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BackgroundVirtual reality (VR) is increasingly being used in higher education for clinical skills training and role-playing among health care students. Using 360° videos in VR headsets, followed by peer debrief and group discussions, may strengthen students’ social and emotional learning. ObjectiveThis study aimed to explore student-perceived usability of VR simulation in three health care education programs in Norway. MethodsStudents from one university participated in a VR simulation program. Of these, students in social education (n=74), nursing (n=45), and occupational therapy (n=27) completed a questionnaire asking about their perceptions of the usability of the VR simulation and the related learning activities. Differences between groups of students were examined with Pearson chi-square tests and with 1-way ANOVA. Qualitative content analysis was used to analyze data from open-ended questions. ResultsThe nursing students were most satisfied with the usability of the VR simulation, while the occupational therapy students were least satisfied. The nursing students had more often prior experience from using VR technology (60%), while occupational therapy students less often had prior experience (37%). Nevertheless, high mean scores indicated that the students experienced the VR simulation and the related learning activities as very useful. The results also showed that by using realistic scenarios in VR simulation, health care students can be prepared for complex clinical situations in a safe environment. Also, group debriefing sessions are a vital part of the learning process that enhance active involvement with peers. ConclusionsVR simulation has promise and potential as a pedagogical tool in health care education, especially for training soft skills relevant for clinical practice, such as communication, decision-making, time management, and critical thinking.

OBJECTIVE: The aim of the study was to investigate the longitudinal association between multi-dimensionally measured precarious employment (PE) trajectories and mental health among older employees in Germany. METHODS: Current data from the German lidA study was used, including panel cases, who participated in all four survey waves (2011, 2014, 2018, 2022). The study comprised 1636 subjects, aged 46 and 52 years at baseline. Group-based trajectory modelling was used to model PE trajectories based on a score combining multiple items from the dimensions employment insecurity and income inadequacy. The association between PE trajectories (2011–2022) and mental health (2022) was tested using weighted logistic regression. RESULTS: We identified a PE trajectory with upward movement that best described 13.6% of the study sample. Representation in this group was socially unequally distributed with noticeably larger shares of female, lower-educated and lower-skilled workers in PE. Women following this trajectory had increased odds [odds ratio (OR) 1.68–1.82] of reporting poor mental health in 2022 compared to their counterparts in constant non-PE. This was not the case for men (OR 0.37–0.51). CONCLUSIONS: Our findings highlight horizontal and vertical inequalities with respect to exposure to and consequences of PE. Future labor market reforms should improve protection of women, who will likely be disadvantaged by accumulating employment-related mental health risks over the course of their lives.

ObjectiveThis study aimed to validate the newly developed composite acceptability endpoint to investigate acceptability of oral pediatric drug formulations that integrates swallowability and palatability assessments.MethodsIn this open-label study acceptability of oral formulations was tested in three age groups (1–

Purpose: The impact of winter moisture on root metabolism and root integrity has potential consequences for the geographical distribution of drought-adapted succulent species and for their long-term performance on green roofs. The interacting effects of soil characteristics and precipitation frequency on root mortality under winter conditions and the potential to grow new roots in spring were evaluated for six Sedum species under controlled conditions. Methods: To test for the impact of soil moisture during winter on root regrowth potential in six Sedum species, we used a combination of two substrates with differing water-holding capacity and four contrasting watering regimes. Specially, for the fine and coarse substrates, total pore volume was 42 and 46 %, respectively, and maximum water-holding capacity (i.e. field capacity) was 0.50 and 0.33 kg water per L, respectively. The four watering treatments involved overhead watering to runoff (approx. 10 mm): once every second week, once a week, three times per week and three times per week with 1 cm standing water in trays from January to March 2019. Results: It was found that winter soil moisture had no major impact on root mortality or root regrowth potential in spring. Root mortality was not affected by watering frequency and regrowth potential showed no directional response to increased watering frequency, although species-specific responses were involved. Root diameter did not differ between the substrates, but there were some differences between the species. Sedum rupestre had on average the thickest roots (0.17 mm), followed by S. acre, S. anglicum and S. sexangulare (0.15–0.16 mm), while S. album and S. hispanicum had the thinnest roots (0.12–0.13 mm). Moreover, effects of watering frequency on root mortality and regrowth potential were not influenced by soil water-holding capacity across species. We concluded that winter soil moisture had no negative effects on root performance within the range of treatments tested here. Conclusions: Root response to transient waterlogging or moist but unsaturated soil may not be an important mechanism for determining the survival and distribution of temperate Sedum species during winter.

Abstract Metadata from epidemiological studies, including chronic disease outcome metadata (CDOM), are important to be findable to allow interpretability and reusability. We propose a comprehensive metadata schema and used it to assess public availability and findability of CDOM from German population-based observational studies participating in the consortium National Research Data Infrastructure for Personal Health Data (NFDI4Health). Additionally, principal investigators from the included studies completed a checklist evaluating consistency with FAIR principles (Findability, Accessibility, Interoperability, Reusability) within their studies. Overall, six of sixteen studies had complete publicly available CDOM. The most frequent CDOM source was scientific publications and the most frequently missing metadata were availability of codes of the International Classification of Diseases, Tenth Revision (ICD-10). Principal investigators’ main perceived barriers for consistency with FAIR principles were limited human and financial resources. Our results reveal that CDOM from German population-based studies have incomplete availability and limited findability. There is a need to make CDOM publicly available in searchable platforms or metadata catalogues to improve their FAIRness, which requires human and financial resources.

Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

To facilitate nutrient management and the use of manure as a feedstock for biogas production, manure is often separated into a solid and a liquid fraction. The former fraction is usually high in P and low in N, so when incorporated in the soil as fertilizer, it needs to be supplemented by N from, e.g., mineral fertilizers or nitrogen-fixing species. To explore strategies to manage N with solid-separated manure, we examined how the amount of digestate and the N:P ratio of pig digestate, i.e., manure that had partially undergone anaerobic digestion, affected the productivity of Westerwolds ryegrass and red clover in a pot experiment with one soil which was rich and another which was poor in plant nutrients. The soil and plant species treatments were combined with four doses of digestate, which gave plant available phosphorus (P) concentrations of 2, 4, 8, or 16 mg P100 g−1 soil. Ammonium nitrate was dosed to obtain factorial combinations of digestate amount and N:P ratios of 1.8, 4, 8, and 16. Clover was harvested once at the beginning of flowering (15 weeks after seeding), while Westerwolds ryegrass was allowed to regrow three times after being cut at the shooting stage (in total, 4 cuts, 6, 9, 12, and 15 weeks after seeding). Ryegrass yield increased by up to 2.9 times with digestate dosage. Interactions with the N:P ratio and soil type were weak. Hence, the effect of increasing the N:P ratio was additive across digestate dosages. Red clover biomass also increased by up to 39% with digestate dosage. Residual nutrients in the soil after red clover cultivation were affected by the initial differences in soil characteristics but not by digestate treatment or biomass of harvested red clover. A targeted N management is required to benefit from the P-rich digestate in grass cultivation, while the long-term effects of red clover culture on N input need further investigation.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Summary: Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

Abstract Analysis of selected cancer genes has become an important tool in precision oncology but cannot fully capture the molecular features and, most importantly, vulnerabilities of individual tumors. Observational and interventional studies have shown that decision-making based on comprehensive molecular characterization adds significant clinical value. However, the complexity and heterogeneity of the resulting data are major challenges for disciplines involved in interpretation and recommendations for individualized care, and limited information exists on how to approach multilayered tumor profiles in clinical routine. We report our experience with the practical use of data from whole-genome or exome and RNA sequencing and DNA methylation profiling within the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) program of the National Center for Tumor Diseases (NCT) Heidelberg and Dresden and the German Cancer Research Center (DKFZ). We cover all relevant steps of an end-to-end precision oncology workflow, from sample collection, molecular analysis, and variant prioritization to assigning treatment recommendations and discussion in the molecular tumor board. To provide insight into our approach to multidimensional tumor profiles and guidance on interpreting their biological impact and diagnostic and therapeutic implications, we present case studies from the NCT/DKFZ molecular tumor board that illustrate our daily practice. This manual is intended to be useful for physicians, biologists, and bioinformaticians involved in the clinical interpretation of genome-wide molecular information.

Gravure printing is a type of printing method that uses metal cylinders with engraved cells that hold ink. The ink is transferred directly to the paper or other material by pressing it against the cylinder. The flow associated with gravure printing includes a flow in a liquid bridge formed in the contact region of the cylinders and a thin-film coating flow of the ink. The flow is governed by viscous and capillary forces. In many cases, the flow is unstable, which leads to the formation of instability patterns on the printed surfaces. The analysis of these instabilities is a very challenging problem, especially since industrial inks are usually rheologically complex. In this experimental and theoretical study, the flow of inks on a rotating cylinder is analysed, accounting for the shear-rate-dependent liquid viscosity. A theoretical solution for the film flow allows us to predict the width of the liquid bridge between two cylinders. Moreover, it is shown that the measured characteristic size of the printed pattern is of the same order as the predicted liquid bridge width. We observe a nearly linear dependence of pattern size and liquid bridge width.

Introduction: The World Health Organization (WHO)'s Research and Development (R&D) Blueprint for Action to Prevent Epidemics, a plan of action, highlighted several infectious diseases as crucial targets for prevention. These infections were selected based on a thorough assessment of factors such as transmissibility, infectivity, severity, and evolutionary potential. In line with this blueprint, the VACCELERATE Site Network approached infectious disease experts to rank the diseases listed in the WHO R&D Blueprint according to their perceived risk of triggering a pandemic. VACCELERATE is an EU-funded collaborative European network of clinical trial sites, established to respond to emerging pandemics and enhance vaccine development capabilities. Methods: Between February and June 2023, a survey was conducted using an online form to collect data from members of the VACCELERATE Site Network and infectious disease experts worldwide. Participants were asked to rank various pathogens based on their perceived risk of causing a pandemic, including those listed in the WHO R&D Blueprint and additional pathogens. Results: A total of 187 responses were obtained from infectious disease experts representing 57 countries, with Germany, Spain, and Italy providing the highest number of replies. Influenza viruses received the highest rankings among the pathogens, with 79 % of participants including them in their top rankings. Disease X, SARS-CoV-2, SARS-CoV, and Ebola virus were also ranked highly. Hantavirus, Lassa virus, Nipah virus, and henipavirus were among the bottom-ranked pathogens in terms of pandemic potential. Conclusion: Influenza, SARS-CoV, SARS-CoV-2, and Ebola virus were found to be the most concerning pathogens with pandemic potential, characterised by transmissibility through respiratory droplets and a reported history of epidemic or pandemic outbreaks.

Background: Health technology assessment (HTA) bodies across Europe rely on explicit factors for decision making. However, additional undefined factors play a role. This mixed-methods research aimed to identify the implicit factors involved in HTA deliberative processes in five European countries, and to analyze their impact on decision making. Methods: Between February and May 2021, semi-structured interviews (n = 20) were conducted with HTA experts of three different profiles (chair, advisor, and committee member) from France, Germany, Italy, Spain, and the United Kingdom. The degree of influence of a set of implicit factors and attributes that play a role in the HTA deliberative process, as previously identified in a systematic literature review, was scored by the experts. Experts were also asked to make recommendations on ways of improving the deliberative process. A qualitative analysis and descriptive statistics of quantitative variables are reported. Results: Most (18/20) experts concurred that implicit factors play a role in the HTA deliberative process. Recommendations for improving the process fell into three categories: transparency, methodology improvement, and stakeholder involvement. The results suggest a need for 1) increased external involvement HTA and 2) development of a methodology to mitigate the influence of implicit factors in the deliberative process. This could be achieved by updating the current frameworks to acknowledge these implicit factors and by developing methods to address them.

Objective: To predict the required mitral annular area reduction in patients with Barlow's disease to obtain a predefined leaflet area index by a novel in silico modeling method. Methods: Three-dimensional echocardiography was used to create patient-specific mitral valve models of 8 patients diagnosed with Barlow's disease and bileaflet prolapse preoperatively. Six patients were also studied postoperatively in a finite element framework, to quantify the optimal coaptation area index. For the patient-specific finite element analyses, realistic papillary muscle and annular motion are incorporated, also for the in silico annuloplasty analyses. The annuloplasty ring size is reduced moderately until the optimal coaptation area index is achieved for each patient. Results: The mean mitral annular area at end-diastole was reduced by 58 ± 7% postoperatively (P

Abstract In times of demographic change, better job quality is needed to promote health and thereby extend employment participation among older workers. Past research has focussed on the investigation of single job quality characteristics, but neglected their combined effects on health and employment. To address this limitation, we have built upon an established typology based on nine job quality characteristics and representing five profiles of overall poor or good job quality constellations among manual and non-manual older workers, respectively. It was investigated how constant and changing job quality affects non-employment and how mental and physical health mediate this association. Analyses were based on representative data from N = 2,952 employees born in 1959 or 1965, who participated in all current waves (in the years 2011, 2014 and 2018) of the German lidA cohort study. Job quality was measured in 2011 and 2014 according to profile assignment per wave, composite mental and physical health scores from 2014 were used as mediators and non-employment (vs. employment) in 2018 represented the outcome. Two separate mediation models were calculated, one for manuals and one for non-manuals. Among manuals with constantly poor job quality, the risk of non-employment was increased through both poor mental and physical health. Deteriorating job quality increased this risk through poor mental health, while changing from manual to non-manual work reduced this risk through better physical health. Among non-manuals, poor job quality was not related to the risk of non-employment and no health effects were found to significantly mediate such a risk. In conclusion, the health risks of poor later-life job quality demand critical consideration to maintain employability, particularly of manual workers in poor quality jobs. Timely workplace improvements for certain groups are needed to increase employment participation in good health, thereby increasing efficiency and fairness of measures promoting longer working lives.

Abstract Establishing the optimal treatment for COVID-19 patients remains challenging. Specifically, immunocompromised and pre-diseased patients are at high risk for severe disease course and face limited therapeutic options. Convalescent plasma (CP) has been considered as therapeutic approach, but reliable data are lacking, especially for high-risk patients. We performed a retrospective analysis of 55 hospitalized COVID-19 patients from University Hospital Duesseldorf (UKD) at high risk for disease progression, in a substantial proportion due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis. A matched-pairs analysis (1:4) was performed with 220 patients from the Lean European Open Survey on SARS-CoV-2-infected Patients (LEOSS) who were treated or not treated with CP. Both cohorts had high mortality (UKD 41.8%, LEOSS 34.1%). A matched-pairs analysis showed no significant effect on mortality. CP administration before the formation of pulmonary infiltrates showed the lowest mortality in both cohorts (10%), whereas mortality in the complicated phase was 27.8%. CP administration during the critical phase revealed the highest mortality: UKD 60.9%, LEOSS 48.3%. In our cohort of COVID-19 patients with severe comorbidities CP did not significantly reduce mortality in a retrospective matched-pairs analysis. However, our data supports the concept that a reduction in mortality is achievable by early CP administration.

Abstract Synchrotron X-ray computed tomography (SXCT) allows 3D imaging of tissue with a very large field of view and an excellent micron resolution and enables the investigation of muscle fiber atrophy in 3D. The study aimed to explore the 3D micro-architecture of healthy skeletal muscle fibers and muscle fibers at different stages of atrophy (stroke sample = muscle atrophy; spinal cord injury (SCI) sample = severe muscle atrophy). Three muscle samples: a healthy control sample; a stroke sample (atrophic sample), and an SCI sample (severe atrophic sample) were imaged using SXCT, and muscle fiber populations were segmented and quantified for microarchitecture and morphology differences. The volume fraction of muscle fibers was 74.7%, 70.2%, and 35.3% in the healthy, stroke (atrophic), and SCI (severe atrophic) muscle fiber population samples respectively. In the SCI (severe atrophic sample), 3D image analysis revealed fiber splitting and fiber swelling. In the stroke sample (atrophic sample) muscle fiber buckling was observed but was only visible in the 3D analysis. 3D muscle fiber population analysis revealed new insights into the different stages of muscle fiber atrophy not to be observed nor quantified with a 2D histological analysis including fiber buckling, loss of fibers and fiber splitting.

In his “The Star of Redemption”, Rosenzweig engages not only in an argument with philosophy, but also with theology. Next to Augustine and Friedrich Schleiermacher Martin Luther was a counterpart in whose face he developed his dialogical “new thinking”. The essay takes up the traces of this dispute in the letters to focus here on Rosenzweig's reading of Ricarda Huch's “Luther’s Faith”. This literary picture is then related in a sketch to Luther's Reformation theology as it emerges from contemporary research. In a next step, the “Star” is interpreted as a book that, on the one hand, owes much to a previous reception of Luther, but on the other hand, also shows the Reformator's thinking in a new light. Finally, the late writings on the problem of translation come into view in order to justify Rosenzweig’s “Verdeutschung” of the Hebrew Bible, undertaken together with Buber, to Luther’s “German Bible”.

OBJECTIVE: The aim of this study was to investigate the contribution of work factors, health, and work ability to social inequalities in early exit from employment among older employees in Germany. METHODS: Longitudinal data from the representative German lidA Cohort study was linked with employment register data to obtain maximum information on exit routes out of paid employment. Information of N=2438 respondents, aged 46 and 52 at baseline, were obtained for a follow-up of six years (2011–2017). Causal mediation analysis with inverse odds weighting was conducted using discrete-time survival outcomes and baseline measurements of the socioeconomic status (SES: education), work factors, health, and work ability. RESULTS: Older employees with low SES were at an increased risk of exiting employment early by receiving disability pension and through long-term unemployment but not through an unspecified labor market exit when compared to those with high and moderate SES. Low work ability accounted for up to 38% of the social inequalities in work exits into disability pension. Less-than-good physical health accounted for up to 59% of inequalities in work exits into long-term unemployment. Work factors contributed considerably to inequalities in exits through unemployment but not disability pension. CONCLUSIONS: This study finds social inequalities in early exits through disability pension and long-term unemployment among older employees in Germany, predominantly attributable to differences in work ability (disability pension) and physical health (unemployment). Investments in work ability and promotion of physical health may constitute promising approaches to counteract an increase of these inequalities.

Objectives: In resource-limited settings, intestinal Cryptosporidial or coccidian infections are common causes of chronic diarrhea but usually remain undiagnosed by routine stool investigation. Here, the addition of the Kinyoun staining technique after stool concentration was evaluated as an easy and inexpensive method for diagnosis of intestinal parasitic infection in patients with HIV. Methods: This cross-sectional study investigated patients with HIV with diarrhea and randomly selected patients with HIV without diarrhea as controls. Stool samples were examined by wet mount microscopy and Kinyoun staining after stool concentration. Clinical, sociodemographic, and behavioral data were collected. Statistical analysis was performed using chi-squared test and multivariate regression analysis. Results: In total, 163 participants were included (62.0% female, mean age 38.2 [SD ± 10.7] years). Diarrhea was present in 52.1% (85/163). The prevalence of intestinal parasites was 18.4% (30/163). Cryptosporidial infections were more frequent among patients with diarrhea (12.9% [11/85] vs 1.3% [1/78], P = 0.005) and in patients with CD4+ cell count

Although drug acceptability can have a significant impact on patient adherence in pediatric therapy, data are limited, even for common therapeutic areas. We present the second part of an acceptability study conducted at the University Children’s Hospital Düsseldorf, Germany. The study investigated the acceptability of most commonly used antibiotics in a pediatric hospital setting. The researchers used the acceptability reference framework to score the acceptability of five antibiotics based on 150 real-life observer reports of medicine intake. Four antibiotics assessed in this study were formulated as preparations for injection (ampicillin, ampicillin/sulbactam, ceftriaxone, and gentamicin) and one as a powder for oral liquid suspension (co-amoxiclav). All the antibiotics formulated as preparations for injection were rated negatively due to high rates of negative reactions (80%), the use of restraint (51%), the use of extra devices (99%), and long preparation and administration times (100%). The antibiotic formulated as a powder was significantly more well accepted. The study concluded that there is a lack of appropriate formulations for antibiotics for use in children. These findings are important in improving knowledge on acceptability drivers and might help in formulating and prescribing better medicines for children. The study highlights the need for healthcare professionals to have knowledge about the acceptability of different products to select the best-adapted product for each patient.

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition with uncontrolled activation of lymphocytes and macrophages. Besides a primary (genetic) form, HLH can also be triggered by malignant, autoimmune and infectious diseases. HLH recurrences are rarely described, usually only in primary HLH. Parvovirus B19 (PVB19) Infection is one of the rare and rather benign causes of HLH. Since the infection usually results in long-lasting immunity, recurrent viremia is very uncommon. Case presentation We report an unusual case of a young female with recurrent PVB19 infection that led to repeated episodes of HLH. The first episode occurred at the age of 25 years with a three-week history of high fever and nonspecific accompanying symptoms. The diagnosis of HLH was confirmed by HLH-2004 criteria and HScore, PVB19 viremia was detected as underlying cause. Following guideline-based therapy, the patient was symptom-free for one year, before similar symptoms recurred in a milder form. Again, PVB19 was detected and HLH was diagnosed according to HScore. After successful treatment and a nine-month symptom-free interval, a third phase of hyperinflammation with low PVB19 viremia occurred; this time, treatment with a corticosteroid and intravenous immunoglobulin was initiated before the presence of clear diagnostic criteria for HLH. No further events occurred in the following three years. Conclusions In the case of our patient, the recurrent viremia triggered three episodes of hyperinflammation, two of which were clearly diagnosed as HLH. To our knowledge, this is the first published case of recurrent HLH due to PVB19 infection. Therefore, the case gives new insights in triggering mechanisms for HLH.

Abstract The purpose of this study was to investigate the effects of loading conditions and left ventricular (LV) contractility on mitral annular dynamics. In 10 anesthetized pigs, eight piezoelectric transducers were implanted equidistantly around the mitral annulus. High‐fidelity catheters measured left ventricular pressures and the slope of the end‐systolic pressure‐volume relationship (Ees) determined LV contractility. Adjustments of pre‐ and afterload were done by constriction of the inferior caval vein and occlusion of the descending aorta. Mitral annulus area indexed to body surface area (MAAi), annular circularity index (ACI), and non‐planarity angle (NPA) were calculated by computational analysis. MAAi was more dynamic in response to loading interventions than ACI and NPA. However, MAAi maximal cyclical reduction (−Δr) and average deformational velocity (−v¯) did not change accordingly (p = 0.31 and p = 0.22). Reduced Ees was associated to attenuation in MAAi‐Δr and MAAi‐v¯ (r2 = 0.744; p = 0.001 and r2 = 0.467; p = 0.029). In conclusion, increased cardiac load and reduced LV contractility may cause deterioration of mitral annular dynamics, likely impairing coaptation and increasing susceptibility to valvular incompetence.

OBJECTIVES: The aim of this discussion paper is to (i) identify the differentiated roles of health in the work–retirement transition, and, with respect to these, (ii) highlight topics related to conceptual and methodological problems and challenges in research, and (iii) present avenues for future research. METHODS: This discussion paper summarizes an OMEGA-NET working group discussion ongoing from November 2018 to September 2021 with face-to-face and online meetings as well as a written online discourse. RESULTS: ‘Health’ and ‘retirement’ are ambiguous concepts. With respect to both, in retirement research, the choice of concept and indicator influences the findings. In addition, the impact of health on retirement is not necessarily a direct one, but can be influenced by further factors such as the ability, motivation and opportunity to work. The strong overall association of poor health with retiring early (path 1) bears the risk of masking distinct and deviating mechanisms in subgroups. In fact, there is evidence that also good health may lead to early retirement (path 2), while both poor health (path 3) and good health (path 4) may also make people retire later. CONCLUSIONS: An increased awareness of the differentiated roles that health may have in the work–retirement transition as outlined in this discussion paper may support research to address questions relevant for policy and practice and increase the impact of research. Recommendations for occupational health and social research are given.

Individuals with diabetes at risk of developing diabetic kidney disease (DKD) are challenging to identify using currently available clinical methods. Prognostic accuracy and initiation of treatment could be improved by a quantification of the renal microvascular rarefaction and the increased vascular tortuosity during the development of DKD. Super-resolution ultrasound (SRUS) imaging is an in vivo technique capable of visualizing blood vessels at sizes below 75 µm. This preclinical study aimed to investigate the alterations in renal blood vessels’ density and tortuosity in a type 2 diabetes rat model, Zucker diabetic fatty (ZDF) rats, as a prediction of DKD. Lean age-matched Zucker rats were used as controls. A total of 36 rats were studied, subdivided into ages of 12, 22, and 40 weeks. Measured albuminuria indicated the early stage of DKD, and the SRUS was compared with the ex vivo micro-computed tomography (µCT) of the same kidneys. Assessed using the SRUS imaging, a significantly decreased cortical vascular density was detected in the ZDF rats from 22 weeks of age compared to the healthy controls, concomitant with a significantly increased albuminuria. Already by week 12, a trend towards a decreased cortical vascular density was found prior to the increased albuminuria. The quantified vascular density in µCT corresponded with the in vivo SRUS imaging, presenting a consistently lower vascular density in the ZDF rats. Regarding vessel tortuosity, an overall trend towards an increased tortuosity was present in the ZDF rats. SRUS shows promise for becoming an additional tool for monitoring and prognosing DKD. In the future, large-scale animal studies and human trials are needed for confirmation.

We demonstrate the successful implementation of an artificial neural network (ANN) to eliminate detrimental spectral shifts imposed in the measurement of laser absorption spectrometers (LASs). Since LASs rely on the analysis of the spectral characteristics of biological and chemical molecules, their accuracy and precision is especially prone to the presence of unwanted spectral shift in the measured molecular absorption spectrum over the reference spectrum. In this paper, an ANN was applied to a scanning grating-based mid-infrared trace gas sensing system, which suffers from temperature-induced spectral shifts. Using the HITRAN database, we generated synthetic gas absorbance spectra with random spectral shifts for training and validation. The ANN was trained with these synthetic spectra to identify the occurrence of spectral shifts. Our experimental verification unambiguously proves that such an ANN can be an excellent tool to accurately retrieve the gas concentration from imprecise or distorted spectra of gas absorption. Due to the global shift of the measured gas absorption spectrum, the accuracy of the retrieved gas concentration using a typical least-mean-squares fitting algorithm was considerably degraded by 40.3%. However, when the gas concentration of the same measurement dataset was predicted by the proposed multilayer perceptron network, the sensing accuracy significantly improved by reducing the error to less than ±1% while preserving the sensing sensitivity.

Abstract Background Understanding the diversity of eyes is crucial to unravel how different animals use vision to interact with their respective environments. To date, comparative studies of eye anatomy are scarce because they often involve time-consuming or inefficient methods. X-ray micro-tomography (micro-CT) is a promising high-throughput imaging technique that enables to reconstruct the 3D anatomy of eyes, but powerful tools are needed to perform fast conversions of anatomical reconstructions into functional eye models. Results We developed a computing method named InSegtCone to automatically segment the crystalline cones in the apposition compound eyes of arthropods. Here, we describe the full auto-segmentation process, showcase its application to three different insect compound eyes and evaluate its performance. The auto-segmentation could successfully label the full individual shapes of 60-80% of the crystalline cones and is about as accurate and 250 times faster than manual labelling of the individual cones. Conclusions We believe that InSegtCone can be an important tool for peer scientists to measure the orientation, size and dynamics of crystalline cones, leading to the accurate optical modelling of the diversity of arthropod eyes with micro-CT.

Abstract Nucleophosmin‐1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3‐internal tandem duplication (FLT3‐ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo‐HCT). We identified 1572 adult (age ≥ 18 year) patients with NPM1‐mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow‐up for survivors was 23.7 months. FLT3‐ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia‐free survival (LFS) were negatively affected by concomitant FLT3‐ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p

Abstract Background Infectious diseases are among the leading causes of death in many low-income countries, such as Ethiopia. Without reliable local data concerning causative pathogens and antimicrobial resistance, empiric treatment is suboptimal. The objective of this study was to characterize gram-negative bacteria (GNB) as pathogens and their resistance pattern in hospitalized patients with infections in central Ethiopia. Methods Patients ≥ 1 year of age with fever admitted to the Asella Referral and Teaching Hospital from April 2016 to June 2018 were included. Blood and other appropriate clinical specimens were collected and cultured on appropriate media. Antibiotic susceptibility testing (AST) was performed using the Kirby–Bauer method and VITEK® 2. Species identification and detection of resistance genes were conducted using MALDI-ToF MS (VITEK® MS) and PCR, respectively. Results Among the 684 study participants, 54.2% were male, and the median age was 22.0 (IQR: 14–35) years. Blood cultures were positive in 5.4% (n = 37) of cases. Among other clinical samples, 60.6% (20/33), 20.8% (5/24), and 37.5% (3/8) of swabs/pus, urine and other body fluid cultures, respectively, were positive. Among 66 pathogenic isolates, 57.6% (n = 38) were GNB, 39.4% (n = 26) were gram-positive, and 3.0% (n = 2) were Candida species. Among the isolated GNB, 42.1% (16/38) were Escherichia coli, 23.7% (9/38) Klebsiella pneumoniae and 10.5% (4/38) Pseudomonas aeruginosa. In total, 27/38 gram-negative isolates were available for further analysis. Resistance rates were as follows: ampicillin/sulbactam, 92.6% (n = 25); cefotaxime, 88.9% (n = 24); ceftazidime, 74.1% (n = 20); cefepime, 74.1% (n = 20); gentamicin, 55.6% (n = 15); piperacillin/tazobactam, 48.1% (n = 13); meropenem, 7.4% (n = 2); and amikacin, 3.7% (n = 1). The bla NDM-1 gene was detected in one K. pneumoniae and one Acinetobacter baumannii isolate, which carried an additional bla OXA-51 gene. The ESBL enzymes were detected in 81.5% (n = 22) of isolates as follows: TEM, 77.2% (n = 17); CTX-M-1 group, 68.2% (n = 15); SHV group, 27.3% (n = 6); and CTX-M-9 group, 9.1% (n = 2). Based on the in vitro antimicrobial susceptibility results, empiric treatment initiated in 13 of 18 (72.2%) patients was likely ineffective. Conclusion We report a high prevalence of ESBL-producing bacteria (81.5%) and carbapenem resistance (7.4%), with more than half of GNB carrying two or more ESBL enzymes resulting in suboptimal empiric antibiotic therapy. These findings indicate a need for local and national antimicrobial resistance surveillance and the strengthening of antimicrobial stewardship programs.

Abstract Super-resolution ultrasound imaging (SRUS) enables in vivo microvascular imaging of deeper-lying tissues and organs, such as the kidneys or liver. The technique allows new insights into microvascular anatomy and physiology and the development of disease-related microvascular abnormalities. However, the microvascular anatomy is intricate and challenging to depict with the currently available imaging techniques, and validation of the microvascular structures of deeper-lying organs obtained with SRUS remains difficult. Our study aimed to directly compare the vascular anatomy in two in vivo 2D SRUS images of a Sprague–Dawley rat kidney with ex vivo μCT of the same kidney. Co-registering the SRUS images to the μCT volume revealed visually very similar vascular features of vessels ranging from ~ 100 to 1300 μm in diameter and illustrated a high level of vessel branching complexity captured in the 2D SRUS images. Additionally, it was shown that it is difficult to use μCT data of a whole rat kidney specimen to validate the super-resolution capability of our ultrasound scans, i.e., validating the actual microvasculature of the rat kidney. Lastly, by comparing the two imaging modalities, fundamental challenges for 2D SRUS were demonstrated, including the complexity of projecting a 3D vessel network into 2D. These challenges should be considered when interpreting clinical or preclinical SRUS data in future studies.

There are contemporary tendencies to regard the human consciousness as an algorithm, or to reduce the human subjective to organic-natural processes or to see it as a social construction depending on cultural conditions. Such approaches pose a challenge to ethical humanism, as it seems, as if it requires new justification and groundings. How can we grasp and defend the concept of embodied subjectivity of man and its freedom to act? How can we think of its unity including thought, will and feeling, preventing it from getting lost in specialized potentials, and maintaining the person as an alert, responsible and self-founded unit? Furthermore, how is it possible to preserve the meaning of the name of the soul, since the notion of this traditional limit concept of the human subjective has fallen into disuse and likely vanished from the horizon? The essay asks for answer with the help of Hermann Cohen, the great Jewish philosopher of Neo-Kantianism, following the traces of his repeatedly stated, however never written systematic psychology. This first part of investigation confines itself to understand Cohen's early interpretation of Plato as the "primordial cell" of his psychology in order to show how the first three parts of his system of philosophy (Logic, Ethics, Aesthetics) answer to some of the questions and problems the early work had raised, with special attention to Cohens philosophy of religion. Self-movement of soul and its deep connection with the human body could be viewed and grasped from the unity of human culture as well as of the allness of man.

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities.

Cryptococcosis is the leading cause of death among people with HIV in Sub-Saharan Africa. The lack of optimum diagnoses and medications significantly impair the management of the disease. We investigated the burden of cryptococcosis and related mortality among people with HIV and suspected sepsis in Ethiopia. We conducted a prospective study at (1) Adama Hospital Medical College and (2) Asella Referral and Teaching Hospital from September 2019 to November 2020. We enrolled adult, HIV-infected patients presenting with suspected sepsis and assessed their 28-day survival rates. We performed blood cultures and cryptococcal antigen (CrAg) testing. In total, 82 participants were enrolled with a median age of 35 years, and 61% were female. Overall, eleven (13%) had positive CrAg tests, of which five grew Cryptococcus in blood cultures. Despite high-dose fluconazole (1200 mg/d) monotherapy being given to those with positive CrAg tests, the 28-day mortality was 64% (7/11), with mortality being significantly higher than among the CrAg-negative patients (9% (6/71); p < 0.001). Cryptococcosis was the leading cause of mortality among HIV-infected sepsis patients in this Ethiopian cohort. The CrAg screening of HIV-infected patients attending an emergency department can minimize the number of missed cryptococcosis cases irrespective of the CD4 T cell count and viral load. These findings warrant the need for a bundle approach for the diagnosis of HIV-infected persons presenting with sepsis in low- and middle-income countries.

Mini-tablets are advantageous over liquid formulations in overcoming challenges related to stability, taste, and dosage. This open-label, single-dose, cross-over study investigated the acceptability and safety of drug-free, film-coated mini-tablets in children aged 1 month–6 years (stratified: 4–6 years, 2–

Advanced pancreatic cancer is characterized by few treatment options and poor outcomes. Oncolytic virotherapy and chemotherapy involve complementary pharmacodynamics and could synergize to improve therapeutic efficacy. Likewise, multimodality treatment may cause additional toxicity, and new agents have to be safe. Balancing both aims, we generated an oncolytic measles virus for 5-fluorouracil-based chemovirotherapy of pancreatic cancer with enhanced tumor specificity through microRNA-regulated vector tropism. The resulting vector encodes a bacterial prodrug convertase, cytosine deaminase-uracil phosphoribosyl transferase, and carries synthetic miR-148a target sites in the viral F gene. Combination of the armed and targeted virus with 5-fluorocytosine, a prodrug of 5-fluorouracil, resulted in cytotoxicity toward both infected and bystander pancreatic cancer cells. In pancreatic cancer xenografts, a single intratumoral injection of the virus induced robust in vivo expression of prodrug convertase. Based on intratumoral transgene expression kinetics, we devised a chemovirotherapy regimen to assess treatment efficacy. Concerted multimodality treatment with intratumoral virus and systemic prodrug administration delayed tumor growth and prolonged survival of xenograft-bearing mice. Our results demonstrate that 5-fluorouracil-based chemovirotherapy with microRNA-sensitive measles virus is an effective strategy against pancreatic cancer at a favorable therapeutic index that warrants future clinical translation.

Nature-based solutions are promising for climate adaptation and environmental management in urban areas, but urban conditions are stressful for vegetation. In particular, the interaction of drought and high temperatures may be detrimental. Guiding plant selection for urban greening with native species requires a far better knowledge of plant adaptations and stress acclimation. We tested the physiological responses of four candidate calcareous grassland species for green roofs and walls to the combined effects of drought and high temperatures under controlled conditions. The tested species proved relatively resistant to stress despite different strategies to protect the photosynthetic apparatus, maintain water balance, and repair damages. Based on the physiological responses, we rank the species in descending order of resistance to the stress factors tested: Trifolium medium > Festuca ovina > Carex flacca > Potentilla reptans, but all four can serve as potential candidates for green walls and roofs. Physiological stress screening of plant species for use on green roofs and walls supplements the habitat template approach to provide a stronger and wider base for prioritizations.

Abstract Lenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN (n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1–21 of 28 day cycles) followed by 10–15 mg/day for 2 years. The BTZ cohort more frequently received tandem ASCT (91% vs. 33%) due to different tandem ASCT strategies. In the LEN and BTZ cohort, 43% and 46% of patients completed 2 years of MT as intended (p = 0.57). Progression-free survival (PFS; HR = 0.83, p = 0.18) and overall survival (OS; HR = 0.70, p = 0.15) did not differ significantly with LEN vs. BTZ MT. Patients with

Noninvasive estimation of axon diameter with diffusion MRI holds the potential to investigate the dynamic properties of the brain network and pathology of neurodegenerative diseases. Recent studies use powder averaging to account for complex white matter architectures, but these have not been validated for real axonal geometries from regions that contain fibre crossings. Here, we present 120−304 μm long segmented axons from X-ray nano-holotomography volumes of a splenium and crossing fibre region of a vervet monkey brain. We show that the axons in the complex crossing fibre region, which contains callosal, association, and corticospinal connections, exhibit a wider diameter distribution than those of the splenium region. To accurately estimate the axon diameter in these regions, therefore, sensitivity to a wide range of diameters is required. We demonstrate how the q-value, b-value, signal-to-noise ratio and the assumed intra-axonal parallel diffusivity influence the range of measurable diameters with powder average approaches. Furthermore, we show how Gaussian distributed noise results in a wider range of measurable diameter at high b-values than Rician distributed noise, even at high signal-to-noise ratios of 100. The number of gradient directions is also shown to impose a lower bound on measurable diameter. Our results indicate that axon diameter estimation can be performed with only few b-shells, and that additional shells do not improve the accuracy of the estimate. For strong gradients available on human Connectom and preclinical scanners, Monte Carlo simulations of diffusion confirm that powder averaging techniques succeed in providing accurate estimates of axon diameter across a range of diameters, sequence parameters and diffusion times, even in complex white matter architectures. At relatively low b-values, the diameter estimate becomes sensitive to axonal microdispersion and the intra-axonal parallel diffusivity shows time dependency at both in vivo and ex vivo intrinsic diffusivities.

Abstract Background Local data from the Asella Teaching and Referral Hospital in the town of Asella, Ethiopia reveal a high prevalence of extended-spectrum β-lactamase- (ESBL) producing Gram-negative bacteria (GNB) in clinical isolates. To investigate a possible route of transmission, we determined the proportions ESBL-producing GNB in isolates from flies caught in the hospital and in the town of Asella. Methods Flies were collected in August 2019 from the neonatal intensive care unit (NICU), the orthopedic ward, the hospital’s waste disposal area, and from a butchery situated 1.5 km from the hospital. After trapping, the flies were macerated and suspended in sterile normal saline. The suspensions were inoculated on MacConkey agar and incubated overnight. Species identification and antimicrobial susceptibility testing were performed using Vitek®-MS and VITEK® 2. Results In total, 103 bacterial isolates were obtained from 85 flies (NICU: 11 isolates from 20 flies, orthopedic ward: 10 isolates from 12 flies, waste disposal area: 37 isolates from 26 flies, butchery: 45 isolates from 27 flies). The proportions of ESBL-producing bacteria among isolates obtained from flies collected in the hospital compound were significantly higher (82%, 90%, and 57% in NICU, orthopedic ward and waste disposal area, respectively) compared to flies collected outside of the hospital compound (2% (@1/45) in the butchery) (p ≤ 0.001). The proportion of ESBL was 67% (6/9) among Raoultella spp. 67% (4/6) among Kluyvera spp., 56% (5/9) among Enterobacter spp., 50% (5/10) among E. coli, and 44% (8/18) among Klebsiella spp.. Of the 40 ESBL-genes detected, 85% were CTX-M-like, 83% TEM-like, 23% SHV-like, and 2% CTX-M-2-like. ESBL-producing bacteria showed higher rates of resistance against ciprofloxacin (66% vs. 5%), gentamicin (68% vs. 3%), piperacillin-tazobactam (78% vs. 5%), and trimethoprim-sulfamethoxazole (88% vs. 16%), compared to non-ESBL-producing bacteria. Conclusion A high proportion of ESBL was identified in isolates from flies caught in the hospital compound compared with isolates of flies collected at a distance of 1.5 km from the hospital. Flies can be potential vectors for transmission of multidrug-resistant (MDR) bacteria within hospitals. Further studies are needed to determine the source of MDR colonization in flies and possible impact of MDR for nosocomial infections.

Abstract Background This study investigates whether a typology of work exposure can be established among older workers in Germany. Work exposure comprises physical work, working time quality, work intensity, skills & discretion, social environment, leadership, continued education, earnings and work prospects. Methods Latent profile analysis was conducted on a representative sample of the socially insured workforce in Germany born in 1959 or 1965 (N = 6277). Seven year-prospective associations between the typology and work-related outcomes (physical and mental health, work ability and work-privacy-conflict) were investigated to establish the distinctness of the profiles. Results Five profiles were identified: “Poor Quality” (19%), “Relaxed Manuals” (30%), “Strained non-Manuals” (16%), “Smooth Running” (33%) and “High Flying” (3%). These profiles exhibited diverging patterns of association with the selected outcomes, thus representing qualitatively distinct subgroups of older workers in Germany. Conclusions We conclude that a typological approach may broaden the understanding of the ageing work force and the complex interplay of the overall work situation with outcomes of high individual and social relevance such as health, work ability and employment. The five work profiles identified in this study may constitute crucial clusters needed to reliably mirror today’s over-all work exposure patterns in the older work force in Germany. They may allow for the comprehensible monitoring of quality of work and personal life among the older work force during their last working years and their transition to retirement in current times of extending working lives.

Abstract Background An ageing and a shrinking labour force implies that the prevention of a premature exit from work due to poor health will become more relevant in the future. Medical rehabilitation is a health service that aims at active participation in working life. The provision of this service will be relevant for an increasing part of the ageing labour force, namely, employees with a migrant background and their different subgroups. Thus, this study examines whether first- and second-generation employees with migrant background differ from non-migrants in their utilisation of rehabilitation services and whether within the subsample of migrant employees, those persons with foreign nationality differ from those with German nationality. Methods Socially insured employees born in 1959 or 1965 were surveyed nationwide in 2011 as part of the lidA cohort study (n=6303). Survey data of the first study wave were used to identify the dependent variable of the utilisation of rehabilitation (in- and outpatient), the independent variable of migrant status and the covariates of sociodemographic, work- and non-work-related factors. Applying bivariate statistics with tests of independence and block-wise logistic regressions, differences between the groups were investigated. Additionally, average marginal effects were computed to directly compare the adjusted models. Results The study showed that first-generation migrants had a significantly lower likelihood of utilising outpatient rehabilitation than non-migrants (fully adj. OR 0.42, 95% CI 0.22-0.82) and that average marginal effects indicated higher differences in the full model than in the null model. No significant differences were found between the first- or second-generation migrants and non-migrants when comparing the utilisation of inpatient rehabilitation or any rehabilitation or when analysing German and foreign employees with migrant background (n=1148). Conclusions Significant differences in the utilisation of outpatient rehabilitation between first-generation migrants and non-migrants were found, which could not be explained by sociodemographic, work- and non-work-related factors. Thus, further factors might play a role. The second-generation migrants resemble the non-migrants rather than their parent generation (first-generation migrants). This detailed investigation shows the heterogeneity in the utilisation of health services such as medical rehabilitation, which is why service sensitive to diversity should be considered.

This single-centre, open-label, randomised, parallel-group study assessed the acceptability, swallowability, palatability, and safety of film-coated, 3 mm diameter mini-tablets in children aged ≥2–

Convergent disk migration has long been suspected to be responsible for forming planetary systems with a chain of mean-motion resonances (MMRs). Dynamical evolution over time could disrupt the delicate resonant configuration. We present TOI-1136, a 700 ± 150 Myr old G star hosting at least six transiting planets between ∼2 and 5 R _⊕ . The orbital period ratios deviate from exact commensurability by only 10 ^−4 , smaller than the ∼10 ^−2 deviations seen in typical Kepler near-resonant systems. A transit-timing analysis measured the masses of the planets (3–8 M _⊕ ) and demonstrated that the planets in TOI-1136 are in true resonances with librating resonant angles. Based on a Rossiter–McLaughlin measurement of planet d, the star’s rotation appears to be aligned with the planetary orbital planes. The well-aligned planetary system and the lack of a detected binary companion together suggest that TOI-1136's resonant chain formed in an isolated, quiescent disk with no stellar flyby, disk warp, or significant axial asymmetry. With period ratios near 3:2, 2:1, 3:2, 7:5, and 3:2, TOI-1136 is the first known resonant chain involving a second-order MMR (7:5) between two first-order MMRs. The formation of the delicate 7:5 resonance places strong constraints on the system’s migration history. Short-scale (starting from ∼0.1 au) Type-I migration with an inner disk edge is most consistent with the formation of TOI-1136. A low disk surface density (Σ _1 au ≲ 10 ^3 g cm ^−2 ; lower than the minimum-mass solar nebula) and the resultant slower migration rate likely facilitated the formation of the 7:5 second-order MMR.

BackgroundTransjugular intrahepatic portosystemic shunt (TIPS) and shunt surgery are established treatment options for portal hypertension, but have not been systematically evaluated in patients with portal hypertension due to hepatosplenic schistosomiasis (HSS), one of the neglected tropical diseases with major impact on morbidity and mortality in endemic areas.MethodsIn this retrospective case study, patients with chronic portal hypertension due to schistosomiasis treated with those therapeutic approaches in four tertiary referral hospitals in Germany and Italy between 2012 and 2020 were included. We have summarized pre-interventional clinical data, indication, technical aspects of the interventions and clinical outcome.FindingsOverall, 13 patients with confirmed HSS were included. 11 patients received TIPS for primary or secondary prophylaxis of variceal bleeding due to advanced portal hypertension and failure of conservative management. In two patients with contraindications for TIPS or technically unsuccessful TIPS procedure, proximal splenorenal shunt surgery in combination with splenectomy was conducted. During follow-up (mean follow-up 23 months, cumulative follow-up time 31 patient years) no bleeding events were documented. In five patients, moderate and transient episodes of overt hepatic encephalopathy were observed. In one patient each, liver failure, portal vein thrombosis and catheter associated sepsis occurred after TIPS insertion. All complications were well manageable and had favorable outcomes.ConclusionsTIPS implantation and shunt surgery are safe and effective treatment options for patients with advanced HSS and sequelae of portal hypertension in experienced centers, but require careful patient selection.

Background: The extent to which children and adolescents contribute to SARS-CoV-2 transmission remains not fully understood. Novel high-capacity testing methods may provide real-time epidemiological data in educational settings helping to establish a rational approach to prevent and minimize SARS-CoV-2 transmission. We investigated whether pooling of samples for SARS-CoV-2 detection by RT-qPCR is a sensitive and feasible high-capacity diagnostic strategy for surveillance of SARS-CoV-2 infections in schools. Methods: In this study, students and school staff of 14 educational facilities in Germany were tested sequentially between November 9 and December 23, 2020, two or three times per week for at least three consecutive weeks. Participants were randomized for evaluation of two different age adjusted swab sampling methods (oropharyngeal swabs or buccal swabs compared to saliva swabs using a ‘lolli method’). Swabs were collected and pooled for SARS-CoV-2 RT-qPCR. Individuals of positive pooled tests were retested by RT-qPCR the same or the following day. Positive individuals were quarantined while the SARS-CoV-2 negative individuals remained in class with continued pooled RT-qPCR surveillance. The study is registered with the German Clinical Trials register (registration number: DRKS00023911). Findings: 5,537 individuals were eligible and 3970 participants were enroled and included in the analysis. In students, a total of 21,978 swabs were taken and combined in 2218 pooled RT-qPCR tests. We detected 41 positive pooled tests (1·8%) leading to 36 SARS-CoV-2 cases among students which could be identified by individual re-testing. The cumulative 3-week incidence for primary schools was 564/100,000 (6/1064, additionally 1 infection detected in week 4) and 1249/100,000 (29/2322) for secondary schools. In secondary schools, there was no difference in the number of SARS-CoV-2 positive students identified from pooled oropharyngeal swabs compared to those identified from pooled saliva samples (lolli method) (14 vs. 15 cases; 1·3% vs. 1·3%; OR 1.1; 95%-CI 0·5–2·5). A single secondary school accounted for 17 of 36 cases (47%) indicating a high burden of asymptomatic prevalent SARS-CoV-2 cases in the respective school and community. Interpretation: In educational settings, SARS-CoV-2 screening by RT-qPCR-based pooled testing with easily obtainable saliva samples is a feasible method to detect incident cases and observe transmission dynamics. Funding: Federal Ministry of education and research (BMBF; Project B-FAST in “NaFoUniMedCovid19”; registration number: 01KX2021).

We report on a novel, cost-effective non-dispersive infrared (NDIR) multi-gas sensor aimed at environmental air pollution monitoring. The rugged design of the K96 sensor core combines highest compactness and low-power consumption with our unique multi-channel cell design, featuring the detection of up to three different gases simultaneously, including CO2, CH4, N2O, and H2O. Our sensing platform allows the selection of the target gases as well as the concentration ranges, thus providing highly customizable gas sensor systems targeting application-specific gas monitoring settings. The sensor core comes with an implemented calibration model, and can address in real time any cross-sensitivity between the NDIR gas-sensing channels. We provide an immensely versatile sensing system while ensuring high sensing stability combined with high precision (2 and N2O, 4). The K96 multi-gas sensor core offers a resilient sensor solution for the increasing demand of compact monitoring systems in the field of environmental monitoring at reasonable costs for medium-to-high volumes.

Abstract Background Aseptic meningitis epidemics may pose various health care challenges. Methods We describe the German enterovirus meningitis epidemics in the university hospital centers of Düsseldorf, Cologne and Berlin between January 1st and December 31st, 2013 in order to scrutinize clinical differences from other aseptic meningitis cases. Results A total of 72 enterovirus (EV-positive) meningitis cases were detected in our multicenter cohort, corresponding to 5.8% of all EV-positive cases which were voluntarily reported within the National Enterovirus surveillance (EVSurv, based on investigation of patients with suspected aseptic meningitis/encephalitis and/or acute flaccid paralysis) by physicians within this period of time. Among these 72 patients, 38 (52.8%) were enterovirus positive and typed as echovirus (18 pediatric and 20 adult cases, median age 18.5 years; echovirus 18 (1), echovirus 2 (1), echovirus 30 (31), echovirus 33 (1), echovirus 9 (4)). At the same time, 45 aseptic meningitis cases in our cohort were excluded to be due to enteroviral infection (EV-negative). Three EV-negative patients were tested positive for varicella zoster virus (VZV) and 1 EV-negative patient for herpes simplex virus 2. Hospitalization was significantly longer in EV-negative cases. Cerebrospinal fluid analysis did not reveal significant differences between the two groups. After discharge, EV-meningitis resulted in significant burden of sick leave in our pediatric cohort as parents had to care for the children at home. Conclusions Voluntary syndromic surveillance, such as provided by the EVSurv in our study may be a valuable tool for epidemiological research. Our analyses suggest that EV-positive meningitis predominantly affects younger patients and may be associated with a rather benign clinical course, compared to EV-negative cases.