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Revealing the Auxetic Behavior of Biomimetic Multimaterial and Region-Specific Nanofibrous Fascicle-Inspired Scaffolds via Synchrotron Multiscale Digital Volume Correlation:Innovative Building Blocks for the Enthesis Regeneration
No full textEnthesis lesions are one of the prevalent causes of injuries in the tendon tissue. The gradient of mineralization, extracellular matrix organization and auxetic mechanical properties, make enthesis regeneration challenging. Innovative electrospun fascicle-inspired nanofibrous poly(L-lactic)acid/collagen type I blend scaffolds are developed. Specifically, a mineralized fibrocartilage-inspired region (with/without nano-mineralization with hydroxyapatite), where random and aligned nanofibers coexist, is connected to a tendon-like region made of aligned nanofibers, through a conical non-mineralized fibrocartilage-inspired junction. Scanning electron microscopy and synchrotron X-ray nano-tomography show the morphological biomimicry of scaffolds with the natural tendon fascicles. Cultures of human mesenchymal stromal cell spheroids confirm a balanced expression of both tendon, cartilage, and bone markers on the non-mineralized scaffolds compared with the mineralized ones. Mechanical tests, at different physiological strain-rates, reveal a biomimetic mechanical behavior of scaffolds and the ability of junctions to tune the mechanics of their surrounding sites. Multiscale synchrotron in situ tensile tests, coupled with digital volume correlation, elucidate the full-field strain distribution of scaffolds from the structural down to the nanofiber level, highlighting the auxetic mechanical behavior of junctions typical of the natural enthesis. The findings and cutting-edge investigations of this study suggest the suitability of these enthesis-inspired fascicles as innovative scaffolds for enhanced enthesis regeneration
Unsupervised learning with GNNs for QUBO-based combinatorial optimization
No full textRecent advances in deep learning techniques pose a question of whether they can facilitate the task of finding good quality solutions to combinatorial optimization (CO) problems in a practically relevant solution time. Specifically, it is of practical relevance to determine to what extent graph neural networks (GNNs) can be applied to CO problems that can be formulated as QUBOs and thus be naturally interpreted as graph problems. In this research a GNN solver is applied to two classical CO problems–the maximum cut problem and maximum independent set problem–in an unsupervised learning setting. We show that while GNN solver consistently finds good quality solutions for the Max Cut problem irrespective of the size and density of the graph, solving MIS problems is challenging for all but very sparse graphs. We further show how this problem can be addressed by embedding transfer between these two problems and compare two different GNN architectures–GCN and GraphSAGE on their robustness with respect to graph density and symmetry. Finally we demonstrate that changing the widely used Adam optimizer to Rprop optimizer can lead to considerable reduction in solution times
Maternal death surveillance in Addis Ababa, Ethiopia, 2017–2021:Causes and contributing factors
No full textBackground: Despite national efforts, maternal mortality remains a major public health challenge in Ethiopia. Identifying context-specific causes and delays in receiving appropriate and timely healthcare is essential to guide targeted interventions. This study analysed maternal mortality in Addis Ababa over a 5-year period to identify the causes and contributing factors. Methods: A retrospective analysis was conducted using maternal death surveillance data collected from 2017 and 2021 in Addis Ababa. The data were extracted from health facility-based maternal death case-based reports and the verbal autopsy tool utilized for community-based maternal death investigations. The data are part of the national surveillance system owned by the Public Health Emergency Management Center of the Ethiopian Public Health Institute. Information included in the dataset included socio-demographic characteristics, the underlying causes of death, the timing of death, and type of delays in receiving healthcare. Results: A total of 309 maternal deaths were recorded in Addis Ababa. The maternal mortality ratio was 74 maternal deaths per 100,000 live births. The majority of deaths (86.4 %) occurred after delivery. Direct obstetric causes were responsible for 94.2 % of deaths, with obstetric haemorrhage identified as the leading cause (41.1 %). Other direct causes included hypertensive disorders (23.0 %) and puerperal sepsis (12.6 %). An additional 5.8 % of deaths were resulting from indirect causes. Among the deaths resulting from direct obstetric causes, 62.2 % were due to delays in receiving appropriate and timely care after reaching health facilities. Common reasons for the delays in receiving care were delayed facility referrals (46.0 %), case management challenges (43.1 %), and lack of supplies and equipment (28.7 %). Furthermore, 37.5 % of deaths were resulting from delays in deciding to seek health care, primarily contributed by a failure to recognize the problem. About a quarter of deaths (24.7 %), were contributed by delays in reaching health facility, predominantly due to delayed arrival at referral receiving health facilities. Conclusion: Although the maternal mortality ratio in Addis Ababa is lower than the national rate, it is still above the WHO target. Almost all maternal deaths were results of the direct obstetric causes. Delays in receiving appropriate and timely care remain the leading contributing factor to maternal deaths. Strengthening emergency referral systems, enhancing facility-based management capacity through health worker training, and increasing community awareness could address key gaps in reducing preventable maternal mortality. Enhanced surveillance can be used to monitor the impact of interventions over time
The effects of norepinephrine in shockable cardiac arrest, a scoping review
No full textBackground: Out-of-hospital cardiac arrest is considered a major public health issue with an incidence of 67–170 per 100.000 inhabitants in Europe. Sufficient coronary perfusion pressure is a requisite for successful defibrillation and return of spontaneous circulation (ROSC). Although epinephrine (E) was found to increase ROSC and hospital survival when compared to placebo, its role in shockable arrest is under debate due to the absence of favorable neurological outcome. Objective: Norepinephrine (NE) increases coronary perfusion pressure and may be an alternative for epinephrine because of differences in affinity in alpha- and beta- adrenergic receptors. Methods: An extensive literature search was conducted in PreMedline, Medline, Embase and Cochrane electronic databases. All original studies (randomized controlled trials, experimental and observational studies, including case-reports) were included; guidelines, (editorial) reviews and commentaries were excluded, no date constraints were applied. Articles were included in the literature review if they described intra-arrest administration of norepinephrine and contained at least an abstract in English, French, or German. Results: A total of 3308 articles were screened after deduplication. Following initial title/ abstract screening, full-texts analysis was performed in n = 46 studies. A total of 18 articles were included, consisting of 5 human and 13 animal studies. Norepinephrine appears to optimize macrocirculatory-and myocardial hemodynamics, increased regional cerebral blood flow and might improve survival. Conclusion: Norepinephrine has shown several beneficial effects when administered during shockable cardiac arrest in animal studies, with similar signals suggested in human studies. Despite the limited evidence, norepinephrine appears to offer potential advantages over epinephrine in terms of multiple haemodynamic parameters and possible survival
Prescriptive strategy selection in station-based car sharing:Profit optimization using reinforcement learning
No full textMany car sharing operators struggle to operate at profit. In previous work, it has been shown that trip selection is an important lever to make car sharing systems more profitable and efficient by enabling them to automatically decide whether to accept or reject customer requests. By actively selecting customer requests to be served, car sharing providers are able to implement operative strategies to increase profit, namely increasing collected base fares, increasing collected time-/distant-dependent fares, or reducing operational costs such as relocation costs. However, trip selection has mostly been investigated assuming knowledge of future demands for a fixed horizon and can thus not be unrestrictedly applied in real-time. This paper suggests a prescriptive algorithm, namely a deep reinforcement learning approach (RLA), to solve the trip selection problem solely based on real-time information. Being a machine learning approach, RLA learns which of the above strategies has the highest potential, without the need to specify the booking regime in advance. Based on a simulation of a real car sharing system, we can show that the novel approach can resemble the general structure of optimal offline solutions that were obtained given global information in large parts. It significantly outperforms solutions provided by the state-of-the-art approach widely applied in practice and shows robustness by maintaining the lead even under changing conditions. Narrowly analyzing the solutions found by the novel approach, we apply it to answer complex managerial questions like determining promising relocation rates
Association between the exposome score for schizophrenia and functioning in remitted first-episode psychosis:results from the HAMLETT study
No full textBackground: Environmental risk factors contribute to functional impairment, which can persist even after symptomatic remission of a first episode of psychosis (FEP). To quantify this effect, we calculated the association between exposome score for schizophrenia (ES-SCZ), a cumulative environmental liability score, and functioning in remitted FEP patients. Methods: Data of 286 participants were derived from the HAMLETT study. General functioning was assessed using the Global Assessment of Functioning (GAF) scale at baseline, when participants were in remission for 3–6 months. ES-SCZ was calculated based on previously validated estimates and included childhood adversity domains (emotional and physical neglect; emotional, physical and sexual abuse; and bullying), cannabis use, hearing impairment, and winter birth. The association between ES-SCZ and GAF was evaluated in three multiple linear regression models, with each successive model including additional covariates. Results: ES-SCZ was negatively associated with the GAF score, even after accounting for age, sex at birth, education, migrant status, antipsychotic type, and FEP duration [B = -1.51 (-2.78 to -0.24), p = .022]. This final model explained 8.6 % of the variance (R2) in the GAF score, with ES-SCZ being the primary contributor, accounting for 35.5 % of this explained variance. Conclusions: This study independently replicated the finding that ES-SCZ predicts general functioning in FEP, showing its potential for forecasting functioning in remitted FEP patients
De fraudebenadering van het HvJ EU in de Europese btw
No full textAls het gaat om btw-fraude is de rechtspraak van het Hof van Justitie EU (HvJ EU) van groot belang. Zo heeft het HvJ EU vastgesteld wat btw-fraude is, en wat de rechtsgevolgen ervan zijn. Bovendien volgt uit de Europese rechtspraak hoe de bestrijding van btw-fraude dient plaats te vinden, door zowel de overheid als de belastingplichtige. In dit artikel bespreekt de auteur de fraudebenadering van het HvJ EU in de Europese btw. Hij concludeert dat het HvJ EU zich autonoom en activistisch opstelt door talloze regels te formuleren die niet direct volgen uit het primaire of secundaire EU-recht. Het gaat dan bijvoorbeeld om concrete inspanningsverplichtingen, verboden, voorschriften en bewijsregels. Opvallend is dat een duidelijke grondslag voor de heffing van btw in fraudesituaties ontbreekt wanneer men de rechtsregels van het HvJ EU zelf buiten beschouwing laat. Hierdoor kan de regularisatie van dergelijke situaties een nogal arbitraire uitwerking hebben. Daarnaast leidt de rechtspraak tot een aantal vragen. Mag een lidstaat bijvoorbeeld meerdere rechten in dezelfde fraudeketen weigeren? En hoe ver mag het HvJ EU gaan wanneer het zelf regels in het leven roept? Zolang de systemische zwaktes van het btw-stelsel niet door de Europese regelgever worden verholpen, is de activistische opstelling van het HvJ EU volgens de auteur gerechtvaardigd
Fundamentals of EU VAT Law
No full textFundamentals of EU VAT Law, currently in its third edition, is an immensely useful book offering not only an exhaustive description of the current state of EU Value added tax (VAT) law but also an in-depth explanation of the system’s rationale and its legislative provisions. VAT is responsible for generating almost EUR 1200 billion per year in tax revenues across the European Union – revenues that play a huge role in budgetary policymaking in the Member States. This book sheds light on the elements of the system and demonstrates how and why they are linked to each other
A response to Kerin Developing a curriculum-wide assessment strategy:Assessment in Legal Education Back to the future
No full textCosts of mental health care resource use in people with obesity:A systematic review
No full textIntroduction Obesity is a complex condition with significant economic implications. Healthcare costs associated with obesity are spread across all categories of health services, including mental health care. However, little evidence is available regarding the magnitude and types of costs associated with mental health care resource use by people with obesity.Objectives This systematic review aimed to synthesise the evidence on the costs of mental health care resource use by people with obesity.Methods A systematic literature search was conducted in PubMed (Medline), Embase (Ovid), PsycINFO (EBSCO), and Econlit (EBSCO) based on PRISMA guidelines to identify cost-of-illness (COI) studies of obesity published in English since 2016. Peer-reviewed studies estimating obesity-related costs using primary or secondary data in children or adults were included. The COI studies quality tool by Schnitzler et al. was adopted to assess the methodological quality of studies. Data extracted included general study characteristics and costs associated with mental health care. Results were synthesised narratively.Results A total of 5,565 records were identified post-duplication removal. Following selection, 33 COI studies were included, which mentioned mental health care costs; fifteen considered the monetary value of mental health care costs as separate costs in their analyses. The proportion of total annual healthcare costs attributable to mental health care ranged between 0.70% and 25.10%.Discussion Our findings suggest that people with obesity incur substantial costs related to the use of mental health care, yet less than half of the included COI studies reported mental health care costs separately from total healthcare costs attributable to obesity. This highlights the importance of greater transparency and granularity when reporting costs. Furthermore, it is imperative to shed more light on the economic impact of co-morbid obesity and mental health. This research is essential for facilitating effective resource allocation and addressing the healthcare needs of this population