Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial

<div><p>Background</p><p>Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts.</p><p>Methods</p><p>The trial was conducted at 34 sites in the US. Vaccinia-naïve adults aged 18-40 years were randomly allocated to one of four groups using a 1:1:1:1 randomization scheme. Subjects received either two MVA injections from three consecutive lots (Groups 1-3), or two placebo injections (Group 4), four weeks apart. Everyone except personnel involved in vaccine handling and administration was blinded to treatment. Safety assessment focused on cardiac monitoring throughout the trial. Vaccinia-specific antibody titers were measured using a Plaque Reduction Neutralization Test (PRNT) and an Enzyme-Linked Immunosorbent Assay (ELISA). The primary immunogenicity endpoint was Geometric Mean Titers (GMTs) after two MVA vaccinations measured by PRNT at trial visit 4. This trial is registered with ClinicalTrials.gov, number NCT01144637.</p><p>Results</p><p>Between March 2013 and May 2014, 4005 subjects were enrolled and received at least one injection of MVA (n = 3003) or placebo (n = 1002). The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). Overall, 180 (6·0%) subjects receiving MVA and 29 (2·9%) subjects in the placebo group reported at least one unsolicited Adverse Event (AE) that was considered trial-related. Vaccination was well tolerated without significant safety concerns, particularly regarding cardiac assessment.</p><p>Conclusions</p><p>The neutralizing and total antibody titers induced by each of the three lots were equivalent. No significant safety concerns emerged in this healthy trial population, especially regarding cardiac safety, thus confirming the excellent safety and tolerability profile of MVA.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01144637" target="_blank">NCT01144637</a></p></div

Strontium doping in mullite-type bismuth aluminate: A vacancy investigation using neutrons, photons and electrons

We report on strontium doped dibismuth-nonaoxoaluminate(III) produced at 1023 K. Partial substitution of bismuth by strontium in the structure yields oxygen vacancies for charge balance. Introducing oxygen vacancies rearranged the associated Al2O7 double-tetrahedra forming “Al3O10” tri-clusters which were identified by multi-quantum 27Al MAS NMR. Both STEM-EDX and XPS showed homogeneous distribution of strontium in the bulk and on the surface, respectively. Moreover, XPS confirms the valence state of bismuth after doping. The orientations of bismuth 6s2 lone electron pairs were calculated using DFT methods. The amount of strontium in the crystal structure was further confirmed from the decomposition product SrAl12O19 formed during the temperature-dependent X-ray powder diffraction. The structural proof was carried out by refining the structure of (Bi0.94Sr0.06)2Al4O8.94 from powder neutron and X-ray diffraction data. Rietveld refinements clearly showed the under occupation of one oxygen site and the shift of two aluminum atoms from the double-tetrahedra to two tri-cluster sites

Electronic Structure of the Complex Hydride NaAlH4

Density functional calculations of the electronic structure of the complex hydride NaAlH4 and the reference systems NaH and AlH3 are reported. We find a substantially ionic electronic structure for NaAlH4, which emphasizes the importance of solid state effects in this material. The relaxed hydrogen positions in NaAlH4 are in good agreement with recent experiment. The electronic structure of AlH3 is also ionic. Implications for the binding of complex hydrides are discussed.Comment: 4 pages, 5 figure

First crystal structure studies of CaAlH5

A new member of the aluminum hydride family, CaAlH5, is formed during the decomposition of Ca(AlH4)2. The crystal structure of this new compound was calculated by density functional theory band-structure calculations and confirmed by X-ray powder diffraction analysis. The structure crystallizes in space group P21/n (No. 14), with a = 8.3797(9) Å, b = 6.9293(8) Å, c = 9.8138(11) Å, β = 93.78(1)°, and Z = 8

Smarte Sensorik in der Schwangerschaft: Eine umfragebasierte Evaluation der Bereitschaft zur Nutzung tragbarer sensorischer Anwendungen in der Schwangerschaftsvorsorge

Tragbare Technologien (Wearables) sind elektronische Messgeräte, die direkt am Körper getragen werden können. Zu typischen und bereits weit verbreiteten Vertretern zählen Smartwatches und Fitness-Tracker. Diese Geräte verfügen über zahlreiche, gesundheitlich relevante Funktionen, wie Herzfrequenz-, Kalorienverbrauchs-, Temperatur-, EKG-Messungen oder Schlafüberwachung. Die medizinische Bedeutung solcher Geräte nimmt stetig zu. In Zukunft könnten solche Technologien auch für Routineuntersuchungen der Schwangerschaftsvorsorge eingesetzt werden und so Messungen bequem von zu Hause durchgeführt und direkt an den behandelnden Arzt oder Ärztin übertragen werden. In dieser Arbeit wurde die Einstellung und Bereitschaft schwangerer Frauen zur Nutzung smarter Geräte im Rahmen der Schwangerschaftsvorsorge untersucht. Ziel war es, den Einfluss der allgemeinen Technologiebereitschaft zu evaluieren und die Studienpopulation diesbezüglich zu segmentieren. Für die Datenerhebung wurde ein Fragebogenkomplex entworfen, im Rahmen dessen vier smarte Geräte (Smartwatch, Schlafsensor, Blutdruckmessgerät und Kontraktionszähler) vorgestellt wurden. Der Studienfragebogen enthielt Fragen zur Demografie, Schwangerschaft, Technologieerfahrung und -nutzung sowie zur schwangerschaftsbezogenen Angst. Des Weiteren wurden das Gesundheitsbewusstsein, der soziale Einfluss und das wahrgenommene Datenschutzrisiko evaluiert. Die Technologiebereitschaft wurde über den Technology Readiness Index (TRI 2.0) und die schwangerschaftsbezogene Angst über den Pregnancy-Related Anxiety Questionnaire (PRAQ-R2) analysiert. Es wurden schwangere Frauen ab der 9. Schwangerschaftswoche im Zeitraum von Dezember 2021 bis Mai 2022 eingeschlossen (SMART Start Studie). Insgesamt wurden 214 Fragebögen ausgewertet. Die Zusammenhänge zwischen den Variablen und der Bereitschaft zur Nutzung smarter Geräte für die Schwangerschaftsvorsorge wurden statistisch durch Spearman-Korrelationen (Spearman-Rho) analysiert. Ein p-Wert von ≤ 0,05 wurde als signifikant definiert. Ein Smartphone oder ein Tablet besitzen 100 % der Befragten. 24 % der Frauen benutzten zum Zeitpunkt der Befragung eine Smartwatch oder einen Fitness-Tracker. 23 % der Frauen gaben an, eine Smartwatch oder einen Fitness-Tracker zu besitzen, diese aber aktuell nicht zu verwenden. 67 % der Frauen nutzten eine Schwangerschafts-App. Es zeigte sich eine positive Einstellung zur Nutzung smarter Geräte in der Schwangerschaftsvorsorge. Über 50 % der Befragten beabsichtigen, in Zukunft eine Smartwatch, einen Kontraktionszähler oder ein Blutdruckmessgerät einzusetzen, wenn sie die Möglichkeit im Rahmen der Schwangerschaftsvorsorge bekommen würden. Die Technologiebereitschaft (TR) des untersuchten Kollektivs lag auf der 57. Perzentile im Vergleich zur US-amerikanischen Erwachsenenpopulation. Anhand der Ergebnisse wurde unser Kollektiv in fünf TRI-Segmente eingeteilt. Am häufigsten vertreten war die Gruppe der „Skeptiker“. Skeptiker sind empfänglich für Innovationen, wenn sie gut verstehen, warum sie davon profitieren. In unserem Kollektiv lag keine signifikante Korrelation zwischen dem Alter (p = 0,302) oder dem Bildungsniveau (p = 0,785) und der Bereitschaft zur Nutzung smarter Geräte vor. Es zeigte sich jedoch eine signifikant niedrigere Bereitschaft bei höherer Parität (p = 0,007). Die Schwangeren, die angaben, bereits eine Smartwatch oder einen Fitness-Tracker zu besitzen, hatten eine signifikant höhere Bereitschaft eine solche Technologie auch für die Schwangerschaftsvorsorge einzusetzen (p < 0,001). Die Bereitschaft zur Nutzung smarter Geräte in der Schwangerschaftsvorsorge stieg signifikant mit steigender schwangerschaftsbezogener Angst (p = 0,008). Einsatz smarter Geräte in der Schwangerschaftsvorsorge könnte zur deutlichen Effizienzsteigerung der Versorgung führen. Die nötigen Technologien für die digitale Transformation sind bereits vorhanden und weit verbreitet. Aus den Daten dieser Arbeit geht hervor, dass schwangere Frauen technologisch gut ausgestattet sind. Die allgemeine Technologiebereitschaft und die Bereitschaft zur Nutzung smarter Geräte in der Schwangerschaftsvorsorge waren in unserem Kollektiv vergleichsweise hoch, bei ängstlichen Frauen sogar signifikant erhöht. Auf Grund der Ergebnisse aus dem TRI, kann man davon ausgehen, dass eine gute Strategie zur Überzeugung der Schwangeren mit niedrigerer Bereitschaft, die gezielte Aufklärung über den Nutzen solcher Innovationen ist.Wearable Technology (Wearables) is a category of electronic measuring devices that can be worn directly on the body. Typical and already widespread representatives include smartwatches and fitness trackers. These devices have numerous health-related functions, such as monitoring of heart rate, temperature, ECG, sleep or calorie counter. The medical importance of such devices is constantly increasing. In the future, smart devices could be used for routine prenatal check-ups, allowing measurements to be carried out conveniently at home and transmitted directly to the doctor. In this work, the attitude and the intention of pregnant women to use smart devices in the context of prenatal care was examined. Furthermore, one major aim was to evaluate the general technology readiness and to segment the study population accordingly. A comprehensive questionnaire was designed, in which four smart devices (smartwatch, sleep analyzer, blood pressure monitor and contraction counter) were introduced to the study participants. The study questionnaire included questions about demographics, pregnancy, technology experience and use, and pregnancy-related anxiety. Furthermore, health consciousness, social influence and the perceived privacy risk were evaluated. Technology readiness was analyzed using the Technology Readiness Index (TRI 2.0) and pregnancy-related anxiety using the Pregnancy-Related Anxiety Questionnaire (PRAQ-R2). Pregnant women from the 9th week of pregnancy were enrolled between December 2021 and May 2022 (SMART Start study). A total of 214 questionnaires were evaluated. The relationships between the variables and the intention to use smart devices for prenatal care were statistically analyzed using Spearman’s correlation (Spearman’s Rho). A p-value of ≤ 0.05 was defined as significant. All respondents owned a smartphone or a tablet. 24 % of the pregnant women were using a smartwatch or a fitness tracker at the time of the survey. 23 % of the women stated, that they owned a smartwatch or a fitness tracker but didn´t currently use them. 67 % of the women used a pregnancy app. There is a positive attitude towards the use of smart devices in prenatal care. Over 50% of the study population showed an intention to use a smartwatch, contraction counter or a smart blood pressure monitor in the future, if given the opportunity as part of prenatal care. The technology readiness (TR) of the studied collective was in the 57th percentile compared to the U.S. adult population. Based on the results, our collective was divided into five TRI segments. The group of “skeptics” was represented most frequently. Skeptics are receptive to adopting innovations if they have a good understanding of why it benefits them. In our collective, there was no significant correlation between age (p = 0.302) or level of education (p = 0.785) and intention to use smart devices. However, there was a significantly lower intention with higher parity (p = 0.007). Pregnant women who stated, that they already had a smartwatch or a fitness tracker were significantly more willing to use them for prenatal care (p < 0.001). Intention to use smart devices in prenatal care increased significantly with increasing pregnancy-related anxiety (p = 0.008). The use of smart devices could lead to a considerable improvement of the efficiency in prenatal care. The technologies required for digital transformation are already widely available. Our data indicates that pregnant women are well-equipped with technology. In our study group, there was a high level of readiness for technology and willingness to use smart devices for prenatal care. This was particularly true for anxious women. Based on the results of the TRI, it can be assumed that providing targeted information about the benefits of such innovations would be an effective strategy for convincing pregnant women who are less willing to adopt them

Zeolite Rho Loaded with Methylamines. I. Monomethylamine Loadings

Samples of two differently prepared zeolite rho loaded with different amounts of monomethylamine (MMA) were studied in their hydrated and dehydrated forms by X-ray and neutron diffraction. Both zeolites are partially dealuminated, as indicated by nonframework alumina, which is assumed to be Al2O3 or AlOOH. Series I was prepared from dry-calcined NH4-rho at 873 K, series II from steam-calcined NH4-rho at 773 K. The samples were loaded with different amounts of deuterated MMA, Rietveld refinements yielded the following results for series I (dry): (1) H3.8(H-MMA)5Cs0.2Al9Si39O2.Al2O3.28H2O, X-ray data collection at room temperature, Im3̅m, a = 14.9991 (2) Å, Rwp = 0.095; (2) composition as in (1), anhydrous and deuterated, neutron data collected at 5 K, disproportionation into two phases in I4̄3m, with a = 14.8410 (7) and 14.5273 (11) Å, Rwp = 0.038; (3) (H-MMA)8.8Cs0.2Al9Si39O96.Al2O3.25H2O, X-ray data collection at room temperature, I4̄3m, a = 14.9771 (2) Å, Rwp = 0.090. Series II (steam): (4) H0.3(H-MMA)5Cs0.7Al6Si42O96.2.5Al2O3.23H2O, X-ray data collected at room temperature, Im3̅m, a = 15.0323 (2) Å, Rwp = 0.124; (5) composition as in (4), anhydrous and deuterated, neutron data collected at 5 K, disproportionation into two phases in I4̄3m with a = 14.9151 (2) and 14.6475(8) Å, Rwp = 0.031. In the hydrated samples MMA resides on the center axis in the α-cage with the N atoms pointing to the single eight-ring; upon dehydration it migrates into the double eight-rings

The Role of the Immune Phenotype in Tumor Progression and Prognosis of Patients with Mycosis Fungoides: A Quantitative Immunohistology Whole Slide Approach

Background and objectives: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphomas, characterized by mature, skin-tropic CD4+ T-helper cells. In order to study the immune tumor microenvironment in MF patients, we performed immunohistochemical stains on MF biopsies, digitized whole-slide tissue sections, and performed quantitative analysis of the different immune cell subsets to correlate tissue parameters with the clinical data of patients, such as progression-free survival or overall survival. Patients and methods: Overall, 35 patients who were treated between 2009 and 2019 and for whom one or more paraffin tissue blocks were available have been included in the present study (58 tissue specimens in total). Conventional immunohistochemistry stains for CD3, CD4, CD8, CD20 and CD30 were used for the analysis of the immune phenotype, and quantitative analysis was performed using QuPath as a quantitative digital pathology tool for bioimage analysis of whole slides. Results: Analysis of tissue parameters for prognostic significance revealed that patients with a stronger infiltration by CD8+ lymphocytes within the tumor cell compartment had a higher risk of disease progression (p = 0.031) and showed a shorter progress-free survival (p = 0.038). Furthermore, a significant association of the percentage of CD30+ cells (median: 7.8%) with the risk of disease progression (p = 0.023) and progression-free survival (p = 0.023) was found. In relation to the clinical features of our patient cohort, a higher risk of disease progression (p = 0.015) and a shorter progression-free survival (p = 0.032) for older patients (>61 years) were observed. Conclusions: Our results demonstrated the prognostic relevance of large-cell transformation in mycosis fungoides and its strong association with the presence of CD30+ lymphocytes. Unlike previous reports, our study suggests an adverse prognostic role for CD8+ T cells in patients with mycosis fungoides. Moreover, our data indicate that the immune phenotype within the tumor microenvironment shows strong temporal heterogeneity and is altered in the course of tumor progression

Selective Hydrogenation of Benzofurans Using Ruthenium Nanoparticles in Lewis Acid-Modified Ruthenium-Supported Ionic Liquid Phases

Ruthenium nanoparticles immobilized on a Lewis-acid-functionalized supported ionic liquid phase (Ru@SILP-LA) act as effective catalysts for the selective hydrogenation of benzofuran derivatives to dihydrobenzofurans. The individual components (nanoparticles, chlorozincate-based Lewis-acid, ionic liquid, support) of the catalytic system are assembled using a molecular approach to bring metal and acid sites in close contact on the support material, allowing the hydrogenation of O-containing heteroaromatic rings while keeping the aromaticity of C6-rings intact. The chlorozincate species were identified to be predominantly [ZnCl4]2– anions using X-ray photoelectron spectroscopy and are in close interaction with the metal nanoparticles. The Ru@SILP-[ZnCl4]2– catalyst exhibited high activity, selectivity, and stability for the catalytic hydrogenation of a variety of substituted benzofurans, providing easy access to biologically relevant dihydrobenzofuran motifs under continuous flow conditions

Zeolite Rho Loaded with Methylamines. II. Dimethylamine Loadings

Samples of two differently prepared zeolite rho loaded with different amounts of dimethylamine (DMA) were studied in their hydrated forms by X-ray diffraction. Both zeolites are partially dealuminated, as indicated by nonframework A1 which is assumed to be Al2O3 or AlOOH. Series I was prepared from dry-calcined NHn-rho at 873 K, series II from steam-calcined NHn-rho at 773 K. The samples were loaded with different amounts of DMA. Rietveld refinements yielded the following results for series I: (1) H3.8(H-DMA)5Cs0.2Al9Si39O96.Al2O3.21H2O, X-ray data collection at room temperature, Im3̅m, a = 15.0590 (2) Å, Rwp = 0.089; (2) (H-DMA)8.8Cs0.2Al9Si39O96.Al2O3.18H2O, X-ray data collection at room temperature, Im3̅m, a = 15.0680 (2) Å, Rwp = 0.091. Series II: (3) H0.3(H-DMA)5Cs0.7Al6Si42O96.2.5Al2O3.24H2O, X-ray data collection at room temperature, Im3̅m, a = 15.0596 (2) Å, Rwp = 0.120. DMA resides on the center axis through the α-cage with the N atoms pointing to the single eight-ring and the two methyl groups oriented towards the center of the α-cage