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There has been remarkable progress in the field of Deep Learning and Computer Vision, but there is a lack of freely available labeled data, especially when it comes to data for specific industrial applications. However, large volumes of structured, semi-structured and unstructured data are generated in industrial environments, from which meaningful representations can be learned. The effort required for manual labeling is extremely high and can often only be carried out by domain experts. Self-supervised methods have proven their effectiveness in recent years in a wide variety of areas such as natural language processing or computer vision. In contrast to supervised methods, self-supervised techniques are rarely used in real industrial applications. In this paper, we present a self-supervised contrastive learning approach that outperforms existing supervised approaches on the used scrap dataset. We use different types of augmentations to extract the fine-grained structures that are typical for this type of images of intrinsically unordered items. This extracts a wider range of features and encodes more aspects of the input image. This approach makes it possible to learn characteristics from images that are common for applications in the industry, such as quality control. In addition, we show that this self-supervised learning approach can be successfully applied to scene-like images for classification.

Oenophiles are aware that the temperature at the time of drinking can profoundly shape wine’s sensory attributes. Wine is usually served and drunk below room temperature but warms up after pouring due to heat exchange with warmer surroundings. This study investigates how quickly wine warms up in a wine glass and identifies the relevant heating effects. A numerical simulation using conjugate heat transfer is established, representing the complex multi-physical process. Experiments are conducted to validate the simulation. It is shown that the simulation must take into account thermal conduction, convection, and even radiation to provide accurate results. Without simulating radiation and convection of the room air, the predicted temperature is off by 66.3% or 3.3 °C. As warming is independent of the alcohol content, the simulation results are valid for non-sparkling wine types with moderate sugar levels within the considered configuration. A parameter study investigated the temperature increase over time depending on the ambient temperature and the initial wine temperature for 150 mL wine in a medium-sized red wine glass. The results can provide information on preparing a wine to obtain the desired drinking temperature.

Abstract DOES - Dataset of European scrap classes. Today, scrap is already an important raw material for industry. Due to the transformation to green steel, the secondary raw material scrap will become increasingly important in the coming years. With DOES a free dataset is presented, which represents common non-alloyed European scrap classes. Two important points were considered in this dataset. First, scrap oxidizes under normal external conditions and the visual appearance changes, which plays an important role in visual inspections. Therefore, DOES includes scrap images of different degrees of corrosion attack. Second, images of scrap metal (mostly scrap piles) usually have no intrinsic order. For this reason, a technique to extract many overlapping rectangles from raw images was used, which can be used to train deep learning algorithms without any disadvantage. This dataset is very suitable to develop industrial applications or to research classification algorithms. The dataset was validated by experts and through machine learning models.

In this work we construct a surrogate model using artificial neural networks (ANN) to predict the steady-state behavior of an unmanned combat aircraft. We employ various strategies to improve the model’s accuracy, including the consideration of design tolerances, creating independent surrogate models for the different flow regimes and encoding non-numeric input features. We also explore alternative machine learning models, albeit they demonstrated a lower reliability than ANNs. Two scenarios are considered for the target variable: one focusing solely on predicting the pitching moment coefficient, and the other incorporating the roll moment coefficient as well. We investigate different methods for handling multiple targets, finding that constructing a single model with multiple outputs consistently outperforms developing separate models for each target variable. Overall, the ANN provides predictions that show excellent agreement with the experimental data, demonstrating its effectiveness and reliability in aerodynamic modeling.

Abstract Though wind power predictions have been consistently improved in the last decade, persistent reasons for remaining uncertainties are sudden large changes in wind speed, so‐called ramps. Here, we analyse the occurrence of ramp events in a wind farm in Eastern Germany and the performance of a wind power prediction tool in forecasting these events for forecasting horizons of 15 and 30 min. Results on the seasonality of ramp events and their diurnal cycle are presented for multiple ramp definition thresholds. Ramps were found to be most frequent in March and April and least frequent in November and December. For the analysis, the wind power prediction tool is fed by different wind velocity forecast products, for example, numerical weather prediction (NWP) model and measurement data. It is shown that including observational wind speed data for very short‐term wind power forecasts improves the performance of the power prediction tool compared to the NWP reference, both in terms of ramp detection and in decreasing the mean absolute error between predicted and generated wind power. This improvement is enhanced during ramp events, highlighting the importance of wind observations for very short‐term wind power prediction.

Purpose. Surgical resection is the only curative option for pancreatic carcinoma, but disease-free and overall survival times after surgery are limited due to early tumor recurrence, most often originating from local microscopic tumor residues (R1 resection). The intraoperative identification of microscopic tumor residues within the resection margin in situ could improve surgical performance. The aim of this study was to evaluate the effectiveness of fiber-optic microscopy for detecting microscopic residues in vital pancreatic cancer tissues. Experimental Design. Fresh whole-mount human pancreatic tissues, histological tissue slides, cell culture, and chorioallantoic membrane xenografts were analyzed. Specimens were stained with selected fluorophore-conjugated antibodies and studied using conventional wide-field and self-designed multicolor fiber-optic fluorescence microscopy instruments. Results. Whole-mount vital human tissues and xenografts were stained and imaged using an in situ immunofluorescence protocol. Fiber-optic microscopy enabled the detection of epitope-based fluorescence in vital whole-mount tissue using fluorophore-conjugated antibodies and enabled visualization of microvascular, epithelial, and malignant tumor cells. Among the selected antigen-antibody pairs, antibody clones WM59, AY13, and 9C4 were the most promising for fiber-optic imaging in human tissue samples and for endothelial, tumor and epithelial cell detection. Conclusions. Fresh dissected whole-mount tissue can be stained using direct exposure to selected antibody clones. Several antibody clones were identified that provided excellent immunofluorescence imaging of labeled structures, such as endothelial, epithelial, or EGFR-expressing cells. The combination of in situ immunofluorescence staining and fiber-optic microscopy visualizes structures in vital tissues and could be proposed as an useful tool for the in situ identification of residual tumor mass in patients with a high operative risk for incomplete resection.

Measurement(s) navigation data • temperature of air • atmospheric humidity • radar reflectivity • brightness temperature • cloud properties • radiation • atmospheric wind Technology Type(s) GPS navigation system • dropsondes • radar • microwave radiometer • particle count and size analyzer • imager • noseboom sensors Factor Type(s) temporal • location Sample Characteristic - Environment atmosphere Sample Characteristic - Location Arctic Ocean region

Abstract Background Under inflammatory conditions, the activation of corticotropin-releasing factor (CRF) receptor has been shown to inhibit pain through opioid peptide release from immune cells or neurons. CRF’s effects on human and animal pain modulation depend, however, on the distribution of its receptor subtypes 1 and 2 (CRF-R1 and CRF-R2) along the neuraxis of pain transmission. The objective of this study is to investigate the respective role of each CRF receptor subtype on centrally administered CRF-induced antinociception during inflammatory pain. Methods The present study investigated the role of intracerebroventricular (i.c.v.) CRF receptor agonists on nociception and the contribution of cerebral CRF-R1 and/or CRF-R2 subtypes in an animal model of Freund’s complete adjuvant (FCA)-induced hind paw inflammation. Methods used included behavioral experiments, immunofluorescence confocal analysis, and reverse transcriptase-polymerase chain reaction. Results Intracerebroventricular, but systemically inactive, doses of CRF elicited potent, dose-dependent antinociceptive effects in inflammatory pain which were significantly antagonized by i.c.v. CRF-R1-selective antagonist NBI 27914 (by approximately 60%) but less by CRF-R2-selective antagonist K41498 (by only 20%). In line with these findings, i.c.v. administration of CRF-R1 agonist stressin I produced superior control of inflammatory pain over CRF-R2 agonist urocortin-2. Intriguingly, i.c.v. opioid antagonist naloxone significantly reversed the CRF as well as CRF-R1 agonist-elicited pain inhibition. Consistent with existing evidence of high CRF concentrations in brain areas such as the thalamus, hypothalamus, locus coeruleus, and periaqueductal gray following its i.c.v. administration, double-immunofluorescence confocal microscopy demonstrated primarily CRF-R1-positive neurons that expressed opioid peptides in these pain-relevant brain areas. Finally, PCR analysis confirmed the predominant expression of the CRF-R1 over CRF-R2 in representative brain areas such as the hypothalamus. Conclusion Taken together, these findings suggest that CRF-R1 in opioid-peptide-containing brain areas plays an important role in the modulation of inflammatory pain and may be a useful therapeutic target for inflammatory pain control.

BackgroundSome patients with neuralgia of cranial nerves with otherwise therapy-refractory pain respond to invasive therapy with local anesthetics. Unfortunately, pain regularly relapses despite multimodal pain management. Transcranial direct current stimulation (tDCS) may prolong pain response due to neuro-modulatory effects.MethodsThis controlled clinical pilot trial randomized patients to receive anodal, cathodal or sham-tDCS stimulation prior to local anesthetic infiltration. Pain attenuation, quality-of-life and side effects were assessed and compared with historic controls to estimate effects of tDCS stimulation setting.ResultsAltogether, 17 patients were randomized into three groups with different stimulation protocols. Relative reduction of pain intensity in per protocol treated patients were median 73%, 50% and 69% in anodal, cathodal and sham group, respectively (p = 0.726). Compared with a historic control group, a lower rate of responders with 50% reduction of pain intensity indicates probable placebo effects (OR 3.41 stimulation vs. non-stimulation setting, NNT 3.63). 76.9% (n = 10) of tDCS patients reported mild side-effects. Of all initially included 17 patients, 23.5% (n = 4) withdrew their study participation with highest proportion in the cathodal group (n = 3). A sample size calculation for a confirmatory trial revealed 120 patients using conservative estimations.DiscussionThis pilot trial does not support series of anodal tDCS as neuro-modulatory treatment to enhance pain alleviation of local anesthetic infiltration series. Notably, results may indicate placebo effects of tDCS settings. Feasibility of studies in this population was limited due to relevant drop-out rates. Anodal tDCS warrants further confirmation as neuro-modulatory pain treatment option.

Abstract Background Millions of people in Germany suffer from chronic pain, in which course and intensity are multifactorial. Besides physical injuries, certain psychosocial risk factors are involved in the disease process. The national health care guidelines for the diagnosis and treatment of non-specific low back pain recommend the screening of psychosocial risk factors as early as possible, to be able to adapt the therapy to patient needs (e.g., unimodal or multimodal). However, such a procedure has been difficult to implement in practice and has not yet been integrated into the rehabilitation care structures across the country. Methods The aim of this study is to implement an individualized therapy and aftercare program within the rehabilitation offer of the German Pension Insurance in the area of orthopedics and to examine its success and sustainability in comparison to the previous standard aftercare program. The study is a multicenter randomized controlled trial including 1204 patients from six orthopedic rehabilitation clinics. A 2:1 allocation ratio to intervention (individualized and home-based rehabilitation aftercare) versus the control group (regular outpatient rehabilitation aftercare) is set. Upon admission to the rehabilitation clinic, participants in the intervention group will be screened according to their psychosocial risk profile. They could then receive either unimodal or multimodal, together with an individualized training program. The program is instructed in the clinic (approximately 3 weeks) and will continue independently at home afterwards for 3 months. The success of the program is examined by means of a total of four surveys. The co-primary outcomes are the Characteristic Pain Intensity and Disability Score assessed by the German version of the Chronic Pain Grade questionnaire (CPG). Discussion An improvement in terms of pain, work ability, patient compliance, and acceptance in our intervention program compared to the standard aftercare is expected. The study contributes to provide individualized care also to patients living far away from clinical centers. Trial registration DRKS, DRKS00020373 . Registered on 15 April 2020

BackgroundEmerging evidences indicate that glucocorticoid receptors (GR) play a regulatory role in cardiac function, particularly with regard to the autonomic nervous system. Therefore, this study aimed to demonstrate the expression and the precise anatomical location of GR in relation to the parasympathetic and sympathetic innervations of the heart.MethodsThe present study used tissue samples from rat heart atria to perform conventional reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot, and double immunofluorescence confocal analysis of GR with the neuronal markers vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP) as well as the mineralocorticoid receptor (MR).ResultsDouble immunofluorescence labeling revealed that GRs were co-expressed with VAChT in parasympathetic principal neuronal somata and nerve terminals innervating atrium. Also, GR colocalized with the sympathetic neuronal marker TH in a cluster of small intensely fluorescent (SIF) cells, on intracardiac nerve terminals and in the atrial myocardium. GR immunoreactivity was scarcely identified on CGRP-immunoreactive sensory nerve terminals. Approximately 20% of GR immunoreactive neuronal somata co-localized with MR. Finally, conventional RT-PCR and Western blot confirmed the presence of GR and MR in rat heart atria.ConclusionThis study provides evidence for the existence of GR predominantly on cardiac parasympathetic neurons and TH-immunoreactive SIF cells suggesting a functional role of cardiac GR on cardiovascular function by modulation of the cardiac autonomic nervous system.

The activation of the mineralocorticoid (MR) and glucocorticoid (GR) receptors on peripheral sensory neurons seems to modify pain perception through both direct non-genomic and indirect genomic pathways. These distinct subpopulations of sensory neurons are not known for peripheral human nerves. Therefore, we examined MR and GR on subpopulations of sensory neurons in sectioned human and rat peripheral nerves. Real-time PCR (RT-PCR) and double immunofluorescence confocal analysis of MR and GR with the neuronal markers PGP9.5, neurofilament 200 (NF200), and the potential pain signaling molecules CGRP, Nav1.8, and TRPV1 were performed in human and rat nerve tissue. We evaluated mechanical hyperalgesia after intrathecal administration of GR and MR agonists. We isolated MR- and GR-specific mRNA from human peripheral nerves using RT-PCR. Our double immunofluorescence analysis showed that the majority of GR colocalized with NF200 positive, myelinated, mechanoreceptive A-fibers and, to a lesser extent, with peripheral peptidergic CGRP-immunoreactive sensory nerve fibers in humans and rats. However, the majority of MR colocalized with CGRP in rat as well as human nerve tissue. Importantly, there was an abundant colocalization of MR with the pain signaling molecules TRPV1, CGRP, and Nav1.8 in human as well as rat nerve tissue. The intrathecal application of the GR agonist reduced, and intrathecal administration of an MR agonist increased, mechanical hyperalgesia in rats. Altogether, these findings support a translational approach in mammals that aims to explain the modulation of sensory information through MR and GR activation. Our findings show a significant overlap between humans and rats in MR and GR expression in peripheral sensory neurons.

In previous studies, upregulation of myocardial opioid receptors as well as the precursors of their endogenous ligands were detected in the failing heart due to chronic volume overload. Moreover, opioid receptor blockade by naltrexone improved left ventricular function. In parallel, inflammatory processes through cytokines have been confirmed to play an important role in the pathogenesis of different forms of heart failure. Thus, the present study examined the systemic and myocardial inflammatory response to chronic volume overload and its modulation by chronic naltrexone therapy. Chronic volume overload was induced in male Wistar rats by applying an infrarenal aortocaval fistula (ACF) for 28 days during which the selective opioid receptor antagonist naltrexone (n = 6) or vehicle (n = 6) were administered via a subcutaneously implanted Alzet minipump. The ultrastructural, morphometric and hemodynamic characterization of ACF animals were performed using an intraventricular conductance catheter in vivo and electron microscopy in vitro. Co-localization of mu-, delta- and kappa-opioid receptor subtypes (MOR, DOR, and KOR respectively) with the voltage gated L-type Ca2+ channel (Cav1.2), the ryanodine receptor (RyR), and mitochondria in cardiomyocytes as well as IL-6, IL-12, TNF-alpha, and Malondialdehyde (MDA) were determined using double immunofluorescence confocal microscopy, RT-PCR and ELISA, respectively. In rat left ventricular myocardium, three opioid receptor subtypes MOR, DOR, and KOR colocalized with Cav1.2, RyR and mitochondria suggesting a modulatory role of the excitation-contraction coupling. In rats with ACF-induced volume overload, signs of heart failure and myocardial ultrastructural damage, chronic naltrexone therapy improved cardiac function and reversed the systemic and myocardial inflammatory cytokine expression as well as lipid peroxidation. In conclusion, antagonism of the cardiodepressive effects of the myocardial opioid system does not only improve left ventricular function but also blunts the inflammatory response and lipid peroxidation.

Abstract Background Recently, mineralocorticoid receptors (MR) were identified in peripheral nociceptive neurons, and their acute antagonism was responsible for immediate and short-lasting (non-genomic) antinociceptive effects. The same neurons were shown to produce the endogenous ligand aldosterone by the enzyme aldosterone synthase. Methods Here, we investigate whether endogenous aldosterone contributes to inflammation-induced hyperalgesia via the distinct genomic regulation of specific pain signaling molecules in an animal model of Freund’s complete adjuvant (FCA)-induced hindpaw inflammation. Results Chronic intrathecal application of MR antagonist canrenoate-K (over 4 days) attenuated nociceptive behavior in rats with FCA hindpaw inflammation suggesting a tonic activation of neuronal MR by endogenous aldosterone. Consistently, double immunofluorescence confocal microscopy showed abundant co-localization of MR with several pain signaling molecules such as TRPV1, CGRP, Nav1.8, and trkA whose enhanced expression of mRNA and proteins during inflammation was downregulated following i.t. canrenoate-K. More importantly, inhibition of endogenous aldosterone production in peripheral sensory neurons by continuous intrathecal delivery of a specific aldosterone synthase inhibitor prevented the inflammation-induced enhanced transcriptional expression of TRPV1, CGRP, Nav1.8, and trkA and subsequently attenuated nociceptive behavior. Evidence for such a genomic effect of endogenous aldosterone was supported by the demonstration of an enhanced nuclear translocation of MR in peripheral sensory dorsal root ganglia (DRG) neurons. Conclusion Taken together, chronic inhibition of local production of aldosterone by its processing enzyme aldosterone synthase within peripheral sensory neurons may contribute to long-lasting downregulation of specific pain signaling molecules and may, thus, persistently reduce inflammation-induced hyperalgesia.

BACKGROUND: Patients with neuromuscular knee-instability assisted with orthotic devices experience problems including pain, falls, mobility issues and limited engagement in daily activities. OBJECTIVES: The aim of this study was to analyse current real-life burden, needs and orthotic device outcomes in patients in need for advanced orthotic knee-ankle-foot-orthoses (KAFOs). METHODOLOGY: An observer-based semi-structured telephone interview with orthotic care experts in Germany was applied. Interviews were transcribed and content-analysed. Quantitative questions were analysed descriptively. FINDINGS: Clinical experts from eight centres which delivered an average of 49.9 KAFOs per year and 13.3 microprocessor-stance-and-swing-phase-controlled-knee-ankle-foot orthoses (MP-SSCOs) since product availability participated. Reported underlying conditions comprised incomplete paraplegia (18%), peripheral nerve lesions (20%), poliomyelitis (41%), post-traumatic lesions (8%) and other disorders (13%). The leading observed patient burdens were “restriction of mobility” (n=6), followed by “emotional strain” (n=5) and “impaired gait pattern” (n=4). Corresponding results for potential patient benefits were seen in “improved quality-of-life” (n=8) as well as “improved gait pattern” (n=8) followed by “high reliability of the orthosis” (n=7). In total, experts reported falls occurring in 71.5% of patients at a combined annual frequency of 7.0 fall events per year when using KAFOs or stance control orthoses (SCOs). In contrast, falls were observed in only 7.2 % of MP-SSCO users. CONCLUSION: Advanced orthotic technology might contribute to better quality of life of patients, improved gait pattern and perceived reliability of orthosis. In terms of safety a substantial decrease in frequency of falls was observed when comparing KAFO and MP-SSCO users. Layman's Abstract Patients who are not able to control the muscles of their legs may need to wear a brace to improve their ability to walk. However, some users are reporting problems including pain, falls, mobility issues and limited engagement in daily activities. The aim of this study was to analyse current real-life burden, needs and experiences of patients who need to wear a brace for their knee, ankle and foot (KAFO). Therefor, experts were interviewed via telephone with a structured set of questions. Eight experts provided observations for patients who suffered from several diseases affecting leg muscle control. The leading patient burdens were identified as “restriction of mobility”, followed by “emotional strain” and “impaired way of walking”. Potential patient benefits were seen in “improved quality-of-life” as well as “improved way of walking” followed by a “high trust in the brace”. Experts reported a higher number of falls per year when using KAFO without the active control of a microprocessor. On a long-term basis, experts observed consequences of KAFO use as disorders of the back, reduced amount of muscles as well as swelling in areas not covered by the brace, scrub marks and degenerative impact on joints. Braces with active control of a microprocessor might result in better quality of life of patients, improved normal way of walking and perceived trust in the brace. Article PDF Link: https://jps.library.utoronto.ca/index.php/cpoj/article/view/37795/29114 How To Cite: Brüggenjürgen B., Braatz F., Greitemann B., Drewitz H., Ruetz A., Schäfer M., et al. Experts’ perceived patient burden and outcomes of knee-ankle-foot-orthoses (KAFOs) vs. microprocessor-stance-and-swing-phase-controlled-knee-ankle-foot orthoses (MP-SSCOs). Canadian Prosthetics & Orthotics Journal. 2022; Volume 5, Issue 1, No.7.https://doi.org/10.33137/cpoj.v5i1.37795 Corresponding Author: Prof. Dr. med. Bernd Brüggenjürgen, Head Institute Health Services Research and Technical Orthopedics, Orthopedic Department - Medical School Hannover (MHH) at DIAKOVERE Annastift Hospital, Anna-von-Borries-Str. 1-7, 30625 Hannover, Germany. E-Mail:brueggenjuergen.bernd@mh-hannover.de ORCID ID:https://orcid.org/0000-0002-8866-0809

Recent interest has focused on the mineralocorticoid receptor (MR) and its impact on the myocardium and the performance of the heart. However, there is a lack of evidence about MR expression and its endogenous ligand aldosterone synthesis with specific regard to the intrinsic cardiac nervous system. Therefore, we looked for evidence of MR and aldosterone in sympathetic and parasympathetic neurons of intracardiac ganglia. Tissue samples from rat heart atria were subjected to conventional reverse-transcriptase polymerase chain reaction (PCR), Western blot, and double immunofluorescence confocal analysis of MR, corticosterone-inactivating enzyme 11β-hydroxysteroid-dehydrogenase-2 (11β-HSD2), aldosterone, and its processing enzyme CYP11B2 together with the neuronal markers vesicular acetylcholine transporter (VAChT) and tyrosine hydroxylase (TH). Our results demonstrated MR, 11β-HSD2, and CYP11B2 specific mRNA and protein bands in rat heart atria. Double immunofluorescence labeling revealed coexpression of MR immunoreactivity with VAChT in large diameter parasympathetic principal neurons. In addition, MR immunoreactivity was identified in TH-immunoreactive small intensely fluorescent (SIF) cells and in nearby VAChT- and TH-immunoreactive nerve terminals. Interestingly, the aldosterone and its synthesizing enzyme CYP11B2 and 11β-HSD2 colocalized in MR– immunoreactive neurons of intracardiac ganglia. Overall, this study provides first evidence for the existence of not only local expression of MR, but also of 11β-HSD2 and aldosterone with its processing enzyme CYP11B2 in the neurons of the cardiac autonomic nervous system, suggesting a possible modulatory role of the mineralocorticoid system on the endogenous neuronal activity on heart performance.

Patient-reported outcomes (PROs) are an emerging paradigm in clinical research and healthcare, aiming to capture the patient's self-assessed health status in order to gauge efficacy of treatment from their perspective. As these patient-generated health data provide insights into the effects of healthcare processes in real-life settings beyond the clinical setting, they can also be viewed as a resolution beyond what can be gleaned directly by the clinician. To this end, patients are identified as a key stakeholder of the healthcare decision making process, instead of passively following their doctor's guidance. As this joint decision-making process requires constant and high-quality communication between the patient and his/her healthcare providers, novel methodologies and tools have been proposed to promote richer and preemptive communication to facilitate earlier recognition of potential complications. To this end, as PROs can be used to quantify the patient impact (especially important for chronic conditions such as cancer), they can play a prominent role in providing patient-centric care. In this paper, we introduce the MyPal platform that aims to support adults suffering from hematologic malignancies, focusing on the technical design and highlighting the respective challenges. MyPal is a Horizon 2020 European project aiming to support palliative care for cancer patients via the electronic PROs (ePROs) paradigm, building upon modern eHealth technologies. To this end, MyPal project evaluate the proposed eHealth intervention via clinical studies and assess its potential impact on the provided palliative care. More specifically, MyPal platform provides specialized applications supporting the regular answering of well-defined and standardized questionnaires, spontaneous symptoms reporting, educational material provision, notifications etc. The presented platform has been validated by end-users and is currently in the phase of pilot testing in a clinical study to evaluate its feasibility and its potential impact on the quality of life of palliative care patients with hematologic malignancies.

An approach for the numerical topology optimization of baffled stirred tanks is presented and demonstrated exemplarily on impeller blades. The methodology is based on the well-known Brinkman penalization method, which is used to alter the impeller blade geometry without having to adapt the computational grid. Since the simulation of this time-dependent problem is computationally very expensive, non-uniform rational basis splines are employed to describe the interface between solid and fluid. This method allows topological changes of complex geometries to be realized with a minimum number of design variables, thus speeding up the optimization process. Two test cases are investigated to demonstrate the capabilities of the approach and serve as a proof-of-concept. In the first case, the power requirement of the stirrer is minimized, while the second case aims to maximize the degree of mixing. As the result of the second test case is at first useless from a practical point of view, an additional constraint is introduced to limit the maximum allowable displacement of the impeller blade, which is computed using a finite element analysis.

Empathy influences how we perceive, understand, and interact with our social environment. Previous studies suggested a network of different brain regions as a neural substrate for empathy, including, in particular, insula and anterior cingulate cortex (ACC). In addition, a contribution of the somatosensory cortices for this empathy related network has been suggested. This is remarkable, given that other recent studies have revealed a role for the somatosensory cortex in various social tasks. For example, in experiments using tactile priming, incidental haptic sensations are found to influence judgment recommendations. Here, we aimed to test if this engagement of the somatosensory cortices during tactile priming can be predicted by the participant’s empathy personality traits. We assessed participant’s empathy and personality traits by means of the Interpersonal Reactivity Index (IRI) and NEO-FFI and tested whether trait empathy is associated with the tactile priming effect in social judgments. Results revealed that empathy predicted the tactile priming effect negatively. This was accompanied by a reduced engagement of the somatosensory cortex, which has been shown to be associated with the priming effect. We conclude that empathy seems to protect people from tactile priming effects.

A complex inflammatory process mediated by proinflammatory cytokines and prostaglandins commonly occurs in the synovial tissue of patients with joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). This study systematically investigated the distinct expression profile of prostaglandin E2 (PGE2), its processing enzymes (COX-2), and microsomal PGES-1 (mPGES-1) as well as the corresponding prostanoid receptor subtypes (EP1-4) in representative samples of synovial tissue from these patients (JT, OA, and RA). Quantitative TaqMan®-PCR and double immunofluorescence confocal microscopy of synovial tissue determined the abundance and exact immune cell types expressing these target molecules. Our results demonstrated that PGE2 and its processing enzymes COX-2 and mPGES-1 were highest in the synovial tissue of RA, followed by the synovial tissue of OA and JT patients. Corresponding prostanoid receptor, subtypes EP3 were highly expressed in the synovium of RA, followed by the synovial tissue of OA and JT patients. These proinflammatory target molecules were distinctly identified in JT patients mostly in synovial granulocytes, in OA patients predominantly in synovial macrophages and fibroblasts, whereas in RA patients mainly in synovial fibroblasts and plasma cells. Our findings show a distinct expression profile of EP receptor subtypes and PGE2 as well as the corresponding processing enzymes in human synovium that modulate the inflammatory process in JT, OA, and RA patients.

Collecting and labeling of good balanced training data are usually very difficult and challenging under real conditions. In addition to classic modeling methods, Generative Adversarial Networks (GANs) offer a powerful possibility to generate synthetic training data. In this paper, we evaluate the hybrid usage of real-life and generated synthetic training data in different fractions and the effect on model performance. We found that a usage of up to 75% synthetic training data can compensate for both time-consuming and costly manual annotation while the model performance in our Deep Learning (DL) use case stays in the same range compared to a 100% share in hand-annotated real images. Using synthetic training data specifically tailored to induce a balanced dataset, special care can be taken concerning events that happen only on rare occasions and a prompt industrial application of ML models can be executed without too much delay, making these feasible and economically attractive for a wide scope of industrial applications in process and manufacturing industries. Hence, the main outcome of this paper is that our methodology can help to leverage the implementation of many different industrial Machine Learning and Computer Vision applications by making them economically maintainable. It can be concluded that a multitude of industrial ML use cases that require large and balanced training data containing all information that is relevant for the target model can be solved in the future following the findings that are presented in this study.

The size and shape of snow grains directly impacts the reflection by a snowpack. In this article, different approaches to retrieve the optical-equivalent snow grain size (ropt) or, alternatively, the specific surface area (SSA) using satellite, airborne, and ground-based observations are compared and used to evaluate ICON-ART (ICOsahedral Nonhydrostatic—Aerosols and Reactive Trace gases) simulations. The retrieval methods are based on optical measurements and rely on the ropt-dependent absorption of solar radiation in snow. The measurement data were taken during a three-week campaign that was conducted in the North of Greenland in March/April 2018, such that the retrieval methods and radiation measurements are affected by enhanced uncertainties under these low-Sun conditions. An adjusted airborne retrieval method is applied which uses the albedo at 1700 nm wavelength and combines an atmospheric and snow radiative transfer model to account for the direct-to-global fraction of the solar radiation incident on the snow. From this approach, we achieved a significantly improved uncertainty (ropt of 15 µm within a five-day period after a snowfall event which is small compared to previous observations under similar temperature regimes. ICON-ART captured the observed change of ropt during snowfall events, but systematically overestimated the subsequent snow grain growth by about 100%. Adjusting the growth rate factor to 0.012 µm2 s−1 minimized the difference between model and observations. Satellite-based and airborne retrieval methods showed higher ropt over sea ice (

Reduction of the opioid analgesia in diabetic neuropathic pain (DNP) results from μ-opioid receptor (MOR) reserve reduction. Herein, we examined the antinociceptive and antiallodynic actions of a novel opioid agonist 14-O-methymorphine-6-O-sulfate (14-O-MeM6SU), fentanyl and morphine in rats with streptozocin-evoked DNP of 9–12 weeks following their systemic administration. The antinociceptive dose-response curve of morphine but not of 14-O-MeM6SU or fentanyl showed a significant right-shift in diabetic compared to non-diabetic rats. Only 14-O-MeM6SU produced antiallodynic effects in doses matching antinociceptive doses obtained in non-diabetic rats. Co-administered naloxone methiodide (NAL-M), a peripherally acting opioid receptor antagonist failed to alter the antiallodynic effect of test compounds, indicating the contribution of central opioid receptors. Reduction in spinal MOR binding sites and loss in MOR immunoreactivity of nerve terminals in the spinal cord and dorsal root ganglia in diabetic rats were observed. G-protein coupling assay revealed low efficacy character for morphine and high efficacy character for 14-O-MeM6SU or fentanyl at spinal or supraspinal levels (Emax values). Furthermore, at the spinal level only 14-O-MeM6SU showed equal efficacy in G-protein activation in tissues of diabetic- and non-diabetic animals. Altogether, the reduction of spinal opioid receptors concomitant with reduced analgesic effect of morphine may be circumvented by using high efficacy opioids, which provide superior analgesia over morphine. In conclusion, the reduction in the analgesic action of opioids in DNP might be a consequence of MOR reduction, particularly in the spinal cord. Therefore, developing opioids of high efficacy might provide analgesia exceeding that of currently available opioids.

To achieve the Paris climate protection goals there is an urgent need for action in the energy sector. Innovative concepts in the fields of short-term flexibility, long-term energy storage and energy conversion are required to defossilize all sectors by 2040. Water management is already involved in this field with biogas production and power generation and partly with using flexibility options. However, further steps are possible. Additionally, from a water management perspective, the elimination of organic micropollutants (OMP) is increasingly important. In this feasibility study a concept is presented, reacting to energy surplus and deficits from the energy grid and thus providing the needed long-term storage in combination with the elimination of OMP in municipal wastewater treatment plants (WWTPs). The concept is based on the operation of an electrolyzer, driven by local power production on the plant (photovoltaic (PV), combined heat and power plant (CHP)-units) as well as renewable energy from the grid (to offer system service: automatic frequency restoration reserve (aFRR)), to produce hydrogen and oxygen. Hydrogen is fed into the local gas grid and oxygen used for micropollutant removal via upgrading it to ozone. The feasibility of such a concept was examined for the WWTP in Mainz (Germany). It has been shown that despite partially unfavorable boundary conditions concerning renewable surplus energy in the grid, implementing electrolysis operated with regenerative energy in combination with micropollutant removal using ozonation and activated carbon filter is a reasonable and sustainable option for both, the climate and water protection.

The development of a power system based on high shares of renewable energy sources puts high demands on power grids and the remaining controllable power generation plants, load management and the storage of energy. To reach climate protection goals and a significant reduction of CO2, surplus energies from fluctuating renewables have to be used to defossilize not only the power production sector but the mobility, heat and industry sectors as well, which is called sector coupling. In this article, the role of wastewater treatment plants by means of sector coupling is pictured, discussed and evaluated. The results show significant synergies—for example, using electrical surplus energy to produce hydrogen and oxygen with an electrolyzer to use them for long-term storage and enhancing purification processes on the wastewater treatment plant (WWTP). Furthermore, biofuels and storable methane gas can be produced or integrate the WWTP into a local heating network. An interconnection in many fields of different research sectors are given and show that a practical utilization is possible and reasonable for WWTPs to contribute with sustainable energy concepts to defossilization.

Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. Sham operated and ACF rats were compared for their morphometric and hemodynamic data, for histopathological and ultrastructural changes in the liver as well as differences in the expression of apoptotic factors. ACF-induced heart failure is associated with light microscopic signs of apparent congestion of blood vessels, increased apoptosis and breakdown of hepatocytes and inflammatory cell inifltration were observed. The glycogen content depletion associated with the increased hepatic fibrosis, lipid globule formation was observed in ACF rats. Moreover, cytoplasmic organelles are no longer distinguishable in many ACF hepatocytes with degenerated fragmented rough endoplasmic reticulum, shrunken mitochondria and heavy cytoplasm vacuolization. ACF is associated with the upregulation of the hepatic TUNEL-positive cells and proapoptotic factor Bax protein concomitant with the mitochondrial leakage of cytochrome C into the cell cytoplasm and the transfer of activated caspase 3 from the cytoplasm into the nucleus indicating intrinsic apoptotic events. Taken together, the results demonstrate that ACF-induced congestive heart failure causes liver injury which results in hepatocellular apoptotic cell death mediated by the intrinsic pathway of mitochondrial cytochrome C leakage and subsequent transfer of activated caspase 3 into to the nucleus to initiate overt DNA fragmentation and cell death.

Synovial injury and healing are complex processes including catabolic effects by proinflammatory cytokines and anabolic processes by anti-inflammatory mediators. Here we examined the expression of pro- versus anti-inflammatory mediators in synovium of patients with diagnostic arthroscopy (control), joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). Synovial samples from these patients were subjected to RT-PCR and double immunofluorescence confocal microscopy of pro- and anti-inflammatory mediators as well as immune cell markers. Interestingly, pro- and anti-inflammatory mediators were expressed predominantly in granulocytes in patients with JT and in macrophages, lymphocytes, and plasma cells in patients with OA and RA. Interestingly, parallel to the severity of inflammation, proinflammatory mediators IL-1β, TNF-α, and 5-LOX specific mRNA as well as immunoreactive (IR) cells were significantly more abundant in patients with RA and JT than in those with OA. However, anti-inflammatory mediators 15-LOX, FPR2, and IL-10 specific mRNA as well as IR cells were significantly more abundant in patients with OA than in those with JT and RA. These findings show that upregulation of proinflammatory mediators contributes to the predominantly catabolic inflammatory process in JT and RA synovium, whereas upregulation of anabolic anti-inflammatory mediators counteracts inflammation resulting in the inferior inflammatory process in OA synovium.

The model of infrarenal aortocaval fistula (ACF) has recently gained new interest in its use to investigate cardiac pathophysiology. Since in previous investigations the development of congestive heart failure (CHF) was inconsistent and started to develop earliest 8-10 weeks after fistula induction using a 18G needle, this project aimed to induce a predictable degree of CHF within a definite time period using a modified approach. An aortocaval fistula was induced in male Wistar rats using a 16G needle as a modification of the former 18G needle-technique described by Garcia and Diebold. Results revealed within 28 ± 2 days of ACF significantly increased heart and lung weight indices in the ACF group accompanied by elevated filling pressure. All hemodynamic parameters derived from a pressure-volume conductance-catheter in vivo were significantly altered in the ACF consistent with severe systolic and diastolic left ventricular dysfunction. This was accompanied by systemic neurohumoral activation as demonstrated by elevated rBNP-45 plasma concentrations in every rat of the ACF group. Furthermore, the restriction in overall cardiac function was associated with a β1- and β2-adrenoreceptor mRNA downregulation in the left ventricle. In contrast, β3-adrenoreceptor mRNA was upregulated. Finally, electron microscopy of the left ventricle of rats in the ACF group showed signs of progressive subcellular myocardial fragmentation. In conclusion, the morphometric, hemodynamic and neurohumoral characterization of the modified approach revealed predictable and consistent signs of congestive heart failure within 28 ± 2 days. Therefore, this modified approach might facilitate the examination of various questions specific to CHF and allow for pharmacological interventions to determine pathophysiological pathways.

In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR) and/or toll like receptor (TLR) agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively). Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, beta-endorphin) antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim at selective FPR agonists to boost endogenous analgesia.