und Trabekelanzahl als unabhängige Determinanten der Bruchlast. Mit dem neuen QUS Gerät konnte die akustische Anisotropie von Referenzmaterialien bestimmt werden. Die Daten dokumentieren erweitere Diagnosemöglichkeiten zur Abschätzung von Knochenfragilität durch die neuen Verfahren. Parallel durchgeführte klinische Studien sollen die Frage der optimalen Dauer von Bisphosphonattherapie klären.Fil: Glüer, Claus C.. Universitätsklinikum Schleswig-Holstein; AlemaniaFil: Krausse, Matthias. Universitätsklinikum Hamburg-Eppendorf. Institut für Osteologie und Biomechanik; Alemania. Universitat Hamburg; AlemaniaFil: Museyko, Oleg. Universität Erlangen. Institut für Medizinische Physik; AlemaniaFil: Wulff, Birgit. Universitätsklinikum Hamburg-Eppendorf. Institut für Rechtsmedizin; AlemaniaFil: Campbell, Graeme. Universitätsklinikum Schleswig-Holstein; AlemaniaFil: Damm, Timo. Universitätsklinikum Schleswig-Holstein; AlemaniaFil: Daugschies, Melanie. Universitätsklinikum Schleswig-Holstein; AlemaniaFil: Huber, Gerd. Technische Universität Hamburg-Harburg. Institut für Biomechanik; AlemaniaFil: Lu, Yongtao. Technische Universität Hamburg-Harburg. Institut für Biomechanik; AlemaniaFil: Peña, Jaime. Universitätsklinikum Schleswig-Holstein; AlemaniaFil: Waldhausen, Sonja. Universitätsklinikum Schleswig-Holstein; AlemaniaFil: Bastgen, Jan. Universitätsklinikum Schleswig-Holstein; AlemaniaFil: Rodhe, Kerstin. Universitätsklinikum Schleswig-Holstein; AlemaniaFil: Steinebach, Inga. Alfried Krupp Krankenhaus Steele. Osteologisches Forschungszentrum Essen; AlemaniaFil: Thomsen, Felix Sebastian Leo. Universitätsklinikum Schleswig-Holstein; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahia Blanca; ArgentinaFil: Amling, Michael. Universitätsklinikum Hamburg-Eppendorf. Institut für Osteologie und Biomechanik; AlemaniaFil: Barkmann, Reinhard. Universitätsklinikum Schleswig-Holstein; AlemaniaFil: Engelke, Klaus. Universität Erlangen. Institut für Medizinische Physik; AlemaniaFil: Morlock, Michael M.. Technische Universität Hamburg-Harburg. Institut für Biomechanik; AlemaniaFil: Pfeilschifter, Johannes. Alfried Krupp Krankenhaus Steele. Osteologisches Forschungszentrum Essen; AlemaniaFil: Püschel, Klaus. Universitätsklinikum Hamburg-Eppendorf. Institut für Rechtsmedizin; Alemani