Effectiveness and safety of COVID-19 vaccines on maternal and perinatal outcomes:a systematic review and meta-analysis

Objective: To assess the effects of COVID-19 vaccines in women before or during pregnancy on SARS-CoV-2 infection-related, pregnancy, offspring and reactogenicity outcomes. Design: Systematic review and meta-analysis. Data sources: Major databases between December 2019 and January 2023. Study selection: Nine pairs of reviewers contributed to study selection. We included test-negative designs, comparative cohorts and randomised trials on effects of COVID-19 vaccines on infection-related and pregnancy outcomes. Non-comparative cohort studies reporting reactogenicity outcomes were also included. Quality assessment, data extraction and analysis: Two reviewers independently assessed study quality and extracted data. We undertook random-effects meta-analysis and reported findings as HRs, risk ratios (RRs), ORs or rates with 95% CIs. Results: Sixty-seven studies (1 813 947 women) were included. Overall, in test-negative design studies, pregnant women fully vaccinated with any COVID-19 vaccine had 61% reduced odds of SARS-CoV-2 infection during pregnancy (OR 0.39, 95% CI 0.21 to 0.75; 4 studies, 23 927 women; I2=87.2%) and 94% reduced odds of hospital admission (OR 0.06, 95% CI 0.01 to 0.71; 2 studies, 868 women; I2=92%). In adjusted cohort studies, the risk of hypertensive disorders in pregnancy was reduced by 12% (RR 0.88, 95% CI 0.82 to 0.92; 2 studies; 115 085 women), while caesarean section was reduced by 9% (OR 0.91, 95% CI 0.85 to 0.98; 6 studies; 30 192 women). We observed an 8% reduction in the risk of neonatal intensive care unit admission (RR 0.92, 95% CI 0.87 to 0.97; 2 studies; 54 569 women) in babies born to vaccinated versus not vaccinated women. In general, vaccination during pregnancy was not associated with increased risk of adverse pregnancy or perinatal outcomes. Pain at the injection site was the most common side effect reported (77%, 95% CI 52% to 94%; 11 studies; 27 195 women). Conclusion: COVID-19 vaccines are effective in preventing SARS-CoV-2 infection and related complications in pregnant women. PROSPERO registration number: CRD42020178076

Resonant laser ionization and mass separation of 225^{225}Ac

$^{225}$Ac is a radio-isotope that can be linked to biological vector molecules to treat certain distributed cancers using targeted alpha therapy. However, developing $^{225}$Ac-labelled radiopharmaceuticals remains a challenge due to the supply shortage of pure $^{225}$Ac itself. Several techniques to obtain pure $^{225}$Ac are being investigated, amongst which is the high-energy proton spallation of thorium or uranium combined with resonant laser ionization and mass separation. As a proof-of-principle, we perform off-line resonant ionization mass spectrometry on two samples of $^{225}$Ac, each with a known activity, in different chemical environments. We report overall operational collection efficiencies of 10.1(2)% and 9.9(8)% for the cases in which the $^{225}$Ac was deposited on a rhenium surface and a ThO$_{2}$ mimic target matrix respectively. The bottleneck of the technique was the laser ionization efficiency, which was deduced to be 15.1(6)%

Efficient Production of High Specific Activity Thulium-167 at Paul Scherrer Institute and CERN-MEDICIS

Thulium-167 is a promising radionuclide for nuclear medicine applications with potential use for both diagnosis and therapy (“theragnostics”) in disseminated tumor cells and small metastases, due to suitable gamma-line as well as conversion/Auger electron energies. However, adequate delivery methods are yet to be developed and accompanying radiobiological effects to be investigated, demanding the availability of $^{167}$Tm in appropriate activities and quality. We report herein on the production of radionuclidically pure $^{167}$Tm from proton-irradiated natural erbium oxide targets at a cyclotron and subsequent ion beam mass separation at the CERN-MEDICIS facility, with a particular focus on the process efficiency. Development of the mass separation process with studies on stable $^{169}$Tm yielded 65 and 60% for pure and erbium-excess samples. An enhancement factor of thulium ion beam over that of erbium of up to several 104 was shown by utilizing laser resonance ionization and exploiting differences in their vapor pressures. Three $^{167}$Tm samples produced at the IP2 irradiation station, receiving 22.8 MeV protons from Injector II at Paul Scherrer Institute (PSI), were mass separated with collected radionuclide efficiencies between 11 and 20%. Ion beam sputtering from the collection foils was identified as a limiting factor. In-situ gamma-measurements showed that up to 45% separation efficiency could be fully collected if these limits are overcome. Comparative analyses show possible neighboring mass suppression factors of more than 1,000, and overall $^{167}$Tm/Er purity increase in the same range. Both the actual achieved collection and separation efficiencies present the highest values for the mass separation of external radionuclide sources at MEDICIS to date

Efficient Production of High Specific Activity Thulium-167 at Paul Scherrer Institute and CERN-MEDICIS

none17Thulium-167 is a promising radionuclide for nuclear medicine applications with potential use for both diagnosis and therapy (“theragnostics”) in disseminated tumor cells and small metastases, due to suitable gamma-line as well as conversion/Auger electron energies. However, adequate delivery methods are yet to be developed and accompanying radiobiological effects to be investigated, demanding the availability of 167Tm in appropriate activities and quality. We report herein on the production of radionuclidically pure 167Tm from proton-irradiated natural erbium oxide targets at a cyclotron and subsequent ion beam mass separation at the CERN-MEDICIS facility, with a particular focus on the process efficiency. Development of the mass separation process with studies on stable 169Tm yielded 65 and 60% for pure and erbium-excess samples. An enhancement factor of thulium ion beam over that of erbium of up to several 104 was shown by utilizing laser resonance ionization and exploiting differences in their vapor pressures. Three 167Tm samples produced at the IP2 irradiation station, receiving 22.8 MeV protons from Injector II at Paul Scherrer Institute (PSI), were mass separated with collected radionuclide efficiencies between 11 and 20%. Ion beam sputtering from the collection foils was identified as a limiting factor. In-situ gamma-measurements showed that up to 45% separation efficiency could be fully collected if these limits are overcome. Comparative analyses show possible neighboring mass suppression factors of more than 1,000, and overall 167Tm/Er purity increase in the same range. Both the actual achieved collection and separation efficiencies present the highest values for the mass separation of external radionuclide sources at MEDICIS to date.noneHeinke R.; Chevallay E.; Chrysalidis K.; Cocolios T.E.; Duchemin C.; Fedosseev V.N.; Hurier S.; Lambert L.; Leenders B.; Marsh B.A.; van der Meulen N.P.; Sprung P.; Stora T.; Tosato M.; Wilkins S.G.; Zhang H.; Talip Z.Heinke, R.; Chevallay, E.; Chrysalidis, K.; Cocolios, T. E.; Duchemin, C.; Fedosseev, V. N.; Hurier, S.; Lambert, L.; Leenders, B.; Marsh, B. A.; van der Meulen, N. P.; Sprung, P.; Stora, T.; Tosato, M.; Wilkins, S. G.; Zhang, H.; Talip, Z

Nuclear moments and isotope shifts of the actinide isotopes <math><mmultiscripts><mi>Cf</mi><mprescripts/><none/><mrow><mn>249</mn><mtext>–</mtext><mn>253</mn></mrow></mmultiscripts></math> probed by laser spectroscopy

International audienceWe report on high-resolution laser spectroscopy studies on Cf249–253 with spectral linewidths in the order of 100 MHz carried out at the RISIKO mass separator at Mainz University. In total three atomic ground-state transitions were investigated and the hyperfine parameters for the odd-A isotopes and isotope shift for all examined isotopes have been determined from the measured spectra. The isotope shift measurements allowed tracking of changes in mean-squared charge radii across the deformed nuclear shell closure at N=152, whereby shape discontinuities were not observed. Experimental hyperfine coupling constants of the atomic ground state were combined with relativistic many-body atomic calculations to extract the nuclear magnetic-dipole moment of Cf249 with improved precision to μI(249Cf)=−0.395(17)μN, whereas μI(251Cf)=−0.571(24)μN and μI(253Cf)=−0.731(35)μN were derived for the first time. Additionally, the spectroscopic quadrupole moments QS(249Cf)=6.27(33)eb and QS(253Cf)=5.53(51)eb were extracted

Present and future challenges to quality science in research and practice

Die aktuelle Situation in der Industrie und im Dienstleistungssektor ist durch eine starke Veränderung der Geschäftsmodelle geprägt. Gekoppelt mit der Digitalisierung vieler Geschäftsprozesse bewirkt und erzwingt dies enorme Anpassungen in und zwischen den Organisationen. Diese drastischen Veränderungen müssen vom Qualitätsmanagement (QM) unmittelbar begleitet werden, um mit Methoden und Techniken des Qualitätsmanagements die Prozesse sicher umzugestalten und anschließend angepasste QM-Systeme in einem kontinuierlichen Verbesserungsprozess weiter zu optimieren. Hierzu gibt es keine einheitliche Vorgehensweise. Im Gegenteil, die Heterogenität der Branchen erfordert spezifische Anpassungs- und Umsetzungslösungen. Die GQW-Tagung 2017 trägt dazu bei, unterschiedliche Schwerpunkte in der Transformation der existierenden QM-Systeme im Hinblick auf die neuen Herausforderungen darzustellen.The current situation in industry and in the service sector is characterized by a strong change in business models. Linked with the digitalization of many business processes this leads to major adjustments in and between organizations. These radical changes have to be directly accompanied by quality management (QM) in order to redesign the processes safely with methods and techniques of quality management and subsequently to optimize adapted quality management systems in a continuous improvement process. There is no standardized approach to this. On the contrary, the heterogeneity of the sectors requires specific solutions for adaption and implementation. The GQW conference 2017 helps to show different key aspects in the transformation of existing quality management systems with regard to the new challenges

Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl− homeostasis

A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the gold-standard analgesic morphine and other opiates. We found that hyperalgesia-inducing treatment with morphine resulted in downregulation of the K(+)-Cl(-) co-transporter KCC2, impairing Cl(-) homeostasis in rat spinal lamina l neurons. Restoring the anion equilibrium potential reversed the morphine-induced hyperalgesia without affecting tolerance. The hyperalgesia was also reversed by ablating spinal microglia. Morphine hyperalgesia, but not tolerance, required μ opioid receptor-dependent expression of P2X4 receptors (P2X4Rs) in microglia and μ-independent gating of the release of brain-derived neurotrophic factor (BDNF) by P2X4Rs. Blocking BDNF-TrkB signaling preserved Cl(-) homeostasis and reversed the hyperalgesia. Gene-targeted mice in which Bdnf was deleted from microglia did not develop hyperalgesia to morphine. However, neither morphine antinociception nor tolerance was affected in these mice. Our findings dissociate morphine-induced hyperalgesia from tolerance and suggest the microglia-to-neuron P2X4-BDNF-KCC2 pathway as a therapeutic target for preventing hyperalgesia without affecting morphine analgesia