The difficulty in quantifying the benefit of Structural Health Monitoring (SHM) for decision support is one of the bottlenecks to an extensive adoption of SHM on real-world structures. In this paper, we present a framework for such a quantification of the value of vibration-based SHM, which can be flexibly applied to different use cases. These cover SHM-based decisions at different time scales, from near-real time diagnostics to the prognosis of slowly evolving deterioration processes over the lifetime of a structure. The framework includes an advanced model of the SHM system. It employs a Bayesian filter for the tasks of sequential joint deterioration state-parameter estimation and structural reliability updating, using continuously identified modal and intermittent visual inspection data. It also includes a realistic model of the inspection and maintenance decisions throughout the structural life-cycle. On this basis, the Value of SHM is quantified by the difference in expected total life-cycle costs with and without the SHM. We investigate the framework through application on a numerical model of a two-span bridge system, subjected to gradual and shock deterioration, as well as to changing environmental conditions, over its lifetime. The results show that this framework can be used as an a-priori decision support tool to inform the decision on whether or not to install a vibration-based SHM system on a structure, for a wide range of SHM use cases.
pyFBS is an open-source Python package for frequency-based substructuring. The package implements an object-oriented approach for dynamic substructuring. This tutorial is intended to introduce structural dynamics and NVH engineers to the research toolbox in order to overcome vibration challenges in the future. The focus will be on experimental modeling and post-processing of datasets in the context of dynamic substructuring applications. The state-of-the-art methods of frequency-based substructuring, such as the virtual point transformation, the singular vector transformation, and system-equivalent model mixing, are available in pyFBS and will be presented. Furthermore, basic and application examples, as well as numerical and experimental datasets that are provided, are intended to familiarize users with the workflow of the package. pyFBS is demonstrated with two example structures. First, a simple beam-like structure is used to demonstrate how to start with the experimental modeling, FRF synthesis, virtual point transformation, and mixing of system equivalence models. Second, an automotive test structure is used to demonstrate the use of the pyFBS on a complex structure where in-situ transfer path analysis is used to characterize the blocked forces. This tutorial is intended to provide an informal overview of how research can be powered by open-source tools.
Lightweight design for gears is becoming increasingly important for efficient, sustainable drive trains. Innovative lightweight designs can be achieved by the additive manufacturing process of P.B.F.-L.B./M. (powder bed fusion by laser beam of metals). This contribution presents lightweight hub designs for gears manufactured by P.B.F.-L.B./M. Helical as well as spur gears are 3D-printed out of the case-hardening steel 16MnCr5. After the PBF-LB/M-process, the gears are case-carburized, shot blasted for mechanical cleaning. The gears with lightweight hubs are analyzed concerning their density, microstructure, roughness. The gears are tested regarding their static, dynamic load carrying capacity, the influence of the lightweight hub on the load carrying capacity is analyzed, evaluated. In conclusion, this contribution enables aprofound understanding, prospective evolution of lightweight hub designs for gears.
Shared vehicles architectures for fuel cell and battery electric vehicles offer a high potential for cost reduction by enabling economies of scale in engineering and production. The efficient integration of hydrogen storages in flat box-shaped battery design spaces represents one of the essential basic requirements. As state-of-the-art cylindrical pressure vessels do not allow a high volumetric efficiency in the installation space, two concepts of box-shaped pressure vessels with tension struts are investigated with regard to manufacturability. The first concept focuses on the integration of aramid fibers in a carbon fiber tank by tufting. In a second concept 3D weaving is analyzed with regard to the construction of a pressure vessel with inner tension struts. For both tank designs manufacturing technologies are developed and the concepts are validated using prototypes. Considering technologies for series production of the textile sector possible paths for industrialization are identified.
Nuclei instance segmentation and classification in histology plays a major role in routine pathology image examination, which enable morphological features analysis that further facilitates streamlined diagnosis and prognosis quantification. However, the nuclei in the tissue images obtained from different human organs are characterized with high variability in shape, size, morphology and spatial arrangements. Moreover, during digitization of tissue slide, the image quality is degraded because of added artifacts, poor contrast, blurred regions due to failed auto-focus and inconsistent staining procedure. Owing to these challenges, it is difficult to build a generalized feature representation that can achieve precise segmentation and classification of nuclei instances in complex tumor micro-environment of tissue specimens obtained from various organs. To address these problems, we propose a novel deep learning model, that harnesses horizontal and vertical distance information hidden among the nuclei instances to successfully delineate the challenging nuclei. Our proposed methodology uses soft attention mechanism to generate relevant feature activation and prune irrelevant and noisy information. These attention units produce more precise and refined feature maps resulting in finer instances segmentation and accurate classification in the overlapping nuclei, the nuclei with touching boundaries and reduction in false positives. We train our model on publicly available data-sets (Kumar, CoNSep, CPM-17 and a new data-set PanNuke). Our methodology shows superior performance in nuclei classification and segmentation in comparison with recently published methods. The code and the obtained results have been made public at the following link: http://t.ly/eGkV.
The increasingly aged human population (mainly in developed countries) represents a significant scientific achievement and privilege associated with medical, social, and economic progress. However, it also poses several challenges to national health and social care systems. The uncoupling of biological evolution with the vast and fast technical progress achieved by humanity has minimized the role of natural selection and rendered aging almost an undesirable physiological event that most people desire to delay as much as possible. All this has been challenging modern gerontology to focus on potential strategies to extend the lifespan, but primarily to mitigate the negative thoughts often associated with aging and aged individuals.
α-Diimine Ni and Pd complexes are one of the most examined late-transition organometallics in the application of catalyzed ethylene (co)polymerization. These organometallic catalysts provide unique advantages and particular opportunities to tailor the architectures, composition, and topology of synthesized polymers through catalyzed polymerization. Two decades after their initial discovery, they are still drawing extensive attention in both academia and industry. More recently, researchers have studied the effect of structural modifications on the α-diimine Ni and Pd complexes and their catalytic behaviors in ethylene (co)polymerization. This review highlights the recent progress in the developments of α-diimine Ni and Pd complexes achieved in the last decade. The chain-walking mechanism as a unique catalytic behavior of α-diimine Ni and Pd complexes is also addressed. The versatile synthesis of ligands and complexes enables researchers to tailor the catalytic performance and the microstructures of polyethylene. Correlations between their structural tunes and catalytic behaviors, polymer properties, and the ethylene copolymerization with polar monomers are comparatively presented and discussed. The heterogenization study of α-diimine Ni and Pd complexes on a solid support for heterogeneous catalysis is also comprehensively summarized. The review is broadly classified into four sections which includes i) the coordination-insertion chemistry in ethylene (co)polymerization, ii) the modification of ligand structure, iii) their application in the field of heterogeneous polymerization, iv) and the properties of the synthesized polymers, followed by the short summary and outlook for their potential studies and applications.
The human gastrointestinal tract is home to trillions of microbes. Gut microbial communities have a significant regulatory role in the intestinal physiology, such as gut motility. Microbial effect on gut motility is often evoked by bioactive molecules from various sources, including microbial break down of carbohydrates, fibers or proteins. In turn, gut motility regulates the colonization within the microbial ecosystem. However, the underlying mechanisms of such regulation remain obscure. Deciphering the inter-regulatory mechanisms of the microbiota and bowel function is crucial for the prevention and treatment of gut dysmotility, a comorbidity associated with many diseases. In this review, we present an overview of the current knowledge on the impact of gut microbiota and its products on bowel motility. We discuss the currently available techniques employed to assess the changes in the intestinal motility. Further, we highlight the open challenges, and incorporate biophysical elements of microbes-motility interplay, in an attempt to lay the foundation for describing long-term impacts of microbial metabolite-induced changes in gut motility.
The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological processes and is a promising nucleic acid drug in therapeutic fields of the diabetic wound. However, miRNA therapies have limitations due to lacking an effective delivery system. In the present study, we found a significant reduction of miR-31-5p expression in the full-thickness wounds of diabetic mice compared to normal mice. Further, miR-31-5p has been proven to promote the proliferation, migration, and angiogenesis of endothelial cells. Thus, we conceived the idea of exogenously supplementing miR-31-5p mimics to treat the diabetic wound. We used milk-derived exosomes as a novel system for miR-31-5p delivery and successfully encapsulated miR-31-5p mimics into milk exosomes through electroporation. Then, we proved that the miR-31-5p loaded in exosomes achieved higher cell uptake and was able to resist degradation. Moreover, our miRNA-exosomal formulation demonstrated dramatically improved endothelial cell functions in vitro, together with the promotion of angiogenesis and enhanced diabetic wound healing in vivo. Collectively, our data showed the feasibility of milk exosomes as a scalable, biocompatible, and cost-effective delivery system to enhance the bioavailability and efficacy of miRNAs.
There is a growing debate about the involvement of the gut microbiome in COVID-19, although it is not conclusively understood whether the microbiome has an impact on COVID-19, or vice versa, especially as analysis of amplicon data in hospitalized patients requires sophisticated cohort recruitment and integration of clinical parameters. Here, we analyzed fecal and saliva samples from SARS-CoV-2 infected and post COVID-19 patients and controls considering multiple influencing factors during hospitalization. 16S rRNA gene sequencing was performed on fecal and saliva samples from 108 COVID-19 and 22 post COVID-19 patients, 20 pneumonia controls and 26 asymptomatic controls. Patients were recruited over the first and second corona wave in Germany and detailed clinical parameters were considered. Serial samples per individual allowed intra-individual analysis. We found the gut and oral microbiota to be altered depending on number and type of COVID-19-associated complications and disease severity. The occurrence of individual complications was correlated with low-risk (e.g., Faecalibacterium prausznitzii) and high-risk bacteria (e.g., Parabacteroides ssp.). We demonstrated that a stable gut bacterial composition was associated with a favorable disease progression. Based on gut microbial profiles, we identified a model to estimate mortality in COVID-19. Gut microbiota are associated with the occurrence of complications in COVID-19 and may thereby influencing disease severity. A stable gut microbial composition may contribute to a favorable disease progression and using bacterial signatures to estimate mortality could contribute to diagnostic approaches. Importantly, we highlight challenges in the analysis of microbial data in the context of hospitalization.
The COVID-19 pandemic forced a rapid shift to digital strategies including e-exams in medical schools. However, there are significant concerns, predominately from student perspectives, and further data is required to successfully establish e-assessment in the medical curricula. The objective of the study was to examine medical students’ perceptions, concerns, and needs regarding e-assessment to establish a comprehensive e-exam based on these and previous findings and to evaluate its effectiveness in terms of examinee perceptions and further needs. During the 2021 summer term, a cross-sectional study using qualitative and quantitative methods was conducted among all 1077 students at the School of Medicine, Technical University of Munich. They were asked to provide information regarding their characteristics, preferred exam format, e-assessment perception, concerns, and needs in an online questionnaire. Based on these findings, a pilot e-exam including an e-exam preparation for the students were established and subsequently evaluated among 125 pilot e-exam examinees under study consideration via an online-questionnaire. Of the 317 pre-exam participants (73.2% female), 70.3% preferred in-person exams and showed concerns about the technological framework, privacy, and examination requirements. Qualitative analysis showed that these concerns lead to additional exam stress and fear of failure. The 34 (79.4% female) participants who participated in the evaluation survey showed a significantly more positive e-exam perception. The fairness of the platform, the independence from an internet connection, the organization including the e-exam preparation, and the consideration of participant needs were discussed as particularly positive in the open-ended comments. In both surveys, participants requested uniform platforms and processes for all subjects. This study provides evidence for a positive, complementary role of student participation in a successful e-exam implementation. Furthermore, when establishing an e-exam format in the medical curricula, e-exam training, equal accessibility, availability offline, and all-round fairness should be considered.
Introduction: Although evidence-based treatments for posttraumatic stress disorder (PTSD) in adolescents and young adults exist, affected youth do not have sufficient access to these treatments due to structural and attitudinal barriers. Internet- and mobile-based interventions (IMIs) can help fill this healthcare gap, but such programmes have not yet been sufficiently evaluated in youth with PTSD. Aim: This study aims to investigate the feasibility of an IMI for youth with PTSD in a one-arm, non-randomised, prospective proof-of-concept feasibility study. Methods: We aim to recruit 32 youth between 15 and 21 years old with clinically relevant posttraumatic stress symptoms (CATS ≥ 21), who will receive access to the IMI. The IMI consists of nine sessions involving psychoeducation, emotion regulation and coping skills, written-based imaginal exposure, cognitive restructuring and relapse prevention. Participants will be guided by an eCoach, who provides weekly semi-standardised written feedback on completed sessions and adherence reminders. We will use a formal feasibility framework to assess different dimensions of feasibility: (1) recruitment capability and resulting sample characteristics, (2) data collection procedures and outcome measures, (3) acceptability of the IMI and study procedures, (4) resources and ability to manage and implement the study and IMI and (5) participants' responses to the IMI in terms of symptom severity and satisfaction. Additionally, potential negative effects related to the intervention will be assessed. Assessments take place pre-, mid- and post-intervention and at follow-up, including semi-structured clinical telephone interviews for PTSD diagnostics at pre- and post-intervention assessment. Qualitative interviews will be conducted to investigate the youth perspectives on the IMI. Discussion: This study aims to determine the feasibility of a guided IMI for youth with PTSD to adapt the IMI as closely as possible to youth needs and to inform the design, procedure and safety management of a large-scale efficacy RCT. Trial registration: German Clinical Trials Register identifier: DRKS00023341. Highlights: Evidence-based care for adolescents after trauma is not widely available.• This study evaluates the feasibility of a guided trauma-focused Internet intervention as a time- and location-independent low-threshold treatment option for adolescents and young adults with posttraumatic stress disorder.
An amendment to this paper has been published and can be accessed via the original article.
Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. Conclusion This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
Obsessive-compulsive disorder (OCD) is a highly disabling mental illness that can be divided into frequent primary and rarer organic secondary forms. Its association with secondary autoimmune triggers was introduced through the discovery of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS) and Pediatric Acute onset Neuropsychiatric Syndrome (PANS). Autoimmune encephalitis and systemic autoimmune diseases or other autoimmune brain diseases, such as multiple sclerosis, have also been reported to sometimes present with obsessive-compulsive symptoms (OCS). Subgroups of patients with OCD show elevated proinflammatory cytokines and autoantibodies against targets that include the basal ganglia. In this conceptual review paper, the clinical manifestations, pathophysiological considerations, diagnostic investigations, and treatment approaches of immune-related secondary OCD are summarized. The novel concept of “autoimmune OCD” is proposed for a small subgroup of OCD patients, and clinical signs based on the PANDAS/PANS criteria and from recent experience with autoimmune encephalitis and autoimmune psychosis are suggested. Red flag signs for “autoimmune OCD” could include (sub)acute onset, unusual age of onset, atypical presentation of OCS with neuropsychiatric features (e.g., disproportionate cognitive deficits) or accompanying neurological symptoms (e.g., movement disorders), autonomic dysfunction, treatment resistance, associations of symptom onset with infections such as group A streptococcus, comorbid autoimmune diseases or malignancies. Clinical investigations may also reveal alterations such as increased levels of anti-basal ganglia or dopamine receptor antibodies or inflammatory changes in the basal ganglia in neuroimaging. Based on these red flag signs, the criteria for a possible, probable, and definite autoimmune OCD subtype are proposed.
Background The ability of overstory tree species to regenerate successfully is important for the preservation of tree species diversity and its associated flora and fauna. This study investigated forest regeneration dynamics in the Cat Ba National Park, a biodiversity hotspot in Vietnam. Data was collected from 90 sample plots (500 m ² ) and 450 sub-sample plots (25 m ² ) in regional limestone forests. We evaluated the regeneration status of tree species by developing five ratios relating overstory and regeneration richness and diversity. By examining the effect of environmental factors on these ratios, we aimed to identify the main drivers for maintaining tree species diversity or for potential diversity gaps between the regeneration and the overstory layer. Our results can help to increase the understanding of regeneration patterns in tropical forests of Southeast Asia and to develop successful conservation strategies. Results We found 97 tree species in the regeneration layer compared to 136 species in the overstory layer. The average regeneration density was 3764 ± 1601 per ha. Around 70% of the overstory tree species generated offspring. According to the International Union for Conservation of Nature’s Red List, only 36% of threatened tree species were found in the regeneration layer. A principal component analysis provided evidence that the regeneration of tree species was slightly negatively correlated to terrain factors (percentage of rock surface, slope) and soil properties (cation exchange capacity, pH, humus content, soil moisture, soil depth). Contrary to our expectations, traces of human impact and the prevailing light conditions (total site factor, gap fraction, openness, indirect site factor, direct site factor) had no influence on regeneration density and composition, probably due to the small gradient in light availability. Conclusion We conclude that the tree species richness in Cat Ba National Park appears to be declining at present. We suggest similar investigations in other biodiversity hotspots to learn whether the observed trend is a global phenomenon. In any case, a conservation strategy for the threatened tree species in the Cat Ba National Park needs to be developed if tree species diversity is to be maintained.
Rationale Multiple myeloma (MM) cells synthesize large amounts of paraproteins, making radiolabeled amino acids promising candidates for PET imaging of MM patients. Methods We compare tumor uptake of the two amino acid analogs [ ¹⁸ F]-fluoroethyltyrosine and [ ¹⁸ F]-FACBC in a MM xenograft model and show the feasibility of PET imaging with [ ¹⁸ F]-FACBC in a MM patient. Results Preclinically [ ¹⁸ F]-FACBC showed superior performance, mainly due to the uptake via the ASC-system. In a subsequent proof-of-concept investigation [ ¹⁸ F]-FACBC PET was performed in a MM patient. It allowed identification of both lesions with and without CT correlate (SUVmean 8.0 or 7.9) based on higher uptake compared to normal bone marrow (SUVmean 5.7). Bone signal was elevated compared to non-MM patients, and, thus [ ¹⁸ F]-FACBC potentially allows the assessment of bone marrow infiltration. Conclusion The FDA/EMA approved PET agent [ ¹⁸ F]-FACBC is promising for imaging MM and should be further evaluated in prospective clinical studies.
[This corrects the article DOI: 10.1016/j.ailsci.2021.100020.].
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