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Clinical algorithms used in the assessment of febrile children in the Paediatric Emergency Departments are commonly based on threshold values for vital signs, which in children with fever are often outside the normal range. Our aim was to assess the diagnostic value of heart and respiratory rate for serious bacterial infection (SBI) in children after temperature lowering following administration of antipyretics. A prospective cohort of children presenting with fever between June 2014 and March 2015 at the Paediatric Emergency Department of a large teaching hospital in London, UK, was performed. Seven hundred forty children aged 1 month–16 years presenting with a fever and ≥ 1 warning signs of SBI given antipyretics were included. Tachycardia or tachypnoea were defined by different threshold values: (a) APLS threshold values, (b) age-specific and temperature-adjusted centiles charts and (c) relative difference in z-score. SBI was defined by a composite reference standard (cultures from a sterile site, microbiology and virology results, radiological abnormalities, expert panel). Persistent tachypnoea after body temperature lowering was an important predictor of SBI (OR 1.92, 95% CI 1.15, 3.30). This effect was only observed for pneumonia but not other SBIs. Threshold values for tachypnoea > 97th centile at repeat measurement achieved high specificity (0.95 (0.93, 0.96)) and positive likelihood ratios (LR + 3.25 (1.73, 6.11)) and may be useful for ruling in SBI, specifically pneumonia. Persistent tachycardia was not an independent predictor of SBI and had limited value as a diagnostic test. Conclusion: Among children given antipyretics, tachypnoea at repeat measurement had some value in predicting SBI and was useful to rule in pneumonia. The diagnostic value of tachycardia was poor. Overreliance on heart rate as a diagnostic feature following body temperature lowering may not be justified to facilitate safe discharge. What is Known:• Abnormal vital signs at triage have limited value as a diagnostic test to identify children with SBI, and fever alters the specificity of commonly used threshold values for vital signs.• The observed temperature response after antipyretics is not a clinically useful indicator to differentiate the cause of febrile illness. What is New:• Persistent tachycardia following reduction in body temperature was not associated with an increased risk of SBI and of poor value as a diagnostic test, whilst persistent tachypnoea may indicate the presence of pneumonia.

The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods. Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings. Of 4,611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3,477 (75%) had uncertain aetiology. 1,061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N.meningitidis (OR: 3.37, 95% CI: 1.92 – 5.99), S.pneumoniae (OR: 3.89, 95% CI: 2.07 – 7.59), Group A streptococcus (OR 2.73, 95% CI 1.13 – 6.09) and E.coli (OR 2.7, 95% CI 1.02 – 6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11 – 0.46), Influenza B (OR 0.12, 95% CI 0.02 – 0.37) and RSV (OR 0.16, 95% CI: 0.06 – 0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23 – 0.72) and EBV (OR 0.71, 95% CI 0.56 – 0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation. Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.

Background To investigate the impact of the COVID-19 pandemic and infection prevention measures on children visiting emergency departments across Europe. Methods Routine health data were extracted retrospectively from electronic patient records of children aged 12 months (12

For a safety assessment of repositories, possible accident scenarios must be considered. If radionuclides (RNs) are released from a repository into the groundwater, they can migrate and interact with the biosphere. In addition to microorganisms, higher organisms such as plants also play a role in this context. For this reason, it is necessary that a process understanding on RN plant interactions on the molecular level is elucidated by suitable biochemical and spectroscopic methods to improve biogeochemical models for a reliable modeling of the transfer behavior of RNs in the environment up to the food chain. Interaction with plant cells can lead to immobilization and speciation changes of the RNs. Uranium as the main component (by mass) of spent nuclear fuel rods is of interest for our investigations. Furthermore, we studied europium as a non-radioactive analogue for the trivalent actinides Am(III) and Cm(III), whereby the former in particular will dominate the radiotoxicity in a potential repository. We investigated the time and concentration-dependent immobilization of these two metals to the biomass of different plant cell cultures. Biochemical methods were accompanied by spectroscopic (time-resolved laser-induced fluorescence spectroscopy, TRLFS) and microscopic techniques for determination of speciation and localization of the metals within the plant cells, respectively. In addition, the combination of luminescence spectroscopy with microscopy in the form of chemical microscopy revealed for the first time the spatially resolved localization of different Eu(III) species in plant root tissues. We observed bioassociation (immobilization) of U(VI)/Eu(III), but in some cases also re-mobilization of U(VI), which temporally coincided with a change in the metal speciation in solution. Moreover, we successfully identified metabolites released by the plant cells that can complex with U(VI)/Eu(III) and influence their mobility and thus bioavailability in the environment. Our studies can help to integrate RN plant interactions in assessment strategies of nuclear waste repositories.

In this study, we investigated the interaction of U(VI) and Eu(III) with Brassica napus suspension plant cells as a model system. Concentration-dependent (0-200 µM) bioassociation experiments showed that more than 75% of U(VI) and Eu(III) were immobilized by the cells. In addition to this phenomenon, time-dependent studies for 1 to 72 h of exposure showed a multi-stage bioassociation process for cells that were exposed to 200 µM U(VI), where, after initial immobilization of U(VI) within 1 h of exposure, it was released back into culture medium starting within 24 h. A re-mobilization to this extent has not been previously observed. The MTT assay was used to correlate the bioassociation behavior of Eu and U with the cell vitality. Speciation studies by spectroscopy and in silico methods highlighted various U and Eu species over the course of exposure. We were able to observe a new U species, which emerged simultaneously with the re-mobilization of U back into solution, which we assume to be a U(VI) phosphate species. Thus, the interaction of U(VI) and Eu(III) with released plant metabolites could be concluded.