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The Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser Facility (EuXFEL) is equipped with a multipurpose diagnostic end-station (DES) at the end of the instrument. The imager unit in DES is a key tool for aligning the beam to a standard trajectory and for adjusting optical elements such as focusing lenses or the split-and-delay line. Furthermore, the DES features a bent-diamond-crystal spectrometer to disperse the spectrum of the direct beam to a line detector. This enables pulse-resolved characterization of the EuXFEL spectrum to provide X-ray energy calibration, and the spectrometer is particularly useful in commissioning special modes of the accelerator. Together with diamond-based intensity monitors, the imager and spectrometer form the DES unit which also contains a heavy-duty beamstop at the end of the MID instrument. Here, we describe the setup in detail and provide exemplary beam diagnostic results.

Lasting thalamus volume reduction after preterm birth is a prominent finding. However, whether thalamic nuclei volumes are affected differentially by preterm birth and whether nuclei aberrations are relevant for cognitive functioning remains unknown.Using T1-weighted MR-images of 83 adults born very preterm (≤ 32 weeks’ gestation; VP) and/or with very low body weight (≤ 1,500 g; VLBW) as well as of 92 full-term born (≥ 37 weeks’ gestation) controls, we compared thalamic nuclei volumes of six subregions (anterior, lateral, ventral, intralaminar, medial, and pulvinar) across groups at the age of 26 years. To characterize the functional relevance of volume aberrations, cognitive performance was assessed by full-scale intelligence quotient using the Wechsler Adult Intelligence Scale and linked to volume reductions using multiple linear regression analyses.Thalamic volumes were significantly lower across all examined nuclei in VP/VLBW adults compared to controls, suggesting an overall rather than focal impairment. Lower nuclei volumes were linked to higher intensity of neonatal treatment, indicating vulnerability to stress exposure after birth. Furthermore, we found that single results for lateral, medial, and pulvinar nuclei volumes were associated with full-scale intelligence quotient in preterm adults, albeit not surviving correction for multiple hypotheses testing.These findings provide evidence that lower thalamic volume in preterm adults is observable across all subregions rather than focused on single nuclei. Data suggest the same mechanisms of aberrant thalamus development across all nuclei after premature birth.

Anthelmintic resistance in sheep parasitic gastrointestinal nematodes is widespread and a severe health and economic issue but prevalence of resistance and involved parasite species are unknown in Germany. Here, the faecal egg count reduction test (FECRT) was performed on eight farms using fenbendazole, ivermectin and moxidectin and on four farms using only moxidectin. A questionnaire was used to obtain data on management practices to potentially identify risk factors for presence of resistance. All requirements of the recently revised WAAVP guideline for diagnosing anthelmintic resistance using the FECRT were applied. Nematode species composition in pre- and post-treatment samples was analysed with the nemabiome approach. Using the eggCounts statistic package, resistance against fenbendazole, ivermectin and moxidectin was found on 7/8, 8/8 and 8/12 farms, respectively. No formal risk factor analysis was conducted since resistance was present on most farms. Comparison with the bayescount R package results revealed substantial agreement between methods (Cohen's κ = 0.774). In contrast, interpretation of data comparing revised and original WAAVP guidelines resulted in moderate agreement (Cohen's κ = 0.444). The FECR for moxidectin was significantly higher than for ivermectin and fenbendazole. Nemabiome data identified 4 to 12 species in pre-treatment samples and treatments caused a small but significant decrease in species diversity (inverse Simpson index). Non-metric multidimensional scaling and k-means clustering were used to identify common patterns in pre- and post-treatment samples. However, post-treatment samples were scattered among the pre-treatment samples. Resistant parasite species differed between farms. In conclusion, the revised FECRT guideline allows robust detection of anthelmintic resistance. Resistance was widespread and involved multiple parasite species. Resistance against both drug classes on the same farm was common. Further studies including additional drugs (levamisole, monepantel, closantel) should combine sensitive FECRTs with nemabiome data to comprehensively characterise the anthelmintic susceptibility status of sheep nematodes in Germany.

Abstract Most cancer patients ultimately die from the consequences of distant metastases. As metastasis formation consumes energy mitochondria play an important role during this process as they are the most important cellular organelle to synthesise the energy rich substrate ATP, which provides the necessary energy to enable distant metastasis formation. However, mitochondria are also important for the execution of apoptosis, a process which limits metastasis formation. We therefore wanted to investigate the mitochondrial content in ovarian cancer cells and link its presence to the patient’s prognosis in order to analyse which of the two opposing functions of mitochondria dominates during the malignant progression of ovarian cancer. Monoclonal antibodies directed against different mitochondrial specific proteins, namely heat shock proteins 60 (HSP60), fumarase and succinic dehydrogenase, were used in immunohistochemistry in preliminary experiments to identify the antibody most suited to detect mitochondria in ovarian cancer cells in clinical tissue samples. The clearest staining pattern, which even delineated individual mitochondria, was seen with the anti-HSP60 antibody, which was used for the subsequent clinical study staining primary ovarian cancers (n = 155), borderline tumours (n = 24) and recurrent ovarian cancers (n = 26). The staining results were semi-quantitatively scored into three groups according to their mitochondrial content: low (n = 26), intermediate (n = 50) and high (n = 84). Survival analysis showed that high mitochondrial content correlated with a statistically significant overall reduced survival rate In addition to the clinical tissue samples, mitochondrial content was analysed in ovarian cancer cells grown in vitro (cell lines: OVCAR8, SKOV3, OVCAR3 and COV644) and in vivo in severe combined immunodeficiency (SCID) mice. In in vivo grown SKOV3 and OVCAR8 cells, the number of mitochondria positive cells was markedly down-regulated compared to the in vitro grown cells indicating that mitochondrial number is subject to regulatory processes. As high mitochondrial content is associated with a poor prognosis, the provision of high energy substrates by the mitochondria seems to be more important for metastasis formation than the inhibition of apoptotic cell death, which is also mediated by mitochondria. In vivo and in vitro grown human ovarian cancer cells showed that the mitochondrial content is highly adaptable to the growth condition of the cancer cells.

Abstract Background Person-centredness is considered as best practice for people living with dementia. A frequently used instrument to assess person-centredness of a care environment is the Person-centred Climate Questionnaire (PCQ). The questionnaire comprises of 14 items with the three subscales a climate of safety, a climate of everydayness and a climate of community. Aim The aim of the study is to describe the translation process of the English language Person-centred Climate Questionnaire (Staff version, Patient version, Family version) into German language (PCQ-G) and to evaluate the first psychometric properties of the German language Person-centred Climate Questionnaire– Staff version (PCQ-G-S). Methods We conducted a cross-sectional study. The three versions of the 14-item English PCQ were translated into German language (PCQ-G) based on the recommendations for cross-cultural adaption of measures. Item distribution, internal consistency and structural validity of the questionnaire were assessed among nursing home staff (PCQ-G-S). Item distribution was calculated using descriptive statistics. Structural validity was tested using principal component analysis (PCA), and internal consistency was assessed for the resulting subscales using Cronbach’s alpha. Data collection took place from May to September 2021. Results A total sample of 120 nurses was included in the data analysis. Nine out of 14 items of the PCQ-G-S demonstrated acceptable item difficulty, while five times showed a ceiling effect. The PCA analysis demonstrated a strong structural validity for a three-factor solution explaining 68.6% of the total variance. The three subscales demonstrated a good internal consistency with Cronbach’s alpha scores of 0.8 for each of the subscales. Conclusion The analysis of the 14-item German version (PCQ-G-S) showed first evidence for a strong internal consistency and structural validity for evaluating staff perceptions of the person-centredness in German nursing homes. Based on this, further investigations for scale validity of the PCQ-G versions should be carried out.

The blue-appearing phycocyanin from the cyanobacteria Arthrospira platensis undergoes severe color losses during food production or storage. Thus, many studies have looked at stabilizing phycocyanin against processing conditions such as heat with biopolymer complexes. The promising results have not yet been applied to beverage systems. In this study, complexes of pectin and phycocyanin were evaluated for color stability in double distilled water and a model beverage system. The color stability was tested under severe storage conditions. With a z-average diameter of 326 ± 26 nm, the complexes of phycocyanin and pectin remained smaller than pure phycocyanin (415 ± 71 nm) after heating and storage for 13 days. This could assure a better colloidal stability of the color. Kinetic modelling showed that the color degradation was slowed down by the application of complexes between phycocyanin and pectin from a half-life (t1/2) of 74 days to 117 days. A decreased color degradation could be confirmed in the model beverage although an initial color shift which needs to be considered. The color difference between the original hue at day 0 and the samples stained with phycocyanin alone exceeded that of the beverages stained with the complexes from day 10 to 13.

In the European regulatory context, rodent in vivo studies are the predominant source of neurotoxicity information. Although they form a cornerstone of neurotoxicological assessments, they are costly and the topic of ethical debate. While the public expects chemicals and products to be safe for the developing and mature nervous systems, considerable numbers of chemicals in commerce have not, or only to a limited extent, been assessed for their potential to cause neurotoxicity. As such, there is a societal push toward the replacement of animal models with in vitro or alternative methods. New approach methods (NAMs) can contribute to the regulatory knowledge base, increase chemical safety, and modernize chemical hazard and risk assessment. Provided they reach an acceptable level of regulatory relevance and reliability, NAMs may be considered as replacements for specific in vivo studies. The European Partnership for the Assessment of Risks from Chemicals (PARC) addresses challenges to the development and implementation of NAMs in chemical risk assessment. In collaboration with regulatory agencies, Project 5.2.1e (Neurotoxicity) aims to develop and evaluate NAMs for developmental neurotoxicity (DNT) and adult neurotoxicity (ANT) and to understand the applicability domain of specific NAMs for the detection of endocrine disruption and epigenetic perturbation. To speed up assay time and reduce costs, we identify early indicators of later-onset effects. Ultimately, we will assemble second-generation developmental neurotoxicity and first-generation adult neurotoxicity test batteries, both of which aim to provide regulatory hazard and risk assessors and industry stakeholders with robust, speedy, lower-cost, and informative next-generation hazard and risk assessment tools.

Abstract Background This study evaluates changes in the neonatal morbidity, the neonatal care practices, and the length of hospital stay of surviving very preterm (VP) infants born in the Netherlands in the 1980s and in the 2000s; a period over which historical improvements were introduced into neonatal care. We, herein, also study whether these changes in neonatal morbidity, neonatal care practices and length of hospital stay are associated with sociodemographic, prenatal, and infant characteristics. Methods Two community-based cohorts from 1983 (POPS) and 2002−03 (LOLLIPOP) have provided the perinatal data for our study. The analysis enrolled 1,228 participants born VP (before the 32nd week of gestation) and surviving to 2 years of age without any severe congenital malformation. A rigorous harmonisation protocol ensured a precise comparison of the cohorts by using identical definitions of the perinatal characteristics. Results In 2003, mothers were older when giving birth, had higher multiple birth rates, and significantly more parents had received higher education. In 2003, less VP infants had severe intraventricular haemorrhage and sepsis and relatively more received continuous positive airway pressure, mechanical ventilation and caffeine therapy than in 1983. Antenatal corticosteroids and surfactant therapy were provided only in 2003. The length of the stay in the neonatal intensive care unit and in hospital had decreased in 2003 by 22 and 11 days, respectively. Differences persisted after adjustment for sociodemographic, prenatal, and infant characteristics. Conclusions Neonatal morbidities of the surviving VP infants in this study have not increased, and exhibit improvements for various characteristics in two cohorts born 20 years apart with comparable gestational age and birth weight. Our data suggest that the improvements found are associated with more advanced therapeutic approaches and new national protocols in place, and less so with sociodemographic changes. This analysis provides a basis for further comparative analyses of the health and the development of VP children, particularly with regard to long-term outcomes.

In 38 patients diagnosed as adult sporadic amyotrophic lateral sclerosis (ALS), and negative for relevant anti -ganglioside, anti-borrelia or anti-Boma disease virus antibodies, we determined serum concentrations of neopterin, ~rmicroglobulin, immunoglobulin-G isotypes G1-G", carbohydrate antigen CA-19-9, as well as repeated enzyme linked immuno-assay (ELISA) serum antibodies to human spuma retrovirus (HSRV, human foamy virus=HFV) envelope plus gag./capsid antigen, and competition with maedi-visna virus antibodies in an blocking ELISA Confirmed by specific HFV-gag immunoblots and measured under code, 26% of tested ALS-patients and 4% of 195 other neurological controls reacted ELISA and immunoblot antibody-positive against HFV. In a maedi-visna virus blocking ELISA, 47/50 sera from 28/30 ALS patients competed with anti-visna lentivirus antibodies more than healthy controls (p

2D materials provide a rapidly expanding platform for the observation of novel physical phenomena and for the realization of cutting-edge optoelectronic devices. In addition to their peculiar individual characteristics, 2D materials can be stacked into complex van der Waals heterostructures, greatly expanding their potential. Moreover, thanks to their excellent stretchability, strain can be used as a powerful control knob to tune or boost many of their properties. Here, we present a novel method to reliably and repeatedly apply a high uniaxial tensile strain to suspended van der Waals heterostructures. The reported device is engineered starting from a silicon-on-insulator substrate, allowing for the realization of suspended silicon beams that can amplify the applied strain. The strain module functionality is demonstrated using single- and double-layer graphene layers stacked with a multilayered hexagonal boron nitride flake. The heterostructures can be uniaxially strained, respectively, up to ∼1.2% and ∼1.8%.

Abstract Background Catechol-O-Methyltransferase (COMT) plays a key role in dopamine and estrogen metabolism. Recently, COMT haplotypes rather than the single polymorphism Val158Met have been reported to underlie differences in protein expression by modulating mRNA secondary structure. So far, studies investigating the epigenetic variability of the S-COMT (soluble COMT) promoter region mainly focused on phenotypical aspects, and results have been controversial. Methods We assessed S-COMT promoter methylation in saliva and blood derived DNA with regard to early pre- and postnatal growth as well as to genotype for polymorphisms rs6269, rs4633, and rs4680 (Val158Met) in 20 monozygotic twin pairs (mean age 4 years), who were discordant for intrauterine development due to severe feto-fetal-transfusion syndrome. Methylation levels of two previously reported partially methylated cytosines were determined by the quantitative SIRPH (SNuPE- IP RP HPLC) assay. Results Overall, we observed a high variability of S-COMT promoter methylation, which did not correlate with individual differences in the pre- or postnatal growth pattern. Within the twin pairs however we noted a distinct similarity that could be linked to underlying COMT genotypes. This association was subsequently confirmed in a cohort of 93 unrelated adult controls. Interestingly, 158Val-alleles were found at both ends of the epigenotypical range, which is in accordance with a recently proposed model of COMT haplotypes corresponding to a continuum of phenotypical variability. Conclusion The strong heritable component of S-COMT promoter methylation found in our study needs to be considered in future approaches that focus on interactions between COMT epigenotype and phenotype.

Abstract Background Sleep disturbances are common in nursing home residents and challenging for their nurses. Knowledge about sleep and sleep promoting factors is essential to provide adequate sleep management, where nurses play a key role. Therefore, nurses’ knowledge and attitudes towards sleep and sleep promoting interventions is important as enabling or inhibiting factor for successful sleep management. Methods A multicenter cross-sectional study was conducted among nurses working wholly or partially at night in nursing homes in Germany. Data were collected between February and April 2021 via online or paper and pencil questionnaires, comprising 56 items. Nursing homes were recruited through existing cooperation with the study centers as well as via nursing home registers. Results Finally, 138 nursing homes participated and 271 nurses completed the survey. Nurses agreed that sleep disturbances are an important topic with important impact on resident’ health. Although, the assessment of sleep was seen as nurses’ responsibility, only 40 nurses (14.7%) stated that residents’ sleep was always documented. Only 21.7% reported the availability of policy documents providing guidance regarding the management of sleep disturbances. The vast majority (93.2%) reported never having received training about sleep and management of sleep disturbances after their basic nursing training. Conclusions Our results indicate that nurses working at night can play an important role in residents’ sleep promotion. The findings indicate nurses’ educational needs regarding sleep and sleep promotion. Nursing homes should implement institutional guidelines in order to promote residents’ sleep based on adequate evidence-based non-pharmacological interventions.

Abstract The operation modes for the proposed FCC-ee collider foresee a very small beam spot size and stored beam energies of up to 20.6 MJ in Z production. This necessitates a dedicated beam dumping system. To reduce the complexity of the system as well as to minimize the required space, an optimized, semi-passive system has been designed and is presented here. The beam dilution is done with a defocusing triplet structure, followed by passive beam diluter elements (spoilers). This greatly reduces the risk of possible dilution failure scenarios compared to an active dilution kicker-magnet system. The dump core itself is located ∼ 70 m ${\sim}70~\text{m}$ downstream of the spoilers and is designed following the experience gained from the LHC dump. The dilution performance as well as the interaction effects responsible for the energy deposited in the spoiler, are directly related to the radiation length and the dimension of the device in beam direction. Materials for these spoilers have been studied extensively and key requirements have been identified using both Monte Carlo shower simulations and thermo-mechanical Finite Element Analysis. Even though the maximum temperature reached in the spoilers is well within the working temperature range of the material, the induced mechanical stresses can lead to material failure. Thermo-mechanical simulations have shown that the transversal beam shape plays a key role in the magnitude of mechanical stresses as a result of the beam impact and the abrupt temperature change. This problem is addressed in this paper and an optimized solution is presented.

Objective Researching how public–private engagements may promote universal access to safe obstetric care including caesarean delivery is essential. The aim of this research was to document the utilisation of private general practitioners (GPs) contracted to provide caesarean delivery services in five rural district hospitals in the Western Cape, the profile and outcomes of caesarean deliveries. We also describe stakeholder experiences of these arrangements in order to inform potential models of public–private contracting for obstetric services.Design We used a mixed-methods study design to describe rural district hospitals’ utilisation of private GP contracting for caesarean deliveries. Between April 2021 and March 2022, we collated routine data from delivery and theatre registers to capture the profile of deliveries and maternal outcomes. We conducted 23 semistructured qualitative interviews with district managers, hospital-employed doctors and private GPs to explore their experiences of the contracting arrangements.Setting The study was conducted in five rural district hospitals in the Western Cape province, South Africa.Results The use of private GPs as surgeon or anaesthetist for caesarean deliveries differed widely across the hospitals. Overall, the utilisation of private GPs for anaesthetics was similar (29% of all caesarean deliveries) to the utilisation of private GPs as surgeons (33% of all caesarean deliveries). The proportion of caesarean deliveries undertaken by private GPs as the primary surgeon was inversely related to size of hospital and mean monthly deliveries. Adverse outcomes following a caesarean delivery were rare. Qualitative data provided insights into contributions made by private GPs and the contracting models, which did not incentivise overservicing.Conclusion The findings of this study suggest that private GPs can play an important role in filling gaps and expanding quality care in rural public facilities that have insufficient obstetric skills and expertise. Different approaches to enable access to safe caesarean delivery are needed for different contexts, and contracting with experienced private GP’s is one resource for rural district hospitals to consider.

The human claustrum is a gray matter structure in the white matter between insula and striatum. Previous analysis found altered claustrum microstructure in very preterm-born adults associated with lower cognitive performance. As the claustrum development is related to hypoxia–ischemia sensitive transient cell populations being at-risk in premature birth, we hypothesized that claustrum structure is already altered in preterm-born neonates.We studied anatomical and diffusion-weighted MRIs of 83 preterm- and 83 term-born neonates at term-equivalent age. Additionally, claustrum development was analyzed both in a spectrum of 377 term-born neonates and longitudinally in 53 preterm-born subjects. Data was provided by the developing Human Connectome Project.Claustrum development showed increasing volume, increasing fractional anisotropy (FA), and decreasing mean diffusivity (MD) around term both across term- and preterm-born neonates. Relative to term-born ones, preterm-born neonates had (i) increased absolute and relative claustrum volumes, both indicating increased cellular and/or extracellular matter and being in contrast to other subcortical gray matter regions of decreased volumes such as thalamus; (ii) lower claustrum FA and higher claustrum MD, pointing at increased extracellular matrix and impaired axonal integrity; and (iii) aberrant covariance between claustrum FA and MD, respectively, and that of distributed gray matter regions, hinting at relatively altered claustrum microstructure.Results together demonstrate specifically aberrant claustrum structure in preterm-born neonates, suggesting altered claustrum development in prematurity, potentially relevant for later cognitive performance.

Der Beitrag diskutiert zwei Biografien nicht-traditionell Studierender, die den Hochschulzugang über das Ablegen einer Zulassungsprüfung erhalten haben. Zur Rekonstruktion der Motivstrukturen und der weiterführenden biografischen Verläufe nach dem Studium wurden narrative Interviews mit der Objektiven Hermeneutik ausgewertet. Beide Fälle stehen für ausgeprägte Erfolgsgeschichten, unterscheiden sich jedoch hinsichtlich der Motive, Werthaltungen, Strategien und Zielvorstellungen, die auch durch Familie und Milieu geprägt sind. Abschließend erfolgt ein Fallvergleich, der auf die hohe Bedeutsamkeit von Bildungsoptionen für diese Personengruppe hinweist.

IntroductionPreterm birth is associated with an increased risk for impaired body weight gain. While it is known that in prematurity several somatic and environmental factors (e.g., endocrine factors, nutrition) modulate short- and long-term body weight gain, the contribution of potentially impaired body weight control in the brain remains elusive. We hypothesized that the structure of hypothalamic nuclei involved in body weight control is altered after preterm birth, with these alterations being associated with aberrant body weight development into adulthood.Materials and methodsWe assessed 101 very preterm (i.e.,

The currently accepted methods for neurotoxicity (NT) testing rely on animal studies. However, high costs and low testing throughput hinder their application for large numbers of chemicals. To overcome these limitations, in vitro methods are currently being developed based on human-induced pluripotent stem cells (hiPSC) that allow higher testing throughput at lower costs. We applied six different protocols to generate 3D BrainSphere models for acute NT evaluation. These include three different media for 2D neural induction and two media for subsequent 3D differentiation resulting in self-organized, organotypic neuron/astrocyte microtissues. All induction protocols yielded nearly 100% NESTIN-positive hiPSC-derived neural progenitor cells (hiNPCs), though with different gene expression profiles concerning regional patterning. Moreover, gene expression and immunocytochemistry analyses revealed that the choice of media determines neural differentiation patterns. On the functional level, BrainSpheres exhibited different levels of electrical activity on microelectrode arrays (MEA). Spike sorting allowed BrainSphere functional characterization with the mixed cultures consisting of GABAergic, glutamatergic, dopaminergic, serotonergic, and cholinergic neurons. A test method for acute NT testing, the human multi-neurotransmitter receptor (hMNR) assay, was proposed to apply such MEA-based spike sorting. These models are promising tools not only in toxicology but also for drug development and disease modeling.

Tumor Treating Fields (TTFields) were incorporated into the treatment of glioblastoma, the most malignant brain tumor, after showing an effect on progression-free and overall survival in a phase III clinical trial. The combination of TTFields and an antimitotic drug might further improve this approach. Here, we tested the combination of TTFields with AZD1152, an Aurora B kinase inhibitor, in primary cultures of newly diagnosed (ndGBM) and recurrent glioblastoma (rGBM). AZD1152 concentration was titrated for each cell line and 5–30 nM were used alone or in addition to TTFields (1.6 V/cm RMS; 200 kHz) applied for 72 h using the inovitro™ system. Cell morphological changes were visualized by conventional and confocal laser microscopy. The cytotoxic effects were determined by cell viability assays. Primary cultures of ndGBM and rGBM varied in p53 mutational status; ploidy; EGFR expression and MGMT-promoter methylation status. Nevertheless; in all primary cultures; a significant cytotoxic effect was found following TTFields treatment alone and in all but one, a significant effect after treatment with AZD1152 alone was also observed. Moreover, in all primary cultures the combined treatment had the most pronounced cytotoxic effect in parallel with morphological changes. The combined treatment of TTFields and AZD1152 led to a significant reduction in the number of ndGBM and rGBM cells compared to each treatment alone. Further evaluation of this approach, which has to be considered as a proof of concept, is warranted, before entering into early clinical trials.