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Abstract Background The objective of this study was to demonstrate the utility of an approach in training predoctoral medical students, to enable them to measure electrode-to-modiolus distances (EMDs) and insertion-depth angles (aDOIs) in cochlear implant (CI) imaging at the performance level of a single senior rater. Methods This prospective experimental study was conducted on a clinical training dataset comprising patients undergoing cochlear implantation with a Nucleus® CI532 Slim Modiolar electrode (N = 20) or a CI512 Contour Advance electrode (N = 10). To assess the learning curves of a single medical student in measuring EMD and aDOI, interrater differences (senior–student) were compared with the intrarater differences of a single senior rater (test–retest). The interrater and intrarater range were both calculated as the distance between the 0.1th and 99.9th percentiles. A “deliberate practice” training approach was used to teach knowledge and skills, while correctives were applied to minimize faulty data-gathering and data synthesis. Results Intrarater differences of the senior rater ranged from − 0.5 to 0.5 mm for EMD and − 14° to 16° for aDOI (respective medians: 0 mm and 0°). Use of the training approach led to interrater differences that matched this after the 4th (EMD) and 3rd (aDOI) feedback/measurement series had been provided to the student. Conclusions The training approach enabled the student to evaluate the CI electrode position at the performance level of a senior rater. This finding may offer a basis for ongoing clinical quality assurance for the assessment of CI electrode position.

Abstract Background Cardiac arrest resuscitation requires well-executed teamwork to produce optimal outcomes. Frequency of cardiac arrest events differs by hospital location, which presents unique challenges in care due to variations in responding team composition and comfort levels and familiarity with obtaining and utilizing arrest equipment. The objective of this initiative is to utilize unannounced, in situ, cardiac arrest simulations hospital wide to educate, evaluate, and maximize cardiac arrest teams outside the traditional simulation lab by systematically assessing and capturing areas of opportunity for improvement, latent safety threats (LSTs), and key challenges by hospital location. Methods Unannounced in situ simulations were performed at a city hospital with multidisciplinary cardiac arrest teams responding to a presumed real cardiac arrest. Participants and facilitators identified LSTs during standardized postsimulation debriefings that were classified into equipment, medication, resource/system, or technical skill categories. A hazard matrix was used by multiplying occurrence frequency of LST in simulation and real clinical events (based on expert opinion) and severity of the LST based on agreement between two evaluators. Results Seventy-four in situ cardiac arrest simulations were conducted hospital wide. Hundreds of safety threats were identified, analyzed, and categorized yielding 106 unique latent safety threats: 21 in the equipment category, 8 in the medication category, 41 in the resource/system category, and 36 in the technical skill category. The team worked to mitigate all LSTs with priority mitigation to imminent risk level threats, then high risk threats, followed by non-imminent risk LSTs. Four LSTs were deemed imminent, requiring immediate remediation post debriefing. Fifteen LSTs had a hazard ratio greater than 8 which were deemed high risk for remediation. Depending on the category of threat, a combination of mitigating steps including the immediate fixing of an identified problem, leadership escalation, and programmatic intervention recommendations occurred resulting in mitigation of all identified threats. Conclusions Hospital-wide in situ cardiac arrest team simulation offers an effective way to both identify and mitigate LSTs. Safety during cardiac arrest care is improved through the use of a system in which LSTs are escalated urgently, mitigated, and conveyed back to participants to provide closed loop debriefing. Lastly, this hospital-wide, multidisciplinary initiative additionally served as an educational needs assessment allowing for informed, iterative education and systems improvement initiatives targeted to areas of LSTs and areas of opportunity.

Classifying the degree of relatedness between pairs of individuals has both scientific and commercial applications. As an example, genome-wide association studies (GWAS) may suffer from high rates of false positive results due to unrecognized population structure. This problem becomes especially relevant with recent increases in large-cohort studies. Accurate relationship classification is also required for genetic linkage analysis to identify disease-associated loci. Additionally, DNA relatives matching service is one of the leading drivers for the direct-to-consumer genetic testing market. Despite the availability of scientific and research information on the methods for determining kinship and the accessibility of relevant tools, the assembly of the pipeline, which stably operates on a real-world genotypic data, requires significant research and development resources. Currently, there is no open source end-to-end solution for relatedness detection in genomic data, that is fast, reliable and accurate for both close and distant degrees of kinship, combines all the necessary processing steps to work on a real data, and is ready for production integration. To address this, we developed GRAPE: Genomic RelAtedness detection PipelinE. It combines data preprocessing, identity-by-descent (IBD) segments detection, and accurate relationship estimation. The project uses software development best practices, as well as Global Alliance for Genomics and Health (GA4GH) standards and tools. Pipeline efficiency is demonstrated on both simulated and real-world datasets. GRAPE is available from: https://github.com/genxnetwork/grape.

Early diagnosis and the detection of distant metastases and recurrences in patients with prostate cancer (PCa) have been notably improved in recent decades through advances in imaging techniques. More recently, positron emission tomography (PET) hybrid imaging (PET/computed tomography \[CT] and PET/magnetic resonance imaging \[MRI]) using small molecule radiopharmaceuticals to selectively bind targets unique to PCa has permitted more accurate staging of patients with localized, locally advanced and metastatic disease. Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein overexpressed in most PCa cells, has emerged as one of many specific targets for PCa imaging. Since its introduction in Switzerland in 2016, PSMA-targeted PET/CT with ^68^Gallium(^68^Ga)-labeled and, less commonly, ^18^Flourine(^18^F) -labelled radiotracers, has shown unparalleled precision in detecting metastatic PCa compared with conventional imaging techniques. Furthermore, radioligand therapies such as lutetium-177 (^177^Lu)-PSMA-617 can selectively deliver β-radiation to PSMA-expressing cells. The phase III VISION trial showed that this treatment significantly improved survival outcomes in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). This article discusses the value and impact of ^68^Ga/^18^F-PSMA PET/CT imaging compared with conventional imaging modalities for accurately detecting PCa lesions in a primary setting and for local recurrence or metastases. In addition, an overview of the PSMA ligand therapy, a treatment modality for patients with advanced PCa is presented.

We aimed to investigate whether a selective pre-PCR enrichment step improves test performance of RIDA®GENE EHEC/EPEC to detect diarrheagenic Escherichia coli from stool samples. Each of the 250 stool samples was analyzed for the presence of stx1/2 and eae both with and without pre-PCR enrichment in selective broth. In comparison to a reference method, sensitivities for stx1/2 and eae with and without pre-PCR enrichment were 84% (95%CI 70–93) and 89% (stx1/2, 95%CI 76–96), and 71% (95%CI 58–81) and 72% (eae, 95%CI 60–82), respectively. Specificity exceeded 97% for both methods and target genes. In summary, pre-PCR broth enrichment did not improve test performance.

Abstract Background Racial and ethnic minority groups experience a disproportionate burden of SARS‐CoV‐2 illness and studies suggest that cancer patients are at a particular risk for severe SARS‐CoV‐2 infection. Aims The objective of this study was examine the association between neighborhood characteristics and SARS‐CoV‐2 infection among patients with cancer. Methods and Results We performed a cross‐sectional study of New York City residents receiving treatment for cancer at a tertiary cancer center. Patients were linked by their address to data from the US Census Bureau's American Community Survey and to real estate tax data from New York's Department of City Planning. Models were used to both to estimate odds ratios (ORs) per unit increase and to predict probabilities (and 95% CI) of SARS‐CoV2 infection. We identified 2350 New York City residents with cancer receiving treatment. Overall, 214 (9.1%) were infected with SARS‐CoV‐2. In adjusted models, the percentage of Hispanic/Latino population (aOR = 1.01; 95% CI, 1.005–1.02), unemployment rate (aOR = 1.10; 95% CI, 1.05–1.16), poverty rates (aOR = 1.02; 95% CI, 1.0002–1.03), rate of >1 person per room (aOR = 1.04; 95% CI, 1.01–1.07), average household size (aOR = 1.79; 95% CI, 1.23–2.59) and population density (aOR = 1.86; 95% CI, 1.27–2.72) were associated with SARS‐CoV‐2 infection. Conclusion Among cancer patients in New York City receiving anti‐cancer therapy, SARS‐CoV‐2 infection was associated with neighborhood‐ and building‐level markers of larger household membership, household crowding, and low socioeconomic status. Novelty and impact We performed a cross‐sectional analysis of residents of New York City receiving treatment for cancer in which we linked subjects to census and real estate date. This linkage is a novel way to examine the neighborhood characteristics that influence SARS‐COV‐2 infection. We found that among patients receiving anti‐cancer therapy, SARS‐CoV‐2 infection was associated with building and neighborhood‐level markers of household crowding, larger household membership, and low socioeconomic status. With ongoing surges of SARS‐CoV‐2 infections, these data may help in the development of interventions to decrease the morbidity and mortality associated with SARS‐CoV‐2 among cancer patients.

IntroductionSoil at the Roman site of Vindolanda (Northumberland, UK) provides excellent preservation of wooden artefacts including Roman writing tablets.MethodsIn this study we examined chemical and microbial signature changes within varied occupation contexts of archaeological soil. Analysis included investigating elemental composition, sterol biomarkers, bacterial diversity and community structures from excavation trenches at Vindolanda using pXRF, GC-MS and 16S rRNA gene amplicon sequencing. Samples were taken from varying depths starting at topsoil and working down through layers of Roman occupation including one cavalry stable floor, two infantry barracks and a cook house, and layers which contained Roman writing tablets.Results and DiscussionThe chemical results indicate that areas where wooden artefacts were found had increased soil moisture which was also correlated with specific chemical conditions including shifts in iron, sulphur and phosphorous concentration. Steroid biomarkers indicate the presence of faecal matter in layers, supporting occupation descriptions. Overall microbial diversity did not change across the depth profile but was correlated with soil moisture. Anaerobic soils associated with more optimal preservation differed to other soils with increases in Firmicutes, Proteobacteria, Campilobacterota and Bacteroidota observed. Microbial community structure and putative function as revealed by PICRUSt2 is linked to occupation usage rather than depth of samples with laminated floor layers differing from turf structures. Understanding the complex processes within archaeological soil can help us to understand dynamics of decomposition and preservation. In addition, the apparent preservation of the environmental microbial community as well as the artefacts themselves allows us to understand the microbial environments of the past, how they relate to the present and what this means for our changing environments in the future.

To maintain the information security of a computer system, it is necessary to regularly audit the used system components and their corresponding vulnerabilities. However, accounting for software flaws is a time-consuming task due to the constant emergence of new unstructured information about discovered vulnerabilities. To increase the speed of analyzing relevant information, the algorithm for processing vulnerability descriptions and the XML-based output data presentation format were proposed. Processing a text description means identifying a name and version of vulnerable software, as well as determining the type of a vulnerability and a level of severity. At the current stage of the research, the achieved classification accuracy is 87%.

Abstract Particle transport and localization phenomena in condensed-matter systems can be modeled using a tight-binding lattice Hamiltonian. The ideal experimental emulation of such a model utilizes simultaneous, high-fidelity control and readout of each lattice site in a highly coherent quantum system. Here, we experimentally study quantum transport in one-dimensional and two-dimensional tight-binding lattices, emulated by a fully controllable 3 × 3 array of superconducting qubits. We probe the propagation of entanglement throughout the lattice and extract the degree of localization in the Anderson and Wannier-Stark regimes in the presence of site-tunable disorder strengths and gradients. Our results are in quantitative agreement with numerical simulations and match theoretical predictions based on the tight-binding model. The demonstrated level of experimental control and accuracy in extracting the system observables of interest will enable the exploration of larger, interacting lattices where numerical simulations become intractable.

Abstract Nuclear receptors (NR) are ligand-modulated transcription factors that regulate multiple cell functions and thus represent excellent drug targets. However, due to a considerable NR structural homology, NR ligands often interact with multiple receptors. Here, we describe a multiplex reporter assay (the FACTORIAL NR) that enables parallel assessment of NR ligand activity across all 48 human NRs. The assay comprises one-hybrid GAL4-NR reporter modules transiently transfected into test cells. To evaluate the reporter activity, we assessed their RNA transcripts. We used a homogeneous RNA detection approach that afforded equal detection efficacy and permitted the multiplex detection in a single-well format. For validation, we examined a panel of selective NR ligands and polypharmacological agonists and antagonists of the progestin, estrogen, PPAR, ERR, and ROR receptors. The assay produced highly reproducible NR activity profiles (r > 0.96) permitting quantitative assessment of individual NR responses. The inferred EC50 values agreed with the published data. The assay showed excellent quality ( = 0.73) and low variability ( = 7.2%). Furthermore, the assay permitted distinguishing direct and non-direct NR responses to ligands. Therefore, the FACTORIAL NR enables comprehensive evaluation of NR ligand polypharmacology.

Background and Objectives: Alveolar echinococcosis (AE) is a highly variable disease able to present as structurally diverse cysts in different organs based on the host’s immunological state as well as the time between diagnosis and the primary infection. Bacterial superinfections, especially with anaerobic pathogens from the Clostridiaceae genus, can further alter the radiological findings due to pneumobilia, newly formed abscess formations, and inflammatory changes. Materials and Methods: We present a case of a 71-year-old Caucasian male admitted to our intensive care unit with septic shock, pneumobilia, and a complex cyst of the liver with calcification, as shown by an initial CT. Because of the septic shock, the patient was started on broad-band antibiotics. Clostridiaceae infection was considered an important differential diagnosis due to the presence of pneumobilia observed in the initial CT, without a history of previous endoscopy. Furthermore, serology for echinococcus was positive, and blood cultures showed growth of C. perfringens. Therefore, the patient was additionally treated with albendazole. After recovery, further staging was conducted, showing complete remission of the cyst and a left-over lesion classified as Alveolar Echinococcosis Ulm Classification (AEUC) V. In summary, the patient had a pre-existing, controlled AE infection that became superinfected with C. perfringens, likely attributable to the anaerobic necrotic tissue, leading to septicemia. Results: The anaerobic tissue within the AE cyst provided an ideal medium for C. perfringens to replicate, leading to cyst infection, which subsequently caused septic shock and pneumobilia. The initial findings from CT and MRI were confounded by the superinfection, demonstrating the diagnostic challenges of AE, especially when presenting with complications. Conclusions: Diagnosing AE remains a demanding task, even with the excellent tools available through serology, coupled with CT, FDG-PET-CT, and MRI. Notably, older superinfected cysts can pose difficulties when integrated into the appropriate diagnostic context. Prompt diagnosis is critical for the accurate treatment of echinococcosis and its complications, such as bacterial superinfections. From a clinical perspective, septicemia from Clostridiaceae and infections with C. perfringens—pathogens capable of inducing pneumobilia—should be regarded as significant differential diagnoses for pneumobilia in the absence of a recent history of endoscopy.

Clostridioides difficile is the most important pathogen causing antimicrobial-associated diarrhea and has recently been recognized as a cause of community-associated C. difficile infection (CA-CDI). This study aimed to characterize virulence factors, antimicrobial resistance (AMR), ribotype (RT) distribution and genetic relationship of C. difficile isolates from diverse fecally contaminated environmental sources. C. difficile isolates were recovered from different environmental samples in Northern Germany. Antimicrobial susceptibility testing was determined by E-test or disk diffusion method. Toxin genes (tcdA and tcdB), genes coding for binary toxins (cdtAB) and ribotyping were determined by PCR. Furthermore, 166 isolates were subjected to whole genome sequencing (WGS) for core genome multi-locus sequence typing (cgMLST) and extraction of AMR and virulence-encoding genes. Eighty-nine percent (148/166) of isolates were toxigenic, and 51% (76/148) were positive for cdtAB. Eighteen isolates (11%) were non-toxigenic. Thirty distinct RTs were identified. The most common RTs were RT127, RT126, RT001, RT078, and RT014. MLST identified 32 different sequence types (ST). The dominant STs were ST11, followed by ST2, ST3, and ST109. All isolates were susceptible to vancomycin and metronidazole and displayed a variable rate of resistance to moxifloxacin (14%), clarithromycin (26%) and rifampicin (2%). AMR genes, such as gyrA/B, blaCDD-1/2, aph(3′)-llla-sat-4-ant(6)-la cassette, ermB, tet(M), tet(40), and tetA/B(P), conferring resistance toward fluoroquinolone, beta-lactam, aminoglycoside, macrolide and tetracycline antimicrobials, were found in 166, 137, 29, 32, 21, 72, 17, and 9 isolates, respectively. Eleven “hypervirulent” RT078 strains were detected, and several isolates belonged to RTs (i.e., RT127, RT126, RT023, RT017, RT001, RT014, RT020, and RT106) associated with CA-CDI, indicating possible transmission between humans and environmental sources pointing out to a zoonotic potential.

This paper presents a method for reducing apparent cable capacitance seen by sensors. The proposed method is designed for sensing in extreme environments including ultra-high temperatures, but can be applied in benign environments as well. By reducing the cable capacitance, high speed signals can be transmitted over longer distances, allowing the application of advanced control systems that require high bandwidth data for stable operation. A triaxial cable with an associated guard circuit is developed that actively reduces cable capacitance while also rejecting extraneous electric and magnetic interference on the signal. The active capacitance reduction method developed is tested experimentally and shown to reduce apparent cable capacitance to two percent of the static value.

We propose and demonstrate an architecture for fluxonium-fluxonium two-qubit gates mediated by transmon couplers (FTF, for fluxonium-transmon-fluxonium). Relative to architectures that exclusively rely on a direct coupling between fluxonium qubits, FTF enables stronger couplings for gates using noncomputational states while simultaneously suppressing the static controlled-phase entangling rate (ZZ) down to kilohertz levels, all without requiring strict parameter matching. Here, we implement FTF with a flux-tunable transmon coupler and demonstrate a microwave-activated controlled-Z (CZ) gate whose operation frequency can be tuned over a 2-GHz range, adding frequency allocation freedom for FTFs in larger systems. Across this range, state-of-the-art CZ gate fidelities are observed over many bias points and reproduced across the two devices characterized in this work. After optimizing both the operation frequency and the gate duration, we achieve peak CZ fidelities in the 99.85%–99.9% range. Finally, we implement model-free reinforcement learning of the pulse parameters to boost the mean gate fidelity up to 99.922%±0.009%, averaged over roughly an hour between scheduled training runs. Beyond the microwave-activated CZ gate we present here, FTF can be applied to a variety of other fluxonium gate schemes to improve gate fidelities and passively reduce unwanted ZZ interactions.

Micro-milling is widely used to make micro-channels in various fields. In this study, micro-milling of rectangular bronze microchannels was carried out with carbide end mills with a diameter of 1 mm, processed with fast argon atoms, and coated with anti-friction wear-resistant titanium diboride. It was shown that the removal of a 3 µm thick surface layer from a micro end mill with fast argon atoms makes it possible to reduce the cutting edge radius of the tool to 1.2 µm, which is three times lower than the minimum value of 4 µm achievable in mechanical manufacturing. The subsequent deposition of a 3 μm thick anti-friction coating results in a wear-resistant micro end mill with original geometric parameters but improved performance. The surface roughness of the machined bronze microchannel significantly decreased, and the burrs above the groove practically disappeared after micro-milling.

This paper examines the effectiveness of provincially enacted policies to deter the COVID-19 mortality rate during the pre-vaccine rollout pandemic in Canada. The data has been collected from Statistics Canada and other various online resources including the Blavatnik School of Government and provincial statements. Relevant information was collected for individual provinces from 11 March 2020 to 31 Jan 2021. A two-stage least squares methodology was applied by examining, by province, the cumulative number of deaths reported as due to COVID-19 before and after policy implementation. We examine the effect of each of several policies based on a 20 plus day lagged period after being put into place. Our main finding is that workplace closures and strict gathering restrictions are associated with a decrease in mortality rates of COVID-19 in Canada. We also find that the strength of the policies overall is associated with a decrease in mortality rates of COVID-19 in Canada. Using data from the Google Mobility Report we confirm that the announcements of the policies had significant behavioural effects on individuals’ movements. We interpret that social distance policies, specifically the workplace closure and strict gathering policies, have been effective factors decreasing mortality from the Coronavirus epidemic in Canada.

Debriefing is a critical element in healthcare, both in the clinical environment and in the simulation lab. Often, what is said at a debriefing is not recorded, leading to loss of critical data that could be used to inform future simulations, education, and systems improvement. In this perspective piece, we explain the powerful role that capturing debriefing data can have for identifying themes to improve learners’ knowledge and skills, as well as inform data-driven systems change and initiatives.

Long non-coding RNAs (lncRNAs) have emerged as fundamental regulators in various biological processes, including embryonic development and cellular differentiation. Despite much progress over the past decade, the genome-wide annotation of lncRNAs remains incomplete and many known non-coding loci are still poorly characterized. Here, we report the discovery of a previously unannotated lncRNA that is transcribed 230 kb upstream of the SOX17 gene and located within the same topologically associating domain. We termed it T-REX17 (Transcript Regulating Endoderm and activated by soX17) and show that it is induced following SOX17 activation but its expression is more tightly restricted to early definitive endoderm. Loss of T-REX17 affects crucial functions independent of SOX17 and leads to an aberrant endodermal transcriptome, signaling pathway deregulation and epithelial to mesenchymal transition defects. Consequently, cells lacking the lncRNA cannot further differentiate into more mature endodermal cell types. Taken together, our study identified and characterized T-REX17 as a transiently expressed and essential non-coding regulator in early human endoderm differentiation.

While affordance detection and Human-Object interaction (HOI) detection tasks are related, the theoretical foundation of affordances makes it clear that the two are distinct. In particular, researchers in affordances make distinctions between J. J. Gibson's traditional definition of an affordance, “the action possibilities” of the object within the environment, and the definition of a telic affordance, or one defined by conventionalized purpose or use. We augment the HICO-DET dataset with annotations for Gibsonian and telic affordances and a subset of the dataset with annotations for the orientation of the humans and objects involved. We then train an adapted Human-Object Interaction (HOI) model and evaluate a pre-trained viewpoint estimation system on this augmented dataset. Our model, AffordanceUPT, is based on a two-stage adaptation of the Unary-Pairwise Transformer (UPT), which we modularize to make affordance detection independent of object detection. Our approach exhibits generalization to new objects and actions, can effectively make the Gibsonian/telic distinction, and shows that this distinction is correlated with features in the data that are not captured by the HOI annotations of the HICO-DET dataset.

This article describes a copy of Osip Mandelstam’s Stone with the author’s notes and variants of the poems. It mentions V.I. Ivanov, O.A. Glebova-Sudeikina, the Timofeev family.

Abstract Previous work indicates that SARS-CoV-2 virus entry proteins angiotensin-converting enzyme 2 (ACE-2) and the cell surface transmembrane protease serine 2 (TMPRSS-2) are regulated by sex hormones. However, clinical studies addressing this association have yielded conflicting results. We sought to analyze the impact of sex hormones, age, and cardiovascular disease on ACE-2 and TMPRSS-2 expression in different mouse models. ACE-2 and TMPRSS-2 expression was analyzed by immunostaining in a variety of tissues obtained from FVB/N mice undergoing either gonadectomy or sham-surgery and being subjected to ischemia–reperfusion injury or transverse aortic constriction surgery. In lung tissues sex did not have a significant impact on the expression of ACE-2 and TMPRSS-2. On the contrary, following myocardial injury, female sex was associated to a lower expression of ACE-2 at the level of the kidney tubules. In addition, after myocardial injury, a significant correlation between younger age and higher expression of both ACE-2 and TMPRSS-2 was observed for lung alveoli and bronchioli, kidney tubules, and liver sinusoids. Our experimental data indicate that gonadal hormones and biological sex do not alter ACE-2 and TMPRSS-2 expression in the respiratory tract in mice, independent of disease state. Thus, sex differences in ACE-2 and TMPRSS-2 protein expression observed in mice may not explain the higher disease burden of COVID-19 among men.

Whereas the O104:H4 enterohemorrhagic Escherichia coli (EHEC) outbreak strain from 2011 expresses aggregative adherence fimbriae of subtype I (AAF/I), its close relative, the O104:H4 enteroaggregative Escherichia coli (EAEC) strain 55989, encodes AAF of subtype III. Tight adherence mediated by AAF/I in combination with Shiga toxin 2 production has been suggested to result in the outbreak strain’s exceptional pathogenicity. Furthermore, the O104:H4 outbreak strain adheres significantly better to cultured epithelial cells than archetypal EAEC strains expressing different AAF subtypes. To test whether AAF/I expression is associated with the different virulence phenotypes of the outbreak strain, we heterologously expressed AAF subtypes I, III, IV, and V in an AAF-negative EAEC 55989 mutant and compared AAF-mediated phenotypes, incl. autoaggregation, biofilm formation, as well as bacterial adherence to HEp-2 cells. We observed that the expression of all four AAF subtypes promoted bacterial autoaggregation, though with different kinetics. Disturbance of AAF interaction on the bacterial surface via addition of α-AAF antibodies impeded autoaggregation. Biofilm formation was enhanced upon heterologous expression of AAF variants and inversely correlated with the autoaggregation phenotype. Co-cultivation of bacteria expressing different AAF subtypes resulted in mixed bacterial aggregates. Interestingly, bacteria expressing AAF/I formed the largest bacterial clusters on HEp-2 cells, indicating a stronger host cell adherence similar to the EHEC O104:H4 outbreak strain. Our findings show that, compared to the closely related O104:H4 EAEC strain 55989, not only the acquisition of the Shiga toxin phage, but also the acquisition of the AAF/I subtype might have contributed to the increased EHEC O104:H4 pathogenicity.

Abstract Background The value of mechanical circulatory support (MCS) in cardiogenic shock, especially the combination of the ECMELLA approach (Impella combined with ECMO), remains controversial. Case presentation A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The patient was tested positive for type-A influenza, however negative for SARS-CoV-2. Despite escalated invasive ventilation, refractory hypercapnia (paCO2: 22 kPa) with severe respiratory acidosis (pH: 6.9) and a rising norepinephrine rate occurred within a few hours. Due to a Horovitz-Index

Abstract We present novel co-created transdisciplinary research that uses arts and humanities methods to explore air pollution in an informal settlement (Mukuru) in Nairobi, Kenya. Air pollution is a well-documented major human health issue, but despite many air pollution reduction interventions designed to improve health, these are frequently ineffective. Often this is because they fail to account for local knowledge, cultural practices and priorities of the intended recipients. Designing solutions therefore requires in-depth exploration of relevant issues with stakeholders. Researchers worked collaboratively with local residents to develop a range of methods to explore understandings of air pollution including interviews, storytelling, participatory mapping and theatre. Together, we uncovered contrasting definitions of air pollution, differing perceptions of who was responsible for enacting solutions, and overall a view that air pollution cannot be seen in isolation from the other issues faced by settlement residents. The methods used also allowed us to communicate about the topic with a wide audience. While we acknowledge that this research approach is more time consuming than traditional approaches, we urge other researchers wishing to address multifactorial problems, such as air pollution to use a mixture of qualitative, participatory and creative methods to engage with a wide range of stakeholders to elicit new and unexpected understandings that may not otherwise emerge.

The experience of most countries confirms that the development of modern information technologies does not reduce people's interest in books. The demand for publishing products remains stable, and in the context of the dynamic development of the digital economy and the priority of information as a resource for sustainable development, it is even growing. Thus, in the EU countries, 6 to 8 books are published per capita per year. In Ukraine, there are significantly different trends, because in 2020 the annual circulation of books in Ukraine amounted to 20.2 million copies, that is, 0.48 copies of books and brochures per one inhabitant of Ukraine. Under such conditions, the development of publishing entities requires strategic and conceptual organizational and financial support from the state in the context of more efficient use of limited financial resources. Since 2005, Ukraine has been implementing the "Ukrainian Book" program, which along with providing tax benefits to publishers and book distributors is a form of state support for publishing. The results of the audit of the effectiveness of the use of funds proved that the effectiveness of the use of state budget funds is not high enough, in particular due to the imperfection of the criteria for selecting publications. Based on the results of the study, a list of such criteria was formed. The methodological principles of expert evaluation of book publications declared by the subject of publishing business in accordance with the established criteria for the selection of book products using points have been formed. An evaluation scale based on the selection criteria was developed. Additional characteristics that specify the main criteria for selecting publications included in the program and financed from the budget are proposed. The number of the expert group (7-15 persons) is substantiated, which ensures the reliability of the examination. The developed methodological and practical principles are intended to partially solve the existing problems by establishing scientifically based criteria for more efficient use of state budget funds and satisfying the reading interest of Ukrainian citizens.

The aim of this study is to contribute to the growing literature on electronic participation (e-participation), by analysing various scenarios of participation. The main goal is to gain further insight into the role of perceived advantages concerning citizens’ willingness to engage in digital and non-digital participation. While several studies have identified advantages of e-participation compared to traditional, non-digital alternatives, little research has been conducted into how the perception of these advantages influences citizen willingness to engage in e-participation. This study examines three participation scenarios with different levels of citizen participation. We use a logistic regression model to analyse our data. The findings reveal new insights for both research and practice. First, the results show that simplicity, time savings, location independence, and cost reduction are generally considered to be advantages of e-participation. By comparison, data security and data protection are seen to be advantages of non-digital participation. However, only cost reduction and simplicity have a positive influence on citizens’ willingness to engage in all three scenarios. Additionally, when data security was perceived as an advantage of e-participation, the likelihood of preferring digital over non-digital participation was higher. This is true for the two scenarios with higher participation levels. These findings differ from those in previous studies and raise questions regarding the impact that the participation level has on the results. By studying this topic further, valuable insights can be gained into how governments can use and promote e-participation. Abstrakt Das Ziel dieser Studie ist es, einen Beitrag zur Literatur über E-Partizipation zu leisten, indem verschiedene Szenarien der Beteiligung analysiert werden. Genauer gesagt geht es darum, weitere Erkenntnisse über die Rolle der wahrgenommenen Vorteile in Bezug auf die Bereitschaft der Bürger und Bürgerinnen zur digitalen und nicht-digitalen Partizipation zu gewinnen. Während es verschiedene Studien gibt, die die Vorteile von E-Partizipation im Vergleich zu traditionellen, nicht-digitalen Alternativen aufzeigen, gibt es wenig Forschung darüber, wie die Wahrnehmung dieser Vorteile die Bereitschaft der Bürgerinnen und Bürger beeinflusst, sich an E-Partizipation zu beteiligen. In dieser Studie werden drei Beteiligungsszenarien mit unterschiedlichen Partizipationslevels untersucht. Wir verwenden ein logistisches Regressionsmodell, um unsere Daten zu analysieren. Die Ergebnisse liefern neue Erkenntnisse sowohl für die Forschung als auch für die Praxis. Zunächst zeigen die Ergebnisse, dass Einfachheit, Zeitersparnis, Ortsunabhängigkeit und Kostenreduzierung allgemein als Vorteile von E-Partizipation angesehen werden. Im Vergleich dazu werden Datensicherheit und Datenschutz als Vorteile der nicht-digitalen Beteiligung gesehen. Allerdings haben in allen drei Szenarien nur die Kostenreduktion und die Einfachheit einen positiven Einfluss auf die Bereitschaft, sich digital zu beteiligen. Wurde zudem die Datensicherheit als Vorteil der E-Partizipation wahrgenommen, führt dies auch zu einer höheren Wahrscheinlichkeit, die digitale gegenüber der nicht-digitalen Beteiligung zu bevorzugen. Dies gilt für die beiden Szenarien mit höherem Partizipationslevel. Diese Ergebnisse weichen von früheren Studien ab und werfen die Frage auf, welchen Einfluss das Partizipationslevel auf die Ergebnisse hat. Durch weitere Studien können wichtige Erkenntnisse für politisch Verantwortliche gewonnen werden, wie sie E-Partizipationsinitiativen nutzen und fördern können. Abstraite L‘objectif de cette étude est de contribuer à la littérature croissante sur laparticipation électronique (ou : numérique) en analysant différents scénarios de participation. Plus précisément, il s‘agit d‘acquérir des connaissances supplémentaires sur les avantages perçus en ce qui concerne la disposition (besser : disponibilité/volonté) des citoyens à participer de manière numérique ou non. Alors qu‘il existe plusieurs études montrant les avantages de la participation électronique par rapport aux alternatives traditionnelles non numériques, il existe peu de recherches sur la manière dont la perception de ces avantages influence la volonté des citoyens de participer électroniquement. Dans cette étude, nous examinons trois scénarios de participation avec différents niveaux de participation. Nous utilisons un modèle de régression logistique pour analyser nos données. Les résultats fournissent de nouvelles informations tant pour la recherche que pour la pratique. Tout d‘abord, les résultats montrent que la simplicité, le gain de temps, l‘indépendance du lieu et la réduction des coûts sont généralement considérés comme des avantages de laparticipation électronique. En comparaison, la sécurité des données et la protection des données sont considérées comme des avantages de la participation non numérique. Toutefois, dans les trois scénarios, seule la réduction des coûts et la simplicité ont une influence positive sur la volonté de participer numériquement. Si, en outre, la sécurité des données a été perçue comme un avantage de la participation électronique, cela conduit également à une probabilité plus élevée de préférer la participation numérique à la participation non numérique. Cela vaut pour les deux scénarios avec un niveau de participation plus élevé. Ces résultats diffèrent des études précédentes et soulèvent la question de l‘influence du niveau de participation sur les résultats. D‘autres études permettront de tirer des enseignements importants pour les responsables politiques sur la manière d‘utiliser et de promouvoir les initiatives de la participation électronique. Schlüsselbegriffe: E-Partizipation; nicht-digitale Beteiligung; E-Government; Deliberation Mots-clés: e-Participation/participation électronique; participation non numérique; gouvernement électronique; délibération

ABSTRACT Infection clusters of multidrug-resistant bacteria increase mortality and entail expensive infection control measures. Whereas whole-genome sequencing (WGS) is the current gold standard to confirm infection clusters, PCR-based assays targeting cluster-specific signatures, such as single nucleotide polymorphisms (SNPs) derived from WGS data, are more suitable to initially screen for cluster isolates within large sample sizes. Here, we evaluated four software tools (SeqSphere+, RUCS, Gegenees, and Find Differential Primers) regarding their efficiency to find SNPs within WGS data sets that were specific for two bacterial monospecies infection clusters but were absent from a WGS reference data set comprising several hundred diverse genotypes of the same bacterial species. Cluster-specific SNPs were subsequently used to establish a probe-based real-time PCR screening assay for in vitro differentiation between cluster and noncluster isolates. SeqSphere+ and RUCS found 2 and 24 SNPs for clusters 1 and 14 and 24 SNPs for cluster 2, respectively. However, some signatures detected by RUCS were not cluster specific. Interestingly, all SNPs identified by SeqSphere+ were also detected by RUCS. In contrast, analyses with the remaining tools either resulted in no SNPs (with Find Differential Primers) or failed (Gegenees). Design of six cluster-specific real-time PCR assays enabled reliable cluster screening in vitro. Our evaluation revealed that SeqSphere+ and RUCS identified cluster-specific SNPs that could be used for large-scale screening in surveillance samples via real-time PCR, thereby complementing WGS efforts. This faster and simplified approach for the surveillance of bacterial clusters will improve infection control measures and will enhance protection of patients and physicians. IMPORTANCE Infection clusters of multidrug-resistant bacteria threaten medical facilities worldwide and cause immense health care costs. In recent years, whole-genome sequencing (WGS) has been increasingly applied to detect and to further control bacterial clusters. However, as WGS is still expensive and time-consuming, its exclusive application for screening and confirmation of bacterial infection clusters contributes to high costs and enhanced turnaround times, which many hospitals cannot afford. Therefore, there is need for alternative methods that can enable further surveillance of bacterial clusters that are initially detected by WGS in a faster and more cost-efficient way. Here, we established a system based on real-time PCR that enables rapid large-scale sample screening for bacterial cluster isolates within 7 days after the initial detection of an infection cluster, thereby complementing WGS efforts. This faster and simplified surveillance of bacterial clusters will improve infection control measures and will enhance protection of patients and physicians.