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Abstract The goal of this work was to quantify the effect of school closure during the first year of coronavirus disease 2019 (COVID-19) pandemic in Switzerland. This allowed us to determine the usefulness of school closures as a pandemic countermeasure for emerging coronaviruses in the absence of pharmaceutical interventions. The use of multivariate endemic-epidemic modelling enabled us to analyse disease spread between age groups which we believe is a necessary inclusion in any model seeking to achieve our goal. Sophisticated time-varying contact matrices encapsulating four different contact settings were included in our complex statistical modelling approach to reflect the amount of school closure in place on a given day. Using the model, we projected case counts under various transmission scenarios (driven by implemented social distancing policies). We compared these counterfactual scenarios against the true levels of social distancing policies implemented, where schools closed in the spring and reopened in the autumn. We found that if schools had been kept open, the vast majority of additional cases would be expected among primary school-aged children with a small fraction of cases filtering into other age groups following the contact matrix structure. Under this scenario where schools were kept open, the cases were highly concentrated among the youngest age group. In the scenario where schools had remained closed, most reduction would also be expected in the lowest age group with less effects seen in other groups.

A pervasive challenge in noble gas geochemistry is to ensure that analytical techniques do not modify the composition of the noble gases in the samples. Noble gases are present in the atmosphere and are used in a number of manufacturing procedures and by laboratory equipment. Of particular concern is the introduction of atmospheric or laboratory noble gases to samples during preparation before samples are placed in a vacuum chamber for analysis. Recent work has shown the potential for contamination of crushed samples with air-derived He that is not released by placing the samples under vacuum at room temperature. Using pure He gas as a tracer, we show that the act of crushing samples to a fine powder itself can introduce He contamination but that this is easily avoided by crushing under liquid or in an inert atmosphere. Because the He is trapped during crushing, the same concern does not extend to samples that are naturally fine-grained when collected. We also show model results that demonstrate when this effect might significantly impact samples for (U–Th) / He geochronology or 3He cosmogenic nuclide dating. The degree of He contamination from crushing samples to sizes smaller than the > 63 µm range typically used for geochronology is insignificant for samples with a date of at least 1 Ma and 1 ppm U, and the degree of He contamination from crushing samples to sizes smaller than the 100–500 µm range typically used for cosmogenic nuclide dating is also insignificant for samples with a date of at least 10 ka with typical 3He production rates.

Apatite and zircon are among the best-studied and most widely used accessory minerals for geochronology and thermochronology. Given that apatite and zircon are often present in the same lithologies, distinguishing the two phases in crushed mineral separates is a common task for geochronology, thermochronology, and petrochronology studies. Here we present a method for efficient and accurate apatite and zircon mineral phase identification and verification using X-ray micro-computed tomography (microCT) of grain mounts that provides additional three-dimensional grain size, shape, and inclusion suite information. In this study, we analyze apatite and zircon grains from Fish Canyon Tuff samples that went through methylene iodide (MEI) and lithium heteropolytungstate (LST) heavy liquid density separations. We validate the microCT results using known standards and phase identification with Raman spectroscopy, demonstrating that apatite and zircon are distinguishable from each other and other common phases, e.g., titanite, based on microCT X-ray density. We present recommended microCT scanning protocols after systematically testing the effects of different scanning parameters and sample positions. This methodology can help to reduce time spent performing density separations with highly toxic chemicals and visually inspecting grains under a light microscope, and the improved mineral identification and characterization can make geochronologic data more robust.

Therapeutic viral vectors are an emerging technology with several clinical applications in gene therapy, vaccines, and immunotherapy. Increased demand has required the redevelopment of conventional, low-throughput cell culture and purification manufacturing methods such as static cell stacks and ultracentrifugation. In this work, scalable methods were investigated for the manufacture of an oncolytic virus immunotherapy application consisting of a prototype strain of coxsackievirus A21 (CVA21) produced in adherent MRC-5 cells. Cell culture was established in stirred-tank microcarrier bioreactors, and an efficient affinity chromatography method was developed for the purification of harvested CVA21 through binding of the viral capsids to an immobilized glutathione (GSH) ligand. Bioreactor temperature during infection was investigated to maximize titer, and a decrease in temperature from 37°C to 34°C yielded a two–three-fold increase in infectivity. After purification of the 34°C harvests, the GSH affinity chromatography elution not only maintained a >two-fold increase in infectivity and viral genomes but also increased the proportion of empty capsids compared to 37°C harvests. Using material generated from both infection temperature setpoints, chromatographic parameters and mobile phase compositions were studied at the laboratory scale to maximize infectious particle yields and cell culture impurity clearance. Empty capsids that co-eluted with full capsids from 34°C infection temperature harvests were poorly resolved across the conditions tested, but subsequent polishing anion exchange and cation exchange chromatography steps were developed to clear residual empty capsids and other impurities. Oncolytic CVA21 production was scaled-up 75-fold from the laboratory scale and demonstrated across seven batches in 250 L single-use microcarrier bioreactors and purified with customized, prepacked, single-use 1.5 L GSH affinity chromatography columns. The large-scale bioreactors controlled at 34°C during infection maintained a three-fold increase in productivity in the GSH elution, and excellent clearance of host cell and media impurities was observed across all batches. This study presents a robust method for the manufacture of an oncolytic virus immunotherapy application that may be implemented for the scalable production of other viruses and viral vectors which interact with glutathione.

In this paper, we investigate the possibility of explaining nonclassical correlations between two quantum systems in terms of quantum interferences between collective states of the two systems. We achieve this by mapping the relations between different measurement contexts in the product Hilbert space of a pair of two-level systems onto an analogous sequence of interferences between paths in a single-particle interferometer. The relations between different measurement outcomes are then traced to the distribution of probability currents in the interferometer, where paradoxical relations between the outcomes are identified with currents connecting two states that are orthogonal and should therefore exclude each other. We show that the relation between probability currents and correlations can be represented by continuous conditional (quasi)probability currents through the interferometer, given by weak values; the violation of the noncontextual assumption is expressed by negative conditional currents in some of the paths. Since negative conditional currents correspond to the assignment of negative conditional probabilities to measurements results in different measurement contexts, the necessity of such negative probability currents represents a failure of noncontextual local realism. Our results help to explain the meaning of nonlocal correlations in quantum mechanics, and support Feynman’s claim that interference is the origin of all quantum phenomena.

Information about the internal properties of a system can only be obtained through interactions of the system with an external meter. However, such interactions generally result in entanglement between the system and the meter, making it difficult to trace the measurement result back to a specific value of the physical property in the system. It is therefore possible that the outcomes of quantum measurements depend in a nontrivial manner on the dynamics of the measurement interaction, possibly providing a physical explanation for the role of measurement contexts in quantum mechanics. Here we show that the effects of the measurement interaction on the meter can be described entirely in terms of the quantum coherent system dynamics associated with the back-action on the system. For sufficiently small back-action uncertainties, the physical property of the system is described by a weak value obtained from the Hamilton-Jacobi equation of the back-action dynamics. At higher measurement resolutions, the observed values are determined by quantum interferences between different amounts of back-action. Eigenvalues emerge when the quantum interferences between different back-actions correspond to a Fourier transform in the back-action parameter. We conclude that the values of physical properties obtained in quantum measurements originate from the quantum coherent properties of the back-action dynamics generated by that physical property during an interaction. Measurement outcomes represent elements of the dynamics and cannot be explained by measurement independent elements of reality.

We analyse the quantum Cheshire cat using contextuality theory, to see if this can tell us anything about how best to interpret this paradox. We show that this scenario can be analysed using the relation between three different measurements, which seem to result in a logical contradiction. We discuss how this contextual behaviour links to weak values, and coherences between prohibited states. Rather than showing a property of the particle is disembodied, the quantum Cheshire cat instead demonstrates the effects of these coherences, which are typically found in pre- and post-selected systems.

It is commonly assumed that no accurate experimental information can be obtained on the path taken by a particle when quantum interference between the paths is observed. However, recent progress in the measurement and control of quantum systems may provide the missing information by circumventing the conventional uncertainty limits. Here, we experimentally investigate the possibility that an individual neutron moving through a two-path interferometer may actually be physically distributed between the two paths. For this purpose, it is important to distinguish between the probability of finding the complete particle in one of the paths and the distribution of an individual particle over both paths. We accomplish this distinction by applying a magnetic field in only one of the paths and observing the exact value of its effect on the neutron spin in the two output ports of the interferometer. The results show that individual particles experience a specific fraction of the magnetic field applied in one of the paths, indicating that a fraction or even a multiple of the particle was present in the path before the interference of the two paths was registered. The obtained path presence equals the weak value of the path projector and is not a statistical average but applies to every individual neutron, verified by the recently introduced method of feedback compensation.

Background: Robotic-assisted percutaneous coronary intervention (R-PCI) is an efficacious and safe treatment option for coronary artery disease. However, predictors of manual support during R-PCI are unknown, which we aimed to investigate in a multi-center study., Methods: We utilized patient-level data from R-PCIs carried out from 2020 to 2022 at four sites in Germany. Manual support was defined as the combination of partial manual assistance, where the procedure is ultimately completed using robotic techniques, and manual conversion. A two-step selection process based on akaike information criteria was used to identify the ideal multivariable model predicting manual support., Results: In 210 patients (median age 69.0 years; 25.7% female), a total of 231 coronary lesions were treated by R-PCI. Manual support was needed in 46 lesions (19.9%). Procedures requiring manual support were associated with significantly longer procedural times, greater total contrast fluid volumes, longer fluoroscopy times, and higher dose-area products. Amongst the predictors of manual support were lesions in the left anterior descending artery [OR: 1.09 (95%-CI: 0.99-1.20)], aorto-ostial lesions [OR: 1.35 (95%-CI: 1.11-1.64)], chronic total occlusions [OR: 1.78 (95%-CI: 1.38-2.31)], true bifurcations [OR: 1.37 (95%-CI: 1.17-1.59)], and severe calcification [OR: 1.13 (95%-CI: 1.00-1.27)]., Conclusion: Our findings reveal that nearly one out five of patients undergoing R-PCI required manual support, which was linked to longer procedure durations. Predictors of manual support reflected characteristics of more complex coronary lesions. These results highlight the limitations of current R-PCI platforms and underscore the need for technical advancements to address different clinical scenarios., Competing Interests: Declarations. Conflict of interest: JR reports grants/research support from Shockwave Medical, Philips, Abbott and receipt of honoraria or consultation fees from AstraZeneca, all outside the submitted work. CvzM reports honoraria or consultation fees from Siemens Healthiness. HN reports speaker honorarium and travel grant from Siemens, Abbott, Boston, SMT, Medtronic, Edwards, all outside the submitted work. HM reports personal fees from Abiomed, Abbott, Amgen, Astra Zeneca, BMS, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, Novartis, Pfizer, Siemens, SMT, Zoll, all outside the submitted work. MS reports personal fees from Abiomed, Amgen, AstraZeneca, Bristol-Myers Squibb, Daichii Sankyo, Inari Medical, Pfizer, Shockwave Medical, and Siemens Healthineers, personal fees and non-financial support from Abbott Vascular, Edwards Lifesciences, and Medtronic, and grants, personal fees and non-financial support from Boston Scientific and Philips, all outside the submitted work. FJB reports grants from Daiichi Sankyo, Novartis, Pfizer, and Sanofi, non-financial support from ASAHI INTECC, and Inari Medical, personal fees from Amgen, Daiichi Sankyo, Inari Medical, Novartis, and Shockwave out-side of the submitted work. All other authors declare that there is no conflict of interest., (© 2025. The Author(s).)

We aim to optimize the binary detection of Chronic Obstructive Pulmonary Disease (COPD) based on emphysema presence in the lung with convolutional neural networks (CNN) by exploring manually adjusted versus automated window-setting optimization (WSO) on computed tomography (CT) images. 7194 contrast-enhanced CT images (3597 with COPD; 3597 healthy controls) from 78 subjects were selected retrospectively (01.2018-12.2021) and preprocessed. For each image, intensity values were manually clipped to the emphysema window setting and a baseline 'full-range' window setting. Class-balanced train, validation, and test sets contained 3392, 1114, and 2688 images. The network backbone was optimized by comparing various CNN architectures. Furthermore, automated WSO was implemented by adding a customized layer to the model. The image-level area under the Receiver Operating Characteristics curve (AUC) [lower, upper limit 95% confidence] was utilized to compare model variations. Repeated inference (n = 7) on the test set showed that the DenseNet was the most efficient backbone and achieved a mean AUC of 0.80 [0.76, 0.85] without WSO. Comparably, with input images manually adjusted to the emphysema window, the DenseNet model predicted COPD with a mean AUC of 0.86 [0.82, 0.89]. By adding a customized WSO layer to the DenseNet, an optimal window in the proximity of the emphysema window setting was learned automatically, and a mean AUC of 0.82 [0.78, 0.86] was achieved. Detection of COPD with DenseNet models was improved by WSO of CT data to the emphysema window setting range., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this paper, mixed methods research is presented and discussed in the context of research on reflective writing for the professional development of pre-service teachers. First, we present prominent theoretical frameworks to analyze reflective writings. Second, we review relevant methodological approaches of research on reflective writings in teacher education, such as qualitative, quantitative and mixed methods. Third, we present a study from our research lab combining qualitative content analysis and linguistic analyses as an example for a concurrent mixed method approach. The results of the qualitative content analysis indicated that 198 reflective writings of pre-service teachers were primarily descriptive and on a low level. Computational linguistic analyses revealed that affective and cognitive terminology utilization in reflective writing differed significantly across the different levels of reflection, with a higher frequency of such terms correlating with deeper levels of reflection. Thus, essential challenges and opportunities of implementing such a mixed method study to analyze reflective writings are illustrated and discussed. Finally, we conclude the paper by discussing on how mixed methods approaches might be further advanced in the field of reflective writing research in teacher education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gläser-Zikuda, Zhang, Hofmann, Plößl, Pösse and Artmann.)