Practical Experience with 'Electronic Nose' Systems for Monitoring the Quality of Dairy Products

The present paper reports some practical experience acquired by testing five sensor technologies and four instruments over approximately one year with Swiss Emmental cheese samples of different stage of ripening. Up to now, the metal-oxide semiconductor (MOS) technology has given the best discrimination between the measured samples. However, sensors of this type seem to be damaged by short-chain fatty acids released from Swiss Emmental cheese. Organic conducting polymer sensors showed a poor sensitivity to volatile components of cheese, the main problem being a rapid drift of the sensors. The response of quartz microbalance sensors was too weak to detect differences between cheese samples. Discrimination using a newly designed mass-spectrometry system was difficult due to the low sensitivity of this instrument for the volatile compounds of cheese. Metal-oxide semiconductor field effect transistor sensors did not give good discrimination between the samples. However, their combination with MOS sensors seems to produce a favourable system for application in cheese evaluation. Further studies with other types of cheese and other dairy products are still necessary to define reliable and practical applications of this analytical tool in the dairy industry

Effect of the inhibition of CYP3A4 or CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone

Purpose: The main metabolic pathways of oxycodone, a potent opioid analgetic, are N-demethylation (CYP3A4) to inactive noroxycodone and O-demethylation (CYP2D6) to active oxymorphone. We performed a three-way, placebo-controlled, double-blind cross-over study to assess the pharmacokinetic and pharmacodynamic consequences of drug interactions with oxycodone. Methods: The 12 participants (CYP2D6 extensive metabolizers) were pre-treated with placebo, ketoconazole or paroxetine before oral oxycodone ingestion (0.2mg/kg). Results: Pre-treatment with ketoconazole increased the AUC for oxycodone 2- to 3-fold compared with placebo or paroxetine. In combination with placebo, oxycodone induced the expected decrease in pupil diameter. This decrease was accentuated in the presence of ketoconazole, but blunted by paroxetine. In comparison to pre-treatment with placebo, ketoconazole increased nausea, drowsiness, and pruritus associated with oxycodone. In contrast, the effect of pre-treatment with paroxetine on the above-mentioned adverse events was not different from that of placebo. Ketoconazole increased the analgetic effect of oxycodone, whereas paroxetine was not different from placebo. Conclusions: Inhibition of CYP3A4 by ketoconazole increases the exposure and some pharmacodynamic effects of oxycodone. Paroxetine pretreatment inhibits CYP2D6 without inducing relevant changes in oxycodone exposure, and partially blunts the pharmacodynamic effects of oxycodone due to intrinsic pharmacological activities. Pharmacodynamic changes associated with CYP3A4 inhibition may be clinically important in patients treated with oxycodon

Investigation of the Attachment of Circulating Endothelial Cells to a Cell Probe: Combined Experimental and Numerical Study

Circulating endothelial cells (CECs) are a reliable biomarker for cardiovascular diseases (CVDs). A major unresolved challenge limiting the widespread use of CECs for the diagnosis and monitoring of CVDs is their unreliable detection. This problem is mainly attributed to the low sample volume (5-10 mL) of commonly used ex vivo CEC isolation methods. To overcome this limitation, the BMProbe for the in vivo isolation of CECs is proposed. It consists of a twisted medical flat wire with a polymer-coated surface functionalized with anti-CD105 antibodies. A combined experimental and numerical study is performed to investigate which flow conditions lead to an increased cell attachment to the probe's surface. Endothelial cells are solved in a dextran solution and circulated in a flow system containing the BMProbes. Microscopic images of the attached CECs are taken. In addition, the experiments are simulated using a computational fluid dynamics (CFD) flow solver to quantify the flow conditions at the probe's surface. The microscopic images are superimposed with the CFD data to investigate the influence of wall shear rate and wall normal rate on the attachment of CECs to the probe. Most of all attached cells (85.5%) are found in areas of negative wall normal rate

Report on research data management interviews conducted for HMC Hub Energy in 2022

The Energy Hub of the Helmholtz Metadata Collaboration (HMC) conducted interviews with various stakeholders from the Helmholtz Research Field Energy on the topic of research data management (RDM) in 2022. The intentions were to build and serve a metadata community in the energy research field and to extend the Helmholtz-wide survey conducted by HMC in 2021 Arndt et al., 2022). Besides the deeper insight into the current state of RDM and metadata handling at the Helmholtz sites relevant to the Energy Hub the interviews focused on the related needs and difficulties of researchers and their satisfaction with the current state. Furthermore, we tried to discover already existing workflows and software solutions, to establish contacts and to make HMC better known

Y Chromosomal Variation Tracks the Evolution of Mating Systems in Chimpanzee and Bonobo

The male-specific regions of the Y chromosome (MSY) of the human and the chimpanzee (Pan troglodytes) are fully sequenced. The most striking difference is the dramatic rearrangement of large parts of their respective MSYs. These non-recombining regions include ampliconic gene families that are known to be important for male reproduction,and are consequently under significant selective pressure. However, whether the published Y-chromosomal pattern of ampliconic fertility genes is invariable within P. troglodytes is an open but fundamental question pertinent to discussions of the evolutionary fate of the Y chromosome in different primate mating systems. To solve this question we applied fluorescence in situ hybridisation (FISH) of testis-specific expressed ampliconic fertility genes to metaphase Y chromosomes of 17 chimpanzees derived from 11 wild-born males and 16 bonobos representing seven wild-born males. We show that of eleven P. troglodytes Y-chromosomal lines, ten Y-chromosomal variants were detected based on the number and arrangement of the ampliconic fertility genes DAZ (deleted in azoospermia) and CDY (chromodomain protein Y)—a so-far never-described variation of a species' Y chromosome. In marked contrast, no variation was evident among seven Y-chromosomal lines of the bonobo, P. paniscus, the chimpanzee's closest living relative. Although, loss of variation of the Y chromosome in the bonobo by a founder effect or genetic drift cannot be excluded, these contrasting patterns might be explained in the context of the species' markedly different social and mating behaviour. In chimpanzees, multiple males copulate with a receptive female during a short period of visible anogenital swelling, and this may place significant selection on fertility genes. In bonobos, however, female mate choice may make sperm competition redundant (leading to monomorphism of fertility genes), since ovulation in this species is concealed by the prolonged anogenital swelling, and because female bonobos can occupy high-ranking positions in the group and are thus able to determine mate choice more freely

Showcasing synergies between agriculture, biodiversity and ecosystem services to help farmers capitalising on native biodiversity (SHOWCASE)

The slow adoption by the agricultural sector of practices to promote biodiversity are thought to originate from three interrelated issues. First, we know little about which incentives effectively motivate farmers to integrate biodiversity into daily farm management. Second, few studies so far have produced evidence that biodiversity-based approaches produce benefits in terms of key variables for farmers (yield, profit). Third, there is a large communication gap between the scientists investigating biodiversity-based farming practices and the farmers who have to implement them. To overcome these barriers, SHOWCASE will review and test the effectiveness of a range of economic and societal incentives to implement biodiversity management in farming operations and examine farmer and public acceptance. Focus will be on three promising approaches: (i) result-based incentives, (ii) involvement in citizen science biodiversity monitoring and (iii) biodiversity-based business models. SHOWCASE will co-produce together with stakeholders solid interdisciplinary evidence for the agro-ecological and socio-economic benefits of biodiversity management in 10 contrasting farming systems across Europe. SHOWCASE will also design communication strategies that are tailor-made to farmers and other key stakeholders operating in different socio-economic and environmental conditions.SHOWCASE will develop a multi-actor network of 10 Experimental Biodiversity Areas in contrasting European farming systems that will be used for in-situ research on biodiversity incentives and evidence for benefits as well as knowledge exchange. This network will be used to identify and test biodiversity indicators and targets relevant to all stakeholders and use them in a learning-by-doing approach to improve benefits of biodiversity management on farms, both within the network and beyond

Mobilisation of critically ill patients receiving norepinephrine: a retrospective cohort study

Background: Mobilisation and exercise intervention in general are safe and feasible in critically ill patients. For patients requiring catecholamines, however, doses of norepinephrine safe for mobilisation in the intensive care unit (ICU) are not defined. This study aimed to describe mobilisation practice in our hospital and identify doses of norepinephrine that allowed a safe mobilisation. Methods: We conducted a retrospective single-centre cohort study of 16 ICUs at a university hospital in Germany with patients admitted between March 2018 and November 2021. Data were collected from our patient data management system. We analysed the effect of norepinephrine on level (ICU Mobility Scale) and frequency (units per day) of mobilisation, early mobilisation (within 72 h of ICU admission), mortality, and rate of adverse events. Data were extracted from free-text mobilisation entries using supervised machine learning (support vector machine). Statistical analyses were done using (generalised) linear (mixed-effect) models, as well as chi-square tests and ANOVAs. Results: A total of 12,462 patients were analysed in this study. They received a total of 59,415 mobilisation units. Of these patients, 842 (6.8%) received mobilisation under continuous norepinephrine administration. Norepinephrine administration was negatively associated with the frequency of mobilisation (adjusted difference -0.07 mobilisations per day; 95% CI - 0.09, - 0.05; p 0.1). Higher compared to lower doses of norepinephrine did not lead to a significant increase in adverse events in our practice (p > 0.1). We identified that mobilisation was safe with up to 0.20 mu g/kg/min norepinephrine for out-of-bed (IMS >= 2) and 0.33 mu g/kg/min for in-bed (IMS 0-1) mobilisation. Conclusions: Mobilisation with norepinephrine can be done safely when considering the status of the patient and safety guidelines. We demonstrated that safe mobilisation was possible with norepinephrine doses up to 0.20 mu g/kg/min for out-of-bed (IMS >= 2) and 0.33 mu g/kg/min for in-bed (IMS 0-1) mobilisation

Predicting lethal courses in critically ill COVID-19 patients using a machine learning model trained on patients with non-COVID-19 viral pneumonia

In a pandemic with a novel disease, disease-specific prognosis models are available only with a delay. To bridge the critical early phase, models built for similar diseases might be applied. To test the accuracy of such a knowledge transfer, we investigated how precise lethal courses in critically ill COVID-19 patients can be predicted by a model trained on critically ill non-COVID-19 viral pneumonia patients. We trained gradient boosted decision tree models on 718 (245 deceased) non-COVID-19 viral pneumonia patients to predict individual ICU mortality and applied it to 1054 (369 deceased) COVID-19 patients. Our model showed a significantly better predictive performance (AUROC 0.86 [95% CI 0.86-0.87]) than the clinical scores APACHE2 (0.63 [95% CI 0.61-0.65]), SAPS2 (0.72 [95% CI 0.71-0.74]) and SOFA (0.76 [95% CI 0.75-0.77]), the COVID-19-specific mortality prediction models of Zhou (0.76 [95% CI 0.73-0.78]) and Wang (laboratory: 0.62 [95% CI 0.59-0.65]; clinical: 0.56 [95% CI 0.55-0.58]) and the 4C COVID-19 Mortality score (0.71 [95% CI 0.70-0.72]). We conclude that lethal courses in critically ill COVID-19 patients can be predicted by a machine learning model trained on non-COVID-19 patients. Our results suggest that in a pandemic with a novel disease, prognosis models built for similar diseases can be applied, even when the diseases differ in time courses and in rates of critical and lethal courses

Endoscopic submucosal dissection for early esophageal adenocarcinoma: low rates of metastases in mucosal cancers with poor differentiation

Background and aims Endoscopic resection (ER) is accepted as standard treatment for intramucosal esophageal adenocarcinoma (EAC) with well or moderate differentiation. Poor differentiation (PD) is judged as a risk factor for lymph node metastasis (LNM) and surgery is recommended. However, the evidence for this recommendation is weak. Study aim was to analyze the clinical course of patients after ER of EAC with PD. Patients and methods Patients undergoing endoscopic submucosal dissection for EAC were included from 16 German centers. Inclusion criteria were PD in the resection specimen, R0 resection and endoscopic follow-up. Primary outcome was the metastasis rate during follow-up. Analysis was performed retrospectively in a prospectively collected database. Results 25 patients with PD as single risk factor (group A) and 15 patients with PD and additional risk factors (submucosal invasion and/or lymphovascular invasion) were included. The metastasis rate was was 1/25 (4.0%; 95%CI 0.4-17.2) in group A and 3/15 (20.0%; 95%CI 6.0-44.4%) in group B, respectively (p=0.293). The rate of EAC-associated deaths was 1/25 (4%; 95%CI 0.4-17.2%) versus 3/15 (20%; 95%CI 6.0-44.4%) in group B (p=0.293) while the overall death rate was 7/25 (28.0%; 95%CI 13.5-47.3%) versus 3/15 (20%; 95%CI 6.0-44.4%) (p=0.715). Median follow-up was 30 months (IQR 15-53). Conclusions During long-term follow-up the risk of metastasis is low after ER of mucosal EAC with PD as single risk factor. A conservative approach seems justified in this small patient group. However, the treatment strategy has to be determined on an individualized basis until further prospective data are available